Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity

Abstract

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (THC/CBD, Sativex, nabiximols) is available in numerous countries worldwide for the treatment of multiple sclerosis (MS)-related moderate to severe spasticity in patients who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. Twelve weeks' therapy with THC/CBD improved MS-related spasticity in patients with an inadequate response to other anti-spasticity agents who had undergone a successful initial trial of THC/CBD therapy, according to the results of a pivotal phase 3 trial. Improvements in spasticity were maintained in the longer term with THC/CBD with no evidence of dose tolerance, and results of real-world studies confirm the effectiveness of THC/CBD in everyday clinical practice. Improvements in health-related quality of life and activities of daily living were also seen with THC/CBD. THC/CBD is generally well tolerated; adverse effects such as dizziness may occur whilst the THC/CBD dosage is being optimized. THC/CBD has low abuse potential and a low risk of psychoactive effects. In conclusion, THC/CBD oromucosal spray is a useful option for the treatment of MS-related spasticity not completely relieved with current anti-spasticity medication.

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

“…The phytocannabinoid-derived medicine Sativex was licensed for the first time in 2005 in Canada for the treatment of spasticity and other neurological symptoms in multiple sclerosis patients and has been subsequently approved in over 25 countries for the treatment of spasticity due to multiple sclerosis [12], but it has also been proposed as a promising therapy for other pathological conditions in humans [9][10][11][15][16][17][18]. The use of Sativex could be also extended to Veterinary Medicine for the treatment of dogs and other domestic species affected by human-like or specific central and peripheral pathologies.…”

“…In the multiple dose experiment, dogs received 3 consecutive sprays (equivalent to 8.1 mg of ∆ 9 -THC and 7.5 mg of CBD) daily at the same time over a 14-day period. Blood was collected every day just before the treatment (pre-dose) and 45 min (based on previous literature [11,12]) after treatment (post-dose), except on the last day where the same collection times were used as for the single dose treatment (0, 14, 30, 45, 60, 120, 180, 240, 300, 360, 720 and 1440 min). All tubes were centrifuged for 10 min at 2300 g immediately after collection, and the plasma was extracted, frozen on dry ice and stored at −70 • C until analysis.…”

“…The discovery, and biochemical and physiological characterization of this modulatory system was initiated at the end of the 1980s [4,5] and continued up to the next two decades [6][7][8], but its pharmacological relevance originated long before this, with the discovery of endocannabinoids and their receptors giving support to the old and current uses of cannabis plant and their derived compounds for therapy [9][10][11]. A key step in this process was the formulation and approval of the phytocannabinoid-based medicine Sativex ® (GW Pharmaceuticals, Cambridge, UK) for the first time in 2005 [12]. It was marketed for the treatment of spasticity and pain in multiple sclerosis patients [12][13][14], and it is being investigated for other central and peripheral pathological conditions in humans [15][16][17][18].…”

“…A key step in this process was the formulation and approval of the phytocannabinoid-based medicine Sativex ® (GW Pharmaceuticals, Cambridge, UK) for the first time in 2005 [12]. It was marketed for the treatment of spasticity and pain in multiple sclerosis patients [12][13][14], and it is being investigated for other central and peripheral pathological conditions in humans [15][16][17][18]. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathological conditions.…”

Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor-1 gene (CB1); implications for cannabinoid pharmacogenetics

“…There are numerous examples of the successful use of cannabinoid drugs in the treatment of disease. For example, Sativex (a combination drug comprising of plant cannabinoids, delta-9-tetrahydrocannabidiol (THC) and cannabidiol (CBD)) supresses the chronic pain and spasticity associated with multiple sclerosis (Keating, 2017;Russo et al, 2016). However, the synthetic CB1 antagonist rimonabant, marketed as an appetite suppressor, was withdrawn because 26% of patients reported depression, anxiety and feeling of suicidality (Lazary et al, 2011).…”