Cannabis Use Can Exacerbate Cognitive Declines in Patients With Multiple Sclerosis

Although cannabis use has seen enormous uptake with increased legalization in recent years, pharmacists and other clinicians should counsel patients with multiple sclerosis (MS) to be cautious with frequent cannabis use, according to presenter Anthony Feinstein, MD, PhD, FRCPC, in a session at the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting in Nashville, Tennessee.

Feinstein said that despite a massive growth in the amount of clinical research on the impacts of cannabis in a range of patient populations, many questions still remain about its use in patients with MS. This has led to a lot of questions from clinicians who are unsure how to have conversations with patients asking about cannabis.

“I think that was you’re coming to grips with a new drug, as we do on occasion, you need to understand what the benefits are and what the side effects are,” Feinstein said.

Image credit: Africa Studio | stock.adobe.com

In one Canadian study by Banwell et al., researchers found that among the 225 participants cannabis was used for a wide range of concerns, including sleep, pain management, anxiety, spasticity, depression, recreation, and a combination of factors.² This highlights the many reasons patients might be interested in cannabis use, or might continue cannabis use despite being aware of some of its potential negative effects.

Cannabis contains more than 60 cannabinoids, although the 2 of particular interest are delta-9-tetrahydrocannabinol (THC) and cannabindiol (CBD). Feinstein noted that he is not aware of known deleterious effects of CBD, although he added that he also is not aware of any clinically confirmed positive effects. However, most research focuses on THC. The primary metabolites of THC are 11-hydroxy-THC and 11-Nor-9-carboxy-THC.

Feinstein emphasized that in contrast with common belief, cannabis dependence does exist and can be a challenge. It is characterized by the inability to reduce use despite wanting to, spending considerable time trying to procure cannabis, disruption of social or occupational pursuits, and withdrawal (reduced concentration, irritability, loss of appetite, depression, and insomnia). Notably, he said accounting for withdrawal can be a challenge in clinical research and must be accounted for in studies.

Even among studies of healthy subjects, there is strong evidence for cognitive decline associated with cannabis use. These include short-term residual effects for hours or several days later, during which time deficits linger but are less apparent. Data are equivocal with regard to long-term residual effects, showing deficits in some individuals but not all.

In one study of cognition in chronic heavy users of cannabis who were otherwise healthy, researchers examined 1037 subjects with 25 years of follow-up, including assessments at 18, 21, 26, 32, and 38 years of age. They found that if cannabis use began in adolescence and continued regularly (defined as 4 or more times per week), by middle age these users had significant and probably irreversible cognitive deficits.³

Cognitive difficulties are very common in individuals with MS, even without cannabis use. Feinstein and his colleagues conducted a series of studies investigating how cannabis use impacted these challenges. In the first study, the researchers used a computerized symbol digit modalities test (SDMT) and found that cognition was lower in those who used cannabis, who were approximately 50% slower at the test compared with those with MS who were cannabis-naïve. In a larger study with 2 groups of 25 subjects (25 cannabis users and 25 non-users), Feinstein and his colleagues found that cannabis users had more global impairment, slower processing speed, lower executive functioning, and lower visuospatial perception.⁴

Finally, the investigators brought in imaging. They excluded individuals who had used cannabis within the last 4 to 6 hours and ensured that those who were coming off of cannabis were not going through withdrawal. After conducting the SDMT test in the magnetic resonance imaging (MRI), the investigators found a lower Paced Auditory Serial Addition Test (PASAT) score and spatial memory in cannabis users. Although all participants got faster over time, Feinstein noted the cannabis users always had a slower response time and made more errors.⁵

Based on these studies, Feinstein said cannabis use certainly impacts cognition in individuals with MS, exacerbating challenges that are already present with the disease. Meanwhile, other research has examined what happens to individuals with MS when they stop using cannabis.

In one study, investigators assessed working memory in groups of patients while cannabis was still present in their systems (for 28 days after smoking) and after. By day 28, Feinstein said the group that stopped using cannabis did better across every single cognitive measure (verbal memory, visual memory, informational processing speed, verbal fluency, etc.). When using the N-back working memory paradigm test, researchers found that there was no difference while both groups were still on cannabis, but after day 28 the group that had stopped cannabis use was quicker and more accurate.⁶

Despite all of this clear evidence that cannabis use negatively impacts cognition, Feinstein said patients continue to use it even once made aware of the data. In a study published in Brain and Behavior, Feinstein and his colleagues found that every person whose cognition improved after stopping cannabis use ultimately returned to using. Although the specific reasons are still unclear, one clue is that participants had no perceived differences in cognition between baseline and day 28 (once cannabis was out of their system). The only self-reported difference was in activities, with those who still used cannabis reporting that they felt more comfortable and less anxious in social settings compared with those who stopped cannabis usage.⁷

“We think this is probably a very key reason why they stay on it,” Feinstein said. “They come off it, socially they feel a bit more awkward, they’re not aware of the cognitive benefits, so they go back on it.”

Although this data seems to overwhelmingly suggest that cannabis use has negative impacts for individuals with MS, Feinstein said listening to patients’ reasoning for using it is crucial. If the patient reports that they feel better with cannabis use, clinicians must work with them to understand why that is. Still, Feinstein said he advises patients to be cautious of regular cannabis use and educates them that there likely will be cognitive compromise with frequent use. Like any drug, weighing the risks and benefits is important.

References

1. Feinstein A. Use and Effectiveness of Marijuana in MS: Research Update. Presented at: Consortium of Multiple Sclerosis Center 2024 Annual Meeting. May 29-June 1, 2024; Nashville, Tennessee.

2. Banwell E, Pavisian B, Lee L, Feinstein A. Attitudes to cannabis and patterns of use among Canadians with multiple sclerosis. Mult Scler Relat Disord. 2016;10:123-125. doi:10.1016/j.msard.2016.09.008

3. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci USA. 2012;109(40):E2657-2664. doi:10.1073/pnas.1206820109

4. Pavisian B, Staines WR, Feinstein A. Cannabis-induced alterations in brain activation during a test of information processing speed in patients with MS. Mult Scler J. 2015;1. doi:10.1177/2055217315588223

5. Romero K, Pavisian B, Staines WR, Feinstein A. Multiple sclerosis, cannabis, and cognition: A structural MRI study. Neuroimage Clin. 2015;8:140-147. doi:10.1016/j.nicl.2015.04.006

6. Pavisian B, MacIntosh BJ, Szilagyi G, Staines RW, O’Connor P, Feinstein A. Effects of cannabis on cognition in patients with MS. Neurology. 2014;82(21):1879-1887. doi:10.1212/WNL.000000000000446

7. Feinstein A, Meza C, Stefan C, Staines WR. Impaired awareness: why people with multiple sclerosis continue using cannabis despite evidence to the contrary. Brain Behav. 2021;11(8):e2220. doi:10.1002/brb3.2220