Illustrations by Michael Wandelmaier for BuzzFeed
Fluffy white rodents in a sterile laboratory's row of windowless cages are hooked up to IV tubes, which are connected to levers that allow them to inject tiny hits of cocaine whenever they please. Usually, they go back for more as soon as their high starts to wear off. Turns out, rats love blow just as much as humans.
The soundtrack is Miles Davis' version of the jazz standard “Four,” a jaunty number with looping flutters of trumpet notes, and is oddly fitting: Davis struggled for years with addiction, and he infamously crashed his Lamborghini and broke both his ankles while coked up and speeding on the West Side Highway in New York. But that doesn't interest the rats. They just know that when they hear the familiar horn melody, they have an irresistible urge to press the lever that delivers their fix.
There was a scientific method to this madness. The experiment was the work of Dr. Stanley Glick, former head of the Department of Neuropharmacology and Neuroscience at Albany Medical College. An addiction researcher (who also happens to moonlight as a jazz trumpet player), Glick chose “Four” as a way to mimic the sort of stimuli that can induce relapse in drug-addicted humans.
“Probably the biggest instigator of cravings are cues that are associated with the drug,” Glick explains. Seated in a conference room down the hall from his office at Albany Medical College, the 70-year-old Glick wears a rumpled white lab coat over a gray sweater-vest and tie. He has gray hair, a stubbly white beard, and a thick pair of eyeglasses. “Say a cocaine addict uses a little silver spoon to shovel their cocaine. They manage to get off cocaine, but six months later they go to a party and they see a little silver spoon like the one they used to use. The sight of that little silver spoon will induce intense cravings to take the drug again.”
Scientists long ago confirmed the power that sounds, smells, and familiar places have over recovering addicts. Researchers at the University of Pennsylvania conducted brain scans on individuals with a history of cocaine abuse and found that when these people were exposed to images of drug use, their brains became nearly as active as if they were snorting lines themselves. With the Miles Davis experiment, Glick was not aiming to rehash what others already proved. He wanted to test whether he could eliminate cocaine cravings entirely.
Dr. Stanley Glick
After nearly two decades of research, Glick has developed a drug that has the potential to revolutionize substance abuse treatment. It is called 18-MC (short for 18-methoxycoronaridine) and it is, in essence, a drug to get people off of drugs. Glick has meticulously tested it on animals, observing as rats hopelessly strung out on cocaine suddenly lose their desire to get high after a few doses of 18-MC. It has a similar effect on animals addicted to methamphetamine, morphine, alcohol, and nicotine. It even seems to work with sugar, indicating potential as an obesity treatment. But it's not rats that Glick is trying to help, and that's where this gets tricky.
“We hope it’s a paradigm shift in the way substance abuse is treated,” says Steve Hurst, CEO of Savant HWP, the Bay Area biotech startup developing 18-MC. “But we’re still trying to figure out if it’s OK to give to people in doses that are safe enough to replicate what we see in animal models.”
Naturally, there is cause for skepticism. Although early indications suggest 18-MC is safe, it is related to a naturally occurring substance known to cause severe nausea, intense hallucinations, and other serious side effects. Initial tests on humans haven’t revealed those problems, however, and experts are cautiously hopeful that 18-MC may ultimately allow doctors to prescribe medication that blocks cravings and helps people stay clean.
While a handful of treatments are available to help opiate addicts kick their habits, there are currently no options other than cold turkey for coke, meth, and other addictive stimulants. Glick’s 18-MC is one of several promising new substances to emerge from the rapidly advancing field of anti-addiction science. Glick and Hurst’s competitors include a researcher at Weill Cornell Medical College who has created a vaccine that creates antibodies that he says act “like little Pac-Men floating around in the blood” gobbling up cocaine in the bloodstream before it ever reaches the brain. Another treatment being developed by a Swiss pharmaceutical company and a researcher in New Zealand regulates dopamine, the pleasure-inducing neurotransmitter associated with cocaine, to reduce cravings and prevent relapse.
Despite desperate demand by millions of suffering addicts and their families, it may still take years to determine if these drugs are safe and effective enough to be sold in the United States. Prohibitive costs and red tape have long hindered the development of all types of medication, but public health officials, legislators, academic researchers, and drug developers interviewed for this story say current Food and Drug Administration policies make it especially difficult for companies to bring anti-addiction drugs to market. The FDA requires drugs like 18-MC to produce absolute abstinence in cocaine users in clinical trials, a standard that many believe is impossibly stringent.
Though still staring down a long path of bureaucratic hurdles, Glick and his peers are closer than they’ve ever been before to developing the first medications that combat cocaine and other stimulants. And, after years of shunning anti-addiction science, pharmaceutical companies have begun to realize the potential profits involved and are showing interest in the emerging field.
"Here’s a compound that is effective for models of opioid addiction, stimulant addiction, alcohol addiction, nicotine addiction, and for obesity," says Dr. John Rotrosen, director of the addiction research program at New York University’s Langone Medical Center. Of 18-MC, he says, "It all seems too good to be true."
