Ibudilast

Human RCT evidence is emerging: a Phase 2 trial in progressive MS (SPRINT-MS) slowed brain atrophy, a Phase 2 alcohol use disorder trial reduced heavy-drinking odds, and Phase 1 work established methamphetamine-safety. It is regulatory-approved in Japan for asthma and post-stroke dizziness. Preclinical work is extensive across neuroinflammation, neuropathic pain and addiction models, with neurotrophin up-regulation.

Generally well tolerated; the common effects are nausea, headache, dizziness or somnolence, and fatigue. Some neurologic trials reported depression and abnormal dreams. It did not augment methamphetamine's cardiovascular effects. Despite a long Japanese safety record, it remains investigational (not FDA-approved) for MS, ALS and addiction, and its cognition use is unproven.

Originally developed and marketed in Japan as Ketas for bronchial asthma and post-stroke dizziness, ibudilast was repurposed as MN-166 by MediciNova, who carried it through Phase 2 programs in progressive multiple sclerosis, ALS and substance-use disorders. Its distinctive glial and neuroimmune mechanism made it a recurring candidate wherever neuroinflammation drives disease.

Regarded as one of the more interesting brain-penetrant neuroimmune agents because it targets glia and MIF/TLR4 rather than acting as a plain PDE4 inhibitor. It has a favorable tolerability reputation and a long real-world track record in Japan, but its Western status is firmly investigational.