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Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice

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

Abstract

Psychedelic Harm Reduction and Integration (PHRI) is a transtheoretical and transdiagnostic clinical approach to working with patients who are using or considering using psychedelics in any context. The ongoing discussion of psychedelics in academic research and mainstream media, coupled with recent law enforcement deprioritization of psychedelics and compassionate use approvals for psychedelic-assisted therapy, make this model exceedingly timely. Given the prevalence of psychedelic use, the therapeutic potential of psychedelics, and the unique cultural and historical context in which psychedelics are placed, it is important that mental health providers have an understanding of the unique motivations, experiences, and needs of people who use them. PHRI incorporates elements of harm reduction psychotherapy and psychedelic-assisted psychotherapy, and can be applied in both brief and ongoing psychotherapy interactions. PHRI represents a shift away from assessment limited to untoward outcomes of psychedelic use and abstinence-based addiction treatment paradigms and toward a stance of compassionate, destigmatizing acceptance of patients’ choices. Considerations for assessment, preparation, and working with difficult experiences are presented.

Gorman, I., Nielson, E. M., Molinar, A., Cassidy, K., & Sabbagh, J. (2021). Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice. Frontiers in psychology, 12, 645246. https://doi.org/10.3389/fpsyg.2021.645246

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On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review

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

Abstract

Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly, further understanding of the relationship between classic psychedelics and suicidality is needed. Therefore, we conducted a systematic review of the relationship between classic psychedelics (both non-clinical psychedelic use and psychedelic therapy) and suicidality. We identified a total of 64 articles, including 41 articles on the association between non-clinical classic psychedelic use and suicidality and 23 articles on the effects of psychedelic therapy on suicidality. Findings on the association between lifetime classic psychedelic use and suicidality were mixed, with studies finding positive, negative, and no significant association. A small number of reports of suicide and decreased suicidality following non-clinical classic psychedelic use were identified. Several cases of suicide in early psychedelic therapy were identified; however, it was unclear whether this was due to psychedelic therapy itself. In recent psychedelic therapy clinical trials, we found no reports of increased suicidality and preliminary evidence for acute and sustained decreases in suicidality following treatment. We identify some remaining questions and provide suggestions for future research on the association between classic psychedelics and suicidality.

Zeifman, R. J., Singhal, N., Breslow, L., & Weissman, C. R. (2021). On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review. ACS pharmacology & translational science, 4(2), 436–451. https://doi.org/10.1021/acsptsci.1c00024

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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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Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review

March 14, 2022 / Depressive Disorders, Palliative Care+, Papers, Substance Use Disorder / Leave a Comment / By / , , , ,

Abstract

Background: The use of psychedelic treatments has shown very promising results in some psychiatric and addictive disorders, but not all patients achieved a response.

Aim: The aim of this review is to explore the clinical and biological factors which could predict the response to psychedelics in psychiatric and addictive disorders.

Methods: A systematic research was performed on MEDLINE, PsycInfo, Web of science, and Scopus databases from January 1990 to May 2020. All studies investigating the predictive factors of response to psychedelics regardless of psychiatric or addictive disorders, were included.

Results: Twenty studies investigating addictive disorder, treatment-resistant depression, obsessive-compulsive disorder and depressive and anxiety symptoms in patients with life-threatening cancer were included in this review. We found that, in all indications, the main predictive factor of response to psychedelics is the intensity of the acute psychedelic experience. Indeed, we found this factor for alcohol and tobacco use disorders, treatment-resistant depression, and anxiety and depressive symptoms in patients with life-threatening cancer, but not for obsessive-compulsive disorder.

Conclusion: The intensity of the acute psychedelic experience was the main predicting factor of response. The action mechanism of this experience was not clear, but some hypotheses could be made, such as a modulation of serotoninergic system by 5-HT2A receptors agonism, a modulation of the default mode network (DMN) with an acute modular disintegration of the DMN followed by a re-integration of this network with a normal functioning, or an anti-inflammatory effect of this treatment.

Romeo, B., Hermand, M., Pétillion, A., Karila, L., & Benyamina, A. (2021). Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review. Journal of psychiatric research, 137, 273–282. https://doi.org/10.1016/j.jpsychires.2021.03.002

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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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The Use of Classic Hallucinogens/Psychedelics in a Therapeutic Context: Healthcare Policy Opportunities and Challenges

February 21, 2022 / Papers / Leave a Comment / By / , , , ,

Abstract

Psychedelics or serotonergic hallucinogens are a group of substances that share the agonism of serotonergic 5-HT2A receptors as their main mechanism of action. Its main effects include changes in perception, cognitive process, and mood. Despite being used for centuries by different cultures in ritual contexts, these substances have currently aroused the interest of science and industry for their promising antidepressant, anxiolytic, and anti-addictive effects. Considering this evidence, this article aims to explore some of the possible health policy challenges to integrate these therapeutic tools into broad and heterogeneous health systems. As a main benefit, these substances produce rapid and enduring effects with the administration of single or few doses, which could lead to new treatment possibilities for patients with severe mental disorders resistant to the usual medications. The main challenge is associated with the fact that these substances remain scheduled in most countries and are associated with social stigma related to their recreational use (especially LSD and psilocybin). This situation makes it exceedingly difficult to conduct clinical trials, although international conventions allow such research. Ethically, this could be interpreted as a violation of human rights since thousands of people are prevented from having access to possible benefits. Interestingly, ritual ayahuasca use is more acceptable to the public than the use of psilocybin-containing mushrooms or LSD. The controlled, clinical use of LSD and psilocybin seems to be less criticized and is being explored by the industry. Rigorous scientific evidence coupled with industrial interests (LSD and psilocybin), together with respect for traditional uses (ayahuasca) and international conventions, seems to be the best way for these drugs to be integrated into health systems in the next years. Which highlights the need for an urgent dialogue between science, health system, society, and politics.

Dos Santos, R. G., Bouso, J. C., Rocha, J. M., Rossi, G. N., & Hallak, J. E. (2021). The Use of Classic Hallucinogens/Psychedelics in a Therapeutic Context: Healthcare Policy Opportunities and Challenges. Risk management and healthcare policy, 14, 901–910. https://doi.org/10.2147/RMHP.S300656

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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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Dose-response relationships of psilocybin-induced subjective experiences in humans

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

Abstract

Background: Psilocybin is the psychoactive component in Psilocybe mushrooms (‘magic mushrooms’). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.

Aim: Establishing dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups.

Method: We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose-response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale.

Results: Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose.

Conclusion: Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.

Hirschfeld, T., & Schmidt, T. T. (2021). Dose-response relationships of psilocybin-induced subjective experiences in humans. Journal of psychopharmacology (Oxford, England), 35(4), 384–397. https://doi.org/10.1177/0269881121992676

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Self-blinding citizen science to explore psychedelic microdosing

February 21, 2022 / Microdosing, Papers, Psychology / Leave a Comment / By / , , , , , , ,

Abstract

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Szigeti, B., Kartner, L., Blemings, A., Rosas, F., Feilding, A., Nutt, D. J., Carhart-Harris, R. L., & Erritzoe, D. (2021). Self-blinding citizen science to explore psychedelic microdosing. eLife, 10, e62878. https://doi.org/10.7554/eLife.62878

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