Conference Coverage

Zolpidem does not boost cannabis abstinence during treatment



– Disturbed sleep is one of the symptoms of withdrawal from marijuana, and it can wreak havoc on the lives of people with cannabis use disorder who are trying to quit. Now, a new study provides more evidence about the problem and suggests that the sleep aid zolpidem is not a solution on its own.

Zolpidem seemed to help subjects sleep better, but the effect lasted only as long as they took the drug. And the subjects who took zolpidem were not significantly more likely to abstain from cannabis in the long term.

“Zolpidem or other hypnotics may have some efficacy as a pharmacotherapy to relieve short-term sleep disruption in the treatment of cannabis use disorder. But they should only be used in cases where abstinence-induced insomnia is a significant barrier to cessation and only in combination with other evidence-based interventions to address key aspects of cannabis use disorder,” study coauthor Dustin C. Lee, PhD, of Johns Hopkins University, Baltimore, said in an interview. He presented the study findings at the annual meeting of the College on Problems of Drug Dependence.

Previous research, including studies by some of the authors of the new report, suggests that people trying to withdraw from cannabis often suffer from sleep disturbances.

In a 2010 study, for instance, researchers interviewed 469 adult cannabis users in the Baltimore area who had tried to quit outside of treatment programs. Nearly half reported trouble falling asleep, while 20%-36% reported sleep-related symptoms, such as sleeping more or less than usual, having unusual dreams, and waking during the night (Drug Alcohol Depend. 2010 Sep 1;111[1-2]:120-7).

Another factor could be at play: Cannabis users may sleep better while they use the drug, then lose the benefit when they try to withdraw.

“Studies have demonstrated that acute use of cannabis reduces sleep latency and increases stage 3 sleep, informally referred to as ‘deep’ or ‘slow-wave’ sleep, which means individuals fall asleep faster and remain in deep sleep longer after using cannabis,” Dr. Lee said.

Dr. Dustin C. Lee, Johns Hopkins University, Baltimore

Dr. Dustin C. Lee

Whatever the explanation, the sleep problems during withdrawal are not helpful to users who are trying to quit. “Research indicates that cannabis cessation results in sleep problems that are a barrier to quitting,” Dr. Lee said.

For the new study, Dr. Lee and his colleagues randomly assigned 127 adults – all in a 12-week clinical trial of cannabis use disorder treatment – to receive extended-release zolpidem or placebo.

Participants underwent urine screens to test for drug use and ambulatory polysomnography to measure sleep.

A preliminary analysis found that those who received zolpidem had higher rates of cannabis abstinence during the 12 weeks and at end of treatment. But analysis showed that the differences were not statistically significant, Dr. Lee said, “which suggests that sleep is not the predominant factor driving successful cessation attempts.”

Researchers also found that sleep efficiency and sleep onset latency deteriorated to a clinically significant degree in week 1 of the study for those who took the placebo (mean sleep efficiency fell from 82% to 74%, while sleep onset latency increased from 28 to 82 minutes).

The zolpidem group did not see any significant change in sleep efficiency or sleep onset latency. However, those participants showed signs of rebound insomnia after they stopped taking zolpidem.

As for the risk of abuse of zolpidem, Dr. Lee said: “We did not see any indication of abuse among the individuals who participated in our study. We monitored this via quantitative urine toxicology testing and remote medication adherence monitoring.”

Moving forward, he said, zolpidem “may have some efficacy as a short-term therapy for sleep disruption in a subset of cannabis users. More research is needed to further evaluate the efficacy of zolpidem or other hypnotic medications in individuals who differ in withdrawal severity or demographics.”

Dr. Lee said evaluating behavioral sleep treatments would be a logical next-step in light of his team’s data.

The National Institute on Drug Abuse funded the study. Three of the authors reported no relevant disclosures, and one reported consulting/advisory links to several drug companies and several state-licensed medical cannabis cultivation or dispensary businesses.

Next Article: