Spasticity In Multiple Sclerosis Research Articles

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.

Italian consensus on treatment of spasticity in multiple sclerosis.

Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti-spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. There is a clear need for new larger multicentre well-designed clinical trials with a duration that allows the persistence of the effects and the long-term safety of the interventions to be evaluated.

Benefits and harms of medical cannabis: a scoping review of systematic reviews

BackgroundThere has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition.MethodsA protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review.ResultsAfter screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality.ConclusionsResults from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits.Systematic review registrationThe protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).

PND86 COST-UTILITY ANALYSIS OF DELTA-9-TETRAHIDROCANNABINOL AND CANNABIDIOL OROMUCOSAL SPRAY

Multiple sclerosis (MS) is an autoimmune chronic progressive disease causing a high socioeconomic burden. Associated symptoms to the growing nerve damage, such as spasticity (muscle rigidity) are moderate to severe in about 1/3 of the patients. This study evaluates the impact on costs and health related quality of life of a 1:1 ratio delta-9-tetrahidrocannabinol + cannabidiol (THC+CBD) oromucosal spray for the management of resistant MS spasticity. A Markov model-based cost-utility analysis comparing THC+CBD spray plus standard spasticity care versus standard spasticity care alone was performed over a 5-year time horizon from a Belgian healthcare payer perspective. We used epidemiological and utility data from a recent clinical trial (SAVANT). Costs were based on unit costs updated for 2019 and resource use input from an ad-hoc Delphi panel. The probabilistic sensitivity analysis was implemented using a bootstrap approach over the clinical trial data and the Delphi responses so that the correlation between model parameters was maintained. Adding THC+CBD spray to standard spasticity care was found to dominate standard spasticity care alone, with cost savings of € 7530/patient and a quality adjusted life year (QALY) gain of 0.162 over the 5 year time horizon. The probabilistic sensitivity analyses showed that the probability of THC+CBD spray being cost-saving increased from 50% in the first year to 91% in the third year and 98% in the fifth year. In addition, the probability of adding THC+CBD spray being superior to standard-of-care treatment alone in terms of QALY gains was in access of 99% for all years. This analysis shows that under the modelled conditions the add-on use of THC+CBD spray is a dominant strategy, with both cost-savings and QALY gains, compared to current standard-of-care treatment alone for patients with resistant MS spasticity in Belgium, making it a valuable treatment available for them.

Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD)

BackgroundTreatment of spasticity poses a major challenge in amyotrophic lateral sclerosis (ALS) patient management. Delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (THC:CBD), approved for the treatment of spasticity in multiple sclerosis, serves as a complementary off-label treatment option in ALS-related spasticity. However, few structured data are available on THC:CBD in the treatment of spasticity in ALS.MethodA retrospective mono-centric cohort study was realised in 32 patients that meet the following criteria: 1) diagnosis of ALS, 2) ALS-related spasticity; 3) treatment with THC:CBD. Spasticity was rated using the Numeric Rating Scale (NRS). Patient’s experience with THC:CBD was assessed using the net promoter score (NPS) and treatment satisfaction questionnaire for medication (TSMQ-9) as captured through telephone survey or online assessment.ResultsThe mean dose THC:CBD were 5.5 daily actuations (range < 1 to 20). Three subgroups of patients were identified: 1) high-dose daily use (≥ 7 daily actuations, 34%, n = 11), 2) low-dose daily use (< 7 daily actuations, 50%, n = 16), 3) infrequent use (< 1 daily actuation, 16%, n = 5). Overall NPS was + 4.9 (values above 0 express a positive recommendation to fellow patients). Remarkably, patients with moderate to severe spasticity (NRS ≥ 4) reported a high recommendation rate (NPS: + 29) in contrast to patients with mild spasticity (NRS < 4; NPS: − 44). For the three main domains of TSQM-9 high mean satisfaction levels were found (maximum value 100): effectiveness 70.5 (±22.3), convenience 76.6 (±23.3) and global satisfaction 75.0 (±24.7).ConclusionTHC:CBD is used in a wide dose range suggesting that the drug was applied on the basis of individual patients’ needs and preferences. Contributing to this notion, moderate to severe spasticity was associated with an elevated number of daily THC:CBD actuations and stronger recommendation rate (NPS) as compared to patients with mild spasticity. Overall, treatment satisfaction (TSQM-9) was high. The results suggest that THC:CBD may serve as a valuable addition in the spectrum of symptomatic therapy in ALS. However, prospective studies and head-to-head comparisons to other spasticity medications are of interest to further explore the effectiveness of THC:CBD in the management of spasticity, and other ALS-related symptoms.

Neurological Uses of Cannabis

Cannabis preparations have been used as medications since the 19th century in Europe and much longer as a traditional medicine in other cultures. The American Academy of Neurology recently published a position statement and concluded that medical marijuana is “probably effective” for some symptoms of multiple sclerosis (spasticity, central pain, painful spasms, and urinary dysfunction), “probably ineffective” for levodopa-induced dyskinesias of Parkinson's disease, and of “unknown efficacy” in nonchorea symptoms of Huntington's disease. This article is focused on review of the medicinal use of cannabis in neurological disorders.

