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

Abstract

Study Objectives: Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal. Methods: Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxifi cation completion rates. S leep diffi culties and cannabis use appears to be a bi-directional relationship. Individuals often start using cannabis when they experience sleep diffi culties during stressful times, often for coping reasons 1 ; and this is a risk factor for cannabis lapse (within the fi rst 2 days out of 7) following a self-guided quit attempt.2,3 The most prevalent sleep disturbances with cannabis withdrawal include diffi culty getting to sleep, staying asleep, nightmares and strange dreams, and night sweats.4 During the withdrawal process, sleep diffi culties predict relapse to cannabis use. [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 S C I E N T I F I C I N V E S T I G AT I O N Sfew that quantify sleep patterns using objective means, with the exception of the paper by Vandrey et al. 10 Poor sleep is often the last symptom to remit, and recent trials have started to specifi cally target sleep disturbances during withdrawal. Haney and colleagues conducted a small BRIEF SUMMARY Current Knowledge/Study Rationale: Sleep disturbance is the most consistent, prevalent, and severe symptom of cannabis withdrawal. However, there are currently no evidence-based medicines to assist with cannabis dependence or cannabis withdrawal. Study Impact: This formal RCT demonstrates that, contrary to positive open label clinical fi ndings, lithium carbonate does not improve cannabis withdrawal related sleep disturbances. However, the hypnotic benzodiazepine rescue medication nitrazepam signifi cantly improved multiple objective measures of sleep disturbance during cannabis withdrawal.

What do we know about the pharmacotheraputic management of insomnia in cannabis withdrawal: A systematic review

“…Acute cannabis withdrawal is a valid disorder, but far from being well understood. Withdrawal symptoms usually last up to 2 weeks; however, several studies reported continuation of these symptoms for 1–3 months with sleep being one of the consistently reported persisting withdrawal symptoms . In our review, none of the studies made a distinction between sleep disturbance as part of the withdrawal syndrome and cannabis induced sleep disorder as a separate phenomenon as described by DSM‐5 .…”

“…Cannabis withdrawal symptoms are most pronounced in the first 2 weeks post cessation, with some studies reported symptoms up to 12 weeks . Studies have shown that sleep difficulties occur in 67–73% of adults and 33–43% of adolescents following the cessation of chronic daily cannabis use . Symptoms reported by patients mainly include poor sleep quality, insomnia and strange dreams.…”

“…Polysomnographic studies of cannabis withdrawal have shown increases in wakefulness and sleep‐onset latency, and decreases in total sleep time, efficiency, and slow wave sleep . Sleep disturbance has been reported as one of the most severe and common cannabis withdrawal symptoms, which may persist beyond the acute withdrawal phase . There is a breadth of evidence to support that sleep difficulties following cannabis cessation play a crucial role in predicting treatment outcome and is a risk factor for relapse .…”

Cannabis Use Disorders in Primary Care: Screening and Treatment Suggestions

“…Lithium carbonate was not helpful in managing sleep disturbances. 44 Gabapentin at 1200 mg per day improved withdrawal symptoms in a small study of adults and improved cognitive functioning. 45 In adolescents, emerging evidence seems to point to a role of Nacetyl-cysteine (NAC) in establishing abstinence.…”

“…12, 13 The onset of withdrawal is typically 24-48 hours after last use and peaks at 4-6 days. The total duration, as a result of the intense fat solubility of THC, is 1-3 weeks.…”