Quantitative studies in humans on the antagonism of lysergic acid diethylamide by chlorpromazine and phenoxybenzamine

Abstract

In human volunteers, 198 trials were made to determine the threshold dose for recognition of lysergic acid diethylamide (LSD‐25) and the effect upon this of chlorpromazine and phenoxybenzamine. The threshold dose of LSD was determined to be 20 P‐g or 0.260 to 0.295 P‐g per kilogram. Chlorpromazine, in a dose of 25 mg., given 30 minutes beforehand or phenoxybenzamine, in a 10 mg. dose, given at the same time blocked recognition of this dose of LSD, i.e., raised the threshold. The same dose of chlorpromazine when given at the same time as or 30 minutes after LSD did not block this recognition. Neither chlorpromazine in this dosage nor phenoxybenzamine in doses up to 30 mg. had any significant physiologic or subjective effect. The results suggest that the mechanisms through which these compounds block the recognition of LSD are different from those producing their peripheral autonomic effects. Henry