A Cannabis Cortisol Pilot’s Association Changed After Accounting for Time
A small rimonabant experiment found an association between drug concentration and cortisol that was no longer significant after time terms were included. A hormone association should therefore not be presented without its model and sampling context.
Ten completers and only two placebo participants
The study involved cannabis-dependent men who received repeated oral THC before a single dose of rimonabant or placebo. Ten completed: eight received active rimonabant at one of two doses and two received placebo. The trial ended early when the manufacturer discontinued the drug’s development program.
Plasma cortisol was the measured endpoint
Single 20- or 40-mg rimonabant doses did not significantly increase plasma cortisol overall. Four active-treatment participants nevertheless had a later morning cortisol value above their earlier morning value. Individual trajectories and the group treatment comparison answer different questions.
Why adjustment changed the interpretation
A simpler analysis linked change in cortisol to rimonabant concentration. When time and interaction terms were added, the concentration term was nonsignificant. Cortisol normally varies over the day, making sampling time an important competing explanation. The study also reported null associations for several cannabinoid-related comparisons.
What remains unresolved
With eight active-treatment subjects and two controls, the experiment provides limited precision. It did not establish cortisol as a diagnostic test for cannabis withdrawal or show that an individual increase proves a withdrawal mechanism. Its findings are specific to the administered antagonist and prior THC regimen. They are not evidence about the safety of currently available cannabis products or a recommendation to use rimonabant.
Related analysis: evaluating cannabis tolerance claims.
Primary research
Goodwin RS; Baumann MH; Gorelick DA; Schwilke E; Schwope DM; Darwin WD; Kelly DL; Schroeder JR; Ortemann-Renon C; Bonnet D; Huestis MA. CB1 – cannabinoid receptor antagonist effects on cortisol in cannabis-dependent men. The American journal of drug and alcohol abuse (2012). DOI: 10.3109/00952990.2011.600398.
