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Did you mean psilocybin micro dosing (9 results)?
Review
. 2024 Jun 14:2698811241254831.
doi: 10.1177/02698811241254831. Online ahead of print.

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research

Affiliations
Review

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research

Vince Polito et al. J Psychopharmacol. .

Abstract

Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

Keywords: LSD; Microdosing; expectation; hallucinogen; low dose; placebo; psilocybin; psychedelics.

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Vince Polito has received research funding from Mydecine Innovations Group and Woke Pharmaceuticals. Paul Liknaitzky has received research funding from Incannex Healthcare Ltd, the Multidisciplinary Association for Psychedelic Studies, and Beckley Psytech and is a member of the Medical Advisory Board of Incannex Healthcare Ltd and the Scientific Advisory Board of The MIND Foundation. These organisations were not involved in any aspect of this paper, including the decision to write it, drafting the paper, or its publication.

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Review
. 2024 May;9(5):512-521.
doi: 10.1016/j.bpsc.2024.02.004. Epub 2024 Feb 20.

Expectancy Effects in Psychedelic Trials

Affiliations
Review

Expectancy Effects in Psychedelic Trials

Balázs Szigeti et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May.

Abstract

Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the classic double-blind, placebo-controlled trial design. As widespread public enthusiasm for the promise of psychedelic therapy grows, so do questions regarding whether and how much trial results are biased by positive expectancy. First, we review the key concepts related to expectancy and its measurement. Then, we review expectancy effects that have been reported in both micro- and macrodose psychedelic trials from the modern era. Finally, we consider expectancy as a discrete physiological process that can be independent of, or even interact with, the drug effect. Expectancy effects can be harnessed to improve treatment outcomes and can also be actively managed in controlled studies to enhance the rigor and generalizability of future psychedelic trials.

Keywords: Blinding; Expectancy; Microdosing; Placebo; Psychedelic; Trial design.

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. 2024 Feb 5:15:1217102.
doi: 10.3389/fpsyt.2024.1217102. eCollection 2024.

Keeping the promise: a critique of the current state of microdosing research

Affiliations

Keeping the promise: a critique of the current state of microdosing research

Rotem Petranker et al. Front Psychiatry. .

Abstract

Introduction: The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing.

Methods: This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022.

Results: Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory.

Discussion: We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.

Keywords: LSD; microdosing; psilocybin; psychedelics; review.

Conflict of interest statement

MH is the CEO of Energia Holdings Incorporated, a Managing Partner of Tabula Rasa Ventures, and the Executive Director of the Energia Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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. 2024 Feb 10:1-12.
doi: 10.1080/02791072.2024.2313684. Online ahead of print.

Psychedelic Microdosing among Young Adults from Southern California

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Psychedelic Microdosing among Young Adults from Southern California

Alyssa F Harlow et al. J Psychoactive Drugs. .

Abstract

Despite common depictions in the media, there is little scientific evidence on microdosing psychedelic drugs. We assessed awareness, prevalence, and dosing practices of microdosing psychedelic drugs among young adults 18-22 years old from Southern California (2018-2019). We examined whether sociodemographic factors, personality traits, mental health, or other substance use behaviors were correlated with having ever microdosed. Among 2,396 participants, 293 (12%) had heard of microdosing and 74 (3%) ever microdosed. Among those who had heard of microdosing, 79% correctly defined microdosing as taking an amount of a psychedelic much lower than a standard dose, whereas 15% misperceived microdosing as a standard psychedelic dose. Psilocybin was the most common drug ever microdosed (70%), followed by lysergic acid diethylamide (LSD, 57%). Among those who ever microdosed, ~18% reported using psychoactive doses far higher than would be generally considered a microdose. White race, male/masculine gender identity, bisexual identity, past 6-month other drug use, greater attention deficit/hyperactivity disorder symptoms, mindfulness, and sensation-seeking were positively associated with having ever microdosed in multivariable models. Young adult microdosing merits further attention from scientific and public health professionals to help prevent misperceptions and potential adverse consequences as well as explore its potential therapeutic applications.

Keywords: LSD; MDMA; microdosing; psilocybin; psychedelics; young adults.

