Cannabidiol alleviates chemotherapy-induced cognitive decline and neuropathology.

Chemotherapy is frequently associated with long-term cognitive impairments in cancer survivors that negatively impact their quality of life. Effective mitigation strategies for cancer therapy-related cognitive impairments (CRCI) are still underdeveloped. Our clinical studies on breast cancer patients treated with doxorubicin (Adriamycin®, ADR) and cyclophosphamide (CYP) found significant CRCI associated with neurodegenerative and neuroinflammatory signatures. Current preclinical and clinical studies highlight the potential of cannabidiol (CBD) for alleviating cognitive deficits in neurodegenerative conditions. For example, Epidiolex® is an FDA-approved 99% pure formulation of CBD for treating pediatric epilepsy. CBD, a non-psychoactive component of cannabis, is recognized for its neuroprotective and anti-inflammatory effects. This study, using a mouse model of adjuvant chemotherapy (ADR and CYP)-induced cognitive decline, tested the efficacy of oral administration of 99% pure CBD (20 mg/kg) in sesame oil. ADR + CYP-treated mice receiving CBD for one month showed significant neurocognitive improvements in learning and memory, executive function, and memory consolidation tasks often impaired in cancer survivors. CBD treatment also restored brain endocannabinoid (ECB) levels and reduced ECB-metabolizing enzymes in vivo. Notably, CBD mitigated chemotherapy-induced loss of neurogenesis, neuronal plasticity, synaptic density, and elevated gliosis. In summary, this data provides preclinical evidence for a translationally feasible approach to alleviate CRCI, an unmet medical need.