Huntingtons Disease

Huntington’s Disease

PrintHuntington’s Disease (HD) is an inherited degenerative brain disorder characterized by motor abnormalities and dementia produced by selective lesions in the cerebral cortex and, in particular, the striatum. There are presently no known conventional therapies available to alleviate HD symptoms or delay HD-associated striatal degeneration.

Cannabinoids possess various properties that make it attractive in the potential treatment of neurodegenerative disorders like Huntington’s disease,[1-3] and cannabinoid administration has shown efficacy in the treatment of HD in preclinical models[4-6] as well as in case studies.[7] As a result, scientists have called for clinical trials evaluating the effect of cannabinoid pharmacology in HD patients.[8-9] To date, however, no controlled human trials exist assessing cannabis for this clinical condition.

REFERENCES

[1] Luvone et al. 2009. Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neuroscience & Therapeutics 15: 65-75.

[2] Sagredo et al. 2012. Cannabinoids: Novel Medicines for the Treatment of Huntington’s DiseaseRecent Patents on CNS Drug Discovery 7: 41-48.

[3] Gowran et al. 2011. The multiplicity of action of cannabinoids: implications for treating neurodegenerationCNS Neuroscience & Therapeutics 17: 637-644.

[4] Sagredo et al. 2011. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington’s diseaseJournal of Neuroscience Research 89: 1509-1518.

[5] Valdeolivas et al. 2012. Sativex-like combination of phytocannabinoids in neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington’s disease: role of CB1 and CB2 receptorsACS Chemical Neuroscience16: 400-406.

[6] Valdeolivas et al. Effects of a Sativex-like combination of phytocannabinoids on disease progression in R6/2 mice, an experimental model of Huntington’s diseaseInternational Journal of Molecular Sciences 18. [online ahead of print]

[7] Meisel and Friedman. 2012. Medical marijuana in Huntington’s disease: report of two casesMedicine and Health, Rhode Island 95: 178-179.

[8] Sagredo et al. 2011 op. cit.

[9] Sagredo et al. 2012. Cannabinoids: novel medicines for the treatment of Huntington’s diseaseRecent Patents on CNS Drug Discovery 7: 41-48.

OVERVIEW OF HUNTINGTON’S DISEASE

Huntington’s disease is an inherited progressive degenerative disease that causes nerve cells in the basal ganglia of the brain to waste away. The disease, also commonly referred to as HD or Huntington’s chorea, causes psychiatric disorders and affects a person’s movement and cognitive abilities. People with Huntington’s disease are born with the defective gene, as there’s a 50 percent chance of getting it if one parent has the disease, according to the National Institute of Neurological Disorders and Stroke. However, symptoms most commonly don’t develop until middle age.

Movement-related symptoms of Huntington’s disease typically begin with uncontrolled movements, balance problems, and overall clumsiness. Patients can experience dystonia, involuntary jerking movements, and impaired gait and posture. Eventually, the disease can take away the ability to walk, talk, and swallow. Cognitive impairments commonly associated with the disease can include a difficulty organizing, prioritizing, and focusing on tasks, a tendency to get stuck on a thought or action, difficulty learning new information, and a lack of impulse control. The most common psychiatric disorder caused by Huntington’s disease is depression, but the disease can also lead to insomnia, fatigue and loss of energy, social withdrawal, and feelings of irritability, sadness, and apathy.

Functional, cognitive, and psychiatric health worsens over time after the onset of Huntington’s disease. The rate of disease progression and duration varies, but eventually a person requires daily living help. There is no cure for the disorder, but some medications can help manage symptoms. Additionally, physical, occupational, speech, and psychotherapies can help patients address movement, behavioral, and psychiatric problems.

FINDINGS: EFFECTS OF CANNABIS ON HUNTINGTON’S DISEASE

Research has shown that cannabis helps slow the progression of Huntington’s disease through its interaction with the endocannabinoid system. After studies determined that Huntington’s disease was related to a loss of cannabinoid receptors in the basal ganglia, researchers set out to examine whether increasing endocannabinoid activity could be therapeutically beneficial for treating the disease1. Results have been encouraging.

In preclinical trials, the major cannabinoids found in cannabis have been found to be effective at protecting the life of neurons in the brain. Research has shown that through the activation of cannabinoid 2 receptors (CB2), the inflammation and toxicity of microglial cells is reduced, which in turn slows the neurodegeneration caused by Huntington’s disease2. Through the activation of cannabinoid 1 receptors (CB1), cannabinoids have shown to effectively alleviate specific motor symptoms like tremors and movement disorders and reduce the process in which neurons are damaged and killed to slow the progression of the disease1.

Additionally, studies examining the effect of cannabis-based medications on Huntington’s disease have proven cannabinoids effective at delaying the progression of the disorder7.

Researchers suggest that targeting the cannabinoid system with cannabinoids may have a potential therapeutic benefit for treating basal ganglia disorders like Parkinson’s disease and Huntington’s disease. Cannabinoids are effective at providing neuroprotection through three methods: reducing inflammation by activating CB2 receptors, limiting cell death by activating CB1receptors, and providing an antioxidant effect through a mechanism independent of cannabinoid receptors6,7. Studies also indicate that cannabinoids are effective at reducing muscle spasms and the inability to concentrate through their direct activation of vanilloid TRPV(1) receptors6.

STATES THAT HAVE APPROVED MEDICAL MARIJUANA FOR HUNTINGTON’S DISEASE

Currently, MaineNew MexicoNew YorkPennsylvania and West Virginia have approved medical marijuana for the treatment of Huntington’s disease.

Huntington’s disease patients may be able to get legal access to medical marijuana in other states. In Washington D.C., any condition recommended by DC-licensed physician can be approved for medical marijuana. California allows medical marijuana for “any debilitating illness where the medical use of marijuana has been deemed appropriate and has been recommended by a physician.’” In Connecticut, “other medical conditions may be approved by the Department of Consumer Protection.” Huntington’s disease patients in Massachusetts may be able to get legal access, as the state approves “other conditions as determined in writing by a qualifying patient’s physician.” The state of Washington allows medical marijuana for “any terminal or debilitating condition.” In NevadaOregon, and Rhode Island, “other conditions are subject to approval.”

RECENT STUDIES ON CANNABIS’ EFFECT ON HUNTINGTON’S DISEASE

  • The administration of substances that increase endocannabinoid activity caused a significant improvement of motor disturbances and neurochemical deficits in mice with Huntington’s disease.
    Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington’s disease.
    http://onlinelibrary.wiley.com/doi/10.1002/syn.10054/pdf

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., 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.
  3. Huntington’s Disease. (2016, February 24). MedlinePlus. Retrieved from https://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html.
  4. Huntington’s disease. (2014, July 24). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/huntingtons-disease/basics/definition/con-20030685.
  5. Latres-Becker, I., Hansen, H.H., Berrendero, F., De Miguel, R., Pérez-Rosado, A., Manzanares, J., Ramos, J.A., and Fernández-Ruiz, J. (2002, April). Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington’s disease. Synapse, 44(1), 23-35. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/syn.10054/pdf.
  6. 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 http://www.eurekaselect.com/67570/article.
  7. 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 http://link.springer.com/article/10.1007%2Fs12035-007-0004-3.
 
 
 

 
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