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Mushrooms / Psilocybin

Implications for psychedelic-assisted psychotherapy: Functional magnetic resonance imaging study with psilocybin

March 1, 2012 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / , , , , , ,

Abstract

Background: Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.

Aims: To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.

Method: Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis.

Results: Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01).

Conclusions: Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Carhart-Harris, R. L., Leech, R., Williams, T. M., Erritzoe, D., Abbasi, N., Bargiotas, T., … & Wise, R. G. (2012). Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. The British Journal of Psychiatry, 200(3), 238-244. http://dx.doi.org/10.1192/bjp.bp.111.103309
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Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

January 29, 2012 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.

Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., … Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences of the United States of America, 109(6), 2138-2143. http://dx.doi.org/10.1073/pnas.1119598109
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Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

September 28, 2011 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , ,

Abstract

The serotonin-2A receptor (5-HT2AR) 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-HT2AR or 5-HT1AR 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-HT2A/2CR 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-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system.

Quednow, B. B., Kometer, M., Geyerand, M. A., & Vollenweider, F. X. (2012). Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers. Neuropsychopharmacology, 37, 630-640. http://dx.doi.org/10.1038/npp.2011.228
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Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness

September 28, 2011 / Mushrooms / Psilocybin, Mystical experiences, Papers, Personality, Psychology, Publications, Spirituality / By / , ,

Abstract

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.

MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness. Journal of Psychopharmacology, 25(11), 1453-1461. http://dx.doi.org/10.1177/0269881111420188
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Revisiting Wasson's Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria

September 20, 2011 / Ethnobotany, History, Indigenous use, Mushrooms / Psilocybin, Other disciplines, Other subjects, Other substances, Papers, Publications / By /

Abstract

In 1968 R. Gordon Wasson first proposed his groundbreaking theory identifying Soma, the hallucinogenic sacrament of the Vedas, as the Amanita muscaria mushroom. While Wasson’s theory has garnered acclaim, it is not without its faults. One omission in Wasson’s theory is his failure to explain how pressing and filtering Soma, as described in the Rig Veda, supports his theory of Soma’s identity. Several critics have reasoned that such preparation should be unnecessary if equivalent results can be obtained by consuming the raw plant, as is done with other psychoactive mushrooms. In order to address these specific criticisms over 600 anecdotal accounts of Amanita muscaria inebriation were collected and analyzed to determine the impact of preparation on Amanita muscaria’s effects. The findings of this study demonstrated that the effects of Amanita muscaria were related to the type of preparation employed, and that its toxic effects were considerably reduced by preparations that paralleled those described for Soma in the Rig Veda. While unlikely to end debate over the identity of Soma, this study’s findings help to solidify the foundation of Wasson’s theory, and also to demonstrate the importance of preparation in understanding and uncovering the true identity of Soma.

Feeney, K. (2010). Revisiting Wasson’s Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria. Journal of psychoactive drugs, 42(4), 499-506. https://dx.doi.org/ 10.1080/02791072.2010.10400712
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Psychedelic Experience as a Heuristic Tool for Exploring the Mind and the Brain

September 11, 2011 / Mushrooms / Psilocybin, Other disciplines, Other subjects, Papers, Publications / By /

Abstract

I discuss the ontological nature and heuristic value of psychedelic experience. I argue that psychedelic phenomena may manifest the activity of certain mental formations and brain mechanisms that otherwise remain hidden. Thus, psychedelic phenomena can be heuristic tools and intriguing objects of the scientific study. I consider two types of psychedelic phenomena in particular. The first is the moral cleansing that may accompany a psychedelic trip. The second is the appearance of visual and auditory hallucinations. I establish a unified explanatory ground for the phenomena that are commonly viewed as distinct in their genesis. I explain both types of phenomena as products of the amplified imaginative ability of the brain under a substance’s influence. I suggest that the activation of imagination causes an increased empathy and thus accentuates moral feelings. I propose the hypothesis that hallucinations are mental objects of a quantum nature. I argue that no ontologically separate reality stands behind psychedelic visions.

Alyushin, A. (2011). Psychedelic Experience as a Heuristic Tool for Exploring the Mind and the Brain. NeuroQuantology, 9(3), 577‐590. http://dx.doi.org/10.14704/nq.2011.9.3.419
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Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

June 15, 2011 / Mushrooms / Psilocybin, Mystical experiences, Papers, Personality, Psychology, Psychopharmacology, Publications, Safety, Spirituality / 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, Cacti / Mescaline, DMT, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, 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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Psilocybin cuts brain blood flow and connections

December 6, 2021 / Articles, Background articles, Mushrooms / Psilocybin, Publications, Research / 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.

Harm potential of magic mushroom use: A review

April 1, 2011 / History, Mushrooms / Psilocybin, Other disciplines, Papers, Psychology, Publications, Safety, Sociology, Toxicology / 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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30 April - Q&A with Rick Strassman

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