Herbal Highs: Effects and

Consequences

Andrea Zangara

Flordis Natural Medicines

Medicinal Plant Research Centre (Newcastle University, UK)

Brain Science Institute (Swinburne University, AU)

andrea@flordis.com

Embracing Diversity, Drugs and Differences

15th October 09

Marriott Hotel, Cardiff

Classification of

Psychoactive Drugs:

drugs which alter

mood states and

consciousness

drugs used in the

treatment of

psychopathology

stimulants

hallucinogens

depressants anxiolytics

anti-depressants

antipsychotics

Cocaine: background

• isolated from coca plant (Erythroxylon coca)

• historical use in Colombia and Bolivia (largely

to aid strenuous manual work)

Cocaine: history

• cocaine itself isolated in

mid nineteenth century

• historical use in various

beverages and tonics

advertisement 1885

Vin Mariani introduced 1863

Cocaine: properties

• 0.6 - 1.8% in coca leaves

• usually administered as powder (cocaine hydrochloride) or crystalline rocks

Administration

• oral ingestion

– slow rate of absorption

– relatively steady state

• onset from other routes

– snorting - 3 mins

– injection - 15 secs

– smoking - 5 secs

‘rush’ ‘crash’

Acute behavioural effects

• increased confidence, exhilaration and

alertness

• decreased fatigue and boredom

• delays onset of REM sleep

• facilitates sustained effort

• enhances athletic performance

Cocaine risks and damages

• psychological addiction, compulsion

• breathing troubles, risk of stroke, heart attack,

seizures

• insomnia, weight loss, depression, irritability,

exhaustion, incoherence, delusions aggression

• toxic psychosis (similar to paranoid psychosis)

• symptoms caused by ‘crack’ may be more persistent

• large doses can directly damage neurons

• physical damage

Cocaine mix • Alcohol: cocaethylene extends effects and increases

cardiovascular toxicity

• Amphetamines: rare, similar effects; increase toxicity and cardiac stress

• Cannabis: smoked to relax (might increase blood pressure and heart rate)

• Ecstasy: popular mix as ‘dance drug’; increases physical and mental stress

• Heroine: ‘speedball’, the 2 drugs amplify each other and the heart can ‘lose rhythm’

• Ketamine: popular mix for dancing

• Viagra: can be dangerous (cardiovascular)

Amphetamine: background

• 1924 ephedrine isolated from Chinese ma

huang (Ephedra vulgaris)

• replaced by synthesised amphetamine in

1927

– rediscovered from 1887 as ephedrine substitute

• chemical structure related to adrenaline and

noradrenalin

• widely used in military scenarios (to this day)

• popular recreational drug in certain

subcultures

Amphetamines

• Speed (amphetamine sulphate)

• Base

• Methamphetamine

• Ritalin

Amphetamines: effects

• snorted, injected, smoked, ingested

• administration influences onset

• effects similar to cocaine but longer

• CNS continually stimulated

• suppression of appetite, sleep, increased concentration, confidence

• grinding teeth

• ‘crash’, in 3-8 hours

Amphetamines: risks and

consequences • risk of overdose (injection)

• chronic use: paranoia, tension, depression, fatigue, total exhaustion

• chronic use and large acute intake can trigger amphetamine psychosis (paranoia, obsessions)

• highly addictive

• tolerance is rapid

• withdrawal = opposite symptoms

Amphetamines mix

• Additional strain on the heart and increased blood pressure

• Alcohol: very popular, can drink more

• Cannabis: to relax

• Cocaine: similar effects, increase cardiovascular risk

• MDMA: extend and intensify; body temperature up

• Heroine: popular mix, decreases paranoia

• Ketamine: perception changes (time)

• Magic mushrooms: more paranoia

• Tobacco: more cigarettes

LSD (acids, trips)

• Lysergic Acid Diethylamide

• Synthetic, with profound effects on perception and cognition at very low doses (40-150 mcg)

• LSD has main effects on 5-HT (serotonin) neurons

• Colourless, odourless, tasteless: generally LSD is typically delivered orally, usually on a substrate such as absorbent blotted paper, sugar, or gelatine

• Difficult to understand quality and quantity as it rapidly degrades

Effects

• effects appear from 20 mins to 2 hours

• initially euphoria, goose bumps, increase in heart rate, jaw clenching, perspiration, pupil dilation, hypothermia, nausea

• between 30-45 minutes to reach their peak

• profound modification of consciousness, synaesthesia

• 8-12 ore in total

• after effect: tiredness, positive or negative feelings

• set e del setting very important

LSD: risks and

consequences

• bad trips

• excessive dose

• irresponsible actions

• flashbacks

• insomnia

• extreme paranoia

• personality disintegration / psychosis

MDMA (Ecstasy) (3,4-methylenedioxymethamphetamine)

• Related to both amphetamines and hallucinogenic (DA e

5HT)

• Empathogens as first ‘designer drugs’

• MDMA, MDA, MDE, 2CB, 2CT, 4-MTA, DOB....

