Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal

Abstract

Background Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal. Methods Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad-libitum cannabis use and short-term cannabis abstinence (3 days). Placebo was administered at bedtime during one abstinence period (withdrawal test) and extended-release zolpidem, a non-benzodiazepine GABAA receptor agonist, was administered during the other. Polysomnographic (PSG) sleep architecture measures, subjective ratings, and cognitive performance effects were assessed each day. Results During the placebo-abstinence period, participants had decreased sleep efficiency, total sleep time, percent time spent in Stage 1 and Stage 2 sleep, REM latency and subjective sleep quality, as well as increased sleep latency and time spent in REM sleep compared with when they were using cannabis. Zolpidem attenuated the effects of abstinence on sleep architecture and normalized sleep efficiency scores, but had no effect on sleep latency. Zolpidem was not associated with any significant side effects or next-day cognitive performance impairments. Conclusions These data extend prior research that indicates abrupt abstinence from cannabis can lead to clinically significant sleep disruption in daily users. The findings also indicate that sleep disruption associated with cannabis withdrawal can be attenuated by zolpidem, suggesting that hypnotic medications might be useful adjunct pharmacotherapies in the treatment of cannabis use disorders.

The Effects of Lithium Carbonate Supplemented with Nitrazepam on Sleep Disturbance during Cannabis Abstinence

“…Similar observations were made by Vandrey, who also noted decreased sleep efficiency and increased sleep latency among 20 subjects in a controlled laboratory study. 10 An increase, rather than reduction in REM sleep was observed in the Vandrey study. It is uncertain whether the differences between these studies were due to participant variations or research-design differences.…”

“…[5][6][7][8] There is some evidence that pharmacotherapy during cannabis abstinence attenuates withdrawal related sleep disturbances, 9 including improvements in polysomnographic measures of sleep effi ciency (but not latency) with the nonbenzodiazepine GABA(A) receptor agonist zolpidem. 10 While there is a plethora of studies exploring self-reported sleep disturbances associated with cannabis withdrawal, there are very laboratory study examining the muscle relaxant baclofen and the antidepressant mirtazapine. 11 Mirtazapine improved sleep but was not effective in relation to withdrawal symptoms or relapse rates.…”

“…Vandrey and colleagues recently ran the first pharmacotherapy trial specifically targeting sleep disruption during cannabis withdrawal in an inpatient setting. 10 The researchers randomized 20 adults, using a within-subject crossover design of extended release of zolpidem, a non-benzodiazepine GABA(A) receptor agonist during short periods of cannabis abstinence. Zolpidem was found to attenuate symptoms of sleep disruption during cannabis withdrawal, but there was a trend for sleep to become progressively worse over the short three-day abstinence period.…”

“…4,5,9,10 Recent studies have demonstrated high endorsement frequencies on ratings of sleep disturbances across research and clinical treatment seeking samples (67% to 73% of adults and 33% to 43% of adolescents) lasting months after cessation of cannabis use. 6,10,[15][16][17] Clinically, this is an important issue warranting further attention as it is likely that sleep disturbance during withdrawal impacts on the success of the quit attempt or is associated with relapse. Thus the development of interventions to ameliorate sleep disturbances may improve outcomes in treatments for cannabis dependence.…”

Cannabis Use Disorders in Primary Care: Screening and Treatment Suggestions

“…42 Zolpidem was found to normalize sleep efficiency and improved self-reports of sleep quality, but had no effect on sleep latency abnormalities common in cannabis withdrawal. 43 Nitrazepam improved several objective sleep-related abnormalities but was not effective in improving subjective sleep symptoms. This may indicate that sedatives and/or hypnotics are an effective class to help with sleep-related abnormalities associated with cannabis withdrawal, but further research is required and likely this class of medication should be limited to the withdrawal period (i.e.…”