Treatment of Cannabis Use Among People with

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Treatment of Cannabis Use Among People with Psychotic Disorders: A Critical Review of Randomised Controlled Trials Amanda L. Baker1*, Louise K. Thornton2, Leanne Hides3 and Adrian Dunlop4 1 Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia 2308; 2Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia 2308; 3Institute of Health & Biomedical Innovation (IHBI) and School of Psychology & Counselling, Queensland University of Technology (QUT), GPO Box 2434, Kelvin Grove, Brisbane, Queensland, Australia, 4001; 4School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia 2308

Abstract: There is growing and converging evidence that cannabis may be a major risk factor in people with psychotic disorders and prodromal psychotic symptoms. The lack of available pharmacological treatments for cannabis use indicates that psychological interventions should be a high priority, especially among people with psychotic disorders. However, there have been few randomised controlled trials (RCTs) of psychological interventions among this group. In the present study we critically overview RCTs of psychological and pharmacologic interventions among people with psychotic disorders, giving particular attention to those studies which report cannabis use outcomes. We then review data regarding treatment preferences among this group. RCTs of interventions within “real world” mental health systems among adults with severe mental disorders suggest that cannabis use is amenable to treatment in real world settings among people with psychotic disorders. RCTs of manual guided interventions among cannabis users indicate that while brief interventions are associated with reductions in cannabis use, longer interventions may be more effective. Additionally, RCTs reviewed suggest treatment with antipsychotic medication is not associated with a worsening of cannabis cravings or use and may be beneficial. The development of cannabinoid agonist medication may be an effective strategy for cannabis dependence and suitable for people with psychotic disorders. The development of cannabis use interventions for people with psychotic disorders should also consider patients’ treatment preferences. Initial results indicate face-to-face interventions focussed on cannabis use may be preferred. Further research investigating the treatment preferences of people with psychotic disorders using cannabis is needed.

Keywords: Cannabis, marijuana, psychosis, treatment, motivational interviewing, cognitive behaviour therapy. INTRODUCTION Cannabis is the most widely used illicit substance, with annual prevalence rates among people aged 15-64 years of 10.7% in North America, 7.1% in West and Central Europe and 10% in Australia.[1] There is an additional public heath concern with respect to the increasing trend toward the use of hydroponically grown cannabis with significantly higher tetrahydrocannabinol (d9THC) content at younger ages, due to increasing evidence of a relationship between cannabis use and a range of mental health problems.[2] In fact, the most recent Australian National Drug Strategy Household Survey [3] reported that people who had used cannabis in the previous 12 months were more likely to have been diagnosed with a mental illness (18.7% versus 11.3%) and to report high or very high levels of psychological distress (16.3% versus 9.1%) compared to those who had not used cannabis in the last year. Research and clinical evidence suggest that cannabis can produce a range of transient psychotic symptoms and cognitive deficits [e.g., 4]. There is also evidence that early onset and heavy cannabis exposure could increase the risk of developing a frank psychotic disorder such as schizophrenia [e.g., 5]. Just over 50% of adolescents (aged 15 to 16 years) who had used cannabis in their lifetime reported a number of sub-threshold psychotic-like symptoms in the past six months [6]. Even higher rates of psychotic-like symptoms have been found in current cannabis users (past 30 days); up to 90% over a 7 day period [7]. A recent 10-year follow-up cohort study confirmed cannabis use was a risk factor for the development *Address correspondence to this author at the Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia 2308; Tel: 61 2 40335690; Fax 61 2 40335692; E-mail: [email protected] 1873-4286/12 $58.00+.00

of psychotic symptoms and that continued cannabis use increased the risk of psychotic disorder by impacting on the persistence of symptoms [8]. The dramatic impact of cannabis on the onset of psychotic symptoms has been further supported by research into high risk subjects who have an enhanced probability of developing the disease over a short period of time. A recent prospective multicentre, naturalistic field study with an 18-month follow-up period in 245 help-seeking individuals clinically at high risk for psychosis showed younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of subtle psychotic symptoms [9]. Similar findings have been reported in first episode psychosis (FEP) groups [10-12] and in chronic schizophrenia [for metaanalyses see 13, 14]. Although the majority of studies did not examine important confounding variables (e.g., baseline illness severity, alcohol or other drug use), cannabis use has been associated with higher rates of psychotic relapse among individuals in the early stages of psychosis in three studies which controlled for these factors [15-17]. There is thus growing and converging evidence that cannabis may be a major risk factor in people with prodromal psychotic symptoms as well as in cohorts of first episode or chronic subjects. However, despite the burden of such a negative impact, there have been few randomised controlled trials (RCTs) of psychological or pharmacological interventions among this group. In the present study we will critically overview RCTs of psychological and pharmacologic interventions among people with co-existing psychotic disorders, giving particular attention to those studies which report cannabis use outcomes. Following a critical overview of the treatment literature, we then review data regarding treatment preferences among this group, focusing on RCTs. Finally, we discuss © 2012 Bentham Science Publishers

4924 Current Pharmaceutical Design, 2012, Vol. 18, No. 32

recommendations for the treatment of cannabis use among people with psychotic disorders and future research. Effect sizes (Cohen’s d: small effect size (.20); medium effect size (.50); large effect size (.80)) [18] of results reported in studies of manual guided interventions and pharmacologic interventions were calculated using the program Comprehensive Meta-Analysis, version 2 [19]. RCTS OF TREATMENT PROGRAMS CONDUCTED WITHIN MENTAL HEALTH SERVICE SETTINGS Studies conducted within “real world” service settings suggest that substance use is amenable to treatment among people with psychotic disorders. As far as the authors are aware, eight RCTs of treatment programs within mental health systems have been reported among adults with severe mental disorders and have described cannabis use at intake into the studies [20-28]. The main features of these studies are shown in Table 1. The wide range of treatment modalities investigated and the heterogeneity of control conditions limit our ability to determine which type of treatment may be most effective. In addition, the lack of common cannabis use measures employed across the studies limits the conclusions that can be drawn regarding the effectiveness of treatment for cannabis use among this group. Nevertheless, the results of these studies suggest that cannabis use is amenable to treatment in real world settings among people with psychotic disorders. Several RCTs of psychological interventions for substance use among people with psychotic disorders have been conducted, with samples including cannabis users. These RCTs evaluate well specified and manual guided interventions which help progress our knowledge of the effectiveness of specific interventions for psychotic disorders and allow wide dissemination of treatments if shown to be effective. In the paragraphs below here we will first discuss the available RCTs for psychological interventions, with respect to general substance use outcomes (inpatient or outpatient psychotic subjects) or to cannabis-related outcomes (inpatient or outpatient psychotic subjects). In another section we will focus on potential psychopharmacological treatment of cannabis use. PSYCHOLOGICAL INTERVENTIONS FOR SUBSTANCE USE IN PSYCHOTIC PATIENTS RCTs of Manual Guided Interventions Among Cannabis Users with Psychotic Disorders Reporting General Substance Use Outcomes The lack of available pharmacological treatments for cannabis use [e.g., 29] indicates that psychological interventions for cannabis use should be a high priority [30], particularly among people with psychotic disorders or with potentially prodromal features of the illness. Common elements of psychological interventions for substance abuse among people with psychotic disorders include: • use of therapeutic strategies matched to the motivational state of the client; • adoption of a harm minimisation rather than abstinence-based approach; • communication that takes account of information-processing problems often experienced by individuals with psychotic disorders; • and use of motivational interviewing (MI) and/or cognitive behaviour therapy (CBT) [31]. MI is a counselling style first developed by Miller [32] to address the ambivalence often encountered when working with problem drinkers. It has evolved over time and is commonly employed by counsellors to address health behaviour change [e.g., 33]. Rather than directly confront ambivalence about behaviour change, MI seeks to elicit self-motivational statements from the patient, through open-ended questions and reflective statements, acknowledging the rewarding aspects of engaging in unhealthy behaviours and, at the

