Cannabinoid Drugs-Related Neuroprotection as a Potential Therapeutic Tool Against Chemotherapy-Induced Cognitive Impairment

Abstract

In recent years, and particularly associated with the increase of cancer patients’ life expectancy, the occurrence of cancer treatment sequelae, including cognitive impairments, has received considerable attention. Chemotherapy-induced cognitive impairments (CICI) can be observed not only during pharmacological treatment of the disease but also long after cessation of this therapy. The lack of effective tools for its diagnosis together with the limited treatments currently available for alleviation of the side-effects induced by chemotherapeutic agents, demonstrates the need of a better understanding of the mechanisms underlying the pathology. This review focuses on the comprehensive appraisal of two main processes associated with the development of CICI: neuroinflammation and oxidative stress, and proposes the endogenous cannabinoid system (ECS) as a new therapeutic target against CICI. The neuroprotective role of the ECS, well described in other cognitive-related neuropathologies, seems to be able to reduce the activation of pro-inflammatory cytokines involved in the neuroinflammatory supraspinal processes underlying CICI. This review also provides evidence supporting the role of cannabinoid-based drugs in the modulation of oxidative stress processes that underpin cognitive impairments, and warrant the investigation of endocannabinoid components, still unknown, that may mediate the molecular mechanism behind this neuroprotective activity. Finally, this review points forward the urgent need of research focused on the understanding of CICI and the investigation of new therapeutic targets.

Cannabidiol (CBD) in Cancer Management

“…As mentioned previously, a mice study found that CBD is protective against paclitaxel-induced neurotoxicity and in a separate experiment, found that CBD did not reduce the paclitaxel-induced inhibition of breast cancer cell viability [ 190 ]. Boullon and colleagues’ review suggests the potential for cannabinoids to address chemotherapy-induced cognitive impairment, given evidence of cannabinoids for the modulation of neuroinflammation and oxidative stress in different pathologies with a similar cognitive phenotype to CICI [ 199 ].…”

Mechanisms of Chemotherapy-Induced Neurotoxicity

“…Although it cannot be discarded that other treatments received by the cancer patients (opiates, neuroleptics) and other confounders, like inadequate nutritional status, may contribute to the problem, preclinical in vitro and in vivo studies do support that chemotherapy causes brain neurotoxicity ( Rzeski et al, 2004 ; Matsos and Johnston, 2019 ; Boullon et al, 2021 ; Bagues et al, 2022 ). Indeed, currently, chemofog is hypothesized to be the result of neuronal injury with abnormal brain remodeling.…”

Cannabinoid drugs against chemotherapy-induced adverse effects: focus on nausea/vomiting, peripheral neuropathy and chemofog in animal models

“…The occurrence of CICI (chemobrain) has been demonstrated in both preclinical models and patients and different biological mechanisms may contribute. As shown above, the ECS is implicated in at least two of the biological mechanisms in which chemotherapeutic drugs are thought to induce CICI, that is, neuroinflammation and oxidative stress (Boullon et al , 2021). Importantly, several reports have pointed out that pharmacological modulation of the ECS is able to reverse cognitive impairments in neuropathologies in which these mechanisms are involved, such as AD, PD and TBI.…”