Are Cannabinoids effective in the treatment of Parkinson's disease?
Localization of central cannabinoid receptor in the brain as well as results obtained from animal studies suggest that cannabinoids might be effective in the treatment of neurological movement disorders. So far, clinical trials in a limited number of patients provide evidence that cannabinoids are useful in the treatment of tics in Tourette-Syndrome and other hyperkinetic movement disorders such as dystonia.
To date only anecdotal reports are available investigating the clinical effect of cannabinoids in the treatment of Parkinson's disease. In a 1990 study no change in clinical symptomatology occured in 5 patients suffering from Parkinson's disease when smoking a marihuana cigarette. In another study the effect of cannabidiol (CBD) has been investigated in 8 patients suffering from dystonia, a hyperkinetic movement disorder. While there was a beneficial effect of CBD on dystonia, a deterioration of "coexisting parkinsonian features" was noted in 2 of these patients.
However, several animal studies provide evidence that in Parkinson's disease there is not only a reduction of dopamine concentrations but that there might also be an abnormalitiy in the central cannabinoid receptor system. Furthermore, it has been suggested that dopamine and endocannabinoids may have a close functional relationship. In an animal model of Parkinson's disease a sevenfold increase of the levels of endocannabinoids was found. Treatment with anti-parkinsonian drugs (dopamine receptor agonists) resulted in an improvement of parkinsonian symptoms. Simultaneously, the increased levels of endocannabinoids were reduced.
In addition, it has been suggested from animal studies that treatment with L-Dopa (an anti-parkinsonian drug) resulted in changes of the central CB1 receptor system (increased numbers of cannabinoid receptors in specific brain regions). In animal models of Parkinson's disease it has been demonstrated that treatment with anti-parkinsonian drugs improved voluntary movements while co-administration of cannabinoids produced Parkinson-like symptoms.
Based on available investigations it can be speculated that cannabinoid receptor blocking drugs (antagonists) - acting exactly the opposite compared to cannabinoids - might be useful in the treatment of Parkinson's disease. However, so far the effect of cannabinoid receptor antagonists has not been investigated in patients with Parkinson's disease.
(Sieradzan and colleagues):
Levodopa (L-Dopa) is the most effective anti-parkinsonian drug known so far. However, long term treatment with L-Dopa is often complicated by the incidence of levodopa-induced dyskinesia. Therapeutic options for managing these hyperkinetic movements are limited. We performed a randomised, double-blind, placebo-controlled, crossover trial in 7 patients with Parkinson's disease to investigate the effect of the cannabinoid receptor agonist nabilone in the treatment of levodopa-induced dyskinesia. Our results demonstrated a significant reduction of dyskinetic movements after treatment with nabilone. Nabilone had no effect on the antiparkinsonian action of L-Dopa. Surprisingly, from animal studies it has been demonstrated that a potent cannabinoid receptor antagonist (SR141716A) as well has antidyskinetic actions. We suggest that nabilone might act preferentially in another brain region than SR141716A. Both actions, however, may result in a reduction of dyskinetic movements.
Modified according to: Sieradzan KA, Fox SH, Hill M, Dick JPR, Crossman AR, Brotchie JM. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology 2001;57:2108-2111.