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. 2024 Jan 16;26(1):23r03581.
doi: 10.4088/PCC.23r03581.

Modern Psychedelic Microdosing Research on Mental Health: A Systematic Review

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Free article

Modern Psychedelic Microdosing Research on Mental Health: A Systematic Review

David F Lo et al. Prim Care Companion CNS Disord. .
Free article

Abstract

Objective: To investigate the relationship between psychedelic microdosing and its effects on mental health, aiming to understand if microdosing can improve mental well-being.

Data Sources: PubMed and Scopus were searched on December 25, 2022, using search terms related to psychedelics, microdosing, and mental health. The inclusion criteria focused on studies published between January 1, 2012, and November 30, 2022. There were no language restrictions for the initial search; however, for the study selection, only articles in English were considered.

Study Selection: A total of 45 articles were initially identified. After removing duplicates, 27 unique articles were screened based on their titles and abstracts, resulting in 19 articles included in the final review. The studies were selected based on their relevance to the relationship between mental health and psychedelic microdosing.

Data Extraction: The extracted data from the selected studies included sample sizes, demographics, survey designs, and qualitative and quantitative analyses related to the outcomes of individuals with mental health issues who also engaged in psychedelic microdosing. The QualSyst Quality Assessment Checklist was used to assess the methodological rigor and quality of each study. The data extraction process involved systematically reviewing each article and summarizing key findings related to the impact of microdosing on mental health.

Results: The review revealed that microdosing psychedelics, such as lysergic acid diethylamide and psilocybin, showed potential benefits on mental health. Users reported positive effects, including improved mood, increased focus, and better daily function. However, there were also challenges reported, such as physiologic discomfort and increased anxiety. Some studies observed that positive expectations about microdosing led to positive outcomes. The studies varied in design, with some being observational, others placebo-controlled, and some relying on self-reported data.

Conclusions: There is a growing body of evidence suggesting a positive correlation between psychedelic microdosing and improved mental well-being. However, due to the limited number of controlled studies and the small sample sizes in some of the studies, the causal relationship between microdosing and mental health improvement remains uncertain. The review calls for further research with double-blind experiments, control groups, and larger sample sizes that represent the general population to better understand the potential benefits and risks of psychedelic microdosing on mental health.

Prim Care Companion CNS Disord 2024;26(1):23r03581.

Author affiliations are listed at the end of this article.

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Review
. 2024 Mar;38(3):217-224.
doi: 10.1177/02698811231225609. Epub 2024 Jan 12.

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

Affiliations
Review

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

Antonin Rouaud et al. J Psychopharmacol. 2024 Mar.

Abstract

Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2-4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.

Keywords: Psychedelics; cardiology; psilocybin; serotonin.

Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Review
. 2023 Dec;75(6):1362-1380.
doi: 10.1007/s43440-023-00539-4. Epub 2023 Oct 24.

Cardiovascular safety of psychedelic medicine: current status and future directions

Affiliations
Review

Cardiovascular safety of psychedelic medicine: current status and future directions

Agnieszka Wsół. Pharmacol Rep. 2023 Dec.

Abstract

Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number of recent studies, due to the indisputable resurgence of serotonergic hallucinogens, have shown their efficacy in alleviating depression, anxiety, substance abuse therapies, and existential distress treatment in patients facing life-threatening illness. Psychedelics are generally considered to be physiologically safe with low toxicity and low addictive potential. However, their agonism at serotonergic receptors should be considered in the context of possible serotonin-related cardiotoxicity (5-HT2A/2B and 5-HT4 receptors), influence on platelet aggregation (5-HT2A receptor), and their proarrhythmic potential. The use of psychedelics has also been associated with significant sympathomimetic effects in both experimental and clinical studies. Therefore, the present review aims to provide a critical discussion of the cardiovascular safety of psilocybin, d-lysergic acid diethylamide (LSD), N,N-dimethyltryptamine, ayahuasca, and mescaline, based on the results of experimental research and clinical trials in humans. Experimental studies provide inconsistent information on the potential cardiovascular effects and toxicity of psychedelics. Data from clinical trials point to the relative cardiovascular safety of psychedelic-assisted therapies in the population of "healthy" volunteers. However, there is insufficient evidence from therapies carried out with microdoses of psychedelics, and there is still a lack of data on the safety of psychedelics in the population of patients with cardiovascular disease. Therefore, the exact determination of the cardiovascular safety of psychedelic therapies (especially long-term therapies) requires further research.

