Human brain effects of DMT assessed via EEG-fMRI

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(13)

Published: March 20, 2023

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the of intravenous (IV) N,N-Dimethyltryptamine (DMT) in 20 healthy volunteers. Simultaneous was prior to, during, and after bolus IV administration mg DMT, and, separately, placebo. At dosages consistent with present study, serotonin 2A receptor (5-HT2AR) agonist, induces deeply immersive radically altered state consciousness. DMT is thus useful research tool for probing neural correlates conscious experience. Here, fMRI results revealed robust increases global functional connectivity (GFC), network disintegration desegregation, compression principal cortical gradient under DMT. GFC × subjective intensity maps correlated independent positron emission tomography (PET)-derived 5-HT2AR maps, both overlapped meta-analytical implying human-specific psychological functions. Changes major EEG-measured neurophysiological properties specific changes various metrics, enriching our understanding basis DMT’s effects. The findings advance previous work by confirming predominant action DMT—and likely other agonist psychedelics—on brain’s transmodal association pole, i.e., neurodevelopmentally evolutionarily recent cortex that associated species-specific advancements, high expression 5-HT2A receptors.

Language: Английский

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Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial

Journal of Psychopharmacology, Journal Year: 2023, Volume and Issue: 37(7), P. 698 - 706

Published: March 20, 2023

Background: Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit interpretability of the existing literature. Methods: In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe major depressive disorder were administered placebo ( n = 19) followed by psilocybin (0.3 mg/kg) 15) 4 weeks later. Dosing sessions embedded within manualized course psychotherapy. Enhanced blinding procedures used. Depression, anxiety, quality life measured over a 16-week study period. Results: Depression anxiety significantly improved following both no significant difference in degree change between conditions. effect sizes larger after d′ 1.02–2.27) than 0.65–0.99) there high rates response (66.7%) remission (46.7%) administration. Antidepressant persisted, on average, for 2 months improvements mood-related domains. The strength mystical-type experience during dosing was not correlated subsequent effects. Conclusions: results this highlight complex interplay expectancy, effects, drug/placebo psychedelic-assisted psychotherapy studies. Nonetheless, acute clinical observed support further its potential treatment depression. Future should more explicitly mitigate measure expectancy assess impact repeated different forms psychotherapeutic support.

Language: Английский

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Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 23, 2023

N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use intravenous DMT, data are lacking on clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial 27 healthy participants to test different DMT administration regimens: placebo, low infusion (0.6 mg/min), high (1 bolus + (15 mg 0.6 (25 1 mg/min). Study sessions lasted for 5 h were separated by at least week. Participant's lifetime was ≤20 times. Outcome measures included subjective, autonomic, adverse effects, pharmacokinetics plasma levels brain-derived neurotropic factor (BDNF) oxytocin. Low mg) doses rapidly induced very intense psychedelic that peaked within 2 min. infusions or mg/min) without slowly increasing dose-dependent reached plateaus after 30 Both produced more negative subjective anxiety than infusions. After stopping infusion, all drug decreased completely subsided 15 min, consistent with short early elimination half-life (t1/2α) 5.0-5.8 followed longer late (t1/2β = 14-16 min) 15-20 Subjective stable from 90 despite further concentrations, thus indicating acute tolerance continuous administration. Intravenous particularly as an promising tool controlled induction state can be tailored specific needs patients sessions.Trial registration: ClinicalTrials.gov identifier: NCT04353024.

Language: Английский

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Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis

Psychiatry Research, Journal Year: 2024, Volume and Issue: 335, P. 115886 - 115886

Published: March 28, 2024

Language: Английский

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Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics?

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 27, 2024

The growing interest in the rapid and sustained antidepressant effects of dissociative anesthetic ketamine classic psychedelics, such as psilocybin, is remarkable. However, both psychedelics are known to induce acute mystical experiences; can cause symptoms out-of-body experience, while typically bring about hallucinogenic experiences, like a profound sense unity with universe or nature. role these experiences enhancing outcomes for patients depression currently an area ongoing investigation debate. Clinical studies have shown that following administration (S)-ketamine (esketamine) not directly linked their properties. In contrast, potential (R)-ketamine (arketamine), thought lack side effects, has yet be conclusively proven large-scale clinical trials. Moreover, although activation serotonin 5-HT

Language: Английский

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Adverse Events in Studies of Classic Psychedelics

