Psychiatric Disorders and Comorbid Cannabis Use: When Should We Be Concerned and What Can We Do About It?

This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Psychiatric Disorders and Comorbid Cannabis Use:

When Should We Be Concerned and What Can We Do About It?

Derek D. Satre, PhDa,b,*; Brian Borsari, PhDa,c; D. Andrew Tompkins, MD, MHSa,d; and Danielle Ramo, PhDa

Cannabis use is common among individuals with psychiatric disorders, including those seeking treatment in mental health care settings. Yet, not all cannabis use is harmful, and providers are often unsure how to determine which patients are at risk for cannabis use-related problems and how to help. As cannabis use becomes more widely accepted in some regions of the US and many states move toward legalization, it is crucial for mental health providers to be well equipped to identify, assess, and treat problems of a range of possible severity, including cannabis use disorders. The first article in this 2-part series reviewed the prevalence of cannabis use and related problems among individuals with psychiatric disorders.1 This companion article describes strategies for cannabis use screening, assessment, and intervention in the context of mental health care.

SCREENING AND ASSESSMENT

It is important to screen individuals seeking mental health services for any use of potentially problematic substances, including cannabis. Brief, validated self-report questionnaires such as the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST)2 are useful and can be integrated into self-administered computerized screening systems.3,4 Key questions on the ASSIST include frequency of use; presence of health, social, legal, or financial cannabis-related problems; and symptoms of cannabis and other substance use disorders. Although some uncertainties remain regarding the impact of cannabis use on mental health, more frequent use and use at younger ages are consistently associated with worse mental health outcomes than occasional use or nonuse.5 Therefore, it is essential to determine the age at which patients began regular use and current frequency of use. It is also important to ask about newer forms of use including vaping and THC concentrates.6 Urine drug screens, used often in outpatient addiction treatment, court, and workplace settings, may not be needed in addition to validated self-report measures.7 However, if used in a psychiatric setting, drug screens should be used consistently with all patients to reduce stigma.

Several brief scales have been developed for adolescents and adults to help assess severity and interest in reducing use. Examples include the 5-item Severity of Dependence Scale,8 the 8-item Cannabis Use Disorders Identification Test-Revised (CUDIT-R),9 and the 6-item Cannabis Abuse Screening Test (CAST).10 The CUDIT-R and the CAST also include useful items on difficulties with memory or concentration. In a review of these measures, results of validation studies varied depending on population and standards for validity, but sensitivity, specificity, and predictive power in identifying cannabis use disorder were generally acceptable.11 Regardless of the measure used, providers should be attuned to patients’ own sense of how cannabis use may cause problems and what might motivate reduction in use.

Cannabis use disorder in the DSM-5 is coded as F12.10 (mild) or F12.20 (moderate or severe) and is defined as "a problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least 2 or more symptoms occurring within a 12-month period."12(p509) DSM-5 also includes diagnoses for withdrawal as well as cannabis-induced psychotic, anxiety, and sleep disorders. There is considerable potential for patients with more extensive use to exhibit withdrawal symptoms if they stop altogether.13 In a sample of 170 adolescents and young adults with depression and cannabis use and/or dependence (using DSM-IV criteria), withdrawal was found in 92% of participants with dependence, and the most common withdrawal symptoms were craving (82%), irritability (76%), restlessness (58%), anxiety (55%), and depression (52%).14 Thus, providers should be mindful of withdrawal in differential diagnosis and in planning intervention strategies.

BEHAVIORAL INTERVENTIONS

Given the extent of cannabis use and potential adverse effects, there is a need to initiate treatment efforts in mental health treatment contexts. Many adults with depression and other psychiatric disorders try to stop using,15 suggesting that patients may be willing to engage with interventions. In determining approach, providers should consider the extent of cannabis problems, psychiatric severity, willingness of patients to reduce use, and availability of specialty addiction treatment services.

