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Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

June 15, 2011 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Rationale: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.

Objectives: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.

Methods: Participants were 18 adults (17 hallucinogennaïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.

Results: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.

Conclusions: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218(4), 649-665. http://dx.doi.org/10.1007/s00213-011-2358-5
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In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in MDMA and Hallucinogen Users

June 6, 2011 / Ayahuasca, DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Context:
Both hallucinogens and 3,4-methylenedioxy-methamphetamine (MDMA or “ecstasy”) have direct agonistic effects on postsynaptic serotonin 2A receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.

Objective:
To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2Areceptor binding.

Design:
A positron emission tomography study of 24 young adult drug users and 21 nonusing control partici-pants performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzo-nitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).

Participants:
Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.

Main Outcome Measures:
In vivo cerebral SERT and serotonin 2A receptor binding.

Results:
Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, −56%; pallidostriatum, −19%; and amygdala, −32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of life-time MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin 2A receptor binding in the serotonin 2A receptor agonist users (both user groups) was also detected.

Conclusions
We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin 2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin 2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

Erritzoe, D., Frokjaer, V. G., Holst, K. K., Christoffersen, M., Johansen, S. S., Svarer, C., … Knudsen, G. M. (2011). In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users. Archives of General Psychiatry, 68(6), 562-576. http://dx.doi.org/10.1001/archgenpsychiatry.2011.56
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Darwin's Pharmacy: Sex, Plants, and the Evolution of the Noosphere

May 16, 2011 / Publications / By

DarwinspharmacyAre humans unwitting partners in evolution with psychedelic plants? Darwin’s Pharmacy weaves the evolutionary theory of sexual selection and the study of rhetoric together with the science and literature of psychedelic drugs. Long suppressed as components of the human tool kit, psychedelic plants can be usefully modelled as “eloquence adjuncts” that intensify a crucial component of sexual selection in humans: discourse. In doing so, they engage our awareness of the noosphere, defined by V.I. Vernadsky as the thinking stratum of the earth, the realm of consciousness feeding back onto the biosphere. Sharing intelligence, connecting with the noosphere and integrating individuality into its eco-systemic context offers powerful and promising ways to respond to ecosystems in crisis, and formed the backdrop of what Doyle dubs the “ecodelic” thought of the environmental movement. Yet current policies criminalize the use of plant-based psychedelics while simultaneously feeding a violent global black market for refined and chemically-derived drugs. In this tour de force of “first-person science,” Doyle takes his readers on a mind bending journey through the work of William Burroughs, Kary Mullis, Lynn Margulis, Timothy Leary, Norma Panduro, Albert Hoffman, Aldous Huxley, Dennis and Terrence McKenna, John Lilly and Phillip K. Dick. Readers who take the journey that is Darwin’s Pharmacy will experience extraordinary insights into evolutionary theory, the war on drugs, the internet, and the nature of human consciousness itself. Richard M. Doyle is professor of English and science, technology, and society at Pennsylvania State University. He is the author of On Beyond Living and Wetwares.

Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noosphere (In Vivo), door Richard Doyle, University of Washington Press, 336 pagina’s.

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Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noosphere

