Dr. Bodkin is project director for the Center of Prevention and Evaluation (C.O.P.E.) in the Department of Psychiatry at Columbia University at the New York State Psychiatric Institute in New York City. Ms. Singh is graduate student in the masters program for Clinical Psychology at Teacher’s College at Columbia University. Dr. Corcoran is Florence Irving assistant professor of clinical psychiatry and director of C.O.P.E.
Disclosure: Dr. Bodkin and Ms. Singh report no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Corcoran receives research support from the National Institute of Mental Health.
Please direct all correspondence to: Cheryl Corcoran, MD, Director, Center of Prevention and Evaluation, New York State Psychiatric Institute, 1051 Riverside Dr, Room 4804, New York, NY 10032; Tel: 212-543-6177; Fax: 212-543-6176; E-mail: email@example.com.
Smoking cannabis is common among adolescents and young adults and has numerous negative effects. This article describes data which support the hypothesis that cannabis may induce psychotic symptoms and contribute to the onset of psychotic disorders, specifically in a vulnerable subset of youths. This vulnerability, which consists of genetic variation and which may be manifest in particular behaviors and experiences, including schizotypy, is explored. Possible motivations for use among vulnerable teenagers are discussed, the understanding of which may inform treatment efforts by clinicians to curtail use. As various psychotherapies appear equally effective in reducing cannabis use in comparable populations, there may be a nonspecific component consisting of clinician contact and education which may be of use to nonspecialists in addressing cannabis abuse.
According to the National Institute on Drug Abuse, cannabis, or marijuana, is the most widely used illegal drug in the United States.1 Nearly 45% of teenagers in the US have smoked cannabis before graduation from high school. Numerous adverse consequences of cannabis use by teenagers have been described, including difficulties with problem-solving, memory, learning, judgment, and perception.2,3 These problems in thinking can interfere with academic, social, and athletic performance as well as aggravate risk-taking behaviors, including having unprotected sex and driving recklessly.1 There are also medical consequences for cannabis use in youths, including immunosuppression, coughing and wheezing, and a greater risk of pneumonia.1 In terms of exposure to cancer-causing chemicals, it has been estimated that smoking five joints of marijuana/day may be equivalent to smoking one pack of cigarettes.4 In addition, cannabis use can lead to anxiety, feelings of paranoia, and perceptual disturbances.1
In reviewing the evidence from many studies, some investigators have concluded that, in fact, cannabis use can lead in some youths to the development of psychotic disorders such as schizophrenia.5,6 It has been estimated that cannabis use accounts for 1–2 new cases of schizophrenia for every 100 individuals annually7 and that 8% to 13% of all cases of schizophrenia can be attributed to cannabis use (ie, attributable risk).8 Of note, this percentage is larger than the 5.5% associated with genetic risk for schizophrenia, ie, having an affected first-degree relative.9 Whereas a teenager cannot change who his or her parents or siblings are, smoking cannabis is a behavior that potentially can be modified.
This article describes evidence that cannabis may contribute to psychotic symptoms and disorders, particularly in a subset of vulnerable youths, and reviews their possible motives for use of cannabis. The article also discusses the ways psychiatrists on the front lines can address the problem of cannabis use.
Evidence that Cannabis Use May Increase the Risk for Psychotic Disorder
Much evidence shows that psychotic disorders and the use of drugs, especially cannabis, occur together more often than chance would predict. For example, schizophrenia patients have far higher rates of substance abuse or dependence (approximately 50%) than the general population (17%).10-12 It does not appear that the drug use is simply a consequence of having a psychotic disorder, ie, “self-medication” of symptoms, as up to 50% of youths experiencing a first episode of psychosis already have a diagnosis of substance abuse or dependence.13 Cannabis abuse and dependence are especially prevalent in first-episode psychosis patients (approximately 20% to 40%),13 particularly in adolescents.14,15 Retrospective studies of first-episode psychosis patients suggest that cannabis use almost always precedes the development of psychotic-like symptoms.16
The observed co-occurrence of cannabis use and psychotic disorder shows only that there is an association, however, and does not necessarily support the hypothesis that cannabis use can play a causal role in psychosis and psychotic disorders. However, three types of studies—prospective cohort, experience sampling, and challenge studies—provide evidence that, in fact, cannabis use may lead to psychosis, particularly in vulnerable individuals.
