Effects of Δ9-THC and Type-1 Cannabinoid Receptor Agonists in the Elevated Plus Maze Test of Anxiety: A Systematic Review and Meta-Analysis.
Lia P Iglesias, Lucas Bedeschi, Daniele C Aguiar, Laila Asth, Fabrício A Moreira
Cannabis and Cannabinoid Research February 2023 DOI: 10.1089/can.2022.0078 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Population | Rodents (experimental animals) exposed to the elevated plus maze |
| Interventions | type-1 cannabinoid receptor agonists (full or partial selective or not) |
| Dose | THC: 0.075-1 mg/kg (low-dose anxiolytic range) and 1-10 mg/kg (high-dose anxiogenic range) |
| Measures | elevated plus maze |
| Topics | Anxiety Cannabis |
| Keywords | Cb1 receptor Animal models Anxiolytics Cannabinoids Elevated plus maze |
| Key findings | Cannabinoids tend to reduce anxiety-like behavior at low doses, but THC produces anxiolytic-like effects at low doses (0.075-1 mg/kg) and anxiogenic-like effects at high doses (1-10 mg/kg). Some studies report no effect regardless of dose, and motor impairment at high doses may confound results. |
Abstract
Δ9-THC (the main active compound from Cannabis sativa) and related cannabinoids have been used as drugs of abuse and as medications. They induce a complex set of emotional responses in humans and experimental animals, consisting of either anxiolysis or heightened anxiety. These discrepant effects pose a major challenge for data reproducibility and for developing new cannabinoid-based medicines. In this study, we review and analyze previous data on cannabinoids and anxiety-like behavior in experimental animals. Systematic review and meta-analysis on the effects of type-1 cannabinoid receptor agonists (full or partial, selective or not) in rodents exposed to the elevated plus maze, a widely used test of anxiety-like behavior. Cannabinoids tend to reduce anxiety-like behavior if administered at low doses. THC effects are moderated by the dose factor, with anxiolytic- and anxiogenic-like effects occurring at low-dose (0.075-1 mg/kg) and high-dose (1-10 mg/kg) ranges, respectively. However, some studies report no effect at all regardless of the dose tested. Finally, motor impairment represents a potential confounding factor when high doses are administered. The present analysis may contribute to elucidate the experimental factors underlying cannabinoid effects on anxiety-like behavior and facilitate data reproducibility in future studies.