(P09-038-25) CBD Dysregulates Synaptic Plasticity Gene Expression Under HIV Infection

Objectives: Synaptic plasticity is the change of synapse strength in response to stimuli. This ability is essential for learning, memory, and overall fitness cognition and can be affected by neurocognitive disorders.  HIV-associated neurocognitive disorder (HAND) is characterized by the development of cognitive, behavioral, and motor issues and occurs in approximately 12-25% of HIV-infected individuals. Notably, Cannabidiol, CBD, a non-psychoactive cannabinoid found in the Cannabis plant, is a trendy supplement nowadays, recognized for its anxiolytic, antioxidant, and anti-inflammatory properties and beneficial improvement on cognition.

Methods: Thus, we aimed to elucidate the impact of CBD on synaptic plasticity in the presence of HIV. For that, we studied the influence of CBD on synaptic plasticity genes by RT PCR array and neurite outgrowth using SH-S5Y5, a neuroblastoma cell, after 6 days of HIV exposure.

Results: Our results showed that CBD significantly dysregulated NTRK2 (1.27; p=0.02194), MMP9 (-1.44; p=0.0492), NR4A1 (-1.53; p=0.01709) in the presence of HIV, and still in the absence of the virus the downregulation of the inflammatory enzyme MMP9 was predominant (-1.72; p=0.04564). Additionally, CBD (-1.53; p=0.01709) reversed the regulation exerted on the NR4A1 by HIV (1.87; p=0.02269).  Further, CBD upregulated the CDH2 gene, which maintains dendrites in post and presynaptic neurons. Moreover, CBD significantly promoted the growth of neurites after 24 hours of HIV exposure.

Conclusions: We concluded that CBD is a natural herbal supplement with promising therapeutic potential for cognition disorders present in HIV patients. However, more studies are required to obtain confirmatory protein dysregulation during the exposure course, the contribution of the HIV-rich environments promoted by other brain cells, such as glial cells, and the impact of these dysregulations on cognition.

Funding Sources: This work was supported by NIDA & NIA, National Institute of Health (Dr Lakshmana R01DA052271;  Dr Vashist R03AG087475).