Case Report Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report J. A. S. Crippa* MD, PhD, J. E. C. Hallak* MD, PhD, J. P. Machado-de-Sousa* PhD, R. H. C. Queiroz PhD, M. Bergamaschi PhD, M. H. N. Chagas* MD, MSc and A. W. Zuardi* MD, PhD *Department of Neuroscience and Behavior, Ribeira ˜o Preto Medical School, University of Sa ˜o Paulo and INCT Translational Medicine (CNPq) – Sa ˜o Paulo, and  Department of Clinical, Toxicological and Food Sciences Analysis, School of Pharmaceutical Sciences of Ribeira ˜o Preto, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil Received 16 July 2011, Accepted 24 September 2012 Keywords: (MeSH), cannabidiol, cannabis, substance withdrawal syndrome SUMMARY What is known and Objective: Cannabis withdrawal in heavy users is commonly followed by increased anxiety, insomnia, loss of appetite, migraine, irritability, restlessness and other physical and psychological signs. Tolerance to cannabis and cannabis withdrawal symptoms are believed to be the result of the desensitization of CB 1 receptors by THC. Case summary: This report describes the case of a 19-year-old woman with cannabis withdrawal syndrome treated with cannabidiol (CBD) for 10 days. Daily symptom assessments demonstrated the absence of significant withdrawal, anxiety and dissociative symptoms during the treatment. What is new and Conclusion: CBD can be effective for the treatment of cannabis withdrawal syndrome. WHAT IS KNOWN AND OBJECTIVE The current scientific literature shows that cannabis withdrawal effects are not uncommon in chronic users, disappear with the reintroduction of the drug and result from the deprivation of a specific cannabinoid: THC. 1 The onset of symptoms of the mari- juana withdrawal syndrome in chronic users typically occur between the 2nd and 6th day after withdrawal and usually reach their peak after 2 or 3 days. 1,2 This contributes to the diffi- culty in interrupting use and the persistence of abuse and dependence. 3 Among the various withdrawal symptoms, anxi- ety and insomnia are the principal manifestations and are con- sidered disruptive to daily living. Although there are over 160 million cannabis users worldwide today and despite the fact that cannabis dependence remains higher than that of any other illicit substance, no currently avail- able pharmacological therapy is considered adequate to treat cannabis use disorders. 3,4 Drugs that modulate the function of the endocannabinoid system may play an important role in the treatment of canna- bis dependence. Chronic exposure to cannabis leads to desensi- tization and reduced density of type 1 cannabinoid receptors (CB 1 ), eventually resulting in tolerance. 5,6 Animal experimental evidence shows that the CB1 receptor is involved in the development of dependence, as well as in the expression of abstinence symptoms. 7 Therefore, the replacement of low doses of CB1 receptor agonists, such as D 9 -THC, could be expected to reduce the severity of abstinence symptoms. Low doses of D 9 -THC with no significant intoxication effects were found to improve abstinence symptoms. 8,9 Nevertheless, even low doses such as the ones used in these studies have rein- forcing properties in chronic cannabis users, suggesting that THC-based treatment does not preclude the possibility of abuse. 10 An alternative to the use of D 9 -THC would be the potentia- tion of endocannabinoid transmission by inhibiting their degra- dation. Cannabidiol (CBD), one of the components of the cannabis plant that is devoid of psychoactive effects, inhibits the reuptake and hydrolysis of anandamide. 11 CBD has a broad spectrum of pharmacological effects, including anxiolytic, anti- psychotic, neuroprotective, anti-inflammatory and anti-emetic actions. 12,13 In addition to the effect of maintaining the stimula- tion of CB1 receptors by anandamide, CBD’s anxiolytic effects in men 14–17 and animals, 18,19 its antidepressant properties 20 and biphasic effects on sleep 21–23 can be useful in the treatment of cannabis abstinence. CBD has proven to be a safe drug with no significant adverse effects in humans, even with chronic use 24 and in high doses. 12,25,26 Based on these findings, we investigated the effects of CBD in a subject with cannabis dependence and a history of cannabis withdrawal syndrome. DETAILS OF THE CASE A 19-year-old woman had a history of heavy and continued use of cannabis, smoking 4–8 cannabis cigarettes per day since age 13. She would spend virtually all her money to get the drug, besides much time and effort. In the clinical evaluation, she reported memory, concentration and attention deficits that affected her academic and professional performance. The patient described that all her previous attempts to quit smoking cannabis were associated with increased anxiety, insomnia, loss of appetite, migraine, restlessness, irritability, nightmares and sweating. The symptoms appeared between 4 and 6 days after cessation and disappeared when use was resumed. She was diagnosed with cannabis dependence with the Structured Clini- cal Interview for DSM-IV (SCID-CV, 27 ). The diagnostic interview and subsequent assessments were performed by a clinical Correspondence: Jose ´ Alexandre S. Crippa, Hospital das Clı ´nicas - Terceiro Andar, Av. Bandeirantes 3900, 14048-900-Ribeira ˜o Preto - SP – Brasil. Tel.: +55 16 36022201; fax: +55 16 36022703; e-mail: jcrippa@fmrp.usp.br Journal of Clinical Pharmacy and Therapeutics, 2013, 38, 162–164 doi: 10.1111/jcpt.12018 ª 2012 Blackwell Publishing Ltd 162