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Mushrooms / Psilocybin

Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review

November 26, 2021 / LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / ,

Abstract

Microdosing psychedelic drugs-that is, taking sub-behavioral doses of lysergic acid diethylamide (LSD) or psilocybin-is a growing practice in Western societies. Taken mainly for creative or mood-enhancing purposes, thousands of users are increasingly being exposed to (micro)doses of psychedelic drugs. In this systematic review, we searched the available evidence from human studies, focusing our results in terms of three main axes: efficacy, safety, and the influence of the placebo effect in microdosing practices. While the available evidence has some strengths (e.g. large sample sizes, robust methodologies) there are also remarkable limitations (e.g. gender bias, heterogeneity of dosing schedules and drugs used). Highly contradictory results have been found, showing both the benefits and detriments of microdosing in terms of mood, creative processes, and energy, among other regards. This review provides a general overview of the methods and approaches used, which could be useful for improving future studies.

Ona, G., & Bouso, J. C. (2020). Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review. Neuroscience and biobehavioral reviews, 119, 194–203. https://doi.org/10.1016/j.neubiorev.2020.09.035

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The emerging role of psilocybin and MDMA in the treatment of mental illness

November 26, 2021 / MDMA, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , , , , , , , , , , ,

Abstract

Introduction: Mental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive, and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of mental illness is estimated to exceed $1.8 trillion USD over the next 30 years. A significant number of individuals affected by mental illness fail to respond to first-line treatment options. Therefore, there remains an unmet need for rapidly attenuating therapeutic options for mental health disorders with minimal social and economic burden.

Areas covered: The paucity of novel treatment options warrants a renewed investigation of psychedelic-based psychotherapy. Herein, the authors will evaluate the therapeutic potential of traditional psychedelics, psilocybin, and MDMA, in the treatment of mental illness with a narrative review of available literature.

Expert opinion: Psychedelics, such as psilocybin and MDMA, offer an alternative avenue of therapy for many mental health disorders. Available evidence indicates that psychedelics may offer a single-dose, rapid effect model that have robust effects with treatment-resistant mental disorders and a unique advantage as a possible monotherapy for mental illness. Novel clinical trials that evaluate the safety, tolerability, and efficacy in clinically representative populations are warranted.

Gill, H., Gill, B., Chen-Li, D., El-Halabi, S., Rodrigues, N. B., Cha, D. S., Lipsitz, O., Lee, Y., Rosenblat, J. D., Majeed, A., Mansur, R. B., Nasri, F., Ho, R., & McIntyre, R. S. (2020). The emerging role of psilocybin and MDMA in the treatment of mental illness. Expert review of neurotherapeutics, 20(12), 1263–1273. https://doi.org/10.1080/14737175.2020.1826931

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Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study

December 2, 2021 / Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , , , , , , , ,

Abstract

Background: Psilocybin therapy has shown promise as a rapid-acting treatment for depression, anxiety, and demoralization in patients with serious medical illness (e.g., cancer) when paired with individual psychotherapy. This study assessed the safety and feasibility of psilocybin-assisted group therapy for demoralization in older long-term AIDS survivor (OLTAS) men, a population with a high degree of demoralization and traumatic loss.

Methods: Self-identified gay men OLTAS with moderate-to-severe demoralization (Demoralization Scale-II ≥8) were recruited from the community of a major US city for a single-site open-label study of psilocybin-assisted group therapy comprising 8-10 group therapy visits and one psilocybin administration visit (0·3-0·36 mg/kg po). Primary outcomes were rate and severity of adverse events, and participant recruitment and retention. The primary clinical outcome was change in mean demoralization from baseline to end-of-treatment and to 3-month follow-up assessed with a two-way repeated measures ANOVA. Trial registration: Clinicaltrials.gov (NCT02950467).

Findings: From 17 July 2017 to 16 January 2019, 18 participants (mean age 59·2 years (SD 4·4)) were enrolled, administered group therapy and psilocybin, and included in intent-to-treat analyses. We detected zero serious adverse reactions and two unexpected adverse reactions to psilocybin; seven participants experienced self-limited, severe expected adverse reactions. We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], ηp 2 = 0·47, 90% CI 0·21-0·60).

Interpretation: We demonstrated the feasibility, relative safety, and potential efficacy of psilocybin-assisted group therapy for demoralization in OLTAS. Groups may be an effective and efficient means of delivering psychotherapy pre- and post-psilocybin to patients with complex medical and psychiatric needs.

