American researchers conducted pilot clinical trials and found that the neuroimmune modulator ibudilast is not effective in treating alcohol use disorder. The report on the work was published in the journal JAMA Network Open.
Recently, there has been accumulating evidence that the immune system plays a central role in the development of alcohol use disorder (AUD). Chronic heavy alcohol consumption increases neuroinflammation, which in turn provokes 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 the treatment of AUD.
Lara Ray and colleagues at the University of California, Los Angeles, conducted a double-blind, randomized phase III trial of 102 patients (mean age, 44.3 years; 59.8 percent men) seeking help for moderate to severe AUD. They were randomly assigned to receive either 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, broncho- and vasodilator and antiplatelet agent. In some countries, it is used for bronchial asthma, allergic conjunctivitis, hay fever and dizziness after ischemic stroke, and its potential use in multiple sclerosis and addictions is being studied.
It turned out that when taking the active drug, the percentage of days with excessive alcohol consumption did not differ significantly from placebo (β = 0.06; p = 0.46). Also, its use did not lead to significant changes in the levels of peripheral inflammation markers - tumor necrosis factor α, interleukins 6, 8 and 10 and interferon γ. The profile of adverse events was similar in the main and control groups.
The data obtained do not support the use of ibudilast in RUA. Almost simultaneously, Marisa Roberto from the Scripps Research Institute with colleagues from the USA and Italy published the results of preclinical trials on rats of another phosphodiesterase 4 inhibitor, apremilast, in the journal JCI Insight. They turned out to be the exact opposite and demonstrated the effectiveness of the drug in RUA, so the studies of neuroimmune modulation in alcoholism do not stop there.
Earlier, American researchers identified a neuroimmune signaling network in the brain of mice responsible for the feeling of fear, and also showed that psychedelics modulate its activity, reducing this feeling. The presence of a similar signaling system was also shown in human cells.