When you swallow a bite of pizza, microbes in your gut spring into action, helping to digest your food and deliver vital nutrients to your cells. But their influence goes even further. They directly affect your nervous system, shaping your mood. In fact, the trillions of microbial residents in your gut also communicate with your brain . Without them, we wouldn’t be who we are.

So it makes sense that your resident microbiota, a collection of bacteria, viruses, fungi, and archaea (single-celled microorganisms with structure similar to bacteria), would have something to say about any drugs you swallow, too. Researchers are just beginning to explore how an individual’s particular composition of gut microbiota may shape how their body and brain respond to psychedelic drugs. This apparent connection means that, eventually, scientists may be able to figure out how to tailor a psychoactive experience to an individual for maximum therapeutic effect.

The use of psychedelic compounds such as psilocybin—the hallucinogenic in magic mushrooms —and ayahuasca—a psychoactive mixture traditionally used by Amazonian Indigenous cultures—is already used in a therapeutic setting. However, the treatment of certain mental disorders such as addiction, PTSD and depression is not the norm, because evidence of its effectiveness is still mainly anecdotal. Now, scientists are on the cusp of novel research that could unveil a whole new branch of investigation in psychedelics—pinpointing exactly how your microbiome responds to such compounds with a set of reactions. If scientists could isolate those reactions as biomarkers, they could tell a more specific story of what an individual’s psychedelic trip is doing inside their body.

So far, “there is not much research out there investigating the link between psychedelics and the gut microbiome,” says Giorgia Caspani, Ph.D., who was lead author on a September 2024 review paper in the journal Pharmacological Research that discusses how the gut microbiota can control the metabolism of psychedelics and actually modulate the psychedelic compounds’ behavioural effects on an individual’s brain.

At the time, Caspani, a neuroscientist and computational biologist, was studying certain effects of psychedelics like psilocybin on the mouse brain and other tissues with co-author and mentor, Wilfred Jefferies, at his University of British Columbia lab. Caspani was initially interested in the impact of the gut microbiome on different brain diseases, and later, in how the gut microbiome affects our brain and our mood. Eventually, her interest flowed into psychedelic treatment of depression and other psychological conditions. These lines of investigation seemed to point naturally at examining the relationship between psychedelics and the gut microbiome.

Everything you ingest moves down your esophagus, into your stomach, and then your small intestine and large intestine. Deep inside your bowels, that ingested material comes into contact with your body’s vast and (mostly) friendly collection of microorganisms. They live in a symbiotic relationship with your own body, and can ultimately be the deciding team that determines how the stuff you swallowed will affect your entire body.

“For drugs that are given orally, my hypothesis is that the gut microbiome plays a very important role…It can metabolize the drug, can activate it or deactivate it,” says Caspani. The drug could also compete with your own body for certain compounds, called precursors. For example, the amino acid tryptophan is a precursor—a molecular building block—of serotonin, a neurotransmitter hormone which regulates digestion, sleep and mood. Gut microbes create about 90 percent of the serotonin in your body. It’s very important to your brain. That’s why microbes and their human host are “constantly competing” for tryptophan, Caspani says. “And depending on your gut microbial composition, you will get more or less serotonin available to the host, which has an impact on mood and behavior.”

Similarly, your microbiota may compete for the chemical compounds in psychedelics, and could learn to recognize them after repeated exposure, Caspani says. Psychedelic compounds like psilocybin, LSD and DMT have structures similar to serotonin, so they activate serotonin receptors found in the brain. Direct evidence shows that these kinds of drugs are also antimicrobial, altering the composition of the gut microbiome. All of that means users’ gut microbiota have probably developed a specific set of reactions to the compounds.

There’s another reason to study how the gut microbiome handles psychedelic exposure. These microbial populations can modify the permeability of the gut barrier and the blood-brain barrier. Normally, these chemical and physical barriers are tight, to prevent harmful substances entering the bloodstream from the gut, and harmful substances entering the brain from the bloodstream. But some bacteria can make these barriers leaky, Caspani says. “Obviously, that will have an impact on how compounds like psychedelic drugs are absorbed into the blood and eventually into the brain.”

Your gut microbiome might change the way your body reacts to psychedelic influence at every step after ingestion: the metabolization of the drugs, how they’re absorbed, reach the brain, and the eventual effect. Along the way, your microbes could even change the drugs’ composition, even as the drugs change your microbial composition.

“And that links back to the whole idea of personalized medicine. It’s not just a distant reality,” Caspani says. For example, doctors can already treat conditions such as cancer through genetic screening to help determine a personalized treatment. “For things like depression, PTSD…I think that’s a lot more complex because of the inherent complexity of the gut microbiome.”

So this kind of individualized treatment for psychedelics will take a lot of research before we see the application, but the good news is that researchers already know that there are probably a lot of distinct biomarkers—biological effects—involved. The patterns exist; they just have to be discovered and studied carefully. “But now, with the advent of AI and machine learning, I think this is becoming more of a reality. So who knows about timelines, but I am very positive that it is going to happen sooner rather than later,” says Caspani, who is now working at AI biotech company Owkin in London.

Currently, Caspani is running a study looking at the impact of ceremonial ayahuasca on the psychological state of veterans who have experienced war trauma. Funded by Onaya Science, a Peru-based non-profit that investigates ayahuasca and Amazonian plant medicines, the study should help researchers understand if ayahuasca can be beneficial for mental health, Caspani says.

While she and her fellow researchers want to see psychedelics recognized as viable treatments for certain brain disorders, the ultimate goal is to use psychedelics to create personalized medicine. The gut microbiome could be the key to predicting those individual responses.