a uckland uniservi c es limited · 2013-06-23 · a legal dru uckland uniservi c ly availab gs in...
Post on 08-Jul-2020
1 Views
Preview:
TRANSCRIPT
A
Legaldru
Auckland UniServic
lly availabgs in New
Janie Sh
Joanne
ces Limited
ble, unclaw Zealand
based
FINAL
heridan, PRa
ChristineBarnes, Ph
T
assified pd before d survey o
L REPOR
Jun
hD, BPharmachael Butle Y. Dong, hD, BPharm
The Schoohe Univers
New
psychoactand afterof patter
RT OF F
ne 2009
m, BA, FRPer, BA, PGBSc Hons,
m, MRPhar
ol of Pharmsity of Aucw Zealand
tive substr the banns of use
INDING
PharmS, ReDipPH BCom Hon
rmS, RegPh
macy kland
tances ann on BZP: e
GS
egPharmNZ
ns harmNZ, FL
nd illegal a web‐
Z
LS
2
TABLE OF CONTENTS 1 Executive Summary ........................................................................................... 7 2 Introduction .................................................................................................... 11 2.1 Background .............................................................................................. 11
2.1.1 The legislative and regulatory background ................................ 11 2.1.2 The current study ........................................................................ 12
2.2 Study aims ................................................................................................ 12 2.3 Study methods ......................................................................................... 13 2.4 Ethics approval ......................................................................................... 13 2.5 Structure of this report ............................................................................ 13 3 Adverse effects associated with herbal substances used for recreational purposes: a
literature review ............................................................................................. 14 3.1 Introduction ............................................................................................. 14 3.2 Aims.......................................................................................................... 14 3.3 Methods ................................................................................................... 14 3.4 Results ...................................................................................................... 16
3.4.1 Extent and context of use ........................................................... 16 3.4.2 Adverse effects ........................................................................... 17
3.5 Discussion and Conclusions ..................................................................... 31 3.6 References ............................................................................................... 32 4 Web‐based survey .......................................................................................... 39 4.1 Aims.......................................................................................................... 39 4.2 Methodology ............................................................................................ 39 4.3 Methods ................................................................................................... 40
4.3.1 Sample population ...................................................................... 40 4.3.2 Recruitment ................................................................................ 40 4.3.3 Questionnaire and website design ............................................. 41 4.3.4 Data collection ............................................................................ 42 4.3.5 Data analysis ............................................................................... 43
4.4 Results ...................................................................................................... 44 4.4.1 Full sample data .......................................................................... 44 4.4.2 Demographics ............................................................................. 44 4.4.3 Data from all participants ........................................................... 46 4.4.4 Use of BZP party pills .................................................................. 47 4.4.5 Use of BZP‐free party pills ........................................................... 50 4.4.6 Use of legally available smokeable products .............................. 52 4.4.7 Use of other legally available substances ................................... 53 4.4.8 Use of alcohol ............................................................................. 54 4.4.9 Use of cannabis ........................................................................... 55 4.4.10 Use of ecstasy ............................................................................. 56 4.4.11 Use of methamphetamine .......................................................... 56 4.4.12 Use of GHB .................................................................................. 57 4.4.13 Use of ketamine .......................................................................... 58 4.4.14 Use of LSD ................................................................................... 59 4.4.15 Use of prescription drugs (for non‐medical purposes) ............... 59 4.4.16 Use of other illegal drugs ............................................................ 61 4.4.17 Paired data analysis of change over time ................................... 61 4.4.18 Reasons for change in substance use – qualitative data ............ 71
3
4.4.19 Experiences of adverse events ................................................... 77 5 Summary and Discussion................................................................................. 85 5.1 Sample demographics .............................................................................. 85 5.2 Sample substance use .............................................................................. 85 5.3 Change in use over time .......................................................................... 86
5.3.1 Change in BZP party pill use over time ....................................... 86 5.3.2 Change in BZP‐free party pill use over time ............................... 86 5.3.3 Change in legally available smokeable substance use over time86 5.3.4 Change in alcohol use over time ................................................. 86 5.3.5 Change in cannabis use over time .............................................. 87 5.3.6 Change in ecstasy use over time ................................................. 87 5.3.7 Change in methamphetamine use over time ............................. 87 5.3.8 Change in GHB use over time ..................................................... 87 5.3.9 Change in ketamine use over time ............................................. 87 5.3.10 Change in LSD use over time ...................................................... 87 5.3.11 Change in non medical use of prescription drugs over time ...... 88 5.3.12 Qualitative data ‐ self‐reported reasons for a change in substance use
..................................................................................................... 88 5.3.13 Adverse events associated with use of unclassified substances 89
5.4 Limitations and confounders ................................................................... 91 6 Conclusion ...................................................................................................... 93 7 Appendix ........................................................................................................ 95 7.1 The website .............................................................................................. 95 7.2 Advertising material ................................................................................. 96
7.2.1 A5 Flyer ....................................................................................... 96 7.2.2 Promotional cards ....................................................................... 97 7.2.3 Radio advertisement ................................................................... 99 7.2.4 Website advertising .................................................................. 100
8 References .................................................................................................... 101
4
TABLES AND FIGURES Table 1: Plants (selected common name) included in literature searches ............................. 15 Table 2: Botanical nomenclature and other descriptive information for plants discussed in the literature review ................................................................................................................ 19 Table 3: Numbers of spontaneous reports of suspected adverse drug reactions associated with single‐ingredient preparations of herbal substances of interest held in the Vigisearch database of the World Health Organisation Uppsala Monitoring Centre (WHO‐UMC) for the period up to March 30, 2009. .................................................................................................. 30 Table 4: Demographic data 1 .................................................................................................. 45 Table 5: Demographic data 2 ................................................................................................... 46 Table 6: BZP party pills named by respondents ....................................................................... 47 Table 7: Frequency of use of BZP party pills at Waves 1 and 2 ............................................... 49 Table 8: Where BZP party pills were obtained ........................................................................ 49 Table 9: Level of use of BZP party pills..................................................................................... 49 Table 10: BZP‐free party pills named by respondents ............................................................. 50 Table 11: Self‐reported frequency of use of BZP‐free party pills ............................................ 51 Table 12: Where BZP‐free party pills were obtained .............................................................. 51 Table 13: Level of use of BZP‐free party pills ........................................................................... 51 Table 14: Legally available smokeable products named by respondents ............................... 52 Table 15: Frequency of use of legally available smokeable products ..................................... 52 Table 16: Where legally available smokeable products were obtained .................................. 53 Table 17: Level of use of legally available smokeable products .............................................. 53 Table 18: Legally available substances named by respondents .............................................. 54 Table 19: Frequency of alcohol use ......................................................................................... 54 Table 20: Level of alcohol use .................................................................................................. 55 Table 21: Frequency of cannabis use ....................................................................................... 55 Table 22: Level of cannabis use ............................................................................................... 55 Table 23: Frequency of ecstasy use ......................................................................................... 56 Table 24: Level of ecstasy use .................................................................................................. 56 Table 25: Frequency of methamphetamine use ...................................................................... 57 Table 26: Level of methamphetamine use .............................................................................. 57 Table 27: Frequency of GHB use .............................................................................................. 57 Table 28: Level of GHB use ...................................................................................................... 58 Table 29: Frequency of ketamine use ...................................................................................... 58 Table 30: Level of ketamine use .............................................................................................. 58 Table 31: Frequency of LSD use ............................................................................................... 59 Table 32: Level of LSD use ........................................................................................................ 59 Table 33: Prescription drugs named by respondents .............................................................. 60 Table 34: Frequency of non‐medical use of prescription drugs .............................................. 60 Table 35: Level of non‐medical use of prescription drugs ....................................................... 61 Table 36: Other illegal drugs named by respondents .............................................................. 61 Table 37: Paired data comparison of substance use over time............................................... 63 Table 38: Reasons for a change in substance use (W1) ........................................................... 73 Table 39: Reasons for a change in substance use (W2) ........................................................... 75 Table 40: Summary details for self‐reported adverse effects involving herbal substances and BZP‐free party pills ................................................................................................................... 80
5
Table 41: Labelled ingredients of herbal products and BZP‐free party pills containing herbal ingredients ............................................................................................................................... 84 Figure 1: Use of substance in previous 6 months at W1 and W2 (N=273) .............................. 63 Figure 2: Change in self‐reported frequency of use of BZP party pill use ............................... 65 Figure 3: Change in self‐reported frequency of use of BZP‐free party pills ............................ 66 Figure 4: Change in self‐reported frequency of use of smokeable products .......................... 66 Figure 5: Change in self‐reported frequency of use of alcohol ............................................... 67 Figure 6: Change in self‐reported frequency of use of cannabis ............................................. 67 Figure 7: Change in self‐reported frequency of use of ecstasy ............................................... 68 Figure 8: Change in self‐reported frequency of use of methamphetamine ............................ 68 Figure 9: Change in self‐reported frequency of use of GHB .................................................... 69 Figure 10: Change in self‐reported frequency of use of ketamine .......................................... 69 Figure 11: Change in self‐reported frequency of use of LSD ................................................... 70 Figure 12: Change in self‐reported frequency of non‐medical use of prescription drugs ...... 70
6
ACKNOWLEDGEMENTS
We would like to acknowledge the contribution of a number of individuals and organisations who provided support and advice at different stages of the project.
We are grateful to Joanna Stewart for her valuable guidance on statistical and data analysis issues, and to Youthline (especially Nao Guy) for its assistance during the pilot phase and in promoting the research. Damien Pivac (Wellington) and Mike Ikilei (Auckland) from the Community Action on Youth and Drugs (CAYAD) project, and Jarra Borman from UPFM, made significant contributions during the questionnaire development and recruitment phase. We are also appreciative of the many other individuals who helped publicise the research through a range of networks.
The contribution of research participants was central to this study. We warmly thank all those who participated and shared their views and experiences, particularly those who took the time to take part in both waves of the survey.
The study was funded from the National Drug Policy Discretionary Grant Fund which is jointly managed by the Inter‐Agency Committee on Drugs and the Ministerial Committee on Drug Policy. The views expressed in this report do not necessarily reflect those of the funder.
7
1 EXECUTIVE SUMMARY
Introduction
• In recent years there has been much interest in the burgeoning availability of legally available psychoactive substances in New Zealand, in particular, piperazine‐based ‘party pills’ containing benzylpiperazine (BZP) or trifluoromethylphenylpiperazine (TFMPP). Whilst BZP and related phenylpiperazines were rescheduled as Class C1 substances in 2008, psychoactive plants, such as Salvia divinorum, pills that are BZP‐free and smokeable products (e.g. “Spice”) are currently available to purchase legally in New Zealand. Very little is known about the use of these unclassified substances, or the impact of the rescheduling of BZP on drug‐taking behaviour in New Zealand
Aims
• The main aims of the research were to explore: the literature around the use and harms of emerging herbal substances; the use and sources of piperazine‐based ‘party pills’ and other illegal and legal substances over time; factors associated with changes in substance use; adverse events/effects associated with the use of legally available or unregulated substances. This study is not designed to ‘test’ cause and effect, with regard to the impact of the banning of BZP on use of both legal and illegal substances.
Method
• The research consisted of two stages: a literature review and a cross‐sectional study utilising a web‐based survey instrument.
• The web‐based survey comprised a self‐complete questionnaire which participants (aged 18‐30 years) completed on‐line, on two separate occasions. The Wave one survey was completed during July 2008 (and was three months after the ban on BZP) and the Wave two survey was completed during December 2008 (and was 2‐3 months after the end of the amnesty period for BZP and related products). Those who completed the questionnaire at W1 were invited to complete it at W2. The use of a unique identifier code meant that data for individuals were able to be linked across the two waves of the survey, whilst maintaining the anonymity of the information.
Respondents
• The sample size for W1 was 508 and W2 was 344. Around three quarters of the sample identified as New Zealand European, more than half were male, and a little over half were in full‐ or part‐time study. The study sample is over‐representative of those living in the Auckland region.
Total sample data at W1
• The results from W1 are presented below. The majority of the total sample at W1 had used alcohol (92.9%), 45.1% had used cannabis, 33.5% had used ecstasy, 15.9% LSD, 8.1% ketamine, 6.3% GHB, and 5.5% methamphetamine in the previous 6 months. In addition, 9.1% had used prescription drugs for non‐medical purposes and 8.5% had used ‘other illegal drugs’ in the previous 6 months.
8
• Around one third of the W1 total sample (31.3%) had used BZP party pills in the previous six months. Few of the users had obtained products from ‘dealers’, and this remained the same at W2, although friends were a large source of BZP and we cannot know where they obtained products from.
• Around one in ten of the W1 total sample (11.0%) had used BZP‐free party pills at in the 6 months prior to W1.
• Use of legally available smokeable products was slightly higher, with 13.8% having used them in the previous six months at W1. The most commonly used smokeable product was ‘Salvia’ (S. divinorum).
• At W1, only 5.3% of the total sample used ‘other legally available substances (excluding tobacco and alcohol). The most commonly reported substance in this category was amyl nitrate.
• The majority of BZP, BZP‐free, legal smokeable substances, ecstasy, methamphetamine, GHB and LSD users used these substances once a month or less frequently. Around half of cannabis and prescription drug users used these substances once a month or less frequently.
• For all substances, the majority indicated the amount they used had remained the same ‘since the ban on party pills’, except BZP users where the majority reported the amount had decreased, and BZP‐free users where results were mixed.
Paired data analysis of W1 and W2 data
• Paired data analysis undertaken for those who completed the survey at both waves provides strong evidence that: more participants switched from being BZP party pills users at W1 to being non users of BZP party pills at W2; more participants switched from being legally available smokeable products users at W1 to legally available smokeable products non‐users at W2; more participants switched from being non‐medical prescription drug non‐users to being users between W1 and W2 than the other way around. There is weak evidence that more participants switched from being ecstasy users at W1 to non‐users of ecstasy at W2 than the other way around, mainly accounted for by non‐users of BZP.
• Analysis was also undertaken to explore the differences between BZP party pill users (defined as those who had used BZP party pills at W1) and non‐BZP users (defined as all remaining participants) in terms of changes in substance use. Results were significant in relation to use of ‘legally available smokeable products’ only. BZP party pills users were more likely to be non users of ‘legally available smokeable products’ at W2 than W1, whereas non‐users of BZP were more likely to be users of ‘legally available smokeable products’ at W2 than W1 (p=0.02).
• Regression analysis for change in frequency of use over time was conducted over three subgroups as classified at W1: GP0 – non drug users (i.e. used alcohol only or nothing at all); GP1 – non‐users of BZP party pills (i.e. not used BZP party pills, but used at least one illicit substance or BZP‐free party pills); GP2 – BZP party pill users (i.e. had used BZP party pills at first time point in W1 and may have used illict drugs as well). When comparing the three groups, there was a decrease in frequency of BZP party pill use over time amongst GP2 while the other two groups stayed about
9
the same in frequency of BZP party pill use over time. For BZP‐free product use, GP2 and GP1 use frequency increased over time then decreased after the end of the amnesty period while the change in corresponding frequencies for the GP0 was minimal and for smokeable products there was a significant drop in frequency of use amongst GP2 while there were slightly increase in the corresponding frequencies of use amongst GP1 and GP0 after the ban. Of note, GP2 had a higher frequency of use of all susbtances except LSD.
• More ecstasy users reported an ‘increase’ in use than a ‘decrease’ in use when asked at both W1 (3 months after the BZP ban); however, overall there was a move towards reporting a decreased use (e.g. from ‘increased’ at W1 to ‘no change’ at W2, or ‘no change’ at W1 to ‘decreased’ at W2) overall over time.
Qualitative data
• A limited number of the total sample provided qualitative data. A substantial proportion of the qualitative sample indicated that there had been no change in their substance use. However, data from both waves of the survey reveal that the banning of BZP was a key self‐reported reason for a change in drug taking behaviour, resulting in a self‐reported increase in use of both alcohol and illicit drugs (in particular, ecstasy) to replace BZP. Many also attributed any change to reasons beyond the ban (e.g. seasonal influences). These findings needed to be treated with caution, however, due to the small numbers involved.
Adverse events related to herbal substances
• Across both waves, a total of 63 respondents provided summary details of 73 experiences of adverse events (AEs) related to the use of a range of drugs. After excluding reports involving products and substances outside of the study remit (e.g. ones involving illicit substances such as cannabis) a total of 20 reports was analysed. Of these, two AEs can be classified as serious since they resulted in hospital admission (one involved use of Salvia divinorum and alcohol, and the other AE occurred following use of Hummer pills). Two of the 20 reports involved the use of smoked S. divinorum with alcohol or 'weed', one involved the use of smoked Spice and Dream, and one involved the use of Dream orally. Six reports involved the use of products (Comet, Hummer, Vegas Nights) stated to contain the 'Floradrene' blend of ingredients. All respondents reporting adverse events said that they fully recovered from the experience and, where advice was sought, this was accessed from family/friends rather than health professionals.
Limitations
• The limitations of the methodology and potential confounding factors associated with the study require acknowledgement. The study has not been designed to test cause and effect, and the use of a web‐based methodology may have limited its scope and may have resulted in some participants making multiple submissions and/or falsifying information (although there was no evidence of this).
• The study sample cannot be generalisable to the New Zealand 18‐30 year old population due to bias in the sample demographics and the possibility that substance users may have been more likely to take part than non users.
10
• Other issues particular to the study include the timing of data collection, difficulties in matching paired data, and poor quality of data collected on AEs.
• The timeframe for this study was short, and thus some changes, which might be slower to occur, might not have been picked up. Furthermore, the numbers using some substances were very low, so that further decreases would be difficult to detect. In addition, small numbers for some sub‐groups mean that the study may not be powered to detect change and there is an increased chance of false positive results.
• Wave 1 also included the period just after the New Year and thus might be affected by an increased use of substances over the summer period (seasonal effect).
• Information is lacking on the extent of use of herbal substances for recreational purposes. Their inclusion as ingredients of ‘recreational’ products is unclear: several have no history of use for, or scientific evidence of, psychoactive effects. Adverse effects have been reported with both medicinal and recreational use of these substances. However, in general, there is limited information on their safety profile, including adverse effects following long‐term use, drug interactions, effects of withdrawal, addictive potential, and so forth. Most information available comes from published case reports, many of which are of poor quality.
• In summary, this study has not been designed to ‘test’ cause and effect. Thus, although we have shown a temporal relationship between the BZP ban and a reduction in BZP use, and some other changes in substance use, a causal relationship cannot be inferred from our data.
11
2 INTRODUCTION
2.1 Background
In recent years there has been much interest in the burgeoning availability of legally available psychoactive substances in New Zealand, in particular, piperazine‐based ‘party pills’ ‐ e.g. pills containing benzylpiperazine (BZP) or trifluoromethylphenylpiperazine (TFMPP). It has been estimated that 1 in 5 people has ever used these products, with use highest in the 18‐24 year old age group 1. Although piperazine‐based ‘party pills’ have been by far the most popular legally available substances in New Zealand, substances such as smokeable products (e.g. “Spice”), pills that are BZP‐free and may contain other materials of plant origin (e.g. Salvia divinorum), are also available. Products of this type are available in New Zealand through specialist ‘party pill’ and drug paraphernalia outlets and via the internet (e.g. see: http://www.mindfuel.co.nz/details.aspx?itemID=17).
2.1.1 The legislative and regulatory background
BZP containing party pills, including those also containing TFMPP, were first made available for sale in New Zealand in 2000. At this time, and up until 2004, the products were legally uncontrolled and thus faced no restrictions in terms of advertising, where they were able to be sold, and to whom. In 2004, the Expert Advisory Committee on Drugs1 (EACD) undertook a review of the available evidence on BZP and made a series of recommendations based on the findings. At this time they noted that “there is no current schedule of the Misuse of Drugs Act 1975 under which BZP could reasonably be placed” and recommended that options for new categories of classification2 be explored 2. In recognition of the paucity of available evidence on BZP at this time it was also recommended that further research be conducted to explore the potential harms linked with the use of BZP. Subsequent studies (some funded by the National Drug Policy Discretionary Grant Fund) explored a range of topics including prevalence and harms of ‘legal’ party pills 3, young people’s use of the substances 4, BZP‐related poisoning 5, an assessment of the effects of BZP/TFMPP on sleep/mood/cardiovascular parameters/psychological functioning and driving performance 6, and BZP‐related hospital presentations 7.
In 20053, legislation was introduced in the form of a new schedule within the Misuse of Drugs Amendment Act 2005 to control ‘Restricted Substances’. BZP was the first substance to be regulated in this way, with restrictions placed on who the products were able to be sold or supplied to (only those aged over 18 years) and a ban on print and television advertising. In addition, the distribution of free samples of the products at events or as part of other promotional activity was also prohibited. Beyond this, there were no other controls introduced, although the ‘Restricted Substances’ category incorporated a provision for other regulations to be made (relating to where substances could be sold) that could be enacted at some point in the future.
1 The EACD provides expert advice to the Minister of Health regarding drug classification issues.
2 It was proposed that these “incorporate some levels of control and regulation, such as an 18 plus age limit, without prohibiting access to these substances completely” (EACD, 2004)
3 This was following the release of findings from some of the commissioned and other research studies, although not all of these had been completed prior to the new legislation being introduced.
12
Following a review of the available evidence, in December 2006, the EACD advised the government that BZP posed a “moderate risk of harm” and recommended that BZP4 be classified under Schedule 3, Part 1 (Class C1) of the Misuse of Drugs Act 1975. This placed it in the same classification as cannabis (fruit, plant and seed), coca leaf and ‘khat’ (Catha edulis), thus making it illegal to manufacture, import, export or supply BZP and related substances. The legislation was introduced on April 1st 2008, with a six‐month amnesty period that allowed users to possess small amounts of the drug (less than 100 tablets/pills or 5 grams of BZP and related substances) until September 1st when the amnesty expired.
At the time of writing, substances such as Salvia divinorum (Diviner’s sage) and Piper methysticum (kava) remain unregulated. However, the previous Associate Minister of Health accepted the advice of the EACD that preparations of Salvia divinorum be made Restricted Substances, and it is likely that these may be regulated using this classification at some point in the future.
2.1.2 The current study
Since BZP and related piperazines were reclassified in 2008 there has been much discussion about the potential impact of this on New Zealand’s legal and illicit drug markets, and consequently the drug‐using population. Furthermore, whilst a body of research now exists regarding the prevalence of use and harms associated with the use of piperazine‐containing party pills 1,3,4,7, very little is known about the use of other unclassified substances (e.g. Salvia divinorum, kava, morning glory, etc.). A summary of information on safety aspects of many of these herbal substances is presented in the literature review in Section 3.0 of this report.
At the time this research was carried out (2008), the legislative and regulatory environment provided a unique opportunity to conduct research into the short‐term impacts of prohibition as a policy and the impact of legislative changes on substance‐using behaviours and associated harms, and is the backdrop against which this current study was developed.
2.2 Study aims
The main aims of the research were to:
1. Explore the literature around the use of, and harms associated with substances such as Salvia divinorum (‘magic mint’, ‘hallucinogenic sage’, ‘Diviner’s sage’), morning glory (Rivea corymbosa seeds, also Ipomoea tricolor and other Ipomoea species), kava (Piper methysticum), kratom (Mitragyna speciosa).
2. Explore the use of, changing patterns of use, and sources of:
a. piperazine‐containing ‘party pills’
b. legally available substances as in 1. above
c. other legal and illegal substances.
3. Explore the factors which young people associate with their change in substance use – e.g. changes to the law, availability, price, personal experience, adverse effects.
4 This also included all known analogues and derivatives of benzylpiperazine and phenylpiperazine that have no therapeutic use.
13
4. Explore the harms and adverse effects/events5 associated with the use of substances such as in 1. above6.
5. Explore user use of medical services and support for the management of adverse events as in 4 above.
6. Where possible, to obtain data from the New Zealand Centre for Adverse Reactions Monitoring7 (CARM) and other relevant national and international reporting centres, such as the World Health Organisation’s Collaborating Centre for International Drug Monitoring (Uppsala Monitoring Centre) and, where available, compare descriptively with data obtained in this study.
2.3 Study methods
The research consisted of two stages:
• A review of the literature on (unregulated) plant‐based substances used recreationally for their psychoactive effects.
• A web‐based survey of 18‐30 year olds resident in New Zealand.
2.4 Ethics approval
Ethical approval for the study was granted by the University of Auckland Human Participants Ethics Committee (ref: 2007 / Q / 052).
2.5 Structure of this report
The remainder of this report is divided into three sections as follows:
• Section 3 presents findings from the literature review
• Section 4 presents findings from the web survey
• Section 5 contains a discussion of the implications of the research findings.
5 Adverse events are any clinical or physical change or disease experienced by a user, whether or not considered related to the use of drug/s in question. An adverse effect (or unwanted side effect) is a psychical or psychological outcome associated with the drug used. The two terms may at times be used interchangeably [but it is incorrect to do so].
6 Adverse events and adverse reactions will be based on self report. Furthermore, the ability of participants to dissociate their expectations, set and setting from objective adverse events is difficult, as is the impact of other drugs used. Nonetheless, these self‐reported events will provide useful insights into currently little researched areas of substance use.
