Frances Levin, MD

It is vital that physicians-particularly psychiatrists who are on the frontlines with patients who struggle with cannabis use-are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics by walking through clinical decision-making with a case vignette that touches on common experiences in treating a patient with cannabis use disorder.

A separate and important issue is screening for emerging drugs of abuse, including synthetic “marijuana” products such as K2 and spice. Although these products are chemically distinct from the psychoactive compounds in the traditional cannabis plant, some cannabis users have tried synthetic “marijuana” products because of their gross physical similarity to cannabis plant matter.

Mr. M is a 43-year-old legal clerk who has been working in the same office for 20 years. He presents as a referral from his primary care physician to your outpatient psychiatry office for an initial evaluation regarding “managing some mid-life issues.” He states that while he likes his job, it is the only job he has had since graduating college and he finds the work boring, noting that most of his co-workers have gone on to law school or more senior positions in the firm. When asked what factors have prevented him from seeking different career opportunities, he states that he would “fail a drug test.” Upon further inquiry, Mr. M says he has been smoking 2 or 3 “joints” or taking a few hits off of his “vaping pen” of cannabis daily for many years, for which he spends approximately $70 to $100 a week.

He first used cannabis in college and initially only smoked “a couple hits” in social settings. Over time, he has needed more cannabis to “take the edge off” and has strong cravings to use daily. He reports liking how cannabis decreases his anxiety and helps him fall asleep, although he thinks the cannabis sometimes makes him “paranoid,” which results in his avoidance of family and friends.

More recently, he identifies conflict and regular arguments with his wife over his cannabis use-she feels it prevents him from being present with his family and is a financial burden. He admits missing an important awards ceremony for her work and sporting events for his children, for which he had to “come up with excuses,” but the truth is that he ended up smoking more than he had intended and lost track of the time.

Mr. M reports multiple previous unsuccessful attempts to reduce his use and 2 days when he stopped completely, which resulted in “terrible dreams,” poor sleep, sweating, no appetite, anxiety, irritability, and strong cravings for cannabis. Resumption of his cannabis use relieved these symptoms. He denies tobacco or other drug use, including use of synthetic marijuana products such as K2 or spice, and reports having a glass of wine or champagne once or twice a year for special occasions.

In the transition from DSM IV-TR to DSM-5, cannabis use disorders, along with all substance use disorders, have been redefined in line with characterizing a spectrum of pathology and impairment. The criteria to qualify for a cannabis use disorder remain the same except for the following:

 The criterion for recurrent legal problems has been removed.

 A new criterion for craving or a strong desire or urge to use cannabis has been added, and the terms abuse and dependence were eliminated.

To qualify as having a cannabis use disorder, a threshold of 2 criteria must be met. Severity of the disorder is characterized as “mild” if 2 or 3 criteria are met, “moderate” if 4 or 5 criteria are met, and “severe” if 6 or more criteria are met. Mr. M demonstrates 3 symptoms of impaired control: using longer than intended, unsuccessful efforts to cut back, and craving; 3 symptoms of social impairment: failure to fulfill home obligations, persistent problems with his wife, and reduced pursuit of occupational opportunities; 1 symptom of risky use: continued use despite paranoia; and 2 symptoms of pharmacological properties: tolerance and withdrawal. As such, he meets 9 criteria, which qualify him for a diagnosis of severe cannabis use disorder.

You summarize Mr. M’s 9 symptoms and counsel him about severe cannabis use disorder. He becomes upset and states that he was not aware one could develop an “addiction” to cannabis. He expresses an interest in treatment and asks what options are available.

Psychotherapeutic treatments, including motivational enhancement treatment (MET), cognitive behavioral therapy (CBT), and contingency management (CM), have demonstrated effectiveness in reducing frequency and quantity of cannabis use, but abstinence rates remain modest and decline after treatment. Generally, MET is effective at engaging individuals who are ambivalent about treatment; CM can lead to longer periods of abstinence during treatment by incentivizing abstinence; and CBT can work to enhance abstinence following treatment (preventing relapse). Longer duration of psychotherapy is associated with better outcomes. However, access to evidence-based psychotherapy is frequently limited, and poor adherence to evidence-based psychotherapy is common.