Prospective Cohort Studies
Prospective cohort studies follow a whole population or “cohort” over several years to determine if earlier exposures are associated with later outcomes. Relevant to this article, “cannabis use” is the “exposure” and “schizophrenia” is the “outcome”; in fact, several studies demonstrate the association of earlier cannabis use with later schizophrenia.5,6 In such studies, one must always be wary of potential “confounds,” ie, factors that are related both to the exposure and to the outcome. For example, an apparent association of “sunburn” with children not going to school can in fact be explained by the fact that both tend to occur during the summer months. In the case of cannabis use and schizophrenia, one can imagine that early “prodromal” symptoms of schizophrenia, which include odd thinking, social dysfunction, and symptoms of anxiety, might both herald a later onset of schizophrenia yet also contribute to the use of cannabis. When an association of cannabis use at 15 years of age and schizophrenia at 26 years of age was “adjusted” statistically for earlier “prodromal” symptoms at 11 years of age, the risk for schizophrenia was less but still statistically significant.8 This suggests that whereas prodromal symptoms might lead to cannabis use, they cannot fully explain the association of teen cannabis use with later schizophrenia. In this same “cohort” it was found that it was only among some teenagers that cannabis use predicted later schizophrenia, ie, those with a variation of a gene that regulates dopamine metabolism—specifically catechol-O-methyl transferase (COMT).17 This is especially relevant as dopaminergic circuits have been implicated in psychosis and schizophrenia.18
Experience Sampling Studies
Relevant experience sampling studies are those in which an individual, usually a college student, is prompted by a beep from a watch numerous times a day to answer questions about cannabis use and transient symptoms such as anxiety, perceptual disturbances, and feelings of suspiciousness. These transient symptoms are, of course, not equivalent to psychotic disorders per se, but an association in this short time frame would support the plausibility of a connection. In fact, cannabis use at one time point was found to be associated with anxiety and psychotic-like symptoms at the following time point (using “time-lag analysis”).19 By contrast, symptoms did not precede use, which works against the idea of simple self-medication. As with the prospective cohort studies, only some youths appeared to be vulnerable to developing psychotic-like symptoms in the context of cannabis use, in this case those identified as “prone” to psychosis.19
Relevant challenge studies are those in which an active ingredient of cannabis, delta 9 tetrahydrocannabinol (Δ9THC), is administered. Intravenous injection of Δ9THC leads in both healthy individuals and in schizophrenia patients to transient psychotic symptoms as well as anxiety, cognitive deficits, and negative symptoms.20,21 In another study,22 smoking of a cigarette containing Δ9THC led to psychotic symptoms only in those youths who have the same gene variant implicated in the aforementioned cohort study, namely COMT, especially in those individuals with psychosis proneness.
Although cannabis smoking does not typically induce psychotic symptoms in most normal individuals,23 it does transiently worsen psychotic symptoms in schizophrenia patients, an effect accompanied by changes in dopamine release, as evident from brain imaging.24 These challenge studies all support the notion that cannabis can induce psychotic symptoms, but primarily only in those with an existing vulnerability, either by virtue of genetic predisposition or by behavioral symptoms.
Prospective cohort studies suggest teenage cannabis use can lead to adult psychotic disorders in a subgroup of youths. Both experience sampling and challenge studies demonstrate that cannabis use can lead to transient psychotic symptoms, particularly in vulnerable individuals. Of note, such transient symptoms are not benign because among youths psychotic-like symptoms confer greater risk for later psychotic8,25 and substance abuse/dependence diagnoses.26
What Constitutes the Vulnerability to Psychotic Symptoms in the Context of Cannabis Use?
As mentioned, not all individuals develop psychotic symptoms in the context of cannabis use. In a survey of youths, only 14% described developing “strange, unpleasant experiences such as hearing voices or becoming convinced that someone is trying to harm them” after smoking cannabis.27 It is important for the general practitioner to understand what may characterize this subset of youths who have such experiences.