7 The Centre for Adverse Reactions Monitoring (CARM) is New Zealand’s national monitoring centre for adverse drug reactions (ADRs). It collects and evaluates spontaneous reports from doctors, pharmacists and other healthcare professionals of suspected adverse drug reactions (ADRs) associated with the use of prescription and non‐prescription medicines, including herbal medicines, ‘legal party pills’ and other substances.
14
3 ADVERSE EFFECTS ASSOCIATED WITH HERBAL SUBSTANCES USED FOR RECREATIONAL PURPOSES: A LITERATURE REVIEW
3.1 Introduction
Alongside the extensive use of herbal medicines for their putative health benefits, in recent years, recreational use (i.e. for psychoactive effects) and misuse of certain herbal substances has emerged. These substances include Salvia divinorum (diviner's sage), Mitragyna speciosa (kratom), Rivea corymbosa, Ipomoea tricolor (morning glory), Catha edulis (khat) and the caffeine‐containing herbal substances Paullinia cupana (guarana) and Ilex paraguariensis (maté). Several of these plant substances have a long history of traditional use among certain ethnic groups for ceremonial, religious and/or other societal purposes, and have become popular as contemporary 'herbal highs'; several others have no history of recreational use, but have received attention because of their putative properties as anxiolytics, central nervous system (CNS) stimulants and hallucinogens.
Access to herbal substances used recreationally is straightforward due to weak regulation of these products and wide availability via internet websites and unregulated retail outlets. Other factors that are likely to be considered by users and potential users in their decisions to use herbal recreational substances are the portrayal of these substances, particularly by websites proffering herbal substances for recreational use, as having similar effects to those of well‐known psychoactive agents, as being alternatives to illicit substances and/or as being natural and 'safe'.1‐3
Herbal preparations are chemically rich complex mixtures that can cause clinical adverse effects, whether they are used recreationally or for therapeutic purposes. Further, there are issues regarding quality of herbal substances that impact on their safety. Against this background, this paper reviews literature examining the extent of use of herbal substances for recreational purposes and reported adverse effects associated with their medicinal and/or recreational use.
3.2 Aims
The aims of this literature review are:
• To identify, review and summarise published literature concerning a) the extent of use of herbal recreational substances; b) reports of clinical adverse effects associated with the use of a defined list of herbal recreational substances.
• To summarise spontaneous reports of suspected adverse drug reactions (ADRs) associated with these herbal substances held in the World Health Organization Uppsala Monitoring Centre (WHO‐UMC) Vigisearch database.
3.3 Methods
A list of herbal substances with actual or potential recreational use was compiled from data collected in a research study examining recreational substances used by young adults in New Zealand (i.e. the study described in this report), from herbal ingredients of products
15
listed for sale on a New Zealand‐based website (www.mindfuel.co.nz) and from the authors' knowledge of herbal recreational drugs of emerging interest [Table 1]. Herbal substances with well‐established contemporary recreational use (e.g. Cannabis sativa) were excluded. Literature searches were performed using the databases Medline and EMBASE for the period up to December 2008 using appropriate keywords for these substances together with general search terms for adverse effects. From the results, publications of interest were selected and reviewed by one author (JB). Searches were also conducted for all herbal substances listed in Table 1 using the World Health Organization Uppsala Monitoring Centre (WHO‐UMC) Vigisearch database, which holds summary details of spontaneous reports of suspected adverse drug reactions received by the national pharmacovigilance centres of around 90 countries worldwide and subsequently submitted to the WHO‐UMC. These searches were conducted at species level, or otherwise the closest relevant level.
While this work has involved extensive literature searches and the information has been selected and reviewed objectively, this remains a narrative, not a systematic, review.
Table 1: Plants (selected common name) included in literature searches Acorus calamus (calamus) Althaea officinalis (marshmallow) Camellia sinensis (green/black tea) Canavalia maritime (baybean) Catha edulis (khat) Citrus aurantium (bitter orange) Datura stramonium (datura) Eleutherococcus senticosus (Siberian ginseng) Ephedra sinica (ephedra) Hamelia patens (firebush) Heimia salicifolia (sun opener) Ilex paraguariensis (maté) Leonotis leonurus (lion's tail) Leonotis sibricus (Siberian motherwort) Ipomoea tricolor (morning glory) Mitragyna speciosa (kratom) Nelumbo nucifera (pink lotus) Panax ginseng (ginseng) Paullinia cupana (guarana) Pedicularis densiflora (lousewort) Pelargonium graveolens (pelargonium) Polygonum multiflorum (He Shou Wu) Piper methysticum (kava) Rhodiola rosea (rhodiola) Rosa gallica (rose) Salvia divinorum (salvia) Scutellaria nana (dwarf skullcap) Turnera diffusa (damiana) Vanilla planifolia (vanilla)
16
3.4 Results
3.4.1 Extent and context of use
At present, information is limited on the extent of use of herbal substances for recreational purposes. A cross‐sectional study at a New Zealand Hospital explored the prevalence of use of 'herbal party pills' among individuals attending the emergency department, but this term was used to describe manufactured pills containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP).4
Several studies provide information specifically on the extent of use of S. divinorum. A cross‐sectional study involving interviews with attendees (average age 25.1 years) of musical events and 'raves' in Italy found that 10.4% had ever used S. divinorum; in contrast, a greater proportion had ever used marijuana* (66.2%), hashish* (56.3%), cocaine (27.9%), 'poppers' (19.3%), hallucinogenic mushrooms (17.1%), ecstasy (17.0%), amphetamines (15.3%), and LSD (14.2%), whereas fewer had used opium, ketamine, psychiatric medication, crack, heroin and benzodiazepines.5 S. divinorum was among the most commonly used of those substances recently introduced to the market (stated in the study to include S. divinorum, ketamine and hallucinogenic mushrooms). In an internet‐based survey involving a random sample of 7350 university students (response rate 20%, n = 1514) in a state in the USA where S. divinorum is legal, 4.4% of respondents had used S. divinorum in the previous year.6 Similar proportions had used ecstasy (5.0%) and cocaine (7.1%), whereas fewer had used heroin (0.3%) and methamphetamine (1.2%); 34.9% had used marijuana. Unpublished data from a similar study (also in the USA in a state where S. divinorum was legal) involving 826 undergraduate students found that 6.7% had used S. divinorum in the previous year.7 Both studies found self‐reported marijuana use to be the strongest predictor of S. divinorum use.6,7 Patterns of use of S. divinorum were explored in a small study in Spain involving 32 users (mean age 25 years) identified using adaptive sampling (where participants referred to acquaintances who also had experience with the substance). Participants had used S. divinorum an average of two times, and 88% had used it for the first time in the previous year.8
Several other studies have examined the extent of use of certain other herbal substances of interest, including ephedra, guarana and bitter orange (Citrus aurantium), although this has been in the context of their use to aid bodyweight loss (e.g. as stimulants)9,10 or to boost energy.11,12 In the USA National Physical Activity and Weight Loss Survey 2002 (n = 11,211), ephedra was the most commonly used 'stimulant' among respondents who had used weight‐loss products in the previous year,9 and in a cross‐sectional internet‐based study involving adolescents in the USA, 46.2% of respondents had ever used dietary supplements, of whom 2.1% had taken ephedra and 10.7% had used herbal weight‐loss products.10 The 2004 California Behavioral Risk Factor Surveillance Study reported that 2% of the 4010 respondents had taken a product containing bitter orange in the previous year, most commonly to increase energy.11
*Marijuana is the dried flowering tops of cannabis; hashish is the name usually given to cannabis resin.
17
3.4.2 Adverse effects
3.4.2.1 General issues with herbal substances
Quality issues with herbal medicines In contrast with most conventional substances (i.e. single chemical entities), herbal medicines are chemically rich complex mixtures comprising several hundreds of constituents, often more. Many manufactured herbal products contain several herbal ingredients, further adding to the chemical complexity. Their chemical complexity creates difficulties in determining their clinical effects and, where a safety concern has been identified, establishing which constituent(s), even which herbal ingredient(s) for multi‐ingredient products, are implicated is problematic.
For many herbal substances, the specific chemical constituents and, therefore, their safety, are unknown, and even for herbal medicines with well‐documented phytochemistry, there are few for which the specific constituents responsible for pharmacological activity (including adverse effects) are fully understood.13 The profile of constituents is not uniform throughout a plant and, for many plants, only a specific plant part, or parts, such as roots or leaves, is (or should be) used. Moreover, the precise profile of constituents can vary both qualitatively and quantitatively between different batches of herbal starting materials because of inter‐ or intraspecies variation in constituents, environmental factors (such as climate and growing conditions), time of harvesting (the profile of constituents can vary even over the course of a day) and post‐harvesting factors (such as storage conditions, drying and processing).13
There will also be variations in the chemical composition of herbal products containing the same herbal ingredient(s), but produced by different manufacturers; this occurs even with regulated herbal medicinal products. Numerous studies have found important differences in the pharmaceutical quality of marketed herbal products, for example, variations in the content of major constituents in products containing eleutherococcus ginseng.14
Standardisation for content of certain constituents is an approach used by some manufacturers, but some products claiming to be standardised do not meet the standards stated on their labels. Laboratory analysis of five samples of different herbal products containing S. divinorum purchased from websites and 'herbal high' shops in the USA found that the salvinorin A content of the samples ranged from 0.126 to 1.137 mg/g and that the actual concentration in each product was substantially lower than the labelled content (range from 1 to 16% of labelled content).15
Safety problems arising from poor‐quality herbal substances The pharmaceutical quality of herbal substances in ensuring their safety (and efficacy) is critical,16‐18 yet problems with the quality of herbal substances are common. A majority of quality problems is associated with unauthorised herbal products; in particular, traditional Chinese and Asian (Ayurvedic, Unani) products often lack effective quality controls and may give rise to public health concerns.13 In some traditional systems, substitution of herbal ingredients is an accepted practice (one herbal ingredient is substituted for another with a reputedly similar action; the similarity is determined on a traditional basis, and not on the pharmacology or chemical composition of the herbal ingredient). Several other quality problems with herbal substances can occur, including:
18
• use of poor‐quality raw materials, including plant parts other than those intended;
• deliberate or accidental inclusion of prohibited or restricted herbal ingredients;
• adulteration with conventional prescription medicines;
• contamination with toxic substances (e.g. heavy metals);
• qualitative and quantitative differences between labeled and actual contents;
• presence of foreign organic matter;
• microbial contamination;
• presence of pesticides, fumigants.
The problems are compounded by demand exceeding supply of good‐quality herbal ingredients, differences in nomenclature for plant species, and cultural differences in views on toxicity.13 Some examples where adverse effects have occurred due to poor‐quality herbal products include:
• substitution of Aristolochia species (which contain constituents that are nephrotoxic, carcinogenic and mutagenic) for other herbs in the formulation of a product claimed to aid weight loss resulted in cases of nephropathy and urothelial cancer;19
• cases of poisoning, including epileptic‐type seizures in babies who received star anise infusions and other neurotoxicities in infants, in Europe and the USA due to the accidental use of Japanese rather than Chinese star anise.20,21 (The dried fruits of Japanese star anise (Illicium anisatum L.), which can cause neurologic and gastrointestinal toxicities due to the presence of anisatin, and Chinese star anise (Illicium verum f. Hook) cannot be distinguished through visual examination).13
The adulteration of many traditional herbal products with conventional drugs is a major problem internationally, and carries a substantial potential impact on the public health. In these cases, typically, the conventional drugs contained within the product are not declared on labelling as ingredients; their presence is detected only when suspect products are subjected to pharmaceutical analysis, or when the user experiences adverse effects that are serious enough to warrant medical attention. Recent examples of adulterated products include traditional Chinese medicine (TCM) 'slimming' products containing fenfluramine, nitrosofenfluramine, sibutramine and/or methylphenidate, TCM topical preparations used for eczema containing corticosteroids, and TCM sexual enhancement products containing sildenafil.13
The problem of potentially harmful ingredients also includes the presence of high concentrations of heavy metals in some traditional herbal products. While, in some cases, these may arise from the plant material itself or be introduced as trace elements during processing, they are also often added intentionally and declared as ingredients in some TCM and Ayurvedic medicine formulations.13 For example, the Chinese Pharmacopoeia includes monographs for realgar (arsenic disulphide), calomel (mercurous chloride), cinnabaris (mercuric sulphide) and hydrargyri oxydum rubrum (red mercuric oxide), and formulations for almost 50 preparations that include one or more of these substances.22
Several cross‐sectional studies involving pharmaceutical analysis of products have found substantial proportions of products to be adulterated with conventional drugs, or to contain high concentrations of heavy metals,23‐25 and cases where human toxicity has resulted from
19
the ingestion of conventional drugs or heavy metals present in traditional herbal products have been described.26‐30
3.4.2.2 Specific adverse effects associated with herbal substances used recreationally
Literature searches revealed relevant information for around 15 of the plant species for which searches were conducted. Information on clinical adverse effects is summarised below for these individual herbal substances. Adverse effects described are not necessarily in relation to recreational use of a herbal substance of interest; in fact, much of the literature relates to medicinal use of the herbal substances of interest. Botanical nomenclature, including some common names, and other descriptive information is provided for herbal substances of interest in Table 2.
Table 2: Botanical nomenclature and other descriptive information for plants discussed in the literature review Scientific name Synonyms (selected) Part used Family Acorus calamus L. calamus, sweet flag root/rhizome Acoraceae Camellia sinensis (L.) Kuntze
green tea leaves Theaceae
Catha edulis Forsk. khat, miraa, qat leaves, twigs CelastraceaeCitrus aurantium L. bitter orange, Zhi Shi, Zhi Ke
(unripe fruit) fruit Rutaceae
Datura stramonium L. datura, Jimson weed, thorn apple
seeds, root, leaves
Solanaceae
Eleutherococcus senticosus (Rupr. & Maxim.) Maxim.
devil's shrub, eleuthero, Siberian ginseng, Acanthopanax senticosus (Rupr. & Maxim.) Maxim., Hedera senticosa Rupr. & Maxim.
root Araliaceae
Ephedra sinica Stapf E. mahuang Liu, ephedra, ma huang
aerial parts Ephedraceae
Heimia salicifolia (HBK.) Link & Otto
H. syphilitica DC., Nesaea salicifolia HBK., N. syphilitica Steud., sun opener, sinicuichi
leaves Lythraceae
Ilex paraguariensis A. St. Hil.
ilex, maté, yerba maté, Paraguay tea, St Bartolomew's tea
leaves Aquifoliaceae
Ipomoea tricolor Cav. I. violacea, morning glory, ololiuqui
seeds Convolvulaceae
Mitragyna speciosa Korth.
kratom leaves Rubiaceae
Panax ginseng Meyer Ren Shen, Asian ginseng, Chinese ginseng, Korean ginseng, Oriental ginseng, P. quinquefolius var. coreensis, P. schin‐seng T. Nees, P. schin‐seng var. coraiensis T. Nees
root Araliaceae
20
Scientific name Synonyms (selected) Part used Family Paullinia cupana var sorbilis (Mart.) Ducke
Paullinia sorbilis, guarana, Brazilian cocoa
seeds Sapindaceae
Piper methysticum Forst. f
kava, kava‐kava, kawa, kawa‐kawa, Macropiper methysticum (G. Forst.) Hook. & Arn., M. latifoliumMiq.
peeled dry rhizome
Piperaceae
Polygonum multiflorum Thunb.
he shou wu, fleeceflower root tuber Polygonaceae
Rhodiola rosea L. rhodiola, arctic root, golden root, rose root, Hong Jing Tian, Sedum rosea (L.) Scop., Sedum roseum Scop.
root and rhizome
Crassulaceae
Salvia divinorum Epling & Jativa
diviner's sage, salvia, Mexican tripping weed, ska Maria
leaves Lamiaceae
Turnera diffusa Willd. ex Schult
T. aphrodisiaca Ward, T. diffusa var aphrodisiaca (Ward) Urb, damiana
leaves Turneraceae
Acorus calamus (calamus)
In Ayurvedic medicine, A. calamus rhizome is believed to have stimulant, aphrodisiac, diuretic, antispasmodic and laxative properties, among others, and this herbal medicine has been used traditionally for the treatment of a range of diseases.31 A wide range of constituents has been reported, with α‐ and β‐asarone the main bioactive constituents. Correspondingly, various pharmacological activities have been reported in animal studies, including sedative and hypnotic effects, CNS depressant activities. A. calamus root/rhizome has been described on certain websites as having hallucinogenic effects.32
α‐ and β‐asarone have mutagenic activity and β‐asarone has genotoxicity activity;13,31 thus, only preparations free from, or with a low content of, β‐asarone should be used in humans.33
An isolated case report describes a 19‐year‐old man who presented with persistent vomiting four hours after ingesting an eight‐inch length of calamus root with water; the man had consumed the root believing it had euphoric effects.32 The patient received supportive care and his symptoms resolved over the next four hours.
Camellia sinensis (green tea, black tea)
C. sinensis is consumed extensively worldwide as a beverage. Green tea is unfermented, whereas black tea is fermented. Some products containing green tea are currently marketed to assist achieving bodyweight loss; green tea is also an ingredient in several products promoted as 'party pills' on internet websites selling herbal products as recreational substances for achieving a feeling of euphoria. The constituents of green tea include catechols (mainly epigallocatechin gallate and epicatechin gallate) and alkaloids.34
The consumption of products containing green tea extracts has recently been associated with reports of hepatotoxicity. A systematic review of published case reports and reports
21
received by the national drug surveillance systems of the USA, Canada, UK, Australia, France and Spain, identified 34 reports of hepatotoxicity associated with green tea consumption.34 Causality assessment for these reports determined a probable association with green tea consumption for seven reports and a possible association for the remainder. The adverse effects reported ranged from raised liver enzyme concentrations to acute liver failure and fulminant hepatitis requiring liver transplantation.
Catha edulis (khat)
C. edulis is used widely as a stimulant in parts of Africa (Ethiopia, Kenya, Tanzania) and Yemen, and also by migrant communities in Western countries.35 The fresh leaves and twigs of the plant are chewed, typically for several hours each day. The active constituents include the alkaloids cathine (norpseudoephedrine) and cathinone, with the latter being more potent.36
The clinical and experimental pharmacology and toxicology of khat are well documented.36,37 In addition to producing euphoria, the effect sought by users, unwanted effects of khat include: sympathomimetic activity (increases in blood pressure, heart rate, respiratory rate and body temperature); gastrointestinal effects (constipation); low birth weight babies born to women who are khat users;36 endocrine effects (enhanced release of growth hormone and corticotrophin,36 and hyperglycaemia in diabetics, and inhibition of lactation in breast‐feeding women).38 Several small studies have investigated possible associations between khat use and the occurrence of various types of cancer (e.g. oral, head and neck, oesophageal); at present there is no convincing body of evidence to support such an association, although the role of khat when taken with tobacco smoking and/or alcohol use in the development of cancer requires further examination.36
CNS and psychiatric adverse effects have also been reported in association with khat use. CNS effects include insomnia and anorexia.36,38 In a small study involving aviation workers, khat users performed more poorly than non‐users in tests assessing perceptual‐visual memory and decision speed.39 Use of khat may also impair driving ability.40 There does not appear to be evidence that khat use leads to greater than mild dependence; users typically experience a hangover effect characterised by drowsiness and dysphoria.36 Isolated reports relating to psychiatric adverse effects include cases of psychoses38,41‐45 and hypnagogic hallucinations.46
Acute and chronic adverse effects have also been described in association with the chemical pesticides used for cultivation of khat.47
Citrus aurantium (bitter orange)
C. aurantium has some history of medicinal use, particularly in Asian medical systems, to treat gastrointestinal disorders.48 Recent contemporary interest is focused on its inclusion as an ingredient in (usually multi‐ingredient) preparations promoted for assisting bodyweight loss. C. aurantium contains synephrine alkaloids, including synephrine, a sympathomimetic agent which has effects similar to those of adrenaline (epinephrine).49
There is only limited information available on the safety of bitter orange. At present, safety concerns relate mainly to the potential for cardiovascular and cerebrovascular adverse reactions because of the synephrine alkaloid content. Placebo‐controlled studies involving
22
healthy volunteers given preparations containing C. aurantium have reported conflicting results for effects on blood pressure. In one study, a single dose of bitter orange fruit extract (standardised for synephrine 27mg) had no significant effect on blood pressure or QTc interval,50 whereas a single dose of a product containing synephrine 21mg with caffeine 304mg led to an increase in post‐exercise diastolic blood pressure (but not systolic blood pressure or heart rate).51
There are case reports from the USA of myocardial infarction52 and angina53 in individuals who had ingested products containing C. aurantium together with other herbal (but not ephedra) and non‐herbal ingredients. In Canada, during a nine‐year period (1998 to 2006), over 30 reports of cardiovascular adverse reactions associated with the use of synephrine‐containing products were received by Health Canada's national drug monitoring scheme.54 At least ten of these reactions were considered serious, including one case of myocardial infarction. Case reports of cardiovascular adverse reactions associated with the ingestion of C. aurantium‐containing products also originate outside North America.55 Case reports of other adverse reactions associated with multi‐ingredient products containing bitter orange or synephrine include ischaemic colitis,56,57 reduced blood concentrations of ciclosporin in three patients who had undergone a renal transplant58 and acute tubular necrosis;59 in the latter case, another ingredient, chromium picolinate was suspected of being the cause of the adverse effect.
Datura stramonium (datura)
D. stramonium has long been known as a plant with hallucinogenic properties, due to the presence of antimuscarinic alkaloids. The seeds have the highest concentration of atropine, although atropine as well as other antimuscarinic compounds such as hyoscine and hyoscyamine are also found in the roots and leaves. Typically, users smoke the dried leaves, chew seeds or leaves, or ingest orally an aqueous infusion (a tea) prepared from plant material.60
Cases of poisoning due to ingestion of datura were first reported in the literature over 40 years ago. More recent reports include cases of accidental poisoning,61 as well as poisoning following intentional ingestion for recreational62‐68 or, less commonly, suicidal purposes.69 Adverse effects following ingestion include tachycardia, dry mouth, dilatation of the pupils often with difficulty in visual accommodation, blurred vision, hallucinations, confusion and difficulty urinating. Serious complications can occur since the lethal concentration of atropine is close to the concentration at which delirium occurs.66 Deaths have been reported.67
Eleutherococcus senticosus (Siberian ginseng)
E. senticosus has a history of traditional use in the former Soviet Union, principally as an 'adaptogen': to increase the body's resistance to stress and to build up general vitality.13
There are only limited clinical data on safety aspects of E. senticosus. The Russian literature includes several contraindications and warnings with respect to its use, although the scientific basis for such statements is not clear and some contradict recent research.13 These include the recommendation that Siberian ginseng should be avoided by healthy individuals who are aged less than forty years, that it should not be taken with stimulants, such as coffee, and that users should abstain from ingestion of alcoholic beverages during use.
23
Ephedra sinica (ephedra, ma huang)
E. sinica has a long history of use in traditional Chinese medicine for the treatment of asthma and other respiratory diseases. The effects of ephedra are due to the ephedrine alkaloid constituents, which include ephedrine and pseudoephedrine, both of which have uses in modern medicine.
Contemporary use of ephedra is as an ingredient in, typically, multi‐ingredient products promoted for achieving bodyweight loss, increasing energy, and improving athletic performance, and as an alternative to illegal drugs of abuse. The clinical pharmacology and toxicology are well‐documented for the ephedrine alkaloids ephedrine and pseudoephedrine, but less so for ephedra herb. The most common adverse effects of ephedrine and pseudoephedrine are tachycardia, anxiety, restlessness and insomnia. Tremor, dry mouth, impaired circulation to the extremities, hypertension and cardiac arrhythmias may also occur with ephedrine, and skin rashes and urinary retention have been reported for pseudoephedrine.70
Information on clinical adverse effects associated with ephedra comes from adverse drug reaction reports and small clinical studies. A review assessed 140 reports of adverse events related to the use of products containing ephedra alkaloids, usually combined with caffeine, submitted to the USA FDA between June 1997 and March 1999.71 The main reasons for use of these products were weight loss (59%) and to increase athletic performance (16%); the reason for use was unknown in 17% of cases. In total, 31% of cases (n = 43) were considered to be “definitely” or “probably” related to the use of products containing ephedra alkaloids, and a further 31% (n = 44) were judged to be “possibly” related; for 29 cases, insufficient information was available to assess causation, and 24 cases were deemed to be “unrelated” to use of these products. In several cases, individuals were thought to be ingesting up to 60mg ephedra alkaloids daily. Of the 87 cases where causality was assessed, cardiovascular symptoms (mainly hypertension, palpitations, tachycardia) were the most common adverse events (47%). The most common CNS events were stroke (n = 10) and seizures (n = 7). Where events were “definitely” or “probably” related (n = 43), clinical outcomes were death (3 cases), permanent impairment (7) and ongoing treatment (4); a full recovery occurred in 29 cases.71
A systematic review of adverse events associated with dietary supplements promoted for achieving bodyweight loss included descriptions of over 30 case reports since 2003 for which the product implicated contained ephedra; in almost all cases, the product also contained several other herbal ingredients, such as guarana [see Paullinia cupana], bitter orange [see Citrus aurantium], damiana [see Turnera diffusa] and ginseng [see Panax ginseng and Eleutherococcus senticosus].72 The cases included a wide range of adverse effects, including cardiovascular, psychiatric and gastrointestinal adverse reactions.
