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Pain Res Manage Vol 10 Suppl A Autumn 200538A

Addiction and pain medicine

Douglas Gourlay MD FRCPC FASAM

Centre for Addiction and Mental Health, Toronto, OntarioCorrespondence: Dr Douglas Gourlay, Addiction Medicine Clinic, Centre for Addiction and Mental Health, 33 Russell Street, Toronto,

Ontario M5S 2S1. Telephone 416-535-8501 ext 6754, fax 416-595-6821, e-mail [email protected]

D Gourlay. Addiction and pain medicine. Pain Res Manage

2005;10(Suppl A):38A-43A.

The adequate cotreatment of chronic pain and addiction disorders isa complex and challenging problem for health care professionals.There is great potential for cannabinoids in the treatment of pain;however, the increasing prevalence of recreational cannabis use hasled to a considerable increase in the number of people seeking treat-ment for cannabis use disorders. Evidence that cannabis abuse liabilityis higher than previously thought suggests that individuals with a his-tory of substance abuse may be at an increased risk after takingcannabinoids, even for medicinal purposes. Smoked cannabis is sig-nificantly more reinforcing than other cannabinoid administrationmethods. In addition, it is clear that the smoked route of cannabisdelivery is associated with a number of adverse health consequences.Thus, there is a need for pharmaceutical-grade products of knownpurity and concentration using delivery systems optimized for safety.Another factor that needs to be considered when assessing the prac-ticality of prescribing medicinal cannabinoids is the difficulty in dif-ferentiating illicit from prescribed cannabinoids in urine drug testing.Overall, a thorough assessment of the risk/benefit profile of cannabi-noids as they relate to a patient’s substance abuse history is suggested.

Key Words: Addiction; Cannabis; Risk management; Substance abuse;

Urine drug testing

La dépendance et les analgésiques

Le cotraitement pertinent de la douleur chronique et des troubles de

dépendance est un problème complexe et ambitieux pour les profession-

nels de la santé. Les cannabinoïdes ont un grand potentiel dans le traite-

ment de la douleur, mais la prévalence croissante d’utilisation récréative

du cannabis s’associe à une augmentation considérable du nombre de per-

sonnes qui cherchent à se faire traiter pour des troubles reliés à l’utilisa-

tion du cannabis. Des données démontrant que les dommages reliés à

l’usage de cannabis sont plus élevés qu’on le pensait auparavant laissent

supposer que les personnes ayant des antécédents d’abus de drogues

seraient plus vulnérables après avoir pris des cannabinoïdes, même pour

des besoins médicinaux. Le cannabis fumé est un agent considérablement

plus renforçant que les cannabinoïdes administrés autrement. En outre, il

est clair que la voie d’administration du cannabis fumé entraîne diverses

conséquences nocives pour la santé. Ainsi, il est nécessaire de mettre au

point des produits de qualité pharmaceutique dont la pureté et la concen-

tration sont connues, au moyen de systèmes de perfusion à l’innocuité

optimisée. Un autre facteur dont il faut tenir compte lorsqu’on évalue la

possibilité de prescrire des cannabinoïdes médicinaux demeure la diffi-

culté de distinguer les cannabinoïdes prescrits des cannabinoïdes illicites

dans les tests de dopage. Dans l’ensemble, une analyse approfondie du pro-

fil risque-avantage des cannabinoïdes par rapport aux antécédents d’abus

de drogues du patient est suggérée.

Depending on the prevailing attitudes of the time, certainpharmacotherapies have been perceived as either villains

or heros. At the crux of this debate has been the risk of sub-stance misuse and addiction in the management of chronicpain. As cannabis enters the field of pain medicine, it mustalso be examined in this light.

THE PAIN AND ADDICTION CONTINUUMThe notion that pain and addiction can coexist is a relativelyrecent concept. Previously, the literature suggested that theprevalence of addictive disorders in the pain population was souncommon that it did not merit investigation (1,2). This beliefstill persists today (albeit much less so) despite the fact that theprevalence of addictive disorders within the general populationis typically quoted as 10% (3). The reasons for this are complex.

A dichotomous approach to pain and addiction is simple,even if it is potentially incorrect. The only requirement for thisapproach is to establish a ‘legitimate’ pain diagnosis and, thus,obviate the need to enquire into issues related to substancemisuse and addiction. In some circles, asking questions relatedto drug and alcohol use is seen as tantamount to dismissing thepatients’ complaints of pain. In no other area of medicinewould such a conclusion be drawn. It is becoming clear thatpain and addiction can, and do, coexist (4-7).

