Pharmacological Treatment of Cannabis Dependence
Both cannabis abuse and dependence are recognized in the United States’ Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Classification of Diseases, Tenth Revision (ICD-10). The number of individuals with cannabis-related disorders is twice that of any other illicit drug within the United States,  as four million people meet the criteria for a lifetime diagnosis of cannabis dependence. Unfortunately, for those who do seek help, relapse rates are comparable to those of other drugs of abuse. From the Department of Medical Biophysics and Nuclear Medicine at Hadassah Medical Organization at Ein Kerem in Jerusalem, A.M. Weinstein and colleague David Gorelick from the National Institute of Drug Abuse discuss treatment options for cannabis dependence in their article “Pharmacological Treatment of Cannabis Dependence.”
Cannabis intoxication is recognized in both the DSM-IV1 and the ICD-10.2 It is known to have psychological and behavioral manifestations, such as euphoria, relaxation, increased appetite, and impaired memory and concentration, as well as physical manifestations, like motor incoordination, tachycardia, and orthostatic hypotension. According to Weinstein and Gorelick, the most severe effects, such as anxiety, panic, and psychosis, are best treated with either a benzodiazepine or a second-generation atypical antipsychotic.6 Currently, there are no medicines approved specifically for the treatment of cannabis intoxication; however, several are currently being examined.6
Cannabis Withdrawal Syndrome
According to Weinstein and Gorelick, there is also such thing as cannabis withdrawal syndrome, established by several studies.6 In fact, it is even proposed for inclusion in the DSM-V. Some studies have stated that half of patients who are in treatment for cannabis use have experienced withdrawal symptoms, such as anxiety, irritability, depressed mood, restlessness, disturbed sleep, GI symptoms, and decreased appetite.6 Symptoms often begin during the first week of abstinence and resolve after a couple weeks.6 However, as symptoms of withdrawal may be negative reinforcement for relapse in individuals who are trying to abstain, pharmacological treatment may be needed to prevent relapse and reduce dependence.
Long-Term Cannabis Treatment
Weinstein and Gorelick state that one way to treat drug dependence is through long-term treatment with the same agonist drug or with a cross-tolerant drug so withdrawal effects and drug cravings are suppressed.6 Currently, these approaches are used with tobacco dependence (nicotine substitutions) and opiate dependence (methadone and buprenorphine).6 Studies are underway, examining certain forms of synthetic THC, which are legal in many countries as a medicine for appetite stimulation and suppression of nausea and vomiting due to chemotherapy.6
Another approach would be the antagonist approach, according to Weinstein and Gorelick.6 This approach uses long-term treatment with a CB1 antagonist, in order to prevent patients from experiencing the pleasurable effects of cannabis use.6 The result is to stop the drug-seeking behavior in patients.6 This has been seen as a successful approach with patients who are dependent upon opiates and are treated with naltrexone. Currently, no antagonists for the CB1 receptor are known.6
As dopamine (DA) is a major neurotransmitter that is involved in the brain’s meso-cortico-limbic reward pathway, involved in drug-seeking for all drugs of abuse, a DA deficiency could cause compulsion and craving. Therefore, regulating levels of DA is thought to decrease drug cravings.6 Studies are ongoing. 6 Also, according to Weinstein and Gorelick, buspirone shares properties with benzodiazepines, and in a 12-week study of 10 cannabis-dependent men, buspirone doses of 60 mg per day was shown to decrease the frequency and duration of cannabis craving and use.6 Therefore, buspirone is one of the only promising treatments for cannabis dependence thus far.6
According to Weinstein and Gorelick, receptor agonists, should they become available, would be an effective treatment for cannabis abuse and dependence, as would oral synthetic THC and buspirone.6Future studies should focus further on pharmacological treatments for cannabi
 American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. Artigas F, Nutt DJ, Shelton R. Mechanism of action of antidepressants. Psychopharmacol Bull. 2002; 36 Suppl 2:123–132.
 World Health Organization (WHO). Geneva: WHO; 2007. International Classification of Diseases, Tenth Revision (ICD-10) – Clinical Modification.
 United Nations Office on Drugs and Crime (ONODC). World Drug Report 2010. United Nations Office on Drugs and Crime. http://unp.un.org
 Stinson FS, Ruan WJ, Pickering R, Grant BF. Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. Psycholl Med. 2006; 36:1447–1460.
 Copeland J, Swift W, Roffman R, Stephens RS. A randomized controlled trial of brief cognitive–behavioral interventions for cannabis use disorder. J Subste Abuse Treat. 2001; 21:55–64.
 Weinstein, A.M. and Gorelick, D.A. (2011). Pharmacological Treatment of Cannabis Dependence. Curr Pharm Des; 17(14): 1351-1358.
 Jaffe, JH. Drug addiction and drug abuse. In: Gilman, AG.; Goodman, LS.; Murad, F., editors. The Pharmacological Basis of Therapeutics. 7th Edition. USA: Macmillan; 1985.
 American Psychiatric Association DSM V development. www.dsm5.org
 Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiat. 2006; 19:233–238.
 Comer SD, Sullivan MA, Yu E, Rothenberg JL, Kleber HD, Kampman K, Dackis C, O’Brien CP. Injectable, Sustained-Release Naltrexone for the Treatment of Opioid Dependence A Randomized, Placebo-Controlled Trial. ArcGen Psychiat. 2006; 63:210–218.
 Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci. 1992; 13:177–184. cannabis.