Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol.

RATIONALE: Preclinical evidence suggests that non-cannabinoid neurotransmitter systems are involved in the behavioral and physiological effects of cannabinoids, but relatively little research has been conducted in humans.
OBJECTIVES: The aims of this study were to assess whether oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC) would function as a discriminative stimulus in humans and to examine the substitution profile of drugs acting at opioid, GABA, and dopamine systems.
METHODS: Healthy subjects who reported moderate cannabis use were enrolled. Subjects learned to identify when they received oral 25 mg Delta(9)-THC or placebo under double-blind conditions. Once subjects acquired the discrimination (i.e., > or =80% drug-appropriate responding for four consecutive sessions), multiple doses of Delta(9)-THC, the GABA(A) positive modulator triazolam, the micro-opioid agonist hydromorphone and the dopamine reuptake inhibitor methylphenidate were tested to determine if they shared discriminative-stimulus effects with the training dose of Delta(9)-THC.
RESULTS: Eight subjects (N = 8) accurately discriminated Delta(9)-THC and completed the study. The training dose of Delta(9)-THC functioned as a discriminative stimulus and produced prototypical subject-rated drug effects. All of the drugs tested produced significant effects on the self-report questionnaires, but only Delta(9)-THC substituted for the training dose.
CONCLUSION: These results suggest that the discriminative-stimulus effects of Delta(9)-THC in humans are not directly mediated through central neurotransmitter systems acted upon by the drugs tested in this study.

RCT Entities:   Population Interventions Outcomes