Exploring the impact of chronic intermittent EU-GMP certified Cannabis sativa L. therapy and its relevance in a rat model of aging.

BACKGROUND: Aging is a multifaceted process marked by the progressive accumulation of cellular damage in various tissues, resulting in a decline in physiological functions. The primary aim of aging research is to identify compounds that can delay or mitigate these detrimental changes. As cannabis legalization becomes more widespread and with limited empirical studies on its effects in the aging human population, there is a pressing need for research into the impact of Cannabis and cannabinoids on healthy aging and age-related diseases. METHODS: Our study aims to evaluate the effects of chronic, intermittent exposure, defined as 6 weeks of use of EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos) administration, dosed at 6.25 and 25 mg/kg on neurobiological changes in naturally aged rats and its potential efficacy in mitigating age-related alterations. The impact of the Cannabixir® Medium Flos was assessed through clinical, histopathological, immunohistochemical, and behavioral evaluations. RESULTS: Cannabixir® Medium Flos was found to be generally safe, with no significant effects on motor performance and a neutral effect on anxiety-like behavior. Histological analysis revealed that the hippocampus of aged rats treated with this compound-an area known for its abundance of endocannabinoids and cannabinoid receptor type 1-exhibited characteristics similar to those observed in young adult rats. Additionally, the study suggests that chronic, intermittent treatment with Cannabixir® Medium Flos may modulate astrocyte function, reduce neuroinflammation, and potentially influence cell proliferation and neuronal apoptosis in a dose-dependent manner. However, these preliminary findings should be interpreted with caution, as the study's exploratory nature. CONCLUSIONS: These preliminary findings suggest that cannabinoid therapy targeting the endocannabinoid system may offer potential neuroprotective benefits in aging. While the study offers valuable preclinical insights into the effects of an EU-GMP-certified cannabinoid receptor ligand in reducing age-related cognitive decline, these effects are likely mediated by a combination of mechanisms. Given the complex phytochemical composition, the observed outcomes cannot be attributed exclusively to cannabinoid receptor activation. Accordingly, these findings should be interpreted with caution, and further studies employing more targeted methodologies are needed to elucidate the underlying mechanisms.