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Survey of subjective “God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT.

April 23, 2019 / Ayahuasca, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose “Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
Griffiths, R. R., Hurwitz, E. S., Davis, A. K., Johnson, M. W., & Jesse, R. (2019). Survey of subjective” God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PloS one, 14(4), e0214377., https://doi.org/10.1371/journal.pone.0214377
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Survey of subjective "God encounter experiences": Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT.

April 23, 2019 / Ayahuasca, DMT, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose “Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
Griffiths, R. R., Hurwitz, E. S., Davis, A. K., Johnson, M. W., & Jesse, R. (2019). Survey of subjective” God encounter experiences”: Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PloS one, 14(4), e0214377., https://doi.org/10.1371/journal.pone.0214377
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Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use

April 11, 2019 / LSD, Neuroscience, Papers, Pharmacology & Chemistry / By / , , , ,

Abstract

In recent years, experimental research on lysergic acid diethylamide (LSD) in humans has gained new momentum. In humans, LSD is metabolized rapidly into several metabolites but knowledge of the involved metabolizing enzymes is limited. The aim of the current study was to identify the cytochrome P450 (CYP) isoforms involved in the metabolism of LSD to 6-norlysergic acid diethylamide (nor-LSD) and 2-oxo-3-hydroxy-LSD (O-H-LSD) in vitro, in order to evaluate potential effects of enzyme polymorphisms or prescription drugs on LSD pharmacokinetics. Additionally, interactions of LSD and both metabolites with 5-hydroxytryptamine (5-HT) receptors were assessed. LSD was incubated with human liver microsomes over 4 h and the production of nor-LSD and O-H-LSD was quantified by liquid chromatography tandem mass spectrometry. Metabolism was inhibited by the addition of specific CYP inhibitors. Additionally, recombinant CYPs were used to verify the inhibition results obtained with microsomes and induction of metabolism was investigated in human hepatocyte-derived cells. Radioligand binding and calcium mobilization assays were used to determine 5-HT receptor affinities and activities, respectively. Human liver microsomes displayed minor metabolite formation (<1% metabolized) over 4 h. CYP2D6, 2E1, and 3A4 significantly contributed to the formation of nor-LSD, and CYP1A2, 2C9, 2E1, and 3A4 were significantly involved in the formation of O-H-LSD. These findings could be verified using recombinant CYPs. Enzyme induction with rifampicin distinctly increased the formation of both metabolites, whereas treatment with omeprazole only slightly increased formation of nor-LSD. LSD and nor-LSD were pharmacologically active at the 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors. Nor-LSD mainly differed from the parent compound by having a lower affinity to the 5-HT2C receptor. O-H-LSD displayed substantially weaker affinity and activity at serotonergic receptors in comparison to LSD. To conclude, human liver microsomes converted only small amounts of LSD to nor-LSD and O-H-LSD but several CYPs significantly contributed. Genetic polymorphisms and drug interactions could therefore influence pharmacokinetics and pharmacodynamics of LSD. Nor-LSD likely has hallucinogenic activity similar to LSD, whereas O-H-LSD is inactive. Drug-drug interaction studies in humans are required to further assess the clinical relevance of these findings.

Luethi, D., Hoener, M. C., Krähenbühl, S., Liechti, M. E., & Duthaler, U. (2019). Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use. Biochemical pharmacology, 164, 129-138., 10.1016/j.bcp.2019.04.013
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Psychedelic-Assisted Group Therapy: A Systematic Review.

April 5, 2019 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Contemporary research with classic psychedelic drugs (e.g., lysergic acid diethylamide (LSD) and psilocybin) is indebted to the twentieth-century researchers and clinicians who generated valuable clinical knowledge of these substances through experimentation. Several recent reviews that highlight the contributions of this early literature have focused on psychedelic-assisted individual psychotherapy modalities. None have attempted to systematically identify and compile experimental studies of psychedelic-assisted group therapy. In therapeutic settings, psychedelics were often used to enhance group therapy for a variety of populations and clinical indications. We report on the results of a systematic review of the published literature in English and Spanish on psychedelic-assisted group therapies. Publications are characterized by their clinical approach, experimental method, and clinical outcomes. Given the renewed interest in the clinical use of psychedelic medicines, this review aims to stimulate hypotheses to be tested in future research on psychedelic-assisted psychotherapy, group process, and interpersonal functioning.
Trope, A., Anderson, B. T., Hooker, A. R., Glick, G., Stauffer, C., & Woolley, J. D. (2019). Psychedelic-assisted group therapy: a systematic review. Journal of Psychoactive Drugs, 51(2), 174-188., https://doi.org/10.1080/02791072.2019.1593559
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Classic psychedelics: the special role of the visual system

April 2, 2019 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Here, we briefly overview the various aspects of classic serotonergic hallucinogens reported by a number of studies. One of the key hypotheses of our paper is that the visual effects of psychedelics might play a key role in resetting fears. Namely, we especially focus on visual processes because they are among the most prominent features of hallucinogen-induced hallucinations. We hypothesize that our brain has an ancient visual-based (preverbal) intrinsic cognitive process that, during the transient inhibition of top-down convergent and abstract thinking (mediated by the prefrontal cortex) by psychedelics, can neutralize emotional fears of unconscious and conscious life experiences from the past. In these processes, the decreased functional integrity of the self-referencing processes of the default mode network, the modified multisensory integration (linked to bodily self-consciousness and self-awareness), and the modified amygdala activity may also play key roles. Moreover, the emotional reset (elimination of stress-related emotions) by psychedelics may induce psychological changes and overwrite the stress-related neuroepigenetic information of past unconscious and conscious emotional fears.

