Cannabidiol Oromucosal Spray Research Articles

A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis

BackgroundSpasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. MethodsThis was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. ResultsOf 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were −0.23 for nabiximols and −0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. ConclusionDespite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. Clinical trial registration number (ClinicalTrials.gov): NCT04657666

The effect of tetrahydrocannabinol:cannabidiol oromucosal spray on cognition: a systematic review.

Previous studies have shown that tetrahydrocannabinol (THC), the main psychoactive component of cannabis, can impair cognitive abilities. There is also some evidence that cannabidiol (CBD), the most abundant non-intoxicating constituent of cannabis, can attenuate these effects. The purpose of this study was to investigate the effects of THC:CBD oromucosal spray (with equal parts THC and CBD) on cognition compared with control conditions in human studies. A systematic literature search was performed on four major bibliographic databases. Studies were included in the present review if they evaluated the cognitive effects of THC:CBD oromucosal spray compared with a control condition. Ten studies were identified (7 on patients with multiple sclerosis, 1 on those with Huntington, and 2 on healthy volunteers) with 510 participants in total. There was considerable heterogeneity among the studies in terms of dose and duration of administration. All studies have used an equal or nearly equal dose of THC and CBD. Although the results across studies were somewhat inconsistent, most evidence revealed that there is no significant difference between THC:CBD oromucosal spray and control treatments in terms of cognitive outcomes. However, more trials are needed with longer follow-up periods, and dose considerations, particularly comparing lower and higher doses of the spray.

Nabiximols plus robotic assisted gait training in improving motor performances in people with Multiple Sclerosis.

BackgroundMultiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain. ObjectivesTo clarify the role of delta-9-tetrahydrocannabinol(THC):cannabidiol(CBD) oromucosal spray, coupled to robot-aided gait training (RAGT) using the Lokomat©Pro to improve functional ambulation in patients with MS. MethodsWe compared 20 patients with MS, who were treated with THC:CBD oromucosal spray in add-on to the ongoing oral antispastic therapy (OAT) (group A), with 20 individuals with MS (matched for clinical-demographic characteristics) who were treated only with OAT (group B). Both the groups underwent RAGT using the Lokomat-Pro (three 45-minute sessions per week). Our primary outcome measures were the Functional Independence Measure (FIM) and the 10 meters walking test (10MWT). As secondary outcome measures we evaluated the brain cortical excitability by using Transcranial Magnetic Stimulation. Both parameters were taken before and after the end of the RAGT. ResultsFIM improved in group A more than in group B (p<0.001). Moreover, 10MWT decreased in group A more than in group B (p<0.001). These clinical findings were paralleled by a more evident reshape of intracortical excitability in both upper and lower limbs, as suggested by motor evoked potential amplitude increase (p<0.001), intracortical inhibition strengthening (p<0.001), and intracortical facilitation decrease (p=0.01) in group A as compared to group B. ConclusionsOur results suggest that the combined THC:CBD-RAGT approach could be useful in improving gait performance in patients with MS.

Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial

Objective: To determine whether differences in disability status, spasticity severity, and spasticity duration at treatment start in patients with resistant multiple sclerosis (MS) spasticity might influence response to add-on tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (nabiximols) versus further re-adjustment of optimized first-line antispasticity medication.Methods: Using the database from the Sativex® as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) study, this post hoc analysis evaluated spasticity severity (0-10 numerical rating scale [NRS] scores) and pain severity (0–10 NRS scores) evolution from randomization (baseline) to week 12 (end of double-blind treatment) in defined subgroups: Expanded disability status scale [EDSS] score subgroups (<6 and ≥6); spasticity severity 0-10 NRS score subgroups (4 to ≤6 and >6), and spasticity duration subgroups (<5 and ≥5 years).Results: THC:CBD oromucosal spray (nabiximols) halved mean severity scores for spasticity and pain in all subgroups. Active treatment significantly improved mean spasticity severity scores versus placebo from week 4 onwards in both EDSS subgroups, in the severe spasticity subgroup, and in both spasticity duration subgroups. Active treatment significantly improved mean pain severity scores versus placebo in the ≥6 EDSS subgroup, in the severe spasticity subgroup and in both spasticity duration subgroups.Conclusion: Add-on THC:CBD oromucosal spray (nabiximols) consistently relieves resistant spasticity across subgroups defined by baseline EDSS score, spasticity severity NRS score and spasticity duration. Patients with moderate resistant MS spasticity benefit numerically from treatment; patients with severe resistant spasticity achieve significant therapeutic gains. Spasticity-associated pain often improves similarly in the same subgroups.

