Can marijuana help with mental health issues?

"Marijuana is like rock 'n' roll; it's here to stay," says neuroscientist Staci Gruber, PhD, an associate professor of psychiatry at Harvard Medical School.

While marijuana's popularity has grown, research into its therapeutic benefits has lagged behind, particularly in terms of mental health and other results. Despite the numerous challenges provided by cannabis's unresolved legal status, academics like Gruber have been motivated to investigate it.

"Given the large number of individuals who use marijuana, it's my job to help patients and consumers figure out the safest and most effective ways to use these products," Gruber says.

The National Academies of Sciences, Engineering, and Medicine published an in-depth study on the health consequences of cannabis and its 113 chemical constituents, known as cannabinoids, in 2017. Only three therapeutic uses were found to be backed by substantial or conclusive evidence, according to the review, which looked at a wide range of studies published since 1999: treating chronic pain, reducing nausea caused by chemotherapy treatment, and reducing spasticity associated with multiple sclerosis.

"Despite what we hear in the media and popular belief, there is actually very little known about the therapeutic effects in the human population," says Ziva Cooper, PhD, a behavioral pharmacologist and associate professor of clinical neurobiology at Columbia University Medical Center and one of the review's authors.

Chronic pain is the most common reason people seek medicinal marijuana, according to the study, with 94 percent of Colorado medical marijuana ID cards reporting "severe suffering." At the same time, the research found 27 randomized trials involving nearly 2,500 people with chronic pain, usually from neuropathy, that found cannabis and cannabinoids gave much better pain relief than a placebo.

Given this evidence, Cooper decided to investigate if cannabis could assist reduce or perhaps replace opiate use for pain management. She also mentioned that cannabinoids have been shown in animal tests to help lower the amount of opioids needed to relieve pain. According to studies published in JAMA Internal Medicine, prescription opioid use and rates of opioid-related mortality have dropped in states that have authorized medical marijuana (Vol. 174, No. 10, 2014, and Vol. 178, No. 5, 2018).

Cooper and colleagues ran a double-blind placebo-controlled research to see how effective cannabis is for pain management when used with opioids (Neuropsychopharmacology, Vol. 43, 2018). By immersing healthy volunteers' hands in cold water, the researchers were able to determine their pain thresholds and tolerance levels. Patients experienced powerful pain relief when cannabis was combined with a very tiny amount of an opioid that was not effective on its own, according to the researchers.

Cooper says, "It was really encouraging." "It suggests that cannabinoids could be used as a supplement to opioids for pain management, potentially reducing the opioids' side effects."

Her next study, which will use a similar approach, will look at the effects of cannabis with various levels of cannabinoids in combination with opioids. Cooper is particularly interested in learning if tetrahydrocannabinol, or THC, the primary psychoactive component of cannabis, is required for pain treatment. She intends to investigate whether cannabidiol, or CBD, a nonpsychoactive cannabinoid, could have the same effect.

The void in research

Marcel Bonn-Miller, PhD, an adjunct assistant professor of psychology in psychiatry at the University of Pennsylvania, is also investigating the benefits of these two cannabinoids, but for a different type of pain: psychological anguish induced by post-traumatic stress disorder (PTSD).

When Bonn-Miller first began researching PTSD at the University of Vermont 15 years ago, he heard numerous patients say they used marijuana to relieve their symptoms, but he could only locate two published papers on the subject. "It seemed like there was such a big hole that needed to be filled," he recalls.

Behavioral therapies such as prolonged exposure and cognitive processing therapy are currently used to treat PTSD sufferers. These treatments may be effective for some people, but they are not for everyone. Bonn-Miller said, "A lot of people are looking for medication." "And there aren't any drugs that actually help."

Bonn-Miller is directing two of the largest and most comprehensive studies on cannabis and PTSD ever conducted. The first study examines different cannabinoids in a double-blind controlled trial. About 76 individuals, largely PTSD veterans, will be randomly assigned to one of four groups: cannabis with high THC, cannabis with high CBD, a strain with equal levels of both, or a placebo.

The cannabis used in this study was cultivated entirely at the University of Mississippi, which is the only federally permitted source of cannabis for research labs. (It's worth mentioning, too, that the sorts of cannabis people actually consume are generally much stronger and come in a wider range of varieties than the cannabis developed at the university.)

The second initiative of Bonn-Miller aims to address this issue. It's an observational study in which half of the 150 participants buy marijuana from Denver dispensaries. The remaining half are non-users. For a year, Bonn-team Miller's will track individuals' PTSD symptoms and examine the strains of cannabis they used.

Mallory Loflin, PhD, a research scientist with the VA San Diego Healthcare System's Center of Excellence for Stress and Mental Health, is launching a double-blind placebo-controlled trial to see if CBD will help with prolonged exposure therapy. While prolonged exposure therapy is one of the most successful PTSD therapies, it does not always result in complete symptom remission and might be emotionally demanding for some patients. Loflin will investigate if CBD can improve the efficiency and efficacy of prolonged exposure therapy in PTSD patients, as well as the tolerability of the treatment.

The study, which will include 136 military veterans with PTSD, is significant not only because of its subject matter, but also because of its funder: it is the Department of Veterans Affairs' first research initiative employing cannabis.

Beyond the sky's limit

Gruber is also the director of Marijuana Investigations for Neuroscientific Discovery, a privately sponsored study (MIND). MIND's aim, which began in 2014, is to investigate the effects of cannabis and cannabinoids on patients' cognitive performance, traditional medicine use, sleep, quality of life, brain structure and function, mental health, and other factors.

Gruber, who is also the head of McLean Hospital's Brain Imaging Center's Cognitive and Clinical Neuroimaging Core, has worked with recreational marijuana users for over 20 years, but the MIND program focuses on medical marijuana users—and the two groups are vastly different.

Many recreational marijuana users say they use marijuana to change their minds, but many of Gruber's medical marijuana patients say they don't want to get high; they just want to feel better.

MIND has undertaken a variety of research on individuals who use cannabis for medical purposes, looking at the influence on their cognitive performance over time, commencing before usage and monitoring them for up to two years at three- and six-month intervals.

Patients who used cannabis to treat a variety of medical problems, including anxiety, had significantly improved cognitive performance, reduced clinical symptoms and anxiety-related symptoms, and used fewer conventional medications, such as opioids, benzodiazepines, and other mood stabilizers and antidepressants, according to these studies.

Gruber's open-label to double-blind clinical research on patients with anxiety utilizing a whole-plant, high-CBD tincture was inspired by and guided by their findings. While some studies have revealed a link between smoked whole-plant marijuana and social anxiety, a double-blind placebo-controlled experiment examining CBD and anxiety has yet to be conducted. Gruber is optimistic that this groundbreaking clinical investigation will deliver much-needed CBD research. Participants are currently being enrolled in the trial.

Medical marijuana study is difficult, but Gruber, like many other experts in this field, is optimistic.

"While the promise of cannabis and cannabinoid-based medicines for a variety of indications, symptoms, and illnesses is remarkable," she says, "we are in critical need of empirically reliable research."