Effects Of Psilocybin Research Articles

Prediction of psilocybin response in healthy volunteers.

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

Current Research on the Human Experience of Spirituality Following the Ingestion of ‘Magic’ Psilocybin Mushrooms: An Annotated Bibliography for Social Workers and Other Health Care Professionals

Brief review of the current scientific research on the therapeutic effects of psilocybin and psilocin on humans, reported rates of use of psilocybin in the United States, the types of social and legal discrimination and stigma surrounding the illegal possession and use of psilocybin, benefits of psilocybin research for understanding affect regulation, dysregulation and psychosis, and providing internet-based resources for clinicians. Provides list of questionnaires and other research tools used to assess psilocybin-induced spiritual and mystical experiences.

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

Introduction: Coding of high-order cognition grounded onto spatial representation

Hallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that displays altered FC in depressive disorders. In this study, we investigated the effects of psilocybin on FC across the entire brain with a view to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin- relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and cortical areas, including elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interactions between 5-HT- and DA-regulated neural networks contribute to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis. The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation. This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 microg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects. Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin's "positive" psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug's "negative-type symptoms" associated with reduced arousal and vigilance. Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin's effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Effects of psilocybin on time perception and temporal control of behaviour in humans

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint. In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

Commentary on: Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance by Griffiths et al.

The study by Griffiths et al. is noteworthy both for the rigorousness of its design and execution, as well as the clarity of its results. It demonstrates that psilocybin can be safely studied in normal human beings who do not have a history of hallucinogenic drug use. As would be expected, during the psilocybin session participants showed perceptual changes and labile mood. It is striking that majority of the participants reported 2 months later that the psilocybininduced experience was personally very meaningful and spiritually significant. Indeed, most of them rated the psilocybin-induced experience as one of the top five most important experiences in their life. It is especially notable that participants reported that the drug produced positive changes in attitudes and behaviors well after the sessions, and these self-observations were consistent with ratings by friends and relatives. These participants were well-prepared for the psilocybin experience by an experienced monitor, who expressly stated that psilocybin might produce increased personal awareness and insight. However, it is clear that the effects of psilocybin were more than expectancy effects because the active drug control condition (40 mg of methylphenidate) did not produce similar effects on ratings of significance or on measures of spirituality, positive attitude, or behavior. The term psychedelic, when applied to drugs, implies that the drug experience is “mind-expanding.” The paper by Griffiths et al. illustrates the accuracy of this description for psilocybin, and I hope that this landmark paper will also be “field-expanding.” The report clearly demonstrates that we can objectively study the experiences reported by many to be profoundly spiritual and meaningful, and that we can investigate the long-term positive consequences for the individual’s attitudes and behavior. It will open the way to study the neural mechanisms responsible for these drugaltered states of consciousness. It is entirely conceivable that psychotropic agents that produce these experiences may have a role in the treatment of addictive states. Spirituality has long been a major component of the 12step approach to the treatment of alcoholism and other forms of drug addiction. Although the investigations of LSD for the treatment of alcoholism failed to show any clear-cut significant beneficial effects, the possibility that a spiritual experience, such as that reported in the present study, might be useful cannot be discounted. The set and setting in which the drug is administered may dramatically alter the drug experience. In the present study by Griffiths et al., the set was well-established for a positive experience by the preparatory sessions with the monitor, and the setting was one that was designed to produce an introspective state. This may be an important determinant of the experience and could well alter any possible therapeutic efficacy. The possibility of easing the ennui and anguish of impending death with agents such as psilocybin is also suggested in the study by Kast (1966) and those that are reviewed in the commentary of Professor Nichols. It is likely that psilocybin might have the same salutary effects. This is not an insignificant issue especially considering the large numbers of aging individuals in our society who may be in need of hospice care. In summary, I hope that this paper by Griffiths et al. renews interest in a fascinating and potentially useful class of psychotropic agents. The misuse of these substances that led to their control in Schedule I of the Controlled Substances Act cannot be allowed to continue to curtail their use as tools for understanding the neurobiology of Psychopharmacology DOI 10.1007/s00213-006-0460-x

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states.

529 The hallucinogen psilocybin increases prepulse inhibition of the startle reflex in healthy humans

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.

Methodological issues of human experimental research with hallucinogens.

Human experimental research with hallucinogenic drugs is potentially able to identify linking variables between the psycho(patho)logical conditions and neurobiological alterations involved in both pharmacologically induced and naturally occurring acute psychotic states. A number of methodological aspects should be considered when planning modern experimental studies with hallucinogenic drugs. The issues of subject selection, repeated measures, and adequate control groups are discussed in this paper. Examples of recent experimental studies are presented which take these aspects into account. The first study examined psychopathological changes, facial expression and semantic priming effects during a psilocybin-induced state. In the second study, semantic priming effects after intake of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE), and d-methamphetamine were investigated. Results confirmed time-dependent effects of psilocybin and the restriction of increased priming effects in the psilocybin group.

