title: Lithium carbonate in the management of cannabis withdrawal: a randomized placebo-controlled trial in an inpatient setting.
abstract: BACKGROUND
  Preclinical studies suggest that lithium carbonate (lithium) can reduce precipitated cannabinoid withdrawal in rats by stimulating release of the neuropeptide oxytocin, while two open-label studies indicate lithium may ameliorate cannabis withdrawal symptoms in humans.
  
  
  OBJECTIVE
  This study was conducted to examine the efficacy and safety of lithium in the inpatient management of cannabis withdrawal and to determine whether lithium affects plasma oxytocin and the rate of elimination of plasma cannabinoids during abstinence.
  
  
  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 given twice a day under double-blind randomized controlled trial (RCT) conditions. Primary outcomes included withdrawal severity [cannabis withdrawal scale (CWS)], rates of detoxification completion, and adverse events. Plasma cannabinoids, plasma oxytocin and serum lithium levels were measured repeatedly over admission. Follow-up research interviews were conducted at 14, 30, and 90 days postdischarge.
  
  
  RESULTS
  Lithium did not significantly affect total CWS scores relative to placebo, although it significantly reduced individual symptoms of "loss of appetite," "stomach aches," and "nightmares/strange dreams." No significant group differences were found in treatment retention or adverse events. Lithium did not increase plasma oxytocin levels nor influence the rate of elimination of cannabinoids. Both placebo- and lithium-treated participants showed reduced levels of cannabis use (verified by urinalysis) and improved health and psychosocial outcomes at 30- and 90-day follow-up relative to pretreatment baselines.
  
  
  CONCLUSIONS
  Despite the strong rationale for the present study, the efficacy of lithium over placebo in the management of cannabis withdrawal was not demonstrated.
authors.affiliation: Discipline of Addiction Medicine, University of Sydney, Camperdown, NSW, 2050, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Johnston
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lintzeris
authors.forename: David J
authors.initials: DJ
authors.lastname: Allsop
authors.forename: Anastasia
authors.initials: A
authors.lastname: Suraev
authors.forename: Jessica
authors.initials: J
authors.lastname: Booth
authors.forename: Dean S
authors.initials: DS
authors.lastname: Carson
authors.forename: David
authors.initials: D
authors.lastname: Helliwell
authors.forename: Adam
authors.initials: A
authors.lastname: Winstock
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001066:Appetite; D002186:Cannabinoids / Q000097:blood; D002188:Cannabis / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007297:Inpatients; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008385:Marijuana Smoking; D008875:Middle Aged; D010121:Oxytocin / Q000097:blood; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D002186:Cannabinoids; D016651:Lithium Carbonate; D010121:Oxytocin