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Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial

March 16, 2022 / Ayahuasca, Papers, Psychology / Leave a Comment / By / , , , , , , , , ,

Abstract

Background: The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the REFE.

Methods: Twenty-two healthy volunteers participated in a pilot, proof-of-concept, randomized trial. Study variables included a REFE task performed before and 4 hours after drug intake, subjective effects (self-reports/observer impressions), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. The REFE task was applied again 1, 7, 14, and 21 days and 3 months after drug intake. Stability of ayahuasca alkaloids during the study was also assessed (room temperature, 18 months).

Findings: Compared with placebo, ayahuasca did not modify the REFE. No significant effects were observed on cardiovascular measures and brain-derived neurotrophic factor levels. Volunteers reported visual effects, tranquility/relaxation, and well-being, with few reports of transient anxiety/confusion. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. A significant time-dependent deterioration of alkaloids was observed, especially for dimethyltryptamine.

Conclusions: Absence of significant effects on the REFE task could be due to lack of effects of ayahuasca (at the doses used), alkaloid degradation, learning effects, and the high educational level of the sample. Further trials with different samples are needed to better understand the effects of ayahuasca and other serotonergic hallucinogens on the REFE. Future trials should improve methods to guarantee the stability of ayahuasca alkaloids.

Rocha, J. M., Rossi, G. N., de Lima Osório, F., Bouso, J. C., de Oliveira Silveira, G., Yonamine, M., Campos, A. C., Bertozi, G., Cecílio Hallak, J. E., & Dos Santos, R. G. (2021). Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial. Journal of clinical psychopharmacology, 41(3), 267–274. https://doi.org/10.1097/JCP.0000000000001396

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Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial

January 3, 2022 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , , , , ,

Abstract

Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.

Objective: To investigate the effect of psilocybin therapy in patients with MDD.

Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).

Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.

Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).

Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).

Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.

Trial registration: ClinicalTrials.gov Identifier: NCT03181529.

Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285

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Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

March 16, 2022 / Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus-a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR-independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression.

Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B., & Thompson, S. M. (2021). Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proceedings of the National Academy of Sciences of the United States of America, 118(17), e2022489118. https://doi.org/10.1073/pnas.2022489118

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Spontaneous and deliberate creative cognition during and after psilocybin exposure

March 14, 2022 / Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / , , , , , , , , ,

Abstract

Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking. Acutely, psilocybin increased ratings of (spontaneous) creative insights, while decreasing (deliberate) task-based creativity. Seven days after psilocybin, number of novel ideas increased. Furthermore, we utilized an ultrahigh field multimodal brain imaging approach, and found that acute and persisting effects were predicted by within- and between-network connectivity of the default mode network. Findings add some support to historical claims that psychedelics can influence aspects of the creative process, potentially indicating them as a tool to investigate creativity and subsequent underlying neural mechanisms. Trial NL6007; psilocybin as a tool for enhanced cognitive flexibility; https://www.trialregister.nl/trial/6007 .

Mason, N. L., Kuypers, K., Reckweg, J. T., Müller, F., Tse, D., Da Rios, B., Toennes, S. W., Stiers, P., Feilding, A., & Ramaekers, J. G. (2021). Spontaneous and deliberate creative cognition during and after psilocybin exposure. Translational psychiatry, 11(1), 209. https://doi.org/10.1038/s41398-021-01335-5

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LSD and ketanserin and their impact on the human autonomic nervous system

March 14, 2022 / LSD, Neuroscience, Papers / Leave a Comment / By / , ,

Abstract

The interest in lysergic acid diethylamide (LSD) has sparked again due to its supposed positive effects on psychopathological conditions. Yet, most research focuses on the actions of LSD on the central nervous system. The interaction with the autonomic nervous system (ANS) has been neglected so far. Therefore, the aim was to assess the effects of LSD and the serotonin 2A receptor antagonist ketanserin on the ANS as assessed by heart rate variability (HRV) measures and their correlation with subjective drug-induced effects in a randomized, placebo-controlled crossover trial. Thus, ANS activity was derived from electrocardiogram recordings after intake of placebo, LSD or ketanserin, and LSD by calculating R-peak-based measures of sympathetic and parasympathetic activity. Repeated measure ANOVA and partial correlation for HRV measures and subjective experience questionnaires were performed. LSD predominantly increased sympathetic activity, while ketanserin counteracted this effect on the ANS via an increase of parasympathetic tone. Sympathetic activity was positively and parasympathetic activity negatively associated with psychedelic effects of LSD. Furthermore, Placebo HRV measures predicted subjective experiences after LSD intake. The association between trait ANS activity and LSD-induced subjective experiences may serve as a candidate biomarker set for the effectiveness of LSD in the treatment of psychopathological conditions.

