Human behavioral pharmacology of Cannabis: Insights on Cannabis use disorder.

Haney M.; Arout C.; Bedillion M. · Preventive medicine · 2026

**Background & Methods** This is a narrative review synthesizing over 25 years of human laboratory research on cannabis behavioral pharmacology rather than a primary RCT. The authors examined how human behavioral pharmacology studies provide a rigorous framework for modeling Cannabis Use Disorder (CUD) and informing treatment development, drawing on controlled laboratory research examining dose-response relationships, placebo effects, and medication-induced behavioral changes. **Key Findings** • Cannabis potency cannot be reduced to simple Δ9-tetrahydrocannabinol (THC) dosing; participants actively adjust inhalation patterns based on cannabis strength, suggesting dose-response relationships are more complex than linear THC content and require consideration of user compensation behaviors in real-world contexts. • Placebo responding demonstrates robust effects even among experienced cannabis smokers, with placebo-controlled study designs being essential for distinguishing true pharmacological effects from expectancy effects; however, regulatory barriers currently limit the conduct of such rigorous studies. • Medications' ability to alter CUD-relevant behavioral outcomes (reinforcement, misuse-related ratings) and non-specific effects (sedation) predicts both clinical efficacy and tolerability, with variable effects depending on individual participant phenotypes. **Dosage & Administration** Not reported. This is a narrative review synthesizing previous studies rather than a primary intervention study with specified dosing protocols. **Safety & Adverse Effects** Not reported. While sedation is mentioned as a non-specific behavioral effect that may occur with certain medications in the context of CUD treatment, specific adverse effects from cannabis or treatments are not detailed in this review's abstract. **Evidence Quality** This narrative review represents a lower level of evidence (Level 4) compared to primary RCTs or systematic reviews. The authors acknowledge significant limitations including regulatory barriers to conducting rigorous placebo-controlled human studies, the complexity of cannabis as a plant with multiple active constituents beyond THC, and industry narratives that may complicate the scientific understanding. The strength of this work lies in synthesizing 25+ years of controlled laboratory research to identify key principles for understanding CUD mechanisms, but conclusions are limited by the heterogeneity and regulatory constraints of the underlying studies reviewed rather than new primary data.

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