In understanding the relationship between pain and addic-tion, part of the problem seems to be nomenclature. Pain spe-cialists and addiction practitioners alike have used commonterms that, depending on the individual’s point of view andtraining, have come to mean entirely different things. To thisend, in 1999, the American Pain Society, the AmericanAcademy of Pain Medicine and the American Society ofAddiction Medicine formed a group called the LiaisonCommittee for Pain and Addiction. The first task for this groupwas the creation of a set of definitions for addiction, depend-ence and tolerance that could be embraced by all three organi-zations. These definitions were published in 2003 (8).

Addiction

“Addiction is a primary, chronic, neurobiologic disease,with genetic, psychosocial and environmental factorsinfluencing its development and manifestations. It ischaracterized by behaviours that include one or more ofthe following: impaired control over drug use, compul-sive use, continued use despite harm and craving.” (8)

Unlike the Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition (DSM-IV) (9) definition for addiction,

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physical dependency (withdrawal) and tolerance are not consid-ered in making the diagnosis.

The usefulness of the DSM-IV definition is severelyreduced when the identified drug of misuse is also a drug whichcould ultimately be an appropriate part of the patients’ phar-macological management. Although validated tools to assessrisk in the context of pain and addiction are being developed(10), at the present time there are no tools that can differenti-ate between appropriate and problematic use (either misuse oraddiction) of a medication where the identified drug of choicemay also play a useful role in the management of chronic pain.This is currently the case with opioids used in chronic non-cancer pain management (11) and will undoubtedly present adiagnostic challenge when cannabis becomes more widely usedto treat chronic pain.

Physical dependence

“Physical dependence is a state of adaptation that ismanifested by a drug class specific withdrawal syndromethat can be produced by abrupt cessation, rapid dosereduction, decreasing blood level of the drug, and/oradministration of an antagonist.” (8)

The phenomenon of physical dependence is an expected,neuroadaptive change that occurs in response to chronic expo-sure to certain drugs. It is not, in itself, suggestive of anythingbeyond this.

Tolerance

“Tolerance is a state of adaptation in which exposure toa drug induces changes that result in a diminution of oneor more of the drug’s effects over time.” (8)

In the case of tolerance, it is important to remember that it isneither good nor bad; it simply is. In some cases, such as the cog-nitive blunting effects of opioids, tolerance occurs relativelyquickly and is considered positive. On the other hand, toleranceto the constipating effects of opioids virtually never occurs.

What is particularly important about these definitions isthat the boards of representative organizations from both thepain management and addiction medicine communities haveendorsed them. While these definitions represent a compro-mise, they are an important step forward in reducing the risk ofthe continued use of imprecise terms in both the pain manage-ment and addiction medicine literature.

Although the true prevalence of addiction within thechronic pain management population is unknown, the enor-mous problem that chronic pain represents in the substanceabuse treatment population is beginning to be appreciated(12,13). A study by Rosenblum et al (14) found that 37% ofpatients surveyed within methadone maintenance treatmentprograms suffered from chronic severe pain. They also con-cluded that self-medication with psychoactive drugs for painwas especially problematic for substance abusers enrolled indrug-free (abstinence-based) treatment programs.

THE DISEASE OF ADDICTIONDrug abuse and addiction represent challenges to society atseveral levels. While it is tempting to focus on the impact of

addiction on individualistic health, there is also an adverseimpact on public health.

In 1998, the Substance Abuse and Mental Health ServicesAdministration estimated that 13.6 million Americans aged12 years and older had used an illicit drug in the previousmonth (15). The harm done by this use occurs not only at thelevel of the brain, but is also seen in increased rates of HIV trans-mission, hepatitis B and C, and tuberculosis. The societal cost ofassociated criminality and social dysfunction is difficult toaccurately ascertain but has been estimated at US$109 billionannually (16).

There are many different factors that lead to drug useincluding genetic, physiological and even social factors (17). Inaddition, there are both risk and protective factors that modifythe expression of a substance use disorder. Risk factors includeweak family structure, peer group pressures and growing up inhigh-crime neighbourhoods. On the other hand, strong familybonds and academic achievement may be protective (18).

By stepping beyond the question of why some people chooseto use drugs recreationally and by focusing only on those who do,it is realized that in the at-risk individual, the chronic exposure tocertain psychotropic substances causes changes in brain struc-ture and function. Addiction is not only a ‘disease of the brain’(19) but also a disease with both behavioural and social expres-sion. Treatment of addiction requires changes to be made bothwithin the patient and in the surrounding environment.

