The landscape surrounding cannabis use is changing dramatically. Legalized medical and recreational use is spreading, habitual use is growing, perceptions of harm are decreasing and the concentration of THC, the main psychoactive ingredient, is rising; consequently, increased problems associated with cannabis use have been predicted. A better understanding of the mechanisms that underlie cannabis use disorder and effective treatments are therefore needed. This presentation will describe the use of human drug discrimination procedures to determine the neuropharmacological mechanisms of the interoceptive effects of THC and identify targets for treatment. This research has demonstrated that GABA and voltage-dependent calcium channels (VDCC) are involved in the response to cannabis in humans. This presentation will then discuss the use of human laboratory drug self-administration procedures, combined with medication maintenance, as a strategy for determining the initial safety, tolerability and efficacy of ligands at these targets as potential treatments. Studies with the GABA reuptake inhibitor tiagabine and the VDCC ligand pregabalin will be described. Lastly, the presentation will include initial results from research that has integrated neuroimaging, non-invasive electrical brain stimulation and acute drug administration techniques to study cannabis-use disorder.
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