After being banned in the United States in 1970, psychedelic compounds have recently made their way back into the attention sphere of the mainstream medical community for their efficacy in treating mental illnesses such as PTSD, depression, and anxiety.1,2 Current research into psychedelic drugs primarily focuses on their potential in treating mental illnesses, however, there exists some evidence for their potential in treating another field of illnesses called autoimmune disorders. In this article, the potential link between autoimmune disorders and mental illnesses will be explored, along with possible biochemical pathways that might explain psychedelic’s efficacy in treating both types of conditions.
What are Autoimmune Disorders?
Autoimmunity is when the body’s immune system malfunctions and attacks healthy tissue. The link between autoimmune disorders and mental disorders has received increasing attention in the past twenty years.3 Being diagnosed with an autoimmune condition increases one’s chances of being diagnosed with a mood disorder.4 Research into how these two disorders are related has revealed several potential pathways, ranging from chronic inflammation, dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis), disruptions in the gut microbiome, and chronic stress and trauma.5-6 Examining these potential causes, there are many points in which psychedelics might be acting on to explain their treatment efficacy.
Psychedelic Pharmacology
Classic psychedelics exhibit agonistic activity at various serotonin (5-HT) receptors, with the most commonly shared feature being 5-HT2A receptor agonist binding. The table below details some common psychedelics and the receptor subtypes they are known to bind to.7-11
| Psychedelic | 5-HT Subtype Affinity | Other Receptor Affinity |
|---|---|---|
| LSD | 1A, 1B, 1D, 1E, 2A, 2B, 2C, 5A, 6, and 7 | Dopaminergic receptors subtypes D1 and D2 |
| Psilocin | 1A, 1D, 2A, 2C | Adrenergic alpha A and B, dopamine D3, histamine H1 |
| DMT | 1A, 1B, 1D, 2A, 2B, 2C, 5A, 6 and 7 | Glutamate receptors, dopamine, acetylcholine, and the opioid-like receptor Sig1R |
Other psychedelic compounds like ketamine affect N-Methyl-D-aspartate (NMDA) receptors as well, which research shows might affect autoimmune disorders via its effect on glutamate pathways.10,12
Inflammation and Immune Modulation
Research has shown that chronic inflammation plays a key role in autoimmune disorders.7 Dysregulated inflammation is present in many autoimmune disorders, such as lupus, rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome.13-17 Correspondingly, there has been much research into the 5HT system and its inflammation and immune regulation properties.12,18,20-22 Sig1R, another receptor that psychedelics like DMT effect, also modulates inflammatory and immune responses.23,24-26 Via their effect on the 5HT system and Sig1R system, psychedelics might have anti-inflammatory properties that could explain their potential in treating autoimmune disorders.27-29
Trauma and Stress
Another pathway where mental disorders and autoimmune disorders might be linked lies in stressful and traumatic childhood events. Adverse childhood experiences (ACEs) are strongly correlated with autoimmune disorders in later life.30-32 Research into the effect that psychological stress has on the immune system reveals that psychological stress can compromise the immune system function as well.33-37 This leads to disorders such as food sensitivity, HPA axis dysregulation, and leaky gut syndrome, all of which are strongly correlated with autoimmune disorders.34-38 This research hints at how psychedelic treatment of trauma-related illnesses might also improve physiological ailments related to trauma.39-41
Glutamate and Brain-Derived Neurotrophic Factor
Glutamate excitotoxicity involves overactive glutamate receptors in the brain. Chronic excitation of glutamate receptors can contribute to oxidative stress, causing brain damage.38,42,43 Glutamate excitotoxicity is related to depression, addiction, and other neurodegenerative diseases.42-44 Examining ketamine’s effect on NMDA glutamate receptors, it is possible that ketamine’s effect on depression might be related to glutamate regulation.10 Agonists of the Sig1R receptor subtype have also shown to be neuroprotective glutamate excitotoxicity.45,46 Also, DMT has been shown to have potent neuroprotective effects via the Sig1R.29
Psychedelics might increase levels of brain-derived neurotrophic factor (BDNF) gene expression, which facilitates neurogenesis.47-49 Low BDNF expression has been linked to depression, anxiety, schizophrenia, and neurodegenerative diseases.50-53 This pathway is related to 5-HT2A receptor agonist activity of classic psychedelics – in an experiment, administration of a 5-HT2A antagonist reduced the neuroplastic effects of classic psychedelics LSD, DMT, and DOI.48 It is feasible that the BDNF-upregulating qualities of psychedelics could reduce the inflammatory effects of glutamate excitotoxicity in autoimmune disease.54
Gut Microbiome Dysregulation
The gut microbiome refers to the microorganisms present in the gastrointestinal tract (GIT). The gut microbiome produces many neurotransmitters in the body, including dopamine, serotonin, norepinephrine, and gamma-aminobutyric acid (GABA).55 Chronic infections with bacteria, fungi, and viruses are common in those with autoimmune disorders.13,54,56-59 Microbiome bacterial populations appear to play a significant role in a number of immune responses, and influence the presence of autoimmune disorders.1
Psychedelic plants like ayahuasca and peyote have been shown to exhibit anti-microbial properties, which may explain how psychedelics can effectively treat autoimmune conditions.27,60-62 Also, experiments that introduced serotonin to the gut microbiome indicate the presence of a bidirectional signalling system between the host serotonin system and the gut microbiome.63 This highlights the potential for psychedelic serotonin analogues psilocybin, DMT, and 5-MeO-DMT interacting with bacterial receptors.
