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Huntington’s Disease

Huntington’s Disease is an inherited condition in which nerve cells in the brain break down over time.

DALL·E 2024-02-01 17.19.20 - Create an image of a neuron with a highly detailed structure,

Research Summary:

Huntington's disease is a hereditary neurodegenerative disorder that typically begins in adulthood, leading to a gradual decline in motor control and cognitive function. It usually starts with mood changes, followed by coordination difficulties and an unsteady walk, and eventually results in severe uncoordinated body movements and dementia. Patients with this condition typically succumb to it within 20 years of diagnosis. Huntington's disease primarily affects the basal ganglia in the brain, which is responsible for movement control, and it is associated with a faulty form of a protein called huntingtin. This protein interacts with over 100 others and can be harmful to specific cell types. At a biochemical level, Huntington's disease disrupts the balance of dopamine and glutamate, a key neurotransmitter in the brain, leading to overexcitation and neuron death, a process known as excitotoxicity. Unfortunately, there is no known cure for Huntington's disease, but available treatments can provide some relief from symptoms and improve the patient's quality of life.

One notable feature of this disease is the early loss of CB1 receptors and disruptions in the endocannabinoid system, particularly in the basal ganglia. This leads to an inability to control glutamate levels in the brain, resulting in excessive excitation. While there is some promise in using cannabinoids as a potential treatment, human studies have yielded mixed results. For example, a double-blind study involving 24 patients treated with Sativex (a 1:1 THC:CBD formulation) for 12 weeks showed no significant improvement in symptoms. However, seven case studies reported improvements in various motor symptoms and behavioral issues with cannabinoid treatment. Another study involving nabilone, a pharmaceutical derivative of THC, in 44 patients found improvements in motor control, chorea (involuntary spasmodic movements), cognition, and behavior, although another study found that nabilone increased choreatic movements. An early study using isolated CBD at a daily dose of 700 mg for six weeks in 15 individuals showed no toxic effects but also no significant symptom improvement.

Despite the mixed results in human studies, preclinical models in animals suggest that further exploration of clinical trials involving cannabinoids is warranted. In mouse models of Huntington's disease, activation of the CB1 receptor helped prevent and rescue memory deficits, and CBD or delta-8 THC extracts protected the basal ganglia by regulating metabolism and energy levels. Mice engineered to lack CB1 receptors experienced more severe motor symptoms when Huntington's disease was induced compared to wildtype mice. In a rat model of the disease, Sativex, acting through both CB1 and CB2 receptors, reduced brain leaks, neuron degeneration, glial activation (immune cells in the brain), and neuroinflammation. Activation of the CB2 receptor also provided protection against excitotoxicity. CBD and THC extracts were found to be protective due to their ability to increase antioxidants and reduce brain atrophy.

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