Baker et al.

same time, the less positive aspects. The patient is assisted in decision making about whether they wish to address the behaviour and, if so, how they might set goals and begin change. Five RCTs have reported results of manual guided interventions among cannabis users and have reported general substance use outcomes (rather than cannabis use outcomes). The methodological details of these studies are described in Table 2. Manual Guided Interventions Among Inpatients with Psychosis A study by Kavanagh et al. [34] evaluated a MI intervention (6 to 9 sessions within 10 days) for substance misuse among 25 individuals admitted to hospital for FEP or recent-onset psychosis. The primary outcome was a rating of abstinence or substantial improvement on all substances, conducted by blind assessors. Engagement and retention were problematic. Based on analyses for “treated” individuals, significantly more individuals who received at least some of the MI intervention showed improvement in substance use at 6 and 12 months following initial assessment compared to individuals who received standard care. However, differences in outcome between the two groups were no longer significant when intention-to-treat analyses were performed. Given the small sample size, the results of this study do not provide strong evidence for the effectiveness of MI over usual treatment for substance use among inpatients. Manual Guided Interventions Among Outpatients with Psychosis Barrowclough et al. [35] randomly allocated 36 patientcaregiver dyads to a manual guided program of MI, CBT and a family intervention for up to 9 months or to standard care. The MI/CBT occurred over 29 individual sessions and the family intervention consisted of 10-16 sessions. Sessions took place in the care givers’ and patients’ homes. Although engagement was difficult, retention in treatment among those enrolled in the study was good. The intervention condition showed an improvement in general functioning, a reduction in the severity of positive symptoms and a lower rate of psychotic relapse at 12 months (following initial assessment) compared to individuals who received standard care, as assessed by blind interviewers. The intervention group reported a greater percentage of days abstinent from all substances relative to baseline at all time-points, although the differences were not statistically significant. At 18-months following initial assessment, the intervention group maintained improvements in general functioning and had less severe negative symptoms compared to controls but there were no significant differences between groups on substance use measures.[36] Thus, some symptom and functioning advantages of this intensive intervention were shown at follow-up but these improvements did not extend to substance use outcomes. James et al. [37] queried the practicality of applying the intensive intervention implemented by Barrowclough and colleagues [35] in routine mental health service settings. They reported 3month follow-up results for a sample of 63 people with a nonorganic psychotic disorder, with an average of just over two years contact with mental health services. Randomization was performed by alternate allocation of subjects to either six weekly group sessions outlined in a treatment manual covering core aspects which focused on stage of change and motives for substance use or to a single session of education. Follow-up was conducted by a research assistant blind to treatment allocation. The intervention group showed significantly greater improvement in psychopathology, drug abuse and antipsychotic medication dose at 3 months postintervention compared to controls. The authors also reported statistically greater reductions in cannabis use, alcohol consumption, poly substance use and severity of dependence compared to controls. A longer structured group intervention, twice per week for six months, combined with individual MI at baseline and three and six

Treatment of Cannabis Use Among Psychotic Disorders

Table 1.

Current Pharmaceutical Design, 2012, Vol. 18, No. 32

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Details of RCTs of Treatment Programs Conducted within Mental Health Service Settings

Study

Sample

Diagnoses

Cannabis use at

(%)

baseline

Design

Main Results

Methodological limitations

Lehman et

N=54

DSM-III-R

Cannabis misuse by

TAS (SCM, day

At 12 mths:

Small sample size,

al. (1993)

Outpatients

68% SCZ/SA

62%

rehab, housing if

• NS between conditions of psychiatric inpatient

predominantly

Male=74%

23% BP

Mean age=31

9% MD

needed) vs. TAS+ICM+Gp

days or self-reported alcohol, drug, psychiatric

male sample,

severity, life satisfaction.

participation rate not reported, not reported if asses-

Participation

sors were blinded

54% SUD

rate: not reported Burnam et al. (1995)

N=276 Outpatients Male=84%

DSM-III-R

Cannabis use in last

Control vs. Non-

At 3 mths:

Predominantly

45% SCZ

mth by 47%

residential vs.

• Res and Nores had greater fall in days used alcohol

male sample, poor

Residential

93% Aff

(Nonres and Res

Mean age=37

had Ed + S-H + Gp + SCM +

100% SUD

Activities

Participation

than controls

• NS between Res and Nonres, except Nonres had more time in independent housing

participation rate (57%), Blinded assessors not used

At 6 mths:

• Res and Nonres had greater fall in drug use seve-

rate: 57%

rity than controls

• NS between Nonres and Res at 6 and 9 mths Hellerstein et al. (1995)

N=47 Outpatients Male=77%

RDC

Cannabis misuse by

TAS (Parallel tx

At 4 mths:

Small sample size,

30% SCZ

77%

by MH and SUD

• Int. had greater retention in tx than TAS

predominantly

services) vs. Int.

70% SA

(Supportive Gp +

Mean age=32

Ed + S-H)

• NS across conditions for addiction or psychiatric severity (overall sample improved)

male sample, participation rate not reported, not

At 8 mths:

reported if asses-

Participation

• Int. had greater retention than TAS

sors were blinded

rate: not

• NS across conditions for hospitalization days.

reported

Overall sample improved across conditions on addiction and psychiatric severity

Herman et al. (1997, 2000)

N=485 Inpatients Male=74% Mean age=33

Participation

DSM-III-R

9.5% were depen-

TAS vs. Int. (Ed

At discharge:

Predominantly

28% SCZ

dent on cannabis

+ R-Ed + S-H +

• Int. had greater engagement, knowledge of SU and

male sample, not

Gp)

21% Organic disorders

12-step programs, and motivation to control SU

reported if diagno-

than TAS

sis was confirmed

29% Aff

At 2 mths post discharge

26% Other

• Int had greater drop in alcohol use

by structured interview or if assessors were blinded

rate: 77% SUD: Alcohol 45.9% Cocaine 37.3% Cannabis 9.5% Uploads 4.4% Drake et al.

