Abstract

Combined histochemical and biochemical analysis revealed that psilocybin (5-50 mg/kg i.p.) and dimethyltryptamine (40-200 mg/kg i.p.) reduced the 5-hydroxytryptamine (5-HT) depletion in the brain and the spinal cord after amine synthesis inhibition, indicating reduced 5-HT turnover. This effect was not due to monoamine oxidase inhibition. The turnover of norepinephrine in the central nervous system was somewhat accelerated after the higher doses of psilocybin and dimethyltryptamine. In experiments on rat hindlimb reflexes, psilocybin (1-50 mg/kg i.p.) and N, N-dimethyltryptamine (10-50 mg/kg i.p.) caused changes similar to those seen after treatment with the 5-HT precursor 5-hydroxytryptophan, i.e., hyperextensions and athetoid movements. In this respect, tryptamine (50 mg/kg i.p.) was weakly effective and bufotenine (5-hydroxy-N, N-dimethyltryptamine) (50-100 mg/kg i.p.) was not effective. These findings indicate a 5-HT receptor stimulation by psilocybin and dimethyltryptamine in the same way as has previously been found for d-lysergic acid diethylamide (LSD), since the effects were independent of the known stores of 5-HT. The retardation of the 5-HT turnover after psilocybin and dimethyltryptamine may be caused by a negative feedback mechanism on the 5-HT neurons induced by the 5-HT receptor stimulation.