Though he officially retired in June, Stanley Glick still teaches at the graduate school, and his vitality belies his senior citizen status. His roots as a native New Yorker show through as he talks a mile a minute while recounting the path he traveled to develop 18-MC.
It began one day around 1989 when he received a phone call from a former heroin addict touting a miracle cure for drug addiction. The ex-junkie was named Howard Lotsof, and his purported cure was a substance called ibogaine, a bitter white powder derived from the roots of a plant indigenous to the rainforests of western Central Africa. Ibogaine is something like the African equivalent of peyote or ayahuasca, a potent hallucinogen used to induce spiritual visions during tribal ceremonies.
Glick wasn’t buying it. As both a Ph.D. and medical doctor specializing in substance abuse treatment, he had been studying the effects of addictive drugs on the brain long before Lotsof came calling.
“I’ve gotten a number of calls over the years from people who want me to study something,” Glick says. “Most of them are just crackpots. But he kept calling back. The more I looked into it, the more my curiosity was piqued.”
Ibogaine is illegal and considered a Schedule I drug in the United States (meaning it officially has a high potential for abuse and no medicinal value), but Lotsof, who died in 2010, was adamant that it eliminated the intense cravings and unpleasant withdrawal symptoms associated with heroin and other opiates. He had obtained a patent for the use of ibogaine in treating addiction, and reportedly had positive results administering it at a clinic in the Netherlands, one of many countries where the drug is legal and still available today.
According to Glick, Howard Lotsof "thought if he told the world about [ibogaine] they would embrace him as a savior and he would rid the world of this terrible scourge of addiction."
“[Lotsof] originally thought if he told the world about this they would embrace him as a savior and he would rid the world of this terrible scourge of addiction,” Glick says. “Then he realized there was such a thing as science, the FDA, and controlled trials. He had to get scientists to study it. He called every drug abuse scientist in the country, and, for better or worse, I was the first one who was fool enough to get interested in it.”
Glick figured a few preliminary tests on rats would debunk Lotsof’s wild claims, but he became intrigued when animals trained to self-administer morphine stopped taking the drug for days and even weeks after being dosed. He set out to find the precise “mechanism of action” in the brain that caused the phenomenon. A few years later, Glick ended up with 18-MC.
The ibogaine research hit a dead end in 1995 when the National Institute on Drug Abuse, the federal agency that funds scientific research on drug abuse, voted to halt the study of ibogaine over concerns the drug causes fatal cardiac issues and possibly brain damage at high doses.
“They just washed their hands of the whole thing,” Glick says. “It became pretty clear to me there was no way, shape, or form that ibogaine would ever be something that would even be pursued as a legitimate medication in this country.”
A few years prior to the NIDA vote, Glick began collaborating with a chemist at the University of Vermont named Martin Kuehne. Kuehne had experience synthesizing medications for cancer and other diseases, and together they had the idea of tweaking the basic chemical structure of ibogaine to eliminate the side effects while keeping the potent anti-addiction properties. After testing about 60 different compounds — all close chemical cousins of ibogaine — Glick settled on 18-MC.
Illustration by Michael Wandelmaier for BuzzFeed
In simple terms — which Glick often has trouble using — 18-MC blocks the pleasurable effects of cocaine by “dampening the response” to dopamine. Glick pulls up several graphs that show the cocaine intake of addicted rats dropping precipitously after they receive 18-MC.
“What the rat is telling you here is, ‘The drug is getting in, I feel it, but it’s not giving me the kick that it used to,’” Glick says. “That’s really the essence of how we think 18-MC works. ... No matter what dose of the addictive drug you take, it’s just not giving you the buzz it used to.”
Virtually every addictive drug known to man — from booze to heroin to cocaine — stimulates an area of the brain commonly known as the reward pathway. When a person snorts a line or downs a shot of liquor, it triggers a surge of dopamine in this pathway. Many others have tried unsuccessfully to create drugs that work directly inside the reward pathway by blocking the release of dopamine or preventing it from binding with neurons. Glick’s drug takes a different tact.
According to Glick, 18-MC works on a specific type of nicotinic receptor, an area strongly associated with tobacco addiction and cravings. Most crucially, it also works in an “alternate reward pathway” that indirectly impacts the way neurons in the brain release and absorb dopamine.
“It turned out that in the early ‘80s there was a flurry of studies on this,” Glick says. “But by the late ‘80s everyone was studying dopamine. We had discovered how rewarding events occur in the brain and everyone had forgotten about this alternate reward pathway. I felt like what happened is we rediscovered the importance of this pathway.”
After Glick made his first discoveries about 18-MC, he set about finding a partner willing to invest in the additional research and development necessary to gain FDA approval for testing in humans. He ended up writing letters to 38 different pharmaceutical companies. Nobody was interested.
“I’d done everything conceivable I could do to try to get some pharmaceutical interest,” Glick says. “I was on the verge of giving up.”
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