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

Introduction

Serotonergic hallucinogens such as LSD, mescaline and psilocybin produce a wide range of visual phenomena, from altered form and depth perception to vivid pseudo-hallucinations that may occur with the eyes closed (closed-eye visions, CEVs) or open (open-eye visions, OEVs). The mechanisms underlying these drug-induced visual changes remain poorly understood; prevailing explanations implicate (1) reduced sensory or perceptual fidelity, (2) abnormally increased cortical excitation, and/or (3) altered cognitive or top-down influences on perception. Previous work has linked visual hallucinations in other conditions to low-level visual deficits (for example, impaired contour detection), to abnormal excitation as in migraine or epilepsy, and to altered use of top-down cues for recognition. Baggott and colleagues set out to probe these putative mechanisms by administering 3,4-methylenedioxyamphetamine (MDA) to healthy, drug-experienced volunteers in a controlled laboratory experiment. The study tested whether MDA would produce self-reported hallucinogen effects (including CEVs and mystical-type experiences) and whether those visual reports would be associated with changes on perceptual tasks designed to index reduced sensory fidelity (contour integration and object recognition) and altered cortical excitability (tilt illusion). The authors therefore aimed to relate subjective visual phenomena to objective measures of perceptual organisation and early visual cortical processing.