DMSO potentiates the suppressive effect of dronabinol, a cannabinoid, on sleep apnea and REM sleep

Abstract

312) 413-0581 Office mcalik@uic.edu ORCID iD: 0000-0001-6295-7420 2 Abstract Purpose: Dimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations of dronabinol, a cannabinoid, dissolved in DMSO demonstrated decreased sleep apnea frequency and time spent in REM sleep in rats. Here, we tested the effects of dronabinol dissolved in 25% DMSO (diluted in phosphate-buffered saline) to rule out potentiating effects of DMSO.Methods: Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections separated by three days: vehicle (25% DMSO/PBS); vehicle and CB 1 antagonist (AM 251); vehicle and CB 2 antagonist (AM 630); vehicle and CB 1 /CB 2 antagonist; dronabinol (CB 1 /CB 2 agonist); dronabinol and CB 1 antagonist; dronabinol and CB 2 antagonist; and dronabinol and CB 1 /CB 2 antagonist. Sleep was manually scored into NREM and REM stages, and apneas were quantified.Results: Dronabinol dissolved in 25% DMSO did not suppress apnea or modify sleep efficiency compared to vehicle controls, in contrast to previously published results. However, dronabinol did suppress REM sleep, which is in line with previously published results. Conclusions: Dronabinol in 25% DMSO partially potentiated dronabinol's effects, suggesting a concomitant biological effect of DMSO on breathing during sleep. 3 1 0100% DMSO, with their known effects on the vagus nerve as previously discussed, might decrease REM sleep to a greater extent.In conclusion, we show that dronabinol, a non-specific cannabinoid receptor agonist shown to suppress sleep-related apneas and REM sleep, does not suppress sleep-related apneas 25% DMSO vehicle. This adds to the growing literature that DMSO is not simply a compound used to dissolve polar and nonpolar compounds, but is a compound with its own innate biological activity.

Sex-specific Effects of the Endocannabinoid Agonist 2-Arachidonoylglycerol on Sleep and Circadian Disruptions during Fentanyl Withdrawal

“…Work in rats has shown that dronabinol decreases REMS in a CB receptor independent manner (Calik and Carley, 2017). Interestingly, Calik and Carley show that this effect is not DMSO-dependent, but that DMSO does in part enhance the effect of dronabinol on sleep (Calik and Carley, 2019). With respect to wake and NREMS levels during withdrawal day 3, only wake bouts were slightly elevated to baseline in 2-AG compared to DMSO in males while all other measures were unchanged.…”