Abstract
BackgroundThe 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 FindingsWe 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/SignificanceDrug-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 RegistrationClinicaltrials.gov NCT00823407
Highlights
Serotonergic hallucinogens —such as LSD, mescaline, and psilocybin— produce a bewildering variety of visual phenomena [1,2,3,4,5,6,7]
MDA was well tolerated by all participants and produced psychological effects consistent with hallucinogenic action along with robust physiological changes
Because anthropological evidence suggests that abstract visuals such as patterns occur before semantically-meaningful visuals during hallucinogen inebriation [1], we examined whether time of maximum change varied between patterns and other categories
Summary
Serotonergic hallucinogens —such as LSD, mescaline, and psilocybin— produce a bewildering variety of visual phenomena [1,2,3,4,5,6,7]. A third factor that may contribute to drug-induced hallucinations is alterations in cognitive functions – such as altered balance of topdown and bottom-up information [37] or impairment in perceptual inference [72] – which could lead to increased acceptance of expectations as reality. This possible mechanism can be tested by providing top-down cues for recognizing images. Hypotheses We predicted that MDA would induce self-report hallucinogen effects and that self-report visual changes would be accompanied by changes in one or more perceptual tasks designed to measure factors potentially contributing to hallucinations
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