Work

Behavioral pharmacology of novel synthetic indazole, indole, and benzimidazole cannabinoids in rodents

Year: 2026

Type: article

Abstract: Background Synthetic cannabinoids (SC) are created as alternatives to delta-9-tetrahydrocannabinol (∆ 9 -THC) and can cause serious side effects like hallucinations and death. The DEA has identified eleven concerning synthetic cannabinoids: ADB-BUTINACA, ADB-HEXINACA, ADB-4en-PINACA, ADB-FUBIATA, 4F-MDMB-BICA, 4F-ABUTINACA, FUB-144, FUB-AKB-48, 5F-EMB-PICA, 5Cl-AKB-48, and MDA-19. These compounds were tested in rodent models to evaluate their effects on locomotion, discrimination, and potency relative to ∆ 9 -THC. Methods The eleven SC were tested for locomotor activity in Swiss-Webster mice and drug discrimination (DD) in Sprague–Dawley rats trained to discriminate ∆ 9 THC. Results In tests for locomotor depression, all the test compounds were more potent than ∆ 9 -THC (ED 50 = 3.3 mg/kg) except for FUB-144, 5Cl-AKB-48, and ADB-FUBIATA (ED 50 > 6.1 mg/kg), which produced weak locomotor depressant effects. Similarly, in the DD assay, most compounds substituted fully with greater potency t than ∆ 9 -THC (ED 50 = 0.55 mg/kg) except for FUB-144 (ED 50 = 1.44 mg/kg), and 5Cl-AKB-48 (ED 50 = 3.21 mg/kg). ADB-FUBIATA and MDA-19 tested in doses up to 100 mg/kg, failed to fully substitute for the discriminative stimulus of ∆ 9 -THC. Conclusion In summary, slight structural differences led to shifts in behavioral pharmacology outcomes in rodent models, which helped predict their potency relative to ∆ 9 -THC. Therefore, future research on emerging SCs, along with structure–activity relationships at the receptor level, should include behavioral pharmacology testing of SCs to better predict their abuse potential and toxicity. Support Supported by NIDA contract N01DA-18–8936; N01DA-23–8936.

Source: Journal of Cannabis Research

DOI: 10.1186/s42238-026-00390-3

Authors: Ritu A. Shetty, Rebecca D. Hill, Jared A. McDonald, Nathalie Sumien, Michael J. Forster, Michael B. Gatch

Institution: University of North Texas Health Science Center

Language: English

Topic: Forensic Toxicology and Drug Analysis

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,590