Abstinence symptoms following oral THC administration to humans.

Dependence can develop at lower daily doses of THC than previously studied. In a 20-day residential study, 12 marijuana smokers received placebo, then 80 mg/day (20 mg four times daily) and 120 mg/day (30 mg four times daily) of oral THC. Both active doses increased ratings of "High," "Good Drug Effect," and "Willingness to Take Dose Again," and increased food intake by 35–45% while decreasing verbal interaction. Tolerance developed to subjective effects but not to effects on food intake or social behavior. Abstinence increased ratings of anxious, depressed, and irritable, reduced sleep quantity and quality, and decreased food intake by 20–30%. These changes suggest that alleviation of abstinence symptoms may contribute to maintaining daily marijuana use.

Study at a glance

Abstract

Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral delta9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in private or social recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1-3, 8-11, and 16-19. Active THC was administered on days 4-7 (20 mg qid) and on days 12-15 (30 mg qid). Both active doses of THC increased ratings of "High," "Good Drug Effect," and "Willingness to Take Dose Again" compared to baseline (days 1-3). THC also increased food intake by 35-45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of "Anxious," "Depressed," and "Irritable," decreased the reported quantity and quality of sleep, and decreased food intake by 20-30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.