The Effects of Lithium Carbonate Supplemented with Nitrazepam on Sleep Disturbance during Cannabis Abstinence.
OBJECTIVE
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 detoxification completion rates.


RESULTS
Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759-0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment.


CONCLUSIONS
Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only.
School of Psychology, University of Sydney, Sydney, NSW, Australia.|Discipline of Addiction Medicine, Central Clinical School, University of Sydney, NSW Australia.|The Langton Centre, Drug and Alcohol Services, South Eastern Sydney Local Health District, Surry Hills, NSW, Australia.
David J
DJ
Allsop
Woolcock Institute of Medical Research &University of Sydney, NSW, Australia.
Delwyn J
DJ
Bartlett
University Centre for Rural Health, University of Sydney, Lismore, NSW, Australia.
Jennifer
J
Johnston
Riverlands Drug and Alcohol Centre, Lismore, NSW, Australia.
David
D
Helliwell
Institute of Psychiatry, Kings College, London, UK.
Adam
A
Winstock
School of Psychology, University of Sydney, Sydney, NSW, Australia.
Iain S
IS
McGregor
Discipline of Addiction Medicine, Central Clinical School, University of Sydney, NSW Australia.|The Langton Centre, Drug and Alcohol Services, South Eastern Sydney Local Health District, Surry Hills, NSW, Australia.
Nicholas
N
Lintzeris
D000328:Adult; D002188:Cannabis / Q000009:adverse effects*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D016651:Lithium Carbonate / Q000494:pharmacology*; D008297:Male; D009567:Nitrazepam / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D016651:Lithium Carbonate; D009567:Nitrazepam
actigraphy; cannabis withdrawal; cannabis withdrawal scale; lithium; nitrazepam; pharmacotherapy; sleep disturbance