Science Races to Unlock Marijuana's Secrets

Elvis Alonzo began smoking cannabis as a last resort. Three years as a Marine Corps officer and 13 years with the Glendale Police Department in Arizona—where he was exposed to murders, suicides and people dying in his arms—had left him emotionally crippled.

Toward the end of his police service, doctors diagnosed Alonzo with post-traumatic stress disorder and prescribed various medications to temper his nightmares and flashbacks.

The drugs “turned me into a zombie,” he says. “I was so out of it that I couldn’t even drive, so they (the police department) had to medically retire me.” Alonzo stopped showering. His wife left him, and he nearly lost his house.

Then a friend suggested he try marijuana to relieve his symptoms. “It’s been a godsend,” he says. “It curbs my anxiety, and it makes me sleep fantastic for at least four hours. It needs to be studied.” Thousands of military veterans have echoed Alonzo’s claim for years. They have pressured federal and state legislators to legalize medicinal cannabis and ease rules on research into the plant’s apparent therapeutic properties, arguing that it could help reduce suicide rates among former soldiers.

Backed by overwhelming public support for broader legalization, their demands are starting to resonate in statehouses across the country.

This past November, New York Gov. Andrew Cuomo chose Veterans Day to make PTSD a qualifying condition for the state’s tightly controlled medical marijuana program. New York joined seven other states this year—and 27 overall—that include PTSD in their lists of conditions that qualify for medical cannabis.

But some cannabis researchers—while acknowledging the urgency of finding better PTSD treatments—remain skeptical of legalizing too quickly and warn that marijuana’s pharmacological properties remain largely unknown.

Still, scientists have long been focusing on two of the plant’s more than 120 active compounds as possible treatments for PTSD symptoms. They are looking at tetrahydrocannabinol, or THC, which is the plant's principal psychoactive ingredient, and cannabidiol, or CBD, which is non-intoxicating and has drawn interest for possible medical applications.

Concentrations of both can vary widely between different genetic lines of cannabis, and even between individual plants.

Of the two compounds, THC is a bit better understood. It binds to specific receptors on brain cells that help regulate mood, sleep patterns and pain perception.

Scientists also believe it interacts with receptors in the brain’s emotional centers—the amygdala and hippocampus—to reduce anxiety, which may help explain Alonzo’s reaction to cannabis. THC research involving PTSD, although scant, has shown some promise.

A 2009 clinical trial in Canada showed that the nighttime administration of THC reduced the frequency and intensity of nightmares in 72 percent of the 47 patients studied. But other trials have presented more mixed results.

They demonstrate that THC’s effectiveness in reducing anxiety and increasing sleep quality depends on dose size, with lower doses improving sleep quality and higher doses producing higher levels of anxiety—and negative long-term outcomes.

Research into CBD remains hazy, partly because it triggers so many biochemical pathways and produces wide-ranging results. It appears to effectively treat some forms of epilepsy, but scientists do not know why.

They have a better sense of how it may relieve some users’ anxiety—by targeting and boosting the signal of 5-HT1A serotonin receptors on brain cells. Serotonin, a neurotransmitter, helps regulate mood and is associated with feelings of well-being.

And CBD, a powerful anti-inflammatory and anti-oxidant, also increases gamma-aminobutyric acid, or GABA, an inhibitory neurotransmitter that produces a calming effect when amplified. But study outcomes are still largely inchoate, marked by small sample sizes, narrow methodological controls and contradictory findings.

Although 29 states have legalized medical or recreational cannabis since 1996, the federal government continues to officially prohibit the drug and has done little to facilitate research into its medicinal potential.

Despite the limited research, many scientists have recently shifted focus from THC to CBD—even if many patients have not—says Marcel Bonn-Miller, a psychology and psychiatry professor at the University of Pennsylvania's Perelman School of Medicine.

“Think of CBD as a shotgun. It hits so many receptors that people are still trying to understand it,” Bonn-Miller explains. “If you want to actually treat PTSD, most of the evidence is pointing toward CBD. But most people with PTSD are gravitating toward [marijuana] products with high THC levels, which may help in the short-term but are likely to worsen their symptoms over time.”

Bonn-Miller and psychiatrist Sue Sisley, a former professor at the University of Arizona College of Medicine, are trying to address these issues. Using cannabis provided by the federal government and a protocol approved by the U.S. Food and Drug Administration, they are leading the first-ever randomized control trial on the efficacy of marijuana for PTSD.

The study, funded with a nearly $2.2-million grant from the Colorado Department of Public Health and Environment, is examining four different strains of cannabis in treatment-resistant military veterans: a high-THC batch, a high-CBD batch, a blend with equal concentrations of THC and CBD, and a placebo control. Sisley notes that a key hallmark of PTSD is insomnia, usually blamed on nightmares and flashbacks—and that if cannabis can help veterans initiate sleep and stay asleep, that is a victory in itself.

"Until we unblind and analyze all the data, we can’t make any conclusions,” Sisley says, referring to the Arizona study. “But I can tell you that we have had almost 30 veterans who have completed the 10-week protocol and the study is progressing well.”

Bonn-Miller is also the principal investigator in an observational study on 150 PTSD patients in Denver, Colorado, funded by a grant from the University of Pennsylvania. Half of the subjects will use cannabis obtained from a dispensary, and half will not consume cannabis.

Bonn-Miller is tracking participant symptoms over the course of a year—with assessments at three, six, nine and 12 months—while scientifically testing the cannabis that users choose to consume, to determine if there are certain cannabinoid concentrations that are more helpful than others for mitigating PTSD symptoms.

The only criteria is that participants acquire their cannabis from local dispensaries, so that researchers can easily test it. What most interests Bonn-Miller is that some participants may switch groups—some non-users at the start of the study may begin using cannabis, and previous users may stop.

This will allow Bonn-Miller to examine the changes that cannabis use produces in PTSD symptoms in real time. “It's early. We really don't understand the mechanisms of action that well at this point,”

Bonn-Miller says of marijuana’s pharmacology, before underlining what he sees as the plant's medical potential: “Something that can reduce seizures, improve anxiety and also reduce inflammation,” he says. “All in the same drug!”