In a retrospective review of dietary supplement related adverse events reported to a poisons control centre for a six‐month period during 2002, multiple‐or single‐ingredient products containing ephedra were involved in 353 of the 480 (74%) reported adverse events and in 65% of the adverse events rated as 'severe' (this term appears to have been used to indicate serious reactions).73 The latter group included reports of tachycardia, changes in electroencephalographic recordings, vomiting, agitation, hypertension, seizures and myocardial infarction. Other researchers have examined 65 adverse drug reaction reports of seizures reported to the USA's Food and Drug Adminstration's MedWatch drug surveillance
24
system for the period 1993 to 1999. Ephedra was associated with 19 of the 20 cases rated as being probably related to the exposure and with 7 of the 13 rated as possibly related.74 In New Zealand, a series of five cases of adverse reactions associated with the ingestion of 'herbal ecstasy' tablets has been described. In one case, a patient experienced severe headache associated with vomiting and photophobia, beginning three hours after ingesting four pills of a product ('The Bomb', now withdrawn from the market) containing ephedrine and several herbal ingredients.75 The contents of the products involved in the four other cases are unknown.
There are also isolated reports of myocarditis,76 rhabdomyolysis,77 exacerbation of autoimmune hepatitis,78 acute hepatitis,79 nephrolithiasis,80 and psychiatric complications81 associated with the use of ephedra‐containing products. There is a report of sudden death associated with ephedrine toxicity in a 23‐year‐old man.82
A meta‐analysis of data from randomised and non‐randomised clinical trials assessing the effects of ephedra and ephedrine‐containing dietary supplements concluded that these preparations are associated with an increased risk of psychiatric, autonomic and gastrointestinal adverse events and heart palpitations.83 A placebo‐controlled study published since the meta‐analysis examined the effects of repeated doses of combinations of ephedra and guarana. Administration of doses in accordance with labelled instructions to healthy volunteers resulted in persistent increases in heart rate and blood pressure, and negatively affected glucose and potassium homeostasis.84 Changes in cardiovascular parameters can also occur following a single dose of a combination product containing both ephedra and guarana.85
Heimia salicifolia (sun opener)
H. salicifolia leaves have been used for ritualistic and medical purposes by indigenous groups in Central and South America. Ingestion of a tea ('sinicuichi tea'), prepared from the leaves by fermenting with water, yeast and sugar, is reputed to produce exhilaration, altered awareness, muscle relaxation, bradycardia and visual stimulation,86 although supporting scientific evidence is lacking.87 The leaves contain a number of biphenylquinolizidine lactones, which have certain antispasmodic and anti‐inflammatory activities.87
A case report describes a 26‐year‐old man who experienced muscle pain in the extremities, raised temperature, nausea, vomiting and headache after ingesting an unknown quantity of sinicuichi tea. Constituents of H. salicifolia leaf were detected in the patient's serum, confirming ingestion. He received supportive treatment and recovered fully within 24 hours.86
Ilex paraguariensis (maté)
I. paraguariensis has a long history of traditional use among indigenous people in South America, and is consumed widely in that region today as a beverage for its stimulant properties.88 Maté is becoming known outside South America, including in Europe and the USA. The dried leaves of the plant are ingested as an infusion (tea). Maté contains xanthine alkaloids, including caffeine, which is present in the highest concentrations and to which the reputed stimulant properties of maté are attributed.
25
Several epidemiological studies report an association between maté consumption and an increased risk of developing certain types of cancer, including oesophageal,89,90 other head and neck,91,92 upper respiratory tract,93 lung,94 bladder and renal,95‐98 although the role of other factors, such as smoking tobacco and alcohol consumption, is not clear.88 The high concentrations of polycyclic aromatic hydrocarbons found in maté may contribute to any carcinogenic effect.99
An isolated report describes a case of neonatal withdrawal syndrome in a five weeks' premature baby whose mother drank approximately one litre of maté regularly during pregnancy.100
Adverse effects due to poor‐quality preparations of maté have also been described. Several cases of anticholinergic poisoning were reported following consumption of a product labelled as containing maté but which was subsequently found to contain belladonna alkaloids but not caffeine.101 Contamination of maté products with pathogenic Aspergillus species has also been reported.102
Ipomoea tricolor (morning glory)
Morning glory is the common name given to many plant species, including I. tricolor, Rivea corymbosa and Argyreia nervosa. The seeds of these species are known for their hallucinogenic potential due to their content of ergot alkaloids, such as D‐lysergic acid amide (ergine) which has effects similar to those of lysergic acid diethylamide (LSD). No specific reports of adverse effects associated with these plant species were identified, but adverse effects known for ergot alkaloids are relevant.
Mitragyna speciosa (kratom)
M. speciosa has a history of traditional use as both a stimulant and sedative and,103 in Thailand, it has been used as a morphine replacement for the treatment of addicts.104 Internet websites exist that describe M. speciosa as an intoxicant and opiate substitute, and members of one website describe self‐treatment with kratom to aid withdrawal from opioid analgesic agents.105 Typically, users chew the fresh, or ground, dried leaves. Mitragynine is the main alkaloid found in the leaves,106 and has been described as a partial opioid agonist.103
There is a lack of research examining the safety profile of kratom. An isolated case report describes a suspected interaction with modafinil and withdrawal symptoms following cessation of kratom treatment. A 43‐year‐old man self‐treated with kratom (ingested as a tea) to manage opioid (hydromorphone) withdrawal and chronic pain, and continued use long term as an opioid replacement. This period of use appeared to be free from adverse effects, but twenty minutes after co‐administering kratom and modafinil 100mg on a single occasion, the man experienced a generalised tonic‐clonic seizure lasting five minutes.107 Examinations were unremarkable, screening did not identify ingestion of any drugs of abuse, or adulterants or contaminants, and the plant material was confirmed as kratom using high‐performance liquid chromatography. The man made a full recovery and after discharge stopped treatment with kratom abruptly, following which he experienced moderate withdrawal symptoms lasting around ten days.107 An opioid abstinence syndrome, characterised by irritability, rhinorrhoea, myalgia, arthralgia and diarrhoea, has been
26
described previously by Suwanlert108 cited by Babu et al.103 Tolerance and withdrawal symptoms induced by 7‐hydroxymitragynine, an opioid alkaloid found in M. speciosa, occurred in experimental studies using mice.109
Some limited information on possible adverse effects of kratom comes from a study in Thailand that examined kratom use among a purposive sample of 149 long‐term (daily for five years or more) and 168 occasional (used socially or medicinally less than once per week) users. Self‐reported dependence on kratom was described by 12 and 61% of occasional and regular users, respectively;110 reasons underpinning the belief of dependence included an inability to cease use, the need for daily use in order to function normally and physical pains and craving for kratom when not using it. Overall, 17% of users believed they had experienced constipation from using kratom, and 32% reported having felt intoxicated at some time during use. 'Negative' effects of kratom use were reported by up to 23% of users, most commonly poor appetite (23%), lower productivity, decreased sexual drive (14% for each), tiredness (13%), and poor health (11%).
Panax ginseng (ginseng)
P. ginseng has a long history of traditional use in Chinese medicine, including use as a stimulant.
There are only limited clinical data available on safety aspects of P. ginseng.13 Several case reports are described in the literature, although for many of the cases there were other factors, such as concurrent medications and cessation of treatment effects, that could explain the observed effects.111 Literature reports include several cases of mania.112‐114 Causality in these cases has not been established.
Paullinia cupana (guarana)
P. cupana seeds are regarded as a source of health and energy by indigenous peoples in the Amazon region and have a long history of traditional use as a stimulant.115 Contemporary use of guarana includes its inclusion as an ingredient in some carbonated soft 'energy' drinks, and in dietary supplements promoted as assisting bodyweight loss. The stimulant properties are usually attributed to caffeine, which is present in high concentrations in dried seeds. While preliminary controlled studies involving healthy volunteers have reported improvements in cognitive performance and reductions in mental fatigue following administration of guarana extract,116‐118 the results of two of these studies suggested that constituents other than caffeine may at least contribute to the observed effects.116,117
At present, most information on safety issues with guarana relates to reports of adverse effects associated with multi‐ingredient products containing guarana and other herbal and/or non‐herbal ingredients. (Information concerning products containing both guarana and ma huang is discussed under Ephedra sinica above). Reports of cardiovascular adverse reactions include a case of sudden death following ventricular fibrillation in a 25‐year‐old woman who had that day ingested a 55mL bottle of an energy drink containing guarana and ginseng [no further details provided] with a caffeine concentration of 10g/litre, more than 50 times the concentration in caffeine‐containing beverages.119 The woman had a caffeine concentration of 19 mg/L in aortic blood (toxicity usually results with serum concentrations greater than 25 mg/L; toxicological screening excluded the ingestion of other substances.
27
Another report describes severe heart palpitations in a 51‐year‐old woman four or more weeks after she began taking two to four tablets daily of two products, both of which were labelled as containing guarana (200mg and 1000mg; one product also contained kola nut 500mg, which also contains caffeine) and numerous other herbal and non‐herbal ingredients.120 The palpitations ceased 7 to 10 days after the woman stopped taking these products. Other case reports of adverse effects associated with multi‐ingredient products containing guarana include new‐onset seizures,121,122 rhabdomyolysis,123 myoglobinuria,124 acute renal failure,125 and cerebral infarction.126 In most cases, the products consumed were not being used for psychoactive effects.
In a clinical toxicology study involving 48 healthy volunteers who received a product containing extracts of guarana and three other herbal ingredients twice daily for 28 days, no serious adverse reactions were recorded, and haematological and biochemical tests and medical examinations were normal. Non‐serious adverse reactions recorded included changes in colour of faeces, stomach ache, insomnia, headache, sleepiness, vomiting and diarrhoea.127 Preclinical toxicology studies have produced mixed results on the toxicity of guarana. Studies using rats have indicated a lack of toxicity in tests assessing mortality and bodyweight, and following histopathological examinations,128 whereas in vitro assays assessing cytotoxic effects of aqueous guarana extracts on Chinese hamster ovary cells and bacterial cells indicated that the concentration of guarana was critical for its cytotoxic activity, raising the question whether prolonged use or use of high doses of guarana extract could cause adverse effects in humans.129
Piper methysticum (kava)
P. methysticum has a long history of traditional medical use in many parts of the South Pacific for a wide range of conditions.13 It is also used in those regions as an intoxicant drink, on either informal or ceremonial occasions, when the rhizome is masticated and ingested as a water extract. Kava has become a popular herbal medicine in western countries for the treatment of anxiety and nervous disorders, and it is included as an ingredient in some preparations used recreationally. There is evidence that the kavalactone constituents are responsible for the pharmacological effects of kava.
While clinical trials assessing the effects of kava preparations have not identified any specific safety concerns, spontaneous reports of hepatotoxicity associated with the use of kava have arisen since the year 2000. By February 2005, 79 cases of hepatotoxicity had been reported worldwide.130 The adverse reactions described in these reports ranged from abnormal liver function test values to irreversible liver failure and death; at least six people received liver transplants, one of whom, as well as at least two other individuals, subsequently died.13 Several countries (UK, Australia, Canada) took regulatory action on the basis of the available information. A subsequent UK review found insufficient new evidence to change the regulatory position;131 kava remains prohibited in unlicensed medicines in the UK. Other reviews have reported conflicting opinions on causality with respect to kava and hepatotoxicity.132,133 Until 2003, it was thought that hepatotoxicity associated with ingestion of kava occurred only with acetonic and ethanolic extracts. However, recent reports have described hepatotoxic effects associated with consumption of traditional aqueous extracts of kava.134,135
Several other adverse reactions have been documented for kava preparations. 'Kava dermopathy' is an ichthyosiform (scaly, non‐inflammatory) skin condition, usually associated
28
with the ingestion of kava prepared according to the traditional method, which has been reported in Polynesia, Micronesia and Melanesia.136 The condition is reversible on cessation of use of kava. Cases of allergic skin reactions associated with kava use have also been reported.137‐140 Reports of CNS adverse effects include involuntary movements and dyskinesia.141,142 Other isolated case reports include dermatomyositis143 and disturbances in visual function.144
Inhibition of certain cytochrome P450 drug metabolising enzymes by kava extracts and individual kavalactones has been shown in vitro and in healthy volunteers. The clinical relevance of these findings is not known, although the potential for kava preparations to interact with concurrently administered drugs metabolised mainly by certain CYP enzymes, including CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4, should be considered.13
Polygonum multiflorum (He Shou Wu)
P. multiflorum is stated as an ingredient of the 'Floradrene' blend of herbal substances, found in several marketed recreational products, including several of the new 'BZP‐free' products that have emerged on the New Zealand market over the last year or so. The reason for the inclusion of this ingredient is not clear; P. multiflorum root tuber is used in traditional Chinese medicine as a tonic and anti‐aging remedy, including for premature greying of hair and hair loss.
Hepatitis associated with P. multiflorum root tuber was first reported in the literature as early as 1996;145 several other cases of hepatotoxic reactions, including acute hepatitis,146‐148 have since been described, although none in association with recreational use. Spontaneous reports of suspected adverse effects on the liver (jaundice and/or hepatitis) have also been received by the UK Medicines and Healthcare Products Regulatory Agency (MHRA).149
Rhodiola rosea (rhodiola)
R. rosea has a long history of traditional use in several medical systems, including Russia and Ukraine; in particular, it is reputed to have been used as a 'brain tonic', to eliminate fatigue and to have stimulant properties.13 Herbal products containing rhodiola are readily available from several sources, including the internet, and such products are often promoted as being beneficial in supporting mental and physical performance, among other uses. Although the chemistry of rhodiola is well‐documented, the precise constituents responsible for the pharmacological effects are not fully understood.
There is a lack of reliable, accessible information relating to the safety and toxicity of preparations of rhodiola: most information is published in Russian. Data from clinical trials are limited. In studies involving small numbers of young (< 35 years) healthy volunteers150,151 and older participants with physical and cognitive deficiencies,152 no adverse events occurred.
Salvia divinorum (salvia)
S. divinorum has a history of use for medical and spiritual purposes by the Mazatec Indians in Mexico and is becoming known beyond this ethnobotanical use as an hallucinogenic
29
agent.153,154 Typically, users smoke the leaves, or a leaf extract, of S. divinorum using a bong or pipe, although traditional use has also involved mastication and swallowing of the leaves, and drinking extracted leaf juice.154 There is limited information on the chemistry of S. divinorum, although an active constituent is stated to be salvinorin A, a neoclerodane diterpene with selective opioid agonist properties.
Hallucinogenic effects of S. divinorum occur rapidly after administration (within seconds following inhalation) and last around 15 minutes following inhalation154 and one to two hours following oral administration,103 although others have reported even shorter time frames;8,155 personal accounts also indicate variations between users in the intensity of the effects experienced.8,156
There is very limited information on the safety and toxicity of S. divinorum. Adverse effects reported by users of S. divinorum include short‐term (less than 24 hours) unpleasant 'hangover' effects, typically physical and mental tiredness.8,155 An isolated case report describes a 15‐year‐old man with a history of smoking S. divinorum and marijuana who presented with paranoia, déjà vu and other acute changes in mental status.157 The man was hospitalised following which his symptoms, apart from feelings of déjà vu, improved.
There are currently no published reports of tolerance or withdrawal in association with use of S. divinorum or salvinorin A.103
Turnera diffusa (damiana)
T. diffusa has a wide range of uses, including as an aphrodisiac, in many traditional medical systems.158 Smoking, or ingestion of an infusion of, the leaves has been claimed to produce euphoria, although supporting evidence is lacking.159 There is only limited information available on the chemistry of T. diffusa, although the leaves are known to contain cyanogenetic glycosides, including tetraphyllin B.13,160
The presence of cyanogenetic glycosides in T. diffusa raises concerns over possible toxicity. (Metabolism of cyanogenetic glycosides leads to hydrogen cyanide release, which can cause cyanide poisoning). Tetanus‐like convulsions and paroxysms resulting in symptoms similar to those of rabies or strychnine poisoning have been described in an individual who ingested around 200g of T. diffusa extract.161
3.4.2.3 World Health Organization Uppsala Monitoring Centre data
In addition to the information from published literature, Table 3 summarises numbers of spontaneous reports of suspected adverse drug reactions identified in the WHO‐UMC Vigisearch database for single‐ingredient preparations of the plants listed in Table 1. No such reports were identified for plants not included in Table 3. Inclusion of a particular plant in Table 3 does not imply causality with the adverse effects described. A further 12 spontaneous reports describing 28 ADR terms were identified in the WHO‐UMC database for multi‐ingredient preparations containing two or more of the plants listed in Table 1. Each of these multi‐ingredient preparations contained C. aurantium and/or P. cupana in addition to other herbal substances.
30
(Caveat statement: The information shown is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction. The information does not represent the opinion of the World Health Organization).
Table 3: Numbers of spontaneous reports of suspected adverse drug reactions associated with single‐ingredient preparations of herbal substances of interest held in the Vigisearch database of the World Health Organisation Uppsala Monitoring Centre (WHO‐UMC) for the period up to March 30, 2009.a
Ao Cs Ca† Ds Ese‡
Esi††
Ip Pg‡‡ Pc P me
Rg Rr Td
Total n reports 7 22 2 6 10 0 1 39 (28)
23 94 1 13 1
Total n ADR terms 15 36 2 14 26 ‐ 2 103 (44)
48 195 1 26 2
n reports (n ADR terms) from NZ
0 0 0 0 0 ‐ 0 0 2 (3)
2 (5)
0 0 0
System organ class Blood & lymphatic system disorders
1 1
Cardiac disorders 1 3 4 (1)
7 4 2
Ear & labyrinth disorders 1 (5)
Eye disorders
1 1 2 3 6 1
Gastrointestinal disorders 6 2 3 15 (3)
7 20 5
General disorders, administration site conditions
2 6 1 13 (3)
7 14 1
Hepatobiliary disorders
14 2 2 40
Immune system disorders 3 2 (1)
6 1
Infections & infestations 1 (1)
1
Injury poisoning & procedural complications
2 2 1 1
Investigations 1 14 (2)
2 19 5
Metabolism & nutrition disorders
1 1 4
Musculoskeletal & connective tissue disorders
1 (3)
2 1 1
Neoplasms benign, malignant & unspecified
(1)
Nervous system disorders 1 1 5 1 17 (1)
6 15 3 1
Psychiatric disorders 2 7 11 1 10 (16)
8 12 5
Renal & urinary disorders
1
Reproductive system & breast disorders
2 1
Respiratory, thoracic and mediastinal disorders
1 1 2 7 1 7
Skin and subcutaneous tissue disorders 1 1 2 2 7 (2)
3 42 2
Social circumstances
1 1
Vascular disorders 2 2 1 2 (5)
1 1
ADR = adverse drug reaction; Ao = Althaea officinalis; Cs = Camellia sinensis; Ca = Citrus aurantium; Ds = Datura stramonium; Ese = Eleutherococcus senticosus; Esi = Ephedra sinica; Ip = Ilex paraguariensis; Pg = Panax ginseng; Pc = Paullinia cupana; Pme = Piper methysticum; Rg = Rosa gallica; Rr = Rhodiola rosea; Td = Turnera diffusa † Both reports relate to Citrus aurantium ssp. bergamia; ‡ E. senticosus and E. senticosus root dry extract; †† The database contains 28 reports listing 164 ADR terms for unspecified Ephedra species; ‡‡ Numbers in brackets relate to products containing P. ginseng and vitamins/minerals a Caveat statement: The information shown is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse reaction. The information does not represent the opinion of the World Health Organization.
31
3.5 Discussion and Conclusions
Most of the herbal substances discussed in this review are listed as ingredients of so‐called 'BZP‐free' products that have emerged on the New Zealand market. In some cases, their reason for inclusion as an ingredient of such products is not clear since they have no history of traditional use for psychoactive effects nor any scientific evidence of such effects.
With the exception of S. divinorum, at present, information is lacking on the extent of use of herbal substances for recreational purposes. Several studies have found the prevalence of use of S. divinorum to be between 5 and 10% of their respondents, with self‐reported marijuana use being the strongest predictor of S. divinorum use. None of these studies had explored use of S. divinorum and other recreational herbal substances in New Zealand, and research examining prevalence, reasons for use, sources of herbal recreational substances and impact of use on use of other substances is warranted. (Several of these questions have been addressed in the study described in the remainder of this report).
Adverse effects associated with herbal substances used recreationally have been reported in the literature in association with both medicinal and recreational use of these substances. However, for most, if not all, of the herbal substances of interest, there is a lack of research on their safety profile, including adverse effects following intermittent and long‐term use, interactions with other recreational substances when used concurrently, effects of withdrawal, addictive potential and relevant characteristics, such as pharmacokinetics of their constituents.
Much of the information available comes from published case reports and reviews of such reports, whereas few pharmacoepidemiological studies have been conducted. Good‐quality published case reports can be extremely useful in raising hypotheses about safety concerns, but usually isolated case reports are not sufficient to be certain that a particular substance is responsible for a particular adverse effect; i.e. typically, it is not possible to establish a causal relationship. Furthermore, the quality of case reports for herbal products is often poor: information on the product ingredients and even the actual product taken is frequently lacking. Even where this information is provided, without pharmaceutical analysis of unauthorised products it is not possible to be certain of their ingredients. Guidelines aimed at improving the quality of reporting of case reports of suspected adverse effects associated with herbal substances have been published and their use should be encouraged.162,163
The WHO‐UMC database holds small numbers of spontaneous reports of suspected adverse drug reactions associated with several of the herbal substances of interest. In some cases, these reports reflect safety concerns described in the literature, e.g. hepatotoxic reactions associated with P. methysticum (kava) and green tea (C. sinensis). Few of the reports originate from New Zealand, and it is not known whether or not these represent all the reports for New Zealand. (For comparison, data have been requested from the New Zealand Centre for Adverse Reactions Monitoring but, at the time of writing, have not yet been received). Under‐reporting of suspected adverse drug reactions is a well‐known problem and, for many reasons, it is likely to be substantially greater for herbal substances used recreationally.
32
3.6 References
1. Richardson WH et al. Herbal drugs of abuse: an emerging problem. Emerg Med Clin N Am 2007;25:435‐457
2. Hoover V et al. Internet access to Salvia divinorum: implications for policy, prevention and treatment. J Subst Abuse Treat 2008;35:22‐27
3. Dennehy CE et al. Evaluation of herbal dietary supplements marketed on the internet for recreational use. Ann Pharmacotherapy 2005;39:1634‐1639
4. Nicholson TC. Prevalance of use, epidemiology and toxicity of 'herbal party pills' among those presenting to the emergency department. Emergency Medicine Australia 2006;18:180‐184
5. Pavarin RM. Substance use and related problems: a study on the abuse of recreational and not recreational drugs in Northern Italy. Ann Ist Super Sanita 2006;42(4):477‐484
6. Lange JE et al. College student use of Salvia divinorum. Drug Alcohol Dependence 2008;94:263‐266
7. Griffin OH et al. Legally high? Legal considerations of Salvia divinorum. J Psychoactive Drugs 2008;40(2):183‐191
8. Gonzalez D et al. Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug Alcohol Dependence 2006;85:157‐162
9. Blanck HM et al. Use of non‐prescription dietary supplements for weight loss is common among Americans. J Am Diet Assoc 2007;107:441‐447
10. Wilson KM et al. Use of complementary medicine and dietary supplements among US adolescents. J Adolescent Health 2006;38:385‐394
11. Klontz KC et al. Consumption of dietary supplements containing Citrus aurantium (bitter orange) ‐ 2004 California behavioural Risk Factor Surveillance Study (BRFSS). Ann Pharmacotherapy 2006;40:1747‐1751
12. O'Dea JA. Consumption of nutritional supplements among adolescents: usage and perceived benefits. Health Education Res 2003;18(1):98‐107
13. Barnes J, Anderson LA, Phillipson JD. Herbal medicines (3rd edition). London: Pharmaceutical Press, 2007
14. Harkey MR et al. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nutr 2001;73:1101‐1106
15. Woolwich WR et al. Analysis of the psychoactive terpenoid salvinorin A content in five Salvia divinorum herbal products. Pharmacotherapy 2006;26(9):1268‐1272
16. Busse W. The significance of quality for efficacy and safety of herbal medicinal products. Drug Inf J 2000;34: 15‐23
17. De Smet PAGM. Health risks of herbal remedies: An update. Clinical Pharmacology Therapeutics 2004;76(1): 1‐17
18. De Smet PAGM, Hänsel R, Keller K, et al., editors. Toxicological outlook on quality assurance of herbal remedies. In: Adverse effects of herbal drugs. Vol 1. Berlin: Springer Verlag, 1992
19. European Medicines Agency (EMEA). Herbal Medicinal Products Working Party. Position paper on the risks associated with the use of herbal products containing Aristolochia species. EMEA website: www.eudra.org/emea.html. October 2001.