Assessment and Measurement of Spasticity in MS: State of the Evidence.

The purpose of this review is to familiarize the reader with assessments and measurement of spasticity in people with multiple sclerosis (MS). Spasticity affects 60-84% of people with MS, worsening as disability worsens and impacting activity, participation, and quality of life. Spasticity manifests in many ways, including spasms, resistance to passive stretch, pain, and perception of tightness, and can affect muscles throughout the body, making assessment and quantification of spasticity challenging but important. Assessment tools include those quantified by clinicians, instrumentation, and patients. Most tools for measuring spasticity are based on clinician scoring, were developed many years ago, and have undergone minimal recent advances. More recent developments are patient-reported outcome measures for spasticity, including the Numeric Rating Scale for Spasticity (NRS-S) and the disease-specific Multiple Sclerosis Spasticity Scale-88 (MSSS), and, most recently, imaging through elastography. MS-related spasticity is common and often disabling. There are various spasticity measurement tools available, each with advantages and limitations. Newer tools are likely to be developed as our understanding of spasticity in MS grows.

Application device for THC:CBD oromucosal spray in the management of resistant spasticity: pre-production testing

ABSTRACTBackground: Patients with multiple sclerosis spasticity (MSS) and upper limb/hand impairment who are taking 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) may have difficulty self-administering their medication, possibly limiting adherence and treatment effectiveness. A Class I EU device is available to support the administration of THC:CBD spray. Pre-production testing was undertaken in a patient sample.Methods: Current users of THC:CBD spray were recruited to review the instruction leaflet and test the device. Patients and observing health-care professionals (HCP) completed a purpose-designed questionnaire which captured user experience and HCP opinion.Results: Fifteen patients participated. Mean treatment time with THC:CBD spray was 4 (range: 0.1–6.1) years. 87% of participants ‘always’, ‘often’ or ‘sometimes’ had hand impairment, and 53% reported difficulty administering THC:CBD spray. Participants reported better application using the device (73%), with less strength required (54%). Most participants (93%) considered the instruction leaflet to be clear and many (66%) expressed interest in using the device. Most HCPs (93%) did not foresee any difficulties in use of the device.Conclusion: The proposed adherence device was useful to address self-application difficulties with THC:CBD spray in our sample. Providing the device to MSS patients with upper limb/hand spasticity impairment may restore autonomy and support adherence to THC:CBD spray.

The effect of cycling using active-passive trainers on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe Multiple Sclerosis (MS); a feasibility study.

BackgroundExercise options for those with moderate to high levels of disability are limited. The aim of the study was to evaluate the feasibility of a progressive, four week lower limb cycling programme using active-passive trainers (APT's) on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe MS. MethodsParticipants were in-patients in the Physical Disability Rehabilitation Unit, Queen Elizabeth University Hospital, Glasgow, UK and randomised to APT + usual care or usual care only. The APT group received 30 min of APT (2 min passive warm up, 26 min active cycling, 2 min passive cool down), five days per week for 4 weeks. Outcome measures; Oxygen Uptake Efficiency Slope, Modified Ashworth Scale, Multiple Sclerosis Spasticity Scale, Functional Independence Measure, Timed 25 foot walk test and the MSQOL-54, were taken before and after the intervention period. Symmetry, distance cycled and active participation were also recorded for each cycling session. Results24 participants were recruited, 15 to the intervention and 9 to the control group. There was a 100% adherence to the intervention and a significant increase in average speed, power output and distance cycled (p < 0.001 for each) over the four weeks. There were no adverse events and both groups improved in average scores for all outcome measures. ConclusionsAPT cycling was well tolerated, while the cycling parameters improved it was difficult to separate the effects of the therapy programme and APT cycling. A longer duration, fully powered trial in a community setting is merited.

Cannabis Use in People with Multiple Sclerosis and Self-Reported Spasticity (P5.2-100)

Cannabis Use in People with Multiple Sclerosis and Self-Reported Spasticity (P5.2-100)

Aplicaciones terapéuticas por acción de los cannabinoides.

The interest on cannabinoids became evident between the 1940 and 1950 decades. Although the active substance of the plant was not known, a series of compounds with cannabinomimetic activity were synthesized, which were investigated in animals and clinically. The most widely tested was Δ6a, 10a-THC hexyl. Δ6a, 10a-THC dimethylheptyl (DMHP) antiepileptic effects were studied in several children, with positive results being obtained in some cases. DMHP differs from sinhexyl in that its side chain is DMHP instead of n-hexyl. The first cannabinoid isolated from Cannabis sativa was cannabinol, although its structure was correctly characterized several years later. Cannabidiol was isolated some years later and was subsequently characterized by Mechoulam and Shvo. In 2013, the National Academy of Medicine and the Faculty of Medicine of the National Autonomous University of Mexico, through the Seminar of Studies on Entirety, decided to carry out a systematic review on a subject that is both complex and controversial: the relationship between marijuana and health. In recent years, studies have been conducted with cannabis in several diseases: controlled clinical trials on spasticity in multiple sclerosis and spinal cord injury, chronic, essentially neuropathic, pain, movement disorders (Gilles de Latourette, dystonia, levodopa dyskinesia), asthma and glaucoma, as well as non-controlled clinical trials on Alzheimer's disease, neuroprotection, intractable hiccups, epilepsy, alcohol and opioid dependence and inflammatory processes.