Lastly, the psychological benefits of psychedelics may indirectly alter microbial communities in the GIT via induced changes in vagal nerve tone and stress response.34,64 Several studies examining the effects of chronic stress and PTSD on microbiome pattern associations found a link between stress and microbiome health.65,66 The psychological and neurological benefits from a psychedelic experience may cause biochemical cascades in the HPA axis and the nervous system, which may influence the ecology of microbial populations.
Conclusion
Autoimmune disorders involve a malfunction of the body’s immune system, causing it to attack the body it is meant to protect. While the causes of autoimmune diseases are varied, several pathways have been proposed involving neurotransmitter dysfunction, gut microbiome dysfunction, and an assortment of other dysregulations present in the nervous system’s biochemistry.
There appears to be an immensely complex biochemical network involving the peripheral nervous system, the gut microbiome, and the immune system. This helps explain psychedelics’ well-known efficacy in treating mental illnesses and also highlights the potential for psychedelics to treat autoimmune disorders.
Further research into the potential biochemical pathways that connect these areas of the body may provide more effective psychedelic treatment programs for mental illnesses. Also, these studies lay the groundwork for using psychedelics for treating of a whole other class of disorders involving the immune system.
Interesting. Going on 13 years of autoimmune diseases I see a correlation between stress events, ptsd, depression, food sensitivity and flairs of inflammation, pain and declining physical health.
Please study this hypothesis. We need hope.
Interesting, I have psoriatic arthritis, undiagnosed gut issues, and am currently on a biologic.
Sign me up!
Fascinating article, thank you. I’m always worried that sketching out potential physiological pathways and speculating as to modes of action, are sometimes taken as proxy evidence of clinical effectiveness. Whilst describing biological plausibility is important, this never answers the fundamental question, ‘does it work’?
I think you may have forgotten to include the most significant citation.
Thompson C, Szabo A. Psychedelics as a novel approach to treating autoimmune conditions. Immunol Lett. 2020 Dec;228:45-54. doi: 10.1016/j.imlet.2020.10.001. Epub 2020 Oct 7. PMID: 33035575.
https://pubmed.ncbi.nlm.nih.gov/33035575/
Please remember to give credit where it is due. 😉
Sincerely,
Caitlin Thompson and Atilla Szabo (the authors of the paper this article is apparently based off of)
As a fellow scientist I wouldn’t assume that lightly – it’s possible that the author wasn’t even aware of such a recent paper. I know the frustration of feeling like you weren’t given credit, but many of the cited papers contain similar information. I’d make absolutely certain before hastily and publicly implying that someone plagiarized.
If you view our paper, you’ll see the headings, content and citations are almost identical. Maybe it’s a coincidence.
The content does seem to match fairly closely, I think Thompson is correct here
This article is true. It does help. It helped me with my darn UC. Been sick w UC for over a year and tired of the med side effects. Im looking to get off the meds for UC. I know CBD helps but it only goes so far. My next quest is to microdose to a point when the inflammation can stay away. Or some other answer for this nonsense..UC
Looking for answers
Straight up, my inflammation goes away with a hit of the DMT pen.
What is a DMT pen and where did you find such a thing?
And what about Diabetes Mellitus I.type? It is autoimmune disorder too. Are there any results?
Diagnosed three years ago with rheumatoid arthritis after receiving 11 vaccinations prior to going to India to do mission surgeries. Have sought natural therapies only as traditional medicine is a complete fail with this disease. I would be very interested in clinical trials if and when they come to fruition. I have been contacting my congressman and women and actively advocating for the medicinal use. Thank you for furthering the cause.
I have RA, as well, and would love to be a part of clinical trials too! This medicine is so powerful, and I have no doubt it could be deeply healing. Love to you on this healing journey!
I developed RA about 5 days after my first Pfizer vaccination in May of 2021, and it quickly became incredibly debilitating. I began microdosing psilocybin just over three months ago and with a very small amount everyday, I am able to function and can remain mostly pain free. It is as close to miraculous a recovery as I could imagine. I take no other meds at the moment. Psilocybin is most definitely anti-inflammatory, at least in my body. 😉 This should be an area of research focus asap!
Hello! Was is prescribed or where did you get it from? Thank you!
I buy it locally (I’m in Oregon, where it grows in the forest, and also has just been decriminalized). You can also try ketamine therapy, either the infusions or sublingually (Dr. Smith in South Carolina is good for sublingual troches). It’s also anti-inflammatory and helps relieve depression and PTSD.
My mother was diagnosed with polymyositis and then IBM within the last 10 years by some of the best medical facilities across the country, including Johns Hopkins. Her body is slowly shutting down as a result and nothing in western medicine has helped, including physical therapy. I firmly believe this is a lifestyle disease from a long history of anxiety, depression, fear, resentment, etc. as a result of the emotional trauma the “system” produces. No one ever mentioned to her she might have a mental disorder or suffer from PTSD. They told her the obvious and tried the worst drugs… Read more »
I’m doing ketamine therapy for the same reason (C-PTSD and PTSD both, causing me to develop several autoimmune disorders). I’m also doing mushroom therapy, acupuncture, massage, red light therapy, and the autoimmune protocol diet. They are really helping!
Have you tried them alone and separate to know what is doing more than the other, what is synergetic working best? like an elimination diet?