Genetic Differences/Family History
In both prospective cohort studies and challenge studies, a variation in a dopamine metabolism gene COMT appears to confer vulnerability to psychotic symptoms in the context of cannabis use.17,22 Although of interest in terms of biologic mechanisms, this finding has limited clinical use, as young patients do not routinely have genetic analyses. However, clinicians may have a good sense of whether a young person has a family history of psychosis, which is a proxy for genetic vulnerability. Interesting work conducted by Caton and colleagues28 shows that among dually diagnosed first-episode psychosis patients, those patients who go on to develop a primary psychotic disorder such as schizophrenia are more likely to have a family history of psychosis and worse premorbid functioning, possibly consistent with a prodromal period. Among youths identified as at heightened risk for schizophrenia by virtue of having two affected relatives, cannabis use is associated with psychotic-like symptoms at baseline29 and increased use of cannabis appears to precede the onset of a psychotic episode.30
In experience sampling studies, college students with “psychosis proneness” are more likely to develop both anxiety and psychotic-like symptoms (unusual perceptions and feelings of thought influence) in response to cannabis use, in contrast to normal college students who tend to find cannabis relaxing.19 Youths with these experiences and a specific variant of the COMT gene are especially likely to develop psychotic-like symptoms in the context of cannabis use.22 Psychosis proneness in these studies was assessed using an instrument called the Community Assessment of Psychic Experiences, a self-report questionnaire that probes the extent to which an individual has had unusual or psychotic-like experiences.19 A causal direction between cannabis use and psychotic-like symptoms in this vulnerable group is supported by time-lag analyses (in experience sampling studies)19 and randomization with placebo in challenge studies.22
Schizotypal symptoms, which overlap with “psychosis proneness,” may also constitute a vulnerability to psychotic symptoms in the context of cannabis use. “Schizotypy” is characterized by social withdrawal, psychotic-like symptoms, socio-emotional dysfunction, and odd behavior. In youths, these symptoms are associated with cannabis use31-34 and are themselves predictors of adult psychotic disorder.8 Although it is not clear whether the symptoms lead to the use, the use leads to the symptoms, or the causal association is “bidirectional,” it is nonetheless worthwhile for clinicians to pay special attention to cannabis use in youths with these sorts of characteristics.
Why Do Vulnerable Youths Smoke Cannabis if it Causes Psychotic-like Symptoms?
As there is enough evidence to support a causal role for cannabis in the development of psychosis in some youths, clinicians should regularly assess whether their teenage patients are using drugs. Attention should be especially focused on teenagers who have a family history of psychosis or who show signs of elevated risk, such as being socially awkward, having unusual ideas, and being socially isolated.
One step in helping these vulnerable adolescents and young adults to stop using cannabis is to understand why they use cannabis in the first place and what keeps them using it despite the potential negative effects it might be having on their mental state. It is possible their reasons for use are similar to those of other teenagers, but it is also possible that they use cannabis to cope with the emerging symptoms that are common among people at elevated risk for psychosis. Cannabis use may help them feel more at ease despite social anxiety. It may make them feel happier (less depressed) or just feel more deeply in general, as they may perceive an absence of feeling or disconnection from feeling. It may also help them feel as though they fit in with peers despite their awareness of being perceived as odd.
One candidate model for understanding cannabis use in vulnerable teenagers is the motivational model, which has been applied to substance use in the general population.35 Motivational models focus on motives for use, suggesting that people use drugs to achieve desired effects, which might include wanting to feel more comfortable with peers, wanting to feel less anxious or depressed, wanting to achieve a high, wanting to fit in, and/or having generally positive expectations about the feelings use will bring. Applying a motivational model to cannabis use in the population of youths at elevated risk would require studies on reasons for use. Motivations for cannabis use in vulnerable teenagers have not been studied, but this could be informed by research on motivations for use in teenagers in the general population.
Several common motivations for use of cannabis by teenagers have been identified, including enjoyment, fitting in, experimentation, social enhancement (such as feeling better in a social situation), boredom, relaxation, habit, activity enhancement, coping (with negative feelings), and altered perception (mind expansion; Table 1).36 Specific reasons for use may also reflect the presence of untreated or insufficiently treated symptoms and help the clinician in identification of youths at risk.
In a recent study37 that examined motives for cannabis use in 2,031 young Swiss adults, it was found that cannabis users who had coping motives for use were more likely to show symptoms of psychopathology, evidence more psychosocial distress, and endorse more distressing life events than those who had social motives. The authors suggested that secondary prevention for cannabis use should target young adults in the general population who report using cannabis in order to cope.
An examination of the literature on reasons for use raises many questions. Are the reasons for use that teens endorse truly motivations for use or are they rationalizations? Are the reasons they endorse consistent with the effects they experience? Are teens really aware of their reasons for use? Do their reasons change over time as they move from initial use to more frequent or heavy use? This again raises the issue of direction of causality in the association between cannabis and psychosis. Is it the symptoms that lead to use or does use itself cause the emerging symptoms, which may in turn lead to greater use, causing a vicious cycle?
