Can marijuana ease mental health conditions?

, 18/12/2021

By Sara Zaske

New studies seek to deliver a better understanding of how cannabis may help reduce pain, PTSD and anxiety

So far, medical marijuana has been legalized in 31 states and nine have legalized its recreational use. The Marijuana Policy Project estimates that more than 2.8 million people in the United States are using marijuana, or cannabis, as medicine. Recreational use is even higher, with more than 22.2 million users, according to a 2015 national survey.

As one researcher, neuroscientist Staci Gruber, PhD, an associate professor of psychiatry at Harvard Medical School, puts it, “Marijuana is like rock ’n’ roll; it’s here to stay.”

While the popularity of marijuana has surged, research on its therapeutic properties has lagged well behind, especially when it comes to mental health and other outcomes. That disconnect has compelled researchers like Gruber to study cannabis despite the many obstacles posed by its unsettled legal status.

“Given that so many people are using marijuana, it’s my job to help patients and consumers figure out the very best ways in which they might be able to use these products safely and effectively,” Gruber says.

In 2017, the National Academies of Sciences, Engineering, and Medicine produced an extensive review on the health effects of cannabis and its 113 chemical constituents, called cannabinoids. While looking at a wide range of studies published since 1999, the review found that only three therapeutic uses were backed by substantial or conclusive evidence: treating chronic pain, reducing nausea induced by chemotherapy treatment and decreasing the spasticity associated with multiple sclerosis.

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

The review noted that chronic pain is the most common reason people cite for seeking medical marijuana—94 percent of Colorado medical marijuana ID cardholders said they had “severe pain.” At the same time, the review identified 27 randomized trials involving a total of nearly 2,500 participants with chronic pain, mostly related to neuropathy, that showed cannabis and cannabinoids provided significant pain relief over that of a placebo.

Given this evidence, Cooper decided to take a closer look at whether cannabinoids might help reduce, or even replace, the use of opioids for pain relief. She also noted that animal studies have indicated that cannabinoids can help decrease the dose of opioids needed to reduce pain. In states that have legalized medical marijuana, prescription opioid use and rates of opioid-related deaths have decreased, according to studies published in JAMA Internal Medicine (Vol. 174, No. 10, 2014, and Vol. 178, No. 5, 2018).

To test the efficacy of cannabis for pain relief, Cooper and colleagues conducted a double-blind placebo-controlled study looking at cannabis use in conjunction with opioids (Neuropsychopharmacology, Vol. 43, 2018). The study measured healthy participants’ pain thresholds and tolerance levels by immersing their hands in cold water. The researchers found that when combining cannabis with a very small dose of an opioid—one that was not analgesic on its own—patients had robust pain relief.

“It was very encouraging,” Cooper says. “It shows cannabinoids might actually be an adjunct for opioids for pain relief and could potentially decrease the adverse effects of the opioids.”

Her next study, which will take a similar approach, will look at the potential impact of cannabis with different amounts of cannabinoids in conjunction with opioids. Specifically, Cooper wants to know if tetrahydrocannabinol, or THC, the primary psychoactive component of cannabis, is necessary to achieve pain relief. She is planning to test whether another non­psychoactive cannabinoid known as cannabidiol, or CBD, could also achieve the same effect.

The research gap

Marcel Bonn-Miller, PhD, an adjunct assistant professor of psychology in psychiatry at the University of Pennsylvania, is also examining the effects of these same two cannabinoids, but to address a different kind of pain: the psychological suffering caused by post-traumatic stress disorder (PTSD).

When Bonn-Miller first started conducting research on the disorder 15 years ago at the University of Vermont, he heard many patients report using marijuana to ease their symptoms, but he could find only two published studies on cannabis and PTSD. “It seemed like such a huge gap that needed to be addressed,” he says.

Currently, PTSD patients are often treated with behavioral therapies, such as prolonged exposure and cognitive processing therapy. While these treatments work well for some people, they don’t work for everyone. “A lot of people are looking for medication,” Bonn-Miller says. “And there really aren’t any medications that work well.”

Bonn­-Miller is leading two of the largest and longest studies ever done on cannabinoids and PTSD. The first study is a double-blind controlled trial that compares different cannabinoids. In the trial, about 76 participants, mostly veterans with PTSD, are being put in one of four groups, receiving either cannabis with high THC, cannabis with high CBD, a strain with equal levels, or a placebo.

The cannabis used in this study is all grown at the University of Mississippi, the only federally approved source for cannabis administered in research labs. (It’s worth noting, however, that the types of cannabis people actually use are often much stronger and come in more varieties than that grown at the university.)

Bonn-Miller’s second project attempts to address this problem. It’s an observational study in which half of the 150 study participants use cannabis purchased at dispensaries in Denver. The other half are nonusers. Bonn-Miller’s team will analyze the types of cannabis used and track participants’ PTSD symptoms every three months for a year.

In related work, Mallory Loflin, PhD, a research scientist with the Center of Excellence for Stress and Mental Health at the VA San Diego Healthcare System, is launching a double-blind placebo-controlled study to test the efficacy of CBD in conjunction with prolonged exposure therapy. While it’s considered to be one of the most effective PTSD treatments, prolonged exposure therapy does not always result in full remission of symptoms and can be emotionally challenging for some patients. Loflin will test the hypothesis that using CBD can increase the efficiency and efficacy of prolonged exposure therapy in PTSD patients as well as improve its tolerability.

The study, which will involve 136 military veterans with PTSD, is a landmark one not only because of its subject matter but also because of its funder: It is the first research project involving cannabinoids to be funded by the Department of Veterans Affairs.

Beyond the high

Gruber also heads a privately funded project, Marijuana Investigations for Neuroscientific Discovery (MIND). Started in 2014, MIND’s mission is to study the effects of cannabis and cannabinoids on patients’ cognitive performance, conventional medication use, sleep, quality of life, measures of brain structure and function, mental health and other variables.

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

Recreational consumers are happy to say they use marijuana because they want to change their mental states, but many of Gruber’s medical marijuana patients tell her they don’t want to get high: They just want to feel better.

MIND has conducted a number of studies on patients using cannabis for medical purposes, looking at the impact on their cognitive performance over time, starting before use and following them at three- and six-month intervals for up to two years.

These studies have found that the patients, who used cannabis to treat a range of medical problems including anxiety, had largely improved cognitive performance, reduced clinical symptoms and anxiety-related symptoms as well as a reduced use of conventional medications, including opioids, benzodiazepines, and other mood stabilizers and antidepressants.

Those results inspired and informed Gruber’s open-label to double-blind clinical trial on patients with anxiety using a whole-plant, high-CBD tincture. While some studies have found a negative connection between smoked whole-plant marijuana and social anxiety specifically, there has yet to be a double- blind placebo-controlled trial looking at CBD and anxiety. Gruber is hoping this first-ever clinical trial will provide much-needed information on CBD. The trial is in the beginning stages of enrolling participants.

Studying medical marijuana remains challenging, but like many researchers in this field, Gruber is optimistic.

“This is a difficult landscape to navigate,” she says, “and while the potential of cannabis and cannabinoid-based therapies for a multitude of indications, symptoms and conditions is extraordinary, we are in desperate need of empirically sound data.”


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