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Wednesday, September 03, 2025
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Beyond the trip: How compounds derived from psychedelics could help treat inflammatory conditions
INTRO: 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.
Immunology
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 .
by University of Birminghamedited by Sadie Harley, reviewed by Robert Egan
03 September 2025
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.
Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?
First published: 28 July 2025
FROM THE ABSTRACT
". . .The dawning of modern pharmacology associated with psychedelic drugs
is often attributed to the work of Albert Hofmann with his synthesis of
lysergic acid diethylamide (LSD)
in 1938. Interestingly, at the time, this ‘no special interest’
molecule was side-lined for 5 years before being plucked from obscurity,
leading to Hofmann's legendary psychedelic experiences on a cycle ride
home (Hoffmann, 1980).
The subsequent explosion in research aimed at understanding the
pharmacological actions of psychedelics occurred alongside the rise in
their misuse by those seeking psychedelic experiences, which peaked in
the 1960s with the so-called ‘flower power’ movement. Alarmed by this
perceived deviant behaviour and concerned by the supposed detrimental
effect upon orderly society, governments around the World introduced
legislation criminalising their use, resulting in the desired dramatic
decline in recreational use. Unfortunately, this legislation also
severely limited legitimate research on psychedelics for several
decades, with only a few pioneers continuing to explore their actions
and mechanisms. For more detail around the historical investigation of
activity and use of psychedelic drugs, please see these excellent
reviews (Carhart & Goodwin, 2017; Kyzar et al., 2017).
In the last decade, there has been a resurgence of interest in the therapeutic potential of psychedelic drugs. This interest is at least partly fuelled by the remaining clear unmet medical need for better treatments for depression, anxiety and some other psychiatric disorders. . .
[...] While it is apparent that psychedelic drugs like (R)-DOI and certain trytamine derivatives display clear anti-inflammatory actions, it is intriguing that this is not the case for all psychedelic molecules, or where anti-inflammatory actions are evident, differences in efficacy are sometimes apparent. Indeed, it may be considered very encouraging for the therapeutic potential that some psychedelic drugs display anti-inflammatory action at doses below those thought to be relevant for a psychedelic effect (taken from either head twitch responses in animals or psychedelic experiences in humans). Such findings may suggest that the precise mechanisms underlying the anti-inflammatory effects are yet to be understood and may again indicate novel signal transduction associated with the anti-inflammatory action of 5-HT2A receptor agonists. . .[...] a clear challenge of clinical assessment of psychedelic drugs is a placebo effect—with the evident ‘psychedelic action’ of the drug signposting to the participant/patient the active agent in a ‘placebo-controlled’ study.
- While placebo effects are perhaps more troublesome in the interpretation of subjective outcomes from patients with psychiatric disease, an inhibitory impact of placebo upon inflammatory biomarkers with disease has been documented (e.g. Vollert et al., 2020). Furthermore, the use of a lower—but still psychedelic—dose of the drug may not be a suitable alternative to a ‘placebo’ given some evidence of anti-inflammatory actions occurring at relatively low concentrations of drug. Although, of course, if sub-psychedelic doses are effective in reducing inflammation—as has been suggested for some psychedelic drugs—then this circumvents the issue. Clearly, results from well-controlled trials assessing the impact of psychedelic drugs upon pathological inflammation in patients are awaited eagerly to further assess the therapeutic potential of this pharmacological strategy. Of interest and potential relevance, a case report documents a patient with rheumatoid arthritis being relieved of his chronic symptoms by self-medicating periodically with psilocybin-containing mushrooms (Lin, 2020). While, of course, lacking a relevant control as well as issues around individual self-reporting, such anecdotal reports further encourage the testing of psychedelic drugs for the clinical benefit of patients with inflammatory disease.
DRUGS INFORMED BY PSYCHEDELICS BUT DEVOID OF PROBABLE PSYCHEDELIC ACTIVITY; POTENTIAL THERAPEUTIC ACTIVITY
It is well recognised that medicine-induced psychedelic activity is undesirable because of worries for patient safety that will rightly concern regulatory authorities. Hence, it is significant that some recent enticing developments in the field provide evidence that a therapeutic drug with pharmacology informed by psychedelic drugs but without psychedelic actions may be realistic. We propose to call such compounds PIPI drugs (Psychedelic drug Informed but Psychedelic experience Inactive).
ACKNOWLEDGEMENTS
This research was supported by the MRC (reference MR/R006008/1; NMB), Celentyx Ltd (OQ, JG, CAB, NMB) and NIHR Oxford Health Biomedical Research Centre (RU, NMB). The views expressed are those of the author(s) and not necessarily those of the MRC, Celentyx Ltd, NIHR or the Department of Health and Social Care.
CONFLICT OF INTEREST STATEMENT
NMB is a Director and shareholder in Celentyx Ltd. John Gordon is a Director and shareholder in Celentyx Ltd. Omar Qureshi and Cartherine Brady are shareholders in Celentyx Ltd. The other authors declare no relevant conflict of interests.
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MAIN ARTICLE CONTINUESBeyond the trip: How compounds derived from psychedelics could help treat inflammatory conditions
"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-HT2A 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."
More information: Omar Qureshi et al, Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?, British Journal of Pharmacology (2025). DOI: 10.1111/bph.70138
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