Keywords: Cardiovascular; LSD; Psilocybin; Psychedelics.

Conflict of interest statement

The author declares no conflict of interest.

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. 2023 Oct 5;9(1):169.
doi: 10.1186/s40814-023-01399-8.

An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1)

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An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1)

Carina Joy Donegan et al. Pilot Feasibility Stud. .

Abstract

Background: Globally, an estimated 260 million people suffer from depression [1], and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments [2], a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin [3]. Beyond anecdotal reports from those who self-medicate in this way, few clinical trials have evaluated this practice. In our recently published phase 1 study in healthy volunteers [4], we determined that LSD microdosing was relatively safe and well tolerated in that cohort. Furthermore, the data demonstrated that conducting such microdosing trials is broadly feasible, with excellent adherence and compliance to the regimen observed. In this open-label pilot trial of patients with major depressive disorder (LSDDEP1), we will test the tolerability and feasibility of an 8-week regimen of LSD microdosing in this patient group prior to a larger subsequent randomised controlled trial (LSDDEP2).

Methods: Twenty patients meeting the DSM-5 criteria for major depressive disorder will receive an 8-week LSD microdosing treatment regimen. The treatment protocol will use a sublingual formulation of LSD (MB-22001) delivered twice per week under a titration schedule using a dose of 5-15 µg. Tolerability will be assessed by quantifying the percentage of participants who withdraw from the trial due to adverse events attributable to the treatment regimen, while feasibility will be assessed by quantifying the percentage of attended clinic visits once enrolled. To determine whether there is any antidepressant response to the LSD microdosing regimen, MADRS scores will be assessed at baseline and 2, 4, 6, and 8 weeks after the commencement of the regimen.

Discussion: The results of LSDDEP1 will provide valuable information regarding the tolerability and feasibility of a proposed LSD microdosing regimen in patients with MDD. Such information is critically important to optimise trial design prior to commencing a subsequent and more resource-intensive randomised controlled trial.

Trial registration: ANZCTR, ACTRN12623000486628. Registered on 12 May 2023.

Keywords: Lysergic acid diethylamide; Major depressive disorder; Microdosing; Psychedelics.

Conflict of interest statement

The authors declare that they have no competing interests.

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. 2023 Sep;28(9):3829-3841.
doi: 10.1038/s41380-023-02280-z. Epub 2023 Oct 2.

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats

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Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats

Kat F Kiilerich et al. Mol Psychiatry. 2023 Sep.

Abstract

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects. Here we establish and validate a psilocybin microdose-like regimen in rats with repeated low doses of psilocybin administration at a dose derived from occupancy at rat brain 5-HT2A receptors in vivo. The rats tolerated the repeated low doses of psilocybin well and did not manifest signs of anhedonia, anxiety, or altered locomotor activity. There were no deficits in pre-pulse inhibition of the startle reflex, nor did the treatment downregulate or desensitize the 5-HT2A receptors. However, the repeated low doses of psilocybin imparted resilience against the stress of multiple subcutaneous injections, and reduced the frequency of self-grooming, a proxy for human compulsive actions, while also increasing 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin. Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.

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. 2023 Nov-Dec;55(5):672-679.
doi: 10.1080/02791072.2023.2253538. Epub 2023 Aug 31.

Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD

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Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD

Alexsandra Kovacevich et al. J Psychoactive Drugs. 2023 Nov-Dec.

Abstract

Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation.

Keywords: Anosmia; COVID-19; LSD; microsmia; psilocybin; psychedelics.

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. 2024 Jan;28(1):153-165.
doi: 10.1002/ejp.2171. Epub 2023 Aug 20.

Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study

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Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study

Mauro Cavarra et al. Eur J Pain. 2024 Jan.