An examination of correlates of cannabis use in teenagers muddies the picture further. Cannabis use and misuse by teenagers is associated with depression and anxiety38,39 mediated by psychosocial factors and stress exposure40-42; academic and functional decline38,40,42-44; and cognitive deficits,45 especially in attention.46 Teenage cannabis use is also related to suicidal behavior47 and premorbid psychopathology for personality, affective, and psychotic disorders.48
What the clinician can take from this research on reasons for use and the questions raised here is that vulnerable teenagers may have reasons for using cannabis that are similar to those of other teenagers. In addition, vulnerable teenagers may weigh the short-term benefits of use against the adverse effects that might come later and decide to use cannabis. This may be similar to what is seen for patients with established psychotic disorder, who report using drugs to cope, socialize, improve mood, reduce anxiety, and relieve boredom,35,49-54 despite admitted worsening of symptoms with use.35,49-52,54
Therefore, asking a vulnerable teenager why he or she uses cannabis may reveal a problem that can be addressed. In addition, discussing reasons for use provides an opportunity for the clinician to offer psychoeducation to vulnerable teenagers on the relatively higher risks of use for them as compared to their peers.
Interventions to Reduce Cannabis Use
There are no available data on effective treatments for cannabis use in vulnerable youths. Therefore, it may be useful to examine what interventions have been effective in reducing cannabis use in other groups, such as teenagers in the general population and patients with first-episode psychosis (Table 2). As for teenagers, little is known about the effectiveness of pharmacologic treatments for cannabis use,55 yet medications are unlikely to be useful given their poor track record in treating cannabis dependence in adults. Medications that have been studied in adults include bupropion,56,57 nefazodone,57,58 and divalproex sodium.59,60 Only rimonabant, a cannabinoid receptor antagonist, has been found to reduce the pleasurable effects of cannabis.61 However, it is not available in the US due to its association with such serious side effects as depression. Naltrexone actually increases cannabis’ pleasurable effects.58 In addition, no drug has been found to reduce consumption of cannabis (ie, oral THC).62
Psychosocial treatments for cannabis use may be more promising. There have been two randomized clinical trials of treatment for cannabis use, one of which focused specifically on young users.63-66 The Cannabis Youth Treatment project examined the benefit of five different psychotherapies for cannabis dependence and found that all five treatments led to improvement, although none were superior.63-66 The five treatments studied were motivational enhancement therapy, cognitive-behavioral therapy, family support network therapy, adolescent community reinforcement, and multidimensional family therapy. Motivational enhancement therapy focuses on reasons for seeking treatment and readiness for treatment as well as personal goals, self-efficacy, prior attempts to quit, and problems associated with cannabis use. Cognitive therapy includes skills training in drug refusal, social networking, time and anger management, problem-solving, anticipation of high-risk situations, and managing craving and relapses. Adolescent community reinforcement focuses on changing environmental contingencies related to cannabis use. Family support network therapy focuses on increasing family cohesion and providing parental support and education; it includes case management and home visits. Multidimensional family therapy emphasized family roles and interactions. As these interventions were all equally effective, it suggests that there may be some nonspecific component common to each of these that is helpful, such as clinician contact or psychoeducation. The good news in this is that no particular skill set or approach may be necessary for clinicians who want to help their young patients reduce cannabis use.
As mentioned, studies of treatments targeting cannabis use in young adults with psychotic disorder may also be useful to review in considering how to help vulnerable teenagers stop cannabis use. In one study,67 both specific cannabis-focused intervention and more general psychoeducation were found to lead to a statistically significant decrease in cannabis use by 3 months, an effect that continued 6 months beyond the end of treatment. Both groups reduced their cannabis use from a median of 4 days in the prior month (at baseline) to a median of 2 days in the prior month (at the end of 3 months of treatment), and then only 1 day in the prior month at follow-up. However, there was no concomitant improvement in symptoms or function.
