Neurological therapeutics have been hampered by their inability to advance beyond the symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, stop, or reversal of pathological processes.
While cannabis-based medicines have demonstrated safety, efficacy, and consistency sufficient for regulatory approval (EU, USA) for drugs in spasticity in multiple sclerosis (MS), and resistant epilepsies like Dravet and Lennox-Gastaut Syndromes (LGS), many other therapeutic challenges remain and wait for new drug discoveries, and cannabis-based medicines might be one of them (Table).
Recent discoveries offer to present neurological therapeutics through the use of phytocannabinoids like tetrahydrocannabinol (THC), cannabidiol (CBD), and their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the potential treatment of five syndromes, currently labeled recalcitrant to therapeutic success: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations provide some support for the treatment of these currently unmanageable conditions through the harness of endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), serotonin 1A receptor (CBD, CBDA) or even, important and interestingly, with nutritional approaches by utilizing prebiotics and probiotics.
Neurological conditions for which cannabis-based treatments have been employed so far are tabulated below (1).
|Condition||Level of evidence||Type of evidence|
|Multiple sclerosis (MS) spasticity ( CBD + THC)||Conclusive||Regulatory approval|
|Epilepsy (Dravet and Lennox-Gastaut syndromes) (CBD)||Conclusive||Regulatory approval|
|Chronic pain||Substantial||Phase II clinical studies|
|Schizophrenia||Substantial||Phase II clinical studies|
|Sleep disturbance secondary to neurological symptoms||Moderate||Phase II–III clinical studies|
|Tourette syndrome||Moderate||Observational studies|
|Dementia with agitation||Limited||Observational studies|
|Parkinson disease symptoms||Limited||Observational studies|
|Post-traumatic stress disorder||Limited||Observational studies|
|Social anxiety||Limited||Observational studies|
Many believe that neurology is facing a new therapeutic challenge: the current single target receptor model of pharmacotherapy has not proven universally salutary in the face of complex neurodegenerative diseases. Therefore, reconsideration should be given to an alternative and older proven model of botanical synergy that may enable polytherapy in single preparations. Such approaches, combined with nutritional and lifestyle management, may make neurology a more preventative and therapeutic specialty and provide better treatment for disorders like epilepsy, Alzheimer and Parkinson’s diseases.
The polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend neurological treatment into a new reality of effective interventional and even preventative treatment.
- B. Russo, Cannabis Therapeutics and the Future of Neurology, Frontiers in Integrative Neuroscience, 12, Article 51, 2018 (DOI: 10.3389/fnint.2018.00051 )
- National Academies of Sciences, Engineering, and Medicine 2017. The Health
Effects of Cannabis and Cannabinoids: The Current State of Evidence and
Recommendations for Research. Washington, DC: The National Academies Press.