Monday, August 18, 2014

Intensification of LSD effects by reserpine, human studies

Certain drugs like reserpine and chlorpromazine, which are regarded as antipsychotics, do not always block LSD intoxication. In some cases, LSD responses are heightened after acute reserpine treatment. Three independent studies from 1957 to 1965 showed this was the case.

In 1965, Resnick studied drug-drug interactions between reserpine and LSD in three male volunteers. Reserpine (Serpasil) 500 mg/day was administered for two weeks, then each participant had a session with 75 ug LSD.
"All three subjects volunteered the information that, following reserpine treatment for two weeks, the experiences produced by LSD-25 were very markedly enhanced." (Resnick,O. 1965)
In an article from the American Journal of Psychiatry, the interactions between LSD and reserpine in patients with chronic schizophrenia were discussed. Freedman wrote,
"In collaboration with Benton, 14 chronically schizophrenic women were tested. Two days after 10 mg of reserpine the patients felt recovered from the reserpine; the only sign of an altered brain milieu was the miosis. They then received 120 ug LSD-25 and showed prolonged and toxic reactions: marked tremor and akathisia in the majority and in 1 an occulogyric crisis. Each felt the drug was less pleasant than her control LSD-25 and that the effects lasted longer." (Freedman,D.X. 1963)
In 1957, Isbell and Logan recruited 12 criminals who were serving sentences for violations of the Harrison Narcotic Act. The subjects reported that reserpine treatment did not block the LSD psychosis, and may make it worse.
“The combinations of reserpine and LSD were so disagreeable that the patients were persuaded to complete all the experiments only with the greatest difficulty. In addition to the usual symptoms experienced after LSD, the patients reported other symptoms, which seemed to be of two sorts: first, the usual side-effects of reserpine such as nasal stuffiness, nausea, diarrhea, vomiting, lethargy, weakness, and dizziness on standing, second, severer mental effects. The latter included nervousness and confusion, which exceeded that experienced after LSD alone." (Isbell,H. 1957)
Table 3 below shows the "patients worse" result, when given LSD plus reserpine.

Most of the human participants had a significant change in perception with reserpine plus LSD, and the evidence shown here is that reserpine gave no particular alleviation of the LSD effect. The unpleasant intensification of effects produced by reserpine plus LSD suggest that reserpine should be avoided prior to and during LSD use.

Reserpine releases 5-HT from bound form, and it is often cited for the monoaminergic depletion and depression theory, since it is known that normal people taking reserpine become clinically depressed. It is possible that the intensification of the LSD effect produced in combination with reserpine is somewhat like that produced when DMT and monoamine oxidase inhibitors are combined, because the chemical structure of reserpine somewhat resembles harmaline and yohimbine, which is an monoamine oxidase inhibitor.


Resnick O., D. M. Krus and M. Raskin (1965). Accentuation of the psychological effects of LSD-25 in normal subjects treated with reserpine. Life Sciences 4, 1433-1437. DOI:10.1016/0024-3205(65)90022-6

FREEDMAN D. X. (1963). Psychotomimetic drugs and brain biogenic amines. The American Journal of psychiatry 119, 843-850.

ISBELL H. and C. R. LOGAN (1957). Studies on the diethylamide of lysergic acid (LSD-25). II. effects of chlorpromazine, azacyclonol, and reserpine on the intensity of the LSD-reaction. A.M.A. Archives of Neurology and Psychiatry 77, 350-358.