Abstract

Background: Chronic pain is a major cause of suffering and disability and is often associated with psychiatric complications. Current treatments carry the risk of severe side effects and may lead to limited or no relief at all in a relevant portion of this patient population. Preliminary evidence suggests that classical psychedelics (e.g. LSD and psilocybin) may have analgesic effects in healthy volunteers, and in certain chronic pain conditions and observational studies reveal that they are used in naturalistic settings as a means to manage pain.

Methods: In order to gain insight on the effectiveness of such compounds in chronic pain conditions, we set up a survey addressed to chronic pain patients inquiring about psychedelic use and the relief levels achieved with both conventional treatments, full psychedelic doses and microdoses. We analysed data related to five conditions selected based on diagnostic homogeneity within each of them: fibromyalgia, arthritis, migraine, tension-type headache and sciatica.

Results: Except for sciatica, volunteers reported that psychedelics led to better pain relief compared to conventional medication in all examined conditions. More specifically, full doses performed better than conventional medication. Microdoses led to significantly better relief compared to conventional medication in migraines and achieved comparable relief in the remaining three categories. Implications for future research are discussed.

Conclusions: Full doses and microdoses may hold value in the treatment of some specific chronic pain conditions.

Significance: Psychedelic substances are receiving increasing attention from the scientific literature because of evidence showing beneficial effects on several measures related to mental health in clinical samples and healthy volunteers samples. Previous evidence suggests that people suffering from chronic pain are using psychedelics to seek relief and the present paper presents the results of a survey study investigating their use and analgesic effects among individuals suffering from fibromyalgia, arthritis, migraine, tension-type headache and sciatica.

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. 2023 Sep;37(9):876-890.
doi: 10.1177/02698811231190865. Epub 2023 Aug 12.

The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

Affiliations
Review

The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

Michael Tagen et al. J Psychopharmacol. 2023 Sep.

Abstract

Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT2B receptor. However, this risk has not yet been comprehensively assessed. This analysis searched for all relevant in vitro, animal, and clinical studies related to the VHD risk of lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT), and the non-psychedelic 3,4-methylenedioxymethamphetamine (MDMA). All five compounds and some metabolites could bind to the 5-HT2B receptor with potency equal to or greater than that of the 5-HT2A receptor, the primary target of psychedelics. All compounds were partial agonists at the 5-HT2B receptor with the exception of mescaline, which could not be adequately assessed due to low potency. Safety margins relative to the maximum plasma concentrations from typical microdoses were greater than known valvulopathogens, but not without potential risk. No animal or clinical studies appropriately designed to evaluate VHD risk were found for the four psychedelics. However, there is some clinical evidence that chronic ingestion of full doses of MDMA is associated with VHD. We conclude that VHD is a potential risk with chronic psychedelic microdosing, but further studies are necessary to better define this risk.

Keywords: Psychedelics; microdosing; valvular heart disease.

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. 2023 Aug 7;24(15):12513.
doi: 10.3390/ijms241512513.

A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression

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Review

A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression

Alexander Pilozzi et al. Int J Mol Sci. .

Abstract

Alzheimer's disease (AD), the most common form of senile dementia, is poised to place an even greater societal and healthcare burden as the population ages. With few treatment options for the symptomatic relief of the disease and its unknown etiopathology, more research into AD is urgently needed. Psychedelic drugs target AD-related psychological pathology and symptoms such as depression. Using microdosing, psychedelic drugs may prove to help combat this devastating disease by eliciting psychiatric benefits via acting through various mechanisms of action such as serotonin and dopamine pathways. Herein, we review the studied benefits of a few psychedelic compounds that may show promise in treating AD and attenuating its related depressive symptoms. We used the listed keywords to search through PubMed for relevant preclinical, clinical research, and review articles. The putative mechanism of action (MOA) for psychedelics is that they act mainly as serotonin receptor agonists and induce potential beneficial effects for treating AD and related depression.

Keywords: Alzheimer’s disease; DMT; LSD; dementia; depression; ketamine; mescaline; psilocybin; psychedelics.

