European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
August 1, 2024
Christopher G Witowski, Mika R Hess, Nate T Jones et al.
7 citations
A transdermal patch for delivering N,N-dimethyltryptamine (DMT) at low, non-hallucinogenic doses was developed and tested in mice. The patch provided consistent, extended drug release, achieving plasma levels below 60 ng/mL. Compared to intravenous administration, the patch extended DMT's half-life by 20-fold and achieved 77% bioavailability. Female and male mice showed notable differences during IV dosing, but transdermal delivery produced steady levels. A head twitch assay indicated no hallucinogenic effects at these low plasma concentrations. The patch could offer a non-invasive, outpatient treatment option for conditions where high, bolus doses are unnecessary.
Psychopharmacology
November 15, 2025
Michael H. Baumann, Grant C. Glatfelter, Sara E Walton et al.
1 citation
Intranasal delivery of the psychedelic compound N,N-dimethyltryptamine (DMT) is feasible and produces rapid drug uptake in rats. DMT given intranasally or subcutaneously caused similar effects, including increased flat body posture and decreased body temperature. Intranasal administration led to faster pharmacokinetics, with a half-life range of 11.9–14.3 minutes compared to 45.5–122.7 minutes for subcutaneous delivery, and higher peak drug concentrations. Importantly, maximal DMT concentrations in rats receiving low intranasal doses (30.2–55.6 ng/mL) overlap with psychoactive levels reported in humans, suggesting this non-invasive route may be viable for therapeutic use.
Figshare
June 23, 2026
Elena Bray, Grant C. Glatfelter, Alexander D. Maitland et al.
A new chemical synthesis of 4-bromo-N,N-dimethyltryptamine (4-Br-DMT) was developed, enabling the creation of novel tryptamine molecules with modifications at the C4 position via palladium cross-coupling reactions. This approach facilitates rapid development of a library of compounds for studying structure-activity relationships with serotonergic targets. Compared to psilocin and DMT, 4-Br-DMT exhibits a serotonergic profile but lacks psychedelic-like effects in mice, though it has a reduced safety profile.
ACS Omega
June 23, 2026
Elena Bray, Grant C. Glatfelter, Alexander D. Maitland et al.
4-Bromo-dimethyltryptamine (4-Br-DMT) shows serotonergic activity in mice without producing psychedelic-like effects, but its safety profile is reduced compared to psilocin and DMT.
bioRxiv : the preprint server for biology
April 21, 2026
Jeanine Yacoub, Elena Bray, Jude Bayyat et al.
Halogenating the 2-position of DMT and psilacetin reduces their activity at 5-HT2A and 5-HT2B receptors, which are linked to psychedelic effects and heart valve toxicity, while preserving activity at other therapeutic targets like 5-HT6. The 2-Br-psilacetin analogue did not cause head-twitch behavior in mice and reduced head-twitch caused by another psychedelic, indicating lower potential for psychedelic effects. Intermediate doses improved stress-related mood measures and cued learning. These findings suggest that 2-halogenated tryptamines could be developed as safer, non-psychedelic therapeutics for psychiatric and neurodegenerative disorders.
Front Psychiatry
April 23, 2025
Martin L Williams, Deborah Rudin, Yasmin Schmid et al.
Psilocybin is one of many compounds that act as agonists of serotonin receptors and produce psychedelic effects. Beyond psilocybin, other classic psychedelics such as mescaline, N,N-DMT, and 5-MeO-DMT, along with novel compounds called psychoplastogens, show promise for treating mental health conditions like depression, PTSD, and anxiety in palliative care. This research topic includes seven articles: case reports on ketamine for depression and 5-MeO-DMT for PTSD; a review of clavine alkaloids; Phase 1 trials of an ayahuasca analog and a novel DMT formulation; a preclinical study of psilacetin; and a discussion of psychedelics for end-of-life distress. The field is expanding beyond psilocybin to explore a wider range of compounds.