Psilocybin and visual perception

“The hallucinogenic serotonin(1a&2a) agonist psilocybin is known for its ability to induce illusions of motion in otherwise stationary objects or textured surfaces. this study investigated the effect of psilocybin on local and global motion processing in nine human volunteers. using a forced choice direction of motion discrimination task we show that psilocybin selectively impairs coherence sensitivity for random dot patterns, likely mediated by high-level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors. these results are in line with those observed within schizophrenic populations and are discussed in respect to the proposition that psilocybin may provide a model to investigate clinical psychosis and the pharmacological underpinnings of visual perception in normal populations.”

“Enhanced color perception and vividly colored visual hallucinations are frequently reported by persons treated with psyehotomimetie drugs (klt~ve~ 1942; landis and clavson, 1954; a]3~a~so~ et al., 1955a; a]3ramson et al., 1955b). these findings are not explained readily by neurophysiologie or psychophysiologie studies of the action of these drugs. in this respect, the vivid and unusual experiences of color asso-ciated with lysergic acid diethylanfide (lsd-25) or mescaline intoxi-cation seem paradoxical in view of evidence of increased thresholds for axonal response beyond the thalamic synapses (evarts, 1955; bishop, 1958), and demonstrations of increased absolute and differential limens for vision (carlson, 1958). if anything, these data suggest that the marked visual effects associated with the action of the psychotomimetie drugs are not due to increased sensitivity to the normally adequate stimuli for color visual experience. some clues to this apparent paradox are provided by the facilitating effects of sensory input from other modalities on the perception of visual hallucinations, commonly referred to as synesthesia. in such cases, perceptual responses may be evoked by stimuli which ordinarily evoke a separate sensory response, for example, sounds evoking colored patterns. one might hypothesize that some psychotomimetics interfere with the normal integration of experience within specific sensory modalities. the way we chose to test this hypothesis was to study the effects of stim-uli varying in degree of adequacy for evoking color experience, both before and during the administration of three psyehotomimetie drugs. the stimuli employed included those directly involving color perception (discrimination of hues and reports of colors of after-images), those usually marginal in terms of color experience (gazing at an episcotister),”

“Research is presented on the altered sensory and cognitive processing as assessed by event-related potential analysis of electroencephalographic data during states of meditation in long-term meditators and due to the effects of psilocybin, a naturally occurring serotonin receptor agonist with hallucinogenic properties. the literature on the neurophysiologic correlates to meditation are reviewed. in a passive auditory oddball paradigm rare tones and distracters are shown to evoke increased sensory processing as indexed by increases in the amplitudes of the n1 and p2 event-related potential components. the distracter stimuli are shown to evoke a later p3a component and increases in frontal theta power associated with attentional engagement. meditation causes a significant reduction in the p3a amplitude and frontal theta power to distracting stimuli implying the disengagement of attentional networks from ongoing sensory processing. psilocybin is shown to cause enhanced early sensory processing of visual stimuli as indexed by the p1 component. this psilocybin-induced alteration is shown to be especially prominent in the brain’s response to distracting stimuli in a visual target detection paradigm. psilocybin is also shown to decrease intermediate object-recognition processing as indexed by the n170 event-related potential. while n170 amplitude is increased due to the perception of illusory contours, psilocybin induces a brain state where fewer additional resources are recruited to the perception of illusory contours. later p3 amplitudes associated with detection and response-related processing as well as distracter processing are shown to be significantly reduced by psilocybin, supporting the notion that attentional networks are disengaged from ongoing sensory processing. psilocybin inhibits the increase in frontal theta activity associated with the perception of illusory contours and visual distracters, adding further support to the model of meditation-induced attentional disengagement. a preliminary model of psilocyb-ininduced changes in neurophysiology and integrative comments on the significance of the similarities and differences between the effects of meditation and psilocybin on the brain’s attentional systems are provided. (psycinfo database record (c) 2012 apa, all rights reserved)”

“Psilocybin is a substance of natural origin, occurring in hallucinogenic mushrooms (most common in the psilocybe family). after its synthesis in 1958 research began on its psychoactive properties, particularly strong effects on visual perception and spatial orientation. due to the very broad spectrum of psilocybin effects research began on the different ranges of its actions–including the effect on physiological processes (such as eye saccada movements). neuro-imaging and neurophysiological research (positron emission tomography-pet and electroencephalography-eeg), indicate a change in the rate of metabolism of the brain and desync cerebral hemispheres. experimental studies show the changes in visual perception and distortion from psilocybin in the handwriting style of patients examined. there are widely described subjective experiences reported by the subjects. there are also efforts to apply testing via questionnaire on people under the influence of psilocybin, in the context of the similarity of psilocybin-induced state to the initial stages of schizophrenia, as well as research aimed at creating an ‘artificial’ model of the disease.”

