Medications May Ease Cannabis Withdrawal But Fail to Achieve Abstinence

Marijuana, or cannabis, remains far and away the most commonly used illicit substance. Nearly 41 million people aged 12 or older used marijuana in 2017, according to the latest National Survey on Drug Use and Health. Though some states would dispute the “illicit” term, the fact remains that 1 in 10 adults who use marijuana will develop a dependency; 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. Frances 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 at APA’s Annual Meeting in May.

One common approach to treating patients with CUD is to manage their withdrawal symptoms, which can include irritability, anxiety, and sleep problems. Studies show that the anxiolytic buspirone; the insomnia medication zolpidem; and guanfacine, which is approved for attention-deficit/hyperactivity disorder, effectively manage symptoms of withdrawal. However, Levin said there is little evidence that easing withdrawal helps promote cannabis abstinence (as measured by reports of cannabis use by participants with CUD in research studies).

Some preliminary studies suggested that quetiapine, an antipsychotic, and gabapentin, an anticonvulsant—both of which reduce withdrawal symptoms—might also promote abstinence. However, larger randomized studies suggest these medications do not increase abstinence in patients with CUD (though quetiapine may somewhat reduce daily cannabis use).

Another approach to reducing cannabis use by patients with CUD may be to treat them with medications that bind to cannabinoid (CBD) receptors, similar to how nicotine replacement therapy works in smokers. To date, synthetic, CBD-binding drugs like dronabinol or rimonabant have not shown an ability to reduce the subjective pleasure of taking cannabis or promote abstinence. 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.

Levin suggested that the most promising compound for decreasing cannabis use appears to be n-acetylcysteine (NAC), an antioxidant that can be purchased over the counter. 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 are more likely to stop using cannabis when given NAC alongside behavioral therapy versus those who receive behavioral therapy alone.

Levin told the audience that that the failure to identify compounds that help patients with CUD achieve abstinence 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.”

She suggested future efforts focus on 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 reducing the total number of days cannabis is consumed or the average consumption per day might reveal that some of these available medications can help patients curb their cannabis consumption. ■