Mapeamento do uso terapêutico e segurança da Cannabis sativa em Alzheimer, esclerose múltipla e Parkinson: revisão de escopo

Abstract

Neurodegenerative diseases (Alzheimer's Disease, Parkinson's Disease, and Multiple Sclerosis) represent a growing global public health challenge, with conventional therapies showing limited efficacy. Cannabis sativa derivatives, especially cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), have attracted interest due to their pleiotropic properties and modulation of the Endocannabinoid System. The entourage effect suggests therapeutic superiority of full-spectrum formulations over chemical isolates. The objective of this study was to map the available scientific evidence on the therapeutic potential and safety profile of Cannabis sativa derivatives in adults and older adults with Alzheimer's Disease, Multiple Sclerosis, and Parkinson's Disease, identifying gaps in the literature. A scoping review was conducted according to the Joanna Briggs Institute (JBI) guidelines and reported following PRISMA-ScR. The search was performed in eight databases (PubMed, Cochrane Library, Web of Science, Scopus, Science Direct, SciELO, LILACS, and Google Scholar) in June 2026, without language or period restrictions. Primary and secondary studies with data on therapeutic efficacy and safety in humans were included. Data synthesis was conducted using basic qualitative content analysis with an inductive approach. A total of 150 studies were included (77 primary and 73 secondary). Multiple Sclerosis concentrated the largest volume of evidence (62.7%), followed by Parkinson's Disease (19.3%) and Alzheimer's Disease (10.0%). The United Kingdom, Italy, and Brazil were the countries with the highest number of publications. In MS, nabiximols (THC:CBD) significantly reduced subjective spasticity (NRS) in 75.0% of RCTs, with responders ranging from 37% to 77.4%, although without objective changes on the Modified Ashworth Scale. In PD, results were inconsistent for motor symptoms but promising for non-motor symptoms (anxiety, quality of life, dyskinesia). In AD, benefits were concentrated on agitation control, without consistent cognitive effects. Full-spectrum formulations showed superior efficacy (77.1%) compared to isolates (35.0%). The safety profile was favorable, with mild to moderate adverse events (dizziness 14-59%, somnolence 5-42%, fatigue 6-62%). Cannabis derivatives present variable therapeutic potential depending on pathology and formulation, with more robust evidence for spasticity in MS and non-motor symptoms in PD. Gaps include dosage standardization, long-term evidence, objective biomarkers, and studies in older populations. Future research should prioritize clinical trials with active comparators and prolonged follow-up to consolidate clinical guidelines.