Psychedelic drugs and perception: a narrative review of the first era of research

Aday and colleagues set out to synthesise research from the first era of psychedelic science (roughly 1895–1975) that investigated how classic psychedelics alter perception. The authors note that LSD, psilocybin, mescaline and N,N-dimethyltryptamine (DMT) produce pronounced alterations in perception—most prominently visual effects—and that extensive early-to-mid 20th century work explored these phenomena prior to regulatory closures of the field. Contemporary laboratories have recently renewed interest in perceptual effects and mechanisms (for example implicating 5-HT2A receptors in imagery and visual-evoked potentials), but there was no single source compiling the older literature. To address that gap, the study is a widespanning narrative review that collates human (and some animal) studies from the first research era examining perception. The authors organised the material into major perceptual domains—vision (subdivided into physiological changes, low-level processing, and complex imagery), auditory processing, body schema and tactile processing, time perception, and other modalities (taste, olfaction, synesthesia)—and emphasise that methodological standards varied widely across the period and are addressed in a dedicated limitations section.

This paper is a narrative review of studies from the first era of psychedelic research, defined by the authors as 1895 through 1975. The authors conducted a broad literature search using multiple search engines (they report using three search engines and an extensive Google Scholar search) and included published studies and self-experiments representative of that historical period. Human samples were the primary focus except where animal data were explicitly reported. Included material covered physiological, behavioural and electrophysiological investigations across perceptual domains; the review grouped studies into the categories listed above rather than following a formal systematic review protocol. The authors acknowledge that reporting of methodological details in many primary studies was inconsistent (for example, variable reporting of screening procedures, routes of administration, blinding and dosage standardisation). Because this is a narrative synthesis, no formal meta-analytic pooling or standard risk-of-bias assessment is reported. The authors also compiled a supplementary table pointing readers to additional primary sources they identified, while noting that their search may not be exhaustive.

Vision: The largest body of early research concerned vision, with evidence spanning peripheral (retinal/ocular) effects through subcortical and cortical changes, and including both simple form/depth/motion alterations and elaborate closed-eye imagery. Peripheral-eye findings included markedly elevated drug concentrations in ocular tissue in some animal studies (one report noted LSD levels 18 times higher in the iris than in cortex in monkeys), pupil dilatation and ERG changes such as a prolonged rod-cone break in dark adaptation. Some animal work found increased spontaneous discharge rates in retinal ganglion cells (peaking 20–30 minutes post-injection and persisting an hour), and cortical-evoked potentials were attenuated when the optic nerve was severed in one study, suggesting retinal contributions. Against a peripheral-only account, several human and animal studies indicated central origins: blockade of drug-induced pupil dilation did not abolish visual distortions, occipital lesions attenuated visual phenomena on LSD, and blind but non-congenitally blind subjects sometimes reported LSD-related visual experiences, particularly if they had a history of spontaneous visual imagery. Subcortically, effects on the lateral geniculate nucleus (LGN) were inconsistent—both inhibition and excitation were reported, sometimes varying with dose—whereas cortical effects were more robust. Cortical findings included altered visually evoked potentials (VEPs) with reports of increased amplitude and decreased latency in some studies but attenuation in others, mixed effects on alpha rhythms (increases in some high-imagery individuals, decreases in others), and early evidence that psilocybin increases P1 amplitude. Simple visual processing: Early studies documented distortions of form, depth and motion—examples include raised apparent horizon and altered apparent verticality under LSD, and contraction of nearby visual space under psilocybin. Low-level thresholds were sometimes affected: LSD elevated visual thresholds in pigeons and analogous tasks in humans suggested diminished sensitivity. Closed-eye elementary visual imagery (EVI) commonly manifested as vivid, dynamic geometric patterns (gratings, lattices, tunnels, spirals, etc.). Colour perception was systematically probed in several studies: in one set of comparisons, 47% (9/19), 85% (17/20) and 45% (9/20) of participants reported altered shapes or colours on psilocybin, mescaline and LSD respectively; all three drugs increased colour evoked on a flicker task and generally impaired colour discrimination relative to baseline, with psilocybin showing significant effects in some analyses. Complex visual imagery: Psychedelics frequently produced vivid, often meaningful closed-eye visions and longer episodic scenographic imagery. Self-experiment reports described sharply focused, richly coloured scenes and symbolic content; the authors note that these effects are idiosyncratic and not readily reducible to standardised measures. Early investigators proposed cognitive contributors such as enhanced metaphorical or symbolic thinking. Auditory processing: Behavioural studies reported reduced auditory sensitivity, increased stimulus generalisation in some work, and typically slowed reaction times to auditory stimuli. Electrophysiological animal studies showed dose-dependent increases in auditory-evoked P1/N1 peak area, latency and amplitude with mescaline, and some human/auditory-cortex recordings reported increased auditory-evoked potentials under LSD. Notably, one study found that AEPs "disappeared" at the peak of DMT sessions and reappeared as effects waned. Auditory hallucinations were reported but appeared less frequent than visual phenomena; one early report cited about 35% incidence with mescaline in a sample, and many auditory effects resembled pseudohallucinations or distortions of veridical sounds. Early clinical commentators also emphasised the role of music in therapeutic sessions, reporting preferences for familiar music and noting that music could guide or deepen experiences. Body schema and tactile processing: Anecdotal distortions of body boundaries and size were common; quantitative data were limited but suggestive. For example, 10/14 participants given psilocybin reported changes in body size on a questionnaire, and dose-dependent body-image changes were reported from about 20 µg of LSD upward in one study. A controlled investigation using volumetric/distance tasks found LSD increased perceived head size while perceived arm length shortened, without analogous changes for external objects; drawings of bodies also increased in size under LSD in multiple reports. Tactile effects included paresthesia, altered temperature perception, numbness and tingling. Time perception: Findings were heterogeneous. The literature leans slightly towards overestimation of durations (a subjective slowing of time), but reports of time feeling faster, mixed effects, timelessness and null results also appear. Proposed reconciliations from the era included mood correlations and individual differences; the authors of the review emphasise that methodological variability (different tasks, possible motor confounds in tapping or reproduction tasks) likely contributed to inconsistency. Other modalities (taste, olfaction, synesthesia): Gustatory disturbances were reported in some studies—one LSD study recorded 33% reporting a "dry" taste, 19% "funny", and 8% "bitter"; another found altered taste in 6/23 (26%) participants. Olfactory hallucinations appear rare in the documented studies (for example, 6/59 patients with schizophrenia experienced olfactory hallucinations on mescaline in one report). Incidence of synesthesia varied greatly across reports: one analysis suggested roughly half of participants experienced synesthesia on LSD, whereas another study recorded 2/19, 2/20 and 3/20 reports of synesthesia for psilocybin, mescaline and LSD respectively. Experimental attempts to elicit consistent audio–visual pairings yielded visual brightening and dynamic patterns more often than stable synesthetic correspondences.

