By Ulrike W. Kaunzner, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Kaunzner reports no financial relationships relevant to this field of study.

SYNOPSIS: The authors of a recent study evaluated the effect of discontinuing cannabis use in patients with multiple sclerosis. Stopping cannabis led to significant improvements in memory, processing speed, and executive function.

SOURCE: Feinstein A, Meza C, Stefan C, Staines RW. Coming off cannabis: A cognitive and magnetic resonance imaging study in patients with multiple sclerosis. Brain 2019;142:2800-2812.

Cannabis, a botanical that is categorized as a Schedule I category drug, is the most commonly used psychoactive substance worldwide. The botanical’s best described compounds are terpenoids, flavonoids, and cannabinoids. Cannabinoids alter the release of neurotransmitters, and can be separated into phytocannabinoids, endocannabinoids, and synthetic cannabinoids. The two best-studied cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD), which interact differently with the known cannabinoid receptors CB1 and CB2. The legal use of cannabis, for recreational purposes as well as in its medically prescribed form, varies internationally as well as throughout the United States.

Patients with multiple sclerosis often suffer from symptoms such as spasticity, pain, paresthesia, insomnia, or depression. Recent studies show that approximately 16-20% of patients with multiple sclerosis (MS) currently are using cannabis, 47% have considered using cannabis, 26% have used cannabis in the past, and 20% have spoken with their physician about using cannabis. However, consistent benefit from cannabis use needs further investigation, and potential harmful effects on the central nervous system require careful evaluation. Because 40-80% of patients with MS have cognitive dysfunction, researchers need to assess cautiously if and how cannabis use might contribute to cognitive changes seen in patients with MS.

Feinstein et al investigated the cognitive response of patients with MS who stopped using cannabis. They enrolled 40 patients who all started cannabis — smoked, vaped, or ingested — after their initial MS diagnosis. Fifteen participants took medically prescribed cannabis, and all participants reported cannabis use of at least four times per week. Only subjects who showed some baseline cognitive impairment were enrolled. Exclusion criteria were other neurological disorders, mental illness, and recent steroid use. Patients were divided into two groups, one continuing to use cannabis and the other discontinuing cannabis use. The latter group was offered counseling and alternative therapies in case of withdrawal symptoms or increased MS symptoms. The two groups matched neurologically and demographically. The tester was blinded at the beginning of the study, and all participants underwent a battery of cognitive testing at baseline and after 28 days. In addition, baseline and 28-day magnetic resonance imaging results were obtained. Participants who stopped using cannabis had better cognitive function on several cognitive tests and faster reactive times after being off cannabis for 28 days. The patients who stopped cannabis also showed increased brain activation in regions associated with the test performance.

COMMENTARY

This is an important study. Feinstein and colleagues demonstrated that cognition and processing speed improved in those patients with MS who were taken off cannabis, indicating that cannabis may have a negative effect on mentation in these patients. A small number of studies so far have evaluated the effect of cannabis on cognition, especially in patients with MS, and this is an excellent and much needed contribution to the field.

As acknowledged by the authors, a challenge was that the subjects were on different forms of recreational and medically prescribed cannabis, and the respective amounts of THC and CBD were not known. They concluded that the majority of products contained potent levels of THC. According to other studies, there is some evidence that THC, the psychoactive cannabinoid, has a positive effect on nausea, sleep, and pain. However, it might have a negative effect on memory, cognitive processing, attention, and executive function. On the other hand, CBD reportedly has anxiolytic, anticonvulsant, and anti-inflammatory effects. There is some preliminary evidence of the effect of CBD on cognition, suggesting that it might have a neutral, beneficial, or, if taken in conjunction with THC, protective effect.

The overall reported cannabis use among patients with MS is around 20%, and the percentage could increase with legalization of cannabis and increased use of prescribed medical marijuana. Because patients with MS subjectively report positive effects after cannabis use, further studies with larger cohorts, longer observation times, and comparisons of patients with relapsing-remitting vs. progressive MS are needed to evaluate the positive and negative effects of cannabis. Recreational cannabis and medically prescribed cannabis contain both THC and CBD, and it might be important to decipher the effects of each compound and investigate their effects on the nervous system independently.

In conclusion, this is an important study, since cannabis is a frequent topic of discussion in daily neurological practice and is more and more part of symptom management of patients with MS. This study prompts a careful review of risks and benefits of medical and recreational cannabis use in this patient population, and the effect on cognitive function needs to be discussed carefully.