There is a class of medicines that’s not particularly well-known or well-understood even within alternative or complementary medicine circles: the sacred indigenous medicines. Sacred indigenous medicines include all of the following and more:
- Ayahuasca
- Peyote
- San Pedro (and other mescaline-containing plants)
- Psilocybin mushrooms
- Amanita muscaria mushrooms
- Tobacco (Nicotiana rustica) / Hápe / Ambil
- Sapito
- Iboga / Ibogaine
- Kambo
In conventional medicine, some of the above-listed agents are known as “psychedelics” which suggests that they produce hallucinations and mental-emotional effects to the exclusion of physical-biological effects. But, in fact, the sacred indigenous medicines have very interesting immunopharmacological effects that have been scientifically studied in relation to their ability to heal autoimmune disease.
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What’s the connection between autoimmunity and mental health?
Autoimmune diseases often co-exist with mental and mood disorders. In other words, patients who are diagnosed with autoimmune disease often also have a diagnosis involving a mental health issue. Some of the most common mental health diagnoses that co-occur with autoimmune disease include:
- Major Depressive Disorder / MDD
- Anxiety
- Schizophrenia / Psychosis
- Bipolar Disorder / Manic Depressive Disorder
- Anxiety Disorders
- More…
Patients who are diagnosed with an autoimmune disease are more likely to go on to later develop clinical depression / MDD. This makes sense. Having an autoimmune disease can be a huge burden. But scientists believe that depression and anxiety don’t develop just because of the pragmatics of dealing with autoimmunity, but rather as a result of inflammation within the nervous system and through dysregulated pro-inflammatory cytokine loops between peripheral and central immune cells.
The sacred medicines have a unique mechanism of action that benefits patients with mental health issues as well as autoimmune disease through their unique pharmacology. Most of these medicines are incredibly safe and non-toxic, and research has shown that they are not addictive, but rather anti-addictive. In other words, these medicines are used to get rid of addiction by releasing underlying trauma and rewiring the brain.
A variety of autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and more involve dysregulation of the immune system. The sacred medicines have anti-inflammatory and immune-modulating effects in addition to psychedelic effects.
For example, Ayahuasca produces a decrease in CD4 and CD3 cells while it increases NK cells. It also decreases C-reactive protein levels in both healthy individuals and in those who suffer from depression. Studies have also shown suppression of pro-inflammatory NF-кB cytokine production after the administration of harmine, one of the components in Ayahuasca. Harmine also inhibits Tumor Necrosis Factor-alpha. Through these mechanisms of action, Ayahuasca is able to reduce inflammation and balance immune system effects.
Serotonin, Inflammation, and Immune Modulation
There is a significant amount of research that has been done on the serotonergic system and its effects on inflammation and immune modulation. Serotonin modulates the release of the following:
- IL-1beta,
- IL-6
- IL-8/CXCL8
- IL-12p40
- TNF-α
- Macrophage polarization
- Dendritic cell function
Serotonin reduces inflammation in part through 5-HT2B and 5-HT7 receptor binding within the serotonergic system. There are likely other immune system and inflammatory effects caused by serotonin, but so far, these are primarily studies that have demonstrated connections between serotonin and inflammation in the body.
DMT and 5-MeO-DMT, Inflammation and Immune Modulation
Both DMT and 5-MeO-DMT have high binding affinity for Sig1R which plays a vital role in regulating the following:
- Mitochondrial function
- Apoptosis
- Proliferation
- Neuroprotection
- Inflammation
- Immune response
- Activation of Nuclear Factor kappa-B
- Mitogen-Activated Protein Kinases
Both Nuclear Factor kappa-B and Mitogen-Activated Protein Kinases play an important role in gene transcription involving immune responses and the production of pro-inflammatory cytokines that impact the immune response in autoimmune disease. Abnormal Sig1R function has been implicated as a potential root cause in a number of psychiatric disorders like Major Depressive Disorder / MDD, Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, and cancer. Sig1R also plays a role in promoting the stress response. When Activation of Nuclear Factor kappa-B and Mitogen-Activated Protein Kinases are dysregulated a number of diseases states can develop including autoimmune conditions.
5-MeO-DMT inhibits the NF-κB signaling pathway in the brain while both DMT and 5-MeO-DMT increase anti-inflammatory factors like IL-10 and decrease levels of pro-inflammatory factors like IL-1-beta, IL-6, TNF-alpha, and chemokine CXCL8/IL-8. In other words, both DMT and 5-MeO-DMT have the ability to reduce inflammation in the brain and body. DMT has a noteworthy neuroprotective effect. For those with autoimmune diseases, DMT and 5-MeO-DMT can open a pathway for healing through their ability to reduce inflammation in the body. When inflammation is diminished, the body has a chance to regroup and heal.
