Social, medical, and legal acceptance of cannabis has grown dramatically over the last 15 years, and cannabis use – for medical and recreational purposes – has also increased. From 2002 to 2012, the prevalence of daily cannabis use in the United States increased from 1.3 to 2.1%.2 Along with an increase in the acceptance and use of cannabis, the potency of cannabis available on the market has dramatically increased. Meanwhile, the proportion of the public that perceives important harms from cannabis use has decreased. A recent national survey found that only about 1 in 5 individuals reporting any past-year cannabis use perceived addiction to be a risk associated with cannabis.

In fact, a growing body of evidence shows addiction is a concern. Among regular users, cannabis use can lead to physiologic dependence, with withdrawal symptoms similar to that of other substance use disorders. Cannabis withdrawal symptoms include dysphoric mood, disturbed sleep, gastrointestinal symptoms, and decreased appetite. Between 2.5% and 6.3% of adults are estimated to have cannabis use disorder (CUD) – the diagnosis that, according to DSM V criteria, necessitates clinically significant impairment or distress in more than one realm (eg, tolerance, social, interpersonal, or occupational challenges, or continued use despite adverse consequences). Furthermore, among those reporting any past-year cannabis use, 36% met criteria for CUD over the prior year. Nearly half those with CUD have moderate or severe CUD, and the risk is greatest in young adults and socioeconomically disadvantaged groups. Cannabis use disorder is also a growing concern among Veterans.

While CUD is much more prevalent and of greater severity than many recognize, the vast majority of patients do not seek treatment. The lifetime prevalence of CUD in the general population is 6.3%, but only 5% of those with CUD have sought treatment from a health care provider. Standard treatment of CUD includes psychotherapy, such as cognitive behavior therapy (CBT), motivation enhancement therapy (MET), or contingency management (CM). However, these treatments may be inaccessible to many and are time-intensive. Pharmacotherapy could offer additional treatment options for the growing number of patients with CUD. Currently, there are no FDA-approved pharmacotherapies available for CUD, though a number (eg, cannabinoids, antidepressants, anxiolytics, and glutamatergic modulators) have been proposed for off-label use. The purpose of this systematic review and meta-analysis is to examine the benefits and harms associated with the use of off-label pharmacotherapies to promote the cessation/reduction of cannabis use and to mitigate withdrawal symptoms.

Contents

• Preface
• Acknowledgments
• Executive Summary
  • Abbreviations Table
• Introduction
• Methods
  • Topic Development
  • Search Strategy
  • Study Selection
  • Data Abstraction and Quality Assessment
  • Data Synthesis and Analysis
• Results
  • KEY QUESTION 1. What are the benefits and harms of pharmacotherapy for cannabis use disorder?
  • KEY QUESTION 2. Are there known subpopulations for whom currently used pharmacotherapy is most/least effective for cannabis use disorder?
  • Discussion
  • Limitations
  • Research Gaps/Future Research
  • Implications for the VHA
  • Conclusion
• References
• APPENDIX A. Search Strategies
• APPENDIX B. Study Selection
• APPENDIX C. Quality Assessment Criteria
• APPENDIX D. Quality Assessment of Included Studies
• APPENDIX E. Peer Review

Suggested citation:

Kondo K, Morasco BJ, Nugent S, Ayers C, O’Neil ME, Freeman M, Paynter R, and Kansagara D. Pharmacotherapy for the treatment of cannabis use disorder: a systematic review. VA ESP Project #05-225; 2019. Posted final reports are located on the ESP search page.

This report is based on research conducted by the Evidence Synthesis Program (ESP) Center located at the Portland VA Medical Center, Portland, OR funded by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development. The findings and conclusions in this document are those of the author(s) who are responsible for its contents; the findings and conclusions do not necessarily represent the views of the Department of Veterans Affairs or the United States government. Therefore, no statement in this article should be construed as an official position of the Department of Veterans Affairs. No investigators have any affiliations or financial involvement (eg, employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties) that conflict with material presented in the report.