The effect of methamphetamine and 3,4-methylenedioxymethamphetamine on peripheral endocannabinoid concentrations: a study in healthy adults
Bershad, A. K., de Wit, H., Deutch, A. Y., Haggarty, C. J., Hill, M. N., Mayo, L. M., Petrie, S. R.
This within-subject, double-blind study (n=22) found that acute administration of methamphetamine (14 mg/70 kg) significantly lowered plasma 2-arachidonoylglycerol concentrations compared to placebo at 150-180 minutes post-administration, whilst MDMA (100 mg) did not affect endocannabinoid levels, and higher anandamide concentrations during the placebo condition correlated with disliking the 'drug effects'.
Abstract
Rationale Stimulant drugs such as methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) can impact neurobiological systems implicated in stress, reward processing, and drug use. Although recent preclinical evidence implicates the endocannabinoid (eCB) system in these processes, little is known about the acute effects of stimulants on eCB levels in humans.Objectives The aim of the present study was to investigate the effects of acute administration of the prototypical psychostimulant MA and the psychostimulant-empathogen MDMA on circulating eCB levels in healthy adults.Methods Using a within-subject, double-blind design, this study assessed the acute effects of MA (20 mg), MDMA (100 mg), and placebo on plasma eCB levels in healthy human participants (N = 22) during three separate sessions. Blood samples assessing concentrations of the eCBs anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) were collected between 150- and 180-minutes post-drug administration, and subjective measures of drug effects were collected at regular intervals.Results MA, but not MDMA, was associated with significantly lower 2-AG plasma concentrations compared to placebo. Neither drug impacted AEA concentrations. However, during the placebo condition, higher AEA concentrations were correlated with disliking the ‘drug effects’, suggesting a possible relationship between AEA levels and negative expectations of subjective drug effects.Conclusions These findings provide novel insights into how stimulant drugs act on the eCB system and may help to develop treatments for SUDs.