OPEN Foundation

Mushrooms / Psilocybin

Peak Experiences of Psilocybin Users and Non-Users

Maslow (1970) defined peak experiences as the most wonderful experiences of a person’s life, which may include a sense of awe, well-being, or transcendence. Furthermore, recent research has suggested that psilocybin can produce experiences subjectively rated as uniquely meaningful and significant (Griffiths et al. 2006). It is therefore possible that psilocybin may facilitate or change the nature of peak experiences in users compared to non-users. This study was designed to compare the peak experiences of psilocybin users and non-users, to evaluate the frequency of peak experiences while under the influence of psilocybin, and to assess the perceived degree of alteration of consciousness during these experiences. Participants were recruited through convenience and snowball sampling from undergraduate classes and at a musical event. Participants were divided into three groups, those who reported a peak experience while under the influence of psilocybin (psilocybin peak experience: PPE), participants who had used psilocybin but reported their peak experiences did not occur while they were under the influence of psilocybin (non-psilocybin peak experience: NPPE), and participants who had never used psilocybin (non-user: NU). A total of 101 participants were asked to think about their peak experiences and complete a measure evaluating the degree of alteration of consciousness during that experience. Results indicated that 47% of psilocybin users reported their peak experience occurred while using psilocybin. In addition, there were significant differences among the three groups on all dimensions of alteration of consciousness. Future research is necessary to identify factors that influence the peak experiences of psilocybin users in naturalistic settings and contribute to the different characteristics of peak experiences of psilocybin users and non-users.

Cummins, C., & Lyke, J. (2013). Peak Experiences of Psilocybin Users and Non-Users. Journal of psychoactive drugs, 45(2), 189-194. 10.1080/02791072.2013.785855
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Lecture: Psilocybin in the treatment of end-of-life anxiety

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Dr. Grob will come all the way from Los Angeles to give a lecture on his research into psilocybin, the active ingredient in ‘magic mushrooms’. The main focus of this lecture will be the investigation into the safety and efficacy of psilocybin as a therapeutic aid in the treatment of severe anxiety in adult patients with advanced-stage cancer. Research into substances such as MDMA and ayahuasca, also investigated at the Harbor-UCLA Medical Center, will be addressed as well. There will be ample time for questions and discussion. Students, health care professionals and therapists are encouraged to attend.

Dr. Charles Grob is professor in Psychiatry & Biobehavioral Sciences at UCLA, Los Angeles (USA). He has published extensively on topics such as substance misuse and the history of hallucinogens in psychiatry. He performed the first FDA approved study of the physiological and psychological effects of MDMA; a multi-national study of ayahuasca in Brazil and has performed a pilot investigation of the safety and efficacy of psilocybin in the treatment of anxiety in adult patients with advanced-stage cancer.
The lecture will take place on Friday 14 June, from 16:00 – 18:00.
LOCATION: CREA (Muziekzaal), Nieuwe Achtergracht 170 Amsterdam.
FEE: €5,- regular / students & alumni get in for free

Lezing: Psilocybin in the treatment of end-of-life anxiety

flashback-psychedelic-research-returns

Dr. Charles Grob komt speciaal uit Los Angeles om een lezing te geven over zijn onderzoek naar psilocybine, het actieve bestandsdeel in ‘paddo’s’. De lezing zal zich vooral focussen op zijn onderzoek naar de veiligheid en effectiviteit van psilocybine als therapeutisch hulpmiddel binnen de behandeling van angst bij patiënten met vergevorderde kanker. Daarnaast zal er ook aandacht worden besteed aan zijn eerdere onderzoeken met middelen als MDMA en ayahuasca. Er zal ruim tijd zijn voor vragen en discussie. Studenten, therapeuten, wetenschappers, en gezondheidszorgmedewerkers worden aangemoedigd om te komen.

Dr. Charles Grob is hoogleraar Psychiatrie & Biogedragswetenschappen aan de UCLA, Los Angeles (VS). Hij heeft veel gepubliceerd over onderwerpen als drugsmisbruik en de geschiedenis van hallucinogenen in de psychiatrie. Hij leidde onder andere de eerste door de FDA goedgekeurde studie naar de fysiologische en psychologische effecten van MDMA; een multinationale studie naar het gebruik van ayahuasca in Brazilië en een pilotstudie naar de veiligheid en effectiviteit van psilocybine bij de behandeling van angst in patiënten met vergevorderde kanker.

De lezing (in het Engels) vindt plaats op vrijdag 14 juni 2013, van 16:00 tot 18:00 uur.

