Culinary-Medicinal Lion's Mane Mushroom Hericium erinaceus (Agaricomycetes) Mycelium Mitigates Ketamine Abuse Potential.

Ketamine therapy is effective in alleviating symptoms of psychiatric disorders such as depression and anxiety; however, its increasing recreational use raises concerns about potential abuse. Hericium erinaceus mycelium, which contains the bioactive compound erinacine A, has shown promise in promoting brain health. This study investigated whether H. erinaceus mycelium and erinacine A could reduce ketamine's abuse potential using a rat self-administration model. Male Sprague-Dawley rats were trained to self-administer ketamine (0.5 mg/kg/infusion) or sucrose pellets under fixed ratio (FR) 2 or progressive ratio (PR) schedules. The dose-dependent effects of H. erinaceus mycelium and erinacine A on ketamine and sucrose consumption, as well as motivation to acquire them, were assessed using these reinforcement schedules. At higher doses, both H. erinaceu mycelium and erinacine A significantly reduced ketamine intake and motivation under both schedules. While H. erinaceus mycelium had no effect on food reinforcement, erinacine A reduced it. These findings suggest that H. erinaceus mycelium specifically reduces the reinforcing effectiveness of ketamine, highlighting its potential as a supplement to mitigate abuse risk during ketamine therapy.