The concentration of bioactive androgens is significantly higher in cannabis users, a finding that has been substantiated through a detailed study applying a one-point internal calibration approach to quantify seven major steroid compounds in human serum. The analyzed steroids include androstenedione (A4), testosterone (T), 17α-hydroxyprogesterone (17α-OHP4), progesterone (P4), 11-deoxycortisol (S), cortisol (F), and cortisone (E). The absolute concentrations of these compounds were consistent with established reference ranges for men in their early twenties and aligned with previous findings in a similar Swiss cohort.
Higher Androgen Levels in Cannabis Users
Notably, serum levels of A4 and T were significantly higher in THC-positive individuals, with p-values of 0.008 and 0.002, respectively. A modest but significant increase was also observed for 17α-OHP4 (p=0.03). In contrast, no significant differences were seen for P4, S, F, and E. This supports previous conclusions drawn by Gundersen et al. in Denmark, which reported a 7% higher T concentration in marijuana users after adjusting for confounders. Similarly, another large U.S. study found elevated T levels in THC-positive subjects, regardless of their usage frequency.
Insights from Extended Steroid Profiling
The study’s absolute quantitative data were complemented by extensive steroid profiling, identifying 77 out of 171 target steroids in serum. This included a range of steroids, such as androgens, progestogens, estrogens, corticosteroids, and more. Such comprehensive profiling exceeds previous steroidomic studies and mirrors steroidomes found in certified human blood reference materials.
Among the androgens, 5α-dihydrotestosterone (DHT) was notably higher in THC-positive men, confirming the significance of measuring multiple androgens to understand steroidogenesis and androgen activity. The increased levels of bioactive androgens among cannabis users versus controls is further illustrated through corresponding statistical analyses.
Impact of Cannabis on Androgen Biosynthesis
A multivariate analysis using Orthogonal Partial Least Squares—Discriminant Analysis (OPLS-DA) confirmed the higher levels of T, A4, and DHT in THC-positive individuals. Interestingly, not all androgens contributed equally to the distinction between cannabis users and non-users. Dehydroepiandrosterone (DHEA), a precursor of androgen synthesis, did not aid in group differentiation, suggesting that increases in gonadal androgens may stem from the Δ4 pathway rather than the Δ5 pathway.
This analysis also indicated that adrenal androgen synthesis appears unaffected by cannabis use, highlighting that while circulating concentrations of C11-oxy androgens remained stable, the gonadal androgens showed significant elevation.
Progesterone Metabolites Linked to Cannabis Consumption
The analysis also revealed two metabolites of progesterone, 5β-dihydroprogesterone (5β-DHP4) and 11β-hydroxyprogesterone (11β-OHP4), significantly associated with cannabis use. Their elevated concentrations in the serum of cannabis consumers, confirmed through rigorous statistical testing, suggest a link between cannabis exposure and alterations in progesterone metabolism.
The Role of Phytocannabinoids in Hormonal Alterations
Examining the relationships between androgen levels and THC exposure showed that both THC and its primary metabolite THC-COOH were positively correlated with the main gonadal androgens. This indicates that increased exposure to phytocannabinoids correlates with elevated testosterone levels specifically, while C11-oxy androgens were neither positively nor negatively impacted. This highlights the distinct mechanisms by which cannabis influences gonadal versus adrenal steroidogenesis.
Conclusions and Implications for Mississippi’s Cannabis Industry
The findings of this study provide valuable insights into the hormonal effects of cannabis use, particularly regarding elevated testosterone levels in men. This trend is consistent with broader evidence challenging earlier beliefs that cannabis suppresses testosterone. As Mississippi navigates the legalization and regulation of cannabis, understanding the implications of cannabis on male reproductive health could inform future policies and health guidelines. Notably, as the cannabis industry continues to expand, further research is essential to clarify the relationship between hormonal changes and reproductive outcomes.
Author: MScannaBIZ
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