Review of Available Data for the Efficacy and Effectiveness of Nabiximols Oromucosal Spray (Sativex®) in Multiple Sclerosis Patients with Moderate to Severe Spasticity

Abstract

Background: Sativex (USAN: nabiximols) oromucosal spray is indicated for treatment of multiple sclerosis (MS) patients with moderate to severe spasticity and inadequate response to other antispasticity medications who demonstrate clinically significant improvement during an initial trial of therapy. This narrative review investigated the efficacy and effectiveness of nabiximols oromucosal spray for moderate to severe MS spasticity by examining spasticity 010 Numerical Rating Scale (NRS) data from interventional and observational studies which featured a 4-week trial period as per the European Union approved label. Summary: Across both study types, clinically relevant and statistically significant reductions in mean MS spasticity 0–10 NRS scores were measured soon after treatment start and were maintained in the mid to long term in treatment responders. Initial responder rates (≥ 20% NRS improvement from baseline at week 4) ranged from 47.6% to 81.4%, tending lower in the randomized clinical trials setting. Clinically relevant responder rates (≥ 30% NRS improvement from baseline at week 12) were similar between study types (range 3041%) except for one outlier (74% in an observational study). Two open studies reported treatment continuation for ≥ 18 months in approximately half of patients who initiated treatment. In most longer-term studies, symptomatic improvement in MS spasticity was maintained at mean daily dosages of about 67 sprays/day. Safety was consistent with the known profile of nabiximols. Key messages: Experimental and observational studies of nabiximols oromucosal spray recorded similar findings. About half to two-thirds of MS patients who begin treatment will perceive initial symptomatic relief of spasticity within the 4-week trial period. About 40% of patients who initiate treatment will reach the ≥ 30% NRS improvement threshold at 3 months, comprising the majority of patients who continue long-term treatment. A trial of therapy with nabiximols is useful to identify patients most likely to gain longer-term improvement in spasticity symptoms and discontinue those with insufficient benefit.

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…The activation of CB1 by ∆ 9 -THC is believed to mediate its anti-nausea and anti-emetic effects [169]. Sativex, which contains a combination of ∆ 9 -THC and CBD, has been used for relief of neuropathic pain in multiple sclerosis [170].…”

In Vitro Effect of Δ9-Tetrahydrocannabinol and Cannabidiol on Cancer-Associated Fibroblasts Isolated from Lung Cancer

“…The combined use of THC and powerful CBD has shown the potential to enhance these effects, also reducing the harmful effects of THC at the level of the central nervous system. In fact, there is an FDA-approved drug called Sativex©, which is made up of an equimolar combination of these molecules and is indicated for the treatment of pain and other disorders, including multiple sclerosis [ 30 ]. We previously reported the effect of THC and CBD alone or in combination in an in vitro model carried out on three different cancer cell lines, which showed that CBD potentiated the effects of THC in terms of the inhibition of EMT proliferation and development in these three cell lines [ 20 ].…”

“…CAFs derive from different cell types, including connective tissue-resident fibroblasts, mesenchymal cells, and even cancerous epithelial cells, which undergo extreme epithelial-to-mesenchymal transition (EMT) [ 32 ]. CAFs control the composition of the tumor stroma and induce, among other things, EMT and metastasis in lung cancer, which makes them an attractive pharmacological target in the treatment of this pathology [ 30 , 32 ]. In the present study, we show that treatment with THC and/or CBD decreases cell density and the expression of type I collagen and FSP1 in CAFs isolated from the tumors of patients diagnosed with lung adenocarcinoma.…”

Considerations for Cannabinoids in Perioperative Care by Anesthesiologists

“…Nabiximols (Sativex™) is a combination drug delivering a dose of 2.7 mg THC and 2.5 mg CBD with each spray and is approved to treat dry mucosa in patients with multiple sclerosis [102,111]. Some have suggested using the drug to manage chronic pain, but the medication did not meet this goal [112].…”