Anderson, B. T., Danforth, A., Daroff, P. R., Stauffer, C., Ekman, E., Agin-Liebes, G., Trope, A., Boden, M. T., Dilley, P. J., Mitchell, J., & Woolley, J. (2020). Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study. EClinicalMedicine, 27, 100538. https://doi.org/10.1016/j.eclinm.2020.100538

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Compassionate use of psychedelics

September 23, 2020 / MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. When talking about psychedelics, we mean specifically two substances: psilocybin and MDMA. When administered under supportive conditions and in conjunction with psychotherapy, therapies assisted by these substances show promising results. However, given the publicly controversial nature of psychedelics, compassionate psychedelic psychotherapy calls for ethical justification. We thus review the safety and efficacy of psilocybin- and MDMA-assisted therapies and claim that it can be rational for some patients to try psychedelic therapy. We think it can be rational despite the uncertainty of outcomes associated with compassionate use as an unproven treatment regime, as the expected value of psychedelic psychotherapy can be assessed and can outweigh the expected value of routine care, palliative care, or no care at all. Furthermore, we respond to the objection that psychedelic psychotherapy is morally impermissible because it is epistemically harmful. We argue that given the current level of understanding of psychedelics, this objection is unsubstantiated for a number of reasons, but mainly because there is no experimental evidence to suggest that epistemic harm actually takes place.
Greif, A., & Šurkala, M. (2020). Compassionate use of psychedelics. Medicine, Health Care, and Philosophy.,
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Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin

November 18, 2021 / Anxiety Disorders / PTSD, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , ,

Abstract

The aim of this systematic review was to examine the efficacy of MDMA, ketamine, LSD, and psilocybin for the treatment of posttraumatic stress disorder (PTSD). A search of four databases for English language, peer-reviewed literature published from inception to 18th October 2019 yielded 2,959 records, 34 of which were screened on full-text. Observational studies and RCTs which tested the efficacy of MDMA, ketamine, LSD, or psilocybin for reducing PTSD symptoms in adults, and reported changes to PTSD diagnosis or symptomatology, were included. Nine trials (five ketamine and four MDMA) met inclusion criteria. Trials were rated on a quality and bias checklist and GRADE was used to rank the evidence. The evidence for ketamine as a stand-alone treatment for comorbid PTSD and depression was ranked “very low”, and the evidence for ketamine in combination with psychotherapy as a PTSD treatment was ranked “low”. The evidence for MDMA in combination with psychotherapy as a PTSD treatment was ranked “moderate”.

Varker, T., Watson, L., Gibson, K., Forbes, D., & O’Donnell, M. L. (2021). Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin. Journal of psychoactive drugs, 53(1), 85–95. https://doi.org/10.1080/02791072.2020.1817639

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Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials

November 18, 2021 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , ,

Abstract

Psilocybin is a naturally occurring tryptamine known for its psychedelic properties. Recent research indicates that psilocybin may constitute a valid approach to treat depression and anxiety associated to life-threatening diseases. The aim of this work was to perform a systematic review with meta-analysis of clinical trials to assess the therapeutic effects and safety of psilocybin on those medical conditions. The Beck Depression Inventory (BDI) was used to measure the effects in depression and the State-Trait Anxiety Inventory (STAI) was used to measure the effects in anxiety. For BDI, 11 effect sizes were considered (92 patients) and the intervention group was significantly favored (WMD = -4.589; 95% CI = -4.207 to -0.971; p-value = 0.002). For STAI-Trait, 11 effect sizes were considered (92 patients), being the intervention group significantly favored when compared to the control group (WMD = -5.906; 95% CI = -7.852 to -3.960; p-value ˂ 0.001). For STAI-State, 9 effect sizes were considered (41 patients) and the intervention group was significantly favored (WMD = -6.032; 95% CI = -8.900 to -3.164; p-value ˂ 0.001). The obtained results are promising and emphasize the importance of psilocybin translational research in the management of symptoms of depression and anxiety, since the compound may be effective in reducing symptoms of depression and anxiety in conditions that are either resistant to conventional pharmacotherapy or for which pharmacologic treatment is not yet approved. Moreover, it may be also relevant for first-line treatment, given its safety.