(171) Evaluating the Pain and Discomfort Scale to Assess Spasticity-Related Pain in Cerebral Palsy

Assessing pain among individuals with communicative impairments and developmental disabilities is a clinical challenge. In this preliminary study, we addressed, in part, the issue of the association between chronic pain and spasticity in cerebral palsy (CP). Specifically, we evaluated the measurement performance of a proxy-reported spasticity rating scale (Multiple Sclerosis Spasticity Scale–MSSS) and the feasibility of a range of motion examination procedure (Pain Examination Procedure–PEP) using direct-observation to code behavioral reactivity during the exam (Pain and Discomfort Scale – PADS). Fifteen individuals with CP (mean age=10.9 years, range=6.2-17.2 years; GMFCS=3-5; male=46%) were evaluated pre- (T1) and post- (T2) intrathecal baclofen pump (ITB) surgical implant to treat spasticity. The PEP protocol was successfully completed for all participants in the clinical setting. Cronbach's alpha for the MSSS was 0.96. PADS change scores (T1 to T2) were significantly correlated with MSSS change scores (r=0.80, p=0.006). The strong positive correlation suggests the PADS/PEP protocol may be measuring spasticity-related pain and discomfort, providing initial construct validity evidence between an objective/direct and subjective/indirect assessment method for pain and spasticity in CP. T1 PADS scores were also highly positively correlated with both PADS change and MSSS change scores (r=-0.72, p=0.006; r=-0.85, p=0.002), providing preliminary evidence of the predictive utility of a pre-ITB surgery PADS/PEP protocol. This was not a random sample, therefore the results are specific to the sample and may not hold for the population of individuals living with CP. Given the absence of self-report, we cannot be certain and do not claim to have measured the pain experience of the individuals in the sample. Future work should continue to examine the PADS as a potential pain behavior assessment tool to provide a direct assessment option for the study of pain among individuals with CP and related developmental disabilities. Supported by NICHD Grant No. 73126

Polymorphisms in the CIITA -168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients.

We examined the impact of CIITA polymorphisms -168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA -168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA -168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA -168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. These data suggest that CIITA -168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy. Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism. Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions. The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well. Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia. The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.

Cannabis and cannabinoids-easier access, hype and disappointment : What has been confirmed in therapy?

Cannabis products are being increasingly liberalized all over the world and there is ahuge interest in cannabis-based medicine. Presentation of current studies on the efficacy of different cannabis-based medicine for the treatment of various diseases CURRENT DATA: In German pharmaceutical legislation, nabiximols is approved for the treatment of moderate to severe therapy-resistant spasticity in multiple sclerosis and nabilone is approved for the treatment of therapy-resistant chemotherapy-associated nausea and vomiting. In case of therapy failure cannabinoids, as part of an individual therapeutic attempt, may be considered for the treatment of chronic pain (neuropathic pain, cancer pain, non-neuropathic noncancer pain), cachexia in human immunodeficiency virus as well as for Dravet and Lennox-Gastaut syndrome. From the authors' perspective there is not enough evidence for the use in chemotherapy-associated nausea and vomiting and chronic non-neuropathic pain. Currently, awide use of cannabinoids does not seem probable in the near future. Further studies involving more patients and evaluating long-term effects are necessary.

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.

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.

Evaluation of the Multiple Sclerosis Spasticity Scale 88: A Short Report.

Background:The Multiple Sclerosis Spasticity Scale 88 (MSSS-88) is designed to capture the patient experience and impact of spasticity, but there is limited evaluation against clinician-rated measures of spasticity.Objective:To evaluate the convergent validity and responsiveness of the MSSS-88.Design:Longitudinal study.Setting:University Laboratory.Subjects:Thirty-four people with multiple sclerosis.Methods:People with multiple sclerosis (MS; n = 34) completed the self-reported 12-item Multiple Sclerosis Walking Scale, Multiple Sclerosis Spasticity Scale, Barthel Index alongside the clinician-rated Ashworth Scale, and a laboratory-based measure of ankle spasticity. Spasticity measure responsiveness was evaluated in 20 participants at two time points, an average of 8.75 ± 3.8 months apart.Results:In people with MS (mean age 55.1 ± 8.1 years; Expanded Disability Scale range 4.5-7.0), spasticity symptom specific subscales of the MSSS-88 (stiffness and spasms) showed strong and significant correlations with the clinician-rated Ashworth Scale (r = 0.52-0.53; P < .01). Responsiveness of the MSSS-88 was comparable to a laboratory-based measure of ankle spasticity.Conclusions:Our findings lend additional support to the convergent validity of this measure.

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.