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Mushrooms / Psilocybin

The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis.

January 2, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges’ gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.

Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Research, 112749., https://doi.org/10.1016/j.psychres.2020.112749
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Decreased directed functional connectivity in the psychedelic state.

December 17, 2019 / Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2019). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 116462., https://doi.org/10.1016/j.neuroimage.2019.116462
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From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner.

December 16, 2019 / Anxiety Disorders / PTSD, Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

(1) Background: There appears to be a growing disconnection between humans and their natural environments which has been linked to poor mental health and ecological destruction. Previous research suggests that individual levels of nature relatedness can be increased through the use of classical psychedelic compounds, although a causal link between psychedelic use and nature relatedness has not yet been established. (2) Methods: Using correlations and generalized linear mixed regression modelling, we investigated the association between psychedelic use and nature relatedness in a prospective online study. Individuals planning to use a psychedelic received questionnaires 1 week before (N = 654), plus one day, 2 weeks, 4 weeks, and 2 years after a psychedelic experience. (3) Results: The frequency of lifetime psychedelic use was positively correlated with nature relatedness at baseline. Nature relatedness was significantly increased 2 weeks, 4 weeks and 2 years after the psychedelic experience. This increase was positively correlated with concomitant increases in psychological well-being and was dependent on the extent of ego-dissolution and the perceived influence of natural surroundings during the acute psychedelic state. (4) Conclusions: The here presented evidence for a context- and state-dependent causal effect of psychedelic use on nature relatedness bears relevance for psychedelic treatment models in mental health and, in the face of the current ecological crisis, planetary health.
Kettner, H., Gandy, S., Haijen, E. C., & Carhart-Harris, R. L. (2019). From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner. International Journal of Environmental Research and Public Health, 16(24), 5147., https://doi.org/10.3390/ijerph16245147
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Neurotrophic mechanisms of psychedelic therapy

December 12, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Psychedelic drugs, often referred to as hallucinogens, are quite distinct from other classes of psychotropic drugs. Although the subjective and behavioral effects they induce are quite dramatic, they possess little addictive potential when compared to nicotine, alcohol or opiates. Since the discovery of ketamine antidepressant effects, there has been growing interest for these molecules. Serotonergic psychedelics such as psilocybin and lysergic acid diethylamide (LSD) are gaining attention as potential treatments for depression and addiction, similarly to 3,4-methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD), and ibogaine for addiction. Although they possess distinct pharmacological profiles, their kinetics of action are quite similar: the therapeutic effects are felt within the hours following administration, and last well beyond drug elimination by the organism. This strongly suggests the induction of neurogenic and plastic mechanisms, including the involvement of trophic factors. This review will explore the literature dealing with the effects of psychedelics on neurotrophins, as well as the plastic adaptations that they induce, in an attempt to understand their surprising therapeutic potential. We will show that although ketamine and serotonergic psychedelics have affinity for very different receptors (NMDA, 5-HT2A), they ultimately initiate similar plastic adaptations in the prefrontal cortex through the involvement of the brain-derived neurotrophic factor (BDNF). We will see that although MDMA uses the same receptors as serotonergic psychedelics to alleviate PTSD symptoms, its effect on BDNF levels seem paradoxical and quite different. Finally, we show how ibogaine could exert its anti-addictive properties through a completely different neurotrophic factor than other psychedelic drugs, the glial cell line-derived neurotrophic factor (GDNF). While the current literature concerning the psychiatric applications of psychedelic therapy is encouraging, it remains to be determined whether their benefits could be obtained without their psychotomimetic effects, or concerns over potential toxicity.
Corne, R., & Mongeau, R. (2019). Neurotrophic mechanisms of psychedelic therapy. Biologie aujourd’hui, 213(3-4), 121., https://doi.org/10.1051/jbio/2019015
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Neuropharmacological modulation of the aberrant bodily self through psychedelics

December 6, 2019 / Depressive Disorders, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

As a continual source of sensory input and fundamental component of self-referential processing, the body holds an integral modulatory role in cognition. In a healthy state, predictive coding of multisensory integration promotes the construction of a coherent self. However, several psychiatric disorders comprise aberrant perceptions of the bodily self that are purported to involve discrepancies in the integration and updating of multisensory systems. Changes in functional connectivity of somatomotor and high-level association networks in these disorders could be successfully remediated through 5-HT2A receptor agonism via psychedelics. Reported alterations of bodily self-awareness during psychedelic experiences allude to a potentially central role of the bodily self. In this article, we bridge the domains of (aberrant) bodily self-awareness and psychedelics by discussing the predictive coding mechanisms underlying the bodily self and psychedelics. Furthermore, we propose that psychedelically-induced desynchronization of predictive coding might involve modulation of somatomotor, sensorimotor, and high-level association networks that could remediate aberrant perceptions of the bodily self.

