Medications for Cannabis Use Disorder May Ease Withdrawal But Fail to Achieve Abstinence


Marijuana, or cannabis, remains far and away the most commonly used illicit substance. Though some states would dispute the “illicit” term, the fact remains that cannabis can be misused; and given its widespread use, psychiatrists will likely encounter a patient with cannabis use disorder (CUD).

Currently no medications are approved for CUD, and behavioral therapy remains the preferred treatment. But some studies have pointed to medications that may benefit patients with CUD. Francis Levin, M.D., the Kennedy-Leavy Professor of Clinical Psychiatry at Columbia University Medical Center, reviewed these options during a session on advances in treating substance use disorders.

One common approach for CUD treatment is to manage withdrawal symptoms such as irritability, anxiety, and sleep problems. Examples include zolpidem, buspirone, and guanfacine. While these and other medications are effective at symptom management, Levin said there is little evidence that treating withdrawal helps promote cannabis abstinence (as measured by cannabis self-administration frequency in research studies). Some preliminary studies suggested that quetiapine and gabapentin might promote abstinence as well as reduce withdrawal symptoms, but larger randomized studies have not borne that out (though quetiapine may somewhat reduce daily usage).

Another direction for pharmacology is to target cannabinoid (CBD) receptors and diminish the effects of cannabis in patients with CUD, like the effect of buprenorphine or methadone in patients with opioid use disorder. To date, synthetic cannabinoids like dronabinol or rimonabant have not increased abstinence or reduced the subjective pleasure of taking cannabis. One exception might be the potent CBD agonist nabilone, which has shown efficacy in early studies, but Levin noted the high cost of this medication might limit its use in clinical settings.

The most promising CUD medication might be n-acetylcysteine (NAC), an antioxidant that can be purchased over the counter as a supplement. NAC does not directly target CBD receptors but rather helps restore normal levels of the neurotransmitter glutamate, which is believed to be associated with compulsive, drug-seeking behaviors. NAC does not work for all patients, but data suggest that teens and young adults up to 21 years old do have better cannabis cessation rates if given NAC alongside behavioral therapy.

Levin told the audience that the numerous discouraging clinical findings may have more to do with study design than lack of pharmacological efficacy. “In many cases I believe these studies did not use a strong enough dose or treatment length to uncover an observable reduction in cannabis use,” she said. “Unfortunately, there is little enthusiasm from funding agencies to repeat these studies in larger populations.”

For future studies, she suggested enrolling more specific patient groups—such as adolescents only—or excluding patients with mild CUD since they likely would not benefit as much from treatment.

“We should also address the question of whether abstinence is the ideal outcome when testing medications,” she continued. More moderate “harm-reduction” outcomes like total number of days smoked or average consumption per day might reveal that some of these available medications can help patients curb their cannabis consumption.

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