
- Vol 39, Issue 12
Current Treatments for Cannabis Use Disorder
While there are no FDA-approved medications available for CUD, some studies show potential off-label utility in mitigating withdrawal and maintaining abstinence. Learn more in this CME article.
CATEGORY 1 CME
Premiere Date: December 20, 2022
Expiration Date: June 20, 2024
This activity offers CE credits for:
1. Physicians (CME)
2. Other
All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.
ACTIVITY GOAL
The goal of this activity is to evaluate evidence-based behavioral treatments, medications, and management strategies for cannabis use disorder.
LEARNING OBJECTIVES
1. Review the available evidence-based behavioral treatments for cannabis use disorder.
2. Review evidence of off-label pharmacological options to aid in the management of cannabis use disorder.
TARGET AUDIENCE
This accredited continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals seeking to improve the care of patients with mental health disorders.
ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians’ Education Resource®, LLC, and Psychiatric Times™. Physicians’ Education Resource®, LLC, is accredited by the ACCME to provide continuing medical education for physicians.
Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
This activity is funded entirely by Physicians’ Education Resource®, LLC. No commercial support was received.
OFF-LABEL DISCLOSURE/DISCLAIMER
This accredited CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this accredited CE activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource®, LLC.
FACULTY, STAFF, AND PLANNERS’ DISCLOSURES AND CONFLICT OF INTEREST (COI) MITIGATION
None of the staff of Physicians’ Education Resource®, LLC, or Psychiatric Times™ or the planners of this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients. Dr Mooney and Dr Lochte have nothing to disclose. Dr Cooper disclosed that she is a consultant for, and has done research for, Canopy Growth Corporation.
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HOW TO CLAIM CREDIT
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Cannabis is the most widely used psychoactive substance after alcohol and tobacco; 4% of the global adult population (200 million people) endorses its use (
In the United States, there are nearly 14 million daily or near-daily cannabis users; the prevalence doubled between 2010 and 2019.2 Increased rates of cannabis use likely follow changes in legalization and social acceptance; reduced cost; increased potency; and expanded preparation and routes of administration (ie, edibles, waxes, extracts, and vaping). Despite reduced public perception of risk, research has shown that heavy
For patients seeking treatment for CUD, goals can include sustained abstinence, reduced use, or harm reduction. Treatment of CUD typically occurs in the outpatient setting; however, residential or inpatient treatment may be required for more complex cases.
Behavioral interventions for
Evidence-Based Behavioral Treatments
Various behavioral approaches have been shown to have clinical utility in treating CUD. In a meta-analysis of 7 controlled clinical trials of adults with CUD, psychosocial treatments were shown to double the chances of abstinence at 3 to 4 months’ follow-up (21% versus 10%).6 Treatment outcomes improve with longer durations of therapy and when interventions are combined. However, access to evidence-based therapies is often limited, insurance reimbursement may constrain options, and
Motivational enhancement therapy (MET). MET is an empathetic approach, focusing on individualized goals and psychoeducation. MET is often less time and resource intensive than
Contingency management (CM). CM uses incentives like vouchers or prizes to reinforce milestones in treatment, such as adherence to treatment or negative drug screens. Although CM has limited efficacy as a monotherapy in CUD, it can promote longer periods of abstinence when combined with other treatment modalities like MET or CBT.10
Cognitive-behavioral therapy. CBT is a well-studied approach focusing on the thoughts, behaviors, and triggers that reinforce substance use. This approach encourages patients to utilize coping skills and problem-solving skills and to find healthy alternative behaviors to replace
Other interventions. Other psychosocial treatments (ie, counseling, family-based therapy, mindfulness, and relapse prevention) likely have utility in treating CUD, but they have relatively less supporting research.7 Although mutual support groups are popular and valuable resources for some patients, they should ideally be utilized in addition to evidence-based psychosocial treatments.
