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Can You Stomach It? The Mysterious Relationship Between Psychedelics and Gut Health

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By: burgundy bug

Psilocybin mushrooms illuminated in front of a purple bokeh background

Source: Adobe Stock

By now, it’s no secret the brain and gut are in constant communication – and yet, there’s still an air of mystery shrowding the gut-brain axis.

So far, we know serotonin is central to gut-brain signaling. In fact, 90 percent of serotonin is synthesized in the lining of the gastrointestinal tract, according to a 2016 Nutrients journal review.

Psychedelics, including psilocybin (a.k.a ‘shrooms’), LSD (a.k.a. ‘acid’), and DMT are serotonergic drugs that bind to the 5-HT2A receptor, says a 2018 World Psychiatric article. This is central to triggering the “psychedelic experience.”

Although research on psychedelics in mood, anxiety, and substance abuse disorders has been and currently is being heavily investigated, with a particular focus on serotonin, the impact of psychedelics on gut health remains largely untapped and under-researched.

Now that’s a head trip.

Before diving into the potential impact of psychedelics and gut health, it’s important to further understand the gut-brain axis and gut microbiome.

The Gut-Brain Axis and Gut Microbiome

“Over the past few decades, researchers have found that there is a complex interaction between the host and its microorganisms, which not only affects energy utilization and digestion, but also brain function and behavior,” says a 2018 Current Neuropharmacology study.

“In fact, these microorganisms and humans have evolved together for a long time and have formed a symbiotic relationship. The microbiome is now recognized by some as an organ of the human body.”

The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Patho-physiological Mechanisms and Novel Treatments | Current Neuropharmacology

Microorganisms outnumber cell count within the human body (37.2 trillion) by 10-times, and microorganisms collectively have 100 times the amount of genes a human has, the study explains.

The gut microbiome develops during birth, and how you were born (vaginal delivery versus a C-section) determines the first type of bacteria to colonize your gut.

Throughout the very early years of human development, gut bacteria becomes more diverse. By the age of three, the gut microbiome resembles that of an adult’s, the study adds.

Diet, antibiotics, and other factors (like stress) can lead to long-term gut bacteria imbalances – which is known as “dysbiosis.”

Needless to say, gut bacteria are an integral part of human life, but the scope of their function goes beyond digestion. And the importance of gut-health becomes all the more vital when analyzing the link between dysbiosis and conditions like major depressive disorder, anxiety disorders, autism spectrum disorder, cognitive decline, and development of the central nervous system.

“Many recent studies over the last decade have played an important role in recognizing the importance of gut microbiota in brain function,” the study concludes. “It is now clear that the gut microbiota directly or indirectly affect neuropsychiatric illness. Whether microbial dysbiosis is the cause or a complication of illness must be further investigated.”

Additional studies support the symbiotic relationship between the gut microbiome and the brain. In a 2018 Nestlé Nutrition Institute Workshop Series review, this relationship is investigated for its role in behavior.

Your Gut-Feeling and Your Feelings

“Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake,” the review says. “Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function.”

In cases of depression, chronic stress, autism, Parkinson’s Disease, chronic pain, IBS and other gastrointestinal disorders, researchers observed dysbiotic states.

The study suggests it’s likely that gut microbiota are involved in modulating behavior, brain processes, stress responsiveness, emotions, pain, social and ingestive behavior.

“Based on currently available evidence, there is no question that there is a relationship between the composition and function of the gut microbiota and brain function,” the study concludes.

However, most of the research cited was on rodents, and current research on the gut-brain axis’ role in behavior is limited in humans.

Serotonin: The Common Language Between Your Gut and Your Brain

“Serotonin (5-HT) has been recognized for decades as an important signaling molecule in the gut, but it is still revealing its secrets.”

Serotonin Signaling in the Gastrointestinal Tract | Nature Reviews Gastroenterology & Hepatology

Within the gut, serotonin modulates motility (gut muscle movement during digestion), secretion (dissolving and diluting during digestion), and vasodilation (facilitating the active process of digestion and absorption), explains a 2013 Nature Reviews Gastroenterology & Hepatology review.

Serotonin also plays a role in intestinal inflammation, symptoms of IBS, and communication to the central nervous system.

