Beyond the trip: How compounds derived from psychedelics could help treat inflammatory conditions

Psychedelic drugs, long-known for their powerful effects on perception and emotion, may hold the key to treating a wide range of inflammatory diseases where new therapies are urgently needed - from neurodegenerative conditions to gut and respiratory disorders.

Birmingham researchers have highlighted the emerging therapeutic potential of a new class of compounds derived from psychedelics that could open the door to safe, targeted therapies for widespread use in clinical settings.  They have coined these PIPI drugs (pronounced PiePie; Psychedelic drug Informed but Psychedelic-experience Inactive drugs), that could open the door to safe, targeted therapies for widespread use in clinical settings.

In a review published in the British Journal of Pharmacology, scientists led by Professor Nicholas Barnes, principal founder and CEO of University of Birmingham spin-out Celentyx, examined emerging evidence on how psychedelics may do far more than alter consciousness by influencing immune system function, making psychedelic-derived drugs promising candidates for diseases and conditions featuring inflammation.

Psychedelics also influence neuroinflammation, which is a critical factor in chronic and debilitating brain diseases such as Alzheimer’s and Parkinson’s disease, schizophrenia and depression, and the consequences of neurotrauma.

A key drug target of many psychedelics is the serotonin 5-HT_2A receptor in the brain, yet these receptors are also found in other tissues, including immune cells.

Significantly, the anti-inflammatory actions of psychedelics may be biologically distinct from the mechanisms responsible for their hallucinogenic effects.

This means it may be possible to develop next-generation treatments that harness the therapeutic power of psychedelics without inducing hallucinations or changes in perception, and these molecules are now beginning to emerge. 

Professor Barnes, who has studied the 5-HT receptor system for over 40 years and is the Chair of the IUPHAR 5-HT Receptor Nomenclature Committee, said: "This work highlights a frontier in psychedelic research that could transform how we treat some of the most challenging and persistent diseases of our time. It may mark a major shift in how we address chronic diseases where inflammation delivers pathology. As PIPI drugs move into clinical investigation, we hope their therapeutic potential is translated to deliver benefit to patients."