Psychedelics for the Treatment of Psychiatric Disorders: Interpreting and Translating Available Evidence and Guidance for Future Research

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 21 - 32

Published: Jan. 1, 2025

During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain are effective safe treatment of major depressive disorder, treatment-resistant depression, posttraumatic stress disorder. Preliminary evidence also supports efficacy other disorders (e.g., tobacco alcohol use disorders). Notwithstanding promise psychedelics, concerns have arisen with respect to interpretability translatability study results. For example, aspects related short- long-term safety, abuse liability, essentiality psychedelic "trip" psychological support are, inter alia, insufficiently characterized agents. The overarching aims this overview 1) review methodological affect inferences interpretation extant studies disorders, 2) provide guidance future development psychiatry, critical clinical implementation.

Language: Английский

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Psilocybin: From Psychiatric Pariah to Perceived Panacea

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 54 - 78

Published: Jan. 1, 2025

The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.

Language: Английский

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Psychedelics in Psychiatry: Oh, What A Trip!

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 1 - 5

Published: Jan. 1, 2025

Language: Английский

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

Journal of Psychopharmacology, Journal Year: 2024, Volume and Issue: 38(3), P. 217 - 224

Published: Jan. 12, 2024

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 years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk fibrosis valvulopathy when taken regularly, including methysergide, pergolide, fenfluramine. 3,4-Methylenedioxymethamphetamine, is also reportedly used microdosing, likewise associated heart valve damage chronically. In this review, we evaluate evidence that LSD, more could fibrosis. We discuss relationship between drug-induced 5-HT2B receptor, make recommendations evaluating safety in future studies.

Language: Английский

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Cardiovascular safety of psychedelic medicine: current status and future directions

Pharmacological Reports, Journal Year: 2023, Volume and Issue: 75(6), P. 1362 - 1380

Published: Oct. 24, 2023

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

Language: Английский

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Epigenetic mechanisms of rapid-acting antidepressants

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 4, 2024

Language: Английский

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Role of the gut–brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 189, P. 106348 - 106348

Published: Nov. 11, 2023

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated effects subdiaphragmatic vagotomy (SDV) modulating mice subjected chronic restrain (CRS). Pretreatment (10 mg/kg/day for 14 days) blocked anhedonia-like behavior reduced expression synaptic proteins brain-derived neurotrophic factor prefrontal cortex (PFC) CRS-exposed Interestingly, SDV beneficial on these alterations Analysis gut microbiome revealed four measures α-diversity between sham + CRS group group. Moreover, specific microbes differed vehicle group, differences microbial composition were observed all groups. Untargeted metabolomics analysis showed prevented increase plasma levels three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] positive correlations found two abundance several across In conclusion, our data suggest via vagus nerve might MDMA.

Language: Английский

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

Journal of Psychopharmacology, Journal Year: 2024, Volume and Issue: 38(8), P. 701 - 711

Published: June 14, 2024

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

Language: Английский

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State Cannabis and Psychedelic Legislation and Microdosing Interest in the US

JAMA Health Forum, Journal Year: 2024, Volume and Issue: 5(6), P. e241653 - e241653

Published: June 28, 2024

Importance Despite growing interest in psychedelics, there is a lack of routine population-based surveillance psychedelic microdosing (taking “subperceptual” doses approximately one-twentieth to one-fifth full dose, over prolonged periods). Analyzing Google search queries can provide insights into public and help address this gap. Objective To analyze trends the US through assess their association with cannabis legislative reforms. Design, Setting, Participants In cross-sectional study, dynamic event-time difference-in-difference time series analysis was used impact legislation on rates from January 1, 2010, December 31, 2023. mentioning “microdosing,” “micro dosing,” “microdose,” or dose” within across states were measured aggregate. Exposure Enactment (1) local decriminalization laws; (2) legalization psychedelic-assisted therapy statewide decriminalization; (3) medical use (4) recreational (5) all restricted. Main Outcome Measures Microdosing searches per 10 million measured, examining annual monthly changes US, including frequency nature related searches. Results Searches for remained stable until 2014, then increased annually thereafter, cumulative increase by factor 13.4 2015 2023 (7.9 105.6 searches, respectively). 2023, 3.0 US. Analysis at state level revealed that laws associated an 22.4 (95% CI, 7.5-37.2), therapeutic 28.9 16.5-41.2), 40.9 28.6-53.3), 11.5 6.0-16.9). From August 27.0% variation between explained differences psychedelics legal status. Conclusion Relevance This study found state-led reforms psychedelics.

Language: Английский

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Down the Rabbit Hole: A Large-Scale Survey of Psychedelic Users’ Patterns of Use and Perceived Effects

Journal of Psychoactive Drugs, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Jan. 29, 2025

The ever-changing landscape surrounding legality and accessibility of psychedelics their increasing popularity make it imperative to better understand the nature psychedelic use by general population. To this end, 1,486 eligible respondents (Mage = 29.58, 67.1% male) residing in United States completed an online survey designed assess types used, methods administration dosing, frequency use, intentions for context/environments which they are perceived acute effects, those effects distress about them, residual them. Respondents predominantly endorsed using MDMA, LSD, DMT, psilocybin. predominant were oral. Most reported recreational purposes. most hallucinations, increased heart rate, positive mood, visual tracers, while headaches/migraine, dry mouth, nausea, anxiety. Participants distressed negative mood states, vomiting, nausea when under psychedelics, but mean ratings low. These results can help inform clinical trials, reform policy regarding legal access track changes these metrics as sociocultural landscapes continue shift.

Language: Английский

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