Conflict of interest statement

Mischoulon has received research support from Nordic Naturals and Heckel Medizintechnik GmbH. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Peerpoint Medical Education Institute, LLC, and Harvard blog. He also works with the MGH Clinical Trials Network and Institute (CTNI), which has received research funding from multiple pharmaceutical companies and NIMH. The remaining authors declare no conflicts of interest. The funder had no role in the writing of the manuscript.

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. 2023 Jun 29:14:1136990.
doi: 10.3389/fpsyt.2023.1136990. eCollection 2023.

Psychedelic Assisted Psychotherapy preparing your target using psychohistoriography: a Jamaican perspective

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Psychedelic Assisted Psychotherapy preparing your target using psychohistoriography: a Jamaican perspective

Winston De La Haye et al. Front Psychiatry. .

Abstract

The efficacy of psilocybin and other psychedelics as modes of treatment have been demonstrated through clinical trials and other studies in the management of a number of mental illnesses, including some treatment resistant cases. In Psychedelic Assisted Psychotherapy (PAP), psychedelics catalyze or enhance the experience fostered by psychotherapeutic methods. Psychohistoriographic Brief Psychotherapy, conceptualized by the late Professor Frederick Hickling in the 1970's in Kingston, Jamaica, offers a pathway for exploration in the Jamaican context. Applied to individuals, Psychohistoriographic Brief Therapy (PBT) has already shown success in patients with personality disorders in Jamaica through a process which includes documenting life experiences in a psychohistoriogram. In the De La Haye psilocybin Treatment Protocol (DPTP), micro-doses of crushed, dried psilocybin mushrooms are taken throughout an 8-week outpatient process of documenting the components of the psychohistoriogram, making use of the increased openness and empathy associated with the use of psychedelic agents. These sessions are followed by supervised in-office therapeutic/mystical doses of crushed, dried psilocybin mushrooms in the 9th week. Given the legal status and availability of psilocybin containing products in a few countries like Jamaica, there is a potential role for a regulated psychedelic industry contributing to the body of useful and rigorous clinical research which is needed in this area. Clients could benefit as we venture into this new frontier in psychiatry.

Keywords: Psychedelic Assisted Psychotherapy; new frontier; psilocybin; psychedelics; psychohistoriography.

Conflict of interest statement

WD was employed as Medical Director by Aion Therapeutic Inc. in 2021. This association ended in 2022. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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. 2023 Jul;37(7):635-648.
doi: 10.1177/02698811231179801. Epub 2023 Jul 3.

Psilocybin's effects on cognition and creativity: A scoping review

Affiliations
Review

Psilocybin's effects on cognition and creativity: A scoping review

Justin N Bonnieux et al. J Psychopharmacol. 2023 Jul.

Abstract

Background: Research on psilocybin has become increasingly popular during the current psychedelic renaissance, which began in the early 1990s. Psilocybin's effects on mental health are promising and there are ongoing efforts to investigate its clinical implementation and its effects on cognition.

Aims: The purpose of this study is to report trends in publications, methods, and findings from research examining the effects of psilocybin on cognition and creativity in adults.

Methods: We conducted an Open Science Framework preregistered scoping review, guided by the JBI Manual for Evidence Synthesis, on literature pertaining to psilocybin's effects on cognition and creativity.

Results/outcomes: In the 42 included studies, psilocybin was primarily administered orally (83%) in a bodyweight-adjusted manner (74%) to healthy participants (90%). Of the few studies that explicitly reported safety outcomes (26%), only one reported serious adverse reactions. During the acute phase post-intake (i.e., minutes to hours), macrodoses tended to impair cognitive performance and creativity, whereas microdoses tended toward creative enhancement. The few macrodosing studies that included post-acute measures (i.e., 1-85 days) reported primarily null but some positive effects.

Conclusions/interpretation: This scoping review identified a time-based variation of psilocybin macrodosing effects on cognition and creativity, in which impairment may be observed early post-intake but withdraw over time, and some positive effects may emerge afterward. These findings are limited by methodological concerns and inadequate assessment of long-term effects. We therefore recommend that future psilocybin research be conducted according to existing guidelines and include well-validated measures of cognition and creativity at multiple timepoints.

