Long before Angus Wilfong started testing the nation's first marijuana-based drug meant to treat epilepsy, a 4-year old boy and his parents came to him for help. The healthy child had suddenly begun suffering from as many as 210 seizures a day. He was diagnosed with febrile infection-related epilepsy syndrome, a rare and potentially deadly form of epilepsy. Although his parents tried all the standard treatments, nothing seemed to make a difference.

Wilfong, who is a physician and director of the epilepsy program at Texas Children’s Hospital, put the boy into a coma to protect his brain from further harm. As the boy lay unconscious in bed for four months, his parents and doctor quietly deliberated over what seemed like a hopeless case. “We really thought that he was probably going to die,” Wilfong says.

With consent from the boy's parents, Wilfong decided to try one last option -- he requested access to a drug called Epidiolex, which had not yet been approved by the U.S. Food and Drug Administration. Epidiolex contains a purified version of a compound known as cannabidiol (CBD), which is found in marijuana. It is made by a company called GW Pharmaceuticals, which still needed to put it through a full battery of clinical trials in order to legally sell it.

The boy represents one of more than 12,000 cases in which the parents or physicians of epileptic children have sought access to medical marijuana despite a lack of empirical evidence and frank assessment of risk for this treatment. Research into marijuana as a medicine has been stunted by decades of regulatory hurdles, a dearth of funding and public stigma. The irony is that residents of states that have legalized recreational marijuana arguably have an easier time getting their hands on cannabis than researchers who want to study it due to the federal restrictions marijuana still carries as a Schedule I drug.

"It's a pain in the neck," says Dale Deutsch, a biochemist at Stony Brook University who is researching the mechanisms of compounds, known as cannabinoids, such as CBD in the brain. "The DEA made cannabinoids a Schedule I, which is no medical use, but all over the country people are using it for medical use."

That designation by the Drug Enforcement Administration is reserved for the most dangerous substances that have no medical value, and it places heavy constraints on marijuana's possession or use, thereby limiting scientists’ efforts to figure out whether it has any potential as a medicine. The FDA, which judges the efficacy and safety of potential medicines, has said that Epidiolex and other forms of medical marijuana remain unproven by the standards of the agency’s traditional tests.

Meanwhile, patients have gained unprecedented access to an array of marijuana-based treatments, sometimes under the careful watch of physicians like Wilfong, but more often through medical marijuana dispensaries, which are now legal in 23 states but operate without FDA oversight. These dispensaries now serve about a million estimated medical marijuana users throughout the U.S., and the mysterious promise of marijuana has prompted organizations such as the American Academy of Pediatrics to call for more research into its risks and benefits. Physicians such as Wilfong say a hard look at marijuana's medical potential is long overdue considering marijuana has been widely used throughout the U.S. for decades and one drug based on it -- Marinol -- has been sold here since 1985 to boost the appetite of patients with cancer or AIDS. 

Wilfong knew from word-of-mouth that other physicians had used Epidiolex to treat a handful of children with epilepsy. So after receiving permission from the FDA to administer the drug under a compassionate use program that provides unproven therapies to patients in dire need, Wilfong made one final attempt to save his patient.

"We started it, and within days he was having fewer seizures, and within a week the seizures had stopped," Wilfong says. In the boy’s first month of treatment, he had a total of five seizures.   

The boy is now back at home with his family. “He's still on Epidiolex and he's had over 90 percent reduction in his overall number of seizures,” Wilfong says, adding that on most days, the boy has three to five seizures that last for a few seconds each, while previously the seizures went on for at least 30 seconds and often for as long as one or two minutes.

Physicians such as Wilfong say there’s only one way to safely move marijuana and its derivatives from a fringe treatment to mainstream medicine, and that’s by thoroughly testing each cannabinoid for side effects. “Medical history is punctuated with off-label cases when people were convinced something was working and it actually made people worse," he says. 

Epidiolex has little in common with recreational marijuana other than the fact that they originate from the same plant, but that’s not necessarily true for other forms of “medical marijuana,” which may vary greatly in quality and dosage. One strain known as Charlotte’s Web has shown promise for treating childhood epilepsy, and the waiting list for parents who are signed up to receive it from a nonprofit dispensary in Colorado currently runs 12,000 names long. But the potency and dosage of treatments doled out by such dispensaries can be inconsistent, Wilfong says.  

Even if marijuana treatments can be standardized through a well-vetted process such as FDA approval, no one actually understands how Charlotte’s Web or Epidiolex work. Scientists are stumped since the compound doesn’t seem to work through the most well-known cannabinoid receptors in the brain. Yet the promise that CBD has shown in treating a few cases of childhood epilepsy has researchers wondering what other potential medical breakthroughs may be hiding in cannabis.

In fact, a marijuana plant contains many more compounds, and scientists know very little about any of them. “You can think of cannabis as a medicine chest,” Roger Pertwee, an expert in cannabinoids at the University of Aberdeen in the U.K., says. “There are 104 compounds so far that have been identified and most of them have never been investigated pharmacologically.”

Since interest in medical marijuana has surged in recent years, scientists have made some progress, but not all the news has been good -- they’ve found that exposure to THC, the compound associated with the feeling of being stoned, makes nicotine more addictive to rats and that the brain development of adolescents is stunted by regular marijuana use. But they've also found that CBD  rivals a well-known treatment for alleviating symptoms of schizophrenia, and smoking marijuana seems to lessen pain and improve sleep. “The question is -- how much of it is hype?" Pertwee says. "It works fine in all the models, but what we really need is more human clinical studies."

The jury is still out on whether marijuana is a safe and effective medicine, but now that attitudes toward marijuana are shifting and drugs such as Epidiolex are beginning to show promise, researchers hope they will finally be able to study its health effects and medical potential in a meaningful way.

In addition to earning research freedoms, though, determining marijuana’s usefulness also requires time and investment. So far, few companies or government agencies have been willing to make that commitment. In another rare exception, GW Pharmaceuticals is seeking FDA approval for an oral spray to treat cancer-related pain called Sativex, which also is derived from marijuana and already prescribed in 27 countries.

Epidiolex, meanwhile, is slowly making its way toward regulatory approval. GW Pharmaceuticals filed an application with the FDA for the drug to treat Dravet syndrome and Lennox-Gastaut syndrome, two forms of debilitating childhood epilepsy, in 2014.

The company is now ready to begin testing patients for three months in the second of three phases of clinical trials, and expects to soon begin a phase-3 trial with 200 patients from around 60 hospitals and universities. If approved, Epidiolex may provide another option for the 93,000 children with epilepsy in the U.S. who do not respond to currently available treatments. GW Pharmaceuticals is now providing the drug to 400 patients with 21 forms of epilepsy for free through the compassionate use program, and Stephen Schultz, vice president of investor relations, says it’s likely that the company will announce additional uses for Epidiolex in treating some of these forms later this year.