“Several major conceptual problems regarding specific in vivo functions of the tgf-beta family members remain the key focus of many researchers studying the biology of these secreted signaling molecules. more than 45 members of this family of growth factors have been identified and partially characterized for their molecular roles in numerous processes such as cell proliferation and differentiation, embryonic development, carcinogenesis, immune dysfunction, inflammation and wound healing. the high degree of similarity that exists at the structural level among the isoforms of these growth factors is accompanied by a significant overlap in function, as defined by many in vitro model systems and in vivo systems involving administration of exogenous ligand or of ligand-specific blocking antibodies. the ability to discern the critical functions of these molecules based on patterns of expression has also often been quite difficult. the evolution of more sophisticated functional genomics approaches has been recently instrumental in generating unique perspectives into the mechanisms governing the activity of the members of the tgf-beta family. the studies outlined in this review are significant in that they not only support working hypotheses regarding the activities of tgf-beta generated through extensive in vitro studies but also raise new questions regarding the role of each isoform in numerous processes. with the rapid advances in these approaches to probe activity in a more cell and time-dependent fashion, we will gain valuable insights for designing approaches for targeting the complex cellular pathways mediating their responses and will also help us develop novel therapies to treat disease processes”

“Serotonergic hallucinogens, such as lysergic acid diethylamide (lsd), psilocybin, and n,n-dimethyltryptamine (dmt), are famous for their capacity to temporally and profoundly alter an individual’s visual experiences. these visual alterations show consistent attributes despite large inter- and intra-individual vari- ances. many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment (‘visual intensifications’). environmental objects might be altered in size (‘visual illusions’) or take on a modified and special meaning for the subject (‘altered self-reference’). subjects may perceive light flashes or geometrical figures containing recurrent patterns (‘elementary imagery and hallucinations’)influenced by auditory stimuli (‘audiovisual synesthesia’), or they may envision images of people, animals, or landscapes (‘complex imagery and hallucinations’) without any physical stimuli supporting their percepts. this wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. starting with mechanisms that act at the cellular level, the key role of 5-ht2a receptor activation and the subsequent increased cortical excitation will be considered. next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hal- lucinations. the decrease of alpha oscillations by hallucinogens will then be intro- duced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. finally, the hallucinogen-induced parallel decrease of the n170 visual evoked potential and increased medial p1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications”

“Mescaline, lysergic acid diethylamide (lsd-25) and psilocybin were studied in 20 screened subjects, 18 receiving all three drugs. drugs were administered under similar test conditions, doses were constant between drugs and subjects, assignments to drug followed a latin-square sequence, and subjects were unaware of the drug given on each trial. clinical syndromes were assessed by a questionnaire completed by the subjects following each drug trial. color perception was studied by means of both adequate and inadequate stimuli for eliciting color phenomena, measurements being taken before and two hours after drug was administered. a number of selected biochemical and physiologic measurements were also made at similar times. clinical syndromes were comparable in kind and degree from all three drugs, that from mescaline being most pronounced. somatic manifestations predominated, psychotomimetic symptoms (other than visual hallucinations) being relatively uncommon. color perception was not much altered when adequate stimuli were used, but color phenomena were appreciably enhanced from inadequate stimuli. minor differences in color perceptual effects were noted between the three drugs, but similarities were greater. each of the three drugs significantly decreased urinary excretion of inorganic phosphorus, increased plasma free fatty acids and decreased total circulating eosinophils. of the other biochemical measurements made, only one other significant change was noted; an increase in copper oxidase activity after psilocybin. the three psychotomimetic drugs were quite comparable in the areas studied. one might assume that they have many common mechanisms of action despite their chemical differences. © 1962.”

“Hallucinogen-persisting perception disorder (hppd) is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. hppd was associated with a broader range of lsd (lysergic acid diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (mdma), psilocybin, mescaline, and psychostimulants. the recent emergence of novel psychoactive substances (nps) posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of hppd. symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. although hppd was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the diagnostic and statistical manual of mental disorders (dsm-iv-tr). hppd neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. a critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward hppd, including the association with some novel substances, are provided here, by means of a literature search on pubmed/medline, google scholar, and scopus databases without time restrictions, by using a specific set of keywords. pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.”

