Pharmacokinetics of N,N-dimethyltryptamine in Humans

Area of Science:

• Pharmacology
• Neuroscience
• Psychiatry

Background:

• N,N-dimethyltryptamine (DMT) is being investigated for major depressive disorder (MDD) treatment.
• Preclinical and clinical pharmacokinetic data are crucial for understanding DMT's therapeutic potential.

Purpose of the Study:

• To evaluate the pharmacokinetics and metabolism of DMT in healthy human subjects.
• To assess the safety and tolerability of escalating intravenous DMT doses.

Main Methods:

• In vitro experiments determined DMT's physiochemical properties and metabolic pathways using MAO and CYP inhibitors.
• Phase I of a randomized, double-blind, placebo-controlled trial administered escalating intravenous DMT fumarate doses.
• Pharmacokinetic modeling guided dose escalation based on safety and tolerability.

Main Results:

• DMT clearance was reduced by inhibiting MAO-A, CYP2D6, and CYP2C19.
• Low lipophilicity and plasma protein binding indicate high availability for distribution and metabolism.
• Intravenous DMT (9-21.5 mg) was rapidly cleared (9-12 min half-life) and well-tolerated in 24 subjects.

Conclusions:

• This is the first detailed human pharmacokinetic profile of DMT via slow IV infusion.
• Results confirm rapid peak plasma concentrations and swift clearance of DMT.
• Findings support the development of novel DMT infusion regimens for MDD treatment.