• In pills and powder form (md)

• Effects starts after 20-40 mins, and last 4-5 hours

• Physiological effects similar to amphetamine

• Positive feelings of elation, euphoria, and closeness to others, appreciation of music and touch; replaced by depression and lethargy in the days afterwards

• Regular use may be neurotoxic, with prolonged serotonergic damage

Self-reported memory deficits in

recreational drug users:

findings from web-based studies Andrew Scholey, Jacqui Rodgers, Tom Buchanan,

Tom Heffernan, Jonathan Ling and Andy Parrott 1Human Cognitive Neuroscience Unit, University of Northumbria

2Doctorate in Clinical Psychology, University of Newcastle 3Department of Psychology, University of Westminster

4Psychology Department, Keele University 5Department of Psychology, University of Swansea

Human Cognitive Neuroscience Unit www.hcnu.com

Sydney ICOM July 2006

Summary • self-report data are consistent with laboratory

studies of memory deficits and other impairment

• internet provides insights into perceived problems and motivations

• future studies should include – online cognitive testing

– use of PRMQ

– relationship between subjective and objective measures

– prospective longitudinal studies starting in schools?

Gender effects

• Recent reports have

suggested that women

are more susceptible

than men to acute and

sub-acute effects of

ecstasy

• We found no gender

differences

– chronic effects equivalent

in males and females?

– chronic effects lead to

poorer calibration?

males females

RE

PO

RT

ED

ER

RO

RS

0

1

2

3

males females

ER

RO

RS

0.0

0.5

1.0

PMQ-LT

ERRORS COMPLETING FORM

Rodgers et al (2003) J Psychopharmacology 17, 379-386

Heat, ecstasy and LT-PM

• animal literature

indicates contribution

of hyperthermia to

MDMA serotonergic

toxicity

• here individuals who

stated that they

danced and became

hot while on ecstasy

reported more PM-LT

difficulties

Parrott et al (2006) Hum Psychopharmacology In press

Chronic physiological

effects of MDMA

• Demonstrated to

cause serious 5-HT

neurodegeneration

• In humans regions

of destruction

– Hippocampus

– Frontal cortex

Ketamine

• Dissociative anaesthetic : sense of

detachment from one's physical body

• Appearance: powder, tablets, liquid

• Effects last 45-60 minutes: from mild stimulation to out-of-body and near-death experiences

• Ketamine blocks glutamate activity, the result

is a temporary shut down of some brain areas

(K-hole)

Ketamine: risks and

consequences • ketamine can be extremely habit forming

• relatively safe

• dangerous in combination with other depressants

• danger of physical harm

• chronic use: troubles in digesting properly, urinating, memory weakening, alienated and dissociated states

• tolerance develops quickly, but no withdrawal (restlessness)

The use of psychoactive

plants

Humans have a natural drive to pursue

ecstatic experiences

All cultures have developed methods

for inducing such experiences

Every culture in the world (has) used

psychoactive plants

Cannabis

• The most used drug (illegal)

• Hashish 10-20% THC

• Marijuana 5-15%

• Smoked

• Ingested

• Over sixty active cannabinoids identified

• most prominent intoxicant

- D9-tetrahydrocannabinol (D9-THC)

– also e.g. D8-THC (relatively little)

• up to 20% of dry weight leaf

• also cannabinol (CBN) and cannabidiol (CBD)

– not themselves active

– may alter potency of active ingredients

• burning also modifies CBD into THC

• content is variable and changing historically

• Modern strains contains up to 3 times THC

Active ingredients

Cannabis and psychosis

• International Cannabis and Mental Health

Conference (2007): CBD as anti psychotic;

THC seems to interact with brain areas

related to paranoia and anxiety

• amisulpride and CBD in 42 psychotic

patients: improvement of symptoms and less

side effects with CBD (Leweke, 2007)

• CBD modulates THC?

• New strains unbalanced?