In conjunction with psychotherapy, medication strategies should be considered. Because there are no FDA-approved pharmacological agents for cannabis use disorder, patients should understand during the informed consent process that all pharmacotherapies used to treat this disorder are off-label. A number of clinical trials provide evidence for the off-label use of medications in the treatment of cannabis use disorder. The current strategies for the off-label treatment of cannabis use disorder target withdrawal symptoms, aim to initiate abstinence and prevent relapse or reduce use depending on the patient’s goals, and treat psychiatric comorbidity and symptoms that may be driving cannabis use. Here we focus on the evidence supporting these key strategies.

Cannabis withdrawal is defined by DSM-5 as having 3 or more of the following signs and symptoms that develop after the cessation of prolonged cannabis use:

• At least one of the following physical symptoms that causes discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache

Withdrawal symptoms may be present within the first 24 hours. Overall, they peak within the first week and persist up to 1 month following the last use of cannabis. In the case of Mr. M, insomnia, poor appetite, and irritability as well as sweating are identified, which meet DSM-5 criteria for cannabis withdrawal during the 2 days he abstained from use. He also identifies strong craving and vivid dreams, which are additional withdrawal symptoms included on marijuana withdrawal checklists in research studies, although not included in DSM-5 criteria. These and other symptoms should be considered in clinical treatment.

Medication treatment studies for cannabis withdrawal have hypothesized that if withdrawal symptoms can be reduced or alleviated during cessation from regular cannabis use, people will be less likely to resume cannabis use and will have better treatment outcomes. Studies have shown that dronabinol and nabilone improved multiple withdrawal symptoms, including craving; and quetiapine, zolpidem, and mirtazapine help with withdrawal-induced sleep disturbances.

Combining dronabinol and lofexidine (an alpha-2 agonist) was superior to placebo in reducing craving, withdrawal, and self-administration during abstinence in a laboratory model. However, in a subsequent treatment trial, the combined medication treatment was not superior to placebo in reducing cannabis use or promoting abstinence.

Six double-blind placebo-controlled pharmacotherapy trials in adults with cannabis use disorder have looked at withdrawal as an outcome.

 Of these studies, only dronabinol, bupropion, and gabapentin reduced withdrawal symptoms.

 In addition to reducing withdrawal symptoms, nabiximols/Sativex (a combination tetrahydrocannabinol [THC] and cannabidiol nasal spray not available in the US) increased retention (while actively on the medication in an inpatient setting) but did not reduce outpatient cannabis use at follow-up.

All of the medications available for prescription in the US can be monitored reliably with urine drug screening to assess for illicit cannabis use except dronabinol, which will result in a positive screen for cannabis. When using urine drug screening, remember that for heavy cannabis users the qualitative urine drug screen can be positive for cannabis up to a month following cessation. When selecting a medication, take into account the cost of the medication, particularly since insurance will likely not cover THC agonists such as dronabinol for this indication, and possible misuse or diversion of scheduled substances (eg, dronabinol, nabilone). In addition, monitoring for reductions in substance use and withdrawal symptoms is key.

Abstinence initiation and relapse prevention

Other clinical trials have looked at medications to promote abstinence by reducing stress-induced relapse, craving (not as a component of withdrawal), and the reinforcing aspects of cannabis. Of these trials, the following results show potential promise with positive findings: gabapentin reduced quantitative THC urine levels and improved cognitive functioning (in addition to decreasing withdrawal), and buspirone led to more negative urine drug screens for cannabis (although the difference was not significant compared with placebo).

 However, in a follow-up larger study, no differences were seen compared with placebo and women had worse cannabis use outcomes on buspirone.

