Associations of psychoactive substances and steroid hormones in hair: Findings relevant to stress research from a large cohort of young adults

Objective Epidemiological studies increasingly use hair samples to assess people’s cumulative exposure to steroid hormones, but how use of different psychoactive substances can bias steroid hormone levels in hair is, so far, largely unknown. The current study addresses this gap by establishing the substance use correlates of cortisol, cortisone, and testosterone in hair, while also accounting for a number of relevant covariates. Method Data came from a large urban community-sample of young adults with a high prevalence of substance use (N=1,002, mean age=20.6 years, 50.2% female), who provided 3 cm of hair samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified cortisol, cortisone, and testosterone, as well as delta-9-tetrahydrocannabinol (THC), 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”), cocaine, and several opioids, as well as their respective metabolites. Multiple linear regression models with initially identified covariates were used to predict steroid hormone levels from substance exposure in a four-step approach: In the full sample, low and high substance hair concentrations (median split) were first tested against no use for each substance individually (step 1) and for all substances together (step 2). Then, within the participants with any substance in hair only, the continuous hair concentration of each substance in pg/mg (step 3) and finally of all substances together, were regressed (step 4). Results Low, high, and continuous levels of THC in hair were robustly associated with higher levels of cortisol (sig. in step 1 low THC: β=0.29, p=.021; high THC: β=0.42, p=.001; step 2: low THC: β=0.27, p=0.036, and high THC: β=0.40, p=.004, and step 4: β=0.12, p=.041). Participants with high MDMA levels had higher levels of cortisone (step 1: β=0.34, p=.026), but this effect was weakened in the full model (step 2: β=0.11, p=.057). While high THC levels were associated with lower levels of testosterone in step 2 (β=-0.35, p=.018), MDMA concentration was positively related to testosterone concentration with and without adjusting for other substances (step 3: β=0.24, p=.041; step 4: β=0.17, 95%, p=.015) in male participants. Conclusion The use of psychoactive substances, especially of cannabis and ecstasy, should be considered in studies investigating steroid hormones in hair