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Mushrooms / Psilocybin

The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

March 1, 2011 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

Background: Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson’s disease.

Methods: To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement.

Results: Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations.

Conclusions: These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor–mediated visual hallucinations and aberrant modal object completion potential.

Kometer, M., Cahn, B. R., Andel, D., Carter, O. L., & Vollenweider, F. X. (2011). The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations. Biological Psychiatry, 69, 399–406. http://dx.doi.org/10.1016/j.biopsych.2010.10.002
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A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?

February 17, 2011 / History, Indigenous use, Mushrooms / Psilocybin, Papers, Publications / By / , , ,

Abstract

The Selva Pascuala mural, a work of post-Paleolithic rock art in Spain, contains fungoid figures herein hypothesized to depict neurotropic fungi, especially Psilocybe hispanica, a species that occurs in a neighboring region. This hypothesis is based on features of these figures related to fungal morphology, along with ethnographic analogy, and shamanistic explanations of rock art. If correct, this interpretation would support inference of prehistoric utilization of this fungus in the region. The mural represents the first direct evidence for possible ritual use of Psilocybe in prehistoric Europe.

Akers, B. P., Ruiz, J. F., Piper, A., & Ruck, C. A. P. (2011). A Prehistoric Mural in Spain Depicting Neurotropic Psilocybe Mushrooms?. Economic Botany, 65(2), 1–8. http://dx.doi.org/10.1007/s12231-011-9152-5
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Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

January 20, 2011 / Ayahuasca, Cacti / Mescaline, DMT, LSD, Mushrooms / Psilocybin, Neuroscience, Other subjects, Other substances, Papers, Psychiatry, Psychology, Publications / By / ,

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

Halberstadt, A. L., & Geyer, M.A. (2011). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), 364-381. http://dx.doi.org/10.1016/j.neuropharm.2011.01.017
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Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

January 3, 2011 / Anxiety disorders / PTSD, Depression, Mushrooms / Psilocybin, Mystical experiences, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety, Spirituality / By / , , , , , ,

Abstract

Context: Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer.

Objective: To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety.

Design: A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin.

Setting: A clinical research unit within a large public sector academic medical center.

Participants: Twelve adults with advanced-stage cancer and anxiety.

Main Outcome Measures: In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment.

Results: Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance.

Conclusions: This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field.

Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer. Archives of General Psychiatry, 68(1), 71-78. http://dx.doi.org/10.1001/archgenpsychiatry.2010.116
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Psychobiology of Drug-Induced Religious Experience: From the Brain 'Locus of Religion' to Cognitive Unbinding

November 13, 2010 / Ayahuasca, LSD, Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Papers, Psychology, Publications, Religious studies, Spirituality / By / ,

Abstract

The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the “fitness” of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

Nencini, P., & Grant, G. A. (2010). Psychobiology of Drug-Induced Religious Experience: From the Brain ‘Locus of Religion’ to Cognitive Unbinding. Substance Use & Misuse, 45(13), 2130–2151. http://dx.doi.org/10.3109/10826081003713803
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Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

September 20, 2010 / Mushrooms / Psilocybin, Papers, Psychology, Psychopharmacology, Psychosis, Publications, Safety / By / , , ,

Abstract

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 longterm 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 (45–315mg/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.

Studerus, E., Kometer, M., Hasler, F., & Vollenweider, F. X. (2010). Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. Journal of Psychopharmacology, 25(11), 1434-1452. http://dx.doi.org/10.1177/0269881110382466
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The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

September 10, 2010 / Cacti / Mescaline, Depression, DMT, Ketamine, LSD, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

Vollenweider, F. X., & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11, 642-651. http://dx.doi.org/10.1038/nrn2884
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Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV)

August 31, 2010 / Ketamine, MDMA, Mushrooms / Psilocybin, Other subjects, Papers, Psychology, Publications / By / , ,

Abstract

This paper describes a refinement of Dittrich’s Altered States of Consciousness questionnaire. This questionnaire is among the most widely used self-report questionnaires for retrospectively assessing subjective experiences induced by psychedelics and other psychoactive drugs. Using data collected over many years from 591 human volunteers, they factored the original four subscales developed by Dittrich into 11 new subscales. This new improved instrument will play an important role in more precisely defining the qualitative subjective experiences in research with psychedelics.

Background: The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC.

Methodology/Principal Findings: The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the ‘‘oceanic boundlessness’’ and ‘‘visionary restructuralization’’ factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups.

Conclusions/Significance: The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.

Studerus, E., Gamma, A., & Vollenweider, F. X. (2010). Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV). PLoS ONE, 5(8). http://dx.doi.org/10.1371/journal.pone.0012412
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The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research

February 26, 2010 / Ayahuasca, Cacti / Mescaline, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Other disciplines, Other subjects, Other substances, Papers, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By /

Abstract

The elimination of subjectivity through brain research and the replacement of so-called ‘folk psychology’ by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the ‘Decade of the Brain,’ this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs’ flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the ‘psychedelic experience’ draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology.

Langlitz, N. (2010). The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research. History of Human Sciences, 23(1), 37-57. http://dx.doi.org/10.1177/0952695109352413
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Psychedelics and the Human Receptorome

February 2, 2010 / Cacti / Mescaline, Chemistry, DMT, MDMA, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychopharmacology, Publications / By /

Abstract

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health – Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (Ki) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.

Ray, T. S. (2010). Psychedelics and the Human Receptorome. PLoS ONE, 5(2). http://dx.doi.org/10.1371/journal.pone.0009019
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14 May - Psychedelics & Psychosis with Phoebe Friesen and Dirk Corstens

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