N=223

DSM-III-R

(1998)

Outpatients

53% SCZ

Male=74%

22% SA

Mean age=34

24% BP

Not reported

SCM vs. ACT

At 3 years:

Predominantly

• ACT had less attrition and clinician-rated alcohol

male sample

problems than SCM

• ACT had greater clinician-rated substance abuse recovery and financial support adequacy

Participation rate: 94%

• Equal improvement on alcohol and drug use, clinician-rated drug problems, community days, total BPRS, and life satisfaction


Baker et al.

(Table 1) Contd.... Sample

Study

Diagnoses

Cannabis use at

(%)

baseline

Design

Main Results


Morse et al.

N=196

DSM-IV

Cannabis use by

TAS vs. ACT vs.

At 24 mths:

Predominantly

(2006)

Homeless

48% SCZ

19%

Int ACT

• Int ACT and Act had greater days of stable housing

male sample

Male=80%

19% SA

Mean age=40

and satisfaction than TAS

• ACT had greater treatment costs than Int ACT and

11% Atypical

TAS

psychosis Participation

11% BP

rate: 76%

9% MD

• NS between groups on criminal justice measures, SU, symptoms, Inpatient and emergency shelter costs and patient maintenance costs

2% delusional

100% SUD Essock et al.

N=198

DSM-III-R

(2006)

Outpatient

76% SCZ/SA

Male=72%

17% Aff

Mean age=37

6% Other

Not reported

Int SCM vs. Int

At 3 years:

Predominantly

ACT

• Int SCM had greater inpatients and institutional

male sample

days

• Similar improvement across groups on SU, symptoms and general life satisfaction

Participation

100% SUD

rate: 81% Petersen et al. (2007)

N=547 Inpatients &

ICD-10

Cannabis use in past

65.2% SCZ

year by 35%, heavy cannabis use by

Outpatients Male=72%

TAS vs. Int ACT

23%, cannabis 36.4% SUD

abused by 12%

Mean age = 26

At 2 years:

Assessors were

• Int ACT had greater reductions of negative and

not blinded.

disorganized symptoms than TAS

• Int ACT had spend fewer days in hospital and outpatient visits

• NS between groups on GAF, social outcomes and cannabis abuse

Participation rate: not reported ACT: Assertive Community Treatment Aff: Affective disorder BP: Bipolar disorder DSM-III-R: Diagnostic Statistical Manual of Mental Disorders, Third Edition, Revised DSM-IV: Diagnostic Statistical Manual of Mental Disorders, 4th Edition Ed: Patient education GAF: Global Assessment of Functioning Gp: Group intervention ICD-10: International Classification of Diseases, 10th Edition ICM: Intensive case management Int: Integrated treatment for comorbidity MD: Major depression MH: Mental Health mths: Months NS: No significant differences RDC: Research Diagnositc Criteria R-Ed: Relatives/carer education SCM: Standard case management SCZ: Schizophrenia S-H: AA or other self-help groups SUD: Substance use disorder SA: Schizoaffective disorder TAS: Treatment as usual or routine care

months, was compared with usual treatment in a RCT by Bellack et al. [38] among 110 people with severe mental disorder. The intervention included MI, urinalysis contingency (contingency management, CM) and social skills training. At post-treatment, intervention participants had a significantly higher proportion of clean urine test

results during the six months of treatment compared to controls. The sample size and the use of urinalyses as an outcome measure were strengths of this study. Whilst the urinalysis results of Bellack and colleagues are impressive, there is evidence that CM for cannabis use can result in superior abstinence rates at post-treatment (the


end point in the Bellack study) compared to MI/CBT alone and in combination with CM [39]. Similarly, Carroll et al. [40] found CM in combination with MI/CBT had superior treatment attendance than those who received MI/CBT without CM followed by individuals who received drug counselling (DC) with and without CM among cannabis dependent young adults. Carroll et al. [40] also found participants receiving CM had superior abstinence outcomes to those not receiving CM. No significant effects of MI/CBT versus DC were found, however participants who received CM in combination with MI/CBT were found to have superior abstinence outcomes to those treated with MI/CBT without CM or DC without CM. Whilst small feasibility studies of CM have been conducted among people with severe mental disorders with the aim of reducing cannabis use [41, 42], a trial of CM alone and in combination with MI and CBT for cannabis and other drug use is recommended. Barrowclough et al. [43] recently built on the findings of their 2001 study by conducting a larger RCT to determine the efficacy of a MI/CBT intervention delivered in addition to usual treatment or usual treatment only. Changes to the intervention and study design included an increased emphasis on facilitating motivation, inclusion of patients without carers and extension of the intervention period to 12 months (up to 26 individual sessions, usually delivered in the patient’s home). Participants were 326 people with a current clinical diagnosis of non-affective psychotic disorder. Compared with treatment as usual, MI/CBT was not associated with better outcome on primary measures of deaths and hospitalisations, nor was it associated with improvements in other key clinical outcomes including relapses, psychotic symptoms, functioning, and self harm. Although there was no effect of MI/CBT on the frequency of substance misuse, compared to the control condition, participants in the MI/CBT condition were more likely to have reduced the amount they consumed. An exploratory analysis compared individuals who met only alcohol dependence or abuse criteria at baseline with the remaining participants. The authors suggested that for percentage of days abstinent from the main drug, MI/CBT may be more effective at reducing substance use in individuals who use alcohol only than in individuals who use illicit drugs or both drugs and alcohol. Limitations of the study include the use of clinical diagnoses for psychotic disorders, lack of control for therapist contact and cannabis use outcomes were not reported separately. Overall, it is difficult to draw firm conclusions about the efficacy of psychological interventions for substance use among individuals with psychotic disorders based on findings from the RCTs reviewed above. The studies are commendable in that the client group can be challenging and they also represent improved methodological approaches to research among this group. However, the few trials undertaken have significant methodological limitations including small sample sizes, high attrition, lack of adequate control conditions, and failure to report specific drug class outcomes [31]. In addition, the psychological interventions implemented in several trials were associated with only modest benefits in reducing substance use and/or improving other outcomes compared to the control condition. Follow-up was usually of short duration. Only post treatment results were reported by Bellack et al. [38] and Barrowclough et al. [44], three months post-intervention results were reported by James et al., [37] nine months post-intervention results were reported by Haddock [36] and 12-months post-intervention results were reported by Kavanagh et al. [34]. Certainly, results from four RCTs reporting outcomes in terms of cannabis use may be more informative and these are considered below here. RCTS OF MANUAL GUIDED INTERVENTIONS AMONG PEOPLE WITH PSYCHOSIS REPORTING CANNABIS USE OUTCOMES Psychotic Inpatients The effectiveness of a single session manual guided motivational interview immediately following baseline assessment versus


