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Journal of Psychopharmacology Journal of Psychopharmacology http://jop.sagepub.com Lithium carbonate in the management of cannabis withdrawal in humans: an open-label study AR Winstock, T. Lea and J. Copeland J Psychopharmacol 2009; 23; 84 originally published online May 30, 2008; DOI: 10.1177/0269881108089584 The online version of this article can be found at: http://jop.sagepub.com/cgi/content/abstract/23/1/84 Published by: http://www.sagepublications.com On behalf of: British Association for Psychopharmacology Additional services and information for Journal of Psychopharmacology can be found at: Email Alerts: http://jop.sagepub.com/cgi/alerts Subscriptions: http://jop.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.co.uk/journalsPermissions.nav Citations http://jop.sagepub.com/cgi/content/refs/23/1/84 Downloaded from http://jop.sagepub.com at University of Sydney on May 27, 2009 Original papers Lithium carbonate in the management Journal of Psychopharmacology 23(1) (2009) 84–93 of cannabis withdrawal in humans: © 2009 British Association for Psychopharmacology ISSN 0269-8811 an open-label study SAGE Publications Ltd, Los Angeles, London, New Delhi and Singapore 10.1177/0269881108089584 AR Winstock National Drug and Alcohol Research Centre, University of New South Wales; and Drug Health Services, Sydney South West Area Health Service, Camperdown, New South Wales, Australia. T Lea National Drug and Alcohol Research Centre, University of New South Wales; and Drug Health Services, Sydney South West Area Health Service, Camperdown, New South Wales, Australia. J Copeland National Cannabis Prevention and Information Centre, University of New South Wales, Randwick, New South Wales, Australia. Abstract Cannabis is the most widely used illicit substance in the world. Estimates mean of 107 days following treatment. The mean percentage of days suggest that approximately 10–20% of cannabis users meet criteria for abstinent in the period between treatment cessation and follow-up was cannabis dependence and a significant proportion experience withdrawal 87.57%. Twenty-nine percent of participants (n = 5) reported continuous discomfort on cessation of use. To date, there has been an absence of any abstinence that was biochemically verified at follow-up. Agreement clinically validated treatments to manage withdrawal. The current study is between self-reported cannabis use and urinalysis at follow-up was an open-label trial exploring the utility of lithium carbonate for the moderate (κ = 0.47). Significant reductions in symptoms of depression and management of cannabis withdrawal symptoms in treatment seeking adult anxiety and cannabis-related problems were also reported. This study humans. In total, 20 participants were recruited to the study (19 men). All provides evidence for the potential clinical utility and safety of lithium in met DSM-IV cannabis-dependence criteria and had been smoking cannabis the management of cannabis withdrawal. A randomised, placebo- daily or almost daily for a mean 9 years. Participants were admitted to an controlled trial is recommended. inpatient detoxification facility and prescribed lithium 500 mg b.d. for 7 days. Cannabis withdrawal was assessed daily with the Marijuana Withdrawal Checklist (MWC). Two participants were withdrawn from the trial because of possible adverse effects. Sixty percent of participants Key words completed the 7-day treatment program. Follow-up was conducted at a depression; cannabis; dependence; lithium; withdrawal Introduction ment for cannabis as the main drug of concern increased from 4% in 1990 to 22% in 2004 (AIHW, 2005). Estimates suggest that approximately 10–20% of cannabis Cannabis is the most widely used illicit substance in Australia users meet criteria for cannabis dependence (Swift, et al., with approximately one-third of the population having ever 2001). In addition, there is a growing consensus concerning used it (AIHW, 2005). Worldwide its use is increasingly recog- the existence and clinical relevance of a distinct entity of can- nised as a source of morbidity, with recent concerns focusing nabis withdrawal (Smith, 2002; Budney, 2006; Budney and on its contribution to psychosis in young people (Degenhardt, Hughes, 2006). Recent clinical studies indicate that more than et al., 2003; Semple, et al., 2005; Fergusson, et al., 2006). In half of dependent cannabis users do experience several with- Australia more disability-adjusted healthy years of life were drawal symptoms on cessation of regular use (Copeland, estimated to have been lost in 1996 because of cannabis use et al., 2001a; Budney, et al., 2004; Vandrey, et al., 2005; Bud- and dependence (4416 years) than to HIV, Hepatitis B and ney and Hughes, 2006; Copersino, et