20. Biessels GJ et al. Epileptic seizure after a cup of tea: intoxication with Japanese star anise. Ned Tijdschr Geneeskd 2002;146: 808 –811
21. Diego Ize‐Ludlow MD et al. Neurotoxicities in infants seen with consumption of star anise tea. Pediatrics 2004;114 ( 5): e653‐e656.
22. Pharmacopoeia of the People’s Republic of China (English edition, 2000). Chemical Industry Press, 2005.
23. Huang WF et al. Adulteration by synthetic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol 1997;37: 344–350.
24. Koh H‐L, Woo S‐O. Chinese Proprietary Medicine in Singapore: Regulatory control of toxic heavy metals and undeclared drugs. Drug Safety 2000;23: 351–362.
33
25. Saper RB et al. Heavy metal content of Ayurvedic herbal medicine products. JAMA 2004;292: 2868‐2873.
26. Lau KK et al. Phenytoin poisoning after using Chinese proprietary medicines. Hum Exp Toxicol 2000;19: 385–386.
27. Anon. Hypoglycaemia following the use of Chinese herbal medicine Xiaoke Wan. Curr Probl Pharmacovigilance 2001;27: 8.
28. Anon. Reminder: Safety of Traditional Chinese Medicines and herbal remedies. Current Problems 2004;30:10.
29. Wu M‐S. Multiple tubular dysfunction induced by mixed Chinese herbal medicines containing cadmium. Nephrol Dialysis Transplant 1996;11: 867–870
30. Kew J et al. Arsenic and mercury intoxication due to Indian ethnic remedies. Br Med J 1993;306: 506–507.
31. Mukherjee PK et al. Acorus calamus: scientific validation of Ayurvedic tradition from natural resources. Pharmaceutical Biology 2007;45(8):651‐666
32. Vargas CP et al. Getting to the root (Acorus calamus) of the problem. Clinical Toxicology 1998;36(3):259‐260
33. Göggelmann W, Schimmer O. Mutagenicity testing of β‐asarone and commercial calamus drugs with Salmonella typhimurium. Mutat Res 1983;121:191‐194
34. Sharma D et al. Safety of green tea extracts. A systematic review by the US Pharmacopoeia. Drug Safety 2008;31(6):469‐484
35. Beckerleg S. Khat special edition. Substance Use Misuse 2008;43:749‐761 36. Graziani M et al. Khat chewing from the pharmacological point of view: an update.
Substance Use Misuse 2008;43:762‐783 37. Kalix P. The pharmacology of psychoactive alkaloids from Ephedra and Catha. J
Ethnopharmacol 1991;32:201‐208 38. Pantelis C et al. Use and abuse of khat (Catha edulis): a review of the distribution,
pharmacology, side effects and a description of psychosis attributed to khat chewing. Psychological Med 1989;19:657‐668
39. Khattab NY, Amer G. Undetected neuropsychophysiological sequelae of khat chewing in standard aviation medical examination. Aviation Space Environmental Med 1995;66(8):739‐744
40. Toennes SW, Kauert GF. Driving under the influence of khat ‐ alkaloid concentrations and observations in forensic cases. Forensic Sci Int 2004;140(1):85‐90
41. Critchlow S, Seifert R. Khat‐induced paranoid psychosis. Br J Psychiatry 1987;150:247‐249 42. Jager AD, Sireling L. Natural history of khat psychosis. Aus NZ J Psychiatry 1994;28(2):331‐
332 43. Maitai CK, Dhadphale M. Khat‐induced paranoid psychosis. Br J Psychiatry 1988;152:294 44. McLaren P. Khat psychosis. Br J Psychiatry 1987;150:712‐713 45. Giannini AJ, Castellani S. A manic‐like psychosis due to khat (Catha edulis Forsk.). J Toxicol
Clin Toxicol 1982;19(5):455‐459 46. Granek M et al. Khat‐induced hypnagogic hallucinations. Acta Psychiatr Scand
1988;78(4):458‐461 47. Date J et al. Qat chewing and pesticides: a study of adverse health effects in people of the
mountainous areas of Yemen. Int J Environ Health Res 2004;14(6):405‐414 48. Fugh‐Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed
for weight loss: current status of clinical and basic research. Exp Biol Med 2004;229:698‐704 49. Haaz S et al. Citrus aurantium and synephrine alkaloids in the treatment of overweight and
obesity: an update. Obesity Rev 2006;7:79‐88 50. Min B et al. Absence of QTc‐interval‐prolonging or hemodynamic effects of a single dose of
bitter‐orange extract in healthy subjects. Pharmacotherapy 2005;25(12):1719‐1724 51. Haller CA et al. Human pharmacology of a performance‐enhancing dietary supplement under
resting and exercise conditions. Br J Clin Pharmacol 2008;65(6):833‐840
34
52. Nykamp DL et al. Possible association of acute lateral‐wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38:812‐816
53. Gange CA et al. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin Proc 2006;81(4):545‐548
54. Jack S et al. Bitter orange or synephrine: update on cardiovascular adverse reactions. Can Med Ass J 2007;176(8):1230‐1235
55. Firenzuoli F et al. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12:247‐248
56. Sultan S et al. Ischemic colitis associated with use of a bitter orange‐containing dietary weight‐loss supplement. Mayo Clin Proc 2006;81(12):1630‐1631
57. Ryan CK et al. Ischaemic colitis associated with herbal product use in a young woman. J Am Board Fam Pract 2002;15:309‐312
58. Nowack R, Nowak B. Herbal teas interfere with cyclosporine levels in renal transplant patients. Nephrol Dial Transplant 2005;20:2554‐2556
59. Wani S et al. Acute tubular necrosis associated with chromium picolinate‐containing dietary supplement. Ann Pharmacother 2006;40:563‐566
60. Wills S. Drugs of abuse. London: Pharmaceutical Press, 1997 61. Matsuda K et al. [Toxicological analysis of a case of Datura stramonium poisoning]. Jap J Clin
Pathol 2006;54(10):1003‐1007 62. De Germond‐Burquier V et al. [Intentional datura stramonium intoxication and
circumstances of use in two adolescents]. Presse Medicale 2008;37(6):982‐985 63. Dewitt MS et al. The dangers of jimson weed and its abuse by teenagers in the Kanawha
valley of West Virginia. West Virginia Medical Journal 1997;93(4):182‐185 64. Amlo H et al. [Physostigmine. Antidotal effect in anticholinergic intoxications caused by
Datura stramonium abuse]. Tidsskrift for den Norske Laegeforening 1997;117(18)2610‐2612 65. Spina SP, Taddei A. Teenagers with Jimson weed (Datura stramonium) poisoning. Can J Emer
Med Care 2007;9(6):467‐468 66. Marc B et al. [Acute Datura stramonium poisoning in an emergency department]. Presse
Medicale 2007;36(10):1399‐1403 67. Boumba VA et al. Fatal poisoning from ingestion of Datura stramonium seeds. Vet Hum
Toxicol 2004;46(2):81‐82 68. Arouko H et al. [Voluntary poisoning by ingestion of Datura stramonium. Another cause of
hospitalization in youth seeking strong sensations]. Ann Med Interne 2003;154(1):S46‐S50 69. Ruhwald M. [A case of poisoning with jimsonweed and alcohol, taken with suicidal intent].
Ugeskrift for Laeger 2005;167(19):2064‐2065 70. Sweetman SC (ed). Martindale. The Complete Drug Reference (36th edition). London:
Pharmaceutical Press, 2009 71. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events
associated with dietary supplements containing ephedra alkaloids. New Eng J Med 2000;343:1833‐1838
72. Pittler MH et al. Adverse events of herbal food supplements for body weight reduction: systematic review. Obesity Reviews 2005;6:93‐111
73. Dennehy CE et al. Dietary supplement‐related adverse events reported to the California Poison Control System. Am J Health‐Syst Pharm 2005;62:1476‐1482
74. Haller CA et al. Seizures reported in association with use of dietary supplements. Clinical Toxicology 2005;1:23‐30
75. Yates KM et al. "Herbal ecstasy": a case series of adverse reactions. New Zealand Medical Journal 2000;113:315‐317
76. Zaacks SM, Klein L, Tan CD, Rodriguez ER, Leikin JB. Hypersensitivity myocarditis associated with ephedra use. J Toxicol Clin Toxicol 1999;37:485‐489
77. Scroggie DA et al. Rhabdomyolysis associated with nutritional supplement use. J Clin Rheumatol 2000;6(6):328‐332
35
78. Borum ML. Fulminant exacerbation of autoimmune hepatitis after the use of Ma Huang. Am J Gastroenterol 2001;96(5):1654‐1655
79. Nadir A, Agrawal S, King PD, Marshall JB. Acute hepatitis associated with the use of a Chinese herbal product, ma‐huang. Am J Gastroenterol 1996;91(7):1436‐1438
80. Powell T, Hsu FF, Turk J, Hruska K. Ma‐Huang strikes again: ephedrine nephrolithiasis. Am J Kid Diseases 1998;32(1):153‐159
81. Jacobs KM, Hirsch KA. Psychiatric complications of Ma‐huang. Psychosomatics 2000;41(1):58‐62
82. Theoharides TC. Sudden death of a healthy college student related to ephedrine toxicity from a ma huang‐containing drink. J Clin Psychopharmacol 1997;17(5):437‐9
83. Shekelle PG et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance. JAMA 2003;289:1537‐1545
84. Haller CA et al. Short‐term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol Ther 2005;77:560‐571
85. Haller CA et al. Pharmacology of ephedra alkaloids and caffeine after single‐dose dietary supplement use. Clin Pharmacol Ther 2002;71:421‐432
86. Kempf J et al. Identification of sinicuichi alkaloids in human serum after intoxication caused by oral intake of a Heimia salicifolia extract. Forensic Science International 2008;179:e57‐e61
87. Malone MH, Rother A. Heimia salicifolia: a phytochemical and phytopharmacologic review. J Ethnopharmacol 1994;42(3):135‐159
88. Heck CI, De Mejia EG. Yerba mate tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci 2007;72(9):R138‐R151
89. Vassallo A et al. Esophageal cancer in Uruguary: a case‐control study. J Nat Cancer Institute 1985;75(6):1005‐1009
90. Sewram V et al. Maté consumption and the risk of squamous cell esophageal cancer in Uruguay. Cancer Epidemiol Biomarkers Prevention 2003;12:508‐513
91. Goldenberg D et al. The beverage mate: a risk factor for cancer of the head and neck. Head Neck 2003;25:595‐601
92. Goldenberg D et al. Habitual risk factors for head and neck cancer. Otolaryngol Head Neck Surg 2004;131:986‐993
93. Pintos J et al. Maté, coffee, and tea consumption and risk of cancers of the upper aerodigestive tract in Southern Brazil. Epidemiology 1994;5:583‐590
94. De Stefani E et al. Mate drinking and risk of lung cancer in males: a case‐control study from Uruguay. Cancer Epidemiol Biomarkers Prevention 1996;5:515‐519
95. De Stefani E et al. Meat intake, 'mate' drinking and renal cell cancer in Uruguay: a case‐control study. Br J Cancer 1998;78(9):1239‐1243
96. De Stefani E et al. Non‐alcoholic beverages and risk of bladder cancer in Uruguay. BMC Cancer 2007;7:57 doi:10.1186/1471‐2407‐7‐57
97. De Stefani E et al. Black tobacco, maté, and bladder cancer. A case‐control study from Uruguay. Cancer 1991;67:536‐540
98. Bates MN et al. Bladder cancer and mate consumption in Argentina: a case‐control study. Cancer Lett 2007;246:268‐273
99. Kamangar F et al. High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks. Cancer Epidemiol Biomarkers Prevention 2008;17(5):1262‐1268
100. Martin I et al. Neonatal withdrawal syndrome after chronic maternal drinking of mate. Ther Drug Monit 2007;29:127‐129
101. Hsu CK et al. Anticholinergic poisoning associated with herbal tea. Arch Intern Med 1995;155:2245‐2248
102. Di Pentima MC et al. Are your patients at risk? Fungal contamination of Ilex paraguariensis St. Hil (yerba maté). Transpl Infect Dis 2005;7:47‐48
36
103. Babu KM et al. Opioid receptors and legal highs: Salvia divinorum and Kratom. Clinical Toxicology 2008;46:146‐152
104. Jansen KLR, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacology 1988;23:115‐119 [letter]
105. Boyer EW et al. Self‐treatment of opioid withdrawal with a dietary supplement, kratom. Am J Addictions 2007;16:352‐356
106. Shellard EJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacology 1989;25:123‐124 [letter]
107. Boyer EW et al. Self‐treatment of opioid withdrawal using kratom (Mitragynia [sic] speciosa korth). Addiction 2008;103:1048‐1050
108. Suwanlert S. A study of kratom eaters in Thailand. Bull Narc 1975;27(3):21‐27 109. Matsumoto K et al. Antinociception, tolerance and withdrawal symptoms induced by 7‐
hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sci 2005;78:2‐7
110. Assanangkornchai S et al. The use of Mitragynine [sic] speciosa ("Krathom"), an addictive plant, in Thailand. Substance Use Misuse 2006;42:2145‐2157
111. Coon JT, Ernst E. Panax ginseng. A systematic review of adverse effects and drug interactions. Drug Safety 2002;25(5):323‐344
112. Gonzalez‐Seijo JC, Ramos YM, Lastra I. Manic episode and ginseng: report of a possible case. J Clin Psychopharmacol 1995;15:447‐8
113. Engelberg D, McCutcheon A, Wiseman S. A case of ginseng‐induced mania. J Clin Psychopharmacol 2001;21(5):535‐537
114. Vazquez I, Aguera‐Ortiz LF. Herbal products and serious side effects: a case of ginseng‐induced manic episode. Acta Psychiatr Scand 2002;105:76‐78
115. Henman AR. Guarana (Paullinia cupana var sorbilis): ecological and social perspectives on an economic plant of the Central Amazon Basin. J Ethnopharmacol 1982;6:311‐338
116. Kennedy DO et al. Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng. Pharmacol Biochem Behav 2004;79:401‐411
117. Haskell CF et al. A double‐blind, placebo‐controlled, multi‐dose evaluation of the acute behavioural effects of guarana in humans. J Psychopharmacol 2007;21(1):65‐70
118. Kennedy DO et al. Improved cognitive performance and mental fatigue following a multi‐vitamin and mineral supplement with added guarana (Paullinia cupana). Appetite 2008;50:506‐513
119. Cannon ME et al. Caffeine‐induced cardiac arrhythmia: an unrecognised danger of healthfood products. Med J Aust 2001;174:520‐524
120. Baghkhani L, Jafari M. Cardiovascular adverse reactions associated with guarana: is there a causal effect? J Herb Pharmacotherapy 2002;2(1):57‐61
121. Iyadurai SJP, Chung SS. New‐onset seizures in adults: possible association with consumption of popular energy drinks. Epilepsy Behavior 2007;10:504‐508
122. Kockler DR et al. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21(5):647‐651
123. Mansi IA, Huang J. Rhabdomyolysis in response to weight‐loss herbal medicine. Am J Med Sci 2004;327(6):356‐357
124. Donadio V et al. Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava. Neurol Sci 2000;21:124
125. Katalin V et al. Növényi kivonat okozta akut veseelégtelenség. Orvosi Hetilap 2007;148:421‐424
126. Du Boisgueheneuc F et al. Infarctus cerebral compliquant la prise d'une association diététique de ma huang et de guarana. La Presse Medicale 2001;30(4):166‐167
37
127. Oliveira CH et al. Clinical toxicology study of an herbal medicinal extract of Paullinia cupana, Trichilia catigua, Ptychopetalum olacoides and Zingiber officinale (Catumba®) in healthy volunteers. Phytotherapy Res 2005;19:54‐57
128. Mattei R et al. Guarana (Paullinia cupana): toxic behavioural effects in laboratory animals and antioxidant activity in vitro. J Ethnopharmacology 1998;60:111‐116
129. Santa Maria A et al. Evaluation of the toxicity of guarana with in vitro bioassays. Ecotoxicology Environmental Safety 1998;39:164‐167
130. Anon. Kava‐kava. The Medicines for Human Use (Kava‐kava) (Prohibition) Order 2002. Herbal Safety News, Medicines and Healthcare products Regulatory Agency. www.mhra.gov.uk [accessed January 26, 2006]
131. Committee on Safety of Medicines’ Expert Working Group (Kava). Report of the CSM’s expert working group on the safety of kava. Medicines and Healthcare products Regulatory Agency, July 2006. Available at www.mhra.gov.uk [accessed September 25, 2006]
132. Schulze J et al. Toxicity of kava pyrones, drug safety and precautions – a case study. Phytomedicine 2003; 10: 68–73.
133. Stickel F et al. Hepatitis induced by kava (Piper methysticum rhizoma). J Hepatol 2003; 39: 62–67.
134. Russmann S, Barguil Y, Cabalion P, Kritsanida M, Duhet D, Lauterburg BH. Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia. Eur J Gastroenterol Hepatol 2003;15:1033‐1036
135. Clough AR, Bailie RS, Currie B. Liver function test abnormalities in users of aqueous kava extracts. J Toxicol Clin Toxicol 2003;41(6):821‐829
136. Norton SA, Ruze P. Kava dermopathy. J Am Acad Dermatol 1994; 31: 89–97. 137. Levine R, Taylor WB. Take tea and see [letter]. Arch Dermatol 1988; 122: 856. 138. Süss R, Lehmann P. Hämatogenes Kontaktekzem durch pflanzliche Medikamente am Beispiel
des Kavawurzelextraktes. Hautarzt 1996; 47: 459–461. 139. Jappe U et al. Sebotropic drug reaction resulting from kava‐kava extract therapy: a new
entity? J Am Acad Dermatol 1998; 38: 104–106. 140. Schmidt P, Boehncke W‐H. Delayed‐type hypersensitivity reaction to kava‐kava extract.
Contact Dermatitis 2000; 42: 363. 141. Schelosky L et al. Kava and dopamine antagonism. J Neurol Neurosurg Psychiatry 1995; 58:
639–640. 142. Spillane PK et al. Neurological manifestations of kava intoxication. Med J Aust 1997; 167:
172–173. 143. Guro‐Razuman S et al. Dermatomyositis‐like illness following kava‐kava ingestion. J Clin
Rheumatol 1999; 6: 342–345. 144. Garner LF, Klinger JD. Some visual effects caused by the beverage kava. J Ethnopharmacol
1985; 13: 307–311. 145. But PP‐H, Tomlinson B, Lee K‐L. Hepatitis related to the Chinese medicine Shou‐wu‐pian
manufactured from Polygonum multiflorum. Vet Human Toxicol 1996;38(4):280‐282 146. Mazzanti G, Battinelli L, Daniele C, Mastroianni CM, Lichtner M, Coletta S, Costantini S. New
case of acute hepatitis following the consumption of Shou Wu Pian, a Chinese herbal product derived from Polygonum multiflorum. Ann Int Med 2004;140(7):W‐30
147. Park GJ‐H, Mann SP, Hgu MC. Acute hepatitis induced by Shou‐Wu‐Pian, a herbal product derived from Polygonum multiflorum. J Gastroenterol Hepatol 2001;16:115‐7
148. Panis B, Wong DR, Hooymans PM, de Smet PAGM, Rosias PPR. Recurrent toxic hepatitis in a Caucasian girl related to the use of Shou‐Wu‐Pian, a Chinese herbal preparation. J Pediatr Gastroenterol Nutr 2005;41(2):256‐8
149. MHRA. Medicines and Healthcare products Regulatory Agency. Polygonum multiflorum and liver reactions. Available at: http://www.mhra.gov.uk/Howweregulate/Medicines/Herbalandhomoeopathicmedicines/H
38
erbalmedicines/HerbalSafetyNews/Currentsafetyissues/CON2023590 [accessed 5 June 2008]
150. Darbinyan V et al. Rhodiola rosea in stress induced fatigue – a double blind cross‐over study of a standardized extract SHR‐5 with a repeated low‐dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000; 7: 365–371.
151. Spasov AA et al. A double‐blind, placebo‐controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR‐5 extract on the fatigue of students caused by stress during an examination period with a repeated low‐dose regimen. Phytomedicine 2000; 7: 85–89.
152. Fintelmann V, Gruenwald J. Efficacy and tolerability of a Rhodiola rosea extract in adults with physical and cognitive deficiencies. Adv Therapy 2007;24(4):929‐939
153. Prisinzano TE. Psychopharmacology of the hallucinogenic sage Salvia divinorum. Life Sciences 2005;78:527‐531
154. Grundmann O et al. Salvia divinorum and salvinorin A: an update on pharmacology and analytical methodology. Planta Med 2007;73:1039‐1046
155. Bücheler R et al. Use of nonprohibited hallucinogenic plants: increasing relevance for public health? A case report and literature review on the consumption of Salvia divinorum (Diviner's sage). Pharmacopsychiatry 2005;38:1‐5
156. Dalgarno P. Subjective effects of Salvia divinorum. J Psychoactive Drugs 2007;39(2):143‐149 157. Singh S. Adolescent salvia substance abuse. Addiction 2007;102:823‐824 158. Kumar S et al. The genus Turnera: a review update. Pharmaceutical Biology 2005;43(5):383‐
391 159. Tyler VE. Hallucinogenic drug hoaxes of the American hippies. In: Beal JL, Reinhard E (eds).
Natural products as medicinal agents. Strasbourg: Hippokrates Verlag Stuttgart, 1980:339‐350
160. Zhao J et al. Phytochemical investigation of Turnera diffusa. J Nat Prod 2007;70:289‐292 161. Dominguez XA, Hinojosa M. Mexican medicinal plants. XXVIII. Isolation of 5‐hydroxy‐7',3',4'‐
trimethoxyflavone from Turnera diffusa. Planta Med 1976;30:68‐71 162. Kelly WN et al. Guidelines for submitting adverse event reports for publication. Drug Safety
2007;30(5):367‐373 163. Gagnier JJ et al for the CONSORT Group. Reporting randomized, controlled trials of herbal
interventions: an elaborated CONSORT statement. Ann Int Med 2006;144:364‐367
39
4 WEB‐BASED SURVEY This section of the report details the aims, methods and results of the web‐based survey.
4.1 Aims
The aims of the web‐based survey were to:
1. Explore the use of, changing patterns of use, and sources of:
a. piperazine‐containing party pills
b. unclassified substances
c. other legal and illegal substances
2. Explore the factors which young people associate with their change in substance use – e.g. changes to the law, availability, price, personal experience, adverse effects.
3. Explore the harms and adverse effects/events associated with the use of unclassified substances such as Salvia divinorum, morning glory, kava and kratom.
4. Explore user use of medical services and support for the management of adverse events as in 3 above.
The study was not designed to test a causal relationship between the BZP ban and changes in substance use, although associations can be shown.
4.2 Methodology
The use of web‐based surveys in exploring issues related to substance use, and with ‘hidden’ or difficult to reach populations, is well established 8‐13. Reneau et al successfully surveyed adult recreational drug users about their general well‐being using an internet‐based survey 10, and Kypri and colleagues utilised a web survey to explore the use of alcohol amongst college students aged 16‐29 years 14. The key advantages of such an approach in the area of illicit drug research include the potentially greater level of anonymity provided 8 and increased self‐disclosure on more sensitive or personal topics 15,16. In addition, when compared with more traditional survey methods (e.g. those conducted by telephone), web‐based surveys offer significant practical advantages, such as reduced costs 17 and more expedient data collection 15.
Web‐based surveys are particularly appropriate when young people are the sample population, given their level of familiarity with the Internet. It has also been shown that young people use the Internet as a source of drug information 18 and as a social tool for gathering information on event listings etc.
Such a methodology is not without its limitations. Clearly, it requires potential participants to have access to the Internet, and response rates cannot be calculated due to difficulties in measuring the number of potential respondents 15. Others have highlighted the potential for respondents to make multiple submissions 15 and for demographic information to be falsified 17. On balance, it was decided that the advantages afforded by a web‐based survey mitigated against any potential limitations – in particular, its ability to facilitate access to the target population whilst providing a high level of anonymity. Moreover, it was recognised that Internet access in New Zealand is particularly high relative to other countries in the
40
developed world 19, and additional steps were put in place to combat some of the potential constraints of the approach (see Section 4.3).
4.3 Methods
This stage of the research consisted of a self‐complete survey conducted via the internet on two separate occasions.
4.3.1 Sample population
Based on data on piperazine‐based, party pill use from the Massey University household survey 1, and the fact that many of the unclassified psychoactive, legally available substances were sold by the same specialist retailers and websites as piperazine‐based products at the time the research was initially conceived, it was hypothesised that younger people aged 16‐30 years would be the main users of unclassified psychoactive plants such as Salvia divinorum, kratom, etc. It was also recognised that younger people are more likely to experiment with substances 20‐22, and thus were an appropriate sentinel group in the observation of any changes in drug use behaviour. Against this background, the target population for the study was adults aged 18‐30 years, who had access to the Internet. The minimum age for inclusion in the study of 18, as opposed to 16, was set as there are ethical considerations with respect to potentially educating younger people about the availability of psychoactive substances that they may not have otherwise heard of.