Keywords: Psilocybin; cognition; creativity; evidence synthesis; executive function; scoping review.

Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AGR is a paid scientific advisor to NeonMind Biosciences, InnerWell, and ETHA Natural Botanicals. AGR has received research funding from MicroDoz Therapy Inc., Mydecine Innovations Group Inc., Unlimited Sciences, the Council on Spiritual Practices, the Heffter Research Institute, and National Institutes of Health. Effort from AGR on this work was supported through the Johns Hopkins Center for Psychedelic and Consciousness Research with funding provided by Tim Ferriss, Matt Mullenweg, Blake Mycoskie, Craig Nerenberg, and the Steven and Alexandra Cohen Foundation.

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. 2023 Aug;21(4):697-704.
doi: 10.1017/S147895152300069X.

Psychedelic medicines for end-of-life care: Pipeline clinical trial review 2022

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Review

Psychedelic medicines for end-of-life care: Pipeline clinical trial review 2022

Xuepeng Jing et al. Palliat Support Care. 2023 Aug.

Abstract

Objectives: People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life.

Methods: Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials.

Results: In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine (n = 11), psilocybin (n = 10), 3,4-methylenedioxymethamphetamine (n = 2), and lysergic acid diethylamide (n = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy.

Significance of results: A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.

Keywords: End-of-life; Existential distress; Palliative care; Psychedelics; Scoping review.

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. 2023 Mar 14;23(1):160.
doi: 10.1186/s12888-023-04628-9.

Experiences of microdosing psychedelics in an attempt to support wellbeing and mental health

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Experiences of microdosing psychedelics in an attempt to support wellbeing and mental health

Rebecca S Ryan et al. BMC Psychiatry. .

Abstract

Background: Microdosing psychedelic drugs is a growing phenomenon, but little is known about the experiences surrounding this. Research broadly suggests that people may use psychedelics in an attempt to self-medicate for mental health and wellbeing. However, the precise details, rationale and meaning of such attempts remains unclear, and would benefit from clarification, using tailored experiential methods. This research therefore aimed to explore the way that users make sense of microdosing psychedelics, with a particular focus on the experience of any perceived mental health or wellbeing changes.

Method: Participants were recruited via websites and online forums. An internet text-based, semi-structured interview was conducted anonymously with 13 participants regarding their experiences of microdosing psychedelic drugs. Interpretive Phenomenological Analysis was used to analyse the transcripts.

Results: Three superordinate themes were identified through the interviews: 1) Seeking a solution: Agency and rationale; 2) Microdosers as scientists; 3) Catalysing desirable and beneficial effects.

Conclusions: All participants approached microdosing methodically and with purpose. Participants reported that they had experienced beneficial effects of microdosing on their mental health, alongside cognitive, physical and social changes. By microdosing, participants reported that they had supported their own mental health and wellbeing, with microdosing described as a catalyst to achieving their aims in this area. This study provided additional knowledge and understanding of the experience, rationale and personal meaning of the microdosing phenomenon which can be used to inform future investigations in the areas of psychedelic use and mental health.

Keywords: LSD; Mental health; Microdosing; Psilocybin; Psychedelics; Wellbeing.

Conflict of interest statement

The authors declare that they have no competing interests.

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Case Reports
. 2023 Mar 3:16:109-115.
doi: 10.2147/IMCRJ.S395342. eCollection 2023.

The Effectiveness of Microdosed Psilocybin in the Treatment of Neuropsychiatric Lyme Disease: A Case Study

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Case Reports

The Effectiveness of Microdosed Psilocybin in the Treatment of Neuropsychiatric Lyme Disease: A Case Study

Daniel A Kinderlehrer. Int Med Case Rep J. .

Abstract

Lyme disease can result in severe neuropsychiatric symptoms that may be resistant to treatment. The pathogenesis of neuropsychiatric Lyme disease is associated with autoimmune induced neuroinflammation. This case report describes an immunocompetent male with serologically positive neuropsychiatric Lyme disease who did not tolerate antimicrobial or psychotropic medications and whose symptoms remitted when he began psilocybin in microdosed (sub-hallucinogenic) amounts. A literature review of its therapeutic benefits reveals that psilocybin is both serotonergic and anti-inflammatory and therefore may offer significant therapeutic benefits to patients with mental illness secondary to autoimmune inflammation. The role of microdosed psilocybin in the treatment of neuropsychiatric Lyme disease and autoimmune encephalopathies warrants further study.

