Application of microarray patches for the transdermal administration of psychedelic drugs in micro-doses.

Hydrogel-forming microarray patches (HF-MAPs) can deliver small doses of the psychedelic compounds N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and mescaline (MES) through the skin. In tests using excised neonatal porcine skin, a reservoir containing polyethylene glycol 400 enabled permeation of 60.71% for DMT, 59.61% for 5-MeO-DMT, and 41.85% for MES. Pharmacokinetic studies in rats showed that DMT delivered via HF-MAP had a significantly greater area under the curve (7186 ± 1296 ng/mL*h) compared to intramuscular injection (1803 ± 53.25 ng/mL*h), with a relative bioavailability of about 72%. This suggests HF-MAP technology could reduce dosing frequency for DMT microdosing.

Study at a glance

Abstract

Throughout history, psychedelic compounds have been used for religious, spiritual and recreational purposes. A plethora of studies have reported the use of psychedelic compounds in the treatment of various conditions, such as alcoholism, addictions, depressive state to borderline schizophrenia, personality disorder, among other mental disorders. Psychedelic microdosing, a common technique in recent years, involves the consumption of small doses of psychedelic drugs for therapeutic purposes. This study investigated the potential of hydrogel-forming microarray patches (HF-MAPs) to deliver N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and mescaline (MES) in small doses through the skin. To this purpose, HF-MAPs were prepared using poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP), using citric acid as the crosslinker. Two different reservoirs, containing PVP and PVA as the main components and poly(ethylene)glycol 400 (PEG400) and glycerol as plasticising agents, were used to deliver all the drugs from the HF-MAPs. Franz cells studies in excised neonatal porcine skin demonstrated that the permeation of DMT, 5-MeO-DMT and MES was better from the PEG400 reservoir, showing a permeation of 60.71 %, 59.61 % and 41.85 % respectively. Pharmacokinetic studies in rats showed that HF-MAP technology as a strategy for microdosing psychedelic compounds was also demonstrated with DMT. AUCt0-final for the HF-MAP cohort (7186 ± 1296 ng/mL*h) was significantly greater than the IM cohort (1803 ± 53.25 ng/mL*h) (p = 0.0020), with a relative bioavailability of ∼ 72 %. Considering their pharmacokinetic profile, the frequency of DMT dosing could be reduced with HF-MAP when compared to the IM route.