This UK professor might be close to inventing a medication to treat meth use disorder
When Dr. Linda Dwoskin first began researching new therapeutics to help wean people with methamphetamine use disorder off the drug, she didn’t anticipate the letters, emails and phone calls.
“Dear research team, when I discovered your existence, I was so grateful,” Debi Luther of Florida wrote to Dwoskin in an August email. Attached were pictures of her family, including her two adult sons, both of whom have struggled with addiction. “I am so thankful to know that there is a team working on my family’s behalf to battle this devastating disease.”
Correspondence like this arrives at the University of Kentucky pharmacologist’s office about twice a month, said Dwoskin, asking essentially, “how long do I think it’ll be until their son or their daughter, or their mother” each of whom is suffering from meth use disorder, can get the prescription drug the UK team is working to put on the market.
“I have to say, I’m not sure, but we’re trying as hard as we can to help them. Hopefully it won’t be too much longer,” Dwoskin said.
Dwoskin’s career research has centered on amphetamines, and for more than 20 years, she’s been working to develop a long-term prescription drug that works on the brain for meth users the same way naltrexone, or Vivitrol, works for those with opioid use disorder, which is to essentially block the drug’s pharmacological effects in order to help with recovery. Her research team’s work is currently funded by a multi-million dollar grant from the National Institute on Drug Abuse. She estimates she’s one of fewer than a dozen others across the country working toward the same goal.
The prevalence of meth addiction across the state and country has ebbed and flowed since Dwoskin began her work in the late 1990s, but parts of Kentucky are experiencing a meteoric rise of the drug once again. While the rate of fatal overdoses dropped last year in Kentucky by 15 percent, use of two drugs in overdose cases notably grew in prominence: the opioid fentanyl and its analogues — which is still responsible for the majority of Kentucky’s fatal overdoses — and, by nearly 20 percent, methamphetamine. Many in Kentucky who use illicit drugs are polysubstance users, meaning they actively use more than one drug.
Between January 2017 and April 2019, hospitalizations, trafficking citations and overall deaths related to opioids, including heroin, declined by double digits, according to data released in October by the Kentucky Injury Prevention and Research Center. Heroin-related deaths, specifically, decreased by nearly 55 percent during that time. Meanwhile, all meth-related events have increased by 42 percent.
For someone with opioid use disorder, there’s more than one option for medication to assist with treatment and recovery, including Vivitrol, and buprenorphine, also known as Suboxone. There’s also the fast-acting opioid overdose reversal drug, administered as a nasal spray, that’s carried by first responders and law enforcement officials in Kentucky: naloxone, or Narcan.
But there’s no U.S. Food and Drug Administration-approved equivalent for people struggling with methamphetamine addiction, meaning there’s no option for medication-assisted treatment, or MAT. MAT is the use of FDA-approved drugs in conjunction with counseling and behavioral therapy to treat substance use disorder. There’s strong consensus among medical providers that the MAT model is the most effective way to treat addiction, including for opioids.
At this point, the lack of a FDA-approved prescription for meth addiction means “the bar is very low, because there’s nothing to compare it, too,” Dwoskin said. “Any efficacy would be good.”
What her team, which includes chemists, pharmacologists, and behavioral scientists, are trying to produce is a long-lasting meth antagonist. That means, when dosed correctly, the drug should neutralize meth’s effect on the brain. Dwoskin, who’s a professor and associate dean of research in UK’s College of Pharmacy, describes it as a “detox as well as prevention.”
The first alkaloidal compound her team began working with years ago was lobeline, from the plant, Lobelia inflata, that grows along the east coast, as well as in parts of Kentucky, and was historically used by American Indians in tribal ceremonies, she said. Visitors to Red River Gorge in the warmer months may have seen the plant, marked by its light purple blooms.
Lobeline was fairly successful at inhibiting meth’s effects, her team found, but it had also had other unwanted side effects, even after modifications. They’ve since tested around 600 new molecules, and Dwoskin said they’ve settled on a couple that allow them to directly target the protein in the brain they’re after.
That target protein is the Vesicular monoamine transporter 2 (VMAT2, for short). It’s job is to transport, store and package dopamine in vesicles within a neuron until a physiological stimulus comes along, such as eating food, that prompts their release — a natural process that produces a feeling of reward or reinforcement. Methamphetamine hot-wires this protein and causes dopamine to flood the brain — the effect is an intense and prolonged high.
What Dwoskin hopes her compound will do is keep this physiological process intact, even when meth is present, by neutering the drug’s effect on the VMAT2 protein. The compound would eliminate the reward feeling that meth brings, and hopefully remove the incentive to keep using the illicit drug.
Because Dwoskin is working toward something historic, her team’s efforts have been publicized over the years in national medical publications and journals.
Almost four years ago, their work was highlighted by the National Institute on Drug Abuse. About that time, the letters, emails and phone calls started flooding in from across the country, she said. They’ve arrived steadily since, and Dwoskin does her best to respond to each of them and, in some cases, share them with her colleagues.
When Luther, a nurse in Crestview, Florida, reached out to Dwoskin in August, Dwoskin asked to share Luther’s message with her research team. “I think it would help motivate them, just as your thoughts keep me focused on the goal,” she wrote. Luther also gave the Herald-Leader permission to print details of her story.
Addiction has plagued Luther’s family for years — first her father, then her brother and eventually she and her two sons. As a result, researching substance abuse and treatment methods became somewhat of a necessity, she said earlier this month by phone. That’s how she came across Dwoskin’s work.
Luther is in recovery from alcoholism and has been sober 19 years. Seven years ago, her youngest, 22-year old Caleb, died in a fire in Tennessee. She said an autopsy later found opioids in his system. Her eldest, Joshua, 33, a father to three young sons, has struggled with addiction for most of his adult life, she said. He recently spent half a year in jail waiting for an open slot at a drug treatment facility for meth use disorder. He eventually got one and stayed for six months, but he left earlier this year. In May, he was arrested again for meth possession and violating parole, which came with a three-year prison sentence.
“When I look at the personal cost addiction has played in my family, and I look at my grandchildren, my heart says you cannot watch their destruction,” Luther wrote Dwoskin. “However, I know we have a team working on our behalf.”
“I appreciate the hours you push yourselves and the sacrifices made by your families,” Luther wrote. “I am so glad to know that a team of experts (I will call you, ‘my team’) is working to understand stimulant addiction.”
“Thank you for the encouragement,” Dwoskin wrote back. “Please know we are doing our very best to help those that suffer from this awful disease.”
Best case scenario, if approved by the FDA, the new drug would hit the market in three to five years. Dwoskin hopes to finish engineering the compound in 2020, adjust the dose from being used on animals to humans, and then submit it to the FDA for requisite clinical trials.
Even though that’s still a ways away, “I’m very optimistic we can do this,” Dwoskin said. “I’ve dedicated my life to trying to make this happen, and I hope I can before too long.”
By Alex Acquisto
Lexington Herald-Leader