Aday and colleagues interpret the historical literature as demonstrating a concentrated research effort into the perceptual effects of psychedelics during the first era, with vision receiving by far the most attention. They conclude that both peripheral (retinal/ocular) and central (subcortical and cortical) mechanisms were investigated, but cortical effects—consistent with modern 5-HT2A-centred accounts—appear more prominent and more consistently reported. At the same time, the authors note unresolved discrepancies across studies, for example mixed findings on alpha oscillations and VEP directionality, which may reflect methodological heterogeneity, dose-dependent effects, and individual differences in imagery ability or attentional state. The authors emphasise several limitations of the primary literature that constrain confident interpretation: small sample sizes, variable or absent blinding and control procedures, inconsistent dosage reporting, diverse and sometimes rudimentary outcome measures, and the inclusion of self-experiments with attendant bias concerns. They stress that these historical practices can produce conflicting results and that contemporary researchers should examine primary sources closely before incorporating older findings. In terms of implications, the review is presented primarily as a resource to save modern investigators time and to prevent redundant research questions; the authors encourage revisiting specific unresolved topics (for example retinal/peripheral effects, the neural basis of closed-eye imagery, body-schema alterations, synesthesia and the role of music) using contemporary, preregistered, double-blind, placebo-controlled designs and modern neuroimaging and psychophysical methods. They also note potential clinical relevance for conditions such as hallucinogen persisting perception disorder (HPPD), while acknowledging that the early literature is insufficiently rigorous to support direct clinical claims.

The authors conclude that early psychedelic research produced a rich but methodologically varied body of evidence showing that classic psychedelics affect perception across multiple domains, especially vision. They highlight under-studied areas (body schema, synesthesia, gustation and olfaction) and call for modern, rigorous follow-up studies to reconcile discrepant findings and to elucidate mechanisms, while positioning their review as a curated guide to the historical literature for contemporary investigators.