4927

a self-help booklet was assessed by Baker et al. [45, 46] among 160 hospitalised psychiatric patients with comorbid substance use (see Table 3 for the details of RCTs manual guided interventions reporting cannabis use outcomes). At 3-month follow-up there was a significant reduction in cannabis use from a mean of 7.09 to 2.82 cones per day, with no significant differences between intervention conditions. A ‘cone’ is a colloquial term that refers to a small conical object in which cannabis is placed in a water pipe or ‘bong’ and 12 cones equal 1 g of cannabis [47]. At 12-months, whilst the proportion of alcohol and amphetamine users meeting intervention threshold had halved, the majority of cannabis users continued to use at least weekly. In a follow-up of this sample four years later, the decline in alcohol and amphetamine use remained fairly steady whilst the group of people who were above hazardous threshold for cannabis use at baseline did not decrease their use during the follow-up period, continuing to use an average of five cones per day [48]. Although the number of people followed-up at four years was small (47/160), the authors suggested that the results showed that different classes of drugs may have a unique effect on outcome measures and that outcomes of various levels of substance use for individual classes of drugs should be reported. Limitations of the study include the absence of information regarding the proportion of inpatients who were approached but who refused or were denied entry into the study, the mixed mental health diagnoses, with only just over one-third of the sample having a psychotic disorder, and diagnoses were made from clinical files. Psychotic Outpatients 130 people with a psychotic disorder and comorbid substance use were randomly assigned to either 10 weekly individual sessions of manual guided MI/CBT or to treatment as usual by Baker et al. [49]. The intervention condition reported greater improvement in depressive symptoms at 6 months and better general functioning at 12 months compared to controls. There was a non-significant trend for a differential reduction in cannabis use between baseline and post-treatment for the treatment group compared with the control group, with the treatment groups reducing use from an average of 8.18 cones per day at baseline to 5.09 at post-treatment and the control subjects reporting use of 4.80 cones per day at baseline versus 5.66 at post-treatment. At 12-months follow-up, the treatment group reported a return to previously high levels of cannabis use, with a mean daily use of 8.53 cones. The control group reported use of a mean of 4.12 cones per day. There was no attention placebo condition included in this study so changes associated with the intervention cannot be attributed to the intervention per se. Forty seven individuals with stabilised FEP were randomly assigned to either 10 individual sessions of psychoeducation only or psychoeducation, MI and CBT by Edwards et al. [50]. No significant differences were found between conditions on cannabis use, symptom severity or general functioning at the end of treatment or at 6-months follow-up. Both groups showed a similar reduction in cannabis use during the follow-up period. The intervention condition reduced cannabis use from an average of 39.4 days in the past month at baseline to 32.4 days at six months and the psychoeducation subjects reduced their cannabis use from an average of 26 days per month to 19.3 days per month. The low level of cannabis use reported at baseline in this study limits generalizability of the findings to heavier cannabis users. Forty four people with psychotic disorder (duration unspecified) and at least one day of primary drug use in the previous two months were randomly assigned by Martino et al. [51] to either two individual sessions of manual guided MI or a two session manualized standard psychiatric interview. Whilst primary cocaine users reduced their cocaine use significantly more over time than participants in the standard interview condition, the reverse was true of primary cannabis users, who reduced their cannabis by 92.1% compared to no reduction in the MI condition. The authors suggest that


Table 2.

Baker et al.

Details of RCTs of Manual Guided Interventions Reporting General Substance Use Outcomes Sample

Study

Kavanagh et al. (2004) Australia

Diagnoses (%)

N=25

DSM-IV

Inpatients

48% SCZ

Male=60%

68% FEP

Mean age=23 Participation rate: 25/41 (60.9%)

Cannabis use at baseline Use of cannabis in previous 3 months (76%), daily cannabis use (52%)

100% SUD

Main Results

Design

TAS vs. TAS+MI Follow up: 6 wks, 3-, 6(96%) and 12mths (68%).

Outcome

Cohen’s d

Substance use

Significantly greater improvement for MI than TAU at 6- and 12mths follow-up (Based on analyses of treated participants)

6 mths =1.06 Small sample size, poor participation 12 rate. mths=1.12

Substance use

NS between groups (intention to treat analyses).

6 mths=.61

Greater improvement for TAS+Int than TAS

12 mths=1.38

Attendance: 38% in TAS+MI group received only rapport building. Barrowclough et al. (2001) Haddock et al. (2003)

N=32 Outpatients and their carers

DSM-IV & ICD- Use of cannabis 10 (61%) 100% SCZ/SA

Male=92% Mean age=31

100% SUD

TAS vs TAS+Int (MI + CBT for symptoms + FI) Follow up: 9(89%) ,12(89%) and 18 mths (78%)

UK Participation rate: 36/66 (54.5%) Attendance: Median number of 22 MI+CBT sessions and 11 FI sessions attended by TAS+Int group

N=63

ICD-10

Outpatients/ Inpatients

57% SCZ

Australia

Male=71% Mean age=28

43% other psychosis 100% SUD

Attendance: Mean of 4.7/6 sessions attended in TAS+Gp group

GAF

12 mths=.79

18 mths=.41 Severity of negative symptoms

Greater reduction for TAS+Int than TAS

18 mths=1.22

Severity of positive symptoms


12 mths =.966

Small sample size, diagnosis not confirmed by structured interview, primarily male sample

Psychotic relapse Lower rate for TAS+Int 9 mths = than TAS 12 mths = .71

James et al. (2004)

Participation rate: 63/73 (86.3%)


Variable

Not reported

% days abstinent

NS between groups

Unable to calculate

Severity of negative symptoms


18 mths=1.222

TAS+Ed (SUD) Psychopathology Greater improvement vs. TAS +Gp (BPRS and GSI) for TAS+Gp than (Ed,MI,CBT) TAS+Ed Follow up: 3 mths (92%).

3mths: BPRS=.713 GSI=.240

Drug abuse

Greater improvement for TAS+Gp than TAS+Ed

3 mths=1.071

Antipsychotic medication dose

Greater improvement for TAS+Gp than TAS+Ed

3 mths=.725

Cannabis use

Greater reductions for TAS+Gp than TAS+Ed

3 mths=.680

Alcohol consumption


3 mths=.680

Poly substance use


3 mths=.685

Hospitalization

Lower rate for TAS+Gp Unable to than TAS+Ed calculate

Severity of dependence


3 mths= 1.121

Small sample size, diagnosis not confirmed by structured interview, primarily male sample



4929

(Table 2) Contd.... Sample

Study

Bellack et al. (2006) US

Diagnoses (%)

N=110

DSM-IV

Outpatients

38.2% SCZ/SA

Male=63%

54.9% AFF

Mean age =43 100% SUD

Cannabis use at baseline Cannabis predominant drug of abuse (6.86%), mean years of cannabis use (10.2)

Main Results

Design Variable Support+Ed vs. Proportion of clean MI+CBT for urine tests SUD

Outcome

Cohen’s d


Greater proportion for =.813 MI+CBT for SUD than Support+Ed

Poor participation rate, diagnosis not confirmed by structured interview, lack of follow up

Greater for CM than no CM, greater for MI/CBT than DC

Primarily male sample

Follow up: nil

Participation rate: 110/251 (43.8%) Attendance: Mean of 29/48 session attended in MI+CBT for SUD group Carroll et al. (2006).