PREVALENCE OF DRUG USE AND

DEPENDENCEThere is considerable variation in the prevalence of drug usedepending on the drug being considered and the populationunder study. Alcohol, tobacco and caffeine are the most com-monly used psychotropics (20). Drugs like heroin and cocaineare much less commonly used.

In general, the use of cannabis has remained relatively con-stant over recent years; however, it is on the rise among youngadults in certain ethnic and racial groups (21). In fact,cannabis has been shown to be the most widely used illicit sub-stance in communities around the world (22-24).

In the United States, according to the 2000 United StatesNational Household Survey on Drug Abuse (22), 2.8 millionAmericans met the criteria in the previous year for eithercannabis dependence (1.6 million) or abuse (1.2 million).Furthermore, this survey reported that 25% (713,000) of thosewith cannabis use disorder actually seek treatment. That is morethan those seeking treatment for cocaine, hallucinogens, stimu-lants, pain relievers, inhalants, tranquilizers, heroin or sedatives(25).

In the United States, it is estimated that of those who haveever used cannabis, 10% will develop dependence (26). Of thosewho try cannabis more than once, approximately one-third willbecome regular users even though most will have stopped usingit by their late 20s or 30s (27). In fact, the relative potential fordependence on cannabis, expressed in terms of conditionaldependence (the risk of developing dependence among thosewho have ever used that substance) (26), is approximately 9%,which is lower than other substances such as alcohol (15%),cocaine (17%), heroin (23%) or tobacco (32%) (26,28).

In Canada, the number of Canadians aged 15 years and olderwho admit to using cannabis nearly doubled between 1989 and2002, with the highest rate among teenagers (29). In fact,6.5% of Canadians reported using cannabis in 1989, 7.4% in


Pain Res Manage Vol 10 Suppl A Autumn 2005 39A


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1994 and 12.2% in 2002. Of those who reported use in theprevious year, approximately 47% had used cannabis less thanonce per month. However, 20% reported regular use, with one-half of these using it weekly and the other one-half using it daily(29). In the Ontario Student Drug Use Survey of grades 7, 9and 11 students, 21.8% had used cannabis in the past year in1977, 9.9% in 1991 and 27.8% in 2003 (30).

A recent study (31) in Nova Scotia examining cannabis usein patients suffering from chronic pain showed that 36% had pre-viously used cannabis, 15% had tried it for pain relief and 10%were currently using it for the treatment of their chronic pain.

CANNABIS USECannabis as a drug with abuse liabilityFor some time, cannabinoids were considered unimportant inbrain reward systems, despite the fact that they are clearlyeuphorigenic in humans and do have abuse liability (32,33).More recent work over the past 15 years has shown cannabi-noids to interact with the brain reward systems in a similarfashion to other drugs with addiction liability (34,35).

Drugs with addiction liability often share certain qualities,which can be demonstrated in the animal laboratory setting.One of these is the involvement of the endogenous opioidsystem even for nonopioid addictive drugs.

In this case, the rewarding effect of cannabinoids can beattenuated by opioid antagonists, which is characteristic ofdrugs with addiction liability (32). More recently, Justinova et al(36) demonstrated this attenuating effect of the opioid antag-onist naltrexone on the reinforcing effects of delta-9-tetrahy-drocannabinol (THC) in squirrel monkeys.

Finally, in previously dependent but now abstinent animals,drugs with addiction liability are often able to reinstate drug-seeking and self-administration behaviour in response to a‘priming’ dose of the drug. Although there is a paucity of datain this area, there is evidence that the intravenous priming offormer heroin-dependent rats with cannabinoid agonists canlead to reinstatement of drug-seeking behaviour (32,37).

Recently, it has been demonstrated with cannabis-naïvesquirrel monkeys that THC can act as an effective reinforcer ofdrug-taking behaviour in monkeys with no history of exposureto other drugs. This suggests that self-administration of THCby monkeys may provide a reliable animal model of humancannabis abuse (38).

Thus, it would be reasonable to conclude that cannabinoidsshare many of the qualities demonstrated in other drugs, whichare clearly seen as having a high addiction liability (33). Thisbecomes important when assessing risk in the use of this class ofdrug for the management of pain, especially in those individualswith a history or an increased risk of a substance use disorder.

