Cannabinoids in Late Life Parkinson's Disease and Dementia: Biological Pathways and Clinical Challenges

Brain Sci. 2022 Nov 22;12(12):1596. doi: 10.3390/brainsci12121596.

Abstract

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of tremor, non-motor symptoms, anxiety, and sleep assistance in PD, and managing responsive behaviors of dementia such as agitation. However, strong evidence from clinical trials is scarce for most indications. Some clinicians consider cannabinoids an alternative for older adults bearing Parkinson's disease and Alzheimer's dementia with a poor response to first-line treatments. In our concept and experience, cannabinoids should never be considered a first-line treatment but could be regarded as an adjuvant therapy in specific situations commonly seen in clinical practice. To mitigate the risk of adverse events, the traditional dogma of geriatric medicine, starting with a low dose and proceeding with a slow titration regime, should also be employed with cannabinoids. In this review, we aimed to address preclinical evidence of cannabinoids in neurodegenerative disorders such as PD and AD and discuss potential off-label use of cannabinoids in clinical practice of these disorders.

Keywords: CBD; THC; cannabinoids; cannabis; elderly; neurological disorders; psychiatric disorders.

Publication types

  • Review

Grants and funding

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (Grant 2017/26291-2), Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN—Grant No. 2014/50873-3), Conselho Nacional de Desenvolvimento Científico—CNPq and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES. Ivan Aprahamian receives an individual national public grant level two (303302/2020-8) from the National Council for Scientific and Technological Development (Ministry of Science, Technology, Innovation and Communications, Brazil).