Vargas, A. S., Luís, Â., Barroso, M., Gallardo, E., & Pereira, L. (2020). Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials. Biomedicines, 8(9), 331. https://doi.org/10.3390/biomedicines8090331

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Phytochemical, Cytotoxicity, Antioxidant and Anti-Inflammatory Effects of Psilocybe Natalensis Magic Mushroom

August 31, 2020 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , ,

Abstract

Psilocybin-containing mushrooms, commonly known as magic mushrooms, have been used since ancient and recent times for depression and to improve quality of life. However, their anti-inflammatory properties are not known. The study aims at investing cytotoxicity; antioxidant; and, for the first time, anti-inflammatory effects of Psilocybe natalensis, a psilocybin-containing mushroom that grows in South Africa, on lipopolysaccharide-induced RAW 264.7 macrophages. Macrophage cells were stimulated with lipopolysaccharide and treated with different concentrations of Psilocybe natalensis mushroom extracted with boiling hot water, cold water and ethanol over 24 h. Quercetin and N-nitro-L-arginine methyl ester were used as positive controls. Effects of extracts on the lipopolysaccharide-induced nitric oxide, prostaglandin E2, and cytokine activities were investigated. Phytochemical analysis, and the antioxidant and cytotoxicity of extracts, were determined. Results showed that the three extracts inhibited the lipopolysaccharide-induced nitric oxide, prostaglandin E2, and interleukin 1β cytokine production significantly in a dose-dependent manner close to that of the positive controls. A study proposed that ethanol and water extracts of Psilocybe natalensis mushroom were safe at concentrations used, and have antioxidant and anti-inflammatory effects. Phytochemical analysis confirmed the presence of natural antioxidant and anti-inflammatory compounds in the mushroom extracts.

Nkadimeng, S. M., Nabatanzi, A., Steinmann, C. M., & Eloff, J. N. (2020). Phytochemical, Cytotoxicity, Antioxidant and Anti-Inflammatory Effects of Psilocybe Natalensis Magic Mushroom. Plants, 9(9), 1127; https://doi.org/10.3390/plants9091127

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The therapeutic potential of microdosing psychedelics in depression

November 18, 2021 / Depressive Disorders, LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By /

Abstract

Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10-20 mcg) and psilocybin (<1-3 mg) have subtle (positive) effects on cognitive processes (time perception, convergent and divergent thinking) and brain regions involved in affective processes. Besides the pleasant experience, increased anxiety and a cycling pattern of depressive and euphoric mood were also found. With regard to safety, it was demonstrated that low doses are well tolerated (in healthy volunteers) and have no-to-minimal effects on physiological measures. While it is yet unclear whether psychedelic microdosing is of therapeutic value for depression, the aforementioned effects on selective processes suggest that low doses of psychedelics could play a role in depression by inducing some kind of cognitive flexibility, which might lead to decreased rumination. While previous studies were conducted mostly in small samples of healthy volunteers, future placebo-controlled clinical trials in depressed patients are required to understand the therapeutic value of microdosing psychedelics, how this differs from therapy using full psychedelic doses, and whether different psychedelics have different effect patterns. The proposed research will give new insights into the potential of future alternative psychiatric treatment forms that are fiercely needed.

Kuypers K. (2020). The therapeutic potential of microdosing psychedelics in depression. Therapeutic advances in psychopharmacology, 10, 2045125320950567. https://doi.org/10.1177/2045125320950567

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Plasma psilocin critically determines behavioral and neurobiological effects of psilocybin

August 25, 2020 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / ,

Madsen, M. K., & Knudsen, G. M. (2021). Plasma psilocin critically determines behavioral and neurobiological effects of psilocybin. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 46(1), 257-258; 10.1038/s41386-020-00823-4
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Psychedelics as a Treatment for Alzheimer’s Disease Dementia

January 3, 2022 / LSD, Microdosing, Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / ,

Abstract

Currently, there are no disease-modifying treatments for Alzheimer’s disease (AD) or any other dementia subtype. The renaissance in psychedelic research in recent years, in particular studies involving psilocybin and lysergic acid diethylamide (LSD), coupled with anecdotal reports of cognitive benefits from micro-dosing, suggests that they may have a therapeutic role in a range of psychiatric and neurological conditions due to their potential to stimulate neurogenesis, provoke neuroplastic changes and reduce neuroinflammation. This inevitably makes them interesting candidates for therapeutics in dementia. This mini-review will look at the basic science and current clinical evidence for the role of psychedelics in treating dementia, especially early AD, with a particular focus on micro-dosing of the classical psychedelics LSD and psilocybin.

Vann Jones, S. A., & O’Kelly, A. (2020). Psychedelics as a Treatment for Alzheimer’s Disease Dementia. Frontiers in synaptic neuroscience, 12, 34. https://doi.org/10.3389/fnsyn.2020.607194

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