LOCATIE: CREA (Muziekzaal), Nieuwe Achtergracht 170 Amsterdam.

KOSTEN: €5,- algemeen / studenten en alumni gratis

Hallucinogen persisting perception disorder: what do we know after 50 years?

Abstract

‘Flashbacks’ following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as ‘Hallucinogen Persisting Perception Disorder (Flashbacks)’, or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term ‘flashbacks’ is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD.

Halpern, J. H., & Harrison, G. P. Jr. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109-119. http://dx.doi.org/10.1016/S0376-8716(02)00306-X
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Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin

Abstract

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Bogenschutz, M. P. (2013). Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin. Current Drug Abuse Reviews, 6(1), 17-29.
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Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

Abstract

Background
Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects. However, the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown.

Methods
In a randomized, double-blind study, 17 healthy human subjects received on 4 separate days placebo, psilocybin (215 g/kg), the preferential 5-HT2A antagonist ketanserin (50 mg), or psilocybin plus ketanserin. Mood states were assessed by self-report ratings, and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.

Results
Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression.

Conclusions
This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. These findings may not only have implications for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin’s putative antidepressant effects.

Kometer, M., Schmidt, A., Bachmann, R., Studerus, E., Seifritz, E., & Vollenweider, F. X. (2012). Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors. Biological Psychiatry, 72(11), 898-906. http://dx.doi.org/10.1016/j.biopsych.2012.04.005
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Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis

Abstract

Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very differ -ent functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, inde -pendent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psy -chedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psi -locybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenol -ogy and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.

Carhart-Harris, R. L., Leech, R., Erritzoe, D., Williams, T. M.,  Stone, J. M.,  Evans, J., …. Nutt, D. J. (2012). Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis. Schizophrenia Bulletin, 39(6), 1343-1351. http://dx.doi.org/10.1093/schbul/sbs117
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The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

Abstract

Rationale
Both glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases.

Objectives
This study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases.

Methods
S-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP.

Results
Both S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces.

Conclusion
This study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biases.

Schmidt, A., Kometer, M., Bachmann, R., Seifritz, E., & Vollenweider, F.X. (2012). The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions. Psychopharmacology, 225(1), 227-239. http://dx.doi.org/doi:10.1007/s00213-012-2811-0
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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

Abstract

Background

Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.

Methods

We collected 1000 reports of 10 drugs from the drug information website Erowid.org and formed a term-document frequency matrix. Using variable selection and a random-forest classifier, we identified a subset of words that differentiated between drugs.

Results

A random forest using a subset of 110 predictor variables classified with accuracy comparable to a random forest using the full set of 3934 predictors. Our estimated accuracy was 51.1%, which compares favorably to the 10% expected from chance. Reports of MDMA had the highest accuracy at 86.9%; those describing DPT had the lowest at 20.1%. Hierarchical clustering suggested similarities between certain drugs, such as DMT and Salvia divinorum.

Conclusion

Machine-learning techniques can reveal consistencies in descriptions of drug use experiences that vary by drug class. This may be useful for developing hypotheses about the pharmacology and toxicity of new and poorly characterized drugs.

Coyle, J. R., Presti, D. E., Baggott, M. J. (2012). Quantitative Analysis of Narrative Reports of Psychedelic Drugs.
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Serotonergic Hallucinogens and Emerging Targets for Addiction Pharmacotherapies

Abstract

• Converging lines of evidence from pharmacologic, electrophysiologic, and behavioral
research in animals strongly suggest that activation of cortical 5-hydroxytryptamine-2A
receptors is the most critical step in initiating a cascade of biological events that accounts
for serotonergic hallucinogen (SH) psychoactive properties.
• Psilocybin produces hyperfrontality with divergent prefrontal–subcortical activation in such
a way as to increase cognitive and affective processing in the context of reduced gating
and reduced focus on external stimulus processing.
• In contrast to all other drugs of abuse, SHs are not considered to be capable of producing
sufficient reinforcing effects to cause dependence (addiction) syndromes.
• Given that SHs increase extracellular glutamate levels and activity in the prefrontal–
limbic circuitry, it is possible that a normalization in functional connectivity in this
network through a glutamate-dependent neuroplastic adaptation could produce an
anti-addictive effect.

Ross, S. (2012). Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatric Clinics of North America, 35(2), 357-374. http://dx.doi.org/10.1016/j.psc.2012.04.002
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27 March - Exclusive Presentation on Analytic Idealism Followed by a Live Q&A!

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