Trauma and Autoimmune Disease
A large number of studies have shown that significant trauma or prolonged stress in early childhood can lead to the development of autoimmune disease. Studies have specifically looked at rheumatoid arthritis, systemic lupus erythematosus, and fibromyalgia though other autoimmune diseases are likely correlated with significant trauma and chronic stress as well.
Physiologically, our bodies respond to stress and trauma through the development of vagal nerve disruption that plays a significant role in autoimmune disease. Stress and trauma compromise the immune system which can lead to chronic infections and gut dysbiosis among other things. When a person experiences chronic stress, they produce more inflammatory cytokines and they experience glutamate toxicity which can inhibit good digestion and nutrient absorption. This, in turn, can lead to disruptions in the hypothalamus-pituitary-adrenal axis.
Stress has also been shown to increase intestinal permeability leading to food sensitivity and inflammation that’s colloquially known as Leaky Gut Syndrome. A variety of sacred medicines like psilocybin mushrooms, Iboga, Sapito (5-MeO-DMT) and Ayahuasca are essential in the release of trauma. These and other sacred medicines have been used to overcome PTSD, Major Depressive Disorder / MDD, and addiction. Specifically, Ayahuasca modulates the cortisol response to treat MDD and PTSD as well as addiction to alcohol and stimulants. By modulating cortisol, the endocrine system can be rebalanced. Cortisol acts like the base drum beat in the symphony of hormones that are released in the body. The endocrine system, in turn, is the system that modulates immunity in the body so as it rebalances, the rest of the physiology can also rebalance to produce autoimmune disease healing.
Iboga is best suited for alcohol addiction and opiate addiction though it should be used as part of a protocol that includes other sacred medicines like psilocybin that are administered at a separate time from the Iboga. Many of these medicines work by reducing chronic sympathetic nervous system (fight-or-flight) activation in the body. Chronic sympathetic activation is theorized to be a major underlying factor in the development of autoimmune disease. Through modulation of cortisol, stress levels are reduced and chronic sympathetic activation can be brought under control as well.
Glutamate Toxicity and Autoimmune Disease
Those with autoimmune disease also tend to be hyper-sensitive to glutamate. Glutamate excitotoxicity happens when there is an uncontrolled release of glutamate and in turn, the glutamate binds to post-synaptic neurons. This hypersensitization to glutamate happens as a result of pro-inflammatory cytokine release.
Glutamate excitotoxicity is particularly prevalent in nervous system-related autoimmune diseases like multiple sclerosis, depression, addiction, and neurodegenerative disease. When emotional stress is ongoing, chronic excitation of the glutamate receptors can contribute to oxidative stress and cell death in the amygdala, hippocampus, and cortex. Actual brain shrinkage can occur as a result. Luckily, the sacred medicines generally promote neuron production and nervous system healing which is extremely important in the release of trauma and in promoting a healing response in those with autoimmune disease.
Brain Derived Neurotrophic Factor (BDNF) is a natural substance that’s produced in the human body that powerfully impacts neuroplasticity or the brain’s ability to regenerate itself and grow new neural connections. Sacred medicines like Ayahuasca increase BDNF levels in both healthy individuals and in those who suffer from mental illness or autoimmune disease. This substance is vital for repairing the brain and the nervous system. BDNF maintains neurons and promotes their survival. Low levels of BDNF in the brain has been linked to depression, anxiety, schizophrenia, and a variety of neurodegenerative diseases.
Treating Underlying Infection in Autoimmune Disease
Autoimmune disease patients typically have underlying infections. In fact, many scientists believe that these underlying infections are the root cause of the symptoms. In any case, sacred medicines like Ayahuasca or mescaline have significant antimicrobial effects that effectively kill infectious pathogens to assist in getting rid of autoimmune disease symptoms.
Essentially, the sacred indigenous medicines work on many levels to kill pathogens, alter hormone levels (especially cortisol) and rewire the brain and body to maintain a more balanced state in those with autoimmune disease. Conventional medicines target one aspect of a disease state and produce multiple side effects and adverse effects that are often worse than the disease itself. But the sacred indigenous medicine work in an entirely different way, opening up new options for healing autoimmune disease.
Sacred Indigenous Medicines Dosing:
The sacred indigenous medicines are generally administered within ceremonial contexts although microdosing is also a more common practice today in modern society.
