Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.
R. Linge, Laura Jiménez-Sánchez, L. Campa, Fuencisla Pilar-Cuéllar, R. Vidal, Á. Pazos, Albert Adell, Á. Díaz
Neuropharmacology April 1, 2016 DOI: 10.1016/j.neuropharm.2015.12.017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Olfactory bulbectomy (OBX) mouse model of depression |
| Intervention | Cannabidiol (CBD) |
| Duration | Acute and chronic administration |
| Measures | open field test, sucrose preference test, microdialysis, autoradiography of 5-HT1A receptor functionality |
| Topics | CBD Serotonin |
| Key points | CBD produced fast and maintained antidepressant-like effects in OBX mice, reversing hyperactivity and anhedonia. It enhanced serotonin and glutamate levels in the ventromedial prefrontal cortex, and both the behavioral and neurochemical effects were prevented by 5-HT1A receptor blockade, suggesting a 5-HT1A receptor-dependent mechanism. |
Abstract
Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
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- Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey. Psychopharmacology November 4, 2021
- The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors. Neurochemical Research August 27, 2026
- Therapeutic potential of phytocannabinoids in depression and cognitive dysfunction: Evidence from preclinical models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2026
and 11 more in the library
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