N=132 Outpatients Male= 90%

USA

Mean age = 21

DSM-IV

Mean 13 days 11% lifetime Dep cannabis use in previous 28 days 22% lifetime Anx 43% APD

Participation rate: 132/174 (75.9%) of eligible participants

DC vs. DC+CM vs. MI/CBT vs. MI/CBT+CM Follow up: 6 mths (81.8%).

SUD: 100% cannabis

Treatment attendence

N=326 Outpatients Males= 87%

UK

Mean age= 38

DSM-IV & ICD- Use of cannabis 10 (48.9%), canna91% SCZ/SA/SP bis main substance of use 9% Psychosis (25%) NOS

Participation rate: 326/722 (45.2%) Attendance: Mean of 16.7 sessions attended

Aff: Affective disorder Anx: Anxiety disorder APD: Antisocial personality disorder. BPRS: Brief Psychiatric Rating Scale CBT: Cognitive-behaviour therapy CM: Contingency management DC: Drug counselling Dep: Depression DSM-IV: Diagnostic Statistical Manual of Mental Disorders, 4th Edition Ed: Patient education FEP: first episode psychosis FEP: First episode psychosis GAF: Global Assessment of Functioning Gp: Group intervention GSI: Global Severity Index ICD-10: International Classification of Diseases, 10th Edition Int: Integrated treatment for comorbidity MI: Motivational interviewing Mths: Months NOS: Not otherwise specified NS: No significant differences SA: Schizoaffective SCZ: Schizophrenia SP: Schizophreniform disorder SUD: Substance use disorder TAS: Treatment as usual or routine care

TAS vs. TAS+MI/CBT Follow up: End of treatment (82%) and 24mths (75%)

MI/CBT vs DC=.339

Duration of continu- Greater for CM than ous abstinence no CM,

CM vs no CM =.45

Consecutive cannabis-free urine samples

Greater for CM vs no CM, Greater for MI/CBT+CM than MI/CBT, DC and DC+CM

CM vs no CM =.29, MI/CBT+CM vs others = .25

Total negative urine samples

Greater for CM vs no CM

CM vs no CM =.29

Deaths and hospitalisations

NS between groups

24 mths= .082

Attendance: Mean of 5.1/8 sessions attended

Barrowclough et al. (2010)

CM vs no CM = .47

Psychotic relapse

NS between groups

24 mths=.027

Positive and Negative symptoms

NS between groups

Unable to calculate

Self harm

NS between groups

24 mths=.216

GAF

NS between groups

Unable to calculate

Change in use of main substance

Greater reduction for TAS+MI/CBT than TAS

24 mths=.224

Primarily male sample, poor participation rate


Table 3.

Baker et al.

Details of RCTs of Manual Guided Interventions Reporting Cannabis Use Outcomes

Study

Sample

Diagnoses (%)

Cannabis use at baseline

Design

Variable Baker et al. (2002a,b)

Australia

N=160, Inpatients

DSM-IV

Male=75%

37.0% SCZ

Mean age=31

29.6% Mood

Outcome

Cohen’s d

Cones per day

NS between groups

3 mths=.230

Baseline participation rate not reported; Therapy adherence and fidelity not rated.

At least weekly use of cannabis (66.3%)

MI vs. TAS

Mean cones per day =7.72

Long term follow up of Baker et al. (2002a,b)

Substance use

Significant decrease in alcohol and amphetamine consumption over time, No significant change in cannabis consumption over time

Unable to calculate

Small sample size, poor participation rate.

TAS vs. TAS+MI+Int. CBT

Greater improvement for MI/CBT than TAS

6mths=.519

Follow up: 15(93.1%) wk; 6(94.6%) & 12 (80.0%) mths

Depressive symptoms

Therapy adherence and fidelity not rated

GAF

Greater improvement for MI/CBT than TAS

12 mths=.534

Cannabis use

Greater reduction for MI/CBT than TAS (nonsignificant trend) at 15mks, NS between groups at 12 mths

15 wks =.586

NS between groups

End of treatment =.012

12.3% Other Participation rate: not reported


Main results

19.8% None

Follow up (participation rate): 3 (70.0%). 6- (73.1%) & 12- (71.9%) mths

SUD:

Greig et al. (2006)

Australia

Attendance: All participants in MI group attended 1 session

90% Any SUD

N=47

DSM-IV

Inpatients

41.3% SCZ

Male=70%

30.4% Mood

Mean age=36

13% Axis II

51% cannabis

10.9% Other Participation rate: 47/116 (40.5%)

17.4% None

SUD: Attendance: N/A

53.2% Any SUD 10.9% cannabis

Baker et al. (2006)

N=130, Outpatients Male=78.2%

ICD-10 psychosis:

Mean age=28

62.2% SZ

At least weekly use of cannabis

12.6% SA

(60.8%)

Australia Participation rate: 130/158 (82.3%) of eligible participants

9.2% BP 4.2% Aff

SUD:

Edwards et al. (2006)

Australia

Attendance: All session attended by 70.8% of TAS+MI+Int.CBT group, some sessions attended by 16.9%

73.1% cannabis

N=47, Outpatients

DSM-IV

Male=72%

71.7% SZ/SP

Mean age=21

10.9% Affective psychosis

Participation rate: 47/76 (62%) of eligible participants

67.3% alcohol 47.0% amphetamines

17.4% NOS/ delusional/other

SUD: Attendance: Median of 8/10 session attended for TAS+MI+Ed+Int.CBT group

48.9% cannabis; 2.2% alcohol

Use of cannabis in past 4 weeks (100%), % days used cannabis past 4 weeks (32.7%)

TAS+Ed vs. TAS+MI+Ed+Int. CBT

Severity of cannabis use

12 mths= .020

6 mths=.009 Follow up: 6 -mths (70.4%)

Symptom severity

NS between groups

End of treatment=.309 6 mths=.029

Small sample size, low participation rate, categorical outcomes only. Therapy adherence and fidelity not rated.



