REVIEW ARTICLE. Psychiatric Morbidity of Cannabis Abuse ABSTRACT

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1 INDIAN JOURNAL OF PSYCHIATRY, 003, 45 (III), 8-88 REVIEW ARTICLE Psychiatric Morbidity of Caabis Abuse JAYDIP SARKAR, PRATIMA MURTHY, SWARAN P SINGH ABSTRACT The paper evaluates the hypothesis that caabis abuse is associated with a broad rage of psychiatric disorders i Idia, a area with relatively high prevalece of caabis use. Retrospective case-ote review of all cases with caabis related diagosis over a -year period, for subjects presetig to a tertiary psychiatric hospital i souther Idia was carried out. Iformatio pertaiig to sociodemographic, persoal, social, substace-use related, psychiatric ad treatmet histories, was gathered. Stadardized diagoses were made accordig to Diagostic Criteria for Research of the World Health Orgaizatio, o the basis of iformatio available. Caabis abuse is associated with widespread psychiatric morbidity that spas the major categories of metal disorders uder the ICD-0 system, although proportio of patiets with psychotic disorders far outweighed those with o-psychotic disorders. Whilst paraoid psychoses were more prevalet, a sigificat umber of patiets with affective psychoses, particularly maia, was also oted. Besides beig kow as either the causative aget or a potet risk factor i cases of paraoid psychoses, caabis appears to have similar capabilities with regard to affective psychoses, particularly i cases of maia. It is suggested that caabis has the potetial to act as a "life evet stressor" amogst subjects vulerable to develop affective psychoses ad the possible aetiopathogeesis of such a fidig is discussed. Key words: Caabis, psychiatric disorders INTRODUCTION Caabis is oe of the most frequetly abused psychoactive drugs (Grispoo ad Bakalar 993). Psychiatric disturbaces associated with caabis use rage from mior psychological resposes such as axiety ad paic (Thomas 9), to depressive disorders (Troisi et al 998), the more serious metal illesses such as the putative 'caabis psvehosis' (Talbott ad Teaguc 969), acute fuctioal psvehosis (Johs KM), chroic psychosis (Ghodse 986) ad the poorly validated etity of ' motivatioal svdrome (Hall ct al 999). The ature of associatio ad the directio of causality betwee caabis use ad various metal disorders await elucidatio (Thomas 993). The strogest evidece of a specific cotributory role of caabis use exists oly i relatio to schizophreia (Adrease et al 987). Idia has a log traditio of caabis use, which is ofte socially sactioed (Natioal Istitute of Social Defese 99). The associatio betwee caabis use ad metal disorders has bee recorded for well over a cetury (Idia Hemp Commissio Report 894). Whilst cosiderable attetio has bee paid to the associatio betwee caabis use ad psychotic disorders (Basu et al 999, Thacore ad Shukla 976, Chopra ad Smith 974), relatively little is kow about the impact of caabis abuse o wider psychiatric morbidity. We preset a retrospective study as prelimiary exploratio to evaluate the hypothesis that caabis abuse will be associated with a broad rage of psychiatric disorders, through a case-ote review of patiets abusig caabis who preseted to a large tertiary psychiatric hospital i south Idia. We also explored the patter of caabis use by this populatio. METHODS The Catchmet Populatio: The study was coducted at a tertiary referral ceter i Bagalore, caterig to a large catchmet area. All patiets receive a diagostic code accordig to the criteria laid dow i successive revisios of the Iteratioal Classificatio of Diseases - ICD-9, (prior to 99) ad ICD-0 (thereafter). I keepig with WHO recommedatios, all comorbid psychiatric diagoses are coded for each patiet. Sample: Selected case-otes with ay caabis related diagosis were idetified for the period betwee Data: Iformatio was recorded for socio-demographic data, history of substace use ad other cliical history variables. Socio-demographic variables icluded subject's age, sex, completed years of_. educatio, ad occupatio. Substace use variables were age of oset of caabis use, reaso for iitiatio, duratio of caabis