Nabiximols (NBX) suppresses tremor in a rat Harmaline model of essential tremor

Background

Essential tremor (ET) is one of the most prevalent movement disorders; despite this, there remains an unmet need for novel therapies. The treatment of rats with harmaline modulates the rhythmicity of inferior olivary neurons, resulting in generalized tremor with a frequency of 9–12 Hz in rats, comparable to that of human ET (4–12 Hz).

Purpose

Interestingly, cannabinoids reduce tremor, therefore we have assessed the cannabinoid nabiximols (NBX; marketed as Sativex) a complex botanical drug mixture, in the harmaline-rat model of ET.

Method

We tested the effects of acute (single dose) and subchronic (10 days) treatment of NBX (at 5.2, 10.4 and 20.8 mg kg⁻¹ p.o.) administered prior to harmaline and acute NBX (20.8 mg kg⁻¹) administered post-harmaline in male SD rats. Propranolol (20 mg kg⁻¹ i.p.) was used as a positive control. Observed Scoring (OS) was carried out prior to placement in a tremor-monitoring apparatus for the calculation of Tremor Index (TI) and Motion Power Percentage (MPP).

Results

Acute and subchronic NBX significantly attenuated harmaline-induced tremor at 10.4 and 20.8 mg kg⁻¹, respectively, for each parameter (OS, TI, and MPP) when administered pre-harmaline as did propranolol (20 mg kg⁻¹). NBX did not attenuate harmaline-induced tremor when administered post-harmaline.

Conclusions

These data suggest efficacy of acute and subchronic NBX to reduce tremors, based on OS, TI and MPP readouts if administered prior to harmaline. These data are the first to indicate the preclinical effects of an oral botanical cannabinoid formulation, NBX, in an animal model of ET.