Search and Rescue: Identification of Cannabinoid Actions Relevant for Neuronal Survival and Protection

The use of cannabinoids for medicinal purposes has attracted wide interest in recent years, especially after the discovery of the endocannabinoid system. However, mechanisms relevant for neuroprotection and recovery of both exogenously applied and endogenous cannabinoids are only partly established. Supported by the observation that cannabinoids are released after neuronal injury and disorder, various CNS applications are currently investigated and both clinical and experimental data are now emerging. The present review describes possible mechanisms of cannabinoid actions relevant for neuroprotection, with a focus on excitotoxic cascades, oxidative stress and inflammation. The complexity of the system is outlined with regards to different cannabinoids, the receptors and cascades they activate, as well as the cell types and experimental approaches utilised to study their action. Furthermore, the unresolved problem of targeting protective pathways, while avoiding psychoactive and detrimental cascades is discussed.