Medications to Reduce Cannabis Use
Given the limitations of behavioral interventions, pharmacological interventions have been actively researched over the past 20 years. However, there are still no FDA-approved medications to treat CUD. Although some medications may have potential clinical utility for off-label use, clear treatment recommendations with respect to both safety and efficacy cannot be made without additional clinical trials.5 Off-label use of FDA-approved medications is sometimes considered in combination with behavioral treatments to target withdrawal symptoms, craving, or relapse, or to augment behavioral treatment approaches.
The following medications have been approved by the FDA for alternative indications and may have efficacy in reducing
Gabapentin. Gabapentin is a medication that blocks the α٢δ subunit of voltage-gated calcium channels and indirectly modulates γ-aminobutyric acid (GABA) signaling. The FDA has approved it for a variety of conditions including neuropathic pain, and it is frequently used off-label for anxiety and insomnia, and to treat craving associated with alcohol withdrawal. In a placebo-controlled trial (N=50), gabapentin administered at 1200 mg/day showed significant reductions in objective and subjective markers of cannabis use, withdrawal, and craving.12
N-acetylcysteine (NAC). NAC is a prodrug of the amino acid cysteine, and it plays a role in controlling glutamate levels. It has been FDA-approved for more than 50 years and is beneficial in preventing liver damage associated with acetaminophen overdose. In a randomized controlled trial (RCT) of individuals aged 15 to 21 years with CUD, participants (N=58) taking NAC at a dose of 1200 mg twice a day had twice the odds of having a negative urine
Naltrexone. Naltrexone is a µ-opioid receptor antagonist that is approved by the FDA to treat opioid and alcohol use disorders. Single doses of
Varenicline. Varenicline is a selective nicotinic acetylcholine receptor agonist approved for
Nabilone. Nabilone is a cannabinoid 1 (CB1) receptor agonist with greater CB1 receptor affinity and efficacy, and superior bioavailability compared with oral Δ-9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Similar to cannabis, it has misuse potential. Nabilone is FDA approved as a second-line treatment for nausea and vomiting associated with chemotherapy. In a laboratory study, 6 to 8 mg/day of nabilone reduced cannabis use in a laboratory model of relapse and reduced symptoms of cannabis withdrawal.19
Cannabidiol (CBD). CBD is the second most abundant phytocannabinoid in cannabis and cannabis-based products after THC. It is nonintoxicating, has a favorable safety profile, and is the principal compound of Epidiolex, which is FDA-approved for specific seizure disorders. Unlike THC, it has minimal direct actions at the CB1 and CB2 receptors. In a recent RCT with individuals seeking treatment for CUD (N=48), oral CBD (400-800 mg/day) was associated with reduced cannabis use, favorable retention, and no significant adverse events.20 Of note, commercially available OTC CBD products should not be used for medical treatment because they usually contain lower doses of CBD (eg, 5-100 mg) than those administered in these studies, are generally not manufactured according to the Good Manufacturing Practices, and frequently contain THC.
Management of Cannabis Withdrawal
Cannabis withdrawal symptoms (
Nabiximols. Nabiximols is an oromucosal spray that delivers 2.7 mg THC and 2.5 mg CBD per actuation. The FDA has not approved nabiximols for any indication in the United States; however, it is approved in many countries for indications that include
Dronabinol. Dronabinol is an oral synthetic THC, and it has an FDA-approved indication for treating
Quetiapine. Quetiapine is an atypical antipsychotic that acts at multiple neurotransmitter receptors, and it is used for its sedating and mood-stabilizing properties at lower doses. It is FDA approved for treatment of acute manic episodes as well as depressive episodes in
Mirtazapine. Mirtazapine is an FDA-approved antidepressant known for its sedating and appetite-inducing properties. Mirtazapine enhances noradrenergic and serotonergic transmission by blocking presynaptic inhibitory α2 auto receptors. It has been found to improve appetite and sleep; however, it had no effect in reducing cannabis use in a laboratory model of relapse.27
Zolpidem and benzodiazepines. Zolpidem is a benzodiazepine-like sedative hypnotic and GABAA receptor agonist, FDA approved for treating sleep onset
Guanfacine. Guanfacine is an α2A-adrenergic agonist that has been approved by the FDA to treat
Other Treatments
Medications from other drug classes have been tested in the treatment of CUD, but most have shown little or no effect on reducing cannabis use. Some medications, such as topiramate32 and lorcaserin,33 have shown preliminary efficacy in treating CUD, but they have tolerability issues or are no longer FDA approved. Oxytocin has some evidence for supplementing psychosocial interventions,34 but it is unlikely to be used without further study. Novel drugs not yet approved by the FDA for any indication, such as fatty acid amide hydrolase inhibitors, have potential efficacy in treating CUD and are undergoing multisite trials, but they are not available for clinical use at this time.35
Concluding Thoughts
The prevalence of CUD is increasing in lock step with rates of cannabis use due to changes in legalization and other sociopolitical factors. Behavioral interventions are the current mainstay of evidence-based treatment; nevertheless, they can be challenging to implement and show limited efficacy in maintaining long-term abstinence. No FDA-approved medications are available for CUD, but some studies show potential off-label utility in mitigating withdrawal and maintaining abstinence. Further research will be needed to clarify definitive treatment guidelines for this increasingly relevant condition.
