Subjective Reports Positive for Cannabis in MS, but Caution Urged

Nancy A. Melville

June 13, 2018

NASHVILLE, Tennessee — As patient demand for cannabis treatment of multiple sclerosis (MS) rises with loosening medical marijuana laws, patients report benefits that even include the ability to reduce other pain medications, but experts continue to urge caution of potential cognitive and other side effects that may be unique to MS.

In reporting on their own experience in treating patients with MS in New York, where use of medical cannabis has been legalized and one of the first accepted diagnoses was MS, researchers from the Dent Neurologic Institute, Amherst, New York, described a positive response from patients.

"The most notable findings from our retrospective review was that the patients demonstrated discontinuation of medications such as muscle relaxers, opioids, and benzodiazepines," first author Katelyn McCormack, FNP, told Medscape Medical News.

"There also was a low discontinuation rate of the medical cannabis, and the most common side effect was somnolence and only 6% noticed this, indicating it is well tolerated," she said. 

In the retrospective chart review, presented here at the Consortium of Multiple Sclerosis Centers (CMSC) 2018 Annual Meeting, McCormack and her colleagues reported outcomes on 77 patients with MS receiving medical cannabis for symptom management.

Of the patients, 61 (79%) were being treated for chronic pain, 24 (31%) for spasticity, 4 (5%) for numbness or dysesthagia, and 1 for restless legs syndrome.

Of the patients, 69% were female, and the average starting age of medical cannabis was 49 years. Thirty-one patients (40%) had disability and 30% had a history of recreational cannabis use.

The starting dosage of cannabis was 1:1, representing 1 component of tetrahydrocannabinol (THC) matched to 1 of cannabidiol for 54 (70%) patients, and as high as 20:1 for 20 (26%) patients.

Twenty-five (32%) patients had changes in dose throughout their therapy.

"Patients would either use the [oral] tincture or the vapor [as a mode of administration] depending on their tolerance," McCormack said.

"We did not specifically extrapolate that data, but going forward that may be further elucidated."

With an average time from initiation of medical cannabis to submission of self-rating scores of 345 days, 55 patients improved in pain; 33 in measures of spasticity; 32 in sleep; 11 in anxiety; 10 in quality of life; 7 each in gait and mood; 3 in numbness; 2 in focus; and 1 each in symptoms of balance, energy, genitourinary issues, heat sensitivity, appetite, memory, restless legs, and tremor.

No significant changes were observed from baseline to follow-up in objective measures, including the 25-foot timed walk, Montreal Cognitive Assessment, Mini-Mental Status Examination, and pain scales.

Notably, numerous reductions in the use of other medications were reported: Six patients in the study decreased use of muscle relaxers and 5 discontinued those drugs; 4 had decreases in opioid use and another 4 discontinued opioids; 3 had decreases in benzodiazepines and 1 patient each had a discontinuation of benzodiazepine, gabapentin, and zolpidem, and 1 had a decrease in stimulant use.

Weight did not significantly change throughout the study period.

The most common adverse events, rated with a Naranjo Adverse Drug Reaction Probability score of 1 or greater, included somnolence (5 [6%], with 1 leading to discontinuation), dizziness (3 [4%]), feeling "high"/cognitive impairment (3 [4%]), poor taste (tincture: 2 [3%]), incontinence (1), increased appetite (1), upset stomach (1), and throat discomfort (vapor: 1).

Eleven (14%) patients discontinued the treatment after an average of 132 days, with 4 patients each discontinuing because of cost or a lack of efficacy,  because of an adverse event, and 1 because of an unknown cause. The average cost of the medical cannabis treatment can range from about $100 a month to $300 a month, depending on the extent of use, McCormack said.

McCormack noted that patients who seem most appropriate for the treatment are those who have not responded well to other approaches.

"Generally, they use medical cannabis when typical therapies that are commonly used have not been providing the expected benefit," she said.