4.3.2 Recruitment
Participants were recruited via a range of methods, as follows.
‐ An on‐line banner advertisement alerting people to the study and the survey web address was designed and placed on a range of websites (these are listed in the Appendix at the rear of this report).
‐ Emails containing information about the study8 were sent to groups of potential respondents9 in the target age range (e.g. students) and individuals working in associated areas (e.g. youth health, music promotion etc.) who forwarded the information to prospective participants. Further distribution of emails by recipients was anticipated, creating a ‘snowballing’ effect.
‐ Flyers and cards were distributed in specialist party pill and other drug paraphernalia outlets, youth‐based health centres, tertiary education campuses, pubs and clubs, youth organisations and retail outlets appropriate to the study population (e.g. the music/DVD store “Real Groovy”). These were distributed over a wide geographical area across the North and South islands, and included a mix of urban and rural locales (e.g. Timaru, Dunedin, Taupo, Nelson, Wellington, Christchurch, Auckland, etc.). Copies of the flyer and business card promotional materials are attached in the Appendix.
‐ A series of print‐based advertisements were placed in the ‘Groove Guide’, a weekly national publication with event listings, music reviews etc.
8 Permission was sought from appropriate individuals (e.g. list moderators) in all instances where information was distributed via email lists.
9 This term is used interchangeably with participant and refers to individuals who took part in the web survey.
41
‐ A radio advertisement was aired on Mai FM.
‐ The research team promoted the research via youth and substance use networks, and other informal sets of contacts.
All recruitment and advertising material contained basic information about the study (e.g. the target audience, the research method, length of time required to complete the survey, etc.) highlighted the confidential nature of participation, and listed the address of the website where the survey was hosted (www.tickit.org.nz), and contact details of the lead researcher for any enquiries.
Participants who took part in both waves of the study (and provided contact details – see below) were entered into a prize draw to win mobile phones and movie and music vouchers. This information was also contained in some of the advertising material (e.g. on flyers).
4.3.3 Questionnaire and website design
The questionnaire was designed using the research and technical expertise of the research team, with input from a number of individuals selected for their expertise in several areas relevant to the study (e.g. drug treatment, youth media, etc.), who were consulted on issues such as questionnaire content, promotion of the study, and website design. Technical expertise in relation to hosting the survey and construction of the website was provided by an independent contractor with experience in this field.
In order to facilitate participation and survey completion, key considerations in the design of the survey were its length, ease of completion and visual impact. A graphic designer was employed to design the website, including the front page and overall look of the questionnaire, to ensure appeal to the target audience. Other tools utilised included a ‘questionnaire completion progress bar’ at the bottom of the screen on each page of the survey to alert respondents how far through the questionnaire they were, and ‘drop‐down boxes’ to facilitate completion of the questions and reduce missing data. In addition, the questionnaire was segmented so that it consisted of a series of short pages10.
The questionnaire underwent a two‐stage pilot process as follows.
• A paper‐based version of the survey was piloted amongst nine people in the target age range (i.e. 18‐30 years). Feedback gathered from this stage of the pilot was incorporated into a revised questionnaire which was developed further into a ‘mock‐up’ on‐line version of the survey with draft design elements.
• An on‐line version was piloted amongst 55 people, who were sent a link to the draft and asked to complete the survey as though they were participating in the actual study. Feedback (via a short questionnaire attached to the on‐line pilot questionnaire) was sought on a range of issues, including length of time taken to complete the survey, ease of understanding of the questions and instructions, level of comfort with being asked to create a ‘unique identifier’ code (see later), and design elements. This phase of the pilot also allowed for testing of the technical elements of the data collection. Further data entries were made by research staff as quality assurance checks.
10 This was on the recommendation of experiences web survey researchers who advised that long pages requiring participants to scroll down could be off‐putting and result in respondents not completing the full questionnaire.
42
4.3.4 Data collection
Data collection took place at two time points; wave 1 (W1) was three months after the ban on BZP and wave 2 (W2) was 2‐3 months after the end of the amnesty period. The study was set up so that anyone could participate at W1 if they were eligible and consented, but only those who completed W1 and provided contact details were invited to complete W2, thus allowing for paired data analysis for change over time. All data in the questionnaire were anonymous and could not be linked to contact details (see later).
A website was set up specifically for the project (www.tickit.org.nz) and housed on the secure University of Auckland (UoA) server. This contained the participant information sheet (detailing the aims of the study, and background on what taking part in the research involved), a consent form, and the questionnaire itself. Once a person had consented to take part they were able to complete the survey. All questionnaire data were automatically logged into a secure location on the UoA server. Data at W1 and W2 were logged in identical ways. At the end of the questionnaire, when people were asked to provide contact details for follow‐up, these data were automatically logged into a separate database, unlinked to the first database, but housed on the same server. Access to databases was only available to the website designer/data manager, and data from these were transferred to password‐protected Excel spreadsheets for the research team to use. To enable data from W1 and W2 to be matched across the two time points, whilst also maintaining the anonymity of participants, each participant was asked to create a six‐item unique identifier (comprising a combination of letters and numbers) at the end of the W1 questionnaire. This information consisted of the following: the date of the month in which they were born; the first and last letter of their mother’s first name; and, the first and last letter of their place of birth. The unique identifier for each participant was stored with their survey responses.
4.3.4.1 Wave one
W1 data were collected over a five‐week period between 18th July and 25th August, 2008. As highlighted above, all respondents were required to read a participant information sheet and agree to a set of conditions outlined on a consent form prior to completing the survey. Following this, they were directed to a web page that contained the questionnaire. This was divided into four main sections as follows:
• Section 1 consisted of questions on the use, frequency of use, and source of BZP party pills, BZP‐free party pills, legally available smokeable products, and ‘other legally available substances’. W1 questions focussed on use during two time periods: 1st January and 30th March 2008 (i.e. whilst BZP party pills were still legally available) and 1st April and 30th June 2008 (i.e. during the first three months of the amnesty period whereby prohibition was in place for suppliers, but not enforced for users of these substances). This section related to Aims 1a and 1b of the study.
• Section 2 consisted of questions on the adverse effects (“unpleasant health effects or side effects”) experienced after use of any of the substances noted above. This included questions on the number and nature of the effects experienced, other substances consumed, steps taken on experiencing adverse effects, outcome and impact on subsequent substance use. W1 questions focussed on use of these
43
substances during the same time periods as those utilised in section 1 of the questionnaire. This section related to Aims 3 and 4 of the study.
• Section 3 consisted of questions on the use and frequency of use of a range of other substances, including alcohol, cannabis, ecstasy, methamphetamine, GHB, ketamine, LSD, prescription drugs (“for non‐medical/recreational purposes”) and “any other illegal drugs” (respondents were required to specify what these were). This section related to Aim 1c of the study.
• Section 4 consisted of an open question on the reasons for any increase or decrease in substance use since BZP party pills were banned. This section related to Aim 2.1 of the study.
In addition, demographic data on the age, gender, ethnicity, current work and study situation, and area of residence (by region) for each participant were also collected.
Upon completion of the questionnaire, participants were asked to provide contact details11 to allow the research team to contact them at a later date to invite them to take part in the second wave of the study, and to inform them at the completion of the research if they had won a prize.
4.3.4.2 Wave two
W2 data were collected between 5th and 23rd December, 2008. All W1 participants who provided either an email address or mobile phone number were contacted by email or SMS text message and invited to complete the second questionnaire via the same web page established for the first wave of the study (n=511). In order to overcome potential attrition of participants at the second wave, two sets of reminder emails/texts were sent at weekly intervals.
To enable comparison of the findings across the two time points, the W2 questionnaire was identical to W1 with regard to the key questions asked (e.g. frequency of use of the same set of substances). The main difference between the two questionnaires was the time periods covered. In W2, respondents were required to indicate their frequency of use of the substances between 1st July and 30th September, 2008 (i.e. during the final three months of the amnesty period) and 1st October and the date that they completed the questionnaire (i.e. the time following the end of the amnesty whereby full prohibition of BZP and related substances was in force). As with W1, all participants were required to read a participant information sheet and complete a consent form before completing the survey. They were also required to enter their ‘unique identifier’ at the start of the questionnaire to enable data to be matched across both waves.
4.3.5 Data analysis
Analysis of data was undertaken as follows:
1. Frequency data were obtained for the total samples at W1 and W2. (Analysis for change over time is not valid for the total samples as the W2 sample was a subset of the W1 sample).
11 Participants were given the option of providing either an email address or mobile phone number. There were two key reasons for this: (1) To ensure that individuals who did not have access to one of these communication tools were able to participate in both waves and be entered into the prize draw; (2) Given that email addresses often contain identifiable information (e.g. name and/or workplace) an alternative option was considered important with regard to maintaining participant confidentiality.
44
2. Statistical analysis of change over time, using paired data from W1 and W2, was undertaken for those who completed the questionnaire at both waves, and for whom we had matching unique IDs.
3. For data on adverse events related to the use of licit substances (except alcohol), a descriptive and qualitative approach was taken. The number of respondents reporting adverse events, and the number of adverse events experienced were determined, as well as the number meeting certain criteria (e.g. serious). A causality assessment was undertaken by one author‐assessor (JB), although due to the poor quality of the data collected, its usefulness is limited.
4. Thematic analysis was undertaken on qualitative data generated by the ‘open’ questions in Section four of the questionnaire.
4.4 Results
4.4.1 Full sample data
The following section presents frequency data for everyone who completed the questionnaires at W1 and W2. Percentages may add up to >100% due to rounding to one decimal place. No statistical analyses have been undertaken to compare total sample data from the two waves as the W2 sample is a sub sample of W1 and thus analyses are not appropriate. It is important NOT to use the raw data in this section to draw conclusions about any changes from W1 to W2. Analyses for this have been undertaken in Section 4.4.17.
4.4.1.1 Wave one
At W1, 611 partial or completed questionnaires were logged into the database between 18th July 08 and 25th August, 2008. Of these, 7 were excluded due to the respondent being outside of the eligible age range. A further 96 were excluded as the questionnaires were incomplete (i.e. the respondent did not complete the survey)12. This left a usable sample of 508.
4.4.1.2 Wave two
At W2, 360 partial or completed questionnaires were logged into the database between 5th and 23rd of December, 2008. Of these, 3 were excluded due to the respondent being outside of the eligible age range. A further 6 were excluded as they did not complete the questionnaire (i.e., did not reach the end of the questionnaire). In addition, 7 duplicate entries were identified by matching up unique IDs which were also removed13. This left a usable sample of 344.
4.4.2 Demographics
Tables 4 and 5 display the demographics for the whole sample at W1 and W2.
12 Participants were informed that if they decided part way through that they did not want to complete the survey to close the web page, and that their data would be removed from the study.
13 5 sets of duplicate: one is empty, and thus removed; 2 sets of duplicates: partial entries, and thus they have been combined together
45
Table 4: Demographic data 1 Demographic data Wave 1 Total
Sample (N=508) Wave 2 Total
Sample (N=344) n % n %
Gender (MV=4) (MV=0) Male 288 56.7 205 59.6 Female 216 42.5 139 40.4 Age (MV=0) (MV=1) 18‐20 years 142 28.0 71 20.6 21‐25 years 232 45.7 164 47.7 26‐30 years** 134 26.4 108 31.4 Ethnicity* (MV=5) (MV=1) New Zealand European 382 75.2 273 79.4 Maori 33 6.5 24 7.0 Samoan 4 0.8 3 0.9 Cook Island Maori 4 0.8 1 0.3 Tongan 5 1.0 3 0.9 Niuean 0 0.0 0 0.0 Chinese 44 8.7 35 10.2 Indian 17 3.4 7 2.0Other 67 13.2 44 12.8 Region (MV=1) (MV=0)Northland 2 0.4 3 0.9Auckland 363 71.5 248 72.1Bay of Plenty 4 0.8 4 1.2Waikato 7 1.4 4 1.2Gisborne 1 0.2 0 0.0Hawkes Bay 3 0.6 2 0.6Taranaki region 3 0.6 2 0.6Wellington 41 8.1 30 8.7Manawatu‐Wanganui 5 1.0 2 0.6Tasman 4 0.8 2 0.6Nelson 2 0.4 1 0.3 Marlborough 2 0.4 1 0.3West Coast 0 0.0 0 0.0 Canterbury 53 10.4 37 10.8 Otago 13 2.6 5 1.5 Southland 4 0.8 3 0.9 Percentages will not total 100 if there are missing values. * Percentages may add up to more than 100 as people could choose more than one response ** Note: for W2 this age range was 18‐31 years as it included one participant who had their 31st birthday between waves one and two. MV= missing values
46
Table 5: Demographic data 2 Demographic data continued Wave 1 Total
Sample (N=508) Wave 2 Total
Sample (N=344) n % n %
Which best describes your current work situation?
(MV=3) (MV=1)
I work full time 235 46.3 179 52.0 I work part time 171 33.7 98 28.5 I am not currently in paid employment
99 19.5 66 19.2
Which best describes your current study arrangements?
(MV=4) (MV=0)
I am a full‐time student 236 46.5 146 42.4 I am a part‐time student 54 10.6 42 12.2 I am not currently studying 214 42.1 156 45.4 Have you, or any of your close friends or family, worked in party pill retailing or manufacture?
(MV=3)
(MV=0)
Yes 56 11.0 25 7.3No 426 83.9 305 88.7Don’t know 23 4.5 14 4.1Percentages will not total 100 if there are missing values. MV= missing values
4.4.3 Data from all participants
The following results are based on data from the total samples at Wave 1 and Wave 2. Questions regarding substance use were asked for the following time frames: Wave 1 Wave 2
1st Jan 2008‐ 30th Jun 2008 1st July 2008 – date completed W2 questionnaire W1 time 1 (W1T1) W1 time 2 (W1T2) W2 time 1 (W2T1) W2 time 2 (W2T2) 1st Jan 2008 – 31st March 2008
1st April 2008 ‐ 30th June 2008
1st July 2008 – 30th Sept 2008
1st October 2008 – date of completion of W2 questionnaire (between 5th and 23rd December)
BZP party pills and related substances are still legally available
BZP party pills and related substances are banned, but 6 months’ amnesty for personal use exists
BZP party pills and related substances are banned, but 6 months’ amnesty for personal use exists
BZP party pills and related substances are banned, and amnesty period for personal use ends
47
4.4.4 Use of BZP party pills
At the time of completing the Wave 1 survey, 31.3% (159/508) had used BZP party pills in the previous six months and at Wave 2, 10.8% (37/344). The most commonly used products are listed below in Table 614. Tables 7, 8 and 9 show data on frequency of use, where substances were accessed, and level of use amongst those indicating use during the previous six months at each wave. Table 6: BZP party pills named by respondents Respondents may have noted more than one product
Wave 1 (Number of respondents = 83)
Wave 2 (Number of respondents = 16)
n n Amp 1 0 Big Grin 5 0 Big Red 2 0 Black Window [sic] 1 1 Bliss 1 0 Blue Blanks 2 0 Bolts 2 0 Bulldog 4 0 Butterflies 1 0 BZP powder 2 1 Charge* 26 5 Crank 2 0 Dark Angel 4 0 Dove 1 0 Dreams 1 0 EFX 1 0 Enjoi 3 1 Escape 1 0 ESP 1 0 Euphoria 1 0 Excoit # 1 0 Exodus 1 0 Exotic 0 1 Fast Lane 2 0 Formula 1 1 0 Formula 5 # 1 0 Frenzy 4 0 FREQ 1 0 Grinz 0 1 Grunters 2 0 Have A Smiley Day # 1 0 Havoc # 1 0
14 Whilst most of the products reported by respondents have been confirmed as BZP party pills via an Internet search, a small number were not. However, given the extensive range of brands and products available for purchase in New Zealand, it is possible that some of these would not be able to be identified via such a search (particularly after BZP was banned). These products have been included in the above table and are identified with a #.
48
BZP‐ party pills named by respondents ‐ continuedHerbalman # 0 1 Hummer/Humma 4 2 Ice Diamonds* 14 1 Jax 3 0 Jet 1 0 Jump* 2 2 Kamikaze 1 1 Kandi* 6 3 Mash 0 1 Mickey Finns 1 0 Mystics 1 0 Pink Panthas # 0 1 Pulse 1 0 Pure XTC Gold 1 0 Purple Rain 1 0 Rapture 5 1 REAQ 1 0 Red Candy # 1 0 Red Dragon 1 0 Red Hearts* 11 1 Silver Bullet* 8 3 Silver Dragon # 1 0 Smileys 2 1 Smurf # 2 1 Sonic 1 0 The Good Stuff 3 0 Thumper # 1 0 Turbo Extreme 1 1 Turbos 1 0 TWEQ 1 0 Up 1 0 Volt # 1 0 White Diamonds 0 1 Wizzerd 7 0 XTC 2 0 XXX 4 0 * named in question as an example # not confirmed through Internet search as being BZP party pill
49
Table 7: Frequency of use of BZP party pills at Waves 1 and 2 In a typical month, how often did you use BZP party pills? W1T1 W1T2 W2T1 W2T2
n % n % n % n % Not at all 4 2.5 56 35.2 5 13.5 6 16.2 About once a month or less
117 73.6 81 50.9 29 78.4 27 73
About 2‐4 times a month
31 19.5 15 9.4 2 5.4 3 8.1
About 2‐3 times a week
2 1.3 2 1.3 1 2.7 1 2.7
4 or more times a week
0 0.0 0 0.0 0 0.0 0 0.0
Missing values 5 3.1 5 3.1 0 0.0 0 0.0 TOTAL 159 100 159 100 37 100 37 100
Table 8: Where BZP party pills were obtained If you have used BZP party pills, where do you get them from?
Wave 1 (Number of respondents=103)
Wave 2 (Number of respondents =37)
n % n % A friend gave them to me 52 50.5 20 54.1 A friend sold them to me 14 13.6 6 16.2 A retail outlet 8 7.8 4 10.8 A dealer 2 1.9 2 5.4 Via the internet 3 2.9 0 0.0 Imported them myself from overseas
0 0.0 0 0.0
I stockpiled them before the ban came into effect
50 48.5 14 37.8
Other 8 7.8 1 2.7 Percentages are calculated using number of people responding to this question Percentages may add up to > 100% as people may have indicated more than one source of BZP party pills Data missing on 56 cases at Wave 1 and 1 case at Wave 2.
Table 9: Level of use of BZP party pills In your opinion, has your use of BZP party pills increased, decreased, or stayed about the same since: Wave 1 – they were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 2 1.3 0 0.0 Stayed about the same 59 37.1 14 37.8 Decreased 93 58.5 23 62.2 Don’t know 5 3.1 0 0 Missing values 0 0.0 0 0.0 TOTAL 159 100 37 100
50
4.4.5 Use of BZP‐free party pills
At the time of completing the Wave 1 survey, 11.0% (56/508) had used BZP‐free party pills in the previous six months and at Wave 2, 11.9% (41/344). The most commonly used products are listed below in Table 10. Please note that some BZP and BZP‐free products share the same name (e.g. Hummer). However, where respondents have named one of these products in this section, we have assumed it to be a BZP‐free version. Table 10: BZP‐free party pills named by respondents
Respondents may have noted more than one product
Wave 1 (Number of respondents =18)
Wave 2 (Number of respondents =13)
n n
Vegas Nights: Ace of Spades 4 1
Charge 1 0
Charlies # 0 1
Chuckys 1 2
Clearshot 1 0
Comet * 2 3
Diablo 0 1
Groove 1 1
Hammerd 0 1
Hummer 3 1
Infernal 0 1
LUV * 0 1
Meo $ 2 0
Mr Happy 0 1
Nirvana 3 1
Pepe * 3 3
Phat Freddy's 1 0
Pure XTC # 0 1
Sharpen Up 1 0
Stargate test pills 1 0
Trance 2 1 * named in question as an example # not confirmed through Internet search as being BZP party pill $ Meo contained methoxyphenylpiperazine (MeOPP) which was classified at the same time as BZP. However, as it did not contain BZP, and it was legally available to purchase during W1, it remains in this section
Tables 11, 12 and 13 show data on self‐reported frequency of use, where substances were accessed, and level of use amongst those indicating use during the previous 6 months at each wave.
51
Table 11: Self‐reported frequency of use of BZP‐free party pills In a typical month, how often did you use BZP‐free party pills? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 19 33.9 11 19.6 4 9.8 16 39.0 About once a month or less
32 57.1 39 69.6 33 80.5 24 58.5
About 2‐4 times a month
2 3.6 3 5.4 3 7.3 0 0.0
About 2‐3 times a week
0 0.0 0 0.0 0 0.0 0 0.0
4 or more times a week
0 0.0 0 0.0 0 0.0 0 0.0
Missing values 3 5.4 3 5.4 1 2.4 1 2.4 TOTAL 56 100 56 100 41 100 41 100
Table 12: Where BZP‐free party pills were obtained If you have used BZP‐free party pills, where do you get them from?
Wave 1 (Number of respondents =50)
Wave 2 (Number of respondents =39)
n % n % A friend gave them to me 18 36.0 16 41.0 A friend sold them to me 1 2.0 1 2.6 A retail outlet 34 68.0 23 59.0 A dealer 0 0.0 2 5.1 Via the internet 1 2.0 0 0 Imported them myself from overseas
1 2.0 0 0
Other 2 4.0 1 2.6 Percentages are calculated using number of people responding to this question Percentages may add up to > 100% as people may have indicated more than one source of BZP party pills Data missing on 6 cases at Wave 1 and 2 cases at Wave 2
Table 13: Level of use of BZP‐free party pills In your opinion, has your use of BZP‐free party pills increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 14 25.0 7 17.1 Stayed about the same 23 41.1 16 39.0 Decreased 15 26.8 15 36.6 Don’t know 1 1.8 2 4.9 Missing values 3 5.4 1 2.4 TOTAL 56 100 41 100
52
4.4.6 Use of legally available smokeable products
At the time of completing the Wave 1 survey, 13.8% (70/508) had used legally available smokeable products in the previous six months and at Wave 2, 8.4% (29/344). The most commonly used products are listed below in Table 14. Please note the small sample sizes. Table 14: Legally available smokeable products named by respondents Respondents may have noted more than one product
Wave 1 (Number of respondents =42)
Wave 2 (Number of respondents =14)
n % n % Salvia* 31 73.8 12 85.7
Spice* 9 21.4 5 3.7
Mexican Tripping Weeda 4 9.5 0 0.0
Spice Gold 3 7.1 1 7.1
Zohai SXb 1 2.4 0 0.0
Loins Tail [sic] 1 2.4 0 0.0
Zhoi Buds 1 2.4 0 0.0
Zo hightb 1 2.4 0 0.0
Black Magic 1 2.4 0 0.0
Damiana 2 4.8 0 0.0
Tijuana Tripping Weeda 1 2.4 0 0.0
Aroma 0 0.0 2 14.3
Spice Diamond 0 0.0 1 7.1
Dream 0 0.0 1 7.1
JWH‐018 0 0.0 1 7.1
JWH‐200 0 0.0 1 7.1 * named in question as an example a It is possible that these two products are the same. Also, Salvia divinorum is also known as ‘Mexican tripping weed’, so it is likely that these products refer to this substance b It is possible that these two products are the same
Tables 15, 16,17 show data on self‐reported frequency of use, where substances were accessed, and level of use amongst those indicating use during the previous 6 months.
Table 15: Frequency of use of legally available smokeable products In a typical month, how often did you use legally available smokeable products? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 7 10.0 17 24.3 4 13.8 4 13.8 About once a month or less
53 75.7 43 61.4 21 72.4 20 69.0
About 2‐4 times a month
6 8.6 5 7.1 1 3.5 1 3.5
About 2‐3 times a week
0 0.0 1 1.4 0 0.0 0 0.0
4 or more times a week
0 0.0 0 0.0 3 10.3 3 10.3
Missing data 4 5.7 4 5.7 0 0 1 3.5 TOTAL 70 100 70 100 29 100 29 100
53
Table 16: Where legally available smokeable products were obtained If you have used legally available smokeable products, where do you get them from?
Wave 1 (Number of respondents=66)
Wave 2 (Number of respondents =28)
n % n % A friend gave them to me 28 42.4 7 25.0 A friend sold them to me 4 6.1 1 3.6 A retail outlet 44 66.7 20 71.4 A dealer 2 3.0 0 0.0 Via the internet 5 7.6 2 7.1 Imported them myself from overseas
1 1.5 1 3.6
Other 0 0.0 3 10.7 Percentages are calculated using number of people responding to this question Percentages may add up to > 100% as people may have indicated more than one source of BZP party pills Data missing on 4 cases at Wave 1 and 1 at Wave 2.
