Asthma medications once hoped to treat alcohol use disorders

Asthma medications once hoped to treat alcohol use disorders

A drug that once showed promise as a treatment for alcohol use disorder didn't work as expected, a new clinical trial from UCLA found.

The drug Ibudilast is approved for the treatment of post-stroke asthma and dizziness in Japan, and previous research suggests it could also help people reduce their drinking. The results published in the journalJama Network Openshowed that ibudilast does not work better than a placebo for most people, although it did have a positive effect for a group of study participants.

While ibudilast was not superior to placebo, we saw that some people did better and some people did worse on the drug. Participants in the female study did better, but both men and women who came in with higher levels of depression got worse, which are findings we can use to guide further research. “

Lara Ray, UCLA psychology professor and lead author of Study

The results are the culmination of many years of study of ibudilast by Ray's research group, the UCLA Addiction Laboratory. Although the drug did not turn out to be as effective as they had hoped, the mixed results still point to the roles that inflammation and the immune system may play in alcoholism. Like apremilast, another drug being tested as a potential alcoholism treatment, ibudilast targets immune responses and associated inflammation.

“We believe there is a strong immune contribution to psychiatric disorders, particularly alcohol use disorder,” Ray said. "Women generally have higher levels of inflammation, and the fact that ibudilast works better for them and worse for people with more depressive symptoms suggests we're on the right track. Immune treatments have revolutionized cancer treatment, and we're using this new approach to do the same for alcohol use disorder."

For the study, researchers recruited 102 adults seeking treatment for moderate or severe alcohol use disorder to take ibudilast or a placebo twice daily for 12 weeks and follow-up for four weeks after the end of the treatment period. They tracked the percentage of heavy drinking days, the number of drinks per day, and the percentage of days abstinent. Depressive symptoms and inflammation were also tracked.

"We found that it reduced overall drinking in both the ibudilast and placebo groups," Ray said.

On average, participants started with seven drinks per day of alcohol consumption, and by the end of treatment they had reduced this to, on average, about three to four drinks per drinking day. However, this reduction was seen in the placebo group and the ibudilast group, meaning that researchers could not prove that ibudilast was superior to placebo in reducing drinking.

"One of the challenges in alcohol use disorder studies is that all participants typically improve their drinking across the board. Participants respond to the entire treatment environment, and regardless of the medications, we see a very pronounced beneficial effect on alcohol use disorders. Therefore, it can be difficult to disentangle the placebo effect from the medications," Ray said.

However, women taking ibudilast drank fewer drinks per day. The effect was strong enough that researchers concluded it was worth testing the effectiveness of ibudilast in reducing drinking for women. On the other hand, people who started the study with more depressive symptoms both drank fewer drinks per day while also having more abstinent days while taking the placebo. Ibudilast also did not reduce inflammatory markers.

“Our lab is discovering novel treatments for substance use disorders, and we are pleased that everyone who came into our study has improved,” said Ray. “One of the challenges going forward is to follow people a little bit longer, for example in a six-month trial, so that we can get more of a separation between the treatment context and the active drug effect.”

“Ongoing analyzes of this clinical trial will help us elucidate who responds to this medication for alcohol use disorders, such as:

This process was funded by the National Institute on Alcohol Abuse and Alcoholism, and the ongoing testing of the UCLA addiction laboratory will require continued federal funding from the federal government to develop effective new treatments for a problem that affects nearly 30 million adults in the United States alone.

“People come to our lab because they trust UCLA,” Ray said. “They regularly report their drinking, and that in and of itself causes pretty significant changes in their behavior.”

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