May 16, 2011 / Publications / By

DarwinspharmacyAre humans unwitting partners in evolution with psychedelic plants? Darwin’s Pharmacy weaves the evolutionary theory of sexual selection and the study of rhetoric together with the science and literature of psychedelic drugs. Long suppressed as components of the human tool kit, psychedelic plants can be usefully modelled as “eloquence adjuncts” that intensify a crucial component of sexual selection in humans: discourse. In doing so, they engage our awareness of the noosphere, defined by V.I. Vernadsky as the thinking stratum of the earth, the realm of consciousness feeding back onto the biosphere. Sharing intelligence, connecting with the noosphere and integrating individuality into its eco-systemic context offers powerful and promising ways to respond to ecosystems in crisis, and formed the backdrop of what Doyle dubs the “ecodelic” thought of the environmental movement. Yet current policies criminalize the use of plant-based psychedelics while simultaneously feeding a violent global black market for refined and chemically-derived drugs. In this tour de force of “first-person science,” Doyle takes his readers on a mind bending journey through the work of William Burroughs, Kary Mullis, Lynn Margulis, Timothy Leary, Norma Panduro, Albert Hoffman, Aldous Huxley, Dennis and Terrence McKenna, John Lilly and Phillip K. Dick. Readers who take the journey that is Darwin’s Pharmacy will experience extraordinary insights into evolutionary theory, the war on drugs, the internet, and the nature of human consciousness itself. Richard M. Doyle is professor of English and science, technology, and society at Pennsylvania State University. He is the author of On Beyond Living and Wetwares.

Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noosphere (In Vivo), door Richard Doyle, University of Washington Press, 336 pagina’s.

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β-Carboline Compounds, Including Harmine, Inhibit DYRK1A and Tau Phosphorylation at Multiple Alzheimer's Disease-Related Sites

May 6, 2011 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer’s disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.

Frost, D., Meechoovet, B., Wang, T., Gately, S., Giorgetti, M., Shcherbakova, I., & Dunckley, T. (2011). β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS One, 6(5). https://dx.doi.org/10.1371/journal.pone.0019264

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Ayahuasca, Entheogenic Education & Public Policy

April 18, 2011 / Anthropology & Sociology, Ayahuasca, Papers, Publications / By /

Abstract

Ayahuasca is an entheogenic decoction prepared from two Amazonian plants containing controlled substances, including dimethyltryptamine. Traditionally drunk ritually (and revered as a healing “plant teacher”) by Amazonian indigenous and mestizo peoples, in the 20th century ayahuasca became a sacrament for several new Brazilian religions. One of these, the Santo Daime, has expanded into Canada, where in 2001 a Montreal-based chapter applied for a federal legal exemption to allow drinking of the brew in its rituals. This dissertation undertakes a critical policy analysis of Health Canada’s decision on the Santo Daime request, using government documents obtained through an Access to Information request as data. My goals are to illustrate how modern stereotypes about “drugs” and “drug abuse” in dominant public and political discourses may hinder well-informed policy decision making about ayahuasca, and to consider how entheogenic practices such as ayahuasca drinking are traditional indigenous ways of knowing that should be valued, rather than reflexively demonized and criminalized. My research method is a critical discourse analysis approach to policy analysis, an eclectic means of demonstrating how language contributes to conceptual frames and political responses to public policy issues. I combine insights from recent research on language, discourse and public policy to show how ayahuasca has become an unexpected policy conundrum for liberal democratic states attempting to balance competing interests of criminal justice, public health, and human rights such as religious freedom. I trace ayahuasca’s trajectory as a contemporary policy concern by sketching histories of psychoactive substance use, today’s international drug control regime, and the discursive foundations of its underlying drug war paradigm. Regarding Health Canada’s 2006 decision “in principle” to recommend exemption for the Daime brew, I critique how the government defined ayahuasca as a policy problem, what policy stakeholders it considered in its decision making, and what knowledge about ayahuasca it used. To conclude, I explore modern schooling’s systemic antipathy to wonder and awe, and propose that policy reforms allowing circumspect use of entheogens such as ayahuasca as cognitive tools may help stimulate re-enchantment and appreciation of the need to address human and planetary ecological predicaments of the 21st century.

Tupper, K. W. (2011). Ayahuasca, entheogenic education & public policy (Doctoral dissertation, University of British Columbia). 10.14288/1.0064622
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Psilocybine vermindert doorbloeding hersenen

December 2, 2021 / Uncategorized / By

Gebruikers van psychedelische drugs hebben door de tijd heen hun ervaring als geestverruimend beschreven. Het zal voor hen een verrassing zijn om te horen dat psilocybine – de werkzame stof in paddo’s – eigenlijk de bloedtoevoer naar de hersenen vermindert, alsmede de verbindingen tussen belangrijke gedeeltes van de hersenen die de perceptie en cognitieve vaardigheden regelen.

