When she started collecting brains, neuroscientist Yasmin Hurd’s peers wondered what she could possibly be thinking.
Studying animals made way more sense as a way to trace how chronic drug use changes the brain, they thought — after all, how was Hurd going to parse the long-term effects from the trauma of the overdoses that killed the brain donors?
She waved her colleagues off. She wanted to know what was happening in human brains, not in mice.
So she began filling up freezers with slices of brain tissue from hundreds of overdose victims, most of them killed by too much cocaine.
“We had a lot of freezers, sadly,” said Hurd, who now runs the Addiction Institute at the Mount Sinai School of Medicine. And then, early in the 2000s, she noticed a tidal shift: Suddenly, the overdoses were dominated by heroin.
She saw the opioid crisis coming. Ever since, she’s been trying to figure out how to intervene — could she modify or reverse the way addiction changed the brains being studied in her lab?
Hurd has honed in on cannabidiol, one of the two main compounds plucked from the marijuana plant. She thinks it might hold the potential to curb cravings for heroin and other opioids.
She’s running against the wind. Cannabidiol is classified as a Schedule I drug, meaning the U.S. government thinks it carries severe safety concerns, no medicinal benefits, and a high risk of abuse. Even as a growing number of states legalize marijuana, the hard-line federal stance has made it difficult to do clinical research involving cannabis in this country.
But Hurd is throwing all of her weight into studying whether it can combat addiction. And she’s trying to rally other scientists to do the same, by creating a consortium to conduct cannabidiol clinical trials across the globe.
“If this is something that could be potentially beneficial, and there’s an indication that it could be beneficial,” Hurd said in an interview, “why not put all hands on deck?”
Hurd has the reputation and academic standing to pull this off — last fall, she was named to the prestigious National Academy of Medicine, along with dozens of other top-tier researchers.
More than that, she has determination: On the front of her computer screen, she’s stuck up a yellow Post-it note that says, “GAIN CONTROL.” Only she’s crossed out “GAIN,” and replaced it with “TAKE.”
Unraveling The Biology of Addiction
Hurd has always had what she calls a “pure fascination” with the brain. Her own bounces quickly from one thought to the next, sometimes leaving threads unfinished for the sake of starting a new one. One idea may spin off into a dozen new ones. During a recent interview, she jumped from why she finds outliers in science so intriguing to why she loves murder mysteries (Alfred Hitchcock is a personal favorite).
That mental multitasking is mirrored in her lab, where her team is working on a slew of projects, from how chronic drug use restructures the brain to how the brain’s circuits play a role in psychiatric disease.
“My research, unfortunately, reflects me,” she said.
Her mind is constantly hunting for new ideas in unlikely, often difficult places — like on the list of Schedule I drugs.
Past studies have shown that cannabidiol works on a number of brain circuits involved in addiction and drug-seeking behavior. That’s made it an exciting pharmacological target — but the data, by and large, have just been preliminary and unpersuasive. Hurd started looking for more concrete evidence on cannabidiol.
The compound is one of the two main cannabinoids found in the marijuana plant, the other being tetrahydrocannabinol, or THC. But unlike THC, cannabidiol doesn’t get people high. Scientists are studying whether the compound can treat conditions such as epilepsy and anxiety. Hurd is testing whether cannabidiol can cut down on cravings in patients who are addicted to opioids — and in turn, can prevent relapse.
In her research on animals, the compound has decreased cravings and anxiety without producing any psychoactive effects. But she’s not sure why, exactly, it’s working. So at the same time, she’s orchestrating studies to delve into the biology that underlies addiction.
Some quick background: The neurons in the brain talk to each other through neurotransmitters such as dopamine, serotonin, and endocannabinoids. Those chemical messengers ferry information between brain cells through a synapse, which is the intersection between two neurons. Drugs like heroin are like a car crash — they damage those synapses to the point that other cars can’t get through.
Hurd’s lab is studying the wreckage through research like the experiment that one of her postdoctoral researchers, Noel Warren, is working on. Warren hits rat neurons with a compound that mimics chronic heroin use to see how synaptic plasticity — the way the brain changes the connections among neurons, forming new ones while pruning others — is different in the brain after drug use.
