Staci Gruber, Ph.D.

researcher researching marijuana

How I Became Interested in Marijuana Research

Along with other McLean researchers, I was working on a series of projects designed to look at college students to assess potential differences in cognitive function—mental processes, such as attention and memory, that enable us to acquire knowledge—in those who used marijuana and those who did not. From there, my interest grew, and I began to explore more specific questions about marijuana—for example, how it impacts brain function, brain structure, and mood, and why some patients, for example, those with bipolar disorder, seemed to use it more frequently than other

Studying Recreational Marijuana

One of my primary areas of interest is the impact of marijuana on the brain and behavior in people who begin using regularly before the age of 16 as compared to those who don’t begin using until after 16—given that the brain is vulnerable during development. The results of these studies are quite striking. Chronic marijuana users with earlier onset of use appear to have more difficulty with cognitive tasks, altered patterns of brain activation, and less organized white matter, which is responsible for communication between brain regions, compared to those who began using later or people who don’t use marijuana at all. Interestingly, users who start later in life don’t appear to have the same degree of difficulties as the early users and, in fact, appear more similar to those who don’t use marijuana at all. We’re also looking at former marijuana users who have been abstinent for an extended period to figure out what happens when people stop using marijuana, as well as those with light or casual marijuana use to determine if lighter or less frequent use also results in differences from those who don’t use at all.

Recreational vs Medical Marijuana Use

Currently, 10 states and Washington, D.C., have legalize recreational or adult cannabis use, but the debate about agerelated guidelines or restrictions is ongoing. We certainly need to be mindful about what we know in regard to the developing brain and how vulnerable it is to other drugs and alcohol. My work and that of my colleagues in this field is dedicated to answering a lot of complicated questions designed to help policymakers make sound, fact-based decisions.

Currently, 33 states and Washington, D.C., have fully legalized
marijuana programs for medical use. An additional 14 states have
limited medical programs, leaving only three states without access
to at least some medical marijuana products.

Importantly though, medical marijuana and recreational or adult marijuana use are not the same. People who use marijuana
recreationally are interested in the experience. The goal for recreational users is to change their current state of being, or to be high, perhaps. This is why marijuana products high in tetrahydrocannabinol (THC), the primary psychoactive constituent of the cannabis plant, are so popular among recreational users and why THC levels have increased significantly over the past several years.

Medical marijuana patients, however, are generally not looking to get high or feel altered but to simply feel better. They are quite clear in their goals and often say things like “I just want to be able to go to the store…I just want to get through a day without agonizing pain.” Patients may use products containing considerable amounts of THC, but they often explore the use of products with other constituents, like cannabidiol (CBD), a
primary non-intoxicating compound of the plant that has shown
tremendous therapeutic potential, as well as other cannabinoids.
The major difference between the medical patients and recreational users typically dictates product choice and the ways in which the products are used.

Thoughts on Medical Marijuana

Marijuana has been around for thousands of years and was first legalized for medical use in the U.S. more than two decades ago—it is clearly here to stay. Given recent reports suggesting that cannabis or cannabinoids are effective for some conditions and the growing interest and rates of use, we need to focus on conducting more clinical research studies. It isn’t easy given current regulations, but there are ways to move things forward.

We may be facing the next frontier of personalized medicine for
those who derive a clinical benefit from medical marijuana. Every person
is different and bound to have varied responses to the countless types of cannabinoid-based products that are rapidly becoming available. Given the regulatory limitations, this requires that patients stay educated and invested in their own treatment and ‘partner’ with knowledgeable treaters. It’s also important to remember that as promising as cannabinoid-based therapies may be for many conditions or symptoms, it may not work for every illness or person. Unfortunately, policy has outpaced science, and we know far less than we should at this point.

Public Objection

Medical marijuana is being rigorously contested by some groups due to several issues that make the idea of medical marijuana difficult for some people to support. First, the term “marijuana” is often used to describe anything from the plant cannabis sativa. Not all constituents are the same. THC, the most well-known cannabinoid, has often been associated with negative outcomes when used recreationally, especially during adolescence.

Cannabidiol (CBD), on the other hand, is non-intoxicating and has shown tremendous benefits for a range of conditions and may actually limit or reduce the negative or less desirable effects of THC. There are many other cannabinoids and essential oils (called terpenoids), flavonoids, and other components, so it isn’t just one thing, especially when using whole-plant or full-spectrum products rather than isolated individual compounds.

People often stereotype cannabis users, both recreational and medical, and assume that they will absolutely get high and will have to smoke or vaporize products in order to use cannabis. There are many modes of use that do not require smoking or vaping and may in fact “feel” more like conventional medication use, like using capsules, putting drops underneath the tongue, or delivering it through the skin via patches.

Further, the U.S. government still classifies marijuana as a Schedule
I drug, which, by definition, states there is no acceptable medical
value. That’s tough for people to understand when at the same time states have passed legislation legalizing medical marijuana. For some, the notion that marijuana can be medicine is tough to swallow, as “medicine” conveys a sense of consistency, expected effects or outcome, regulation, and oversight, which simply isn’t in place at this point for marijuana. When you buy Advil in Tuscaloosa, Alabama, it’s the same as Advil that you buy in Boston, Massachusetts. With medical marijuana, a particular product or strain bought in Massachusetts may be very different from what you would buy in New Mexico. Variables, like how much THC and CBD a product contains, for example, are serious considerations.

