THC:CBD Effectively Reduces Severe Spasticity in Treatment-Resistant MS
The following article is part of conference coverage from the 2019 American Academy of Neurology Annual Meeting (AAN 2019) in Philadelphia, PA. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAN 2019.
PHILADELPHIA — Real-life outcomes support the long-term effectiveness of tetrahydrocannabinol and cannabidiol (THC:CBD) to improve spasticity in patients with multiple sclerosis (MS) resistant to other medications. This research was presented at the 2019 American Academy of Neurology Annual Meeting, held May 4-10, in Philadelphia.
The investigators of this observational, prospective, multicenter study sought to evaluate real-life, long-term efficacy outcomes of THC:CBD oromucosal spray to treat a large population of Italian patients with treatment-resistant MS spasticity. Spasticity was assessed using a numerical rating scale (0-10) at baseline, 1 month, 6 months, 12 months, and 18 months after treatment initiation.
After one month, 1502 (81.4%) of 1845 patients achieved ≥20% improvement in numerical rating scale for spasticity and 814 (40.2%) achieved ≥30% improvement. The mean reduction in spasticity scores was 28.9% at month 1 and 36.8% at month 18. A total of 727 (39.4%) participants discontinued treatment: 388 reported a lack of effectiveness whereas 339 experienced adverse events. The most frequently reported adverse events were vertigo (37.5%), sleepiness (34.8%), worsening of fatigue (28.3%), and cognitive symptoms (15.9%). In multivariate analysis, patients with a higher baseline spasticity score (odds ratio 2.21; 95% CI, 1.12-6.28; P <.01) or a greater change in scores between baseline and month 1 (odds ratio 2.03; 95% CI, 1.04-8.14; P <.05) were twice as likely to maintain therapy beyond 18 months.
The investigators suggest these results confirm the effectiveness of THC:CBD therapy to reduce treatment-resistant MS spasticity and sustain improvement for 18 months.
MS-Related Pain and Spasticity: Are Cannabinoids an Option?
Approximately 75 to 86% of people with multiple sclerosis (MS) experience pain. While there are treatments available, particularly for muscle spasticity, adequate pain control, not to mention improved quality of life, is hard to achieve in many. 1 A 2016 web-based investigation by the Michael J. Fox Foundation and the National Multiple Sclerosis Society found that 24% of 595 respondents reported overall high efficacy of cannabis use among those with MS, 2 prompting further research into the safety and efficacy of cannabinoids for treating MS-related pain.
Muscle spasticity, which may occur in up to 80% of patients with MS, is caused by cytokines, prostaglandins, and reactive oxygen species that change neuronal pathways and lead to fluctuations in motor circuit function and muscle tone. 3 Available pharmacological options (eg, baclofen, gabapentin, tizanidine, dantrolene, and botulinum toxin-A) often fail to reduce pain and improve quality of life. 4,5 Nonpharmacological approaches include passive stretching, relaxation techniques (eg, guided imagery, deep breathing), acupuncture, and aquatic therapy. 6
Mixed Results for Cannabinoids on MS Pain and Spasticity
Conclusive data on the efficacy of cannabinoids in MS patients is sparse but most available studies do focus on spasticity-related pain. Nielsen, et al, led a systematic review that examined 32 papers on the use of cannabis and cannabinoids in MS. Reviews included both experimental and epidemiological studies ranging from 2006 to 2014 which analyzed the effects of smoked cannabis sativa, CBD extract, dronabinol, nabilone, nabiximols, and THC extract in MS patients. This review was broad and inclusion criteria and analyzed outcomes were diverse, likely due to the limited evidence available.
When focusing on the effects of cannabinoids on generalized pain as part of MS, Nielsen’s team reported mixed results. Specifically, two medium quality reviews concluded that THC extracts were likely effective in reducing spasticity. The evidence quality of these two reviews was considered “medium,” but the studies involved were actually of “low” or “very low” quality. Other reviews of THC extracts reported positive effects but did not draw conclusions due to insufficient or questionable evidence. See Table Ia for details.