A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain.

The 20% prevalence of chronic pain in the general population is a major health concern given the often profound associated impairment of daily activities, employment status, and health-related quality of life in sufferers. Resource utilization associated with chronic pain represents an enormous burden for healthcare systems. Although analgesia based on the World Health Organization’s pain ladder continues to be the mainstay of chronic pain management, aside from chronic cancer pain or end-of-life care, prolonged use of non-steroidal anti-inflammatory drugs or opioids to manage chronic pain is rarely sustainable. As the endocannabinoid system is known to control pain at peripheral, spinal, and supraspinal levels, interest in medical use of cannabis is growing. A proprietary blend of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as the principal cannabinoids is formulated as an oromucosal spray (USAN name: nabiximols) and standardized to ensure quality, consistency and stability. This review examines evidence for THC:CBD oromucosal spray (nabiximols) in the management of chronic pain conditions. Cumulative evidence from clinical trials and an exploratory analysis of the German Pain e-Registry suggests that add-on THC:CBD oromucosal spray (nabiximols) may have a role in managing chronic neuropathic pain, although further precise clinical trials are required to draw definitive conclusions.

Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry.

Objective: To evaluate effectiveness, tolerability and safety of an oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as add-on treatment in patients with severe chronic pain (SCP).Methods: Exploratory analysis of anonymized 12-week routine/open-label data provided by the German Pain e-Registry (GPR) on adult SCP patients treated with THC:CBD oromucosal spray in 2017.Results: Among those 30.228 cases documented in the GPR in 2017, 800 (2.6%; 57% female, mean ± SD age: 46.3±9.7 years) received a treatment with THC:CBD. All patients fulfilled the legislative preconditions for a treatment with cannabis as medicine as defined by the German Act Amending Narcotics and Other Regulations. THC:CBD-treatment was followed by an aggregated nine-factor symptom relief (ASR-9) improvement at end of week 12 vs baseline of 39.0±26.5% (95%-CI: 36.9–41.1, median: 42, range −41 to 85). A full ASR-9 response (ie, a 50%-improvement in all 9 factors) was found for 123 patients (15.4%), while 488 patients (56.0%) presented with an ≥50% improvement in at least 5 of 9 ASR factors. With a 54.9±17.2% (median: 56%, range: −6 to 85) improvement was significantly superior in the neuropathic pain subgroup (n=497, 62.1%) vs those with mixed (n=249, 31.1%; ASR-9: 18.2±12.0, median: 19, range: −12 to 42%) or nociceptive pain (n=54, 6.8%; ASR-9: −11.9±10.5, median: −11, range: −41% to 12%; p<0.001 for each). 159 patients (19.9%) reported at least one of 206 TEAEs, most of them of mild intensity (n=81.6%). Most frequently reported TEAEs were increased appetite (n=50, 6.3%) and dysgeusia (n=23, 2.9%). TEAE-related discontinuations were reported for 32 patients (4.0%). 113 (14.1%) patients discontinued due to inadequate pain relief, most of them with nociceptive pain (n=40, 74.1%), least with neuropathic pain (n=1, 0.2%; p<0.001).Conclusion: THC:CBD oromucosal spray proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain – especially of neuropathic origin.

Long-term Effectiveness of 9-δ-tetrahydrocannabinol:Cannabidiol Oromucosal Spray in Clinical Practice: results from a 18-months Multicenter Italian Study (P5.2-085)

Long-term Effectiveness of 9-δ-tetrahydrocannabinol:Cannabidiol Oromucosal Spray in Clinical Practice: results from a 18-months Multicenter Italian Study (P5.2-085)

Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from randomized clinical trials.

Subsequent to EMA approval of tetrahydrocannabinol (THC): cannabidiol (CBD) oromucosal spray based on results of various studies, including an enriched-design clinical trial, two newer postapproval randomized trials have confirmed its efficacy and safety for treating resistant multiple sclerosis spasticity, while simultaneously addressing specific authorities' concerns. A double-blind, placebo-controlled, Phase IV trial, conducted as part of the EMA's risk management plan, found no effect of THC:CBD spray on cognition and mood after 50weeks of treatment. In the Sativex® as add-on therapy versus further optimized first-line ANTispastics(SAVANT) study, add-on THC:CBD spray was significantly more effective than readjusting standard antispasticity therapy and provided new evidence of efficacy as requested by German authorities.SAVANT results support practical recommendations for treating resistant multiple sclerosis spasticity in daily practice.

