Tolerance to LSD, mescaline and psilocybin develops rapidly in man and animals, for some if not all behavioral effects.
In our initial efforts, we found that tolerance did not develop to unconditioned behavioral and EEG effects of DMT in cats administered DMT twice daily for 15 days or every 2 hours for 24 hours (34). Also, lack of behavioral tolerance has been reported in squirrel monkeys given DMT once daily for 38 days (35).
More recently, we studied the issue of tolerance in normal male volunteers who received 0.7 mg/kg of DMT intramuscularly twice daily for 5 days. Repeated administration did not consistently alter the peak blood concentration of DMT; autonomic changes in pupil size, pulse, or heart rate; the number of psychological items changed in a psychological scale; or the frequency of errors in a test requiring the subject to cross out a specific number in a list of random numbers. Three of the 4 subjects reported diminished subjective "highs" on a scale of 0 to 10 after two to four injections of DMT, but their subjective responses were variable from trial to trial and did not indicate a general loss of responsiveness to DMT. Rather, these subjects exhibited a variable or aperiodic partial tolerance to DMT. This pattern is reminiscent of Koella and associates' report of a cyclic change in ambulation produced by LSD in goats (36). Further studies, including longer or more frequent trials with DMT, are neccesary to fully evaluate this phenomenon.