Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical serotonin/glutamate neurotransmission

In a novel study by Linge and colleagues, cannabidiol (CBD) was shown to exhibit strong anxiolytic and antidepressant effects in mice. The study also elucidated CBD’s mechanism of action on serotonin receptors in the brain. Their findings indicate that CBD could represent a novel fast-acting antidepressant drug.

CBD is the main non-psychotomimetic component of marijuana. This means that behind THC, the compound responsible for many of the mind-altering affects we collectively refer to as a “high,” CBD produces the majority of it’s therapeutic benefit without inducing highness. Utilizing the olfactory bulbectomy (OBX) mouse model of depression, researchers studied the behavioral efficacy of CBD via the enhancement of serotonergic and glutamatergic transmission through the modulation of 5-HT 1A receptors. Classical antidepressants act through similar serotonergic attenuation whereas the effects of fast-acting antidepressants seem to be mediated mainly by glutamatergic signalling.

The results of this study shows that CBD exerts rapid antidepressant-like effects as evidenced by the reversal of OBX-induced hyperactivity immediately after the first injection. Additionally, its efficacy is maintained and improved with the repeated administration, as anhedonia (inability to feel pleasure) was completely relieved after one week of treatment with a dose of 50 mg/kg. The findings also revealed a crucial role of 5-HT 1A and CB1 receptors in the behavioral and anxiolytic effects of CBD. As anxiety is a complex syndrome affected by different brain processes, the two receptors could be implicated in the anxiety outcome at different levels.

In summary, the fast onset of antidepressant action of CBD and the simultaneous anxiolytic effects, combined with the broad range for therapeutic dosage and the lack of psychotomimetic effects shows a strong therapeutic advantage for its use in clinical practice compared to other antidepressant alternatives.

Linge R, Jiménez-Sánchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuopharmacology 2016;103:16-26