use, duratio of daily use, temporal sequece of oset of psychiatric disorder i relatio to caabis use, ad use of ay other psychoactive substace prior to ad followig the oset of caabis use. Further, family history of substace use ad metal illess, ad the reaso for establishig cotact with the hospital were recorded. Psychopathology variables recorded icluded delusios (referece, persecutio, gradiosity, ifidelity ad others), halluciatios i ay modality, thought disorder (icludig flight of ideas), thought alieatio pheomea, psychomotor activity, mood disturbace, level of sesorium, cogitive deficits ad treatmet offered. < Iformatio pertaiig to psychopathology was recorded i the followig maer: a) for patiets with - cotacts durig the study period, all pheomea displayed (8)

2 CANNABIS AND PSYCHIATRIC MORBIDITY durig each of these cotacts was recorded. I doig so, the 'preset state' format for recordig psychopathology was adopted. b) for patiets with 3-5 cotacts, symptoms cotaied i the most recet cotact were recorded alog with symptoms of a similar type but with a more characteristic symptom profile, employig the otio of a 'represetative episode'. Where the most recet episode of symptoms was differet from the represetative episode (for example, maic episode maifested upo a depressive represetative episode) both sets of symptoms were recorded. c) I cases with more tha 5 cotacts, all varieties of symptoms e.g. psychotic, affective ad eurotic, as had bee displayed by the patiet, were recorded. Where there were two periods or episodes with differet types of symptoms, these were rated as though they were sub-episodes of oe exteded episode employig the otio of symptoms experieced i the 'lifetime before'. This patter is a acceptable method of symptom recordig i order to geerate diagoses [World Health Orgaizatio 993a]. All diagoses were made o the basis of criteria laid dow i the Diagostic Criteria for Research, DCR, (World Health Orgaizatio 993 b). RESULTS Socio-demographic data Two hudred ad forty four otes were idetified as havig a caabis related diagosis. AU 44 subjects were male. Their mea age was 30 years (S.D. ± 9.7; Rage = 8-8 years) ad 53 were sigle (09/04; data urecorded = 40). They had o average 9.7 years (S.D. ± 9.8) of educatio ad 45 had received betwee 5-0 years of formal educatio. Sixty-two percet of patiets were employed with represetatio of professioal, skilled ad uskilled workers beig 3, 7 ad respectively. Substace use history The mea age of iitiatio of caabis use was.4 years (S.D years; Rage = 0-65 years). Forty-three percet (9=05 had started usig caabis durig the secod decades of their lives. Eighty-ie (36) bega use durig the third decade whilst twety-five (0) did so i the fourth decade. For the rest, oset of use was eve later. Where iformatio pertaiig to reasos for caabis use was recorded ( = 5; 47), 57 cited recreatioal ad experimetal use, attributed oset to a dysphoric mood state while cited peer pressure as the primary reaso. Data was uavailable for total duratio of o-cotiuous (regular but ot daily) ad cotiuous (daily) caabis use i 3 (3o) ad 4 (58) cases respectively. The mea duratio of o-cotiuous use of caabis was 80 moths (S.D moths) while the duratio of cotiuous use was 49 moths (S.D. ± 50 moths). Amogst daily users, 3 (3) subjects had bee usig caabis for less tha years, 44 (43 ) patiets had bee usig it betwee -5 years ad 7 (6 ) patiets had cosumed it for over 5 years. TABLE I : Socio-demographic ad substace use variables Relatio of caabis use to oset of psychiatric disorders I 7 patiets (5), a psychiatric disorder had occurred followig caabis use while for 8 patiets (7), psychiatric disturbace had preceded the oset of caabis use. Data were uavailable for 99 patiets (4). For 67 of patiets caabis was the first drug of abuse i their substace use life-trajectories. Alcohol ad opioids were the iitial substace of abuse i 9 ad 4 patiets respectively. Amogst those usig caabis o a cotiuous basis, 5 also used polysubstace (caabis, alcohol ad opioids for this study) while ) ad 9 used oly alcohol ad opioids respectively. Thus, 35 of caabis users also used other substaces cocurredy, whilst for the remaiig 65 caabis remaied the oly substace of use. Data o homotypic comorbidity (other comorbid substace use disorders) was uavailable for 4 cases (see table ). Variable (N=44) Mea S.D. Rage Age of patiet Age of oset of caabis use Duratio of o-cotiuous caabis use Duratio of cotiuous caabis use 30 years.4 years 80 moths 49 moths +_9.7 years +_ 8.4 years +_ 7 moths +_ 50 moths TABLE : Temporal relatio betwee caabis ad other drug use ( =44) Opiates Combiatio of the above Noe Not kow Substace Followig used Caabis 9' Precedig 8-8 years 0-65 years -44 moths -40 moths caabis use (83)