Legal / Herbal Highs

• Legal mind-altering substances, which cause similar

effects to illegal drugs

• Processed and unprocessed psychoactive

herbal/vegetable products (mushrooms, plants, cacti,

seeds, roots etc…)

• Synthetic products

• Various mixes and extracts (5x…)

• Categories:

– Energy (stimulants)

– Relaxant

– Aphrodisiacs

– Psychedelics

– Detox/ Prepare/ Repair

Contexts and Typologies

Contexts • Prohibition

• Harm reduction

• Globalisation

• New musical trends

• Other contexts without music

Typologies

• Sensation seeker (psychonauts)

• Experimental drug users attracted by media

• Those wanting a legal alternative to illegal drugs

• Poli drug users

•Curious

Smart Drugs and Smart Shops

• Eighties: nootropics

• Nineties: detox, prepare and repair,

herbal ecstasy, ‘herbal highs’

• Smart shops: from Netherlands to EU

• Today: synthetic legal highs, increasing

strength, Internet

Number of the total identified online shops

by country

selling legal alternatives to illegal drugs

Country Number of sites

Austria 3

Ireland 1

Portugal 1

Germany 4

Netherlands 25

UK 35

Total 69

7 out of 27 selected for further analysis offered more than one language version

A total of 8 different European languages were covered by the 27 online shops

Source: European Monitoring Centre for Drugs and Drug Addiction

(EMCDDA) 2008

How Safe?

• NZ: Survey of patients and relatives

presenting to an emergency department

(n=1043)

• 11.9% had taken herbal party pills (30%

among 14-25 year olds)

• 84.8% had felt effects from party pills

• 50.4% described effects as “good”

• 4.8% had sought medical attention for effects

Source: Nicholson, T.C. (2006), Prevalence of use, epidemiology and Toxicity of “herbal

party pills” among those presenting to the emergency Department.

60 times than nature!

Herbal Highs: Policies

• ‘Herbal highs’ — pose a range of difficult questions

for drug control policies:

• Conceptual: how to define which products are of

interest

• Practical and methodological: how to monitor the

products sold, identify the synthetic compounds that

they may contain and assess their health risks

• Little knowledge about the pharmacology, toxicology

and safety profile in humans, the type and amount of

synthetic substances added may vary considerably

The Smart Alternative (harm

reduction) • Herbal XTC → MDMA/Stimulants

• Magic mushrooms → LSD

• GHB → Opiates

The ban on them had as consequence:

BZP – Amanita muscaria – Synthetic

cannabinoids – Research chemicals

Herbal ecstasy (ephedra/ ma

huang/ sida cordifolia /sinephrine)

• Sympathomimetic amine acting on adrenergic

receptor system

• Similar in structure and effects to the synthetic

derivatives amphetamine and methamphetamine

• Euphoria, stimulant, appetite suppressant,

bronchodilator, thermogenesis

• Can cause insomnia, nervousness, heart-problems

and high blood pressure, stroke, and seizures

• Cardiovascular risk increases when combined with

other stimulants

• Can increase tolerance to alcohol effects

Synthetic Stimulants/ Legal

Highs

Not so smart ingredients (little or unknown long term risks)

• Butylone

• Methylone

• Methedrone

• Mephedrone

• Methcathinone

• Dimethylcathinone

• Synthetic cannabinoids

• Piperazine

• Benzylpiperazine

• 3-Trifluoromethylphenylpiperazine

Benzylpiperazine (BZP)

• Piperazines, not herbal but sold due to

amphetamine-like effects and legal

• Benzylpiperazine (BZP) is the most common

derivative

• Piperazine was originally used as an

antihelmintic to treat round worm

• Derivatives were further investigated in the

1970’s but trials stopped when abuse

potential was clear

Benzylpiperazine (BZP)

The effects

• Loss of appetite, increased heart rate, tingling skin and flushing ,sense of

euphoria and increased alertness;

• Sense of taste, sound and colour may be enhanced;

• Such effects can last between four to eight hours, depending on the amount

taken, the user's mood, metabolism and environment.

The risks

• Users report an inability to sleep for as long as 10 hours after the effects have

subsided

• Can leave users with symptoms similar to a hangover, such as headache,

fatigue, reduced appetite and nausea

• Possibility of slight memory loss

• BZP has been linked to cases of seizure, renal failure and acute psychosis in

some studies. Mixing BZP with other drugs, including alcohol, may increase risk

of negative effects.

• The law:

• At present, a loophole in the UK law allows BZP to be sold as a soil fertiliser.