Cannabis dependence, tolerance and withdrawalThe existence of a definable withdrawal syndrome with cannabishas long been questioned. Before the publishing of the DSM-IV,cannabis dependence did not exist as a specific diagnostic cate-gory (34). More recently, research has begun to characterize thisphenomenon more clearly. Tolerance to cannabis can developafter periods of daily use as short as one to three weeks. Theresultant withdrawal symptoms that occur on abrupt discontinu-ation of cannabis typically begin after 24 h, peak at 72 h and areusually over within seven to 10 days (39). The symptoms arenonspecific and include irritability, anxiety, physical tension,and decreases in mood and appetite. In some cases, there is

restlessness, tremors, sweating, insomnia and even vividdreams. The time frame is highly variable and appears to be sim-ilar to that seen with other drugs of abuse (40).

Cannabis use disordersRecent studies in the United States have shown that morepeople are self-identifying themselves as having cannabis usedisorders (as indicated by a tremendous increase in admissionsto publicly funded treatment programs). The demand for treat-ment from health professionals, however, remains low relativeto the apparent problem. In 1999, the United StatesTreatment Episode Data Set (41) recorded more than 220,000admissions for cannabis use disorder treatment, which repre-sents 14% of all admissions to these facilities – a doubling inrate compared with 1993 (42). By 2000, cannabis admissionsaccounted for 61% of all adolescent admissions. These trends arealso observed in Australia, where they have seen a doubling inthe national rates of cannabis treatment-seeking individualsfrom 2000/2001 to 2001/2002, with an overall rate of 21% anda specific rate of 45% in those younger than 20 years of age(43). There has also been a concomitant increase in cannabis-related emergency room visits in the United States. Adjustingfor population changes, this represents a 139% increase inreported visits for the period of 1995 to 2002 (44).

In a recent article (21) examining the prevalence ofcannabis use disorders in the United States duing 1991/1992and 2001/2002, the authors indicate that despite an overall stableprevalence of cannabis use, more adults in the United Stateshad a cannabis use disorder in 2001/2002 compared with1991/1992. While these rates did not increase for young, whitemen and women, their rates of use remained high (34.4% for2001/2002). In contrast, the rates of cannabis abuse or depend-ence increased by 18% from 30.2% in 1991/1992 to 35.6% in2001/2002 across the general population surveyed (21).

Two important factors were identified that might help toexplain the increase in cannabis use disorders. The first is thesignificant increase in the potency of cannabis from policeseizures over the time period of 1992 to 2002 (45). In theabsence of any systematic increase in frequency or quantity ofcannabis used over the time frame studied, the increasing ratesof cannabis use disorders may reflect an increased potency ofthe cannabis used (21).

Although research clearly indicates that concentrations ofseized cannabis have been rising, the actual percentage increasehas been difficult to assess (45,46). The cannabinoid concentra-tion of cannabis seized in Canada does appear to have beenincreasing over the years. Although the concentrations quotedvary widely, depending on the sample and method of analysis,the average cannabinoid concentration of cannabis seized in the1980s was less than 1%, while the average over the period of1996 to 2000 was 6.7% (47). The use of selective breeding andhydroponic cultivation has dramatically increased the potencyof today’s cannabis (48). Information from ‘street seizures’ inCanada from April 2000 to April 2002 indicates a mean THCcontent of 10% with a range of 3% to 30% (49). According tothe World Health Organization, the average joint contains 0.5 gto 1.0 g of cannabis plant matter (50). This makes the estima-tion of ‘average dose’ exceedingly difficult.

The second possible factor to explain increased cannabisuse disorders relates to the increase in use observed in theyounger age groups. Because an early onset of drug use has beenconsistently associated with an increased risk of developing a


substance use disorder (51-53), the increase in duration of useassociated with this younger using population may help toaccount for the increased prevalence in rates of cannabis abuseand dependence (21).

Methods of cannabis useCannabis is used in a wide variety of ways. Most commonly, it issmoked either alone as a cannabis cigarette or mixed withtobacco (27). It can also be refined into a smokable resinousmass (hashish) or further refined into a potent oil (‘hash oil’ or‘honey oil’) that is either smoked with tobacco-containing prod-ucts or vaporized with a constant-temperature device (54). Insome cultures, cannabis is taken orally as either an ingredient infoods (55) (eg, ‘hash brownies’) or as a tea (‘ganja tea’). Themode of delivery directly affects the speed of onset and durationof action of the desired (and sometimes undesired) effects of thisdrug and, therefore, affects the abuse liability.

