Letters to the Editor
Lithium and Marijuana Withdrawal
Dear Editor:
Marijuana is the most frequently used illicit drug in North America. There are a many adverse effects to marijuana, and about 60% of chronic users experience withdrawal symptoms following abrupt cessation; however, there are no effective treatments for marijuana dependence (1,2).
We recently reported that lithium inhibits marijuana withdrawal symptoms in animals—probably through the activation of oxytocin neurons in the brain (3). Here we report on marijuana withdrawal symptoms following lithium administration to chronic users who responded to a newspaper advertisement. All participants gave signed informed consent.
This open pilot study included 7 men and 2 women (mean age 27.3 years, SD 7.3). On a Mini International Neuropsychiatric Interview (4,5), none met criteria for any Axis I DSM-IV disorder except for cannabis dependence. They had first smoked marijuana at age 16 years or under and had smoked marijuana 28 to 30 times in the past month. In 6 subjects, past attempts to quit lasted for a few days only and in 3 subjects, for a few weeks. After 1 to 2 days, they reported cravings several times daily, with the intensity rated as 10 out of 10 for 5 subjects and 7 to 9 out of 10 for 4 subjects. The most commonly reported withdrawal symptoms were irritability, anger, sleep difficulties, and craving to smoke. All had tried to quit recently, and none reported any confidence that they would be able to discontinue use.
Before starting the study, one subject smoked a single joint daily at bedtime; the rest smoked 4 to 15 joints daily. During the study, they were allowed to smoke marijuana on days 1 to 4 and encouraged not to smoke on days 5 to 10. Lithium was prescribed at 600 mg on day 4, 900 mg on days 5 to 8, and 600 mg on day 9. It was discontinued on day 10. Data were obtained from the Marijuana Craving Questionnaire. We used the Withdrawal Behavior Checklist to obtain ratings of 27 symptoms on a 4-point scale (6–8).
The sample was small, the response was variable, and 3 participants (one among the improved) admitted that they smoked occasional marijuana between days 5 and 10. Therefore, quantitative results are not meaningful. Two participants reported that lithium greatly improved their withdrawal symptoms, and 2 more reported that lithium helped, particularly with mood symptoms. Five subjects did not feel that lithium helped their withdrawal symptoms.
Lithium was well tolerated; however, the serum levels on day 9 (mean 0.45 mmol/L, SD 0.12) were below therapeutic levels, and the duration of use was only 6 days. It is possible that lithium might be more effective if used longer at the usual therapeutic levels. As noted, the study was small; further, there was no control group. Future studies should include interviews or questionnaires to elicit subthreshold mood symptoms and use an inpatient setting to prevent unauthorized marijuana use (7). To conclude, of 9 regular marijuana users, 4 felt that lithium improved withdrawal symptoms.
References
1. Budney AJ, Kandel DB, Cherek DR, Martin R, Stephens RS, Roffman R. College on problems of drug dependence meeting, Puerto Rico (June 1996): marijuana use and dependence. Drug Alcohol Depend 1997;45:1–11.
2. Johns A. Psychiatric effects of cannabis. Br J Psychiatry, 2001;178:116–22.
3. Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation. J Neurosci 2001;21:9867–76.
4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): American Psychiatric Association; 1994.
5. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, and others. The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:(Suppl 20):22–33.
6. Heishman SJ, Singleton EG, Liguori A. Marijuana Craving Questionnaire: development and initial validation of a self-report instrument. Addiction 2001;96:1023–34.
7. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl) 1999;141:395–404.
8. Brower KJ, Maddahian E, Blow FC, Beresford TP. A comparison of self-reported symptoms and DSM-III-R criteria for cocaine withdrawal. Am J Drug Alcohol Abuse 1988;14:347–56.
Rudy Bowen, MDCM, FRCPC
Joann McIlwrick, MD, FRCPC
Marilyn Baetz, MD, FRCPC
Xia Zhang. MD, PhD
Saskatoon, Saskatchewan
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