Likewise, Addington and Addington68 found that the use of cannabis and other drugs by first-episode psychosis patients was reduced at 1 year after entry into an integrated psychosis treatment program, despite patients’ rejecting the added help of a group specifically devoted to reducing substance use. There were significant reductions in use of both cannabis and hallucinogens, although alcohol consumption was not decreased. The specialty “substance abuse” group was rejected by patients for numerous reasons, including their denial that they had a problem or their feeling that they could quit or manage on their own. Overall, in this comprehensive program, clinicians explained that people with vulnerability to schizophrenia have a “sensitive brain” and that certain environmental stressors could exacerbate symptoms; substance use was framed as a major stressor. The authors68 recognized that the cause for the reduction in substance use was unclear, and they speculated that it may have been due to attitudinal or developmental changes and/or an effect of the education and encouragement provided by staff. What all of these studies suggest is that what might be effective is simply psychoeducation, support, and encouragement. This is something all clinicians can offer.
Clinicians who encounter a seemingly vulnerable adolescent or young adult who may be smoking cannabis should consider the suggested guidelines in Table 3.69
Cannabis use is an important target for intervention with vulnerable youths, as its reduction may prevent the occurrence of psychotic-like symptoms and prevent (or delay) the onset of psychotic disorders, such as schizophrenia. Psychotic-like symptoms, even if they do not lead to a diagnosable disorder, are associated with many negative consequences. In the absence of preventing onset, even a delay in psychosis onset is a desirable goal, as a later onset of psychosis might enable a young person to consolidate academic, vocational, and social achievements and goals.
The vulnerability to psychosis among youths can be identified by examining their family history of psychotic disorders and by their behaviors and experiences, with vulnerability associated with social withdrawal, psychotic-like symptoms, socio-emotional dysfunction, and odd behavior. An absence of friends may be a particularly good sign of vulnerability.
The motivations for cannabis use among such vulnerable teenagers are poorly understood, though they may be similar to those identified both by teenagers in general and by young adults with a first episode of psychosis—essentially, to socialize, cope, feel better, relieve boredom, feel less anxious, and get high. Understanding motivations for use for any particular individual may be a useful first step in helping him or her stop or at least cut back on drug use.
Treatments to reduce cannabis use in vulnerable teenagers have also not been studied. However, numerous psychosocial treatments seem to help with reducing cannabis use by both teenagers in general and by youths with a first episode of psychosis. This suggests that some nonspecific element of these various treatments—listening, encouragement, or provision of education—may be useful in reducing use. These strategies do not require specific training and can be used by all clinicians. PP
1. NIDA. Marijuana. Available at: www.nida.nih.gov/DrugPages/Marijuana.html/. Accessed April 17, 2008.
2. Pope HG Jr, Yurgelun-Todd D. The residual cognitive effects of heavy marijuana use in college students. JAMA. 1996;275(7):521-527.
3. Harder S, Reitbrock S. Concentration-effect relationship of delta-9-tetrahydrocannabinol and prediction of psychotropic effects after smoking marijuana. Int J Clin Pharmacol Ther. 1997;35(4):155-159.
4. Wu TC, Tashkin DP, Djahed B, Rose JE. Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med. 1988;318(6):347-351.
5. Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370(9584):319-28.
6. Murray RM, Morrison PD, Henquet C, Di Forti M. Cannabis, the mind and society: the hash realities. Nat Rev Neurosci. 2007;8(11):885-895.
7. Weiser M, Davidson M, Noy S. Comments on risk for schizophrenia. Schizophr Res. 2005;79(1):15-21.
8. Arseneault L, Cannon M, Witton J, Murray RM. Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry. 2004;184:110-117.
9. Mortensen PB, Pedersen CB, Westergaard T, et al. Effects of family history and place and season of birth on the risk of schizophrenia. N Engl J Med. 1999;340(8):603-608.
10. Mueser KT, Nishith P, Tracy JI, DeGirolamo J, Molinaro M. Expectations and motives for substance use in schizophrenia. Schizophr Bull. 1995;21(3):367-378.
11. Kendler KS, Gallagher TJ, Abelson JM, Kessler RC. Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample. The National Comorbidity Survey. Arch Gen Psychiatry. 1996;53(11):1022-1031.
12. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) study. JAMA. 1990;264(19):2511-2518.
13. Cantwell R, Brewin J, Glazebrook C, et al. Prevalence of substance misuse in first-episode psychosis. Br J Psychiatry. 1999;174:150-153.
14. Pencer A, Addington J. Substance use and cognition in early psychosis. J Psychiatry Neurosci. 2003;28(1):48-54.
15. Pencer A, Addington J, Addington D. Outcome of a first episode of psychosis in adolescence: a 2-year follow-up. Psychiatry Res. 2005;133(1):35-43.