Keywords: Lyme; autoimmune; encephalopathy; mental illness; microdose; neuroinflammation; psilocybin; psychedelic.

Conflict of interest statement

The author reports no conflicts of interest in this work.

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Review
. 2023 Apr 1:227:109426.
doi: 10.1016/j.neuropharm.2023.109426. Epub 2023 Jan 21.

Psychedelics: Science sabotaged by Social Media

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Free article
Review

Psychedelics: Science sabotaged by Social Media

Edward M Sellers et al. Neuropharmacology. .
Free article

Abstract

The substantial challenges facing high and low dose psychedelic drug development to achieve regulatory approval have been documented in the scientific literature. These limitations have not deterred drug developers and social media from repeatedly misleading patients, the public and health professionals. Developing "micro doses" of psychedelics overcomes many of the scientific and regulatory challenges of high dose psychedelics. If micro-dosing could be shown to be efficacious and safe for long term use, it could be administered in the typical model for treatment of mental disorders. Such a model would be more cost effective than the high dose/intense psychotherapy model currently described and could be readily available to all individuals who need another medication option. Outpatient psychotherapeutic agents have a clear route for approval and would be unlikely to be burdened by the extensive Risks Evaluation and Mitigation Strategy needed for high dose use. There may be a different therapeutic role for both high and low dose psychedelic agents. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

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Review
. 2022 Nov 22;14(11):e31796.
doi: 10.7759/cureus.31796. eCollection 2022 Nov.

Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis

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Review

Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis

Ricardo Irizarry et al. Cureus. .

Abstract

Psilocybin is an emerging potential therapy for the treatment of psychiatric illnesses. Microdosing has been shown to result in an overall improvement in patients with anxiety, depression, obsessive-compulsive disorder, post-traumatic stress disorder, and substance abuse. This meta-analysis explores and compiles prior research to make further inferences regarding psilocybin and its use for the treatment of psychiatric illness along with its safety and efficacy. Database searches were conducted to identify peer-reviewed randomized controlled trials and clinical trials mentioning psilocybin use and psychiatric illness. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram was created and analysis was run on the nine articles that met all established inclusion criteria. An event is defined as a participant who showed improvement, in a quantitative method, from baseline after the use of psilocybin. Another analysis was done using depression severity (Quick Inventory of Depressive Symptomatology 16-Item Self Report, QIDS-SR16) at baseline and after the use of psilocybin. Analyses of the original data and the nine articles showed a great deal of heterogeneity with an I2 value of 73.68%, suggesting that the studies in this meta-analysis cannot be considered to be studies of the same population. The Q value of 30.4 was higher than 15.507, which is the critical value for eight degrees of freedom found in a chi-square distribution. This Q value showed a high degree of variation and lacked significance. The second meta-run on QIDS-SR16 scores from three studies showed a Q value of 1.16 which was lower than 5.991, the critical value for two degrees of freedom found in a chi-square distribution. The I2 statistic for this second meta-analysis was -73% which can be equated to zero. This indicated that the data were homogeneous or that there was no observed heterogeneity. Due to low heterogeneity, the fixed-effects model was used. Based on this meta-analysis, psilocybin seems to show symptom improvement in some psychiatric illnesses. The effectiveness of psilocybin microdosing and the use of psilocybin, in general, need to be studied further to determine the efficacy and safety of potential applications in psychiatry.

Keywords: anxiety; depression; magic mushrooms; meta-analysis; psilocybin; psychedelics; psychiatric illness.

Conflict of interest statement

The authors have declared that no competing interests exist.

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. 2023 Jan;240(1):137-147.
doi: 10.1007/s00213-022-06286-3. Epub 2022 Dec 5.

Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome

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Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome

Valeria Buzzelli et al. Psychopharmacology (Berl). 2023 Jan.

Abstract

Rationale: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neuro