3 SARKAR at al Family history Data o family history were available i 0 (83) subjects. 33 subjects (6) had a positive family history of a psychiatric disorder ad 48 (4) had a positive family history of substace abuse. Twety-seve percet of patiets with o-psychotic illesses had a positive family history followed by subjects with affective psychoses (6), paraoid psychoses icludig schizophreia (8), caabis psychosis (6) ad substace misuse disorders (9). Patiets with oly substace misuse disorders had the highest rate of family history of substace misuse (3), followed by subjects with o-psychotic illess (9), paraoid Psychopathology Delusioal thikig was reported i 05 patiets (43). Persecutory delusios were the commoest (6) followed by gradiose () ad referetial (9) delusios. Fortyoe percet of patiets experieced halluciatios, most commoly i the auditory modality (5). Thought disorder, icludig 'flight of ideas', was recorded i 6 patiets (). Elated mood (3) was more commo tha depressed mood (6), i patiets with affective disturbaces. Thought alieatio pheomea such as thought broadcastig, thought isertio ad thought withdrawal were reported i TABLE 3 : Family history of metal illess ad substace misuse Diagostic groups Family History of Family History of Substace No-psychotic Metal Illess Misuse (data uavailable =4, 7) (data uavailable =4l, 7) Affective psychosis (DCR rubric of F30-39) No-affective psychosis (DCR rubric of F0-9) Caabis psychosis Substace misuse disorder Total 4/5 8/3 7/39 8/5 6/65 33/0 psychoses (), caabis psychosis (8) ad affective psychosis (3). Reaso for help seekig For 0 patiets (56) (Data uavailable: = 47; 9), display of abormal behavior usually oted by family members formed the reaso for establishig cotact with the cliical services. A third of the patiets cotacted the hospital for relief from distressig withdrawal symptoms of alcohol ad opioid withdrawal. Subjectively reported depressed mood was the presetig complait i patiets /4 4/30 9/4 9/50 /68 48/ (4) cases. Icreased psychomotor activity (=ll;4), pressure of speech ( =9; 3) ad a combiatio of the two (=7; ) were also evidet i a small proportio of patiets.. Bizarre behaviour that icluded such acts as smearig faeces, spittig, iappropriate ad vacuous laughter, livig i rubbish pits, takig off oe's clothes, self mutilatio, mutism, ad posturig was reported i 3 (3) cases. Catatoic symptoms were icluded amogst these. The case otes also recorded te patiets as havig cloudig of cosciousess (4), ad seve patiets (3) with cogitive deficits Diagosis Two types of comorbidity were idetified i this cohort. Caabis use disorder/s was either associated with other substace use disorder/s (but ot with substace use related metal disorder/s) or with idepedet psychiatric disorder/s, i.e. osubstace use related. The former was referred to as homotypic while the latter as heterotypic comorbidity [Degehardt et al 00]. a) Substace abuse comorbidity (Homotypic comorbidity): There were i all eight differet types of substace related diagoses, other tha caabis-related diagoses, i the total cohort (see table 4). There were 44 cases of caabis depedece, 95 cases of harmful use (abuse) ad five cases of acute itoxicatio. Oe hudred ie patiets (47) also received aother substace misuse disorder diagosis, which icluded fortyie cases of alcohol abuse (=3) or depedece (=6), thirty-six cases of polysubstace abuse (=3) or depedece (=3) ad thirtee cases of opioid depedece. Polysubstace abuse/ depedece was recorded i those abusig three differet substaces