Ho, J. T., Preller, K. H., & Lenggenhager, B. (2019). Neuropharmacological modulation of the aberrant bodily self through psychedelics. Neuroscience & Biobehavioral Reviews., https://doi.org/10.1016/j.neubiorev.2019.12.006
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Injury-Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms

February 6, 2022 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry / Leave a Comment / By / , , , , , , ,

Abstract

Upon injury, psychotropic psilocybin-producing mushrooms instantly develop an intense blue color, the chemical basis and mode of formation of which has remained elusive. We report two enzymes from Psilocybe cubensis that carry out a two-step cascade to prepare psilocybin for oxidative oligomerization that leads to blue products. The phosphatase PsiP removes the 4-O-phosphate group to yield psilocin, while PsiL oxidizes its 4-hydroxy group. The PsiL reaction was monitored by in situ 13 C NMR spectroscopy, which indicated that oxidative coupling of psilocyl residues occurs primarily via C-5. MS and IR spectroscopy indicated the formation of a heterogeneous mixture of preferentially psilocyl 3- to 13-mers and suggest multiple oligomerization routes, depending on oxidative power and substrate concentration. The results also imply that phosphate ester of psilocybin serves a reversible protective function.

Lenz, C., Wick, J., Braga, D., García-Altares, M., Lackner, G., Hertweck, C., Gressler, M., & Hoffmeister, D. (2020). Injury-Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms. Angewandte Chemie (International ed. in English), 59(4), 1450–1454. https://doi.org/10.1002/anie.201910175

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Modulation of Social Cognition via Hallucinogens and “Entactogens”.

December 3, 2019 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.

Preller, K. H., & Vollenweider, F. X. (2019). Modulation of Social Cognition via Hallucinogens and “Entactogens”. Frontiers in Psychiatry, 10., https://doi.org/10.3389/fpsyt.2019.00881
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Modulation of Social Cognition via Hallucinogens and "Entactogens".

December 3, 2019 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.

Preller, K. H., & Vollenweider, F. X. (2019). Modulation of Social Cognition via Hallucinogens and “Entactogens”. Frontiers in Psychiatry, 10., https://doi.org/10.3389/fpsyt.2019.00881
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Therapeutic use of serotoninergic hallucinogens: A review of the evidence and of the biological and psychological mechanisms.

December 3, 2019 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Serotoninergic hallucinogens include drugs such as lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and psilocybin. Recent trials with single/few doses of these compounds show that they induce rapid and sustained antidepressive, anxiolytic, and antiaddictive effects. These effects are also observed in religious groups using the DMT-containing brew ayahuasca. The agonist action of these substances on 5-HT2A receptors expressed in frontal and limbic areas increase glutamatergic transmission and neuroplasticity. These neurochemical effects are associated with acute alterations on self-perception and increases in introspection and positive mood, and with subacute and long-term decreases in psychiatric symptoms, increases in some personality traits such as openness, improvements in emotional processing, and increases in empathy. These are preliminary but promising results that should be further explored in controlled trials with larger sample sizes, especially considering that these compounds could be beneficial in the treatment of treatment-resistant psychiatric disorders.
dos Santos, R. G., & Hallak, J. E. C. (2019). Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neuroscience & Biobehavioral Reviews., https://doi.org/10.1016/j.neubiorev.2019.12.001
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Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics.

November 29, 2019 / Anxiety Disorders / PTSD, Depressive Disorders, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Psychedelic therapies can engender enduring improvements in psychological well-being. However, relatively little is known about the psychological mechanisms through which the salutary effects of psychedelics emerge. Through integrating extant research on psychedelics with contemporary existential psychology, we present a novel hypothesis that reduced death anxiety may be a key mechanism underpinning the therapeutic effects of psychedelics. In developing this hypothesis, we also provide a complementary review of mechanisms through which psychedelics may reduce death anxiety. We conclude that an awareness of the role of death anxiety in psychopathology has the potential to guide future research into psychedelic therapies.

Moreton, S. G., Szalla, L., Menzies, R. E., & Arena, A. F. (2019). Embedding existential psychology within psychedelic science: reduced death anxiety as a mediator of the therapeutic effects of psychedelics. 29, 1-12., https://doi.org/10.1007/s00213-019-05391-0
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