The National Institute on Drug Abuse recommends 3 behavioral approaches for treatment of cannabis use disorders (applicable to both DSM-IV and DSM-5 definitions): motivational interviewing (MI), cognitive-behavioral therapy (CBT), and contingency management.16,17 There is strong evidence for the effectiveness of MI in helping to reduce cannabis use,12 including among psychiatry outpatients.18 MI is a patient-centered "collaborative conversation style for strengthening a person’s own motivation and commitment to change."19(p12) Using MI, which can be integrated into other mental health services, providers can evoke (and ideally resolve) personal ambivalence about reducing use. In a study of 97 individuals with major depression and cannabis use and/or hazardous drinking, intensive MI/CBT was significantly better than a brief intervention alone at reducing cannabis use and hazardous substance use, with computer-based therapy showing the largest effect.20 This finding is consistent with research indicating that the combination of MI and CBT seems to be more effective than either intervention alone.16 The incorporation of MI can be especially effective with patients experiencing current problems yet expressing little desire or motivation to reduce or stop use.

Traditionally, cannabis use disorder and comorbid psychiatric disorders have been addressed either sequentially (the resolution of cannabis use before treating psychiatric disorders, or vice versa) or in parallel (treating both disorders concurrently but with different providers).21 Over time, there has been more acceptance of an integrated approach to addressing cannabis use and psychiatric disorders such as PTSD,22 anxiety,23 depression,24 and psychosis.25 In particular, integrated pharmacologic and psychological treatments can reduce cannabis use in individuals with psychosis or depression.26 Therefore, cannabis use should be assessed throughout mental health treatment with an explicit focus on the link between cannabis use and treatment effectiveness. For example, use of cannabis during exposure treatment for PTSD or anxiety can interfere with the hypothesized mechanisms of action (habituation to feared stimuli or traumatic events). Cannabis use can then be conceptualized and collaboratively addressed as a safety behavior rather than ignored. Another consideration is whether cannabis is used recreationally or medically (either prescribed or perceived to have medical benefits by the patient), as research indicates that medical cannabis users report worse physical and mental health than recreational users.27-29 Therefore, medical users may be hesitant to reduce or stop cannabis use without alternative coping strategies for physical (eg, chronic pain) and psychiatric distress.

Depending on psychiatric severity, adaptations to behavioral interventions may be necessary. For example, Martino and colleagues30,31 made specific recommendations for implementing MI with dually diagnosed patients (substance use and psychotic disorders), such as using simple and concise language; reflecting often; providing frequent summary statements, affirmations, and metaphors; and avoiding reflections on despair or negative life events. These MI modifications are straightforward and can enhance intervention effectiveness.

MEDICATIONS

There are no currently approved medications for treating cannabis use disorder, and trials to date generally have not shown efficacy. Medication development efforts have (1) targeted initial abstinence (time-limited approach), (2) tried to replicate the success of opioid replacement therapy by offering legal cannabinoid receptor agonists, or (3) examined antidepressant treatment outcomes of patients with cannabis use disorder and co-occurring major depressive disorder.

Medications that have targeted initial abstinence include zolpidem, N-acetylcysteine (NAC), lofexidine, multiple serotonergic antidepressants, gabapentin, lithium, quetiapine, baclofen, divalproex, and oxytocin. Most of these studies were done in a controlled human laboratory, and the medication (or combination of medications) did not show dose-dependent decreases in self-administration of cannabis and/or self-reported withdrawal symptoms during a quit attempt. Insomnia is one of the most distressing withdrawal symptoms and can lead to relapse. Zolpidem has been shown to improve subjective sleep quality and objective sleep markers on polysomnogram in persons suddenly stopping daily cannabis use.32 NAC is an over-the-counter dietary supplement that can improve dysregulated glutamatergic activity that occurs in cannabis use disorder. A phase 2 study of NAC 1,200 mg by mouth daily combined with contingency management and brief weekly cessation counseling demonstrated a significant doubling of the odds of abstinence over placebo in treatment-seeking adolescents (aged 15-21 years).33 A larger multisite trial of the same dose of NAC in adults with cannabis use disorder showed no benefit over placebo,34 indicating NAC at this dose may be effective only in persons aged 15-21.