Table 17: Level of use of legally available smokeable products In your opinion, has your use of legally available smokeable products increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 8 11.4 8 27.6 Stayed about the same 43 61.4 12 41.4 Decreased 9 12.9 7 24.1 Don’t know 7 10.0 2 6.9 Missing values 3 4.3 0 0.0 TOTAL 70 100 29 100
4.4.7 Use of other legally available substances
Following questions on use of BZP and BZP‐free party pills, and legally available smokeable products, participants were asked to indicate whether they had used “any other legally available substances [excluding tobacco and alcohol]”. Whilst strictly speaking a small number of items in this section are legally categorised as Prescription Medicines, they would be unlikely to be prescribed by doctors, and may have been available from retail outlets or via international websites, and be perceived by users as ‘legally available’ (see table 18). At the time of completing the W1 and W2 surveys, a number of people claimed to have used other legally available substances during the previous six months. However, many of the drugs subsequently named by these respondents were not legal psychoactive substances (as defined by the question). This included, for example, tobacco and alcohol. These data were either removed during the data‐cleaning process, or re‐coded in other relevant categories, where appropriate. Following this, the revised totals for use of other legally available substances during the previous six months were 5.3% (27/508), (W1) and 3.2% (11/344), (W2) including those who did not provide any drug names or 3.1% (16/508),
54
(W1) and 2.0% (7/344), (W2) excluding those with missing drug names. The most commonly used legally available substances cited by respondents are listed in Table 18. Table 18: Legally available substances named by respondents Respondents may have noted more than one product
Wave 1 (Number of respondents = 16)
Wave 2 (Number of respondents = 7)
n % n % Amyl nitrate*+ 7 43.8 5 71.4 Geranamine 1 6.3 0 0.0 Mitragyna speciosa (Kratom)* 1 6.3 0 0.0 OTC medicine 2 12.5 1 14.3 Pharmacy only medicine 3 18.8 0 0.0 Cough mixture 1 6.3 0 0.0 Kava 1 6.3 1 14.3 Poppy seed tea 1 6.3 0 0.0 Flu tablets 1 6.3 0 0.0 Pseudoephedrine 1 6.3 0 0.0 Valerian 0 0.0 1 14.3 * Both these items are legally categorised as Prescription Medicines (requiring a doctor’s prescription for access). However, they would be unlikely to be prescribed by doctors, and may have been available from retail outlets and websites, and be perceived by users as ‘legally available’. + Whilst people reported using amyl nitrate it is probable that they were in fact referring to amyl nitrite. These two substances are commonly confused. The former is used in the treatment of angina, and the latter (also known as ‘poppers’) is used recreationally, often to enhance sexual pleasure.
4.4.8 Use of alcohol
At the time of completing the Wave 1 survey, 92.9% (472/508) had used alcohol in the previous six months and at Wave 2, 91.6% (315/344). Tables 19 and 20 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 19: Frequency of alcohol use In a typical month, how often did you use alcohol? W1T1 W1T2 W2T1 W2T2 n % N % n % n % Not at all 5 1.1 4 0.9 6 1.9 4 1.3 About once a month or less
77 16.3 78 16.5 55 17.5 46 14.6
About 2‐4 times a month
174 36.9 178 37.7 128 40.6 127 40.3
About 2‐3 times a week
169 35.8 165 35.0 107 34.0 113 35.9
4 or more times a week
46 9.8 44 9.3 19 6.0 23 7.3
Missing values 1 0.2 3 0.6 0 0.0 2 0.6 TOTAL 472 100 472 100 315 100 315 100
55
Table 20: Level of alcohol use In your opinion, has your use of alcohol increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? W1 W2
n % n % Increased 43 9.1 53 16.8 Stayed about the same 390 82.6 226 71.8 Decreased 23 4.9 32 10.2 Don’t know 11 2.3 4 1.3 Missing values 5 1.1 0 0.0 TOTAL 472 100 315 100
4.4.9 Use of cannabis
At the time of completing the Wave 1 survey, 45.1% (229/508) had used cannabis in the previous six months and at Wave 2, 39.8% (137/344). Tables 21 and 22 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 21: Frequency of cannabis use In a typical month, how often did you use cannabis? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 13 5.7 17 7.4 4 2.9 7 5.1 About once a month or less
101 44.1 94 41.1 54 39.4 56 40.9
About 2‐4 times a month
49 21.4 52 22.7 33 24.1 26 19.0
About 2‐3 times a week
30 13.1 28 12.2 27 19.7 26 19.0
4 or more times a week
36 15.7 37 16.2 18 13.1 22 16.1
Missing values 0 0.0 1 0.4 1 0.7 0 0.0 TOTAL 229 100 229 100 137 100 137 100
Table 22: Level of cannabis use In your opinion, has your use of cannabis increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 33 14.4 38 27.7 Stayed about the same 170 74.2 68 49.6 Decreased 18 7.9 28 20.4 Don’t know 7 3.1 3 2.2 Missing values 1 0.4 0 0.0 TOTAL 229 100 137 100
56
4.4.10 Use of ecstasy At the time of completing the Wave 1 survey, 33.5% (170/508) had used ecstasy in the previous six months and at Wave 2, 26.7% (92/344). Tables 23 and 24 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 23: Frequency of ecstasy use In a typical month, how often did you use ecstasy? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 16 9.4 16 9.4 7 7.6 9 9.8 About once a month or less
110 64.7 109 64.1 71 77.2 64 69.6
About 2‐4 times a month
37 21.8 40 23.5 14 15.2 18 19.6
About 2‐3 times a week
5 2.9 3 1.8 0 0.0 0 0.0
4 or more times a week
1 0.6 1 0.6 0 0.0 0 0.0
Missing values 1 0.6 1 0.6 0 0.0 1 1.1 TOTAL 170 100 170 100 92 100 92 100
Table 24: Level of ecstasy use In your opinion, has your use of ecstasy increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 50 29.4 18 19.6 Stayed about the same 101 59.4 55 59.8 Decreased 15 8.8 16 17.4 Don’t know 4 2.4 1 1.1 Missing values 0 0.0 2 2.2 Total 170 100 92 100
4.4.11 Use of methamphetamine
At the time of completing the Wave 1 survey, 5.5% (28/508) had used methamphetamine in the previous six months and at Wave 2, 4.4% (15/344). Tables 25 and 26 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months.
57
Table 25: Frequency of methamphetamine use In a typical month, how often did you use methamphetamine? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 4 14.3 2 7.1 2 13.3 0 0 About once a month or less
18 64.3 20 71.4 8 53.3 10 66.7
About 2‐4 times a month
2 7.1 2 7.1 3 20.0 4 26.7
About 2‐3 times a week
3 10.7 1 3.6 0 0.0 0 0.0
4 or more times a week
1 3.6 2 7.1 2 13.3 1 6.7
Missing values 0 0.0 1 3.6 0 0.0 0 0.0 TOTAL 28 100 28 100 15 100 15 100
Table 26: Level of methamphetamine use In your opinion, has your use of methamphetamine increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 5 17.9 3 20.0 Stayed about the same 17 60.7 7 46.7 Decreased 5 17.9 5 33.3 Don’t know 1 3.6 0 0.0 Missing values 0 0.0 0 0.0 TOTAL 28 100 15 100
4.4.12 Use of GHB At the time of completing the Wave 1 survey, 6.3% (32/508) had used GHB in the previous six months and at Wave 2, 5.5% (19/344). Tables 27 and 28 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 27: Frequency of GHB use In a typical month, how often did you use GHB? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 1 3.1 4 12.5 2 10.5 3 15.8 About once a month or less
22 68.8 20 62.5 12 63.2 9 47.4
About 2‐4 times a month
5 15.6 5 15.6 5 26.3 3 15.8
About 2‐3 times a week
2 6.3 2 6.3 0 0.0 0 0.0
4 or more times a week
1 3.1 1 3.1 0 0.0 2 10.5
Missing values 1 3.1 0 0.0 0 0.0 2 10.5 TOTAL 32 100 32 100 19 100 19 100
58
Table 28: Level of GHB use In your opinion, has your use of GHB increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 6 18.8 8 42.1 Stayed about the same 22 68.8 6 31.6 Decreased 4 12.5 5 26.3 Don’t know 0 0.0 0 0.0 Missing values 0 0.0 0 0.0 TOTAL 32 100 19 100
4.4.13 Use of ketamine
At the time of completing the Wave 1 survey , 8.1% (41/508) had used ketamine in the previous six months and at Wave 2, 6.4% (22/344). Tables 29 and 30 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 29: Frequency of ketamine use In a typical month, how often did you use ketamine? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 4 9.8 4 9.8 4 18.2 1 4.6 About once a month or less
29 70.7 26 63.4 15 68.2 15 68.2
About 2‐4 times a month
4 9.8 6 14.6 1 4.6 3 13.6
About 2‐3 times a week
3 7.3 4 9.8 2 9.1 2 9.1
4 or more times a week
1 2.4 1 2.4 0 0.0 0 0.0
Missing values 0 0.0 0 0.0 0 0.0 1 4.6 TOTAL 41 100 41 100 22 100 22 100
Table 30: Level of ketamine use In your opinion, has your use of ketamine increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 12 29.3 6 27.3 Stayed about the same 22 53.7 11 50.0 Decreased 7 17.1 5 22.7 Don’t know 0 0.0 0 0.0 Missing values 0 0.0 0 0.0 TOTAL 41 100 22 100
59
4.4.14 Use of LSD At the time of completing the Wave 1 survey , 15.9% (81/508) had used LSD in the previous six months and at Wave 2, 13.4% (46/344). Tables 31 and 32 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months. Table 31: Frequency of LSD use In a typical month, how often did you use LSD? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 14 17.3 9 11.1 5 10.9 5 10.9 About once a month or less
60 74.1 65 80.3 36 78.3 40 87.0
About 2‐4 times a month
7 8.6 7 8.6 4 8.7 1 2.2
About 2‐3 times a week
0 0.0 0 0.0 0 0.0 0 0.0
4 or more times a week
0 0.0 0 0.0 0 0.0 0 0.0
Missing values 0 0.0 0 0.0 1 2.2 0 0.0 TOTAL 81 100 81 100 46 100 46 100
Table 32: Level of LSD use In your opinion, has your use of LSD increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 17 21.0 10 21.7 Stayed about the same 51 63.0 27 58.7 Decreased 7 8.6 8 17.4 Don’t know 5 6.2 1 2.2 Missing values 1 1.2 0 0.0 TOTAL 81 100 46 100
4.4.15 Use of prescription drugs (for non‐medical purposes)
At the time of completing the Wave 1 survey W1, 9.1% (46/508) had used prescription drugs in the previous six months and at Wave 2, 9.3% (32/344). The most commonly used prescription drugs are listed below in Table 33. Tables 34 and 35 show data on self‐reported frequency and level of use amongst those indicating use during the previous six months.
60
Table 33: Prescription drugs named by respondents Respondents may have noted more than one product
Wave 1 (Number of respondents=28)
Wave 2 (Number of respondents =20)
n % n % Ritalin™*/methylphenidate 13 46.4 7 35.0 Valium™/diazepam 7 25.0 6 30.0 Duromine™ 1 3.6 0 0.0 Codeine 8 28.6 5 25.0 Morphine* 5 17.9 2 10.0 Tramadol™ 1 3.6 2 10.0 DXM 1 3.6 0 0.0 Xanax™/triazolam 3 10.7 2 10.0 Hydrocodone 2 7.1 1 5.0 Oxycodone 4 14.3 1 5.0 SSRIs# 1 3.6 0 0.0 Modafinil 1 3.6 2 10.0 Immovane™/zopiclone 2 7.1 0 0.0 Rivotril™/clonazepam 3 10.7 2 10.0 Piracetam 1 3.6 2 10.0 Midazolam 1 3.6 0 0.0 Temazepam 2 7.1 3 15.0 ‘sleeping pills’ 1 3.6 0 0.0 Lorazepam 2 7.1 1 5.0 Zolpidem 1 3.6 0 0.0 Lithium 0 0.0 1 5.0 Reboxetine 0 0.0 1 5.0 Promethazine 0 0.0 1 5.0 Venlafaxine 0 0.0 1 5.0 Tianeptine 0 0.0 1 5.0 Alprazolam 0 0.0 1 5.0 * named in question as an example. ‘Benzos’ was also included in the list of examples provided. # Selective serotonin reuptake inhibitors
Table 34: Frequency of non‐medical use of prescription drugs In a typical month, how often did you use prescription drugs? W1T1 W1T2 W2T1 W2T2 n % n % n % n % Not at all 5 10.9 5 10.9 7 21.9 3 9.4 About once a month or less
19 41.3 15 32.6 15 46.9 17 53.1
About 2‐4 times a month
10 21.7 13 28.3 6 18.8 8 25.0
About 2‐3 times a week
6 13.0 6 13.0 2 6.3 2 6.3
4 or more times a week
3 6.5 4 8.7 2 6.3 2 6.3
Missing values 3 6.5 3 6.5 0 0.0 0 0.0 TOTAL 46 100 46 100 32 100 32 100
61
Table 35: Level of non‐medical use of prescription drugs In your opinion, has your use of prescription drugs increased, decreased, or stayed about the same since: Wave 1 – BZP party pills were banned; Wave 2 ‐ the first time you completed this survey in July/August this year? Wave 1 Wave 2
n % n % Increased 15 32.6 9 28.1 Stayed about the same 24 52.2 15 46.9 Decreased 2 4.4 5 15.6 Don’t know 2 4.4 3 9.4 Missing values 3 6.5 0 0.0 TOTAL 46 100 32 100
4.4.16 Use of other illegal drugs After completing questions on use of a range of illicit substances, participants were asked to indicate whether they had used “any other illegal drugs”. At the time of completing the Wave 1 survey, 1, 9.8% (50/508) of the sample reported that they had used other illegal drugs during the previous six months and at Wave 2, 7.3% (25/344). However, a number of the drugs subsequently named by respondents were either not illicit substances or were covered by previous questions in the survey (e.g. cannabis). In addition, the legal status of several of the drugs reported is currently unknown. These data were either removed during the data cleaning process, or re‐coded in other categories, where appropriate. Following this, the revised totals for use of other illegal drugs during the previous six months were 8.5% (43/508), (W1) and 5.8% (20/344), (W2) including those who did not provide any drug names or 7.3% (37/508), (W1) and 5.8% (20/344) (W2) excluding those with missing drug names (no missing at W2). The most commonly used other illegal substances are listed in Table 36. Table 36: Other illegal drugs named by respondents Respondents may have noted more than one product
Wave 1 Wave 2 n n
Magic mushrooms 12 8 Nitrous oxide # 10 6 Cocaine 8 5 Amphetamine 7 2 Mescaline 4 3 Opium 0 1 # Nitrous oxide is legally categorised as a Prescription Medicine (requiring a doctor’s prescription for access). However, it is unlikely to be prescribed by doctors, and may have been accessed from the illicit market or via the hospitality/catering industries where it is used as a propellant.
4.4.17 Paired data analysis of change over time
4.4.17.1 Matching the pairs
A total of 344 participants provided their unique identifier (ID) for pairing data at W2. However, despite having 304 matching contact details, only 182 complete IDs from W2 were
62
able to be matched with W1 IDs, which led us to believe that some problems existed with matching the ID data. The most likely problem was with the request for the first and last letter of participants’ mother’s first name: potentially, people were using their mother’s maiden name by mistake on one occasion. Other possible issues were with place of birth, where at one wave a person might use a city and at the other wave the suburb, or if the place name consisted of two words might use the first and last letter of the first word or second word, and so on. However, statistical analysis of partial matches plus demographic data uncovered a further 91 potential pairs of which we are reasonably confident there is a match15. Furthermore, the following paired analyses were undertaken with and without extra pairs, and because no major differences were found in the results, we are reporting ‘with extra pairs’ results. However, there obviously remains a small element of doubt with regards to the validity of the ‘extra pairs’. The final number of matched IDs including the additional pairs at W1 and W2 was n=273.
4.4.17.2 Paired data analysis between W1 and W2 of change in proportions of respondents using a specific drug
Figure 1 shows the percentages of proportion of drugs used at the two waves. To test whether there were significant changes in use of specific drugs between W1 and W2 of the pairs, Mc Nemar’s Chi‐square tests were undertaken. Table 37 summarises the tests results. There is strong evidence that more participants switched from being BZP party pills users at W1 to BZP party pills non‐users at W2 than the other way around. There is also strong evidence that more participants switched from being legally available smokeable products users at W1 to legally available smokeable products non‐users at W2 than the other way around. There is strong evidence that more participants switched from non‐medical prescription drug non‐use to use between W1 and W2 than the other way around. There is weak evidence that more participants switched from being ecstasy users at W1 to non‐users of ecstasy at W2 than the other way around, mainly accounted for by non‐BZP users (indicating that BZP users had not switched to being non users), although the difference between BZP users and BZP non‐users was not significant with respect to this change.
15 Process for finding additional matches (I). a. Match people at W 1 and W2 using the first and third piece of information only (i.e. exclude the mother’s name question). b. Compare W1 demographics and W2 demographics of the extra pairs. c. Those with same genders and matched ages (e.g., same ages or 1 year older) are our possible new pairs
Process for finding additional matches (II). • Match people at W1 and W2 using the first and second piece of information only (i.e. exclude the place of birth question). • Compare W1 demographics and W2 demographics of the additional pairs. • Those with same genders and matched ages (e.g., same ages or 1 year older) are our possible new pairs
Process for finding additional matches (III). • Match people at W1 and W2 using the first and third piece of information only (i.e. exclude the mother’s name question). • Compare W 1 demographics and W2 demographics of the additional pairs. • Those with same genders and matched ages (e.g., same ages or 1 year older) are our possible new pairs
63
Figure 1: Use of substance in previous 6 months at W1 and W2 (N=273)
0
20
40
60
80
100
%
W1
W2
Table 37: Paired data comparison of substance use over time
NU‐W1 = non‐user wave 1; NU‐W2 = non‐user wave 2; U‐W1 = user wave 1; U‐W2 = user wave 2 MV = missing values; * = significant at 5% level.
16 The total number of discordant pairs is less than 10, therefore, McNemar’s chi‐square test may not be valid in this case.
Drug name NU‐W1, NU‐W2 n (%)
NU‐W1, U‐W 2 n (%)
U‐W1, NU‐W2 n (%)
U‐W1, U‐W 2 n (%)
McNemar’s chi‐square (X2)
p MV
BZP party pills 190 (70.6) 3 (1.1) 52 (19.3) 24 (8.9) 43.65 <.0001* 4
BZP‐free party pills 231 (84.9) 14 (5.2) 11 (4.0) 16 (5.9) 0.36 0.59 1Legally available smokeable products
231 (84.9 9 (3.3) 23 (8.5) 9 (3.3) 6.13 0.01* 1
Alcohol 14 (5.1) 5 (1.8) 6 (2.2) 248 (90.8) 0.09 0.76 0Cannabis 142 (52.0) 14 (5.1) 21 (7.7) 96 (35.2) 1.4 0.24 0Ecstasy 182 (66.7) 7 (2.6) 16 (5.9) 68 (24.9) 3.52 0.06 0Methamphetamine16 257 (94.1) 2 (0.7) 4 (1.5) 10 (3.7) 0.67 0.41 0GHB 255 (93.4) 6 (2.2) 4 (1.5) 8 (2.9) 0.4 0.53 0Ketamine 248 (90.8) 4 (1.5) 8 (2.9) 13 (4.8) 1.33 0.25 0LSD 222 (81.3) 9 (3.3) 11 (4.0) 31 (11.4) 0.2 0.65 0Prescription drugs (non‐med purposes)
242 (88.6) 15 (5.5) 4 (1.5) 12 (4.4) 6.37 0.01* 0
64
4.4.17.3 Analysis of change in using a specific drug between W1 and W2 for BZP users vs. BZP non‐users
Logistic regression for longitudinal data (i.e. GEE model) was undertaken using paired data, to explore the differences between BZP party pill users (defined as those who had used BZP party pills at W1) and non‐BZP users (defined as all remaining participants) in terms of their changes in use of all substances over time (i.e. time by group interaction effect). Results were significant in relation to use of ‘legally available smokeable products’ only. There was a higher proportion of BZP party pill users who did not use ‘legally available smokeable products’ at W2 than W1; on the other hand, a lower proportion of non‐BZP users did not use ‘legally available smokeable products’ at W2 than W1 (p=0.02).
4.4.17.4 Analysis of change in frequency of substance use over time: BZP users, BZP non‐users and non drug users
Longitudinal analysis of change in frequency of drug use was undertaken comparing three groups:
• Group 2: BZP party pill users: defined as those who had used BZP party pills at W1T1 (i.e. 1st January‐31st March 08).
• Group 1: BZP party pill non users: defined as those who had not used BZP party pills but had used at least one of the following substances: BZP‐free party pills, smokeable products, cannabis, ecstasy, methamphetamine, GHB, ketamine, LSD and prescription drugs at W1T1 (i.e. 1st Jan‐31st Mar 08).
• Group 0: Non drug users: defined as those who used alcohol only or used nothing at all at W1T1 (i.e. 1st January‐31st Mar 08).
People who did not use specific drugs at Wave 1 or Wave 2 have been given the value of ‘not at all’ for both W1T1 and W1T2 or W2T1 and W2T2, respectively. Time plots of average frequency of use across the four time points are displayed in the figures on the following pages (Figure 2 – 12). Multiple regression for longitudinal data (assuming an unstructured covariance matrix) was carried out. On the graphs, the timepoints (horizontal axis) are indicated by the following numbers:
• 1 = W1T1 (1st Jan‐31st March 08); • 2 = W1T2 (1st April‐30th June 08); • 3 = W2T1 (1st July‐30th September 08); • 4 = W2T2 (1st October to date of survey completion in December 08).
There was a decrease in frequency of BZP party pill use over time amongst Group 2, but not Groups 0 and 1, on average (p<0.0001). For BZP‐free product use, Group 2 and 1 use frequency increased over time then decreased again after the end of the amnesty period, compared with Groups 0 which remained stable (p=0.014) although for all three groups use remained infrequent at monthly or less. Group 2’s frequency of use of legal smokeable products decreased over time when compared with Group 0, with Groups 0 and 1slightly increased since the ban, and use in all groups infrequent at monthly or less.
65
For LSD, frequency of use overall was low. There was no significant difference in frequency of use between Groups 1 and 0; however, when comparing Groups 2 and 0, there was a slight and statistically significant increase in Group 2’s LSD use after the ban, which plateaued (p=0.02); use in all groups remained infrequent. For ketamine, whilst use was infrequent amongst all groups, there was a statistically significant, but non trend change in Group 2 frequency compared with that of Group 0 (p=0.004). For alcohol, cannabis, ecstasy, methamphetanine and GHB there was no significant change in frequency of use over time. Frequency of prescription drug use increased over time for Group 2, with little change in the other two groups; however this was not statistically significant. For ketamine, GHB and methamphetamine, sample sizes were extremely small and thus the analysis may not be sufficiently powered. Figure 2: Change in self‐reported frequency of use of BZP party pill use
66
Figure 3: Change in self‐reported frequency of use of BZP‐free party pills
Figure 4: Change in self‐reported frequency of use of smokeable products
67
Figure 5: Change in self‐reported frequency of use of alcohol
Figure 6: Change in self‐reported frequency of use of cannabis
68
Figure 7: Change in self‐reported frequency of use of ecstasy
Figure 8: Change in self‐reported frequency of use of methamphetamine
69
Figure 9: Change in self‐reported frequency of use of GHB
Figure 10: Change in self‐reported frequency of use of ketamine
70
Figure 11: Change in self‐reported frequency of use of LSD
Figure 12: Change in self‐reported frequency of non‐medical use of prescription drugs
71
4.4.17.5 Analysis of shift of change in self‐reported change in amount used between Wave 1 and Wave 2
Participants at W1 and W2 were asked to provide a response to the following questions. • W1: In your opinion, has your use of [substance] increased, decreased, or stayed
about the same since BZP party pills were banned? • W2: In your opinion, has your use of [substance] increased, decreased, or stayed
about the same since the first time you completed this survey in July/August this year?
Paired‐data analysis (Wilcoxon Signed Rank Test) was undertaken to see whether any shift had taken place in the ‘self‐reported change’ in amount of drug used during W1 and W2 for participants who used specific drugs at both waves only. Those answering ‘don’t know’ were treated as missing values. For example, a significant result might be if the majority of users reported a decrease in use of a substance at W1 and then reported an increase in use at W2. So the direction of change itself is not being reported, rather that there has been an alteration in the direction of change in use. The results were significant for shift in change in amount of ecstasy use only. On average, the changes in amount of ecstasy use switched from a higher level at W1 to a lower level at W2 (e.g., increasing at W1 to staying about the same at W2; or staying about the same at W1 to decreasing at W2, etc). However, when exploring the two waves separately, more ecstasy users reported an increase in ecstasy use ‘since the ban’ than a decrease in use (30% versus 7% respectively) when asked at Wave 1 (July 2008) and only slightly more reported an increase in use than a decrease in use (20% versus 13%) since “the first time they completed the survey” when asked at Wave 2 (December 2008). The results were not significant for any other substances, which means, for each of those substances, there is no significant shift in the self‐reported change in amount of drug used during W1 and W2 (e.g. increasing at W1 and then continuing to increase at W2; or decreasing at W1 and then continuing to decrease at W2).
4.4.18 Reasons for change in substance use – qualitative data As a means of identifying the reasons behind self‐reported changes in substance use respondents were asked: “If, in your opinion, your use of ANY of the substances we have asked about today has changed (i.e. increased OR decreased) since BZP party pills were banned on April 1st 2008, please write the reasons for this in the box below. Please also indicate which substance you are talking about and describe the way in which your use has changed (e.g. used more or less frequently)”.
