Previous animal and human research suggested that stress regulating systems such as the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (ECB) system might play a role in the development of drug use disorders. For a study, researchers used an advanced hair analysis approach to look for changes in HPA and ECB indicators in people who had a chronic cocaine use problem. They examined glucocorticoids (cortisol, cortisol) and the eCBs 2-arachidonoylglycerol, anandamide (AEA), oleoyl ethanolamide (OEA), and palmitoylethanolamide (PEA) in the hair of 48 recreational cocaine users (RCU), 25 dependent cocaine users (DCU), and 67 stimulant-naive controls. Self-reported drug usage, as well as substance concentrations in hair, were also evaluated.

When compared to controls, RCU and DCU had significantly greater amounts of hair cortisol. DCU had considerably lower OEA and PEA hair concentrations than RCU and controls. Furthermore, increasing cocaine hair concentration was a strong predictor of increased glucocorticoid and decreased OEA hair levels in cocaine users. Furthermore, greater 3,4-methylenedioxymethamphetamine hair concentrations were linked with higher cortisol and AEA, OEA, and PEA levels in hair among cocaine users, but higher self-reported cannabis use was associated with lower eCBs levels in the hair throughout the whole population.

The findings supported the idea that the HPA axis and the ECB system were major regulators of drug use disorders. In the future study, a mechanistic understanding of variations in glucocorticoid and eCB levels might be a viable pharmaceutical target to minimize stress-induced desire and relapse in cocaine use disorder.