There are already over 1.2 million medical marijuana users in the United States who seek treatment for a variety of debilitating symptoms from pain to epilepsy. That number may grow on Tuesday when voters in a number of states will decide whether or not to legalize marijuana possession for medicinal purposes. This may feel like a modern-day issue, where generations of Americans are afforded legal access to medical marijuana for the first time. And beyond legalization, this move may validate marijuana’s medicinal utility to many individuals.

But of course, this is not a new idea.

From 1851 to 1942, marijuana was included in the U.S. Pharmacopeia, which identified and standardized the identity, strength and quality of medicines. Regular submissions detailing the medicinal utility of marijuana were made until pressure from the Federal Bureau of Narcotics (an early predecessor of the DEA) forced its omission. Then, all was quiet.

But with rising momentum from the medical marijuana user and research communities, in February of this year, the U.S. Pharmacopeia agreed to assess the advisability and feasibility of developing standards for re-introducing medical marijuana.

Opponents to legalization will evoke the harmful effects that marijuana may have on cognitive performance. Some will say that it’s ineffective at alleviating symptoms. Others may reference the vast number of medications already available, regardless of their side effects, and conclude that it’s not worth the risk.

While this seems to be a short-sighted, close-minded view, you can’t outright fault this stance. There are numerous contradictory reports about the harms and benefits of marijuana, and it can often be difficult to weed (sorry) through the evidence. One of the challenges in conducting efficacy and harm studies in humans (and yes, to understand drug action in humans, one must study it in humans) is that longitudinal studies—i.e. those that follow an experimental group over a period of time—are especially difficult to conduct.

Sure, there’s added cost, subject drop-out and hosts of individual life-factors that can’t be controlled which enhance variability in the data. But the other significant challenge, and this has been especially tough when studying the long-term effects of medical marijuana, is obtaining pre-marijuana test performance with which to compare against performance at a later date. Researchers therefore must capture subjects before they try marijuana.

Given that over 22 million Americans report using recreational marijuana, there isn’t a large population for researchers to draw from who haven’t used marijuana before but are now looking to explore its medicinal benefits. Consequently, researchers generally fall back to comparing two groups, those who use, and those who don’t.

This simple two-group comparison can be problematic for interpretation. For example, take the issue of marijuana use on impulsivity. Studies merely comparing marijuana users to non-users show that marijuana use is associated with increased impulsive behavior. Does that mean that marijuana caused the increase in impulsivity, or are impulsive people more likely to smoke marijuana? You can see the problem here. Questions regarding whether medical marijuana impacts executive functioning are plagued by the same issue. Until now.

In a pilot study published last month in Frontiers in Pharmacology, researchers affiliated with McLean Hospital in Belmont, Massachusetts, investigated the impact of medical marijuana on changes to executive functioning using a longitudinal assessment method.

What is executive functioning? Think of it like the project manager who facilitates a job from the planning stages to completion. Executive function is therefore a broad measure of attentional control, working memory, inhibitory control and cognitive flexibility.

This study is intriguing on a number of levels, especially in light of the push towards legalization in this year’s election. (Note: Piqued interest in the utility and safety of medicinal marijuana around the election may have contributed to the quick push-to-publish without waiting for a larger sample size or additional longitudinal time points of investigation.)

Importantly, it’s the first known study to investigate the impact of medical marijuana on executive functioning by first establishing pre-marijuana performance levels. Patients reported having never used marijuana on a regular basis and had not used for a minimum of 10 years, so these pre-tests were indeed, testing pre-marijuana brain function.

Patients were then free to use medicinal marijuana products of their choosing (subjects on average consumed medical marijuana 9.3 times each week in a variety of forms), with the option to maintain using their prescribed medications. After three months, patients were re-assessed on clinical symptoms, cognitive performance and medication usage.

At the three-month assessment period, medical marijuana patients reported reduced levels of depression, a trend towards improved sleep, which likely contributed to enhanced energy levels, and a reduction in impulsive tendencies. Coinciding with improved clinical assessment, medical marijuana patients also demonstrated improved performance on two cognitive function tasks. Patients improved their times in the Trail Making Test, which is basically like an adult connect-the-dots but can require cognitive flexibility, and showed enhanced performance rate in the Stroop Color Word Test, where patients must integrate new rules and consciously override previously learned behavior. Additional tests were conducted, but despite not detecting improved performance, there were no instances of impaired performance.

The authors then reported another key outcome: prescription medication use declined, with average opioid use dropping 42 percent and antidepressant use dropping by 18 percent. This finding supports a recent report which found that half of the medicinal marijuana users in California sought marijuana as a substitute for prescription medication, which must have the pharmaceutical industry sweating.

This study isn’t able to address whether medical marijuana itself directly improved executive function in these patients. The improvement in test scores may have been the consequence of reduced symptomatology, as you can imagine that better sleep, or reduced pain, may contribute to improved cognitive ability. Since health is a state of mental and physical well-being, and not just the absence of disease, the effects of medical marijuana in this pilot study support a push towards overall patient health, however it’s achieved. Many will anxiously await the upcoming reports covering longer longitudinal time-points in these patients to see if the medical marijuana “benefits” persist over a longer period of time.

But let’s take a step back before popping the champagne.

Pilot studies are small, and this one is no exception. With only 11 subjects, it’s hard to draw definitive conclusions. On top of that, the researchers used a bit of statistical wizardry (some may call it “deception”) by making it more likely that they’ll detect positive group differences than conventional methods. It reminds us that science is not independent from the influence of media and cultural momentum. The medical marijuana movement is gaining momentum, especially around election season, while increased fear of the opioid epidemic permeates urban and rural environments, alike. We must use caution when interpreting scientific reports and refrain from exaggerating their findings.

We can still draw important conclusions from this study.

For one, medical marijuana use, among these 11 subjects, did not cause decrements in cognitive function. There was no evidence of harm. Opponents to medical marijuana cite studies claiming marijuana has negative impacts on cognitive functioning. While this may be the case in adolescents, medical marijuana, which often has elevated CBD:THC ratios, has so far proven to be safe in adults. Furthermore, it suggests that medical marijuana may serve as an effective alternative treatment strategy to traditionally prescribed medications. Even if these effects prove to be short-lived, they may be substantial enough to break the chains of devastating opioid dependence.

So despite the study’s limitations, add it to the mounting support for legalizing medical marijuana, and let’s wait anxiously for the next round of assessment.

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