Chronic THC Did Not Produce Detected Midazolam Cross-Tolerance in a Small Primate Experiment
Chronic THC changed sensitivity to cannabinoid drugs without significantly changing sensitivity to midazolam or ketamine on the tested primate response-rate measures. Tolerance to THC did not imply general tolerance to sedating drugs.
The relevant comparison involved three monkeys
In the chronic-treatment experiment, rhesus monkeys performed food-maintained and stimulus-shock-termination tasks. Researchers compared dose-response effects before and during a seventy-one-day THC regimen. The paper included additional animals and procedures, but those should not inflate the sample for this particular comparison.
Positive cannabinoid findings accompanied non-cannabinoid nulls
THC sensitivity decreased markedly, and cross-tolerance appeared in selected comparisons with synthetic cannabinoid agonists. Midazolam and ketamine dose-response sensitivity, however, was not significantly modified. These findings help distinguish receptor-related adaptation from a general reduction in responsiveness to any behavior-suppressing drug.
The null was not a combined-use safety result
The experiment assessed challenge-drug effects around a chronic THC history. It did not establish that co-use is safe, measure breathing during clinical sedation or test driving. Nonsignificance in three animals also does not prove exact equivalence or exclude smaller effects.
Use the result at its actual scale
The animals received controlled injected drugs and performed specific learned tasks. Ordinary cannabis products, other benzodiazepines, alcohol and patient populations were not interchangeable with those conditions. The study weighs against assuming universal cross-tolerance from a cannabis history while leaving individual medication response and combined-exposure risks unresolved.
Related analysis: Cannabis Tolerance Claims: Questions to Ask Before Relying on Expert Testimony.
Primary research
Chronic Δ⁹-tetrahydrocannabinol treatment in rhesus monkeys: differential tolerance and cross-tolerance among cannabinoids. British journal of pharmacology (2011). DOI: 10.1111/j.1476-5381.2010.01116.x.
