Researchers have leveraged two new molecules, one of which is currently in clinical oncology trials, to devise a dual-drug therapy for alcohol use disorder (AUD). The goal without the side effects or complications associated with current treatment regimens. The approach had highly successful results in mice and may be applicable to other drugs that are often abused.
At the root of the team’s thinking is the idea that AUD and other substance abuse disorders are the result of reinforced pathways in the brain, and that those pathways can be blocked or redirected, ending cravings and habitual behavior.
“Alcohol use disorder is really a process of maladapted learning and memory. Alcohol is rewarding, and we learn to associate alcohol, and even the environment in which we drink the alcohol, with that reward.”
Current pharmaceutical options for AUD attempt to change behavior by making alcohol consumption an unpleasant experience and some require patients to abstain for several days before beginning treatment. But some researchers are taking a different approach, studying the role of the enzyme mTORC1 in the creation of memories and associations. The goal is to develop a drug to treat the core neurological causes of AUD.
Ordinarily, mTORC1 is involved in brain plasticity, helping to create connections between neurons that reinforce memory. Studies of mTORC1 have shown that consuming alcohol activates this same enzyme in the brain. Also working to block the activity of mTORC1, with the FDA-approved compound rapamycin, has been effectively used to treat some types of cancer, suppressing immune response in transplant patients. It can halt cravings in mice engineered to replicate alcohol use disorder. Additionally, it was found that mTORC1 contributes to a bevy of other bodily tasks related to metabolism and liver function, and people taking it for an extended period often develop liver toxicity, glucose intolerance, and other side effects.
Various drug developments are now being tested in clinical trials.
Tackling addiction from this neurological perspective has potential for broad applications. While addiction ia seen with a wide chemical array of molecules—alcohol, nicotine, cocaine, opiates, and the like—the addictive behavior that results from each is the same.
Study Reference: Ehinger Y, Zhang Z, Phamluong K, et al. Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice. Nat Commun 2021;12:4407. doi: 10.1038/s41467-021-24567-x
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