There was also the opportunity to comment on reasons for any changes in use as part of an additional question in the survey, where respondents were prompted to make general observations about the questionnaire or their drug‐taking experiences. The findings presented in Tables 38 and 39 collate responses to both questions. Where responses were relevant to more than one theme, they have been counted as such. In addition, whilst some
72
responses fall outside of reasons for a change in substance use, they have been included due to their relevance to the broader aim of the study (i.e. to investigate the impact of the 2008 re‐classification of BZP on substance use behaviour). It is important to note that not all participants in the survey answered either or both of these questions. Therefore, we do not know how representative they are of the overall sample. However, they provide some useful insights in the reasons drug users attribute to changes in their substance use behaviour.
4.4.18.1 Wave one
Table 38 presents W1 data on reasons for a change in substance use, as identified by respondents. Whilst many comments (n=71) were received regarding respondents’ views on BZP, a similar number (n=64) made reference to an increase in use of other substances, particularly ecstasy, due to the banning of BZP. Not surprisingly, given the timing of the W1 survey, there was limited indication of users having reduced their use of BZP since the change in legislation. A large number of responses (n=90) referred to the fact that respondents had not had any change in their substance use during the stated time period, and a smaller number (n=26) included statements about changes having been due to reasons unrelated to the banning of BZP (e.g. personal lifestyle changes).
4.4.18.2 Wave two
Table 39 presents W2 data on reasons for a change in substance use, as identified by respondents. As with W1, many of the comments received (n=39) were more general statements about respondents’ views on BZP, particularly the banning of the substance. In W2, other key themes identified in the responses included an increase in use of a range of substances due to the banning of BZP (n=32). These were linked with issues such as using other drugs as a replacement due to the substance not being available or because it was difficult to access. However, a similar number of comments received (n=43) indicated that the ban had had no impact on their use of substances (either legal or illicit).
73
Table 38: Reasons for a change in substance use (W1) Theme N Description of theme Examples from the data BZP – other comment 71 This theme includes any general comments made about BZP (e.g.
the banning of the substance, general observations on the impact of the legislative changes, views on the effects of the substances, and personal previous experience of using BZP). This category excludes any comments relating to the impact of the ban on respondents’ personal substance use.
“In my experience, people who use illegal drugs such as ecstasy or GHB probably aren't high BZP users anyway, so the ban wouldn't have affected them so much”. “Less BZP has lead to a decrease in the number of bad pills ‐ E or similar, that are sold, you would often get BZP from a dealer claiming it was E”.
Increase in use of the following substances – due to the banning of BZP
64 This theme includes any comments relating to an increase in the use of substances where respondents explicitly linked this to the banning of BZP. This include increased use of other drugs:
• as a replacement for BZP • because BZP had become harder to access (or was no
longer available) • due to their increased availability since BZP was banned
(e.g. BZP‐free party pills) • due to changing patterns of substance use as a result of
BZP no longer being available (e.g. drink larger amounts of alcohol whereas previously would have stopped drinking after using BZP).
Alcohol 13 My alcohol consumption has increased slightly, as often when I had taken party pills I did not drink alcohol after taking them ‐ but may have had a few alcoholic drinks before taking one. Now that they are not as readily available, I find myself drinking
Cannabis 4 I did more dope because was depreased [sic] about BZP party pill being banned.
Ecstasy 27 I use ecstasy on a more regular basis now because party pills containing BZP are now hard to find and their price has increased to the point where you may as well buy ecstasy.
Illicit drugs 7 I used to take one herbal at midnight, would last all night till 6am. It was cheap only $10 and by the time I went home I was good to drive‐ no spending $40‐$50 on a taxi. I never really drank alcohol on BZP party pills. Since they have been banned I have increased in binge drinking and have taken more illegal class A drugs that I used to be terrified of taking, such as e, acid and speed. And I tend to mix a lot of substances as well.
Other drugs (including those not specified)
13 My use of Ritalin has increased largely because of easy availability due to getting an ADD diagnosis, but the impetus to get a diagnosis, while mainly for therapeutic reasons was greatly amplified by the ban on BZP so that I could use it recreationally as a partial replacement as well.
74
Theme N Description of theme Examples from the data
Decrease in use of: This category includes any comments relating to a decrease in the use of substances where respondents explicitly linked this to the banning of BZP.
BZP 9 My use of BZP party pills has decreased since they became banned because they are not so easy to get hold of.
Cannabis 2 My use of cannabis decreased as I used to use it mainly to help me sleep after the BZP pill wore off….. [abridged]
Other drugs (including those not specified)
3 …I also don’t need codeine etc to come down, and I don’t think I drink as much as I did when herbals were around. Everyone seems a lot less talkative and a bit more healthier [sic], but then I had a bad experience with them (like most people I know)… [abridged]
No change in substance use 90 This category incorporates any comments made in relation to the ban having had no impact on the use of legal or illicit substances. Some respondents specifically stated that there had been no change due to not having previously used BZP.
My use of BZP has not changed since April 1st 2008 as I have not taken this substance for about three years, however I used to use BZP products regularly prior to this. Has stayed the same. I would never activly [sic] go looking for party pills or ever pay for them, they are shit. Only take them if am given them but still hate them!
Substance use change not related to ban
26 Some respondents indicated that changes in their substances had been due to reasons other than the banning of BZP (e.g. lifestyle or seasonal changes).
My low consumption of alcohol is not related to the fact that BZP pills have been banned but more so because alcohol makes me feel sick whilst drinking it; therefore I only drink about once a month. But in some ways that is probably why I use cannabis more often as a replacement of [sic] alcohol. I have not used any substances more or less frequently since the introduction of the BZP ban, however this may be due to me not going out much in the last 6 months.
Other comment 22 This category includes any general comments made about drug
use (excluding those related to BZP and/or changes in substance use).
The older generations saying drugs are bad just makes them more desireable [sic] to young people. I haven't had any major serious negative side effects from using any of these drugs, the side effects seem minor to me
75
Theme N Description of theme N/A 8 Some respondents recorded n/a as a response to the question. Faulty data 5 A small number of responses contained irrelevant information or
data that were indecipherable.
Table 39: Reasons for a change in substance use (W2)
Theme N= Description of theme Examples from the data BZP – other comment 39 This theme includes any general comments made about BZP (e.g.
the banning of the substance, general observations on the impact of the legislative changes, views on the effects of the substances, and personal previous experience of using BZP). This category excludes any comments relating to the impact of the ban on respondents’ personal substance use.
I have not tried any of the new BZP‐free pills due to bad publicity in media about their safety compared to BZP pills previously available. I found BZP pills, in moderation, to be a fine product to use instead of alcohol, or in combination with it. In my opinion I think it was great that party pills were banned but it frightens me wondering what else are they going to come up with to get a buzz.
Increase in use of the following substances – due to the banning of BZP:
32 This category includes any comments relating to an increase in the use of substances where respondents explicitly linked this to the banning of BZP. This include increased use of other drugs:
• as a replacement for BZP • because BZP had become harder to access (or was no
longer available) • due to their increased availability since BZP was banned
(e.g. BZP‐free party pills) • due to changing patterns of substance use as a result of
BZP no longer being available (e.g. drink larger amounts of alcohol whereas previously would have stopped drinking after using BZP).
Alcohol 3 I have found that my alcohol consumption has increased quite substantially. A reason maybe that when I did take the odd party pill I didn’t consume alcohol because I felt that the pills alone were enough. [abridged]
Cannabis 2 I believe, th[r]ough the observation of my peers, that we simply cannot stay awake as long on a night out now that BZP is illegal, so we are tending to smoke cannabis during the day, almost as if to make up for the fun that we are missing.
Ecstasy 10 I use ecstasy slightly more often now... when BZP was legal I would sometimes take BZP based party pills and occasionally take E. Now if I'm going to take anything, it'll be E.
Illicit drugs
11 Increased, until party pills were banned I had only ever smoked weed, no illegal drugs, now I have taken several and that list will probably increase.
76
Theme N Description of theme Examples from the dataOther drugs (including those not specified)
6 Did acid on an occasion where I would usually take party pills, so yes my use of other substances has increased.
Decrease in use of: This category includes any comments relating to a decrease in
the use of substances where respondents explicitly linked this to the banning of BZP.
BZP 4 BZP pills decreased as they are no longer easily accessible.Other drugs (including those not specified)
2 Due to the flood of BZP based products into the 'black market' other, cleaner high quality illicits have droped [sic] in aviabality [sic]. This would be the reason for any decreases in use.
No change in substance use 43 This category incorporates any comments made in relation to the ban having had no impact on the use of legal or illicit substances. Some respondents specifically stated that there had been no change due to not having previously used BZP.
No. My desire for drugs has stayed exactly the same. My use of BZP has also remained unchanged. This may alter once my stockpile has run out. But for the moment it is all the same.
Substance use change not related to ban
40 Some respondents indicated that changes in their substances had been due to reasons other than the banning of BZP (e.g. lifestyle or seasonal changes).
My intake of alcohol has increased since April 1st 2008 but I think it is more related to finishing uni rather than directly on the banning of BZP party pills.
Other comment 25 This category includes any general comments made about drug
use (excluding those related to BZP and/or changes in substance use).
I travelled overseas where "real" drugs were more easily available, such that I don't have to resort to more harmful surrogates.
N/A 8 Some respondents recorded n/a as a response to the question. Faulty data 2 A small number of responses contained irrelevant information or
data which were indecipherable.
77
4.4.19 Experiences of adverse events In total, at W1, 69 respondents who said they had used substances of interest (i.e. those listed in Sections 1A to 1D of the questionnaire)17 said they had a total of 173 experiences of adverse events (AEs). Of these, 65 respondents provided details for 70 AEs, including seven that related to adverse events associated with alcohol, tobacco/shisha (flavoured tobacco) and/or coffee only. Excluding these, overall, 58 respondents provided details for 63 experiences of AEs at W1. At W2, 24 respondents who said they had used substances of interest (i.e. those listed in sections 1A to 1D of the questionnaire)17 said they had a total of 44 experiences of AEs. Of these, 22 respondents provided details for 23 AEs, including five that related to AEs associated with alcohol, tobacco/shisha (flavoured tobacco) and/or coffee only. Excluding these, overall, 17 respondents provided details for 18 experiences of AEs at W2. At least five respondents who said they had used substances of interest (i.e. those listed in sections 1A to 1D of the survey)17 at both waves reported experiences of AEs at both waves. Therefore, in total, 70 respondents reported a total of 81 experiences of AEs where details were provided.18 However, the quality of eight of these 81 reports from seven respondents (wave 1: 6; wave 2: 1) was poor; these reports did not provide either a substance name or substance category and/or details of the AEs experienced. After excluding these reports, 63 respondents provided adequate details for a total of 73 experiences of AEs. Of these 73 reports, 39 (W1: 35; W2: 4) involved products described only as 'party pills' (W1: 4; W2: 1), those whose contents are unknown or unclear to the researchers (W1: 3 (Extacy, Havoc, Mag [sic] dog); W2: 1 (xtc, millz [same report]), or a BZP‐containing product (W1: 28; W2: 2), specified by respondents as BZP, BZP/TMFPP, or by giving a specific product name (e.g. Enjoi, Charge, Ice Diamonds, Red Hearts, Silver Bullet). In total, 15 reports (W1: 8; W2: 7) involved the use of one or more herbal substances (e.g. Salvia divinorum, 'party pills' marketed as containing one or more herbal ingredients, including Hummer19),20 with or without concomitant use of other substances. Table 40 contains summary details for these reports, as well as details of five reports (W1: 4; W2: 1) involving products described by respondents only as 'BZP‐ 17 These numbers include some people who incorrectly answered sections 1A to 1D and, having done so, were presented with the questions on adverse events, with some respondents subsequently providing reports. These reports have been included in the analysis.
18 Because of the poor quality of the data and the nature of the study/subject area, reports where the substance name was stated only as e.g. 'BZP‐free herbal' have been included.
19 Hummer is the name given to a BZP party pill, but there are also Hummer BZP‐free party pills available; as we cannot be certain which product was used, we have taken an inclusive approach. In addition, the Ministry of Health tested Hummer and found it contained the substance 1,3‐dimethylamylamine (DMAA) which is a synthetic stimulant.
20 Products containing both BZP ingredients and herbal ingredients have been excluded.
78
free', as 'herbal' party pills without naming a specific product, or as 'Pure Bliss', which is marketed as being BZP‐free, but as we cannot ascertain ingredients, the presence of herbal ingredients is unclear. The remaining 14 reports (W1: 9; W2: 5) related to other conventional substances, including prescription medicines (e.g. clonazepam, ketamine, phenazepam), and illegal substances (e.g. marijuana/cannabis/'weed', 'ecstasy', MDMA), used recreationally. Overall, two of the 20 reports summarised in Table 40 can be classed as serious21 since respondents stated that they were admitted or treated at a hospital. One of these reports involved a 20‐year‐old male with alcohol poisoning and vomiting for four days following use of Salvia divinorum and alcohol, and the other involved a 21‐year‐old male who experienced paranoia, hallucinations and loss of appetite following use of Hummer22 pills. A further seven reports, two of which involved vomiting and three of which involved nausea, were rated by respondents as bad enough to affect their activities. All respondents reporting adverse events said that they fully recovered from the experience. None reported the experience to a general practitioner, the Alcohol & Drug helpline or other helpline, or to the National Poisons Centre; rather, respondents sought advice from family/friends or, apart from the two respondents who attended/were admitted to hospital, did nothing in response to experiencing the AE(s). In total, in eleven cases, respondents stated the use of one substance only; in six cases, the herbal substance or BZP‐free party pill had been used with alcohol only (apart from cigarettes and oral contraceptive pill); in a further two cases, the herbal substance or BZP‐free party pill had been used with marijuana/'weed' (in one of these cases alcohol was also used) and in the remaining case, two herbal substances were used together. Two of the 20 reports involved the use of smoked S. divinorum with alcohol or 'weed', one involved the use of smoked Spice and Dream, and one involved the use of Dream orally. Six reports (three from each wave) involved the use of products (Comet, Hummer23, Vegas Nights) stated to contain the 'Floradrene' (see Table 41) blend of ingredients. In four of the six reports, respondents described experiencing nausea after using the product; the two other reports related to paranoia and hallucinations, and insomnia and anxiety. In five of these cases, the product was the only substance respondents claimed to have used; the other respondent used the
21 Serious adverse effects are those that are fatal, life‐threatening, disabling, incapacitating or which result in or prolong hospitalisation, are a congenital defect, or are otherwise medically significant.
22 See footnote 21
23 See footnote 21
79
product with alcohol. One respondent said he was admitted to hospital because of the AE (paranoia, hallucinations, loss of appetite), three rated the AEs (nausea; palpitations, nausea, general malaise; loss of appetite, insomnia) 'bad enough to affect what they were doing' and two rated the AE (nausea) as 'uncomfortable, or a nuisance/irritation but did not affect activities'; all six respondents said they fully recovered. A causality assessment for the 20 reports in Table 40 undertaken by one assessor using the World Health Organisation's Causality Algorithm found five reports to be 'unassessable/unclassifiable' due to missing data (e.g. a specific product was not identified, or the ingredients of the product are unknown) and 15 to be 'possible'.
80
Table 40: Summary details for self‐reported adverse effects involving herbal substances and BZP‐free party pills Sex, age
Wave Adverse effect(s) Severity Substances used
Quantity; Route of administration
How often substance is usually used
Action taken
Outcome Impact Causality Assessment24
m, 20
1 extreme vomiting, stomach ache
1 Pepe 2 pills; oral
1/m sought advice from a friend or family member
fully recovered
will never take BZP‐free again
possible
alcohol few RTDS25; oral
2‐3/w
m, 25
1 insomnia, headaches, low mood
2 Dream n/s; oral 1/m did nothing
fully recovered
none possible
m, 24
1 'itchy brain' and head after the herbal 'kicked in'; next day: nausea, dry throat
1 'Herbal' one; oral 1/m did nothing
fully recovered
haven't taken that herbal since
unassessable/unclassifiable
Alcohol ten; oral 2‐4/m the pill one; oral 4+/w cigarettes 10/d;
inhalation 4+/w
m, 20
1 alcohol poisoning; vomiting for four days
4 Mexican tripping weed
one smoke; inhalation
1/m went to H; advice from f/f
fully recovered
none possible
Bourbon 24 pack; oral 2‐4/m
m, 21
1 paranoia, loss of appetite, hallucinations
4 Hummer 3 pills; oral 1/m did nothing
fully recovered
n/a possible
24 Undertaken by one author (JB) using the World Health Organisation Uppsala Monitoring Centre’s algorithm for causality assessment (see www.who‐umc.org)
25 RTDS assumed to mean Ready to Drink alcoholic beverages
81
Sex, age
Wave Adverse effect(s) Severity Substances used
Quantity; Route of administration
How often substance is usually used
Action taken
Outcome Impact Causality Assessment
m, 24
1 an extreme 'high' one hour after taking pills, and anxiety, insomnia, shakes, vomiting the next day lasting for about two days
1 Unknown brand of 'BZP‐free herbal'
1 tablet; oral 1/m did nothing
fully recovered
unlikely to take again
unassessable/unclassifiable
m, 24
1 tiredness one hour after taking
2 BZP‐free pill two pills; oral 1/m did nothing
fully recovered
will not use again
unassessable/unclassifiable alcohol 7 drinks; oral 2
m, 19
1 paranoia, extreme emotional discomfort, feeling paralysed, desire to be sober
1 Salvia divinorum
3 caps; smoked with bong
1/m did nothing
fully recovered
will not use again
possible
'weed' 3 caps; smoked with bong
1/m
m, 22
1 nausea about 5 hours after taking first pill
2 Vegas Nights two pills, an hour apart; oral
1/m sought advice from f/f
fully recovered
wouldn't take that brand again
possible
f, 28
1 nausea the following day
2 Comet 3 pills; oral 1/m did nothing
fully recovered
cautious but would probably use again
possible
Alcohol 7 drinks; n/s 2‐4/m
m, 21
1 insomnia, enhanced hangover effects of alcohol
5 BZP‐free pills 1 pill; oral 1/m did nothing
fully recovered
do not take
unassessable/unclassifiable
Alcohol 3 RTDS; oral 2‐4/m
82
Sex, age
Wave Adverse effect(s) Severity Substances used
Quantity; Route of administration
How often substance is usually used
Action taken
Outcome Impact Causality Assessment
m, 21
1 vomited 30 minutes after taking the pill
5 Chuckys one pill; oral 1/m did nothing
fully recovered
none possible
f, 29
2 Nausea, palpitations 2 Trance one tablet; oral
1/m did nothing
fully recovered
don't take anymore
possible
f, 22
2 'gross feeling' in stomach, nausea
1 Hummer, Vegas Nights
two pills; oral 1/m sought advice from f/f
fully recovered
don't want to mix them again, hesitant to take again
possible
f, 21
2 vomiting 5 Chuckys one pill; oral 1/m did nothing
fully recovered
none possible
f, 25
2 several hours later can't eat or sleep for up to 36 hours after, anxiety, 'makes me chew the insides of my mouth out'
1 Comet two pills, about two hours apart; oral
1/m did nothing
fully recovered
plan not to use again, but usually do
f, 23
2 tiredness, crankiness, irritation, hunger about 20 minutes after smoking
5 Spice two cones; smoked
1/m did nothing
fully recovered
won't try again but might try another product
possible
Dream two cones; smoked
1/m
83
Sex, age
Wave Adverse effect(s) Severity Substances used
Quantity; Route of administration
How often substance is usually used
Action taken
Outcome Impact Causality Assessment
m, 25
2 upset stomach, feeling of wanting to be somewhere familiar
2 Pure Bliss 3; oral 1/m did nothing
fully recovered
none unassessable/unclassifiable
f, 19
2 nausea, panic attack 2 Pepe one pill; oral 1/m did nothing
fully recovered
none possible 'weed' one joint;
smoked
4+/w
alcohol 8 drinks; oral 2‐3/w m, 20
2 palpitations, severe nausea the next day, general ill health lasting two days
1 Comet two; oral 1/m sought advice from f/f
fully recovered
will not use BZP‐free again
possible
Severity: 1 bad enough to affect what I was doing; 2 uncomfortable, nuisance or irritation but able to carry on what I was doing; 3 no effect; 4 bad enough to be admitted to hospital; 5 mild or slightly uncomfortable; How often: 1/m = about once a month; 2‐3/w = 2‐3 times per week; 2‐4/m = 2‐4 times per month; 4+/m = 4 or more times per month
84
Table 41: Labelled ingredients of herbal products and BZP‐free party pills containing herbal ingredients Name of product Ingredients Chuckys# BZP‐free, includes geranium extract Comet Floradrene blend: amino acids, Citrus aurantium, Hamelia patens,
Paulinia cupana, Pelargonium graveolens, Polygonum multiflorum 1 Dream2 See Spice Gold2. Promoted as being 'stronger' than Spice Gold2 Hummer Floradrene blend: amino acids, Citrus aurantium, Hamelia patens,
Paulinia cupana, Pelargonium graveolens, Polygonum multiflorum 1 Pepe amino acids, caffeine, B vitamins, black pepper extract Pure Bliss BZP‐free Spice/Spice Gold2 baybean (Canavalia maritima), dwarf skullcap (Scuttellaria nana), lions
tail (Leonotis leonurus), lousewort (Pedicularis densiflora), maconha brava (Zornia latifolia), marshmallow (Althaea officinalis), pink lotus (Nelumbo nucifera), red clover (Trifolium pratense), rose (Rosa gallica), Siberian motherwort (Leonotis sibiricus), vanilla (Vanilla planifolia) [n.b. some variations in descriptions of content occur across different vendors]
Trance caffeine, geranium extract, Griffonia seed extract Vegas Nights3 Floradrene blend: amino acids, Citrus aurantium, Hamelia patens,
Paulinia cupana, Pelargonium graveolens, Polygonum multiflorum N.B. Contents of products are as stated on websites marketing the products listed and have not been confirmed by pharmaceutical analysis of samples # Information from manufacturer 1 Floradrene has been identified as containing a synthetic stimulant, 1,3‐dimethylamylamine (DMAA) (Ministry of Health, personal communication, 2009). 2 Spice’ “Spice Gold” “Spice Diamond” and “Dream” were all tested by the Ministry of Health and found to contain the 1,1 dimethyloctyl homologue of the substance CP 47,497. The Ministry is of the view that this substance is substantially similar in chemical structure to THC and accordingly, a controlled drug analogue. With this substance in them, this makes Spice and Dream products illegal class C controlled drugs. 3 Both Vegas Nights and Hummer have been tested and found to contain the synthetic stimulant 1,3‐dimethylamylamine (DMAA)
85
5 SUMMARY AND DISCUSSION
5.1 Sample demographics
Our study sample was drawn from the New Zealand public aged 18‐30 years and with access to the Internet. Over three quarters of the total W1 sample identified as New Zealand European, more than half were male, and over half were in full‐ or part‐time study. Our sample demographics indicate an overrepresentation of males (56% males W1 vs. 48.8% 2006 Census) and of New Zealand Europeans (75% W1 vs. 67.6% 2006 Census) compared with whole population 2006 census data. Māori and Pacific Islanders were underrepresented. Our study sample is also over‐representative of those living in the Auckland region. The sub‐sample at W2 was similar to that at W1 in terms of demographics.
5.2 Sample substance use
The majority of our total sample at W1 had used alcohol, almost half had used cannabis , one third had used ecstasy and BZP , 16% LSD, and fewer than 10% had used ketamine, GHB, or methamphetamine in the previous 6 months. In addition, around one in ten had used prescription drugs for non‐medical purposes, with similar numbers having used ‘other illegal’ substances at W1.
In order to compare our sample with 18‐30 year olds nationally we turned to two national household surveys ‐ the 2003 Health Behaviours Survey (HBS) 23 and the National Household Survey of BZP use (NHS‐BZP) 3. In the HBS the closest reference is use in the last 12 months amongst 18‐24 year olds. For all substances, except methamphetamine26, use was lower in the HBS data (and as HBS data collected data on use over a 12 month period as opposed to a 6 month period as in our study, once might expect HBS percentages to be higher if the two samples are comparable). In comparing our data with those from NHS‐BZP, for use over the past 12 months amongst all party pill users, we find a closer match to our study, although their sample was not limited to 18‐30 year olds (but had highest lifetime use amongst that age group). In the NHS‐BZP study, 60.8% of BZP party pill users had used cannabis in the last year, 21% ecstasy, 15.9% amphetamines (including methamphetamine), 10% LSD and 1.7% GHB 1.
In our study, almost 14% had used legally available smokeable substances, but there are no national data available for comparison.
We may infer from this that our sample is more weighted towards the club drug scene, with higher levels of use of ecstasy, LSD and GHB, but lower levels of use of other substances when compared with the NHS‐BZP study.
26 It should be noted that the HBS recorded use of ‘amphetamine’ rather than ‘methamphetamine’. Last 12 month use of the substance was higher in the HBS data ( 8.7% having used amphetamine compared to 5.5% having used methamphetamine in our study).
