Exploring DMT: Endogenous Role and Therapeutic Potential

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110314 - 110314

Published: Jan. 1, 2025

Language: Английский

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Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis

Clinical Pharmacokinetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

N,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of pharmacokinetics (PK) essential to determine appropriate dose ranges future clinical studies. We conducted a systematic literature review on the PK DMT. Clinical studies that administered known amounts DMT and reported data and/or parameters humans were included. Additionally, raw requested from authors extracted publications. In total, 219 references retrieved, which 13 publications included, covering eight distinct datasets. All intravenously infusion schemes, except one intramuscular administration. High variability dose-normalized exposure differences bolus versus administration observed. extensively redistributed other tissues, based biphasic elimination profile high volume distribution terminal phase (range 123–1084 L). It eliminated rapidly, with half-life 4.8–19.0 min clearance 8.1–46.8 L/min. This result rapid metabolization indole-3-acetic acid (IAA), also reflected fact time maximum concentration IAA similar demonstrates have been characterized limited extent, lack details regards demographics, absolute doses, parameters. Additional are necessary investigate intersubject following or prolonged infusion. Addressing these issues development as pharmacotherapeutic neuropsychiatry.

Language: Английский

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Pharmacokinetics and Pharmacodynamics of an Innovative Psychedelic N,N-Dimethyltryptamine/Harmine Formulation in Healthy Participants: A Randomized Controlled Trial

The International Journal of Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Background Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) β-carboline alkaloids such as harmine. However, its is often accompanied by distressing nausea, vomiting, intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions lack dose standardization. Methods study addresses these limitations testing a novel pharmaceutical formulation containing pure forms DMT harmine double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD monitoring drug metabolite plasma levels, subjective effects, adverse events, cardiovascular parameters. Each participant received three randomized treatments: 1) 100 mg buccal intranasal DMT, 2) placebo, 3) full placebo; using repeated-intermittent dosing scheme, that 10 (or placebo) was administered every 15 minutes. Results produced consistent PK profiles Cmax values 22.1 ng/ml acute resembling psychological duration 2–3 hours. Likewise, sustained-release 32.5 ng/ml, but lacked distinguishable compared placebo. All conditions were safe well tolerated, indicating formulation's suitability for applications. Conclusion underscores potential patient-oriented reduce risks improve outcomes treating mental health disorders.

Language: Английский

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Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: Α factorial dose-escalation study

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117908 - 117908

Published: Feb. 8, 2025

Language: Английский

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Tryptamine based drugs

Comprehensive analytical chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

DMT induces rapid antidepressant effects, but acute sympathomimetic side particularly hypertension and tachycardia, limit its use. This study describes coformulations with short-acting beta-blockers or nitrates, matched to DMT's pharmacokinetics, mitigate peripheral cardiovascular risks without compromising central therapeutic action, facilitating safer psychedelic therapy in vulnerable populations.

Language: Английский

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The impact of the novel σ1 receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177724 - 177724

Published: May 1, 2025

Language: Английский

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