Containing 180mg of BZP

and TFMP. Plus lots of

other nutrients and

minerals

• The combination of BZP and TFMPP has been associated with

a range of side effects (insomnia, anxiety, nausea and vomiting,

headaches and muscle aches similar to migraine, seizures,

impotence, rarely psychosis), as well as a prolonged and

unpleasant hangover effect similar to that produced by alcohol.

These side effects tend to be significantly worsened when the

BZP/TFMPP mix is consumed alongside alcohol (Wilkins C. Et

al., 2007)

Doves

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• Now available BZP & TFMPP free.

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strong root development. Doves Feeder is suitable for use on indoor and outdoor plants.

DOVES are available to customers outside USA, Australia and New Zealand.

Doves are available in 2 packs and 5 packs.

• Recommended dosages

DIRECTIONS: Use one Dove feeder per square meter around garden beds. For potted plants use half a Dove

feeder toward outer edge of the pot. Use half this amount for Violets and ferns.

ALWAYS WATER IN WELL AFTER APLICATION.

•

Do not contain methylone/ethylone

NOT FOR HUMAN CONSUMPTION SOLD AS PLANT FOOD The Dove pills are a state of the art product.

They don't contain the DOMS but a beta ketone.

Structurally this ketone is very similar to MDMA, but while that is controlled under the Misuse of Drugs Act

1971 the ketone isn't. Nor does it fall into any of the Analogue Laws or sub clauses of the Misuse Act. It is not

a phenethylamine

•

Magic

Mushrooms

• Active ingredients: psilocybin and psilocin (varies)

• Both mimic serotonin action - so effects may be through serotonin receptors.

• Over 90 species of magic mushrooms worldwide

• Similar effect to LSD, but shorter, less intense

• Eaten (fresh or dry) or drank as tea

• Dose: 2 gr (dry), 20 gr (fresh)

• Modification of perception dose-dependent

• Effects after 20 mins, peak at 30-45 for 1-2 hours, total 4-6 hours

Risks and consequences

• Exaggerate negative feelings

• Wrong setting

• ‘Bad trip’: fear, nausea, anxiety, confusion, fainting

• Memory impairment

• Latent or pre existent psychosis

• Poisonous mushrooms

• High turnover UK Treasury sales tax on

hallucinogenic mushrooms: 255,000 Euro per year on

a turnover of approx. 1.46 million Euro per annum

(estimations)

Fly Agaric (Amanita

muscaria)

• Ibotenic acid converted to muscimol on

drying or in the body; same effects, but

muscimol is 5-10 times more potent

Effects

• Psilocybe and Amanita are not chemically related with regard to their psychoactive properties: markedly different psychoactive effects

• Effects can be felt 30-120 minutes after ingestion.

The peak will start 1-3 hours after ingestion and can

last 6-10 hours. After effects can last another 1-6

hours. Alcohol can intensify intoxication

• Marijuana can ease any feelings of nausea and

intensify intoxication.

Effects cont.

• Low dose = 1-5 grams dried (1-2 fresh mushrooms)

medium dose = 5-10 grams dried (2-4 fresh

mushrooms) high dose = 10-30 grams dried (4-10

fresh mushrooms)

• Visual distortions, mood changes, euphoria, relaxation, delirium, inebriation, spasms.

• High doses give swollen features, high rage and madness, characterized by bouts of mania, followed by periods of quiet hallucination.

• Fatal dose = 10 mushrooms (ca. 100 g fresh mushroom).

• No antidotes! - stomach pumped

Synthetic Cannabinoids

(Spyce) • Herbal blend that claims to be a legal substitute for

cannabis

• Advertised as an ‘exotic incense blend which

releases a rich aroma’ and ‘not for human

consumption’

• Some of the declared ingredients are plants

traditionally known as ‘marijuana substitutes’

• Most of the ingredients listed on the packaging are

actually not present in the Spice products

• It is assumed effects described by users are due to

added synthetic cannabinoids

Information fom Dr. R. Sedefov, Lisbon, 15 June 2009

Synthetic Cannabinoids

(Spyce) • In 2008 a new psychoactive substance JWH-018 a

cannabinoid receptor (CB) agonist identified in Spice

products in Austria

• Chemical structure differs substantially from THC, but

it produces similar effects and more potent

• Several synthetic cannabinoids discovered

afterwards across EU

• No pharmaceutical product has emerged, no human studies carried out

• Little is known about metabolism and toxicology. The health risk of the inhaled smoke is unknown

Synthetic Cannabinoids

(Spice) • In the case of JWH-018 it can be assumed that due to

structural features there may be a certain carcinogenic potential?

