Margaret Haney, Caroline A Arout, Margaret F Bedillion
Rigorous, placebo-controlled human laboratory studies of the behavioral effects of cannabis are essential to informing a quickly evolving field complicated by the complexity of cannabis as a plant with a myriad of active constituents, regulatory hurdles, and industry narrative.
OBJECTIVE: Cannabis policy, public perception, and consumption patterns have undergone enormous shifts, yet the scientific understanding of these changes has lagged. Our objective is to describe how human behavioral pharmacology studies provide a rigorous framework for modelling Cannabis Use Disorder (CUD) and for informing the development of treatment approaches.
METHODS: This narrative review synthesizes insights from over 25 years of human laboratory research, highlighting how behavioral pharmacology, e.g., dose, placebo control, behavioral specificity, inform the development of evidence-based therapies and targeting the behavioral drivers of CUD.
RESULTS: Key takeaways: (1) Cannabis potency is not Δ9-tetrahydrocannabinol dose. Participants adjust inhalation patterns as a function of cannabis strength. (2) Placebo responding is robust even among experienced cannabis smokers; placebo-controlled studies are limited by regulatory barriers but are essential to distinguish pharmacological effects from expectancy. (3) How medications alter CUD-relevant behaviors (reinforcement, misuse-related ratings) and non-specific behaviors (e.g., sedation) portend clinical efficacy and tolerability and vary as a function of participant phenotype.
CONCLUSIONS: Rigorous, placebo-controlled human laboratory studies of the behavioral effects of cannabis are essential to informing a quickly evolving field complicated by the complexity of cannabis as a plant with a myriad of active constituents, regulatory hurdles, and industry narrative.