Dezelfde gebieden kunnen overactief zijn bij mensen die depressief zijn, waardoor de drug een mogelijk medicijn kan zijn voor deze stoornis. Dit onderzoek meet als eerste de effecten van psilocybine door middel van fMRI, en dit is het eerste Britse experiment in jaren waarvan menselijke proefpersonen en een hallucinogene drug deel uitmaakten.

Robin Carhart-Harris van het Imperial College in Londen en zijn collega’s vonden dertig vrijwilligers die zich lieten injecteren met psilocybine en hun hersenen lieten scannen met fMRI.

Verminderde doorbloeding

Er was sprake van een verminderde doorbloeding in de gebieden van de hersenen die bekend staan als de thalamus, de ‘posterior cingulate’ en de prefrontale cortex. “De vermindering was verrassend. We dachten dat de ervaring zou leiden tot meer activiteit, maar dat idee is duidelijk te simplistisch,” zegt Carhart-Harris. “We zagen nergens een toename.”

Er waren ook minder connecties, zoals tussen de hippocampus en de posterior cingulate en de prefrontale cortex.

“Bij psilocybine zie je een verminderde ‘conversatie’ tussen de hippocampus en die delen van de cortex,” zegt Carhart-Harris. “Veranderingen qua functie in met name de posterior cingulate worden geassocieerd met een bewustzijnsverandering.”

Stemmingswisselingen

Psilocybine lijkt qua chemische structuur op serotonine – een hormoon dat van belang is bij het reguleren van je stemming – en daarom bindt de stof zich aan serotoninereceptoren van zenuwcellen in de hersenen. De drug heeft een mogelijk een therapeutisch potentieel omdat het serotoninesysteem in zenuwcellen ook een doelwit is van bestaande antidepressiva.

Een onderzoek van vorig jaar door Charles Grob aan de universiteit van Californië toonde aan dat mensen in de terminale fase van kanker aanzienlijk minder angstig en minder depressief waren na toediening van psilocybine.

Franz Vollenweider, die werkzaam is in een vergelijkbare branche in het Psychiatric University Hospital in Zurich, Zwitserland, zegt dat de onmiddellijke effecten van psilocybine niet zo belangrijk zijn als de effecten op de langere termijn. Dat komt doordat psilocybine zorgt voor een toename van genexpressie en signaaleiwitten die geassocieerd worden met het aanmaken van zenuwcellen en verbindingen, zegt hij: “We denken dat de antidepressieve werking van psilocybine te wijten kan zijn aan een toename van factoren die neuroplasticiteit op de lange termijn activeren.”

Carhart-Harris heeft zijn werk vorige week gepresenteerd op de Breaking Convention conference aan de Universiteit van Kent in Canterbury (GB).

Psilocybin cuts brain blood flow and connections

December 6, 2021 / Mushrooms / Psilocybin, Publications / By

Psychedelic drug users throughout the ages have described their experiences as mind-expanding. They might be surprised, therefore, to hear that psilocybin – the active ingredient in magic mushrooms – actually decreases blood flow as well as connectivity between important areas of the brain that control perception and cognition.

The same areas can be overactive in people who suffer from depression, making the drug a potential treatment option for the condition. The study is the first time that psilocybin’s effects have been measured with fMRI, and the first experiment involving a hallucinogenic drug and human participants in the UK for decades.

Robin Carhart-Harris at Imperial College London and colleagues recruited 30 volunteers who agreed to be injected with psilocybin and have their brain scanned using fMRI.

Low flow

Less blood flow was seen in the brain regions known as the thalamus, the posterior cingulate and the medial prefrontal cortex. “Seeing a decrease was surprising. We thought profound experience equalled more activity, but this formula is clearly too simplistic,” says Carhart-Harris. “We didn’t see an increase in any regions,” he says.

