Cannabis sativa and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?

Abstract

This work is a literature review, presenting the current state of the use of cannabinoids on neurodegenerative diseases. The emphasis is on Parkinson's (PD) and Alzheimer's (AD) diseases, the two most prevalent neurological diseases. The review goes from Cannabis sativa and its hundreds of bioactive compounds to Δ⁹-tetrahydrocannabinol (THC) and mainly cannabidiol (CBD) and their interactions with the endocannabinoid receptors (CB1 and CB2). CBD molecular targets were also focused on to explain its neuroprotective action mechanism on neurodegenerative diseases. Although THC is the main psychoactive component of C. sativa, and it may induce transient psychosis-like symptoms, growing evidence suggests that CBD may have protective effects against the psychotomimetic effects of THC and therapeutic properties. Furthermore, a great number of recent works on the neuroprotective and anti-inflammatory CBD effects and its molecular targets are also reviewed. We analyzed CBD actions in preclinical and in clinical trials, conducted with PD and AD patients. Although the data on preclinical assays are more convincing, the same is not true with the clinical data. Despite the consensus among researchers on the potential of CBD as a neuroprotective agent, larger and well-designed randomized clinical trials will be necessary to gather conclusive results concerning the use of CBD as a therapeutic strategy for the treatment of diseases such as PD and AD.

Keywords: Cannabidiol; Cannabis sativa; Neurodegeneration; Neuroprotection.

Fig. 1

Main molecular targets for cannabidiol (CBD) in Parkinson's disease (PD). Cannabinoid receptors (CB1/CB2), transient receptor potential cation channel subfamily V member 1 (TRPV1), Wnt/GSK-3β (Wnt/glycogen synthase kinase 3 beta pathway), nerve growth factor (NGF), neurotrophic tyrosine kinase receptor member (TrkA), Janus kinase (JAK), signal transducer and activator of transcription proteins (SATAxin3), nicotinamide adenine dinucleotide (NADH), adenomatous polyposis coli (APC), casein kinase 1 (CK1), beta-catenin (β-catenin), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

Fig. 2

Molecular targets for cannabidiol (CBD) in Alzheimer's disease (AD). Cannabinoid receptors (CB1/CB2), transient receptor potential cation channel subfamily V member 1 (TRPV1), Wnt/GSK-3β (Wnt/glycogen synthase kinase 3 beta pathway), amyloid precursor protein (APP), beta-amyloid (Aβ) peptide, peroxisome proliferator-activated receptors (PPARγ), beta-catenin (β-catenin), neurofibrillary tangles (NFTs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tau protein (TAU), reactive oxygen species (ROS).