Dr Lochte is a psychiatry resident at University of California, Los Angeles (UCLA). Dr Cooper is the director of the UCLA Center for Cannabis and Cannabinoids in the Jane and Terry Semel Institute for Neuroscience and Human Behavior. She is also an associate professor-in-residence in the Department of Psychiatry and Biobehavioral Sciences at UCLA’s David Geffen School of Medicine. Dr Mooney is an addiction psychiatrist and associate clinical professor at UCLA, where she directs the UCLA Addiction Medicine Clinic.
References
1. Leung J, Chan GCK, Hides L, Hall WD.
2. United Nations Office of Drug and Crime. World Drug Report 2021 – Drug Market Trends: Cannabis Opioids. June 2021. Accessed November 11, 2022.
3. World Health Organization (WHO). The health and social effects of nonmedical cannabis use. 2016. Accessed November 11, 2022.
4. Hughes JR, Peters EN, Callas PW, et al.
5. Brezing CA, Levin FR.
6. Patnode CD, Perdue LA, Rushkin M, et al.
7. Gates PJ, Sabioni P, Copeland J, et al.
8. Imtiaz S, Roerecke M, Kurdyak P, et al.
9. Stephens RS, Roffman RA, Curtin L.
10. Carroll KM, Easton CJ, Nich C, et al.
11. Ahmed S, Bachu R, Kotapati P, et al.
12. Mason BJ, Crean R, Goodell V, et al.
13. Gray KM, Carpenter MJ, Baker NL, et al.
14. Gray KM, Sonne SC, McClure EA, et al.
15. Cooper ZD, Haney M.
16. Haney M, Ramesh D, Glass A, et al.
17. McRae-Clark AL, Gray KM, Baker NL, et al.
18. Herrmann ES, Cooper ZD, Bedi G, et al.
19. Haney M, Cooper ZD, Bedi G, et al.
20. Freeman TP, Hindocha C, Baio G, et al.
21. Allsop DJ, Copeland J, Lintzeris N, et al.
22. Lintzeris N, Bhardwaj A, Mills L, et al; Agonist Replacement for Cannabis Dependence (ARCD) Study Group.
23. Haney M, Hart CL, Vosburg SK, et al.
24. Levin FR, Mariani JJ, Brooks DJ, et al.
25. Cooper ZD, Foltin RW, Hart CL, et al.
26. Mariani JJ, Pavlicova M, Mamczur AK, et al.
27. Haney M, Hart CL, Vosburg SK, et al.
28. Vandrey R, Smith MT, McCann UD, Budney AJ, Curran EM.
29. Allsop DJ, Bartlett DJ, Johnston J, et al.
30. Haney M, Cooper ZD, Bedi G, et al.
31. Haney M, Hart CL, Vosburg SK, et al.
32. Miranda Jr R, Treloar H, Blanchard A, et al.
33. Arout CA, Cooper ZD, Collins Reed S, et al.
34. Sherman BJ, Baker NL, McRae-Clark AL.
35. D’Souza DC, Cortes-Briones J, Creatura G, et al.
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