al., 2006). Symptoms Hepatitis C combined (2189 years) (Mathers, et al., 1999). In commonly experienced include sleep difficulty, increased addition, there is a growing demand for cannabis treatment anger and aggression, decreased appetite and weight loss, irri- locally and internationally. In Australia, people seeking treat- tability, nervousness and anxiety, and restlessness (Budney, Corresponding author: Dr Adam R Winstock, Drug Health Services, Page Building, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, 2050, Australia. Email: [email protected] Downloaded from http://jop.sagepub.com at University of Sydney on May 27, 2009 Lithium and cannabis withdrawal 85 et al., 2004). As with other drug withdrawal syndromes, aver- function and poor literacy. Another seven were eligible and sive symptoms may be a barrier to attaining abstinence and either declined to participate or could not be contacted. One may motivate continued use through negative reinforcement participant was eligible and commenced on treatment but was for some users. Accepting the significant adverse psychological withdrawn on day 2 as he was administered an anti-emetic and physical consequences of chronic use, investigators have medication by a new medical officer, unaware that its adminis- begun to explore potential pharmacological interventions to tration would result in the patient being excluded from the address these symptoms and to support increased rates of absti- study. Therefore, data for this participant is not included. No nence. A number of medications have been initially examined participant reported that they had ever been prescribed lithium in recent years as adjuncts to managing cannabis withdrawal, before entering the study. including buspirone, bupropion, nefazodone, divalproex sodium and oral THC (Haney, et al., 2001; Haney, et al., 2003; Haney, et al., 2004; Levin, et al., 2004; McRae, et al., Assessment 2006; Budney, et al., 2007). With the exception of oral THC, Clients seeking treatment for cannabis use from counselling none of these medications have been found to be effective in services at Drug Health Services, SSWAHS are assessed by a reducing a broad selection of experienced symptoms. counsellor using a standard clinical assessment tool covering A preclinical study investigating the effects and mechanism drug use history, previous drug treatment, personal history, of lithium on cannabinoid withdrawal in rats reported that lith- treatment planning and evidence of intoxication, dependence ium inhibited the development of withdrawal symptoms in rats and withdrawal. During the study period, in addition to the pre-treated with a synthetic cannabinoid agonist (Cui, et al., standard assessment, counsellors completed a brief eligibility 2001). The authors proposed that it was increased oxytocin checklist with all cannabis clients presenting for treatment. Cli- levels, consequent with pre-dosing with lithium, which negated ents were eligible to participate if they were between the ages of the symptoms of the withdrawal syndrome. A subsequent small 18 and 55, met DSM-IV criteria for cannabis dependence in the (n = 9), community-based, open-label study of the effects of preceding 12 months, and identified experiencing withdrawal lithium on non-treatment seeking individuals, meeting DSM- symptoms as a barrier in achieving abstinence. Clients were IV criteria for cannabis dependence, reported a variable not eligible to participate if they: 1) were alcohol dependent; response (Bowen, et al., 2005). Lithium has been used exten- 2) used drugs other than cannabis more than twice weekly or sively within psychiatry for over 30 years and is effective in a injected drugs more than once a week; 3) had a history of range of affective disorders, most commonly in the manage- schizophrenia or psychosis; 4) were at significant risk of sui- ment of acute mania and as maintenance therapy for bipolar cide; 5) had abnormal liver, renal or thyroid function; 6) were affective disorder (Tondo, et al., 1998; Geddes, et al., 2004; currently prescribed antidepressant, antipsychotic or mood sta- Ferrier, et al., 2006). The findings of preclinical and human bilising medications; 7) were currently prescribed opioid phar- trials have not supported the role of other mood stabilising macotherapies or 8) had very poor literacy. Female clients, medications as potential therapeutic agents for the alleviation who were breastfeeding, pregnant or planning on becoming of cannabis withdrawal (Cui, et al., 2001; Haney, et al., 2004). pregnant in the following month, were not eligible to The current study is an open-label inpatient trial that aimed participate. to investigate the safety, acceptability and potential utility of Clients meeting
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