-acetylcysteine resulted in twice the odds of a negative urine drug screen in young adults and adolescents (although there was no difference between adolescent groups in self-report of cannabis use).

 reported that no differences were seen between 

-acetylcysteine and placebo (results of the trial are soon to be published). Topiramate resulted in significantly decreased grams of cannabis used but no difference in percent days used or proportion of positive urine drug screens.

 In a recent small clinical trial, reductions in cannabis use were seen with oxytocin in combination with MET.

 Studies with nabilone and long-term naltrexone administration reduced relapse and cannabis self-administration and subjective effects, respectively, which suggests promising avenues yet to be explored by clinical trials.

Other studies have looked at the effects of treating common comorbid psychiatric disorders in adults with cannabis use disorder, postulating that if the psychiatric disorder is treated, the individual may be more likely to abstain or reduce his or her cannabis use. For example, if a person is less depressed, he may better engage in CBT for relapse prevention.

Fluoxetine for depression and cannabis use disorder in adolescents decreased cannabis use and depression, although there was no difference compared with placebo.

 A trial of venlafaxine for adults with depression and cannabis use disorder demonstrated less abstinence with greater withdrawal-like symptoms compared with placebo.

 These findings suggest that this antidepressant might not be beneficial for treatment-seeking individuals with cannabis use disorder and may actually negatively affect outcomes.

After discussing and presenting the different psychotherapy and medication treatment options to Mr. M, you and he decide to start CBT to help with abstinence initiation. In addition, you prescribe 20 mg of dronabinol up to 2 times daily in combination with 50 mg of naltrexone daily, to help globally target Mr. M’s withdrawal symptoms and prevent relapse once abstinence is achieved. However, a few days later, Mr. M calls to say that his insurance will not cover the prescription for dronabinol and he cannot afford the high cost. Given his main concerns of cannabis withdrawal symptoms, you select gabapentin up to 400 mg 3 times daily and continue weekly individual CBT.

Mr. M calls back several days later and reports that he has made some improvements in reducing the frequency of his cannabis use, which he attributes to the medication, but he thinks he needs additional assistance. After reviewing the treatment options again, he gives informed consent to start 1200 mg of 

-acetylcysteine twice daily. After 10 weeks of this medication, his urine screens are negative.

You continue to provide relapse prevention CBT. He reports to you that his anxiety and insomnia are almost resolved, and you suspect that withdrawal was the cause of these symptoms. He reports significant improvement in his relationship with his family and recently received a promotion at work for “going above and beyond” on a project he was given the lead.

Over the next 6 months, he has 2 relapses that in functional analysis with you are determined to be triggered by unsolicited contact from his former drug dealer. Together, you develop a plan to block any further contact from the drug dealer. After several months, both the gabapentin and N-acetylcysteine are tapered and discontinued. Mr. M continues to see you for biweekly therapy sessions with random drug screens every 4 to 6 weeks.

Based on the available evidence, gabapentin, THC agonists, naltrexone, and possibly 

-acetylcysteine show the greatest promise in the off-label treatment of cannabis use disorders. System considerations, such as medication cost, need to be factored into the decision-making as well as combination medication and psychotherapy approaches, which-as demonstrated in the case of Mr. M-may ultimately work best. Until further research elucidates the standard of medication practices for cannabis use disorder, the best off-label medication strategy should target any co-occurring disorders as well as any identified problematic symptoms related to cannabis use and cessation of use. When available, referral for evidence-based psychotherapy should be made.

This article was originally published on June 30, 2017 and has since been updated.

Dr. Brezing is a Fellow in Addiction Psychiatry at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons in New York City; Dr. Levin is Kennedy-Leavy Professor of Clinical Psychiatry, Columbia University College of Physicians and Surgeons, Chief of the Division on Substance Abuse, and Director of the Addiction Psychiatry Fellowship Program at New York Presbyterian Hospital.

The authors report no conflicts of interest concerning the subject matter of this article.

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It is vital that psychiatrists are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics.

Frances Levin, MD

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