4931

(Table 3) Contd.... Cannabis Study

Sample

Diagnoses (%)

use at

Design

Methodologi-

Main results

cal limitations

baseline Variable GAF

Outcome

Cohen’s d

NS between

End of treat-

groups

ment =.018 6 mths =.278

% days used

NS between

cannabis in

groups

6 mths=.058

past month Cocaine use

SI vs MI

12 wks=1.385

Small sample

Martino et

N=44, Inpatients &

DSM- IV psycho-

Cannabis

al. (2006)

Outpatients

sis:

dependen-

tion for MI

Low number of

Male=73.0%

43.2% SCZ

ce/abuse

than SI

days use requi-

USA

Mean age=32

34.1% SA Affective

(50%), Cannabis

Follow up: post tx, 4, 8, & 12 wk by

Cannabis use

primary

Greater reduc-

Greater reduc-

12 wks=-

tion for SI than

2.494

MI

red for entry into the study, follow ups

Participation rate: 44/48

22.7% Psychotic

drug pro-

38 (86%) completed

91.7% of eligible partici-

disorder NOS

blem

1 follow up; 37

non-blinded

(29.5%),

(84%) completed 2

research staff

Mean daily

and 34 (77%)

joints

completed all 3

pants SUD: Attendance: All session attended by 88.6% of participants

54.5% cocaine;

conducted by

(1.44)

50.0% cannabis; 47.7% alcohol; 18.2% illy/ecstasy; 9.1% heroin

Aff: Affective disorder BP: Bipolar disorder CBT: Cognitive-behaviour therapy DSM-IV: Diagnostic Statistical Manual of Mental Disorders, 4th Edition Ed: Patient education GAF: Global Assessment of Functioning ICD-10: International Classification of Diseases, 10th Edition Int: Integrated treatment for comorbidity MI: Motivational interviewing Mood: Mood disorder Mths: Months NOS: Not otherwise specified NS: No significant differences SA: Schizoaffective SCZ: Schizophrenia SI: Standard interview SP: Schizophreniform disorder SUD: Substance use disorder TAS: Treatment as usual or routine care

the superior effectiveness of the standard interview among those with a primary cannabis use problem may have been due to the increased legal problems among these subjects compared to the cocaine subjects. However, they also suggest that the possibility exists that the MI versus standard psychiatric interview interventions were differentially effective for primary cocaine versus cannabis using cohorts, possibly due to the different pharmacological effects of the drugs, motivational factors, or possible independent effects of the pre-treatment interview on behaviour. Whilst the above studies provide selective information about cannabis users with severe mental health problems and the effects of manual guided treatment, methodological limitations include small sample sizes, the recruitment of cannabis users with various

levels of use into the same study (e.g., from monthly to daily) and different definitions and measures of treatment effectiveness between studies. However, the results can be used to generate some more focused and potentially clinically informative research questions worthy of further investigation: (i) do people with earlier stages of mental disorder and/or lighter levels of cannabis use respond equally well to brief versus extended intervention compared to those with more extensive mental or cannabis use disorders; (ii) how brief can interventions be in order to be effective (assessment alone versus assessment plus feedback plus motivational interview); (iii) what is the comparative effectiveness of brief psychoeducation versus brief MI; and (iv) does CM enhance effectiveness of interventions? Existing findings indicate the potential utility of brief


interventions for cannabis users but the findings by Baker et al. [49] would seem to indicate that heavy cannabis users need longer interventions to reduce cannabis use and perhaps booster sessions to maintain behaviour change achieved during the treatment period. MI/CBT interventions in both the Barrowclough et al. [35] and Baker et al. [49] studies were associated with improvements in mental health and functioning that may lead to more distal improvements in cannabis and other drug use not measured within the timeframe of these studies. Thus, two and three year follow-ups are needed. Change in substance use without therapist assistance has been well recognized in the alcohol and other drug field for many years [52] but less well recognized in the comorbidity field. A study by Hinton et al. [53] prospectively examined patterns of substance use, including cannabis, among 130 FEP patients assessed at psychiatric treatment entry and again nine weeks later. Of the 72 people using cannabis at treatment entry, 29 (40.3%) were abstinent at follow-up, and half of these had been daily users. This finding, together with the evidence of change with assessment and brief intervention, suggests that self-change for substance use may be a powerful force among people with severe mental health problems, particularly those in the early stages of mental health treatment (see Table 4). SYNTHESIS OF PSYCHOLOGICAL INTERVENTIONS In a recent analysis of the combined data of the studies above by Baker et al. [30, 45, 46] and Kay-Lambkin et al. [56], the effectiveness of brief versus 10-session psychological interventions among people with severe mental disorders (psychotic disorders or major depression) and comorbid alcohol and/or cannabis use problems was compared [57]. They recommended that, overall, assessment and brief advice and brief motivational interventions are worthwhile among people with severe mental health disorders and substance misuse problems. However, their findings indicated that whilst a sizeable proportion of participants with cannabis use problems did respond to brief interventions, alcohol problems tended to respond even more favourably among these comorbid groups. Nonetheless, brief interventions for cannabis use problems may serve as a potentially helpful first step in intervention. Longer interventions tended to be more effective than brief interventions among people with severe mental health and cannabis use problems and the authors suggested that further research is needed to improve the effectiveness of these interventions. It is noteworthy that people with both psychotic and major affective disorders with comorbid cannabis use problems appear to Table 4.

Baker et al.

benefit differentially from brief interventions for alcohol versus cannabis use problems. This implies that cannabis use, and particularly heavy cannabis use, may be beneficial in some way that is common to people with psychosis and depression. As anxiety is often comorbid with these conditions [58] and cannabis has known anxiolytic properties [59], it is possible that anxiety management is a factor in the heavy use and apparent difficulty in reducing cannabis use. Certainly, relaxation is often cited as a reason for cannabis use among people with severe mental health problems [e.g., 60] and there is a distinct withdrawal syndrome with common symptoms of anxiety that can be alleviated by administration of d9-THC [61]. Further research investigating the reasons why people with various severe mental health problems use cannabis at different levels and how they find the process of reducing use is warranted. RCTS OF PHARMACOLOGIC INTERVENTIONS IN PSYCHOTIC PATIENTS Two double blind RCTs with short-term follow-up assessments have compared the effectiveness of olanzapine or risperidone on cannabis use outcomes among individuals with psychosis (see Table 5). Akerele and Levin [62] screened 76 outpatients with schizophrenia or schizoaffective disorder (duration unspecified) and cooccurring cocaine (71%) and/or cannabis (93%) use disorder(s). After a two week assessment phase, participants were tapered off their previously prescribed medication and onto the study medication, followed by a ten week maintenance period. Participants received 3-9mg of risperidone or 5-20mg of olanzapine, as well as psychotherapy on a weekly basis (not described) and thrice weekly meetings with the research team in order to assess substance use and to provide urine specimens. At 14 weeks, positive psychosis ratings improved for both intervention conditions, with no differences in medication adherence rates reported. Although the risperidone condition reported a significantly greater reduction in cannabis craving compared to the olanzapine condition, both groups demonstrated significantly reduced cannabis-positive urine samples over the course of the study. The generalizability of these findings is limited by the small primarily male (89%) sample, with a high proportion of co-existing cocaine dependence (71%) and many were of African American (54%) or Hispanic (32%) descent. Only around half of participants (55.3%) completed the 14-week study period. In the second study, van Nimwegen et al. [63] recruited 201 young outpatients with schizophrenia, schizoaffective disorder or schizophreniform disorder. Participants received flexible dosing of

Recommendations for the Management of Cannabis use in People with Psychotic Disorders

1.

Screen for cannabis and other drug use (e.g., using the WHO ASSIST [54])

2.

Use the importance and confidence rulers [55] (e.g., “On a scale from 1-10, how important is it for you to reduce your cannabis use?” On a scale from 1 to 10, how confident are you that you can reduce your cannabis use?)

