Huntington’s disease is a fatal genetic disorder where the basal ganglia of the brain progressively deteriorate. Studies have shown that cannabis offers neuroprotective effects that slow the progression of the disease.

Huntington’s Disease Overview

The hereditary disease, also called Huntington’s chorea, causes psychiatric problems and affects movement and cognitive abilities. An individual has a 50% chance of developing the disorder if one of their parents has the disease, according to the National Institute of Neurological Diseases and Stroke. However, the most common symptoms do not appear until middle age.

Some of the movement-related symptoms typically begin with balance problems, lack of motor control and lack of dexterity. Patients may experience dystonia, involuntary jerky movements, poor posture and walking. Eventually the disease can cause the patient to lose the ability to walk, talk and swallow. The most common cognitive impairments include difficulty organizing, prioritizing and focusing on specific tasks, a tendency to get stuck in a thought or activity, difficulty learning, and lack of impulse control. The most common psychiatric problem caused by Huntington’s disease is depression, in addition to insomnia, fatigue and loss of energy, social isolation and feelings of irritability, sadness and indifference.

Cognitive, functional and psychiatric health deteriorates after the onset of the disease. Its progression speed and duration vary, but eventually the person ends up needing daily assistance. There is no cure yet, but some medications can help control symptoms. In addition, physiotherapy, speech therapy, occupational therapy and psychotherapy can help patients with behavioral, psychiatric and movement problems in general.

Effects of cannabis on Huntington’s disease

Research has shown that cannabis helps slow the progression of the disease through its interaction with the endocannabinoid system. After some studies determined that Huntington’s disease is related to the loss of cannabinoid receptors in the basal ganglia, researchers decided to examine whether increasing endocannabinoid activity could be beneficial for treating the disease 1. The results have been encouraging.

In preclinical studies, it was discovered that the main cannabinoids found in cannabis, THC (tetrahydrocannabinol) and CBD (cannabidiol), are effective in protecting neurons in the brain. Research shows that the activation of CB2 cannabinoid receptors reduces inflammation and toxicity of microglial cells, which reduces neurodegeneration caused by Huntington’s disease 3,4,10. Through the activation of CB1 receptors, cannabinoids have been shown to alleviate specific motor symptoms such as tremors and mobility problems, in addition to limiting the process by which neurons are destroyed, slowing the progression of the disease 1,2,12.

Furthermore, studies examining the effect of cannabis-based medications on Huntington’s disease have proven that cannabinoids are effective in slowing the progression of the disease 7,11,13,14,15.

Researchers concluded that modulating the endocannabinoid system with cannabis derivatives offers therapeutic potential for the treatment of diseases that affect the basal ganglia, such as Parkinson’s and Huntington’s disease 2. Cannabinoids are effective in neuroprotection through the following three ways: reducing inflammation by activating CB2 receptors, limiting cell death by activating CB1 receptors and through antioxidant effects independent of cannabinoid receptors 9,11. Studies have also indicated that cannabinoids are effective in reducing muscle spasms and inability to concentrate through direct activation of vanilloid TRPV(1) 9 receptors.

Recent studies on cannabis and Huntington’s disease

• Administration of substances that increase endocannabinoid activity caused a significant improvement in motor disorders and neurochemical deficits in mice with Huntington’s disease. Alleviation of motor hyperactivity and neurochemical deficits by inhibition of endocannabinoid absorption in a mouse model of Huntington’s disease. http://onlinelibrary.wiley.com/doi/10.1002/syn.10054/pdf
• Activation of CB2 receptors protects striatal neurons. Cannabinoid CB2 receptor agonists protect the corpus striatum from malonate toxicity: relevance to Huntington’s disease.
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/
• Cannabis medicine is effective as a neuroprotective agent, capable of slowing the progression of Huntington’s disease through the activation of CB1 and CB2 receptors. A combination of phytocannabinoids, such as Sativex, works as a neuroprotector in rats with malonate damage, an inflammatory model of Huntington’s disease: role of CB1 and CB2 receptors.
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382456/

References:

1. Dowie, M.J., Bradshaw, H.B., Howard, M.L., Nicholson, L.F., Faull, R.L., Hannan, A.J., and Glass, M. (2009, September). Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington’s disease. Neuroscience, 163(1), 456-65. Retrieved from
   http://www.sciencedirect.com/science/article/pii/S030645220901001X.
2. Fernández-Ruiz, J. (2009). The endocannabinoid system as a target for the treatment of motor dysfunction. British Journal of Pharmacology, 156(7), 1029–1040. Retrieved from
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697699/.
3. Fernández-Ruiz, J., Pazos, M.R., García-Arencibia, M., Sagredo, O., and Ramos, J.A. (2008, April). Role of CB2 receptors in neuroprotective effects of cannabinoids. Molecular and Cellular Endocrinology, 286(1-2 Suppl 1): S91-6. Retrieved from
   http://www.sciencedirect.com/science/article/pii/S0303720708000051.
4. Fernández-Ruiz, J., Moreno-Martet, M., Rodríguez-Cueto, C., Palomo-Garo, C., Gómez-Cañas, M., Valdeolivas, S., Guaza, C., Romero, J., Guzman, M., Mechoulam, R., and Ramos, J. A. (2011). Prospects for cannabinoid therapies in basal ganglia disorders. British Journal of Pharmacology, 163(7), 1365–1378. Retrieved from
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   https://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html.
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9. Pazos, M.R., Sagredo, O., and Fernández-Ruiz, J. (2008). The endocannabinoid system in Huntington’s disease. Current Pharmaceutical Design, 14(23), 2317-25. Retrieved from
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10. Sagredo, O., Ramos, J.A., Decio, A., Mechoulam, R., and Fernández-Ruiz, J. (2007, August). Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors. The European Journal of Neuroscience, 26(4), 843-51. Retrieved from
    http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1460-9568.2007.05717.x/full.
11. Sagredo, O., García-Arencibia, M., de Lago, E., Finetti, S., Decio, A., and Fernández-Ruiz, J. (2007, August). Cannabinoids and neuroprotection in basal ganglia disorders. Molecular Neurobiology, 36(1), 82-91. Retrieved from
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12. Sagredo, O., González, S., Aroyo, I., Pazos, M. R., Benito, C., Lastres-Becker, I., Romero, J.P., tolon, R.M., Mechoulam, R., Brouillet, E., Romero, J., and Fernández-Ruiz, J. (2009). Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease. Glia, 57(11), 1154–1167. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706932/.
13. Sagredo, O., Pazos, M.R., Satta, V., Ramos, J.A., Pertwee, R.G., and Fernández-Ruiz, J. (2011, September). Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s disease. Journal of Neuroscience Research, 89(9), 1509-18. Retrieved from
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14. Sagredo, O., Pazos, M.R., Valdeolivas, S., and Fernández-Ruiz, J. (2012, April). Cannabinoids: novel medicines for the treatment of Huntington’s disease. Recent Patents on CNS Drug Discovery, 7(1), 41-8. Retrieved from
    http://www.eurekaselect.com/89300/article.
15. Valdeolivas, S., Satta, V., Pertwee, R. G., Fernández-Ruiz, J., and Sagredo, O. (2012). Sativex-like Combination of Phytocannabinoids is Neuroprotective in Malonate-Lesioned Rats, an Inflammatory Model of Huntington’s Disease: Role of CB1 and CB2 Receptors. ACS Chemical Neuroscience, 3(5), 400–406. Retrieved from
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382456/.