Medical Cannabis Interest Rises, Despite Concerns in MS

In commenting on use of medical cannabis among patients with MS, Anthony Feinstein, MD, PhD, a professor of psychiatry at the University of Toronto and director of the Neuropsychiatry Programme at Sunnybrook and Women's College Health Science Centre, in Toronto, Ontario, Canada, noted that as medical cannabis laws loosen, interest in its use for MS rises.

"About 20% of people with MS use marijuana on a regular basis for all sorts of reasons — pain, spasticity, insomnia and anxiety," he said in a press conference at the meeting.

"Yet there is some emerging evidence that the THC component may be harmful to cognition and memory, and that's a concern in MS, where about 40% of patients with relapsing-remitting MS have cognitive impairment and the rate goes up with progressive MS."

"So, if you're taking a medication with cognitive side effects, that's a potential problem," Feinstein said.

Subjective/Objective Debate "Will Evolve"

Feinstein noted that when more objective measures of improvement are evaluated with medical cannabis in MS, results may not line up. He described a recent study of his own (which has not yet been published) that divided patients with MS who used cannabis into a group that continued cannabis use and another that discontinued the cannabis treatment.

Evaluation of cognitive scores of the two groups showed significant improvements in cognition across all indices, as well as in mood, in those who discontinued cannabis compared with those who continued.

Nevertheless, even with the improvements, most in the discontinuation group wished to continue with their cannabis use.

"Even after hearing that their cognitive scores had improved, the patients who discontinued cannabis still wanted to go back to using it," Feinstein said.

"So clearly there is this subjective benefit and as a clinician, I think you need to listen to that, but there is indeed a concern of the cognitive effects."

In further comments to Medscape Medical News, Feinstein said patient reports of improvement and objective effects seen in patients underscore the unique complexity of cannabis treatment.

"There is a challenge here — how to marry the disconnect between subjective and objective evidence," he said. "There is no easy answer [and] this debate will evolve."

In the meantime, he urged clinicians to make patients aware of what the evidence has shown regarding potentially troublesome effects in MS.

"Patients need to recognize that cannabis can have some side effects that could prove problematic and these might offset the benefits they feel they receive," Feinstein told Medscape Medical News.

"One has to carefully weigh the evidence for and against this, and we are only just starting to make this journey."

Clinicians Often Unprepared  

In further addressing the issue of medical cannabis use among patients with MS in a talk at the meeting, Allen Bowling, MD, PhD, said another concern is that most clinicians are unprepared for the increasing demand.

"Eighty-nine percent of residents and fellows are not prepared to recommend cannabis use to patients, and 33% are not at all prepared to answer any questions about the plant," said Bowling, who is medical director of the Multiple Sclerosis Program at Colorado Neurological Institute and a clinical professor of neurology at the University of Colorado, Denver, in his talk.

In addition, most staff at the medical cannabis dispensaries have no medical or scientific training, even while advising patients on the use of products, which can vary substantially in concentration and formulations.

In terms of the evidence that does exist on the effects of cannabis in MS, the National Academies of Sciences, Engineering, and Medicine states that there is conclusive evidence of improvement in muscle spasms in patients with MS using oral cannabinoids and treatment of chronic pain with cannabis.

Likewise, guidelines from the American Academy of Neurology indicate strong evidence of oral cannabis extract for MS spasticity and pain, while evidence of benefits in the symptoms with smoked cannabis is insufficient.

The authors have disclosed no relevant financial relationships. Feinstein's disclosures include Avanir Pharmaceuticals (scientific advisory board) and Bayer Schering Pharma, Biogen, and Teva Pharmaceuticals Industries Ltd (speakers' bureau). Bowling's disclosures include relationships with Acorda, Bayer, Biogen-Idec, EMD-Serono, Genzyme, Novartis, Pfizer, Questcor, and Teva Neuroscience.

Consortium of Multiple Sclerosis Centers (CMSC) 2018 Annual Meeting. Abstract SX06. Presented May 31, 2018.

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