Other targets have included the cannabinoid receptors, most notably the cannabinoid type 1 receptor (CB1). Dronabinol, nabilone, and nabiximols have been investigated in studies investigating CB1 agonist replacement therapy. Dronabinol and nabilone are synthetic THC analogs that are FDA approved for the treatment of nausea/vomiting associated with cancer chemotherapy. In a phase 2 outpatient clinical trial, dronabinol 40 mg/d combined with behavioral therapies did not result in reduction in cannabis use compared with placebo.35 However, Phase 1 studies have shown that higher dronabinol doses (up to 120 mg/d) may show different results.36,37 Nabilone has higher oral bioavailability compared to dronabinol and has shown promise in suppressing withdrawal and reducing risk for relapse in phase 1 studies.38,39 Lastly, a recently published phase 1 trial of nabiximols, a mixture of THC and cannabidiol plant extracts approved in several European countries for multiple sclerosis treatment, did not show improvements in abstinence compared to placebo but did show reduction in cannabis use frequency.40

Prescribing antidepressants for cannabis use has yielded mixed results. In one small study, individuals with both depression and alcohol dependence who were frequent cannabis users who were prescribed fluoxetine had greater reduction in cannabis use than a control group.41 Another study found no effect for vilazodone on reducing cannabis use, among those with cannabis dependence.42 Similarly, venlafaxine was not effective in a recent trial among individuals with both depression and cannabis dependence.43

In considering which medications to use, clinicians may prescribe NAC for adolescent patients and zolpidem extended release for adult patients reporting sleep difficulties while trying to stop using cannabis. Off-label nabilone may be offered to adults who are unable to quit using zolpidem or are not good candidates for this medication due to co-occurring alcohol or benzodiazepine use. To increase intervention efficacy, clinicians should use medication as part of a comprehensive treatment program involving the behavioral therapies described above.

SPECIALTY ADDICTION TREATMENT

Although there is much that mental health providers can do to address cannabis use, not all patients can be managed effectively in the context of outpatient psychiatric services (eg, weekly psychotherapy and/or periodic medication management), and lower-intensity treatment may not be effective for patients with higher severity cannabis use disorder and significantly reduced functioning.26 These patients could benefit from referral to specialty addiction medicine programs in which inpatient and/or intensive outpatient care is provided. In practice, such higher-severity patients are likely to use other substances in addition to cannabis.

Treatment options and referral processes vary depending on the type of insurance coverage available to patients. Studies show that a majority of individuals diagnosed with substance use disorders fail to initiate specialty addiction treatment,44 although data on referrals from psychiatry are lacking. It is critical for providers to help facilitate a patient’s initiation and engagement with such programs as much as possible, depending on the context of clinical practice, eg, the extent to which mental health services are integrated with addiction medicine. Follow-up at subsequent mental health visits regarding specialty addiction treatment is also essential to addressing barriers to engagement in care.

CONCLUSIONS

Cannabis use by patients in treatment for psychiatric disorders can present significant challenges to providers. This review highlights key strategies for screening, assessment, and intervention that can be effectively integrated into mental health services. Several brief measures are valuable for screening and measurement of cannabis problem severity, in addition to the DSM-5 diagnostic criteria. Although there is a need for additional intervention development, behavioral strategies such as MI and CBT can help reduce cannabis use in those with mental health problems. For those with more severe cannabis use disorders, it is important for providers to assist patients in getting connected to specialty addiction services. Given the high rate of cannabis use prevalence and its adverse effects on psychiatric treatment, addressing cannabis use in the context of psychiatric services can make a positive impact on patient care.

Published online: September 11, 2018.

Potential conflicts of interest: None.

Funding/support: The authors were supported by grants from the National Institute on Alcohol Abuse and Alcoholism (R01 AA020463), the National Institute on Drug Abuse (T32 DA007250 and R21 DA042627), and the Tobacco-Related Disease Research Program (25IR-0025).

REFERENCES

1. Satre DD, Bahorik A, Zaman T, et al. Psychiatric disorders and comorbid marijuana use: how common is it and what is the clinical impact? J Clin Psychiatry. 2018;79(5):18ac12267.

2. WHO ASSIST Working Group. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, reliability and feasibility. Addiction. 2002;97(9):1183-1194. PubMed CrossRef

3. Ramo DE, Bahorik AL, Delucchi KL, et al. Alcohol and drug use, pain and psychiatric symptoms among adults seeking outpatient psychiatric treatment: latent class patterns and relationship to health status. J Psychoactive Drugs. 2018;50(1):43-43. PubMed CrossRef

4. Satre D, Wolfe W, Eisendrath S, et al. Computerized screening for alcohol and drug use among adults seeking outpatient psychiatric services. Psychiatr Serv. 2008;59(4):441-444. PubMed CrossRef

5. Guttmannova K, Kosterman R, White HR, et al. The association between regular marijuana use and adult mental health outcomes. Drug Alcohol Depend. 2017;179:109-116. PubMed CrossRef