“Botanical preparations used by shamans in rituals for divination, prophecy, and ecstasy contain widely different psychoactive compounds, which are incorrectly classified under a single denomination such as ‘hallucinogens,’ ‘psychedelics,’ or ‘entheogens.’ based on extensive ethnopharmacological search, i proposed a psychopharmacological classification of magic plants in 1979. this paper re-evaluates this taxonomy in the context of consciousness research. several groups of psychodysleptic magic plants are proposed: (1) hallucinogens-psilocybin mushrooms, mescaline cacti, dimethyltryptamine snuffs, and the synthetic ergoline lysergic acid diethylamide induce strong perceptual changes, affective intensification, and cognitive enhancement. their ethnobotanical uses include long lasting divination rituals, prophecy, and sacramental practice. (2) trance-inducers-ergoline convolvulaceae and south american banisteriopsis produce quietness, abstraction, lethargy, mild sensorial and cognitive changes, and salient visual imagery changes used in trance rituals and specific divination practices. (3) cognodysleptics-marijuana (tetrahydrocannabinol) and other terpene-containing plants induce changes in thought, imagination, and affective functions and are used in short-term divination or oneiromancy. (4) deliriants-tropane-containing solanaceae, wild tobacco, and amanita muscaria (muscimol) induce a delirium characterized by dim and clouded consciousness, stupor, confusion, disorientation, perception distortion, difficulties in recollection, anxiety, irritability, excitation, and behavioral disorganization employed in sorcery, purification, or exorcism rituals. the core mental effects required for a drug to be used in shamanistic rituals include light-headedness, enhanced imagery, and experience intensification. this constellation was the reason why, in his classification of psychoactive compounds, the pioneer german psychopharmacologist louis lewin established in 1924 a group of drugs under the appropriate name of phantastica. springer science+business media b.v. 2010.”

“Reactions caused by i. m. administration of 0.75 mug./kg. and 1.5 mug./kg. of lysergide (lsd) were compared with those caused by mescaline (2.5 and 5.0 mg./kg.) in the same 10 subjects. both drugs caused pupil dilatation, rise of temperature, pulse rate and systolic blood pressure, and lowering of threshold for elicitation of the knee-jerk. similar abnormal mental states (anxiety, difficulty in thinking, mood changes – generally euphoric, altered sensory perception – particularly visual, and alterations of body image) were reported by the subjects after both drugs. effects of mescaline appeared more slowly and persisted somewhat longer than those of lysergide. weight for weight, lysergide tartrate is 2400-4900 times as potent as mescaline; on a molecular basis lysergide is 4500-9275 times as potent as mescaline. patients receiving lysergide daily developed direct tolerance to lysergide and were also cross-tolerant to mescaline, and vice versa. it is inferred that lysergide,psilocybin and mescaline probably share common mechanisms of action or some common final pathway.”

“Background: in the visual backward masking paradigm, the visibility of a visual target is disrupted by the presence of a mask that is presented after the target. studies using backward masking suggest that conscious and nonconscious responses to complex emotional stimuli (facial expressions) occur via parallel cortical and subcortical circuits [1]. subliminally (nonconscious) presented fearful faces were found to enhance early event-related potentials (erps) like the n170 component, whereas supraliminal (conscious) perception of fearful stimuli was associated with enhanced responses for later components (i.e., n400). although many studies investigated neuronal correlates of facial perception, little is known about specific neurotransmissions during these processes. emotional (facial) processing is disrupted in schizophrenia patients, and there is evidence that serotonergic (5-ht) neurotransmission is involved in the modulation of emotional face processing [2]. to investigate the influence of 5-ht on processing of emotional stimuli the present study assessed erps evoked by emotional facial expressions (happy/fearful) in healthy volunteers receiving a single dose of the psychotomimetic and 5-ht1a/2a agonist psilocybin. methods: in a double-blind, placebo-controlled within-subjects design, 13 healthy volunteers received either psilocybin (115 mug/kg p.o) or placebo in a balanced and random sequence. on drug peak effect (80 min) subjects underwent backward masking test using visual stimuli of emotional (happy/fearful) and neutral facial expression (taken from the ekman-friesen series [3]). targets were happy/fearful and neutral faces presented subliminal (10 ms) or supraliminal (200 ms), and were backward-masked by a neutral face. eeg was acquired at 512 hz using the activetwo system (biosemi, the netherlands) with 64 equally-spaced scalp electrodes (10-20 system). the mean values for the n170 component from the electrodes po7/8 were subjected to a 3 (emotion) x 2 (treatment) repeated measures anova separately for sub- and supraliminal presentation times. upon significant interactions or main effect of the factor ‘emotion’ post-hoc pair-wise comparisons were conducted using fisher’s least significant difference (fisher lsd). the significance level was set to p<0.05. results: subliminal processing: compared to placebo treatment with psilocybin reduced n170 amplitude (p<0.05). furthermore, also the main effect of factor ‘emotion’ (p<0.05), but not the interac…”

“© 2016 bentham science publishers. hallucinogen persistent perception disorder (hppd) is considered an ‘uncommon’ disorder described in association with use of hallucinogens such as lsd, mescaline and psilocybin. despite multiple mentions of persistence of visual disturbances reported by users on online forums, clinicians may not be aware of this complication. there have been few descriptions of hppd in association with use of new psychoactive substances (such as 2c-e). increasing use of these designer stimulants places greater numbers at risk for psychiatric morbidities including hppd. here we report the first documented case of hppd due to high dose 2c-e and blunting of symptoms with addition of lamotrigine.”