gw-1000 and Stroke

It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids). The distribution by type of stroke was as follows: 4 patients with an undetermined type of stroke, 85 with an ischemic stroke and/or a transient ischemic attack, and 9 with a hemorrhagic stroke. The mean age of patients was 32.3±11.8years (range 15-63), and the majority of them were male with a sex ratio of 3.7:1. Cannabis was often smoked with tobacco in 66% of cases. Most of the patients with cannabinoids-related strokes were chronic cannabis users in 81% of cases, and for 18% of them, there was a recent increase of the amount of cannabis consumption during the days before the occurrence of stroke. Even if the prognosis of stroke was globally favorable in 46% of cases, with no or few sequelae, 5 patients died after the neurovascular event. One striking element reported in the majority of the reports was a temporal relationship between cannabinoids use, whether natural or synthetic, and the occurrence of stroke. However, a temporal correlation does not mean causation, and other factors may be involved. Cannabis may be considered as a risk factor of stroke until research shows evidence of an underlying mechanism that, alone or in association with others, contributes to the development of stroke. As of today, reversible cerebral vasoconstriction triggered by cannabinoids use may be a convincing mechanism of stroke in 27% of cases. Indeed, despite the widespread use of cannabinoids, the low frequency of neurovascular complications after their use may be due to a genetic predisposition to their neurovascular toxicity in some individuals. Further studies should focus on this point. More importantly however, this low frequency may be underestimated because the drug consumption may not be systematically researched, neither by questioning nor by laboratory screening. Besides this vascular role of cannabinoids in the occurrence of stroke, a cellular effect of cannabis on b

Topics: Adolescent; Adult; Brain; Brain Ischemia; Cannabidiol; Cannabinoids; Cannabis; Cohort Studies; Dronabinol; Drug Combinations; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Factors; Stroke; Vasoconstriction; Young Adult

Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring.. We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment).. The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee 'Comitato Etico Regionale della Liguria'. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology.

Topics: Cannabidiol; Cross-Over Studies; Double-Blind Method; Dronabinol; Drug Combinations; Humans; Italy; Muscle Spasticity; Pilot Projects; Research Design; Stroke; Treatment Outcome