Abstinence symptoms following oral THC administration to humans

Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral Delta(9)-tetrahydrocannabinol (THC) have be en reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day resident ial study, male (n=6) and female (n=6) marijuana smokers worked on five psy chomotor 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 wa s completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 22 00 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 amon g participants compared to placebo baseline. Tolerance developed to the sub jective effects of THC but not to its effects on food intake or social beha vior. Abstinence from THC increased ratings of "Anxious," "Depressed," and "Irritable," decreased the reported quantity and quality of sleep, and decr eased food intake by 20-30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses o f THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana u se.