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Dr. Brooke Worster discusses a recent study that found an association between lifetime heavy cannabis use and lower brain activation related to working memory.

Lifetime heavy cannabis use is associated with lower brain activation related to working memory, according to study findings published in JAMA Network Open.

“Lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long-lasting,” wrote lead study author Joshua L. Gowin, PhD, and co-authors.

Evaluating History of Cannabis Use

Dr. Gowin and his colleagues analyzed data from 1,003 adults between 22 and 36 years of age who had functional magnetic resonance imaging (fMRI), urine toxicology, and cannabis use results collected at one academic site between 2012 and 2015 as part of the Human Connectome Project.

The cohort (mean age, 28.7 years) comprised 470 men (46.9%) and 533 women (53.1%), most of whom were White (762; 76.0%), with 137 Black (13.7%) and 63 Asian (6.3%) participants. Using the Semi-Structured Assessment for the Genetics of Alcoholism to evaluate history of heavy cannabis use with variables for lifetime history and diagnosis of cannabis dependence, the researchers classified 88 (8.8%) individuals with more than 1,000 uses as heavy lifetime cannabis users, 179 (17.8%) with 10 to 999 uses as moderate users, and 736 (73.4%) with fewer than 10 uses as nonusers. Participants provided urine samples on the day of scanning to detect recent use.

Tasks Recorded During Functional MRI

The study team recorded neural responses related to seven tasks during the fMRI session: working memory, language, motor, relational assessment, reward, emotion, and theory of mind.

“The researchers found that 63% of heavy lifetime cannabis users exhibited reduced brain activity during a working memory task,” according to a press release by the University of Colorado Anschutz Medical Campus.

The working memory task involved participants viewing a series of images and clicking a button when the current image matched one they had previously seen.

Heavy lifetime use [Cohen d=-0.28 (95%CI, -0.50 to -0.06; false discovery rate corrected P=.02)] was associated with lower activation during the working memory task and involved the anterior insula, medial prefrontal cortex, and dorsolateral prefrontal cortex. This association remained after the study team removed participants with recent cannabis use from the analysis. Differences in demographic variables, age at first cannabis use, alcohol use, or nicotine use did not explain these results. No other tasks were associated with lifetime heavy use, recent use, or dependence diagnosis.

Further Research Needed

“These findings suggest that large, longitudinal studies are needed to assess the causality of cannabis use toward altering brain function and the duration over which these effects persist,” the authors concluded.

Study Discussion

Brooke Worster, MD, a clinician not involved in the study, reviewed the findings with Physician’s Weekly (PW) and highlighted strategies for physicians to engage young adult patients in constructive discussions about cannabis use.

PW: Did the results surprise you? Why, or why not?

Dr. Worster: Not entirely. Data have long shown that, as a group, young adults and adolescents whose neurocognitive development and neuronal connections are developing are very susceptible to cannabis and other psychoactive medications.

Cannabis ingestion or inhalation is active at CB1 receptors (among others) in the central nervous system and can change neuronal activity and connections. With age, these changes become more static, so long-term, repeated cannabis use can certainly change neural development.

Why is this study important?

The rate of cannabis use in our country and across the globe is increasing, with more high-potency tetrahydrocannabinol (THC) products more easily available to young adults and adolescents. We need to better understand the guardrails around safe cannabis use and educate the healthcare community and patients.

What criteria can clinicians apply to balance the therapeutic benefits of medical cannabis against the study’s observed associations with diminished brain activation and working memory performance?

This paper supports the concern about cannabis use in young adults and adolescents: this is a particularly vulnerable group, and the healthcare community needs to guide them. Will the benefit outweigh the risk in some cases, such as with cancer and intractable seizures? Sure. But in general, this adds to the worry that youth may be self-medicating for social anxiety disorders or simply be using this recreationally and having access to significantly more potent, high-THC products than ever before.

We need to engage in conversations about what can harm and what can help. The healthcare community cannot take an “all bad or all good” view of cannabis. It’s more complicated than that.

Are any strengths or limitations of the study especially noteworthy?

This is a retrospective, secondary analysis of a large public health data set collected for other purposes, which may introduce significant bias and confounding variables that affect the outcomes. There is also risk for bias from the self-reported data.

Additionally, no details about the cannabis form, potency, or content were collected. All cannabis is not the same, so it’s hard to say that the raw number of “times used” is the same, no matter what form or potency of product was used.

Cannabis is complex, as is our endocannabinoid system. This study adds one more small piece of the puzzle, but it doesn’t tip the scales in any one direction.

What questions remain unanswered for you?

The greatest challenge with cannabis is that it cannot be treated as a single entity; the plant—and the products derived from it—contain hundreds of phytochemicals. We don’t know what the outcomes are when examining specific conditions and compositions of products. A high cannabidiol with low or very low THC orally ingested product is not the same as a high-THC vaporized product.

We also need to understand the therapeutic potential versus the existing harms in specific populations.

What advice can you share with clinicians treating patients who use cannabis?

Exercise caution when treating young adults who use cannabis heavily. Approach them with a non‑judgmental, ongoing dialogue about their reasons for use, which can reveal underlying mental or physical health concerns.