THC–Barbiturate Cross-Tolerance in Rats Depended on Whether Responding Increased or Decreased
A 1983 rat experiment found THC–barbiturate cross-tolerance for decreases in food-maintained responding, while rate-increasing effects remained distinguishable. A single label of drug tolerance would conceal the different dose and behavioral comparisons.
The schedule and dose shaped the response
Low barbiturate doses increased responding, particularly under a fixed-interval component, while higher doses reduced it. Repeated THC produced tolerance to its rate-decreasing effects and cross-tolerance to pentobarbital and, less strongly, barbital. Transfer did not extend to amphetamine's rate-decreasing effects.
The reverse experiment supplied another comparison
In a separate group receiving chronic barbital, tolerance developed to reduced responding and transferred to THC. The rate-increasing barbital effect did not become tolerant. These observations concern performance on reinforcement schedules, not every physiological or subjective action of either drug.
One direction of change cannot stand in for another
An animal can become less sensitive to response suppression without becoming equally insensitive to stimulation. The same preparation can also produce different effects at different doses. Combining all responses into one sensitivity score would erase the distinction the experiment demonstrated.
Interpreting the evidence
For a cross-tolerance claim, name the drug history, challenge dose, schedule and direction of the behavioral effect. This rat study does not establish a human dose conversion, protection from sedation or safety of combining cannabis with a barbiturate.
Related reading: interpreting cannabis tolerance claims.
Research reference
McMillan DE; Hardwick WC; Wells JD (1983). Effects of barbiturates in rats tolerant to delta 9-tetrahydrocannabinol. Archives internationales de pharmacodynamie et de therapie. PubMed research record.
This analysis draws on the supplied abstract.
