Study: Cannabigerol Shows Antidepressant and Cognitive Benefits in New Study

A new preclinical study published in Biomedicine & Pharmacotherapy by researchers from the University of Coimbra, Universitat de Barcelona, and the Carlos III Health Institute in Spain finds that the cannabis compound cannabigerol (CBG) may offer antidepressant-like effects while also improving cognitive function, outperforming several other cannabinoids tested.

Depression remains one of the most widespread mental health conditions globally, with existing medications failing in roughly 30% to 40% of patients. Researchers noted in the study that this gap underscores “the urgent need for novel agents with pleiotropic effects,” prompting an evaluation of five cannabinoids: cannabichromene (CBC), cannabidiol (CBD), cannabidivarin (CBDV), cannabigerol (CBG), and cannabinol (CBN).

The research began with laboratory testing in microglial cells to assess toxicity and anti-inflammatory properties. CBD and CBDV demonstrated the strongest anti-inflammatory effects, significantly reducing markers associated with inflammation. However, when the study moved to animal models, results diverged sharply.

Using both healthy mice and those exposed to a chronic stress model designed to mimic depression, researchers found that “only cannabigerol produced consistent antidepressant-like effects in the forced swimming test compared to ketamine” among healthy subjects. In stressed mice, repeated doses of CBG led to notable improvements in cognitive performance.

By contrast, CBD showed limited therapeutic benefit in this context, failing to significantly improve depressive behaviors or cognitive deficits despite a favorable safety profile. CBDV, while effective in reducing inflammation in early testing, produced negative outcomes in later stages, including anxiety-like effects and impaired cognitive and liver function.

One of the more notable findings involved brain structure. The study reports that CBG’s cognitive benefits were “associated with increased dendritic spine density in the hippocampus,” suggesting it may promote neuroplasticity, a key factor in both mood regulation and cognitive health.

Summarizing their findings, researchers state that “a single administration of cannabigerol ameliorates depressive-like behavior in healthy animals, while multiple administrations improved cognitive function in mice exhibiting depressive-like phenotypes.” They add that CBG combines “low toxicity, antidepressant-like effect, and improved cognitive function, likely via modulation of structural plasticity.”

While the results are limited to preclinical models, the authors say the findings position CBG as a strong candidate for future research into treatments for depression and cognitive disorders. They call for further studies to better understand its mechanisms, evaluate long-term safety, and explore its potential in other conditions, including Alzheimer’s disease.

If confirmed in human trials, these findings could mark a significant step forward in developing new, cannabinoid-based treatments for mental health conditions that remain difficult to treat with existing therapies.

The study’s full abstract can be found below:

Depression is a highly prevalent and incident mental illness. Current pharmacological therapies fail in approximately 30–40% of patients, highlighting the urgent need for novel agents with pleiotropic effects. This preclinical study aimed to identify new antidepressants and cognitive modulators among five phytocannabinoids: cannabichromene, cannabidiol, cannabidivarin, cannabigerol and cannabinol.

Phytocannabinoids were first evaluated in BV-2 microglial cells for cell viability and then, for anti-inflammatory activity, where BV-2 cells were previously stimulated with lipopolysaccharide (50 ng/mL). Based on these profiles, and comparing with ketamine, cannabidiol, cannabidivarin and cannabigerol were selected to be administered (55 µmol/kg, i.p.) once to healthy CD-1 male mice, and subsequently, administered six times to mice submitted to the unpredictable chronic mild stress (UCMS) protocol, which is a validated model of depression.

Among the phytocannabinoids under investigation, cannabigerol exhibited the lowest cytotoxicity, whereas cannabidiol and cannabidivarin demonstrated the strongest anti-inflammatory effects, significantly reducing nitrite, iNOS and pro-IL1β levels. In healthy mice, only cannabigerol produced consistent antidepressant-like effects in the forced swimming test compared to ketamine. Under UCMS protocol, cannabidivarin was anxiogenic and impaired cognitive and hepatic functions. Cannabidiol, despite its favorable safety profile, failed to ameliorate depressive phenotype or cognitive deficits. Notably, cannabigerol significantly improved cognitive performance, associated with increased dendritic spine density in the hippocampus.

Overall, our unprecedented findings demonstrated that a single administration of cannabigerol ameliorates depressive-like behavior in healthy animals, while multiple administrations improved cognitive function in mice exhibiting depressive-like phenotypes. Together, these results highlight the therapeutic potential of cannabigerol in mood and cognitive disorders.