The speed of drug delivery also affects the reinforcingnature of a drug and, hence, its abuse liability. The inhaledroute is a fast and effective method of delivering precise quan-tities of drug at the instant the individual desires it (56). Withinhalation (ie, smoked), the drug is delivered into the cerebralvascular circulation very rapidly. Coupled with the fact thatthe user can titrate the quantity of drug delivered by the degreeof force used during inhalation and the time that the breath isheld, the inhaled route is a fast and very reinforcing means ofdelivering substances to the human brain (57).

Smoking as a delivery systemIt is important to separate the drug from the delivery system inthe assessment of risk. As presented in other articles in thissymposium, there is significant potential for cannabinoids inthe treatment of pain. In addition, it is clear that the smokedroute of delivery is potentially associated with a number ofadverse health consequences (58). Thus, it is a priority to min-imize the risks of smoking. Appreciating this point, both naturalplant extract (59,60) and synthetic oral cannabinoids havebeen developed (61).

SYNTHETIC CANNABINOIDSAt the present time, two synthetic cannabinoids are availablefor medical use in Canada. The first is a true synthetic THC,dronabinol (Marinol, Solvay Pharma Inc, Canada) (62), andthe other is a synthetic cannabinoid called nabilone (Cesamet,Valeant Canada limitée/Limited) (63).

MarinolMarinol was first approved for use in the United States in 1985and it is currently available for two specific indications: thetreatment of anorexia associated with weight loss in patientswith AIDS, and the treatment of nausea and vomiting associ-ated with cancer chemotherapy in patients who have failed torespond adequately to conventional antiemetic treatments(62). Marinol is a synthetic THC dissolved in sesame seed oiland, when taken orally, the drug is unpredictably absorbedfrom the gastrointestinal tract. In contrast to the inhaled routeof administration, there is very little opportunity for thepatient to titrate the dose to effect. Adverse side effects arecommon (64).

In the past, it has been reported that the abuse liability ofMarinol is low (65); the authors support this by stating that thedrug lacks the desirable qualities of rapid onset and titratability

commonly seen in drugs of abuse (65). At the present time,Marinol is available in 2.5 mg, 5 mg and 10 mg capsules.

CesametCesamet is a synthetic cannabinoid that has been developed foruse as an antiemetic agent, notably for chemotherapy-inducednausea. It is available as a pulvule (powder-containing capsule) in0.5 mg and 1 mg strengths. This form of delivery does not appearto lend itself to volatilization or combustion and, thereby, limitsmisuse via the pulmonary route of administration.

Nabilone has been studied in comparison with the reinforcingproperties of oral THC and smoked cannabis in subjects withprevious cannabis experience. These data indicate that smokedcannabis was significantly more reinforcing than all othercannabis compounds studied, regardless of drug use history (66).

DRUG MONITORINGWhenever a drug or member of a class of drugs is legitimatelypresent in a test sample, as is the case with any prescribed med-ication, it becomes very difficult to monitor misuse of that drug orclass of drug. An example of this would be the problems asso-ciated with monitoring an abstinent heroin user who has beenprescribed codeine-containing analgesics for the management ofpain. In this case, morphine that results from the metabolism ofheroin (diacetyl morphine) will be impossible to distinguish fromthe morphine that would be expected to be present due to themetabolism of the prescribed codeine (67,68).

From a monitoring perspective, it is relatively difficult todistinguish smoked cannabis from orally administered orsmoked Marinol. Both routes of administration produceimmunoassay-positive screen results for THC and, because theyare identical molecules, they cannot even be distinguished bygas chromatography/mass spectroscopy. Naturally occurringTHC-containing products are a mix of cannabinoids. Onespecific cannabinoid that can be identified by sophisticatedtesting, delta-9-tetrahydrocannabivarin (THCV), has been pro-posed as a way to specifically identify the naturally occurringproduct from the synthetic agent (69,70).

In 2001, ElSohly et al (69) reported results from a cleverlydesigned study using a small number of cannabis users as testsubjects. The study used a three-session, within-subject,crossover design. Each subject randomly received on separatesessions either an oral dose of Marinol (15 mg), a smoked dose ofpure THC (16.98 mg dronabinol) in a placebo cannabis ciga-rette or an equivalent smoked dose of cannabis (2.11% THCand 0.12 mg THCV/800 mg cigarette = 16.98 mg THC and0.96 mg THCV). They found that use of cannabis with or with-out Marinol could be distinguished from the use of Marinolalone (69). Previously, they had found that the confirmatoryanalytes, THC carboxylic acid and THCV carboxylic acid,found in urine drug specimens supported these findings (70).