In the brain, serotonin regulates mood, cognition, behavior, sleep, appetite, and temperature, according to a 2016 Nutrients journal review.

Read: The Role of Serotonin in Your Daily Life

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During two studies cited in the review, females with IBS displayed altered cognitive performance and impaired memory recall.

Of the seven serotonin receptor groups and their subtypes found throughout the body, 5-HT1A, 5-HT1P, 5-HT2A, 5-HT2B, 5-HT3, 5-HT4, and 5-HT7 are present in the gastrointestinal tract, says a 2013 Techniques in Coloproctology review.

As you may recall, 5-HT2A receptors are associated with the psychedelic effects of various drugs.

So, what’s the connection between the overlap of 5-HT2A receptors in the gut and 5-HT2A agonists like psilocybin?

Psychedelics and Gut-Health: Delving into the Somewhat-Unknown

Psilocybin mushrooms in colorful lighting

Source: Adobe Stock

“5-HT2A and 5-HT2C receptors are known to mediate the neurochemical and behavioral effects of psychostimulants. In the GI tract, they promote contractions of smooth muscle cells.”

Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome | Techniques in Coloproctology

Psychedelic substances have regained interest as therapeutic agents in the treatment of stress-related disorders,” says a 2019 Medicine Hypotheses article. “The effects seem to be of persisting nature even after a single dose.”

Furthermore, “micro-dosing” psychedelics has demonstrated positive effects on cognition and well-being without inducing the altered state of consciousness typically observed in psychedelic use – like hallucinating, for example.

In layman’s terms, micro-dosing is to psychedelics as CBD is to THC… Kind of.

Generally, psychedelic research is focused on how these drugs affect the central nervous system, immune system, large brain networks (i.e. the default mode network), neuroplasticity, and circadian rhythm.

Read: The Default Mode Network: The Center of You

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Yet, the biology behind the “persisting psychological effects is not clear,” the article says. “I propose that low doses of psychedelics exert their effects via an indirect ‘central’ route, i.e., via the gut.”

The article takes into consideration the relationship between the gut microbiome and the central nervous system, while also discussing evidence of other serotonergic drugs (think SSRIs) offering therapeutic benefits for treating gastrointestinal disorders.

However, ayahuasca – a “psychoactive brew” made from various plants – can induce diarrhea, nausea, and vomiting, which may be explained by serotonin signaling in the gut and brain since 5-HT2A modulates contraction of the smooth gut muscle.

Psychedelics may also be seen in the body as a “biological stressor,” since they elevate levels of cortisol, the stress hormone – and stress is known to alter the gut microbiome.

It’s certainly possible that psychedelics may exert their lasting effects through alterations to the gut microbiome, but further research is needed to test this hypothesis.

Further research is also needed in order to understand just how psychedelics may affect gut bacteria and the gut-brain axis.

The role of diet, lifestyle, and how the drugs are administered (naturally-occurring psychedelics versus synthetic versions, consumption versus IV-administration) will need to be factored into the equation during future studies, as well.

In Conclusion

Despite all of the research on the role serotonin plays in the gut-brain axis, various neurological conditions, psychedelics, and how the gut microbiome affects serotonin signaling to the brain, there’s evidently a lack of research on the connection between psychedelics and gut-health.

While there’s certainly been a “psychedelic renaissance” among clinical researchers, these substances remain a Schedule-I drug in the United States, making it difficult to gain access to them for clinical research.

Further investigating the relationship between the gut-microbiome and psychedelics could be central to fully-understanding the long-term effects of psychedelics on the brain and body.

However, moving forward will remain difficult so long as the Drug Enforcement Administration damns psychedelics as “substances with a high potential for abuse” and having “no currently accepted medical treatment use in the United States.”

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burgundy bug


A cynical optimist and mad scientist undercover, burgundy bug is the editor, graphic designer, webmaster, social media manager, and primary photographer for The Burgundy Zine. Entangled in a web of curiosity, burgundy bug’s work embodies a wide variety of topics including: neuroscience, psychology, ecology, biology, cannabis, reviews, fashion, entertainment, and politics. You can learn more about working with burgundy bug by visiting her portfolio website: burgundybug.com

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