Psychedelics probably alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6850 free-form testimonials about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to three-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Coanalyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.

Psychedelics are thought to alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6,850 free-form testimonials with 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to 3D coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite the variable subjective nature of hallucinogenic experiences, our pattern-learning approach delineated how drug-induced changes of conscious awareness (e.g., dissolving self-world boundaries or fractal distortion of visual perception) are linked to cortex-wide anatomical distributions of receptor density proxies. The dominant explanatory factor related ego-dissolution-like phenomena to a constellation of 5-HT2A, D2, KOR, and NMDA receptors, anchored especially in the brain's deep hierarchy (epitomized by the associative higher-order cortex) and shallow hierarchy (epitomized by the visual cortex). Additional factors captured psychological phenomena in which emotions (5-HT2A and Imidazoline1) were in tension with auditory (SERT, 5-HT1A) or visual (5-HT2A) sensations. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Simultaneously considering many psychoactive molecules and thousands of natural language descriptions of drug experiences our framework finds the underlying semantic structure and maps it directly to the brain. These advances could assist in unlocking their wide-ranging potential for medical treatment.

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With novel hallucinogens poised to enter psychiatry, we lack a unified framework for quantifying which changes in consciousness are optimal for treatment. Using transformers (i.e. BERT) and 11,816 publicly-available drug testimonials, we first predicted 28-dimensions of sentiment across each narrative, validated with psychiatrist annotations. Secondly, BERT was trained to predict biochemical and demographic information from testimonials. Thirdly, canonical correlation analysis (CCA) linked 52 drugs' receptor affinities with testimonial word usage, revealing 11 latent receptor-experience factors, mapped to a 3D cortical atlas. Together, these 3 machine learning methods elucidate a neurobiologically-informed, temporally-sensitive portrait of drug-induced subjective experiences. Different models’ results converged, revealing a pervasive distinction between lucid and mundane phenomena. MDMA was linked to "Love", DMT and 5-MeO-DMT to "Mystical Experiences", and other tryptamines to "Surprise", "Curiosity" and "Realization". Applying these models to real-time biofeedback, practitioners could harness them to guide the course of therapeutic sessions.

With novel hallucinogens poised to enter psychiatry, a unified framework for quantifying which changes in consciousness are optimal for treatment is needed. Using transformers (i.e. BERT) and 11,816 publicly-available drug testimonials, we first predicted 28-dimensions of sentiment across each narrative, and then validated these predictions with adjudication by a clinical psychiatrist. Secondly, we fine-tuned BERT to predict biochemical and demographic information from natural language testimonials of drug experiences. Thirdly, canonical correlation analysis (CCA) linked 52 drugs' receptor affinities with word usage, revealing 11 statistically-significant latent receptor-experience factors, each mapped to a 3D cortical atlas. Together, these machine learning methods elucidate a neurobiologically-informed, temporally-sensitive portrait of drug-induced subjective experiences. The models’ results converged, revealing a pervasive distinction between the universal psychedelic heights of feeling in contrast to the grim, mundane, and personal experiences with addiction and mental illness. MDMA was linked to "Love", DMT and 5-MeO-DMT to "Mystical Experiences" and “Entities and Beings”, and other tryptamines to "Surprise", "Curiosity" and "Realization". Applying these models to real-time biofeedback, practitioners could delicately calibrate the course of therapeutic sessions.