GW and Otsuka Pharmaceuticals Fund Research of MJ for Epilepsy

so much for the US DEA myth of Medical Marijuana scam

Proceedings of the British Pharmacological Society at
http://www.pA2online.org/abstracts/Vol9Issue3abst101P.pdf

Effects Of Cannabidiol And Cannabidivarin On Intrinsic Membrane Properties Of Hippocampal
CA1 Pyramidal Neurons

Charlotte L. Hill, Nicholas A. Jones, Andrew J. Hill, Benjamin J. Whalley, Claire M. Williams, Gary J. Stephens. University of Reading, Reading, Berkshire, UK.

Epilepsy is the most common chronic and disabling neurological condition in the UK and is thought to affect approximately 0.5-1% of the population (Bell & Sander, 2001). However, epilepsy remains refractory in about a third of epileptic patients despite optimal pharmacotherapy (Sander, 1993), demonstrating a clear need for the development of new, effective and well-tolerated antiepileptic drug treatments. Cannabidiol (CBD) and its propyl analogue, cannabidivarin (CBDV), are phytocannabinoids that have been shown to inhibit epileptiform activity in vitro and reduce seizure severity and mortality in vivo (Jones et al., 2010; Hill et al., 2010). Here, using in vitro electrophysiological methods, we have begun to investigate the mechanisms underlying the anticonvulsant effects of CBD and CBDV.

Acute, transverse hippocampal brain slices (300 μm) were obtained from adult, male, Wistar rats from which whole-cell patch clamp recordings were made using current clamp mode in visually identified CA1 pyramidal neurons. Slices were perfused with carboxygenated artificial CSF at room temperature.

A steady-state (at least 20 mins) was achieved and a control recording was made of intrinsic, postsynaptic membrane responses to hyperpolarising and depolarising current via the recording micropipette (-350 to 350 pA; 150 ms). Artificial CSF containing CBD or CBDV (both 10 μM; DMSO 0.1%) was then bath perfused and recordings made every 10 mins. The effects of CBD and CBDV reported here were assessed at 30 mins. Data are means ± SEM and statistical significance was determined using two-tailed, paired t-tests.

CBD (n = 6) significantly decreased membrane resistance from 105.0 ± 15.7 MΩ to 72.4 ± 6.2 MΩ (P<0.05), reduced mean spike count from 5.3 ± 0.4 to 3.1 ± 0.4 (P<0.001), decreased the instantaneous firing frequency between the second and third spikes from 40.6 ± 4.3 Hz to 22.6 ± 3.2 Hz (P<0.01) and increased spike width (1st spike, P<0.05; 2nd spike, P<0.001); CBD had no significant effect on spike amplitude when compared to control. In contrast, CBDV (n = 8) had no significant effect on membrane resistance, mean spike count, instantaneous firing frequency, spike width and spike amplitude when compared to control.

The results obtained for CBD on post-synaptic responses appear to be consistent with its anti-convulsant actions in vivo, which, therefore may be explained by CBD’s effects on intrinsic membrane properties. Although CBDV also shows anticonvulsant properties in vivo, it had no significant effect on the specific intrinsic, post-synaptic responses measured in this study. This suggests that the mechanism of action of CBDV may differ from that of CBD and is the subject of further current investigation.

Bell & Sander (2001) Seizure. 10; 306-316
Hill et al., (2010) Proc. Phys. Soc. 19
Jones et al., (2010) J. Pharmacol. Exp. Ther. 332; 569-577
Sander (1993) Epilepsia. 34; 1007-1016.

Work funded, and phytocannabinoids provided, by GW Pharmaceuticals & Otsuka Pharmaceuticals