Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?
British journal of pharmacology – July 28, 2025
Source: PubMed
Summary
Psychedelic drugs, known for activating the 5-HT2A receptor, are revealing a surprising ability to modulate the immune system. Evidence suggests they effectively reduce inflammation, including neuroinflammation, by inhibiting pro-inflammatory responses. Animal and early human data support these positive effects. Crucially, new compounds are being developed that offer these anti-inflammatory benefits without the psychedelic experience, presenting innovative avenues for treatment.
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.