What is DMT (Dimethyltryptamine)?

What is DMT (Dimethyltryptamine)?

DMT is a potent, rapid-onset, short-acting serotonergic psychedelic hallucinogen classified as an indolealkylamines that produces intense visual hallucinations through serotonin 5-HT2A receptor activation. 1

Pharmacological Classification and Mechanism

• DMT (N,N-dimethyltryptamine) is an indole alkaloid naturally occurring in plants and animals that functions primarily as an agonist at 5-HT1A and 5-HT2A receptors 2, 3
• It is categorized medically as a hallucinogen alongside other phenylisopropylamine substances with abuse potential 4
• The drug produces characteristic visual hallucinations, distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution 1, 3

Clinical Pharmacology and Effects

• When administered intravenously or inhaled, DMT causes rapid onset of psychedelic effects that typically resolve within 20-30 minutes 5
• At microdoses, DMT increases somaesthesia (interoceptive and tactile sensations) and reduces volition 6
• The drug produces acute cardiovascular effects including increased blood pressure, heart rate, and anxiety during the acute phase 5, 2
• DMT appears to have limited neurotoxicity except for intense cardiovascular effects when administered intravenously in large doses 2

Current Therapeutic Research Status

• Preliminary phase IIa trial results showed 57% of patients with major depressive disorder experienced remission 12 weeks after receiving a single intravenous dose of DMT 7
• In an exploratory phase 1 study, 0.3 mg/kg intravenous DMT produced significant reductions in HAMD-17 scores (mean difference -4.5 points) the day after administration in treatment-resistant MDD patients 5
• Extended DMT administration via bolus plus continuous infusion over 30 minutes has been demonstrated safe and tolerable, though acute psychological tolerance develops 8

Important Clinical Caveats

• DMT is NOT approved by the FDA for therapeutic use and should not be used outside of clinical trial settings 4
• The U.S. Department of Veterans Affairs and Department of Defense explicitly recommend against using DMT and other unapproved pharmacologic agents outside clinical trials due to its classification as a drug of abuse 4
• All published clinical trials have had small sample sizes (≤34 participants), and only single published double-blind randomized controlled trials exist 7
• There is an FDA-approved topical formulation of dimethyltryptamine labeled as an external analgesic for ages 2 and older, applied to affected areas not more than 3-4 times daily, though this appears to be a different compound or formulation than the psychedelic substance 9

Detection and Drug Testing

• DMT is detected on standard urine drug screens as part of hallucinogen panels 1
• Standard immunoassay screening tests are presumptive only and should be confirmed with gas chromatography-mass spectrometry (GC-MS) when results will impact clinical decisions 10

Endogenous DMT Hypothesis

• While DMT may be synthesized endogenously in humans, it may not be produced at physiologically relevant concentrations 7
• The hypothesis that endogenous DMT is released during the dying process (explaining near-death experiences) continues to be debated without definitive evidence 7
• Increasing evidence suggests endogenous DMT may play roles in peripheral and central nervous system processes and potentially act as a neurotransmitter 2