Based on her findings, Hurd has launched trials to test cannabidiol in humans — but that’s no easy task.
‘The Hurdles Are Enormous’
Studying cannabidiol is daunting, and not just because the brain is so complex. To use cannabidiol or any part of the cannabis plant for research, a scientist has to get a special license from the Drug Enforcement Administration, which can take years. Then, scientists have to get approval from the Food and Drug Administration to administer it to patients.
“The hurdles are enormous,” said Margaret Haney, a neurobiologist at Columbia University who studies cannabis use disorder and the therapeutic potential of cannabinoids in humans. Haney has to keep the cannabis used in her trials in a gun safe that’s stashed inside a freezer that’s sitting in a special room in her lab that can only be accessed with her fingerprint. That’s routine for cannabis research.
And patients who are enrolled in clinical trials involving cannabis have to come to the lab of the researcher who holds a DEA license to get the drug, which isn’t always doable for individuals with serious medical conditions.
“Our hands are tied even though cannabidiol is not addictive,” Hurd said. But because it derives from the cannabis plant, the government classifies it as a Schedule I drug — like heroin, LSD, ecstasy, and peyote — which are considered to be harmful and have no medicinal value.
That means there are relatively few scientists doing research involving cannabis, and even fewer studying its potential to treat addiction or testing cannabidiol in humans. Hurd isn’t in a crowded field.
“There’s really not that many people that do that,” said Dr. Sachin Patel, of Vanderbilt University, who has done research with cannabis to understand how marijuana exposure early in life raises the risk of psychiatric disorders.
And then, there’s the issue of supply.
For decades, the only sanctioned source of marijuana available for U.S. research was the University of Mississippi, which held an exclusive contract with the federal government.
“If you’re trying to do a clinical trial and you need cannabidiol, it’s actually quite difficult to get the types of cannabis needed to do the research,” said Patel.
Hurd said the restricted supply has made it all but impossible for her to study the specific formulations of cannabidiol she suspects would be the most therapeutic.
She is currently running Phase 2 clinical trials in New York to test cannabidiol’s ability to reduce cravings in people addicted to heroin. And she’s initiating similar studies to test cannabidiol soon in Canada and Jamaica.
But for Hurd, the process has felt painstakingly slow when people are dying so quickly. An estimated 63,600 people died of drug overdoses in 2016. Two-thirds of those deaths were caused by opioids.
Hurd is frustrated by how both the government is grappling with the crisis. It’s paled in comparison to the response to the Zika virus and other public health concerns in recent years, she said.
“People swarmed to do something. That did not happen with the opioid epidemic,” Hurd said.
Why not? Hurd blames it, in large part, on discrimination against people who are addicted to drugs. But if there were more federal funding for research, Hurd said, scientists could accelerate the search for solutions.
“You have to treat every epidemic the same,” she said, “whether it’s a drug epidemic or a viral epidemic.”
She’s quick to note that she’s not arguing that cannabidiol is a cure-all for the crisis. Hurd just wants to have enough researchers working on the problem that they can quickly say whether something works — or whether it doesn’t — and then move on.
Haney, the Columbia neurobiologist, echoed that frustration. The DEA said it has not rescheduled cannabis because there aren’t enough studies to show it has medical potential. But until it’s rescheduled, Haney said, those kind of large, randomized studies won’t really be feasible.
“We’re in a vicious cycle,” she said.
And dispensaries and cannabis companies in the 29 states that have already legalized medical marijuana don’t have any incentive to fund or conduct clinical trials on the medical benefits, experts say, because they’re already able to sell their products to patients without government approval.
“The money-making is all happening outside of any data,” Haney said.
So Hurd is trying to spur her fellow scientists to do as much research as possible on the potential of cannabidiol to treat opioid addiction, in a bid to build a cannabinoid consortium. She’s connected with clinicians, pharmacologists, and neuroscientists to talk about how to spur new research. And she’s working to rope in companies interested in cannabidiol, too. Without National Institutes of Health funding for such a project, she’s hopeful they’ll help fund the consortium.
Her goal: build an infrastructure that’s far broader than her own.