cocurredy: caabis, alcohol ad opioids. There were o case of amphetamie, bezodiazepie, cocaie, ecstasy, LSD, ihalat or steroid abuse. The prevalece of icotie ad caffeie use was ot recorded. Substace misuse/depedece was the oly psychiatric diagosis i eighty cases (34). This umber may appear to be smaller tha what the precedig figures suggest as patiet with more tha oe substace abuse/depedece were couted more tha oce uder the respective headigs. For istace a patiet with caabis abuse/depedece who was Comorbidity of Caabis abuse I Caabis diagosis+heterotypic comorbidity ) Caabis diagosis + Homotypic comorbidity I Caabis diagosis + Homotypic comorbidity + Heterotypic comorbidity (84)

4 CANNABIS AND PSYCHIATRIC MORBIDITY TABLE 4 : Psychiatric morbidity i patiets abusig caabis Diagosis Caabis iduced psychosis Schizophreia Delusioal disorder Other o orgaic psychotic disorders B.A.D-maia with psychosis B.A.D.- severe psychotic depressio Severe psychotic depressio Hypomaia Mild depressio Moderate depressio Other depressive disorder Cyclothymia Dysthymia Geeralized axiety disorder Adjustmet reactio - prologed depressio Trace ad possessio disorder Dissocial Persoality disorder Pathological gamblig Exhibitioism Mild Metal Retardatio Caabis iduced uspecified metal & behavior disorder Substace use/depedece oly No. of cases (N=44) delusios, halluciatios ad mood disturbace, most commoly elatio. A further four cases displayed a admixture of paraoia, grossly disorgaized behavior, fleetig halluciatios ad delusios ad were diagosed as mixed psychotic state. The latter diagosis was made by a process of exclusio of other diagostic subtypes. Sigificady, there was o case of a predomiady depressive psychotic state Psychotic disorders I Caabis psychosis I Schizophreia I B.A.D. Maia I Other o-orgaic psychosis I Delusioal disorder I psychotic depressio I B.A.I). - Psychotic depressio Psychotic disorders associated with caabis use Total also abusig alcohol ad opioids was coded uder caabis abuse ad polysubstace abuse respectively. b) Idepedet psychiatric disorder comorbidity (Heterotypic comorbidity) Twety-oe heterotypic comorbid psychiatric diagoses were made for 64 patiets (67), i.e. havig a comorbid psychiatric disorder. Psychotic disorders were experieced by 44 patiets (88 of Heterotypic comorbidity I Paraoid psychosis I Caabis psychosis I Affective psychosis I No-psychotic disorders Heterotypic comorbidity of Caabis use those with comorbid psychiatric disorders), while 0 patiets experieced a o-psychotic illess (). The group of patiets with psychotic disorders was made up of those sufferig with paraoid psychosis icludig schizophreia (=58; 40), caabis psychosis (=5; 35) ad affective psychosis (=35; 5). Depressive ad axiety disorders (=9; 45) were the largest cotributors to the umbers of those with o-psychotic disorders. Caabis psychosis was the commoest diagosis amogst those with psychotic disorders. Six differet subtypes of caabis psychosis were diagosed, the commoest subtype beig a maia-like psychosis (=) with gradiose delusios, elated mood ad icreased psychomotor activity. A predomiady schizophreia-like psychotic state (=8) ad a predomiady delusioal state (=6) were see more ofte tha a further six cases of a predomiatly halluciatory psychosis. Five subjects preseted with a polymorphic ad rapidly chagig cliical picture characterized by Subtypes ol caabis psychosis I Maic I Schizophreia-like I Delusioal I Halluciatory I polymorphic I Mixed Subtypes of caabis psychosis that could be attributed to caabis abuse. Twelve patiets with caabis psychosis had cosumed substaces other tha caabis icludig alcohol (0 cases) ad two cases of polysubstace abuse/depedece. These were diagosed as caabis psychosis because of a temporal lik betwee caabis use ad oset of psychosis. Treatmet give About half the patiets (49.5) received atipsychotic medicatio (49.5); twetythree patiets (9) received a moodstabilizig aget while () were prescribed atidepressats. (85)

