Lithium carbonate in the management of cannabis withdrawal: a randomized placebo-controlled trial in an inpatient setting

Abstract

Despite the strong rationale for the present study, the efficacy of lithium over placebo in the management of cannabis withdrawal was not demonstrated.

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

“…Fragmentation is an indicator of sleep disruption or disturbance 34 and closely approximates the polysomnography measure of microarousals, which are associated with poor health outcomes. 35 While the findings that most sleep quality measures were not affected by lithium treatment is in line with our previous analysis of poor efficacy of lithium carbonate for the overall cannabis withdrawal indication, 20 the effects on fragmentation and nightmares does suggest a possible limited role of lithium in rectifying sleep disturbances during cannabis abstinence treatment. Sleep quality parameters during cannabis abstinence were not affected by the overall quality of self-reported sleep at study entry (baseline AIS scores), nor by baseline measures of plasma THC or oxytocin, similar to their effects on cannabis withdrawal in general.…”

“…Sleep quality parameters during cannabis abstinence were not affected by the overall quality of self-reported sleep at study entry (baseline AIS scores), nor by baseline measures of plasma THC or oxytocin, similar to their effects on cannabis withdrawal in general. 20 These factors may not have influenced sleep during cannabis abstinence owing to limited variability in this population.…”

“…18,19 This paper is a secondary analysis of data from a pharmacotherapy RCT testing the effects of lithium vs. placebo on cannabis withdrawal symptoms in an inpatient setting, which demonstrated no positive benefits of lithium on cannabis withdrawal symptoms. 20 As the study protocol allowed for a strictly limited amount of "rescue" medications, and the detox unit that we performed the study in used the hypnotic benzodiazepine nitrazepam as a matter of routine course for sleep disturbances, we opportunistically explore the impact of nitrazepam use on subjective and objective sleep outcomes. Nitrazepam has previously been shown to have dramatic effects on reducing nightmares, 21 which are one of the most prevalent and persistent cannabis withdrawal symptoms.…”

Endocannabinoids

“…However, a larger clinical trial recently published did not find any overall effects of lithium on withdrawal, although some of the individual withdrawal symptoms, including loss of appetite, stomach aches, and nightmares, were reduced (Johnston et al 2014). While this study concluded that there was no clear advantage of lithium over placebo, the timing of lithium administration was such that its concentrations may not have been in a therapeutic range during the period of greatest withdrawal and further studies are warranted.…”

Screening Medications for the Treatment of Cannabis Use Disorder

“…They found that lithium prevented withdrawal symptoms, that this effect was blocked when lithium was combined with an oxytocin antagonist, and that administration of oxytocin could also prevent precipitated withdrawal. However, when lithium was subsequently tested during withdrawal in treatment-seeking cannabis users, it prevented certain symptoms (loss of appetite, stomach aches, and nightmares/strange dreams), but it did not reduce overall withdrawal scores or increase (Johnston et al, 2014). …”