Olbrich, S., Preller, K. H., & Vollenweider, F. X. (2021). LSD and ketanserin and their impact on the human autonomic nervous system. Psychophysiology, 58(6), e13822. https://doi.org/10.1111/psyp.13822

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Examining changes in personality following shamanic ceremonial use of ayahuasca

March 14, 2022 / Ayahuasca, Papers, Psychology / Leave a Comment / By / , , ,

Abstract

The present study examines the association between the ceremonial use of ayahuasca-a decoction combining the Banistereopsis caapi vine and N,N-Dimethyltryptamine-containing plants-and changes in personality traits as conceived by the Five-Factor model (FFM). We also examine the degree to which demographic characteristics, baseline personality, and acute post-ayahuasca experiences affect personality change. Participants recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 256) completed self-report measures of personality at three timepoints (Baseline, Post, 3-month Follow-up). Informant-report measures of the FFM were also obtained (N = 110). Linear mixed models were used to examine changes in personality and the moderation of those changes by covariates. The most pronounced change was a reduction in Neuroticism dzself-reportT1-T2 = – 1.00; dzself-reportT1-T3 = – .85; dzinformant-reportT1-T3 = – .62), reflected in self- and informant-report data. Moderation of personality change by baseline personality, acute experiences, and purgative experiences was also observed.

Weiss, B., Miller, J. D., Carter, N. T., & Keith Campbell, W. (2021). Examining changes in personality following shamanic ceremonial use of ayahuasca. Scientific reports, 11(1), 6653. https://doi.org/10.1038/s41598-021-84746-0

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A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats

February 21, 2022 / Ayahuasca, DMT, Papers, Psychology / Leave a Comment / By / , , , , , , , ,

Abstract

Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.

Uthaug, M. V., Mason, N. L., Toennes, S. W., Reckweg, J. T., de Sousa Fernandes Perna, E. B., Kuypers, K., van Oorsouw, K., Riba, J., & Ramaekers, J. G. (2021). A placebo-controlled study of the effects of ayahuasca, set and setting on mental health of participants in ayahuasca group retreats. Psychopharmacology, 238(7), 1899–1910. https://doi.org/10.1007/s00213-021-05817-8

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Associations between lifetime classic psychedelic use and markers of physical health

March 14, 2022 / Papers, Psychiatry & Medicine / Leave a Comment / By / , ,

Abstract

Background: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health.

Aims: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health.

Methods: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates.

Results: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once.

Conclusion: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.

Simonsson, O., Sexton, J. D., & Hendricks, P. S. (2021). Associations between lifetime classic psychedelic use and markers of physical health. Journal of psychopharmacology (Oxford, England), 35(4), 447–452. https://doi.org/10.1177/0269881121996863

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Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects

March 16, 2022 / Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Psychedelic drugs are increasingly being incorporated into therapeutic contexts for the purposes of promoting mental health. However, they can also induce adverse reactions in some individuals, and it is difficult to predict before treatment who is likely to experience positive or adverse acute effects. Although consideration of setting and dosage as well as excluding individuals with psychotic predispositions has thus far led to a high degree of safety, it is imperative that researchers develop a more nuanced understanding of how to predict individual reactions. To this end, the current systematic review coalesced the results of 14 studies that included baseline states or traits predictive of the acute effects of psychedelics. Individuals high in the traits of absorption, openness, and acceptance as well as a state of surrender were more likely to have positive and mystical-type experiences, whereas those low in openness and surrender or in preoccupied, apprehensive, or confused psychological states were more likely to experience acute adverse reactions. Participant sex was not a robust predictor of drug effects, but 5-HT2AR binding potential, executive network node diversity, and rACC volume may be potential baseline biomarkers related to acute reactions. Finally, increased age and experience with psychedelics were individual differences related to generally less intense effects, indicating that users may become slightly less sensitive to the effects of the drugs after repeated usage. Although future well-powered, placebo-controlled trials directly comparing the relative importance of these predictors is needed, this review synthesizes the field’s current understanding of how to predict acute reactions to psychedelic drugs.

Aday, J. S., Davis, A. K., Mitzkovitz, C. M., Bloesch, E. K., & Davoli, C. C. (2021). Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects. ACS pharmacology & translational science, 4(2), 424–435. https://doi.org/10.1021/acsptsci.1c00014

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Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity

February 21, 2022 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry / Leave a Comment / By / , , , ,

Abstract

A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from Psilocybe cubensis, chemically synthesized 5-methylpsilocin (2) was enzymatically phosphorylated to provide 5-methylpsilocybin (1). The zwitterionic product was isolated from the enzymatic step with high purity utilizing a solvent-antisolvent precipitation approach. Subsequently, 1 was tested for psychedelic-like activity using the mouse head-twitch response assay, which indicated activity that was more potent than the psychedelic dimethyltryptamine, but less potent than that of psilocybin.

Fricke, J., Sherwood, A. M., Halberstadt, A. L., Kargbo, R. B., & Hoffmeister, D. (2021). Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity. Journal of natural products, 84(4), 1403–1408. https://doi.org/10.1021/acs.jnatprod.1c00087

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