3.

Use decisional balance (e.g., What are the good things about cannabis use? What are the less good things? [33])

4.

Ask about the possible link between cannabis use and symptoms of psychosis and/or mood/anxiety levels

5.

Ask the patient if they would like more information

6.

Explore change options

7.

Discuss a change plan

8.

Provide a psychological intervention or referral

9.

Regularly monitor cannabis and other drug use and mental health symptoms over time to prevent or address relapse


either olanzapine (mean dose received was 11.1mg at six weeks) or risperidone (mean dose of 3.0mg at six weeks). All patients received usual treatment which included disease and stress management programs covering psychoeducation about psychoses, substance abuse and social skills training. In contrast to the study by Akerele and Levin [62] reported above, no significant reductions in cannabis craving were reported for either condition and the reduction in the mean number of joints per week (around 4 for both conditions) was not significant. Changes in psychotic symptoms were not reported. The low proportion of the sample reporting cannabis use at baseline, poor participation rates, the high proportion of males in the sample and the lack of verification of self-reported cannabis use in this study are major limitations. The authors concluded there was no evidence for a differential effect of risperidone or olanzapine on craving for cannabis. Recently, results from a RCT of clozapine versus other antipsychotics for cannabis use disorder in outpatients with schizophrenia or schizoaffective disorder have also been reported [64] (see Table 5). Unblinded study physicians prescribed and adjusted study medications weekly for 12 weeks. Participants either stayed on their current antipsychotic medication or were switched to clozapine, with dosage increased in a flexible manner to reach a daily dose of 400mg by the end of week 4, with concurrent gradual elimination of initial antipsychotic medication. The maximum allowed dose of clozapine was 550mg per day. There was no significant difference between the two groups on cannabis use, although the clozapine group reported 4.5 fewer joints per week compared to the group continuing on their current course of antipsychotic medication. The two groups did not differ in terms of symptoms or functioning. The authors acknowledge the limitations of the trial, namely its small size and non-blinding of prescribing physicians and suggest that further studies of clozapine among people with comorbid schizophrenia and cannabis use disorder are warranted. More double blind RCTs of the effectiveness of different types of antipsychotic medications on cannabis craving and cannabis and other co-existing substance use are needed, particularly among females as existing trials have been comprised of predominantly male samples. The relationship between improvement in psychotic symptomatology and improvement in cannabis cravings and cannabis and other substance use is worthy of further investigation. Based on the findings of the above three RCTs, it would appear that treatment with antipsychotic medication is not associated with a worsening of cannabis cravings or use and may be beneficial. MEDICATIONS FOR PSYCHOSIS AND CANNABIS USE There are a number of reasons that a single medication may not be effective in treating both psychotic symptoms and cannabis use or dependence concurrently. While the role of the dopamine mesolimbic (or reward) pathway is understood to be central to the condition of substance dependence (across many substances) [65], dopamine antagonism does not appear to be an effective strategy in impacting on substance dependence. Atypical antipsychotics such as olanzapine, risperidone and clozapine may be effective in reducing psychotic symptoms in cannabis users, but do not appear to impact significantly in reducing substance use. A lack of effectiveness of dopamine antagonists in impacting on stimulant dependence has also been observed [66, 67]. Combinations of medications have been proposed as possible approaches to responding to stimulant dependence, and whilst no effective combination medication regimen has yet been established [67], this may also be true of cannabis dependence. While a wide range of medications has been explored for cannabis dependence, no medication has yet been demonstrated to be clinically safe and effective [2, 68]. However, pharmacotherapies remain a promising strategy to attract cannabis users to treatment [69]. A number of approaches have been trialled to date. The antidepressants nefazadone and buproprion do not appear to have a


4933

significant impact on cannabis dependence [70]. The alpha-2adrenergic receptor agonist lofexidine, used in opioid withdrawal also has limited effects in treating cannabis dependence [71]. While the cannabis antagonist rimonabant showed some promise [72], concerns remain regarding depression enhancing effects of this medication [73]. Agonist approaches have been successful in the treatment of both opioid dependence disorders [74, 75] and nicotine dependence [76, 77]. Case reports of the cannabinoid agonist dronabinol [78] suggest this approach may be an effective strategy in medication development for cannabis dependence. -9-THC, one of the active components in cannabis, is also a candidate medication for cannabis dependence. Nabiximols, a mucosal spray containing of -9-THC and cannabidiol (CBD) in a 1: 1 ratio, has been developed as an effective treatment for spasticity in multiple sclerosis [79, 80]. CBD is a non-psychoactive cannabinoid found in the cannabis sativa plant [81]. It has recently been hypothesised that CBD may attenuate psychotic symptoms induced by -9-THC [82], suggesting that a combination of CBD and -9-THC could be an effective combination agonist medication. A clinical trial in cannabis users suggests nabiximols may have a reduced abuse liability compared to dronabinol [83]. TREATMENT PREFERENCES AMONG PEOPLE WITH PSYCHOTIC DISORDERS When developing effective cannabis use interventions for people with psychotic disorders it may also be useful to engage with consumers of these treatments, perhaps by considering their treatment preferences. While previous research has found allocating patients to their preferred treatment does not improve, or worsen, treatment outcomes [e.g. 84, 85, 86] treatment preferences have been found to influence initiation of treatment and adherence [85]. Additionally, it is suggested that understanding preferences for treatment is an important factor to consider when determining the best approach to treatment [87]. Surprisingly, very little research investigating the treatment preferences of people with psychotic disorders has been conducted. In a systematic review of studies that measured patient or physician treatment preferences King et al., [86] identified 32 studies. Of these, only four studies were conducted among people with mental disorders and none among people with psychotic disorders. In a study conducted by two of the authors (LT and AB), the preferences of people with psychotic disorders regarding cannabis use treatments were investigated, for what may be the first time. Participants were recruited from: the Australian Schizophrenia Research Bank (ASRB) [88], which enrols research volunteers with a diagnosis of schizophrenia and related disorders; first year psychology students at the University of Newcastle, Australia; the Hunter Medical Research Institute’s Research Register (NSW, Australia), which enrols research volunteers from the general population; and the social networking website ‘Facebook’. Participants were asked to complete a questionnaire, either online or on paper, which listed potential treatment approaches (e.g. support from a counsellor) and to nominate preferences if they were to seek treatment for their cannabis use. Participants were also given the opportunity to list alternative forms of treatment, if their preferences did not appear on the provided list. Of the 1099 participants recruited, 111 were recruited from the ASRB or reported that had been diagnosed with a psychotic disorder. This included 15 participants with psychotic disorders who had used cannabis in the last six months. These 15 participants were aged between 19 and 68 (M= 41.60, SD= 14.60) and 2 were female. The most commonly preferred treatment was detoxification which six people endorsed, followed by support from a counsellor (4). Four participants said they would not seek treatment including one who said they would use their own ‘iron will’ to stop using cannabis. Therapy from a psychologist, support from a GP and a 12 step


Table 5.