Cesamet, however, does not trigger a positive immunoassayscreen or a confirmatory gas chromatography/mass spec-troscopy test for THC (71). In this context, a positive screenfor THC in a patient being prescribed Cesamet is consistentonly with the use of a THC-containing product such ascannabis or Marinol.

PRACTICAL CONSIDERATIONS

IN DRUG TESTINGUrine drug testing can and should play an important role inchronic pain management. There are, however, some limitations



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to its use. Apart from therapeutic drug level monitoring, theapplication of drug toxicology in clinical medicine has beenlargely limited to the emergency room setting. Its use is wellknown within forensic settings, such as the Department ofTransportation testing, and in workplace testing. In this con-text, testing is often adversarial and certainly often not in thepatient’s best clinical interests. Drug testing may, however,be patient-centred if used properly (68,72). Motivatingbehavioural change, encouraging maintenance of healthychanges already made, advocacy with third parties and earlyidentification of undiagnosed substance use disorders, wherethey exist, make the rational use of urine drug testing a wel-come addition to clinical medicine. No medical test should beused to limit treatment or deny appropriate care. Urine drugtesting should be no exception.

Testing techniques can be divided into initial ‘screening’ andthe more definitive ‘confirmatory’ tests. Screening tests are com-monly immunoassay-based and usually identify classes of drugsrather than specific agents. Screen tests are typically very sensi-tive because they often react to all members of the test classrather than to simply one specific drug. However, there areexceptions to this, as in the case of methadone. In contrast, con-firmatory testing is often less sensitive but able to accurately iden-tify specific drugs. For example, a patient taking codeine wouldbe expected to have an initial positive screen for ‘opiates’, butonly on confirmatory testing do the specific agents responsible forthis positive screen (codeine and its active metabolite morphine)become identified (67,68).

It is important to remember that neither screening nor con-firmatory testing can detect all substances that may, in fact, bepresent in a sample. A number of factors, including both con-centration effects (dilute urine) and limitations in the testingmethodology can account for the failure to detect drugs thatmay be present in a sample, including prescription drugs thatthe patient is known to be taking (67,68).

A detailed description of the patient-centred approach tourine drug testing is beyond the scope of this paper; however,useful recommendations for the use of drug testing in theprimary care setting can be found on the Internet at<http://www.alaskaafp.org/udt.pdf> (67), and in a report byHeit and Gourlay (68).

CONCLUSIONSThe abuse liability and reinforcing nature of cannabis are wellestablished. In trying to assess the role of cannabinoids in themanagement of chronic pain, one must consider the risk/benefitprofile of this class of drugs and the population in which theagent will be used. Similarly, when determining the most effec-tive route of administration, the patient’s history must beexamined.

If future research suggests that the smoked route of admin-istration of cannabinoids is the ‘gold standard’ in pain manage-ment, it will be important to know the test populations’previous experience with cannabinoids. If this is the perspec-tive of cannabis-naïve subjects, inhaled cannabis may indeedbe the preferred route of administration. On the other hand, ifthis preference seems to be largely associated with those sub-jects who have extensive histories with smoked cannabis, thisgold standard may become severely tarnished.

This should not diminish the potential role for cannabi-noids in medicine, but rather emphasize the need for pharma-ceutical grade products of known purity and concentrationusing delivery systems optimized for safety, and for furtherresearch on the safety of smoked cannabis when used for ther-apeutic purposes. In particular, in this case, the risks of thedelivery system must be separated from the risks of the drug.

Given that pain and addictive disorders coexist, and thatcannabinoids appear to have similar abuse liability to otherdrugs that activate the brain reward systems, these drugs mustbe approached with an appropriate level of caution. As is oftenthe case, risk lies not solely with the drug, but with the drugused in the context of an at-risk individual.

Taking into account the prevalence of recreational cannabisuse in modern society, coupled with the increased potency ofthe available street product, cannabis use disorder should beseen as a progressive entity. Failure to rationally approach thisissue will put both the patient and the practitioner at an unac-ceptable and potentially reducible risk.

Those who have previously met the DSM-IV criteria for asubstance use disorder with any licit or illicit substance willlikely be at an increased risk when using cannabinoids, evenfor medical purposes. Whether this elevated risk will rise to thelevel of an absolute contraindication remains to be seen.

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