5 SARKAR «t al DISCUSSION This study has a large patiet sample of chroic ad heavy caabis users comig from a wide geographical catchmet area icludig urba, peri-urba, sub-rural, ad rural populatios. The sample is represetative of all strata of the society. The stregths of the study icluded data collected at a academic istitute with a traditio of good record keepig ad diagostic codig. A maual search i additio to electroic search was carried out to locate all case-otes thereby miimizig the chaces of missig cases. Dow-ratig the aetiologies! role of caabis i favour of a fuctioal diagosis would have further reduced ay spurious attributio of metal disorders solely to caabis use. a) Heterotypic Comorbidity Our results suggest that heavy ad chroic use of caabis ca both cause a caabisiduced psychosis ad be associated with fuctioal psychoses. Broadly, the ature of psychosis associated with heavy caabis use is o-specific i that it icludes both paraoid ad affective psychosis but also a polymorphic disorder that caot be categorized withi either of the two groups. A smallet proportio of patiets also developed o-psychotic disorders. The presece of a wide variety of psychiatric disorders associated with caabis abuse therefore cofirmed the study hypothesis. The rate of psychiatric morbidity is comparable to earlier reports [Troisi et al 998, Weller ad Halikas 985]. b) Caabis ad Maic Psychosis The most sigificat fidig of the study was the associatio of caabis abuse with developmet of maic disorder. Whilst there are previous smaller reports of a possible associatio betwee caabis use ad maia, [Dhujibhoy 930, Rottaburg et al 98, Carey et al 984, Hardig ad Kight 973] we believe that our study is the first oe to cofirm this relatioship i a sizable umber of patiets. I our cohort, some patiets with a past history of maia ad caabis abuse appeared to become sesitized to the effects of caabis over a period of time so that for subsequet episodes of maia there appeared to be a progressive decrease i the time gap betwee re-oset of caabis use ad oset of maia. I other words, the relative shorteig of time to relapse followig reitroducrio of caabis use i successive episodes i this select group of patiets appeared aalogous to the process of 'kidlig' [Post et al 989, Post et al 98]. By 'hasteig' maic relapses, caabis appeared to act as a precipitat, aki to the "life-evet stressor" first suggested as a triggerig mechaism i cases of schizophreia [Adreasso et al 987]. The associatio betwee caabis abuse ad maia gais further support from a recet study wherei caabis use durig followup of 50 ew-oset bipolar disorder patiets was associated with the experiece of maia, whilst alcohol abuse was liked to the experiece of depressio [Strakowski et al 000]. There may be possible biological explaatios for the associatio betwee caabis abuse ad maia. Delta-9- tetrahydrocaabiol (THC), the active igrediet of caabis, produces euphoria [Brill ad Nahas 984]. Uder laboratory coditios high doses of THC have bee show to produce visual ad auditory halluciatios, delusios, thought disorder ad symptoms of hypomaia i ormal voluteers [Georgotas ad Zeideberg 979]. Recet evidece also suggests that caabioid receptors, especially CB-, located i substatia igra, hippocampus, cerebellum ad striatum, may be euromodulatory by decreasig the uptake of GABA ad dopamie, thereby potetiatig their actios [D'Souza ad Koste 00]. Further prospective ad case-cotrol studies, which cotrol for other substace misuse are eeded to elucidate this further. ii) Caabis Psychosis Our results suggest that besides the triggerig effect of caabis i established bipolar disorders, caabis psychoses ca also preset as a maic episode. We also foud other psychotic presetatios suggestig that caabis psychosis ca preset as schizophreia-like, predomiatly delusioal or halluciatory, as affective psychosis or as a polymorphic ad rapidly chagig psychosis. We could ot cofirm the previous suggestios that the presece of cofusioal state is a hallmark of caabis psychosis [Johs 00, Chopra ad Smith 974, Chaudhry et al 99, Teat ad Groesbeck 97, Goel ad D'Netto 975] sice oly three patiets i this study displayed a cofusioal state. The DCR positio, which does ot prioritize this particular feature to a positio of primacy i makig a diagosis