Results were mixed for spasticity as well. Many of the reviews assessed outcomes on the Ashworth scale of spasticity, a widely used 5-point scale based on a clinician’s subjective assessments of limb rigidity. Interestingly, improvements were self-reported by participants, even though measured data on the scale did not always match these results. These inconsistent findings suggest cannabinoids may provide spasticity relief via other unknown mechanisms.
Further analysis demonstrated a positive effect in spasticity reduction in all reviewed studies of smoked cannabis and THC extract alone, while mixed findings were reported in other cannabis variations and combinations (see Table Ib). 7 Regrettably, there is still much we do not know about the mechanism of cannabinoids, and without a standard for dosing and administration route, conducting clinical studies is challenging.
Safety must also be considered. According to the COMPASS trial, 8 which evaluated safety concerns of cannabis in MS patients, the most common adverse effects (seen in 2% to 5% of 215 total participants) were headache, nasopharyngitis, nausea, somnolence, dizziness, upper respiratory tract infection, vomiting, and cough. Additional adverse events deemed likely related to use of cannabis included amnesia, euphoria, sweating and paranoia, which were experienced by <0.5% of patients.
Nielsen’s review 7 also examined the diverse adverse effects of cannabis and cannabinoid use in multiple sclerosis. While many of the side effects were considered mild with few severe adverse events, the rate of side effects was greater for cannabinoids than controls in all evaluated studies. The authors noted that while the rate of overall events was higher for cannabinoids, the rate of serious adverse events was comparable to placebo. They concluded that adverse effect profiles were comparable for each cannabinoid and route of administration. 7
In response to subjective survey data, 2 patients were in favor of using cannabis and self-reported relief from their pain conditions. At this time, however, the appropriateness of using cannabinoids for MS-related pain should be evaluated on a patient-by-patient basis.
1. Solaro C, et al. Pain and Multiple Sclerosis: Pathophysiology and Treatment. Curr Neurol Neurosci Rep. 2012;19;13(1):320.
2. Kindred JH, et al. Cannabis use in people with Parkinson’s disease and Multiple Sclerosis: A web-based investigation. Complement Ther Med. 2017;;33:99-104.
3. Patejdl R, Zettl UK. Spasticity in multiple sclerosis: contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions.Autoimmun Rev. 2017 Sep 1;16(9):925-36.
4. Giacoppo S, et al. Sativex in the management of multiple sclerosis related spasticity: An overview of the last decade of clinical evaluation. Mult Scler Relat Disord. 2017;1;17:22-31.
5. Otero-Romero S, et al. Pharmacological management of spasticity in multiple sclerosis: Systemic review and consensus paper. Mult Scler J. 2016;22(11):1386-96.
6. Spasticity (stiffness) | MSAA. Available at: https://mymsaa.org/ms-information/symptoms/spasticity. Accessed April 8, 2020.
7. Nielsen S, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systemic review of reviews. Curr Neurol Neurosci Rep. 2018;13;18(2):8.
8. Rice J, Cameron M. Cannabinoids for treatment of MS symptoms: state of the Evidence. Curr Neurol Neurosci Rep. 2018;18(8):50.
Pharmacist’s Guide to CBD Oil
Cannabidiol (CBD) is becoming more prevalent, and pharmacists must be knowledgeable about these products in order to counsel patients effectively. CBD laws and regulations are determined at the state level in the United States. Non–FDA-approved CBD products are not regulated and may contain harmful chemicals. Pharmacists must counsel patients on where and how to obtain products and to check the amount of CBD and delta-9-tetrahydrocannabinol in the product. CBD has numerous drug interactions that should be evaluated by a pharmacist. CBD is most promising for treatment-resistant seizures, and more research is necessary to evaluate its use for other indications. Sativex is currently being investigated in the U.S. for treatment of spasticity associated with multiple sclerosis and schizophrenia. In general, more studies of CBD are needed.
Cannabidiol (CBD) is gaining popularity across the United States. Pharmacists must be able to answer patients’ questions about CBD and make recommendations. This article will provide specific information about CBD, including laws, how to select a non–FDA-approved CBD product, indications for use, side effects and warnings, drug interactions, dosing and directions, pharmacokinetics, and the future of CBD oil. After reading this article, pharmacists should feel confident about counseling patients about CBD and recommending CBD products.