Huntington's disease is a genetic neurodegenerative disorder, marked by preferential degeneration of neurons in the basal ganglia (caudate and putamen) and accompanied by motor deficits, cognitive impairment and psychiatric symptoms. There is considerable evidence for the involvement of the endocannabinoid system in Huntington's but clinical trials so far have been inconclusive.
The endocannabinoid system has an important role in the patophysiology of Huntington’s Disease (Fernández-Ruiz et al., 2015; Pazos, Sagredo, & Fernández-Ruiz, 2008).
A meta-analysis of human and rodent genetics studies found consistent changes in CB1, PPARα and NAPE-PLD in patients and animal models of Huntington’s Disease (Laprairie et al., 2015), suggesting involvement of the endocannabinoid system.
In mice, blocking or stimulating CB2 function, respectively speeds up or slows down motor deficits, synapse loss and CNS inflammation that is associated with Huntington’s (Bouchard et al., 2012).
In a mouse model for Huntington’s (3NP), CBG showed neuroprotective effects and improved motor deficits (Valdeolivas et al., 2015).
Bouchard, J., Truong, J., Bouchard, K., Dunkelberger, D., Desrayaud, S., Moussaoui, S., … Muchowski, P. J. (2012). cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington’s disease. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 32(50), 18259-18268. https://doi.org/10.1523/JNEUROSCI.4008-12.2012
Fernández-Ruiz, J., Romero, J., & Ramos, J. A. (2015). endocannabinoids and Neurodegenerative Disorders: Parkinson’s Disease, Huntington’s Chorea, Alzheimer’s Disease, and Others. En R. G. Pertwee (Ed.), endocannabinoids (pp. 233-259). Springer International Publishing. https://doi.org/10.1007/978-3-319-20825-1_8
Laprairie, R. B., Bagher, A. M., Precious, S. V., & Denovan-Wright, E. M. (2015). Components of the endocannabinoid and dopamine systems are dysregulated in Huntington’s disease: analysis of publicly available microarray datasets. Pharmacology Research & Perspectives, 3(1). https://doi.org/10.1002/prp2.104
Pazos, M. R., Sagredo, O., & Fernández-Ruiz, J. (2008). The endocannabinoid system in Huntington’s disease. Current Pharmaceutical Design, 14(23), 2317-2325.
Valdeolivas, S., Navarrete, C., Cantarero, I., Bellido, M. L., Muñoz, E., & Sagredo, O. (2015). Neuroprotective properties of cannabigerol in Huntington’s disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 12(1), 185-199. https://doi.org/10.1007/s13311-014-0304-z
In one clinical trial, nabilone (a synthetic variant of THC) was found to improve motor function and reduce cognitive decline in Huntington’s patients (Curtis et al., 2009). In another trial, CBD was found ineffective in treating either the symptoms of Huntington’s or the underlying causes (Consroe et al., 1991).
Consroe, P., Laguna, J., Allender, J., Snider, S., Stern, L., Sandyk, R., Kennedy, K., and Schram, K. (1991). Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol. Biochem. Behav. 40, 701–708.
Curtis, A., Mitchell, I., Patel, S., Ives, N., and Rickards, H. (2009). A pilot study using nabilone for symptomatic treatment in Huntington’s disease. Mov. Disord. Off. J. Mov. Disord. Soc. 24, 2254–2259.