Newest evidence for tetrahydrocannabinol:cannabidiol oromucosal spray from postapproval pragmatic studies.

Postapproval studies have an essential role in demonstrating that an intervention is effective and well tolerated during use in daily clinical practice. Numerous large observational and registry studies of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray have been conducted subsequent to its approval in Europe in 2011. Collectively, these studies provide valuable insight into various aspects of THC:CBD spray during real-world use in patients with multiple sclerosis spasticity, including its long-term effectiveness and tolerability. The Italian Medicines Agency's web-based registry is the largest observational study of THC:CBD oromucosal spray conducted to date, reporting on more than 1600 patients prescribed THC:CBD spray since it was introduced in Italy in 2013, and further supporting its effectiveness and tolerability profile.

Tetrahydrocannabinol: cannabidiol oromucosal spray for treating symptoms of multiple sclerosis spasticity: newest evidence.

Proceedings of an Almirall-sponsored satellite symposium held at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin, Germany, 10 October 2018.

Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies.

Background/purpose:Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability. Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies.Methods:A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria.Results:In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice.Conclusions:The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.

Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial

Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®) as add-on therapy to optimised standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity. Methods: Sativex® as add-on therapy vs. further optimised first-line ANTispastics (SAVANT) was a two-phase trial. In Phase A, eligible patients received add-on THC:CBD spray for 4 weeks to identify initial responders [≥20% improvement from baseline in spasticity 0–10 numerical rating scale (NRS) score]. Following washout, eligible initial responders were randomised to receive THC:CBD spray or placebo for 12 weeks (double-blinded, Phase B). Optimisation of underlying antispasticity medications was permitted in both groups across all study periods. Results: Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically relevant responders after 12 weeks (≥30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs. 32.1%; p < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (p < 0.0001), mean pain NRS (p = 0.0013), and mean modified Ashworth’s scale (p = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns. Conclusions: Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.

Effect of tetrahydrocannabinol:cannabidiol oromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study.

To examine evolution in activities of daily living (ADL) in patients with multiple sclerosis spasticity during long-term use of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray. Functional impairment was assessed retrospectively (prior to start of treatment) and at the present moment using a 16-item ADL survey; results were compared. A control group without add-on THC:CBD oromucosal spray was included to investigate possible recall bias. ADL was maintained or slightly improved with THC:CBD oromucosal spray across treatment time (mean 31.9months) including significant improvement in 'standing up' (p<0.05) and trends in other items. Significant improvements (p<0.01) with THC:CBD oromucosal spray were observed in several multiple sclerosis spasticity-related symptoms. Overall, 96.9% of patients using THC:CBD oromucosal spray had a positive global impression of change during treatment. In this pilot study, THC:CBD oromucosal spray maintained or improved aspects of daily functioning. Further study in a larger trial is warranted.

Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study.

Complaints about Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®; GW Pharma Ltd, Salisbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies. This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects. Patients with multiple sclerosis spasticity (n=52) at six sites in Italy who were receiving THC:CBD oromucosal spray and had associated oral mucosal effects were randomized into Group A (chewing gum; n=15); Group B (cold bottle; n=20); and Group C (cold bottle+chewing gum; n=17). Taste perception in patients receiving chewing gum±cold bottle intervention (Groups A and C combined) was significantly (p=0.0001) improved from baseline to week 4 while maintaining spasticity control. Patient comfort, satisfaction and treatment adherence may benefit from these interventions.

A selective review of medical cannabis in cancer pain management.

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.

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

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.

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice

Background: Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). Aim: The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. Methods: This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months. After 1 month, only responders (≥20% improvement in spasticity) continued treatment. The main endpoints were the evolution of MSS and associated symptoms, quality of life (QoL) and tolerability. Results: Four hundred and thirty three patients (55% female) were recruited (98% in Italy). The mean duration of MSS was 7.4 years and baclofen was used by 78.1% of participants. Three hundred and forty nine participants continued with THC:CBD oromucosal spray after 1 month, and 281 after 3 months. THC:CBD mean dosage was 6 sprays/day. MSS scores and spasticity-related symptoms (spasms, fatigue, pain, sleep quality and bladder dysfunction) were significantly improved by THC:CBD at 3 months, as were activities of daily living, and QoL (EQ-5D VAS). Adverse events, none of which were severe or serious, were reported by 10.4% of patients. Conclusions: In everyday clinical practice, THC:CBD oromucosal spray provided symptomatic relief of MSS and related troublesome symptoms.

