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.
Comparable studies
Other systematic reviews and meta-analyses on cannabis for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review | 2020 | Systematic review | |
| Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties | 2020 | Systematic review | |
| What are the psychological effects of using synthetic cannabinoids? A systematic review Synthetic cannabinoid users, natural cannabis users, and non-users from 17 studies | 2019 | Systematic review | |
| “Noids” in a nutshell: everything you (don’t) want to know about synthetic cannabimimetics | 2014 | Systematic review and descriptive analysis | |
| Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety. Patients with social anxiety disorder or healthy volunteers performing tasks that... | 2024 | Systematic review |
Citations in the library
Cited by 3
- Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety. Reviews in the Neurosciences February 26, 2024
- FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice. Pharmacology, Biochemistry, and Behavior October 2023
- Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [3H] SR141716A receptor binding in the rat brain. Life Sciences August 15, 2023
Cites 16
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and 11 more in the library