6. Budney AJ, Sargent JD, Lee DC. Vaping cannabis (marijuana): parallel concerns to e-cigs? Addiction. 2015;110(11):1699-1704. PubMed CrossRef

7. Hjorthøj CR, Hjorthoj AR, Nordentoft M. Validity of Timeline Follow-Back for self-reported use of cannabis and other illicit substances—systematic review and meta-analysis. Addict Behav. 2012;37(3):225-233. PubMed CrossRef

8. Martin G, Copeland J, Gates P, et al. The Severity of Dependence Scale (SDS) in an adolescent population of cannabis users: reliability, validity and diagnostic cut-off. Drug Alcohol Depend. 2006;83(1):90-93. PubMed CrossRef

9. Adamson SJ, Kay-Lambkin FJ, Baker AL, et al. An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R). Drug Alcohol Depend. 2010;110(1-2):137-143. PubMed CrossRef

10. Legleye S, Karila L, Beck F, et al. Validation of the CAST, a general population Cannabis Abuse Screening Test. J Subst Use. 2009;12(4):233-242. CrossRef

11. Piontek D, Kraus L, Klempova D. Short scales to assess cannabis-related problems: a review of psychometric properties. Subst Abuse Treat Prev Policy. 2008;3(1):25. PubMed CrossRef

12. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. Fifth Edition. Washington, DC: American Psychiatric Association; 2013.

13. Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction. 1999;94(9):1311-1322. PubMed CrossRef

14. Cornelius JR, Chung T, Martin C, et al. Cannabis withdrawal is common among treatment-seeking adolescents with cannabis dependence and major depression, and is associated with rapid relapse to dependence. Addict Behav. 2008;33(11):1500-1505. PubMed CrossRef

15. Shi Y. At high risk and want to quit: marijuana use among adults with depression or serious psychological distress. Addict Behav. 2014;39(4):761-767. PubMed CrossRef

16. Budney AJ, Roffman R, Stephens RS, et al. Marijuana dependence and its treatment. Addict Sci Clin Pract. 2007;4(1):4-16. PubMed CrossRef

17. National Institute on Drug Abuse. Marijuana. NIDA website. https://www.drugabuse.gov/publications/research-reports/marijuana. December 12, 2017. Accessed February 10, 2018

18. Satre DD, Leibowitz A, Sterling SA, et al. A randomized clinical trial of Motivational Interviewing to reduce alcohol and drug use among patients with depression. J Consult Clin Psychol. 2016;84(7):571-579. PubMed CrossRef

19. Miller WR, Rollnick S. Motivational Interviewing: Helping People Change. 3rd ed. New York, NY: Guilford Press; 2013.

20. Kay-Lambkin FJ, Baker AL, Lewin TJ, et al. Computer-based psychological treatment for comorbid depression and problematic alcohol and/or cannabis use: a randomized controlled trial of clinical efficacy. Addiction. 2009;104(3):378-388. PubMed CrossRef

21. Mueser KT, Drake RE, Turner W, et al. Comorbid substance use disorders and psychiatric disorders. In: Miller WR, Carroll KM, eds. Rethinking Substance Abuse: What the Science Shows, and What We Should Do About It. New York, NY: Guilford Press; 2006:115-133.

22. Back SE, Killeen TK, Teer AP, et al. Substance use disorders and PTSD: an exploratory study of treatment preferences among military veterans. Addict Behav. 2014;39(2):369-373. PubMed CrossRef

23. Buckner JD, Ecker AH, Beighley JS, et al. Integrated cognitive behavioral therapy for comorbid cannabis use and anxiety disorders. Clin Case Stud. 2016;15(1):68-83. PubMed CrossRef

24. Lydecker KP, Tate SR, Cummins KM, et al. Clinical outcomes of an integrated treatment for depression and substance use disorders. Psychol Addict Behav. 2010;24(3):453-465. PubMed CrossRef

25. Johnson S, Sheridan Rains L, Marwaha S, et al. A randomised controlled trial of the clinical and cost-effectiveness of a contingency management intervention compared to treatment as usual for reduction of cannabis use and of relapse in early psychosis (CIRCLE): a study protocol for a randomised controlled trial. Trials. 2016;17(1):515. PubMed CrossRef