86
5.3 Change in use over time
The following section summarises changes in each substance use over time, and discusses the potential implications of these.
5.3.1 Change in BZP party pill use over time
When comparing BZP users versus non‐users over time, we can see that there was a significant fall in BZP use (in terms of absolute use and self reported change in use amount), against a backdrop of no increase in for non‐users becoming users. In addition, the paired data analysis confirmed this pattern (i.e. if use decreased at W1 then it continued to decrease in W2 as well). Interestingly, a small proportion was still able to access from retailers after the ban. Although it has been suggested that an illicit market for BZP might emerge, the fact that few respondents said they were accessing these substances from dealers indicates that, thus far, this may not have happened. However, this question of an ‘illicit market’ was not specifically asked of participants. The quantitative data relating to BZP party pills indicate that a ban on BZP and related substances has been successful in reducing use, and that in the short term a significant illicit market does not seem to have developed.
5.3.2 Change in BZP‐free party pill use over time
Full sample data for Waves 1 and 2 indicate that these substances were not used by many respondents (around 11%), and that amongst users, use was mainly monthly or less frequently. More BZP‐free party pill users reported a ‘decrease’ in amount used than a ‘increase’ in use when asked at both W1 (3 months after the ban) and W2 (3 months since W1) from full sample data. The main source of supply was friends or retail outlets. Although one might have predicted these products would become more popular and replace BZP party pills, this does not seem to have been the case.
5.3.3 Change in legally available smokeable substance use over time
As with BZP‐free party pills, the proportion of users was small, with paired data analysis showing a move to non‐use over time. However, when we divided participants into BZP users and non‐BZP users, this trend appeared to exist only amongst the BZP user group; amongst the non‐BZP users there was a slight move towards using ‘legally available smokeable substances’ over time. Access at both time points was typically through friends and retail outlets. Paired data comparisons of BZP users versus others indicate that although frequency of use of legally available smokeable substances was monthly or less, there was a decrease in frequency of use amongst BZP users and a slight increase in frequency of use amongst others. Full sample data indicate self‐reported amount of use tended to be stable. Again, any predicted increase in use amongst BZP users has not emerged.
5.3.4 Change in alcohol use over time
The majority of the samples at W1 and W2 were users of alcohol. Most alcohol users drank alcohol 2‐4 times a week or less frequently, and paired data analysis indicates that the patterns of use remained static over time. When comparing BZP users with
87
the other two groups, there was very little change in frequency of use of alcohol over time, and full sample data indicate most self‐reported amount of use to be stable.
5.3.5 Change in cannabis use over time
The proportion of cannabis users, according to paired data analysis, remained static over time, and full sample data indicate three quarters reporting no change in amount used, and only 14% reporting an increase. W2 data are mixed in this regard. However, frequency of use amongst BZP users increased slightly, but so did use amongst the non substance users/alcohol only group. Conversely, there was a slight decrease in frequency of use amongst those who used other substances apart from BZP. It is difficult to explain these patterns.
5.3.6 Change in ecstasy use over time
There was a decrease in the proportion of those using ecstasy over time, supported by the paired data analysis, although the evidence is weak, and there are weak indications that this might be accounted for mainly by non‐users of BZP becoming non‐users of ecstasy. There were indications of a self reported increase in amount of ecstasy use ‘after the ban’, for a minority of users when asked at both wave 1 and wave 2; however, when undertaking paired analysis of change in extent of ecstasy use over time, the results show that for those participants who had used ecstasy during both waves, participants who reported that their use of ecstasy increased at W1 were tending to shift to decreased use at W2.
5.3.7 Change in methamphetamine use over time
A very small proportion of our sample had used methamphetamine at either time point, and these proportions are lower than found in either the HBS data in 2003 23, or in the Wilkins et al study of BZP users 3. There was no significant change in proportion of use over time, although more methamphetamine users reported a ‘decrease’ in amount of use than ‘increase’ in amount of use at W2, but this was not the case at w1 according to the full sample data.
5.3.8 Change in GHB use over time
As with methamphetamine the proportion of users was small at both waves, with most users using GHB once a month, or less frequently, and no change in frequency of use over time.
5.3.9 Change in ketamine use over time
Ketamine data are remarkably similar to GHB data, although paired analysis indicates a slight increase in frequency of use directly after the BZP ban amongst users of any substance, but not amongst those who were non users at W1. However, this returned to baseline by W2T2.
5.3.10 Change in LSD use over time
The proportion of LSD users in our sample is greater than that found in either the HBS data in 2003 23 or in the NHS‐BZP study of BZP users in 2005 3. When comparing
88
BZP users and users of one other substance (not BZP), the frequency of use amongst BZP users prior to the ban was lower than for the other user group, but increased during the amnesty period. These data indicate that some BZP users may have moved to trying LSD and more frequently. That said, frequency of use still remained low and there is the potential for false positive results. Full sample data indicate that most users continued to use the same amount, although of the remainder, more reported an increase than a decrease, both after the ban and at W2.
5.3.11 Change in non medical use of prescription drugs over time
Interpreting these data needs to be undertaken with caution as the medicines combined in this section included benzodiazepines, opioids and stimulants, each with different effects. We have collated data to look for patterns of change under the assumption that there might be a change to use of quasi‐legal substances (i.e. medically available). Full sample data indicate that around 9% of the sample used prescription drugs at W1 and W2, with frequency of use being 2‐4 times a week or less frequently – higher than that for many of the illicit substances. Full sample data also indicate that most users continued to use the same amount, although of the remainder, more reported an increase than a decrease, both after the ban and at W2. When looking at paired data, there was a significant move from non‐user to user. Amongst BZP users, frequency of use slightly increased. This might indicate that BZP users, having already tried prescription medicines, prefer to remain with drugs they might perceive as less dangerous as they are medically prescribed, rather than moving to using illegal drug of unknown quality. A recent paper on BZP users’ perceptions of BZP party pills indicates that the fact that they were ‘legal’ conferred on them an air of being considered ‘safe’ by the government and having been quality assured 24. This may also be the case with prescription medicines.
5.3.12 Qualitative data ‐ self‐reported reasons for a change in substance use A limited number of respondents reported a range of reasons for their substance use having varied over the study period. These included reasons both unrelated and linked to the BZP ban. In keeping with the sample demographics for this study, which indicate a weighting towards the club drug scene, ecstasy featured highly in relation to use having increased due to the banning of BZP. Reasons for this mostly related to the fact that BZP was now no longer available, or difficult to locate, with ecstasy therefore being used in its place. However, these findings need to be treated with caution due to the small numbers involved.
When reporting on reasons for a change in substance use, only a small number of responses referred to a decrease in BZP use due to the reclassification of the substance, even at W2. Given that there was very little indication at this early stage that an illicit market has developed for the substance, it would be reasonable to expect that more people would have reported a reduction in their use of BZP products. However, as highlighted earlier, it may be that respondents had stockpiled supplies of BZP which they were still using in December 2008 when the W2 survey took place. In addition, the short time period between the end of the amnesty period and the W2 survey needs to be acknowledged (just less than three months),
89
as it is questionable whether this would be a sufficient period of time for any significant drug market changes to be observed. It has also been hypothesised that given reports of BZP’s low level psychoactive effects 4, particularly when compared to ecstasy, users may not consider risking a criminal conviction for a less potent drug.
It is interesting to observe the level of comments received which referred to changes in substance use being due to reasons beyond the ban. As reported by participants, other factors such as personal lifestyle changes or seasonal events had impacted on this occurrence.
In addition, a large number of comments was received under the theme of “BZP – other comment”. These reveal a wide range of opinions regarding the legislative changes introduced in 2008 – including support for and against the ban. This is reflective of the make‐up of the sample, which consisted of both people using a wide range of illicit substances (who could be expected to be less supportive of the ban), as well as those who used alcohol only and stated strong views against use of any illegal drugs.
5.3.13 Adverse events associated with use of unclassified substances The study has revealed that small numbers of users of unclassified recreational substances experienced AEs that they associated with their use of such substances, and that these experiences are, in some cases, sufficiently severe and/or serious that respondents claim they would refrain from, or be cautious about, using such substances again.
The proportion of users who experienced AEs associated with use of unclassified recreational substances is difficult to estimate. Overall, around one third of respondents who had used substances of interest at W1 and/or W2 provided details of AEs they said they had experienced following use of these substances. However, many of the AEs described involved the use of BZP‐containing products, 'conventional' recreational substances (e.g. marijuana, ecstasy) and/or prescription medicines; the number of reports described in association with the use of herbal substances was small ‐ around 15. Of these, most related to the use of proprietary BZP‐free products containing herbal ingredients. Two reports involved the use of S. divinorum, a plant with a history of ethnobotanical use in Mexico and which is becoming known as a hallucinogenic substance. These two reports came from 2 (6%) of the 31 respondents who had used S. divinorum at W1.
Most of the AEs described in association with use of unclassified recreational substances were non‐serious (e.g. nausea, insomnia), although a small number gives some cause for concern: two respondents attended hospital for treatment for alcohol poisoning and paranoia and hallucinations, and five other respondents described paranoia, palpitations and/or other adverse health effects lasting for between 24 and 48 hours.
As with many herbal substances, there are only limited data available on their safety. Several of the herbal products associated with AEs reported by respondents contain herbal ingredients that are currently associated with safety concerns: for example,
90
Polygonum multiflorum has been associated with hepatotoxic reactions and Citrus aurantium has been associated with cardiovascular and cerebrovascular adverse reactions [see Section 3 Literature Review]. The safety profile of a substance following acute and chronic administration may vary and, for most herbal substances, the effects of long‐term recreational use are unknown. For some products, it was not possible to determine what the ingredients are and, even where the ingredients are stated on products or their manufacturers' websites, important information, such as the plant part used, the type of extract, the precise quantity contained in the product, is often lacking. Furthermore, since these products are unregulated, there is no assurance as to their pharmaceutical quality. Testing by government agencies has revealed that indeed some of these products actually contained prohibited herbal and non‐ herbal ingredients. The finding that none of the respondents who experienced AEs associated with unclassified recreational substances reported this to their GP or other healthcare professional, to drug helplines, or to the National Poisons Centre (NPC), indicates that these events would otherwise have gone unreported. Although respondents were not asked specifically if they had reported the AE(s) to CARM, none said they had done so in response to an open question about action they had taken. CARM accepts, but does not encourage, reports of suspected adverse drug reactions submitted by the public, whereas the NPC provides a 24‐hour telephone advice service to professionals and the public on acute poisonings. The NPC and CARM have received calls and reports, respectively, regarding herbal substances of interest (personal communication: NPC, 13 March, 2009; CARM, 8 April, 2009). The National Poisons Centre has received calls from users and/or healthcare professionals for several substances and products of interest, including S. divinorum, guarana (Paullinia cupana), Spice, Dream, Trance and Vegas Nights (see Table 41). CARM has received four reports for products containing C. aurantium as an ingredient; of these, three reports related to a weight‐loss product containing C. aurantium, and one related to 'Turbo Extreme', a 'party pill' that also contains BZP. Two other CARM reports related to a slimming product ('Slimfast') containing 'rose root' (Rhodiola rosea) as well as other herbal ingredients and BZP. Some of the National Poison Centre calls were received after our study had ended, although it is not possible to determine whether our study had alerted any users to the existence of the National Poisons Centre. All the CARM reports were received before our study was conceived. CARM has also received reports for several BZP party pill products. While the small number of reports and the poor quality of the data (see Limitations) would normally preclude detection of new signals27 of safety concerns, it is interesting to note that six reports associated with use of herbal substances involved the use of proprietary products marketed as containing the 'Floradrene' (see Table 41) blend of herbal ingredients. In five of these cases, the product was the only substance respondents claimed to have taken, and in four of these cases, the 27 Signal: reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously (World Health Organisation Uppsala Monitoring Centre).
91
adverse effect was nausea. The precise composition of 'Floradrene' is unclear: it is stated to contain at least five herbal ingredients (plant parts not specified), and has been identified as containing a synthetic stimulant. That users of products containing 'Floradrene' might experience nausea is probably not surprising. More importantly, these data may indicate that web‐based pharmacoepidemiological studies have potential for use as a tool to identify signals of safety concerns associated with use of recreational substances, since such users may be less likely to use established channels to report suspected adverse effects, such as consulting a doctor or pharmacist.
5.4 Limitations and confounders
In considering the findings from the study, it is important to acknowledge the limitations of the methodology and potential confounding factors.
This study has not been designed to ‘test’ cause and effect. Thus, although we have shown a temporal relationship between the BZP ban and a reduction in BZP use, a causal relationship cannot be inferred from our data. The data cannot be generalised to a New Zealand population of 18‐30 year olds due to sample bias.
A web‐based methodology poses a number of challenges, which have been widely reported in the literature 15,25,26. Whilst participation is restricted to those with access to the internet, given the age of the target sample population and the fact that New Zealand has one of the highest rates of Internet access in the world 19, we do not believe that this was a severe restriction in the case of this study. Other possible risks to the data such as multiple submissions by a single individual28 and the potential to falsify information (such as age) have been highlighted in the literature 26. In assessing the likelihood of these events occurring, it is worth considering the reasons why participants may engage in this behaviour. A key motivation could be to increase the chance of winning one of the prizes offered as part of the study or, more generally, a respondent may seek to boost their ‘voice’ in the research (e.g. have their views counted more than once). Whilst the research may have attracted those with strongly held views on the reclassification of BZP, the fact that the legislative changes had occurred prior to the research meant that there was nothing to be gained by seeking to over‐represent a particular viewpoint. With regard to individuals taking part more than once in order to increase their number of entries in the prize draw, this would have required respondents to create ‘fake’ information on a number of levels (including different email addresses/mobile phone numbers and ‘unique identifiers’) and is questionable whether participants would have gone to this level of trouble. A check was made for this, however, and the small number of duplicates identified was removed from the data set.
28 Whilst a potential occurrence within web‐based methodologies, it is worth noting that multiple submissions has not emerged as a significant issue in this field of research (Rhodes et al, 2003).
92
Other possible limitations of this study relate to the self‐reported nature of drug use behaviour. Whilst there is a potential for this to be either under‐ or over‐reported, this is a feature of any research conducted in the substance use field, and it has been shown that, at least amongst injecting drug users, self‐report is accurate 27. Additionally, the fact that data on patterns of drug use were collected retrospectively may have resulted in some inaccurate estimates due to incorrect recollection on the part of respondents. The study sample may also over represent substance users, who may have been more interested in the study, and our sample is also biased demographically.
As well as the inherent limitations of the methodology, it is important to acknowledge a number of issues that were particular to the study itself. First, the timing of the data collection – particularly W2 – may have impacted on the level and nature of participants’ drug use (e.g. W2T2 commenced just prior to the Christmas period, with respondents potentially using more substances due to an increase in social activities associated with this time of the year). There was also a relatively short time period between the end of the amnesty period in the W2 survey. This might have impacted on the likelihood of seeing change in the drug markets. Wave 1 also included the period just after the New Year and Wave 2 ended close to Christmas, thus might be affected by an increased use of substances over the summer period (seasonal effect).
Second, as highlighted in the results, there were problems matching ‘unique identifiers’ between W1 and W2. Whilst we have a high level of confidence that all the pairs identified through secondary analysis are actual pairs, it is possible that the method utilised to detect pairs (see footnote 15) may have resulted in some mistaken pairings.
Third, as is often the case with lay reports of suspected adverse drug reactions (and often with professional reports), the quality of the data is poor. Several reports described the product(s) taken only in vague terms (e.g."herbal"; "unknown brand of BZP‐free herbal"); such reports would usually be excluded from analysis, but have been included here because of the nature of the subject area and because they imply that some users may be unaware of what they have ingested, its contents and potential effects. A further problem is that, following the prohibition of BZP, several BZP‐containing products were reformulated as BZP‐free products but kept the same product name; thus, where a respondent named one of these products, we cannot ascertain whether they used a BZP‐containing or a BZP‐free formulation. In addition, the data posed problems in terms of the interpretation of lay descriptions of AEs (e.g. "itchy brain", "gross feeling in stomach") and poor data on the time course of the reaction (although respondents were not specifically prompted for this in the questionnaire). The poor quality of the data precludes a meaningful causality assessment.
Finally, caution should be exerted in interpretation of analyses of substances where the proportion of users was very small, e.g. GHB, methamphetamine and ketamine, as the study may not have been sufficiently powered to detect significant change,
93
and with small sample sizes there is a higher likelihood of obtaining false significant results.
6 CONCLUSION Whilst this study has only explored use over a relatively short time period, it would appear that a substantial reduction in the use of (and thus by inference – availability of) BZP‐containing products has occurred in the six months after legislation was introduced banning BZP and related substances. Additionally, our study has not identified evidence of a significant illicit market for BZP, although we should acknowledge that a substantial proportion of BZP users obtained them from friends and we do not know where these friends obtained their BZP party pills from. Recent IDMS data from frequent drug users indicates a dramatic fall in the level of use of BZP between 2007 and 2008, and users reported more difficulty in obtaining raw BZP, with prices being higher 28.
Amongst the paired sample, there were significant falls in self‐reported us of BZP party pills and legally smokeable substances, and a significant increase in non‐medical prescription drug use. Concerns about BZP users becoming new users of other illegal substances have not been confirmed through our quantitative data, although for some illegal substances sample sizes may be too small to detect change. However, full sample data on self‐reported change in amount of drug used indicates that, although amount used was stable for the majority, amongst a minority, there might have been an increase in ecstasy, cannabis, LSD and prescription drug use “since the ban” when asked in July 2008, although the reported increase was much smaller when asked at wave 2, and our qualitative data do point to a potential increase in the use of other substances, e.g. ecstasy. The only significant increases in the proportion of BZP users using a substance was in the use of legally available smokeable substances (although there was a concurrent reduction in the frequency of use) and prescription drugs. However, at least in relation to frequency of substance use amongst BZP users, when compared with others, there was a small increase in the use of cannabis, and a small increase in frequency of non‐medical use of prescription medicines, although this still remained infrequent. Despite concerns about increases in methamphetamine and ecstasy use, the evidence in the short term is unclear, and appears to indicate little change.
Adverse events associated with the use of unclassified recreational substances are experienced by users of these preparations, although causality is unclear. There are concerns about the contents and other aspects of the pharmaceutical quality of unregulated products containing herbal ingredients and, for the most part, a lack of or only limited information available on the safety profile of their herbal ingredients. There is a need to encourage healthcare professionals, including those working in the hospital environment, to be alert to the possibility of adverse effects associated with the use of recreational substances among the 18 to 30 year age group, and that they should submit reports of suspected adverse drug reactions associated with these preparations to CARM where relevant. Despite these measures, it is likely that
94
many adverse events associated with use of recreational substances go unreported and research in which users have complete anonymity may be a tool to aid detection of signals of unknown safety concerns.
95
7 APPENDIX
7.1 The website
A screenshot of the front page of the website developed for the research is displayed below.
96
7.2 Advertising material
7.2.1 A5 Flyer
97
7.2.2 Promotional cards
Front of card
Back of card
98
Groove Guide advertisement
99
7.2.3 Radio advertisement
Mai FM ad FINAL VERSION.mp3
100
7.2.4 Website advertising
The research was promoted via an on‐line advertisement placed on a number of websites. These included:
• UPFM • White Elephant Trust • Unitech • Youthline • Victoria University Wellington Student Association.
A screenshot of one of the frames from the on‐line advertisement is displayed below.
101
8 REFERENCES 1. Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J. Legal party pill use in
New Zealand: Prevalence of use, availability, health harms and ‘gateway effects’ of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) <http://www.shore.ac.nz/projects/Legal%20party%20pills%20in%20New%20Zealand%20report.pdf>. Accessed 7.6.2006. Centre for Social and Health Outcomes Research and Evaluation (SHORE), Massey University, Auckland, 2006.
2. EACD. The Expert Advisory Committee on Drugs (EACD) advice to the Minister on: BENZYLPIPERAZINE (BZP). Wellington: EACD; 2004.
3. Wilkins C, Girling M, Sweetsur P. The prevalence of use, dependency and harms of legal party pills containing benzylpiperazine (BZP) and trifluorophenylmethylpiperazine (TFMPP) in New Zealand. Journal of Substance Use. 2007;12(3):213 ‐ 24.
4. Sheridan J, Butler R. Legal party pills and their use by young people in New Zealand: a qualitative study. Final report of findings. Auckland: University of Auckland, 2006.
5. Harnett M. BZP and piperazine‐based party drugs: a retrospective case series of 73 poisonings with "legal highs". Dunedin: National Poisons Centre; 2006.
6. Thompson I, Williams G, Aldington S, et al. The benzylpiperazine (BZP) / trifluoromethylphenylpiperazine (TFMPP) and alcohol safety study. Wellington: Medical Research Institute of New Zealand; 2006.
7. Gee P, Gilbert M, Richardson S. BZP users attending Christchurch Emergency Department: Research Progress Report. Christchurch: Christchurch Hospital, 2006.
8. Nicholson T, White J, Cline R, Minors P. Parents who report using illicit drugs: findings and implications from the Drugnet study. Psychological Reports. 2001;88:245‐51.
9. Nicholson T, White J, Duncan D. Drugnet: A Pilot Study of Adult Recreational Drug Use via the WWW. Substance Abuse. 1998 1998/09/01/;V19(3):109‐21.
10. Reneau J, Nicholson T, White J, Duncan D. The general well‐being of recreational drug users: a survey on the WWW. International Journal of Drug Policy. 2000;11:315‐23.
11. Rodgers J, Buchanan T, Scholey AB, Heffernan TM, Ling J, Parrott A. Differential effects of Ecstasy and cannabis on self‐reports of memory ability: a web‐based study. Human Psychopharmacology: Clinical and Experimental. 2001;16(8):619‐25.
12. Rodgers J, Buchanan T, Scholey AB, Heffernan TM, Ling J, Parrott AC. Patterns of Drug Use and the Influence of Gender on Self‐Reports of Memory Ability in Ecstasy Users: A Web‐Based Study. Journal of Psychopharmacology. 2003 December 1, 2003;17(4):389‐96.
13. Scholey AB, Parrott AC, Buchanan T, Heffernan TM, Ling J, Rodgers J. Increased intensity of Ecstasy and polydrug usage in the more experienced
102
recreational Ecstasy/MDMA users: A WWW study. Addictive Behaviors. 2004;29(4):743‐52.
14. Kypri K, Gallagher S. Incentives to increase participation in an internet survey of alcohol use: a controlled experiment. Alcohol & Alcoholism. 2003;5:427‐41.
15. Rhodes SD, Bowie DA, Hergenrather KC. Collecting behavioural data using the world wide web: considerations for researchers. J Epidemiol Community Health. 2003 January 1, 2003;57(1):68‐73.
16. Duncan DF, White JB, Nicholson T. Using Internet‐based Surveys to Reach Hidden Populations: Case of Nonabusive Illicit Drug Users. American Journal of Health Behavior. 2003;27(3):208.
17. Braunsberger K, Wybenga H, Gates R. A comparison of reliability between telephone and web‐based surveys. Journal of Business Research. 2007;60(7):758‐64.
18. Falck RS, Carlson RG, Wang J, Siegal HA. Sources of information about MDMA (3,4‐methylenedioxymethamphetamine): perceived accuracy, importance, and implications for prevention among young adult users. Drug & Alcohol Dependence. 2004 Apr 9;74(1):45‐54.
19. Social Statistics Division of Statistics New Zealand. Household Access to the Internet Wellington: Social Statistics Division of Statistics New Zealand, 2004 12.3.2009.
20. Raveis V, Kandel D. Changes in drug behavior from the middle to the late twenties: initiation, persistence, and cessation of use. American Journal of Public Health. 1987;77(5):607‐11.
21. Quigley L, Marlatt G. Drinking among young adults: prevalence, patterns and consequences. Alcohol Health and Research World. 1996;20(3):185‐91.
22. Miller P, Plant M. Drinking, smoking and illicit drug use among 15 and 16 year olds in the United Kingdom. BMJ. 1996;313:394‐7.
23. Ministry of Health. Drug Use in New Zealand Analysis of the 2003 New Zealand Health Behaviours Survey – Drug Use. Wellington: Ministry of Health; 2007.
24. Sheridan J, Butler R. "They're legal so they're safe, right?" What did the legal status of BZP‐party pills mean to young people in New Zealand? International Journal of Drug Policy. In press.
25. Hayslett MM, Wildemuth BM. Pixels or pencils? The relative effectiveness of Web‐based versus paper surveys. Library & Information Science Research. 2004 2004/0;26(1):73‐93.
26. Birnbaum MH. Human Research and Data Collection via the Internet. Annual Review of Psychology. 2004;55(1):803‐32.
27. Darke S. Self‐report among injecting drug users: a review. . Drug Alcohol Depend. 1998 51(3):253‐63.
28. Wilkins C, Griffiths R, Sweetsur P. Recent Trends in Illegal Drug Use in New Zealand, 2006‐2008. Findings from the 2006, 2007 and 2008 Illicit Drug Monitoring System (IDMS). Auckland: Massey University, 2009.
top related