JAMA Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Importance A clear and comprehensive understanding of risks associated with psychedelic-assisted therapy is necessary as investigators extend its application to new populations indications. Objective To assess adverse events (AEs) classic psychedelics, particularly serious AEs (SAEs) nonserious (NSAEs) requiring medical or psychiatric evaluation. Data Sources The search for potentially eligible studies was conducted in the Scopus, MEDLINE, PsycINFO, Web Science databases from inception through February 8, 2024. Study Selection Two independent reviewers screened articles psychedelics (lysergic acid diethylamide [LSD], psilocybin, dimethyltryptamine [DMT], 5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT]) involving administration clinical research contexts. Extraction Synthesis AE data were extracted synthesized by 2 used random-effects meta-analysis frequency heterogeneity. Risk bias assessment focused on ascertainment (eg, systematic quality follow-up). Main Outcomes Measures hybrid approach capture all reported following high-dose psychedelic exposure confirmatory special interest, including suicidality, psychotic disorder, manic symptoms, cardiovascular events, hallucinogen persisting perception disorder. stratified timescale study population type. Forest plots common generated, proportions participants affected SAEs NSAEs intervention summarized descriptively. Results total 214 unique included, which 114 (53.3%) analyzable 3504 participants. no healthy approximately 4% preexisting neuropsychiatric disorders; among these worsening depression, suicidal behavior, psychosis, convulsive episodes. paranoia, headache) similarly rare. In contemporary settings, there reports deaths suicide, persistent disorders, disorders psychedelics. However, significant heterogeneity monitoring reporting. Of 68 analyzed published since 2005, only 16 (23.5%) described approaches assessment, 20 (29.4%) AEs, opposed drug reactions. Meta-analyses prevalence headache, anxiety, nausea, fatigue, dizziness) yielded comparable results psilocybin LSD. Conclusions Relevance this review meta-analysis, generally well tolerated settings according existing literature, although did occur. These provide estimates frequencies indicate that certain catastrophic recreational nonclinical contexts have yet be trial Careful, ongoing, improved pharmacovigilance required understand risk benefit profiles substances communicate such prospective public.

Language: Английский

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Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2024, Volume and Issue: 9(5), P. 472 - 489

Published: Feb. 1, 2024

Psychedelic compounds, including psilocybin, LSD, DMT, and 5-MeO-DMT all of which are serotonin (5-HT) 2A receptor agonists being investigated as potential treatments. This review aims to summarize the current clinical research on these four compounds mescaline guide future research. Their mechanism/s action, pharmacokinetics, pharmacodynamics, efficacy, safety were reviewed. While evidence for therapeutic indications, with exception psilocybin depression, is still relatively scarce, we noted no differences in psychedelic effects beyond effect duration. It remains therefore unclear whether different profiles contribute compounds. More needed differentiate order inform might be best uses.

Language: Английский

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Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 5, 2024

Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential efficacy safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, current paper explored experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with single session oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges trust-building expectation management; (2) navigating experience; (3) need more comprehensive Subthemes first theme include general distrust mental healthcare, trust study therapists, limited time preparation, managing expectations. The second included following subthemes: trusting to surrender, profound overwhelming experiences, music as guide. third addressed desire multiple sessions, sensemaking. Patients' provided important insights into potential optimization treatment TRD, including individualized investment trust-building, offering additional providing access sustained (psycho)therapy trusted personalizing approaches, which may also enhance real-world adaption treatments.

Language: Английский

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Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 17, 2024

Abstract Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests improvements in psychological flexibility may mediate effects. no psychedelic trials to date substantiated this finding clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) 15) 4 weeks later. Dosing sessions embedded within manualized psychotherapy incorporated principles Acceptance and Commitment Therapy. Depression severity, flexibility, mindfulness, values-congruent living measured over 16-weeks study period. Psychological several facets significantly improved following maintained through week 16. Additionally, experiential acceptance strongly associated reductions depression severity psilocybin. These findings support theoretical premise integrating treatment psychotherapeutic platforms target add emerging evidence increasing be important putative mechanism change for potentially, other mental health conditions.

Language: Английский

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Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression

American Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 182(1), P. 33 - 46

Published: Jan. 1, 2025

Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with expectation that these can produce effects following an intense but brief psychedelic intervention. The current paper reviews clinical pharmacology 5-MeO-DMT DMT their potential benefits challenges treatment depression. Both compounds display affinities for variety monoamine receptors transporters, mostly so serotonergic (5HT) receptors, including 5HT

Language: Английский

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