Blunted Cortisol Responses to THC Did Not Establish Lower THC Exposure
Frequent cannabis users showed smaller cortisol increases after intravenous THC in pooled human research. The result concerns a hormonal response, not proof that those participants absorbed less THC or were unaffected in every other function.
A pooled analysis of two studies
Investigators analyzed 40 frequent users and 36 controls across controlled intravenous THC experiments. Hormones were assessed in plasma, with post-dose values analyzed while accounting for baseline levels. The use-history groups were not randomized to become frequent users.
Responses differed, but concentrations did not track the same way
THC raised plasma cortisol in a dose-related manner, with a blunted increase among frequent users. Baseline cortisol was similar between groups. Frequent users also had lower baseline prolactin, which is a different hormone and comparison.
The exposure analysis had its own denominator
Plasma THC and THC-COOH were analyzed in 52 of the 76 participants. Parent THC increased with dose without significant group differences or a group-by-dose interaction. Frequent users had higher baseline THC-COOH, an inactive metabolite. Attaching the full 76-person denominator to every concentration result would be incorrect.
Tolerance remains an interpretation
The hormonal pattern is compatible with tolerance, but pre-existing group differences cannot be excluded. Sampling times differed across the pooled studies, baseline early-morning cortisol was not assessed, and the small number of women limited sex-related analyses. A cortisol value cannot diagnose cannabis impairment, establish a person’s stress experience or convert into a THC concentration. The study supports separating exposure from a particular physiological response.
Related analysis: evaluating cannabis tolerance claims.
Primary research
Ranganathan M; Braley G; Pittman B; Cooper T; Perry E; Krystal J; D’Souza DC. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology (2009). DOI: 10.1007/s00213-008-1422-2.