16. Hambrecht M, Hafner H. Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective. Aust N Z J Psychiatry. 2000;34(3):468-475.
17. Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57(10):1117-1127.
18. Carlsson A. The dopamine theory revisited. In: Hirsch SR, Weiberger DR, eds. Schizophrenia. Oxford, UK: Blackwell Science; 1995:379-400.
19. Verdoux H, Gindre C, Sorbara F, Tournier M, Swendsen JD. Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychol Med. 2003;33(1):23-32.
20. D’Souza DC, Perry E, MacDougall L, et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 2004;29(8):1558-1572.
21. D’Souza DC, Abi-Saab WM, Madonick S, et al. Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry. 2005;57(6):594-608.
22. Henquet C, Rosa A, Krabbendam L, et al. An experimental study of catechol-o-methyltransferase Val(158)Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 2006;31(12):2748-2757.
23. Hart CL, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW. Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology (Berl). 2002;164(4):407-415.
24. Voruganti LN, Slomka P, Zabel P, Mattar A, Awad AG. Cannabis induced dopamine release: an in-vivo SPECT study. Psychiatry Res. 2001;107(3):173-177.
25. Henquet C, Murray R, Linszen D, van Os J. The environment and schizophrenia: the role of cannabis use. Schizophr Bull. 2005;31(3):608-612.
26. Kwapil TR. A longitudinal study of drug and alcohol use by psychosis-prone and impulsive-nonconforming individuals. J Abnorm Psychol. 1996;105(1):114-123.
27. Thomas H. A community survey of adverse effects of cannabis use. Drug Alcohol Depend. 1996;42(3):201-207.
28. Caton CL, Hasin DS, Shrout PE, et al. Stability of early-phase primary psychotic disorders with concurrent substance use and substance-induced psychosis. Br J Psychiatry. 2007;190:105-111.
29. Miller P, Lawrie SM, Hodges A, Clafferty R, Cosway R, Johnstone EC. Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia. Soc Psychiatry Psychiatr Epidemiol. 2001;36(7):338-342.
30. Miller PM, Johnstone EC, Lawrie SM, Owens DG. Substance use, psychiatric symptoms and the onset of schizophrenic illness. J Subst Abuse. 2006;11(2):101-113.
31. Dumas P, Saoud M, Bouafia S, et al. Cannabis use correlates with schizotypal personality traits in healthy students. Psychiatry Res. 2002;109(1):27-35.
32. Nunn JA, Rizza F, Peters ER. The incidence of schizotypy among cannabis and alcohol users. J Nerv Ment Dis. 2001;189(11):741-748.
33. Skosnik PD, Spatz-Glenn L, Park S. Cannabis use is associated with schizotypy and attentional disinhibition. Schizophr Res. 2001;48(1):83-92.
34. Williams JH, Wellman NA, Rawlins JN. Cannabis use correlates with schizotypy in healthy people. Addiction. 1996;91(6):869-877.
35. Spencer C. Motives that maintain cannabis use among individuals with psychotic disorders. In: Castle D, Murray R, eds. Marijuana and Madness. Cambridge MA: Cambridge University Press; 2004:166-185.
36. Lee CM, Neighbors C, Woods B. Marijuana motives: young adults’ reasons for using marijuana. Addict Behav. 2007;32:1384-1394.
37. Brodbeck J, Matter M, Page J, Moggi F. Motives for cannabis use as a moderator variable of distress among young adults. Addict Behav. 2007;32(8):1537-1545.
38. Rey JM, Martin A, Krabman P. Is the party over? Cannabis and juvenile psychiatric disorder: the past 10 years. J Am Acad Child Adolesc Psychiatry. 2004;43(10):1194-1205.
39. Hayatbakhsh MR, Najman JM, Jamrozik K, Mamun AA, Alati R, Bor W. Cannabis and anxiety and depression in young adults: a large prospective study. J Am Acad Child Adolesc Psychiatry. 2007;46(3):408-417.
40. Macleod J, Oakes R, Copello A, et al. Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet. 2004;363(9421):1579-1588.
41. Green B, Ritter C. Marijuana use and depression. J Health Soc Behav. 2004;41(1):40-49.
42. Windle M, Wiesner M. Trajectories of marijuana use from adolescence to young adulthood: predictors and outcomes. Dev Psychopathol. 2004;16(4):1007-1027.
43. Fergusson DM, Horwood LJ. Early onset cannabis use and psychosocial adjustment in young adults. Addiction. 1997;92(3):279-296.