Baker et al.

Details of RCTs of Pharmacologic Interventions

Study

Sample

Diagnoses (%)

Cannabis use

Design

at baseline

Variable Akerele & Levin (2007)

N=28, Outpatients Male=89.0%

Methodological

Main results Outcome

limitations Cohen’s d

DSM-IV

Use of cannabis

Rispiridone

Positive psy-

Significant reduc-

Unable to

Small sample

100% SCZ/SA

(93%), Canna-

vs. Olanzap-

chosis ratings

tions in severity

calculate

size, primarily

bis abu-

ine

for both groups.

male sample, no

se/dependence

NS between

long-term follow-

SUD:

(93%), Mean of

groups

up, low comple-

Participation rate:

71.4% cocaine

17.8 days of

28/47 (55.3%) of

93.0% canna-

cannabis use in

eligible participants

bis

last 30 days

Mean age=36 USA

Follow up: nil

Medication

NS between

Unable to

adherence

groups

calculate

Cannabis

Greater reduction

Unable to

craving

for Risperidone

calculate

sessions attended

Cannabis

Significant reduc-

Unable to

by 42.9% in Olan-

positive urine

tions for both

calculate

zapine condition

samples

groups. NS

Attendance: All

and 71.4% in

tion rate

between groups

Risperidone condition Van Nimwe-

N=128

DSM-IV

Use of cannabis

Olanzapine

Cannabis

NS between

End of treat-

Low proportion

gen et al

Outpatients

100%

(32%)

vs. Risperi-

craving

groups. Slight

ment =.840

of cannabis use at

Male= 80%

SCZ/SA/SP

done

(OCDUS)

increase for

baseline, poor

Olanzapine,

participation

reduction for

rates, primarily

Risperidone

male sample, self-

(2008)

Mean age= 25 Netherlands

Follow up: nil Participation rate:

Cannabis

No significant

End of treat-

128/201 (64%) of

craving (DDQ)

reductions for

ment =.017

eligible participants

reported cannabis use.

both groups. NS between groups.

Attendance: All

No. joints per

NS between

End of treat-

sessions attended

weeks

groups

ment =.048

Joints per week

Greater reduction

End of treat-

for Clozapine

ment =.657

by 70% of participants Brunette et al. (2011)

N=31 Outpatients

DSM-IV

Mean days of

Clozapine

100% SCZ/SA

cannabis use per

vs. TAS

week (4.5),

Male=77% USA

Mean age=36

Mean no. joints SUD:

per week (12.3)

100% cannabis Participation rate: 31/41 (75.6%) of eligible participants Attendance: Mean of 11.3/12 weeks on study medications DSM-IV: Diagnostic Statistical Manual of Mental Disorders, 4th Edition DDQ: Drug Desire Questionnaire NS: No significant differences OCDUS: Obsessive-Compulsive Drug Use Scale SA: Schizoaffective SCZ: Schizophrenia SP: Schizophreniform disorder SUD: Substance use disorder TAS: Treatment as usual or routine care

Follow up: nil

Small sample size, non-blinding

than TAS (non-

of prescribing

significant trend)

physicians


program were endorsed as a preferred treatment for cannabis use by two participants each. One participant endorsed use of a self help booklet and another endorsed attendance at group therapy and no participants endorsed telephone counselling or internet delivered treatment (with or without the support of a health professional) as a preferred treatment for cannabis use. While drawn from only a small sample, these results seem to suggest that people with psychotic disorders might prefer traditional face-to-face approaches to treatment (e.g. detoxification; support from a counsellor), over less traditional approaches involving little or no face time with a health professional (e.g. telephone counselling, internet delivered treatment and self-help booklets). These results may also suggest people with psychotic disorders would prefer to address their cannabis use in a context focussed on their drug use (e.g. detoxification and support from a counsellor) rather than within the context of case management of the psychotic illness. This finding may correspond with the description given by Thornton et al.’s [89] participants that cannabis use can allow people with psychotic disorders the opportunity to socialize and gain a sense of belonging to a sub-culture of society that is not related to their mental illness. It may also be important to address ways in which people with psychotic disorders might be motivated to want to reduce their cannabis use, as a number of participants in this small study reported that they would not seek treatment for their cannabis use. In summary, in an endeavour to develop cannabis use interventions that people with psychotic disorders will be willing to engage with and adhere to, it may be important to take into consideration their treatment preferences. Initial results indicate that face to face interventions focussed on cannabis use seem to be preferred. However, further research investigating the treatment preferences of people with psychotic disorders using cannabis is needed. CONCLUSIONS Despite the high prevalence and comorbidity of psychotic and cannabis use disorders, there is a lack of specific interventions and research in this area. Results from the reviewed RCTs suggest that: (i) brief interventions may be effective for cannabis use, particularly less heavy users and those in the earlier stages of psychiatric disorder and that; (ii) longer or more intensive interventions may be effective, particularly among heavier users and those with more chronic mental disorders. However, available interventions are not yet optimally effective and existing studies are flawed. Research investigating ways in which cannabis use interventions for people with psychotic disorders can be improved and high quality RCTs among larger samples of cannabis users with psychotic disorders are needed. An important part of the development of effective and acceptable interventions for cannabis use among people with psychotic disorders may also be engagement with intervention consumers e.g. by considering their treatment preferences. FUTURE CHALLENGES Tobacco smoking rates among people with psychotic disorders remain very high, with 73% of Australian men and 56% of Australian women with psychotic disorders smoking [90]. There are similarities in withdrawal symptom profiles between cannabis and tobacco [61], and simultaneous cessation is associated with more severe withdrawal than either drug alone [91]. Thus, pharmacotherapy for nicotine withdrawal (nicotine replacement therapy, NRT) may be effective in reducing withdrawal symptoms in individuals who simultaneously quit both cannabis and tobacco. Research is needed to investigate whether quitting both tobacco and cannabis use at the same time is associated with better outcomes compared to quitting either drug alone. Furthermore, recent studies indicate that CBD reduces the acute cognitive effects of d9-THC [92] and may exert antipsychotic [93] or anxiolytic properties [94]. Trials of CBD among cannabis users with psychotic disorders may be warranted as more is learned about its efficacy. To fully review the potentials of


4935

CBD in psychotic disorders please see the paper by Crippa et al. presented in this issue. Combined pharmacological and psychological interventions are worthy of further research. CONFLICT OF INTEREST The authors confirm that this article content has no conflicts of interest. ACKNOWLEDGEMENTS Louise Thornton is supported by an Australian Postgraduate Award. Part of this paper was supported by the Australian Schizophrenia Research Bank (ASRB), which is supported by the National Health and Medical Research Council of Australia, the Pratt Foundation, RamsayHealth Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. The authors would like to acknowledge the time and effort of participants recruited from the ASRB and ‘Facebook’. REFERENCES [1] [2] [3] [4] [5] [6] [7] [8]

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Received: April 3, 2012

Accepted: April 10, 2012

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