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.
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.
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.