Császár-Nagy, N., Kapócs, G., & Bókkon, I. (2019). Classic psychedelics: the special role of the visual system. Reviews in the neurosciences.,  10.1515/revneuro-2018-0092
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Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration.

March 29, 2019 / LSD, Papers, Psychology, Publications / By / ,

Abstract

Albert Hoffman suggested that low doses of LSD might be an appropriate alternative to Ritalin. Following this possibility, a systematic exploration of the effects of “microdoses,” comprising hundreds of lengthy descriptive reports, was undertaken. Based on these reports, using a psychedelic in the microdose range (10 micrograms) every three days was determined to be safe across a wide variety of individuals and conditions. Over 18 months, more than a thousand individuals from 59 countries did a daily evaluation of negative and positive emotional state using the PANAS checklist plus written reports for between one week and four months. Participant reports suggested that spaced but repeated microdoses were followed by improvements in negative moods, especially depression, and increases in positive moods. Increased energy, improved work effectiveness, and improved health habits were observed in clinical and non-clinical populations. Smaller samples described alleviation of symptoms in migraine headaches, pre-menstrual syndromes, traumatic brain injury, shingles, and other conditions not previously associated with psychedelic use.
Fadiman, J., & Korb, S. (2019). Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. Journal of psychoactive drugs, 1-5., https://doi.org/10.1080/02791072.2019.1593561
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Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20 th Century

March 6, 2019 / Humanities & Art, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

During the 1950s and 1960s, there was a tremendous surge in research into the effects of psychedelic drugs. When discussing this period of research, the discovery of the psychoactive properties of LSD in 1943 is often presented as the main, and sometimes only, driving force of the boom in research. This “Great Person,” or “Great Chemical,” historiographical lens fails to acknowledge other factors that were fundamental in setting the stage for the research. In particular, other psychedelic drugs, such as mescaline, were already being probed for their uses in psychotherapy and as models for psychosis before the effects of LSD had been discovered. Psilocybin and other classical psychedelics had also been discovered by Western researchers around the same time as the synthesis of LSD. Additionally, many of the dominant zeitgeists (e.g., pharmacological, psychoanalytic, and humanistic) in psychology during this period were congruent with psychedelic research. This article argues that while the discovery of LSD may have been a catalyst for psychedelic research in the 1950s and ’60s, there was a broader psychedelic zeitgeist that deserves acknowledgement for setting the stage.
Aday, J. S., Bloesch, E. K., & Davoli, C. C. (2019). Beyond LSD: A broader psychedelic zeitgeist during the early to mid-20th century. Journal of psychoactive drugs, 51(3), 210-217., https://doi.org/10.1080/02791072.2019.1581961
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Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20th Century.

March 6, 2019 / Humanities & Art, LSD, Papers, Psychology, Publications / By / , ,

Abstract

During the 1950s and 1960s, there was a tremendous surge in research into the effects of psychedelic drugs. When discussing this period of research, the discovery of the psychoactive properties of LSD in 1943 is often presented as the main, and sometimes only, driving force of the boom in research. This “Great Person,” or “Great Chemical,” historiographical lens fails to acknowledge other factors that were fundamental in setting the stage for the research. In particular, other psychedelic drugs, such as mescaline, were already being probed for their uses in psychotherapy and as models for psychosis before the effects of LSD had been discovered. Psilocybin and other classical psychedelics had also been discovered by Western researchers around the same time as the synthesis of LSD. Additionally, many of the dominant zeitgeists (e.g., pharmacological, psychoanalytic, and humanistic) in psychology during this period were congruent with psychedelic research. This article argues that while the discovery of LSD may have been a catalyst for psychedelic research in the 1950s and ’60s, there was a broader psychedelic zeitgeist that deserves acknowledgement for setting the stage.
Aday, J. S., Bloesch, E. K., & Davoli, C. C. (2019). Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20th Century. Journal of psychoactive drugs, 1-8., https://doi.org/10.1080/02791072.2019.1581961
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Psychedelics and Dying Care: A Historical Look at the Relationship between Psychedelics and Palliative Care.

March 1, 2019 / Anxiety Disorders / PTSD, LSD, Papers, Psychology, Publications / By /

Abstract

This article examines the historical relationship between psychedelics and palliative care. Historians have contributed to a growing field of studies about how psychedelics have been used in the past, but much of that scholarship focused on interrogating questions of legitimacy or proving that psychedelics had therapeutic potential. Palliative care had not yet developed as medical sub-specialty, more often leaving dying care on the margins of modern, pharmaceutical-based treatments. As psychedelic researchers in the 1950s began exploring different applications for psychoactive substances such as LSD and mescaline, however, dying care came into clearer focus as a potential avenue for psychedelics. Before that application gained momentum in clinical or philosophical discussions, psychedelics were criminalized and some of those early discussions were lost. This article looks back at historical discussions about LSD’s potential for easing the anxiety associated with dying, and considers how those early conversations might offer insights into today’s more articulated discussions about psychedelics in palliative care.
Dyck, E. (2019). Psychedelics and Dying Care: A Historical Look at the Relationship between Psychedelics and Palliative Care. Journal of psychoactive drugs, 1-6., 10.1080/02791072.2019.1581308
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Effective connectivity changes in LSD-induced altered states of consciousness in humans

February 12, 2019 / LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico–striato–thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

Preller, K. H., Razi, A., Zeidman, P., Stämpfli, P., Friston, K. J., & Vollenweider, F. X. (2019). Effective connectivity changes in LSD-induced altered states of consciousness in humans. Proceedings of the National Academy of Sciences, 201815129., 10.1073/pnas.1815129116
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