26. Baker AL, Hides L, Lubman DI. Treatment of cannabis use among people with psychotic or depressive disorder: A systematic review. J Clin Psychiatry. 2010;71(3):247-254. PubMed CrossRef

27. Metrik J, Jackson K, Bassett SS, et al. The mediating roles of coping, sleep, and anxiety motives in cannabis use and problems among returning veterans with PTSD and MDD. Psychol Addict Behav. 2016;30(7):743-754. PubMed CrossRef

28. Roy-Byrne P, Maynard C, Bumgardner K, et al. Are medical marijuana users different from recreational users? the view from primary care. Am J Addict. 2015;24(7):599-606. PubMed CrossRef

29. Woodruff SI, Shillington AM. Sociodemographic and drug use severity differences between medical marijuana users and non-medical users visiting the emergency department. Am J Addict. 2016;25(5):385-391. PubMed CrossRef

30. Carroll KM, Ball SA, Nich C, et al. Motivational interviewing to improve treatment engagement and outcome in individuals seeking treatment for substance abuse: a multisite effectiveness study. Drug Alcohol Depend. 2006;81(3):301-312. PubMed CrossRef

31. Martino S, Carroll KM, O’ Malley SS, et al. Motivational interviewing with psychiatrically ill substance abusing patients. Am J Addict. 2000;9(1):88-91. PubMed CrossRef

32. Vandrey R, Smith MT, McCann UD, et al. Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend. 2011;117(1):38-44. PubMed CrossRef

33. Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry. 2012;169(8):805-812. PubMed CrossRef

34. Gray KM, Sonne SC, McClure EA, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017;177:249-257. PubMed CrossRef

35. Levin FR, Mariani JJ, Brooks DJ, et al. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2011;116(1-3):142-150. PubMed CrossRef

36. Vandrey R, Stitzer ML, Mintzer MZ, et al. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend. 2013;128(1-2):64-70. PubMed CrossRef

37. Schlienz NJ, Lee DC, Stitzer ML, et al. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration. Drug Alcohol Depend. 2018;187:254-260. PubMed CrossRef

38. Haney M, Cooper ZD, Bedi G, et al. Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology. 2013;38(8):1557-1565. PubMed CrossRef

39. Herrmann ES, Cooper ZD, Bedi G, et al. Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users. Psychopharmacology (Berl). 2016;233(13):2469-2478. PubMed CrossRef

40. Trigo JM, Soliman A, Quilty LC, et al. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial. PLoS One. 2018;13(1):e0190768. PubMed CrossRef

41. Cornelius JR, Salloum IM, Haskett RF, et al. Fluoxetine versus placebo for the marijuana use of depressed alcoholics. Addict Behav. 1999;24(1):111-114. PubMed CrossRef

42. McRae-Clark AL, Baker NL, Gray KM, et al. Vilazodone for cannabis dependence: a randomized, controlled pilot trial. Am J Addict. 2016;25(1):69-75. PubMed CrossRef

43. Levin FR, Mariani J, Brooks DJ, et al. A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders. Addiction. 2013;108(6):1084-1094. PubMed CrossRef

44. Park-Lee E, Lipari RN, Hedden SL, et al. Receipt of services for substance use and mental health issues among adults: results from the 2015 National Survey on Drug Use and Health. NSDUH Data Review. Rockville, MD: Substance Abuse and Mental Health Services Administration website. https://www.samhsa.gov/data/sites/default/files/NSDUH-ServiceUseAdult-2015/NSDUH-ServiceUseAdult-2015/NSDUH-ServiceUseAdult-2015.htm. September 2016. Accessed February 10, 2018.

aDepartment of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, California

bDivision of Research, Kaiser Permanente Northern California, Oakland, California

cSan Francisco Veterans Administration Health Care System, San Francisco, California

dZuckerberg San Francisco General Hospital, San Francisco, California

*Corresponding author: Derek D. Satre, PhD, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Ave, Box 0984, San Francisco, CA 94143 ([email protected]).

J Clin Psychiatry 2018;79(6):18ac12268

To cite: Satre DD, Borsari B, Tompkins DA, et al. Psychiatric disorders and comorbid cannabis use: when should we be concerned and what can we do about it? J Clin Psychiatry. 2018;79(6):18ac12268.

To share: https://doi.org/10.4088/JCP.18ac12268

© Copyright 2018 Physicians Postgraduate Press, Inc.