Statements like cannabis-related “tolerance and physical dependence do not occur” are commonly made in standard pharmacology texts. l The summary report of the National Commission on Marihuana and Drug Abuse, when discussing the “addiction potential” of marijuana concluded that “fact and fancy have become irrationally mixed regarding marijuana’s physiological and psychological properties. Marijuana clearly is not in the same category as heroin insofar as its physiologic and psychological effects are concerned. In a word, cannabis does not lead to physical dependence.” A recent book that describes extensive chronic marijuana studies in man does not even mention the possibility of dependence. 3 Yet, after a comprehensive review of various aspects of cannabis tolerance and dependence, Wikler thinks the evidence indicates that both tolerance and dependence can develop in man. 4 For some years, we and others have noted, in outpatient studies, that very frequent cannabis users show diminished drug effects when compared to less frequent users, 5-though not all investigators agree.? Such indirect evidence of tolerance, of course, could be explained by several alternate hypotheses: personality or genetic differences, other drug use, and so on. Clinical reports of an abstinence syndrome associated with cannabis use are rare. Occasionally, very frequent cannabis users tested in our laboratories have reported the sudden onset of irritability, restlessness, insomnia, and perspiration after cessation of regular use. s Other investigators have reported similar signs and symptoms in small groups of cannabis users and in primates after prolonged high doses of cannabi~.~-l~ Such reports from outpatients should be viewed with some skepticism because of the possibility that these symptoms represent withdrawal from other drugs or concurrent illness. Possible species differences in drug response make the animal data open to question. Williams et al. reported several years ago that experimental subjects given frequent doses of cannabis or synhexyl compound reported a jittery feeling, insomnia, decreased appetite, weight loss, and autonomic symptoms when the experimental drug administration was suddenly st0pped. 1~ In more recent studies of chronic marijuana smoking, Mendelson et d’s experimental subjects experienced rapid weight loss, decreased appetite, tremor, increased urine specific gravity, and irritability after a 21-day period of frequent marijuana smoking. However, the signs and symptoms were not interpreted