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|Title||The effects of the cannabinoid receptor agonist nabilone on L-DOPA induced dyskinesia in patients with idiopathic Parkinson's disease (PD).|
|Author(s)||Sieradzan KA, Fox SH, Dick J, Brotchie JM.|
|Journal, Volume, Issue||Movement Disorders 1998;13(Suppl 2):29.|
|Major outcome(s)||Activation of cannabinoid receptors can reduce L-DOPA-induced dyskinesia in man without aggravating parkinsonism.|
The neural mechanisms underlying L-DOPA-induced dyskinesia involve overactivity of the lateral segment of the globus pallidu (GPI). Cannabinoid receptors are concentrated in the GPI and reduce GABA re-uptake. Thus cannabinoids may reduce GPI activity and hence alleviate L-DOPA-induced dyskinesia (see Fox et al, this meeting). We studied 7 PD patients with severe L-DOPA-induced dyskinesia and assessed the effects of the Cannabinoid receptor agonist nabilone on dyskinesia. Oral nabilone or placebo were tested in a double-blind, randomized, cross-over manner in an acute L-DOPA challenge setting (Madopar 250 mg) after overnight withdrawal of all anti-PD treatment. Trial drugs were given 12h (1-2 mg) and 1h (1 mg) before L-DOPA. The “off” and best “on” Webster motor scores were recorded. Dyskinesia was rated in the “off” state and every 20 min after L-DOPA using the Goetz scale. There was a significant reduction in “onset” (20-40 min post L-DOPA) dyskinesia scores following pre-treatment with nabilone compared to placebo (median 18.5, range 8-28 v 24.5 range17-60, respectively, P < 0.05; Wilcoxon Rank Sign test) but no difference throughout the remaining “on-period”. The latency and duration of “on” response, the percentage “on” with dyskinesia and the “off” state Webster scores on nabilone and placebo were not significantly different. Two patients with painful “off” dystonia had marked symptom relief with nabilone. There were mild psychotropic side effects with nabilone and hypotension was noted in one case. This study suggests that activation of cannabinoid receptors can reduce L-DOPA-induced dyskinesia in man without aggravating parkinsonism. These effects of nabilone on “onset” dyskinesia and “off” dystonia merit further investigation.
|Participants||7 PD patients|
|Type of publication||Medical journal|
|Address of author(s)|