We are, however, beginning to see some legislative changes that will likely impact views of marijuana as a medicine. Following FDA approval, the DEA rescheduled Epidiolex—a purified, cannabis-derived, high-CBD formulation—for the treatment of certain severe pediatric seizure disorders. Importantly, the federal Farm Bill was also amended last June, which should make hemp-derived products legal in the U.S. Just last month, CVS announced it will begin to sell hemp-derived CBD products in select states.

Marijuana Research at McLean

In 2014, I launched MIND, Marijuana Investigations for Neuroscientific Discovery. Even though California has had medical marijuana laws on the books since the 90’s, prior to the launch of MIND, I couldn’t find much in the scientific literature that focused on the impact of medical marijuana on cognitive function or other areas related to brain and mental health.

Policy has outpaced science, and we need scientific studies to begin to fill in the gaps. We need to understand whether medical marijuana adequately addresses clinical symptoms and as a result may improve cognitive function, or if, in fact, there is a loss or impairment in cognitive function secondary to medical marijuana use, like what we’ve seen in the recreational marijuana literature. So far, findings from our work suggests that this is not the case. We also need to know what the impact is on conventional medication use, quality of life, sleep, and many other domains.

We also need to understand how specific cannabinoid-based products work—for example, how does strain A impact symptom X? MIND was conceptualized to begin to address some of these questions. Findings from the first phase of this study have helped to foster a greater understanding of the effects of medical marijuana, which will, in turn, help facilitate the examination of the effectiveness of medical marijuana for a range of conditions.

Several MIND studies are in progress, and we have already published some interesting findings.

Our first study, which began about five years ago, is designed to examine medical marijuana patients over the course of up to two years. Patients have a comprehensive evaluation with us before they begin medical marijuana treatment, and we then follow them over time. In addition to assessing cognitive function, brain structure, mood, sleep, and quality of life, we also get detailed information on the specific strains and types of marijuana products they use, how they use it, frequency and amount of use, and, ultimately, laboratory analyses of actual products. Results are promising, and preliminary data published in Frontiers in Pharmacology shows improvements in cognitive function after three months of treatment. Specifically, once patients began treatment with medical marijuana, they performed better on tasks that reflect skills related to planning, a process that enables us to choose the necessary tasks to achieve a goal; inhibition, the ability to control our impulses; and flexible thinking, which is the ability to think about things in different ways, a key skill for problem solving. Patients also generally appear to feel better, reporting improvements in mood, sleep, and quality of life. Interestingly, they often simultaneously report decreased use of conventional medication use, including opioids and benzodiazepines.

In a second study we published, which is the first-ever neuroimaging study of medical marijuana patients, we found that after three months of treatment, medical marijuana patients exhibited patterns of brain activation that looked more similar to what we normally see in healthy controls—individuals who do not have medical or mental health conditions. These results may suggest “normalization” of brain function after medical marijuana treatment begins. Interestingly, in small samples of control patients—those who have similar conditions as the medical marijuana patients but who do not use cannabis—we aren’t seeing the same improvements over time.

We were surprised by this preliminary data. So far, findings appear to be quite different from what we’ve seen in recreational marijuana users, which is very important, especially given the number of individuals exploring medical marijuana as a potential treatment option.

Phase 2 of MIND

One current study is a clinical trial, which means that we are administering a cannabinoid-based product to volunteer patients. We created a custom-formulated, whole-plant-derived, high-CBD tincture for patients suffering from moderate to severe anxiety. The open-label phase is currently ongoing, and all patients enrolled in the clinical trial receive the study product so we can assess changes in anxiety, mood, and cognition over the course of treatment. Results are only preliminary, but, so far, we are seeing significant improvements in anxiety-related symptoms, and the product appears to be safe and well tolerated. We are excited by these findings and will continue to test this product in the next phase of the trial, which is a double-blind, placebo-controlled study. We also have plans for future clinical trials and recently received FDA approval to study patients with chronic pain.

Planting the Future

There’s still a lot to learn. It is imperative to start with well-designed and factually sound studies that give us some idea what to expect for specific conditions. Educational opportunities for the community are also key.

As we get a better understanding of the impact of medical marijuana, we will also need to continue to look at the effects of recreational use. Our recreational studies remain critical, given the increasing use of marijuana across the nation. Older adults are the fastest growing consumers of marijuana, yet we have little data on how cannabinoids affect aging consumers who may use for either medical or recreational purposes. We are also seeing increased interest in novel products with extremely high THC levels—often referred to as concentrates or “dabs.” We need to continue to assess how changing trends and patterns in marijuana use affect consumers, including adolescents and emerging adults who are particularly vulnerable, given that their brains are still developing.

Without a doubt, this is a very exciting time, and as the nation continues to warm toward the idea of marijuana for both adult and medical use, it is important for us to determine the effects of use so that we can better guide patients and consumers alike.

Staci Gruber, Ph.D., is a leading marijuana research expert who has been at the center of the nation’s ongoing debate regarding the legalization of recreational or adult-use marijuana and the use and impact of medical marijuana use. For Gruber, this attention is necessary to help drive the conversation and inform the public and policymakers about the science of “pot,” more appropriately called cannabis or marijuana.