44. Gruber AJ, Pope HG, Hudson JI, Yurgelun-Todd D. Attributes of long-term heavy cannabis users: a case-control study. Psychol Med. 2003;33(8):1415-1422.
45. Jacobsen LK, Mencl WE, Westerveld M, Pugh KR. Impact of cannabis use on brain function in adolescents. Ann N Y Acad Sci. 2004;1021:384-390.
46. Tims FM, Dennis ML, Hamilton N, et al. Characteristics and problems of 600 adolescent cannabis abusers in outpatient treatment. Addiction. 2002;97(suppl 1):46-57.
47. Maharajh HD, Konings M. Cannabis and suicidal behaviour among adolescents: a pilot study from Trinidad. ScientificWorldJournal. 2005;5:576-585.
48. Shedler J, Block J. Adolescent drug use and psychological health. A longitudinal inquiry. Am Psychol. 1990;45(5):612-630.
49. Baigent M, Holme G, Hafner RJ. Self reports of the interaction between substance abuse and schizophrenia. Aust N Z J Psychiatry. 1995;29(1):69-74.
50. Green AI, Tohen MF, Hamer RM, et al. First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol. Schizophr Res. 2004;66(2-3):125-135.
51. Dixon L, Haas G, Weiden PJ, Sweeney J, Frances AJ. Drug abuse in schizophrenic patients: clinical correlates and reasons for use. Am J Psychiatry. 1991;148(2):224-230.
52. Glynn SM, Sussman S. Why patients smoke. Hosp Community Psychiatry. 1990;41(9):1027-1028.
53. Mueser KT, Nishith P, Tracy JI, DeGirolamo J, Molinaro M. Expectations and motives for substance use in schizophrenia. Schizophr Bull. 1995;21(3):367-378.
54. Schofield D, Tennant C, Nash L, et al. Reasons for cannabis use in psychosis. Aust N Z J Psychiatry. 2006;40(6-7):570-574.
55. Nordstrom BR, Levin FR. Treatment of cannabis use disorders: a review of the literature. Am J Addict. 2007;16(5):331-342.
56. Haney M, Ward AS, Comer SD. Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology (Berl). 2001;155(2):171-179.
57. McDowell D, Levin FR, Brooks DJ, et al. Treatment of cannabis-dependent treatment seekers: a double-blind comparison of nefazodone, bupropion and placebo. Paper presented at: the 68th Annual Scientific Meeting of the College on Problems of Drug Dependence. June 17-22, 2006; Scottsdale, AZ.
58. Haney M, Hart CL, Ward AS, Foltin RW. Nefazodone decrease anxiety during marijuana withdrawal in humans. Psychopharmacology (Berl). 2003;165(2):157-165.
59. Haney M, Hart CL, Vosburg SK, et al. Marijuana withdrawal in humans: effects of oral THC or divalproez. Neuropsychopharmacology. 2004;29(1):158-170.
60. Levin FR, Mcdowell D, Evans SM, et al. Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict. 2004;13(1):21-32.
61. Huestis MA, Boyd SJ, Heishman SJ, et al. Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology (Berl). 2007;194(4):505-515.
62. Hart CL, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW. Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology (Berl). 2002;164(4):407-415.
63. Diamond G, Godley SH, Liddle HA, et al. Five outpatient treatment models for adolescent marijuana use: a description of Cannabis Youth Treatment interventions. Addiction. 2002;97(suppl 1):70-83.
64. Dennis M, Titus JC, Diamond G, et al. The Cannabis Youth Treatments (CYT) experiment: rationale, study design and analysis plans. Addiction. 2002;97(suppl 1):16-34.
65. French MT, Roebuck MC, Dennis ML, et al. The economic cost of outpatient marijuana treatment for adolescents: findings from multi-site field experiment. Addiction. 2002;97(suppl 1):84-97.
66. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat. 2004;27(3):197-213.
67. Edwards J, Elkins K, Hinton M, et al. Randomized controlled trial of a cannabis-focused intervention for young people with first-episode psychosis. Acta Psychiatr Scand. 2006;114(2):109-117.
68. Addington J, Addington D. Impact of an early psychosis program on substance use. Psychiatr Rehabil J. 2001;25(1):60-67.
69. NIDA. Marijuana: Facts for Teens. Available at: www.nida.nih.gov/MarijBroch/Marijteens.html. Accessed April 17, 2008.