An experimental medication targeting reward pathways in the brain helps people addicted to cocaine reduce their drug use – and could treat other substance use disorders, too.
Medications are available to treat alcoholism and opioid use disorder, but none are approved for addictions to stimulants such as cocaine and methamphetamine. These drugs contribute to roughly half of all in the US. “So this is a giant unmet medical need,” says , founder of Tempero Bio, a California-based pharmaceutical company.
Drugs like cocaine are highly addictive because they hijack the brain’s reward system, flooding it with a neurotransmitter called dopamine, which elicits pleasure and motivation. But too much dopamine overwhelms reward pathways. So, the brain adjusts to repeated drug use by decreasing its sensitivity to the neurotransmitter. As a result, it is harder for people with substance use disorders to feel pleasure from everyday activities, which incites them to continue using drugs.
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Previous research has suggested that a medication called mavoglurant may be able to treat cocaine use disorder by restoring the brain’s sensitivity to dopamine. Developed by the Swiss pharmaceutical company Novartis, the drug works by binding to and inhibiting a receptor in the brain that makes cells less responsive to dopamine.
Dolmetsch worked at Novartis prior to founding Tempero Bio, and during his time with the company, he and his colleagues tested mavoglurant as a treatment for cocaine use disorder. The researchers recruited 68 adults with a cocaine use disorder who were seeking treatment for the condition. The participants, aged 18 to 57, lived in Argentina, Switzerland and Spain. Of them, 31 took mavoglurant pills twice daily while the rest received a placebo. Participants reported their cocaine use daily and provided urine samples for drug testing twice a week.
Over 14 weeks, those taking mavoglurant reported using cocaine on an average of 12 days whereas those given a placebo used the drug on about 20 days. More than 27 per cent of those taking mavoglurant reported no cocaine use and tested negative for the drug in the final three weeks of the study. The same was true for around 8 per cent of those in the placebo group. Participants taking mavoglurant also significantly reduced their alcohol intake: 31 per cent of them stopped drinking entirely in the study’s last three weeks compared with about 11 per cent of the placebo group.
“We now have a medicine that has the potential to work for multiple substance use disorders – which is a first, because we don’t have anything like that,” says Dolmetsch. What makes the result even more important, he says, is that it works against stimulant use disorders, which are one of the hardest substance use disorders to treat.
But “this isn’t going to be a silver bullet”, says at the biotechnology company Cessation Therapeutics in North Carolina. “Addiction is such a multifaceted disease, and there is such utter complexity in the neural circuitry involved. Just targeting one single receptor in that complex process is not really going to [stop drug use].”
Dolmetsch agrees, noting the medication will have to be paired alongside talk therapy and peer support groups if it were to be approved. “There is no question: a pill by itself is not enough,” he says.
Mavoglurant also comes with side effects such as dizziness, headache and nausea, which could disincentivise people from taking it. It also isn’t clear how effective it is in more diverse populations – all but one of the study participants were white.
Novartis has since licensed mavoglurant to another Swiss pharmaceutical company, Stalicla. , Stalicla’s chief medical officer and a researcher involved in this study, declined to comment on whether the company is pursuing it as an addiction treatment.
Other medications with similar mechanisms of action are also in the works, says Dolmetsch. Tempero Bio is currently testing one of them in a phase II trial for cocaine use disorder. “The fact that all these companies are pursuing these indications I think is going to be good for the field, and it is going to be good for patients,” says Gomez-Mancilla. “Because it is really needed.”
Science Translational Medicine
