Psychedelic compounds that activate the 5-HT2A receptor might help treat multiple sclerosis by both calming harmful inflammation and promoting repair in the brain and spinal cord. Current MS drugs work on the immune system but do little to fix damage inside the central nervous system. Psychedelics appear to reduce pro-inflammatory signals from glial cells while increasing factors that support nerve cell health and myelin repair. However, most evidence comes from studies of general inflammation, not autoimmune disease, so it is unclear if these effects will work for MS. Major obstacles include heart and mental health risks, plus legal and ethical barriers. The authors suggest that non-hallucinogenic drugs inspired by psychedelics, which activate the same receptor without the mind-altering effects, may be a more practical path forward.
Tabernanthalog (TBG), a non-hallucinogenic analog of ibogaine, was designed to avoid life-threatening cardiotoxicity by eliminating interactions with the hERG potassium channel. Beyond its anti-addictive and antidepressant-like effects, recent 2024-2025 data show TBG is effective in preclinical models of neuropathic and visceral pain and reverses cognitive deficits associated with cancer-related cognitive impairment, including those induced directly by tumors. TBG's mechanism involves a multi-target profile: inhibition of nicotinic acetylcholine receptors, positive modulation of NMDA receptors, and crosstalk with mGlu2 receptors, rather than solely 5-HT2A receptor agonism. It induces structural neuroplasticity without widespread immediate early gene activation, decoupling therapeutic rewiring from psychedelic effects. TBG represents a promising scaffold for next-generation neurotherapeutics.