Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?

Psychedelic drugs that activate 5-HT2A receptors are known for treating psychiatric disorders, but growing evidence shows they also modulate immune responses by inhibiting pro-inflammatory cytokine release. In vivo studies demonstrate that psychedelics like (R)-DOI reduce inflammation in animal models of asthma and other inflammatory diseases. Clinical studies with psilocybin show effects on circulating cytokine levels, supporting translation from animal models to humans. These findings highlight the promise of targeting inflammation therapeutically. Recent research has identified compounds that maintain therapeutic potential without causing psychedelic effects, termed PIPI drugs (Psychedelic drug Informed but Psychedelic experience Inactive), offering new avenues for treating mental health and inflammation.

Study at a glance

Abstract

Psychedelic drugs that activate 5-HT2A receptors have been long used for cultural, medicinal and recreational purposes. Interest in psychedelics for treating psychiatric disorders has resurged recently and is well documented; less well recognised are their anti-inflammatory properties. Growing evidence now demonstrates that psychedelics modulate immune responses, including inhibiting pro-inflammatory cytokine release. Furthermore, in vivo studies demonstrate that psychedelics, like (R)-DOI, reduce inflammation in animal models of acute and chronic inflammatory disease such as asthma. Likewise, some clinical studies with psychedelic drugs (e.g. psilocybin) demonstrate an impact upon circulating cytokine levels, supporting a translation from the animal models to the clinical arena. Such data emphasise the promise of therapeutic approaches targeting inflammation. Interestingly, recent research has also uncovered compounds that maintain therapeutic potential without likely causing psychedelic effects. These discoveries suggest that drugs informed by psychedelic drugs, but which do not evoke psychedelic experiences, which we term PIPI drugs (Psychedelic drug Informed but Psychedelic experience Inactive), could offer effective treatments for mental health and inflammation, presenting new avenues for therapeutic development.