Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans

This interview study (n=32) from 1996 investigated the effects of antidepressants on self-administered LSD. 28 participants who had been taking SSRIs for over 3 weeks reported a subjective decreased response to LSD.

Abstract

“This study investigates the possible interactions of antidepressant agents and hallucinogens in humans through structured interviews using a standardized questionnaire. Volunteer subjects recruited through announcements placed on the Internet or other sources were asked to describe the somatic, hallucinatory, and psychological effects of self-administered LSD prior to and during chronic administration of an antidepressant. Twenty-eight out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin (5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. An additional subject who had taken fluoxetine for only 1 week had an increased response to LSD. These data are in contrast to our previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium. Possible mechanisms of action for the effects from serotonergic antidepressants involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems.”

Authors: K. R. Bonson, J. W. Buckholtz & D. L. Murphy

Summary of Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans

Although recent reviews have focused on interactions of antidepressants with other medically prescribed drugs, less attention has been paid to the interactions of antidepressants with drugs that are used in a social or recreational manner.

Early clinical investigations demonstrated that chronic administration of monoamine oxidase inhibitors (MAOis) or nialamide markedly attenuated the subjective experiences of humans to LSD. Two individuals who were chronically taking MAOis also described diminished responses to LSD, whereas eight other individuals taking lithium or tricyclic antidepressants had exaggerated responses.

Methods

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Study details

Compounds studied
LSD

Topics studied
Safety

Study characteristics
Open-Label

Participants
32 Humans

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