Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

A double-blind placebo-controlled study found that the hallucinogen MDA increases closed-eye visions and mystical-type experiences. People who had more intense visions tended to perform worse on tests of contour integration and object recognition, suggesting that drug-induced hallucinations may be stronger in individuals with poorer perceptual processing. This points to possible shared mechanisms with hallucinations in psychiatric and neurological conditions.

Study at a glance

Abstract

BACKGROUND: The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study. We found that MDA increased self-report measures of mystical-type experience and other hallucinogen-like effects, including reported visual alterations. MDA produced a significant increase in closed-eye visions (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition. CONCLUSIONS/SIGNIFICANCE: Drug-induced visions may have greater intensity in people with poor sensory or perceptual processing, suggesting common mechanisms with other hallucinatory syndromes. MDA is a potential tool to investigate mystical experiences and visual perception. TRIAL REGISTRATION: Clinicaltrials.gov NCT00823407.