Resources:
Thompson, C. and Szabo, A. (2020). Psychedelics as a novel approach to treating autoimmune conditions. Retrieved December 23, 2025 from https://www.sciencedirect.com/science/article/pii/S0165247820303977
Miller, G. E. et al. (2011). Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving towards a model of behavioral and biological mechanisms. Retrieved December 26, 2025 from https://www.scopus.com/pages/publications/82855166054?inward=
McEwen, B. S. (2017). Allostasis and the Epigenetics of Brain and Body Health Over the Life Course: The Brain on Stress. Retrieved December 26, 2025 from https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2619523
Bonaz, B. et al. (2018). The vagus nerve at the interface of the microbiota-gut Brain Axis. Retrieved December 26, 2025 from https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00049/full
Blaylock, R. L. and Maroon, J. (2014). Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression? Retrieved December 26, 2025 from https://link.springer.com/article/10.1007/s00702-014-1187-1
Lau, A. & Tymianski, M. (2011). Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy—a unifying hypothesis. Retrieved December 26, 2025 from https://scholar.google.com/scholar_lookup?title=Immunoexcitotoxicity%20as%20a%20central%20mechanism%20in%20chronic%20traumatic%20encephalopathya%20unifying%20hypothesis&publication_year=2011&author=R.L.%20Blaylock&author=J.%20Maroon
Kostic, M. et al. (2010). Glutamate receptors, neurotoxicity and neurodegeneration. Retrieved December 26, 2025 from https://link.springer.com/article/10.1007/s00424-010-0809-1
Kostic, M. et al. (2017). IL-17 signalling in astrocytes promotes glutamate excitotoxicity: indications for the link between inflammatory and neurodegenerative events in multiple sclerosis. Retrieved December 26, 2025 from https://www.sciencedirect.com/science/article/pii/S2211034816302000/pdfft?crasolve=1&r=9b4301ca7e8260af&ts=1766777576213&rtype=https&vrr=UKN&redir=UKN&redir_fr=UKN&redir_arc=UKN&vhash=UKN&host=d3d3LnNjaWVuY2VkaXJlY3QuY29t&tsoh=d3d3LnNjaWVuY2VkaXJlY3QuY29t&rh=d3d3LnNjaWVuY2VkaXJlY3QuY29t&re=X2JsYW5rXw%3D%3D&ns_h=d3d3LnNjaWVuY2VkaXJlY3QuY29t&ns_e=X2JsYW5rXw%3D%3D&rh_fd=rrr)n%5Ed%60i%5E%60_dm%60%5Eo)%5Ejh&tsoh_fd=rrr)n%5Ed%60i%5E%60_dm%60%5Eo)%5Ejh&hc=~rrr)n%5Ed%60i%5E%60_dm%60%5Eo)%5Ejhwrrr)n%5Ed%60i%5E%60_dm%60%5Eo)%5Ejhwrrr)n%5Ed%60i%5E%60_dm%60%5Eo)%5Ejh&iv=8712320b265cbf1dfba8ac6510b8d269&token=33336163653339373839633138326238343163376334373236333736383462396666666135356664306462386666383639633462303433303463643838353762303231346435303637373131326564356133636539383631326333313862656161366162333063383138643838313134656336393038383466313264666533633a303735303631373562366163666630313735656334373536&text=dfa650793a7be3323f4724e264f235c1d468a202d6dd6649d3d467f4b1c31b1e140db98c79942a77dc9b4a757f6358c4c5c1b2781a9b0d68c31b70b70bea2039879c5830c12a4bcd29cf463fbe13e25b11d232c092d917c4d033daf3cb84d80eb6b7d938673e4fb9b130deec45f2320efa39f401eca7322c34f257e5da6ebf4c94964d9dca608da5b026093c96a769df8e84fc3dacb88f4a2727a054267ded03ff73b28294a48cba36fb325d43bb42bf4155d705ea486d6acc267bda7baf773117d481f78c7788d0f096564758662da4b4e4e487bf6d0282598859133228b5d2bde3a5ae3071e4a2fae6297164349107d2660e297078d559adf09253932c839ddc1547eb726f9d5250267d103520b22050dafc509bc499ed96f815dacb8eeb0009e41ad7be279d39478ee1ec33fac671&original=3f6d64353d6338656463326161663537636536393831373965343464396666356365363432267069643d312d73322e302d53323231313033343831363330323030302d6d61696e2e706466&chkp=1c&rack=9b4301ca7e8260af