Studies on lysergic acid diethylamide (LSD-25). III. Attempts to attenuate the LSD-reaction in man by pretreatment with neurohumoral blocking agents.

Interest in possible chemical transmission of impulses in the central nervous system has been increasing. The neurohumors involved include acetylcholine, 1,2 norepinephrine, 2-4 and serotonin. 4-6 These theories of central chemical synaptic transmission have led, in turn, to hypotheses which ascribe the psychosis induced by lysergic acid diethylamide (LSD-25) and other psychotomimetic drugs to derangements in central nervous system function because of competition with one or another of the neurohumors or, on the contrary, to accentuation of the effects of the neurohumors by the psychotomimetic agents. The greatest interest has centered on possible interactions of serotonin and LSD. Woolley and Shaw 5 and Gaddum 6 independently evolved a hypothesis which ascribes the LSD psychosis to competition between LSD and serotonin for receptor sites on or in neurons. This hypothesis, which might be termed the serotonin-deficiency theory, is based in part on the following evidence: Serotonin is found in brain, 6,7