Cannabis and Huntington”s Chorea
Huntington”s chorea is a fatal degenerative condition inherited via sex chromosomes. It is rare in women who may carry the disease, which usually develops in middle-aged males. There is a gradual loss of mental and cognitive function, commonly associated with depression and progressive loss of voluntary motor control, leading to an increasing dependency on others.
The condition is incurable, although neuroleptic drugs such as haloperidol may be used to control symptoms. It has been suggested that the neuronal degeneration caused by the disease results from excess free-radicals oxidation or glutamate. Skaper et al showed cannabinoids, but not anandamide, to protect against glutamate-mediated neurotoxicity. Peyser et al concluded “Antioxidant therapy may slow the rate of motor decline early in the course of Huntington’s disease. ” Hampson et al found THC and CBD to be “neuroprotective anti-oxidants” improving the recovery prospects of stroke patients by reducing glutamate toxicity, and considered their results to suggest the neuroprotective action not to be receptor-dependent. However Consroe et al found no positive or negative effect of CBD in Huntington”s patients, although this may be due to the degree of neuronal damage already present at the outset of the trial.
Richfield et al demonstrated there to be a selective loss of cannabinoid receptors in specific regions of the brain called the corpus striatum and globus pallidus, and Glass et al showed a “massive loss – 97.5%) of cannabinoid receptors in the substantia nigra (within spinal cord) of Huntington”s patients. N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to delay neurodegeneration, and a synthetic cannabinoid (+)-HU-210 has been found to be a potent antagonist of the NMDA receptor, “giving it a potential for use in … neurodegenerative disorders”.
This is an emerging area of research and clearly more research is needed. However the massive depletion of cannabinoid receptors, coupled with the neuroprotective effects of cannabidiol, would suggest cannabinoids potentially to have a major future role in treating symptomatology of Huntington”s chorea (e.g. uncontrolled muscle spasms/movements) by direct stimulation of remaining receptors by THC or other CB1 receptor agonists; and/or by delaying the development of the disease due to the neuroprotective effects of THC and CBD.
EFFECTS OF CANNABIDIOL IN HUNTINGTON’S DISEASE
Neurology 36 (Suppl 1) April 1986 p. 342
Reuven Sandyk, Paul Consroe, Lawrence Z. Stern, and Stuart R. Snider, Tucson, AZ
Cannabidiol (CBD) is a major nonpsychoactive cannabinoid of marijuana. Based on reports indicating possible efficacy of CBD in dystonic movements (Neurology 1984; 34 [Suppl 1]: 147 and 1985; 35 [Suppl 1]: 201), we tried CBD in three patients with Huntington’s disease (HD). The patients;, aged 30 to 56, had HD of 7 to 12 years’ duration. Their condition has been slowly progressive and unresponsive to prior therapy with neuroleptics. Orally administered CBD was initiated at 300 mg/d and increased 1 week later to 600 mg/d for the next 3 weeks. Mild improvement ( 5 to 15%) in the choreic movements was documented using the tongueprotrusion test (Neurology [Minneap} 1972; 22: 929-33) and a chorea severity evaluation scale (Br J Clin Pharmacol 1981; 11: 129-51) after the first week. Further improvement (20 to 40%) was noticed after the second week of CBD, and this remained stable for the following 2 weeks.
Except for transient, mild hypotension, no side effects were recorded, and laboratory tests were normal. Withdrawal of CBD after 48 hours resulted in return of choreic movements to the pre-CBD state.