of caabis psychosis, is therefore validated. iii) Caabis ad Schizophreic Psychosis Our results cofirm the associatio betwee caabis abuse ad paraoid psychoses, especially schizophreia. However, eve some of these cases have promiet affective features, cosistet with previous reports [Thacore ad Shukla 976, Rottaburg et al 98, Tsuag et al 98]. I additio, i a substatial proportio of our cases, oly a diagosis of 'other oorgaic psychotic disorders' (F9 category) [World Health Orgaizatio 993a] could be made o accout of bizarre symptomatology, particularly grossly disorgaized behavior. Whilst the diagosis of catatoic schizophreia had bee made for several of these patiets by treatig cliical teams, this diagosis was foud usupported by DCR criteria, which specify that catatoic symptoms are ot diagostic of schizophreia ad may be provoked by other aetiologies icludig alcohol or drugs [World Health Orgaizatio 993b]. b) Homotypic Comorbidity: Caabis has bee kow as a 'gateway drug', ad recet evidece suggests that eve after cotrollig for a wide rage of kow risk factors for illicit drug use, caabis use is associated with a icreased risk of progressio to other illicit drug use [Fergusso ad Horwood 000]. Our study cofirms this sice may subjects had alcohol, opioid ad polysubstace abuse (86)

6 ANTIDEPRESSANT INDUCED CANNABIS AND PSYCHIATRIC MORBIDITY ad depedece i this group. Caabis was die first drug of use i the substace use life-trajectories of two-thirds of this populatio, the remaiig third startig with alcohol or opioids. However, for two-thirds of the whole cohort caabis remaied the oly drug of abuse. Whilst this may appear cotradictory to the foregoig, we believe diat it is ot icosistet for people to progress from caabis use to other illicit drugs i experimetal ways, but to cotiue to preferetially use caabis i a depedat maer, thereby cofirmig that i coutries such as Idia that have a traditio of caabis use, the widespread use of other substaces is limited [Basu et al 994]. The study fidigs are limited by the cohort beig exclusively male, die lack of corroborative urie samples, possible recall bias ad uder-reportig by patiets ad, lack of ay structured assessmets, leadig to reliace o case-ote data aloe. CONCLUSIONS Chroic ad heavy abuse of caabis i hospital attedig patiets i Idia is associated with widespread psychiatric morbidity. The oset of caabis use begis at a relatively early age ad heralds the experimetatio with other psychoactive drugs. For the majority, however, caabis remais the oly drug of abuse. Experiece of a psychotic illess is oe of the major adverse effects of heavy caabis use, particularly i those that preset to psychiatric hospitals. Whilst our study cofirms some of die earlier fidigs of associatio of caabis use ad the developmet of caabis psychosis ad schizophreia, most sigificady it reveals that heavy caabis use ca specifically cause a maia-like psychosis ad more geerally act as a precipitat for maic relapse i bipolar patiets. REFERENCES Adreasso, S., Allebeck, P., Egstrom, A., Rydberg, U. (987) Caabis ad schizophreia: a logitudial study of Swedish coscripts. Lacet, (ii), Basu, D., Malhotra, A., Varma, V.K. 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7 SARKAR at al World Health Orgaizatio (993a) Schedules for Cliical Assessmets i Neuropsychiatry, versio, Glossary. Geeva: World Health Orgaizatio. World Health Orgaizatio (993b) The ICD-IO classificatio of metal ad behavioral disorders:oiagostic criteria for research. Geeva: World Health Orgaizatio. World Health Orgaizatio (993c) The ICD-IO classificatio of metal ad behavioral disorders: Cliical descriptios ad diagostic guidelies. Geeva: World Health Orgaizatio. JAYDIP SARKAR, Specialist Registrar i Foresic Psychiatry, Shaftesbury Cliic, Sprigfield Uiversity Hospital, Lodo, SWI7 7DJ, U.K. PRATIMA MURTHY*, Associate Professor of Psychiatry, Natioal Istitute of Metal Health & Neuro Scieces, Hosur Road, Bagalore, 56009, Idia. SWARAN P SINGH, Seior Lecturer i Commuity Psychiatry, Departmet of Geeral Psychiatry, St George's Hospital Medical School, Blackshaw Road, Lodo, SWI7 ORE, U.K. * Correspodece (88)