Tolerance to marihuana was investigated in two experiments. Four men were given smoke from 435 mg of marihuana (1.5 Δ-9-tetrahydrocannabinol [THC]) twice a day for ten days preceded and followed by three days of a placebo twice a day; three additional men were given a higher dose (2.8% THC).
Time estimation was disrupted on the higher dose and gradually improved. Heart rate increase did not show tolerance. Enhancement of postural cradiovascular responses, when present, decreased in duration in three subjects. One developed a brief toxic psychosis, another pneumonitis of uncertain etiology. Dysphoric and psychotoxic effects were evident as a cumulative effect of the high dose.
Three additional men were given the low dosage once a week for six to eight weeks, and time estimation and heart rate changes were similar to those seen with frequent administration at that dose. Tolerance, recently reported in man, probably requires more frequent administration or a different dosage than the schedules employed here.