Anticholinergic Agents

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20 mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3 mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases.

Effects of psilocybin, dimethyltryptamine, mescaline and various allergic acid derivatives on the EEG and on photically induced epilepsy in the baboon ( Papio papio)

Following the demonstration that lysergic acid diethylamide (LSD) inhibits myoclonic responses to intermittent photic stimulation (ILS) in the baboon, some other hallucinogenic drugs and some “non-hallucinogenic” derivatives of lysergic acid have been tested for their effects on the EEG and on photically induced epilepsy in twenty-two adolescent baboons ( Papio papio ). Psilocybin (1–4 mg/kg) and dimethyltryptamine (2–4 mg/kg) produced marked autonomic effects, EEG changes consistent with a severe disturbance of consciousness and a complete abolition of myoclonic or paroxysmal EEG responses to ILS (thus closely resembling the effect of LSD, 40–100 μg/kg). Mescaline (up to 32 mg/kg) was relatively ineffective on both the background EEG and on the myoclonic responses to ILS. After methysergide (2–5 mg/kg), although the autonomic effects were less severe than after psilocybin, there were muscular hypotonia, an abnormal EEG and reduction or abolition of the epileptic responses to ILS. BOL 148 and methergoline appeared less potent than methysergide, but, at 4 mg/kg, both drugs abolished ILS-induced myoclonus. Averaged responses to flash stimulation showed that psilocybin resembled LSD 25 in modifying transmission in the afferent visual pathway, whereas methysergide, in doses blocking ILS-induced myoclonus, did not alter primary evoked responses in the visual cortex. It is suggested that a serotoninergic system is probably involved in the epileptic responses of the baboon to ILS. Après qu'il ait été démontré que chez le babouin le diéthylamide de l'acide lysergique (LSD) inhibe les réponses myocloniques provoquées par la stimulation lumineuse intermittente (SLI), quelques autres drogues hallucinogènes et quelques autres drogues “non hallucinogènes” mais dérivées de l'acide lysergique ont été testées afin de rechercher leur effet sur l'EEG et l'épilepsie provoquée par la lumière chez vingt-deux babouins adolescents ( Papio papio ). La psilocybine (1–4 mg) et la diméthyltryptamine (2–4 mg/kg) provoquent des modifications neurovégétatives importantes et électroencéphalographiques concomitantes avec un trouble sévère de la conscience et une abolition complète des myoclonies et des manifestations paroxystiques EEG induites par la SLI (résultats qui sont très proches des effets du LSD, pour des doses de 40–100 μg/kg). La mescaline (jusqu'à 32 mg/kg) est relativement inefficace, aussi bien sur le tracé EEG que sur les réponses myocloniques à la SLI. Après méthysergide (2–5 mg/kg), bien que les effets neurovégétatifs soient moins sévères qu'après psilocybine, il existe une hypotonie musculaire, un EEG anormal et une réduction ou une abolition des réponses épileptiques à la SLI. Le BOL 148 et la méthergoline apparaissent moins efficaces que la méthysergide mais, pour des doses de 4 mg/kg, les deux drogues abolissent les myoclonies induites par la SLI. Les réponses moyennes, obtenues par stimulation photique, montrent que la psilocybine ressemble au LSD 25 en modifiant la transmission le long de la voie visuelle afférente, alors que la méthysergide, pour des doses capables de bloquer les myoclonies induites par la SLI, n'altère pas les réponses primaires évoquées au niveau du cortex visuel. Ces résultats suggèrent qu'il est probable qu'un système sérotoninergique soit impliqué dans les réponses épileptiques du babouin à la SLI.

Effect of Psilocybin, LSD, and mescaline on small, involuntary eye movements.

The influence of Psilocybin, LSD, mescaline, or alcohol on physiological nystagmus was investigated. Eleven hundred eye-movement records served as control data. In 242 sessions, a significant, dose dependent increase in frequency and, to some extent, amplitude of saccades was found after the oral administration of 10–15 mg of Psilocybin, 120μg of LSD, or 450 mg of mescaline. These three drugs produced a characteristic square-wave pattern of saccades distinctively dissimilar from the saw-tooth pattern produced by alcohol. There was no difference between the control and placebo patterns. The recording of physiological nystagmus may provide a valuable biological parameter for studying the effects of various drugs.

The effects of psilocybin on a test of after-image perception.

It is demonstrated in double-blind conditions that Psilocybin significantly changes an objective measure of after-image perception and that the occurrence of these changes is highly correlated with reports of altered visual experience. A hypothesis of how this effect and the findings of others can be explained on the basis of decreased inhibitory function in visual mechanisms involved in the perception of color and detail is presented with the caution that other explanations are possible. This study, and others, indicate the importance of knowing the nature of any subjective visual disturbance at the time that objective visual functions are performed to facilitate understanding of the mechanisms involved in hallucinogenic effect.