Effectiveness and Tolerability of THC/CBD Oromucosal Spray for Multiple Sclerosis Spasticity in Italy: First Data from a Large Observational Study

Background: The prospective, non-interventional Mobility Improvement (MOVE) 2 study was designed to provide real life data on clinical outcomes of patients with treatment-resistant multiple sclerosis (MS) spasticity receiving routine treatment with tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®), subsequent to its approval in European countries. Methods: This interim analysis reports on MOVE 2 patients from Italy. Results: Interim data from 322 patients (58.3% female; mean age 51.1 ± 10.2 years) were analyzed. From baseline to month 3 of treatment (Visit 3), the mean 0-10 Numerical Rating Scale (NRS) score decreased by -19.1% (-1.6 points, p < 0.0001) and the mean modified Ashworth score decreased from 2.6 to 2.3 points (p < 0.0001). At Visit 3, 24.6% of 203 patients with available data were clinically relevant responders (≥30% improvement from baseline NRS score; p < 0.001 vs. baseline). The mean reported dose of THC:CBD oromucosal spray was 6.1 ± 2.5 sprays/day at Visit 1 (1 month) and 5.1 ± 2.6 sprays/day at Visit 3 (range 1-12 sprays/day at both timepoints). Forty-one (13.1%) patients reported at least one adverse event (AE), which included 3 serious AEs (1 unrelated). AEs with an incidence ≥1% were dizziness (5.6%), confusion (2.5%), nausea (1.25%) and somnolence (1.25%). Conclusion: In everyday clinical practice in Italy, THC:CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant patients.

Observational Safety Study of THC: CBD Oromucosal Spray (Sativex) in Multiple Sclerosis Patients with Spasticity

Abstract Background: Subsequent to introduction in June 2010 in the United Kingdom and Spain of tetrahydrocannabinol (THC) : cannabidiol (CBD) oromucosal spray (Sativex®) for management of multiple sclerosis (MS) spasticity, and as part of a wider initiative to address British health authority requirements for post-marketing surveillance to identify possible short- and long-term risks associated with its use as a condition of marketing authorization, studies were undertaken to evaluate the safety of THC: CBDspray under clinical practice conditions. Methods: This prospective, observational, multicentre study reports on 205 patients with treatment-resistant MS spasticity who were prescribed THC: CBD spray as add-on therapy to existing antispasticity medications at 13 specialist MS centres across Spain. Safety evaluations were performed after 6 and 12 months’ exposure to THC: CBD spray. Results: Add-on THC: CBD spray was well tolerated during up to 12 months’ exposure. No new safety signals emerged and THC: CBD spray was not associated with any clinically-relevant occurrence of adverse events of special interest with cannabinoid-based medications such as falls requiring medical attention, psychiatric or psychotic symptoms, memory impairment, changes in driving ability, addiction or abuse. After 6 months’ and 12 months’ exposure, treating physicians considered that 139 patients (68% of original cohort) and 124 patients (60.5% of original cohort), respectively, were deriving sufficient anti-spasticity benefit from THC: CBD spray to warrant continued treatment. The mean dosage of THC: CBD spray (6.6 sprays/day) and carer requirements (~14.5 hours/day) remained stable throughout the study. Conclusions: THC: CBDspray as add-on therapy showed good tolerability and sustained anti-spasticity benefit in a relevant proportion (60.5%) of Spanish patients with MS-related spasticity treated for up to 12 months in everyday clinical practice.

Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity

This detailed medical charts’ data collection study conducted at a multiple sclerosis (MS) clinic in Germany evaluated the effectiveness of tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray in patients with resistant MS spasticity. Over a 15-month timeframe, THC:CBD spray was initiated in 166 patients. Mean follow-up was 9 months. In all, 120 patients remained on treatment for a response rate of 72%. THC:CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. Among responders, the mean spasticity 0–10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Most patients who withdrew from treatment (40/46) had been receiving THC:CBD spray for less than 60 days. Main reasons for treatment discontinuation were: adverse drug reactions, mainly dizziness, fatigue and oral discomfort (23 patients; 13.9%); lack of efficacy (14 patients; 8.4%); or need for a baclofen pump (9 patients; 5.4%). No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.