• Active in low doses; accidental overdosing with a risk of severe psychiatric complications because the type and amount of cannabinoid may vary considerably

• In general, there may be a risk for the appearance of a full CB receptor agonists; leading to life threatening conditions if overdosed?

• Seems that tolerance may develop fairly fast; arguably this might be associated with relatively high potential to cause dependence

Salvia divinorum

• The Salvia genus is part of the Lamiaceae family (more commonly called the Mint family). The Mint family contains over 200 genera and 3,500 species

• Salvia has a long history of use by the by the

Mazatec people of Oaxaca, Mexico for divination,

entheogenic, and healing purposes

• Dried leaves: smoked (bong), chewed; solid or liquid

extracts (5x-100x)

• The main active chemical in Salvia divinorum is

called salvinorin A

Salvia: Effects and

Consequences • Salvinorin A is an extremely powerful consciousness

altering compound

• When the herb is consumed either by smoking the

dried leaf or chewing the fresh leaves the effects are

usually (but not always) pleasant

• When the dose goes above 500 - 1000 mcg the

effects can be excessive –always need a ‘sitter’

• Hallucinogenic – psychedelic effect, but short (3’5

min), powerful, immediate; not a ‘dance drug’

• May trigger latent psychological and mental problems

• Illegal from 2005 in some EU

Salvia: Effects and

Consequences

• Most harms resulting from the use of psychoactive

drugs like salvia occur as a result of people injuring

themselves when under the influence of the drug

• There is some concern that salvia could trigger

psychotic episodes particularly in young people and

vulnerable individuals with latent mental health

problems

Hawaiian Baby Woodrose

(Argyreia nervosa)

• LSA, simile a LSD (also Ipomoea)

• Medical use: bronchitis, cough, diabetes,

syphilis, tuberculosis, and other maladies. Also

as aphrodisiacs, tonics, cognitive enhancer

• Dose: 3-8 seeds in little pieces

• Effect similar to LSD but more narcotic

• Nausea (remove coating)

• Overdosing is rare

• Trigger psychosis or psychotic states

Kratom

• Mitragyna speciosa is the botanical name of the plant

• From South East Asia; Kratom has been used as medicine in Thailand since ancient times

• The primary active chemicals in kratom are mitragynine

• At lower doses, has physically stimulating effect. At larger doses it is more sedating, with a relaxed, euphoric cerebral sensation, with some pain relieving properties (similar to those of a mild opioid like codeine)

Effects and Consequences

• Can ease the discomfort of withdrawl from opium and

opium based substances like heroin, morphine

• There is a chance of becoming addicted (if only

psychologically) to kratom if abused

• When taken orally, the effects of kratom can be felt

about 30-60 minutes after ingestion, and the peak

lasts 2-3 hours. When smoked, the effects start

quicker and last about 60-90 minutes

• The only common negative comment about kratom is

that it causes nausea at high doses

Other natural psychedelics

• Cacti: Peyote / San Pedro (mescaline)

• Ayahuasca (dmt / armaline)

• Yopo (dmt)

• Iboga (ibogaine)

• Generally not considered ‘trendy’ and

used only by experienced people

RESULTS Sample characteristics

The average age of the interviewees was 24±5 years, 65 (64.4%) of whom were males, 36 (35.6%) females. Female smartshop customers were significantly younger than males (22.6±3.6 vs. 24.9±4.7, p=0.014). The average age at first visit to a smartshop was 20±3.8.

80.2% of the interviewees had bought energy drinks from a smartshop, 76.2% magic mushrooms, 58.4% herbs, 49.5% herbal XTC, 47.5% smart nutrients, 33.7% nootropics, and 20.8% strong psychoactive herbs. The strongest the product, the more the customer tend to be older and informed on the effects and consequences

Conclusions: a missed

chance? • Psychedelic herbs when out of their context or in forms different

from traditional use may produce dangerous and unwanted effects

• Smartshops should be honest source of information and literature

on the contents, effect and safety of legal highs, never instigate or

push use of anything

• The original concept was not to provide completely safe products,

but safer than illegal drugs and identifiable, and to give enough

information for the safest use

• The smart concept should include health and safety monitoring,

quality and purity of products, liaison with health and regulatory

authorities

• Today’s trend seems only to get easy and fast money, and trick the

law with new and potentially dangerous synthetic molecules,

representing a serious hazardr to public health

• A new and effective legal framework is urgently needed

Have conscious dreams

and remember:

You can fly also without drugs!