Asthma drug once hoped to treat alcohol use disorder fails to meet expectations in UCLA trial

A drug that once showed promise as a treatment for alcohol use disorder did not work as expected, a new UCLA clinical trial found. 

The drug, ibudilast, is approved for the treatment of asthma and post-stroke dizziness in Japan, and previous research suggested it might also help people reduce their drinking. The findings, published in the journal JAMA Network Open, showed that ibudilast works no better than a placebo for most people, although it did have a positive effect for one group of study participants.

While ibudilast was not superior to the placebo, we saw that some individuals did better and some did worse with the drug. Female study participants did better, but both men and women who came in with higher levels of depression did worse, which are results we can use to guide further research."

Lara Ray, UCLA psychology professor and study's first author

The findings are the culmination of many years of investigation into ibudilast by Ray's research group, the UCLA Addictions Lab. Although the drug did not turn out to be as effective as they had hoped, the mixed results nonetheless point toward the roles that inflammation and the immune system may play in alcoholism. Like apremilast, another drug undergoing testing as a potential alcoholism treatment, ibudilast targets immune responses and related inflammation.

"We think that there's a strong immune contribution to psychiatric disorders, especially depression and alcohol use disorder," said Ray. "Women generally have higher inflammation levels, and the fact that ibudilast works better for them and worse for people with more depressive symptoms suggests that we may be on the right track. Immune treatments have revolutionized cancer treatment, and we're using this novel approach to do that for alcohol use disorder."

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

"What we found is that there were general reductions in drinking across both the ibudilast and the placebo groups," said Ray.

On average, participants started with seven drinks per drinking day, and by the end of treatment, they had reduced that to around three to four drinks per drinking day, on average. However, this reduction was seen in the placebo group and the ibudilast group, which means that the researchers couldn't establish that ibudilast was superior to the placebo in reducing drinking. 

"One of the challenges in alcohol use disorder trials is that all participants usually improve their drinking across the board. Participants are responding to the whole treatment setting, and regardless of medication, we see a very pronounced beneficial effect on alcohol use disorder. So it can be hard to tease apart the placebo effect from the medication," said Ray. 

Women who took ibudilast, however, drank fewer drinks per drinking day. The effect was strong enough that the researchers concluded that further studies testing the efficacy of ibudilast in reducing drinking for women are worthwhile. On the other hand, people who started the study with more depressive symptoms both drank fewer drinks per day and had more abstinent days while taking the placebo. Ibudilast also did not reduce markers of inflammation.

"Our lab is uncovering novel treatments for substance use disorders, and we're excited that all the people who came into our study improved," said Ray. "One of the challenges going forward is to follow people a little bit longer, say, in a six-month trial, so that we can get more of a separation between the treatment context and the active medication effect." 

"Ongoing analyses of this clinical trial will help us elucidate who responds to this medication for alcohol use disorder, such as individuals reporting co-occurring pain and those with higher levels of inflammation to begin with."

This trial was funded by the National Institute on Alcohol Abuse and Alcoholism, and the UCLA Addiction Lab's ongoing trials will require a continued funding commitment from the federal government to develop effective new treatments for a problem that affects nearly 30 million adults in the United States alone.

"People are coming to our lab because they trust UCLA," said Ray. "They're reporting on their drinking regularly, and that, in and of itself, is causing pretty significant changes in their behavior."