Decreases in connectivity were also observed, such as between the hippocampus and the posterior cingulate and medial prefrontal cortex.

“Under psilocybin you see a relative decrease in ‘talk’ between the hippocampus and these cortical hub regions,” says Carhart-Harris. “Changes in function in the posterior cingulate in particular are associated with changes in consciousness.”

Mood swing

Psilocybin has a similar chemical structure to serotonin – a hormone involved in regulating mood – and therefore binds to serotonin receptors on nerve cells in the brain. The drug may have therapeutic potential because the serotonin system is also a target for existing antidepressants.

A study last year by Charles Grob at the University of California, Los Angeles, showed that people with end-stage cancer had significantly less anxiety and better mood after receiving psilocybin.

Franz Vollenweider, who works in a similar field at the Psychiatric University Hospital Zurich, Switzerland, says that the immediate effects of psilocybin are not as important for clinical benefit as the longer-term effects. That’s because psilocybin increases the expression of genes and signalling proteins associated with nerve growth and connectivity, he says: “We think that the antidepressant effects of psilocybin may be due to a possible increase of factors that activate long-term neuroplasticity.”

Carhart-Harris presented his work at the Breaking Convention conference at the University of Kent in Canterbury, UK, last week.

Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

April 8, 2011 / Anthropology & Sociology, Ayahuasca, Papers, Psychology, Publications / By /

Abstract

In 2010, the Brazilian Government agency responsible for drug-related issues formulated official Resolutions that categorized the consumption of ayahuasca by pregnant women and children in the Santo Daime and Uniatildeo do Vegetal ayahuasca-based religions as an “exercise of parental rights.” Although ayahuasca groups do enjoy a relative degree of social legitimacy and formal legal recognition in Brazil, the participation of pregnant women and children nevertheless continues to provoke heated discussion. This article raises the main issues involved in the public debate over this subject. In the first part, a diverse group of biomedical and health specialists was consulted, and their opinions were briefly analyzed. In the second, a full interview with a follower of one branch of Santo Daime, mother of four children who took ayahuasca during all her pregnancies, and whose children all drink ayahuasca, is presented. Her interview reveals important cultural parameters of ayahuasca consumption. The article explores common themes and contradictions found between the biomedical, anthropological, and ayahuasca-users’ discourses. It raises central issues regarding the limits of freedom of religion and the state’s right to interfere in family matters. The following analysis also has implications regarding the role of science in influencing policy decisions on drug use.

Labate, B. C. (2011). Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives. Journal of Psychoactive Drugs, 43(1), 27-35. http://dx.doi.org/10.1080/02791072.2011.566498
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Harm potential of magic mushroom use: A review

April 1, 2011 / Humanities & Art, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

In 2007, the Minister of Health of the Netherlands requested the CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of magic mushrooms. The present paper is an updated redraft of the review, written to support the assessment by CAM experts. It summarizes the literature on physical or psychological dependence, acute and chronic toxicity, risk for public health and criminal aspects related to the consumption of magic mushrooms.

In the Netherlands, the prevalence of magic mushroom use was declining since 2000 (last year prevalence of 6.3% in 2000 to 2.9% in 2005), and further declined after possession and use became illegal in December 2008.

The CAM concluded that the physical and psychological dependence potential of magic mushrooms was low, that acute toxicity was moderate, chronic toxicity low and public health and criminal aspects negligible. The combined use of mushrooms and alcohol and the quality of the setting in which magic mushrooms are used deserve, however, attention.

In conclusion, the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported. The low prevalent but unpredictable provocation of panic attacks and flash-backs remain, however, a point of concern.

van Amsterdam, J., Opperhuizen, A., & van den Brink, W. (2011). Harm potential of magic mushroom use: a review. Regulatory toxicology and pharmacology, 59(3), 423-429. https://dx.doi.org/10.1016/j.yrtph.2011.01.006
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