Michael Baumann, PhD, is a Staff Scientist and Unit Director at the National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), in Baltimore, MD.  In 2014, he established the Designer Drug Research Unit (DDRU) to collect, analyze, and disseminate the most up-to-date information about the pharmacology and toxicology of newly emerging synthetic drugs of abuse, known as new psychoactive substances (NPS).  Working with partner organizations such as the Center for Forensic Science Research and Education (CFSRE) and the European Union Drug Agency (EUDA) , Dr. Baumann is kept informed about global trends in NPS misuse.  His research team has characterized the molecular mechanisms of action for many “bath salts” cathinones, “spice” cannabinoids, and “nitazene” opioids. Ongoing research is aimed at investigating the biological effects of emerging stimulants, psychedelics, and opioids to determine their adverse effects and potential therapeutic utility.

—

N,N-dimethyltryptamine (DMT) pharmacodynamic effects and pharmacokinetics after intranasal administration in male rats

There is growing interest in the therapeutic utility of psychedelic compounds that act as serotonin-2A 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 surgically-implanted intravenous (IV) catheters and SC temperature transponders received DMT (1, 3, 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 Blood samples were withdrawn via catheters at various times after treatment, with behavioral scores and body temperatures measured prior to each blood draw.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. In general, pharmacodynamic effects correlated with plasma concentrations of DMT after both routes of administration. 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.