American researchers conducted pilot clinical trials and found that the neuroimmune modulator ibudilast is ineffective for alcohol use disorder. The study was published in JAMA Network Open.
Recently, accumulating evidence suggests that the immune system plays a central role in the development of alcohol use disorder (AUD). Chronic heavy alcohol consumption exacerbates neuroinflammation, which in turn triggers various mental and physical disorders. Thus, immune responses and pathological alcohol use are closely interrelated, and the neuroimmune system is considered an important potential target for AUD treatment.
Lara Ray and colleagues at the University of California, Los Angeles, conducted a double-blind, randomized phase III trial involving 102 patients (mean age 44.3 years; 59.8 percent men) seeking relief from moderate to severe AUD. They were randomly assigned to receive either a placebo or 50 milligrams of ibudilast twice daily for 12 weeks.
This drug inhibits phosphodiesterases types 3, 4 (mostly), 10, and 11, as well as macrophage migration inhibitory factor (MIF), and acts as a neuroimmune modulator, bronchodilator, vasodilator, and antiplatelet agent. In some countries, it is used for bronchial asthma, allergic conjunctivitis, hay fever, and dizziness after ischemic stroke. Its potential for use in multiple sclerosis and addictions is being explored.
It was found that the percentage of days with excessive alcohol consumption did not differ significantly between the active drug and placebo (β = 0.06; p = 0.46). Its use also did not lead to significant changes in the levels of peripheral inflammatory markers—tumor necrosis factor-α, interleukins 6, 8, and 10, and interferon-γ. The adverse event profile was similar in the main and control groups.
The data obtained do not support the use of ibudilast in AUD. Almost simultaneously, Marisa Roberto of the Scripps Research Institute and colleagues from the US and Italy published the results of preclinical trials in rats of another phosphodiesterase 4 inhibitor, apremilast, in the journal JCI Insight. These results were completely opposite, demonstrating the drug's effectiveness in AUD, suggesting that research into neuroimmune modulation in alcoholism does not end there.
Previously, American researchers identified a neuroimmune signaling network in the mouse brain responsible for fear, and demonstrated that psychedelics modulate its activity, reducing this feeling. The presence of a similar signaling system has also been demonstrated in human cells.
