Pharmacodynamic effects and plasma pharmacokinetics of N, N-dimethyltryptamine after intranasal versus subcutaneous administration in male rats.
Michael H. Baumann, Grant C. Glatfelter, Sara E Walton, Alex J. Krotulski, Christopher G Witowski, Jacqueline L von Salm
Psychopharmacology November 15, 2025 DOI: 10.1007/s00213-025-06879-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | DMT fumarate (1 3 or 10 mg/kg) or saline vehicle |
| Dose | 1, 3, or 10 mg/kg |
| Topics | 5-MeO-DMT DMT |
| Keywords | N,N-Dimethyltryptamine Flat body posture Hypothermia Mass spectrometry Intranasal delivery: intranasal Intranasal administration Non-invasive method N-dimethyltryptamine: n Psychedelic compound Pharmacokinetics: pharmacokinetics Drug uptake Blood levels Physiological effects: effects |
| Citations | 1 |
| Key findings | Intranasal administration of DMT produces more rapid pharmacokinetics and higher peak concentrations than subcutaneous administration, and low intranasal doses yield plasma DMT levels overlapping with psychoactive concentrations in humans. |
Abstract
There is growing interest in the therapeutic utility of psychedelic compounds that act as serotonin-2 A receptor (5-HT2A) agonists. N,N-dimethyltryptamine (DMT) is a 5-HT2A agonist that produces intense and short-lived psychedelic subjective effects, but the compound requires non-oral routes of administration that bypass gastrointestinal metabolism. Intranasal (IN) delivery of DMT represents one potential non-oral route of administration, but the feasibility of using this route is not well studied. Here, we examined the pharmacodynamic effects and plasma pharmacokinetics of DMT after IN and subcutaneous (SC) administration in rats. Male Sprague-Dawley rats fitted with intravenous (IV) catheters and SC temperature transponders received DMT fumarate (1, 3, or 10 mg/kg) or saline vehicle by IN or SC routes. Blood samples were withdrawn via catheters at various times after treatment, with behavioral scores and body temperatures measured prior to each blood draw. Plasma DMT and its N-oxide metabolite were quantified using liquid chromatography tandem quadrupole mass spectrometry (LC-QQQ-MS). DMT produced a similar spectrum of pharmacodynamic effects after both routes, including increases in flat body posture and decreases in core body temperature. DMT displayed more rapid pharmacokinetics after the IN route (t1/2 range = 11.9-14.3 min) when compared to the SC route (t1/2 range = 45.5-122.7 min), and peak drug concentrations were greater with IN delivery. Our findings show the feasibility of using IN administration to deliver DMT in a reproducible and non-invasive manner. Importantly, the maximal DMT concentrations in rats given low IN doses (i.e., 30.2-55.6 ng/mL DMT) overlap with those reported in humans receiving psychoactive doses.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cites 40
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
and 35 more in the library