Research Summary:

Huntington’s disease is an inherited neurodegenerative disorder that tends to arrive in adulthood with a progressive decline in motor control and cognitive function. It often begins with mood changes, followed by a lack of coordination and an unsteady gait, and ending with severe, uncoordinated movements of the body and dementia. Death usually occurs within 20 years of diagnosis. A disease of the brain’s basal ganglia (movement center), it’s linked to a faulty version of huntingtin – a protein with unknown function but one that interacts with over 100 proteins and can be toxic to certain cell types. At the biochemical level, Huntington’s leads to imbalances in dopamine and glutamate (the brain’s primary excitatory neurotransmitter) which causes excitotoxicity (neuron death via overexcitation). There is no known cure but the available treatments may provide some help with symptom relief and quality of life.

One hallmark of the disease is an early loss of CB1 receptors and endocannabinoid dysregulation, especially in the basal ganglia, leading to a loss of control over glutamate levels and to damaging levels of excitation in the brain. This suggests using cannabinoids as a treatment but despite positive reviews of the literature, the few studies in human have been mixed. In a double-blind study with Sativex (a 1:1 THC:CBD formulation) in 24 patients for 12 weeks, the researchers found no change in symptoms. But in 7 case studies, cannabinoids improved a range of motor symptoms and behavioral problems. A pilot study with nabilone (a pharmaceutical THC derivative) in 44 patients found help with motor control, chorea (involuntary spasmodic movements), cognition, and behavior while another study found that nabilone increased choreatic movements. An early study in 15 people found 6 weeks of 700 mg of isolated CBD per day to be nontoxic but not effective for symptoms.

However, the studies in preclinical models suggest we should continue to explore clinical trials. In a mouse model of Huntington’s disease, activating the CB1 receptor helped to prevent and rescue memory deficits and in another study, CBD or delta-8 THC extracts helped to protect the basal ganglia via regulation of metabolism and energy levels. In mice engineered to have no CB1 receptors, inducing Huntington’s disease led to worse motor symptoms than in wildtype mice. In a rat model of Huntington’s disease, Sativex worked via the CB1 and CB2 receptors to reduce brain leaks, neuron degeneration, glial activation (guardian immune cells of the brain), and neuroinflammation while activating the CB2 receptor protected from excitotoxicity. Extracts of CBD and THC were also shown to be protective because of their ability to increase antioxidation agents and to reduce brain atrophy.

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