Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis

Kelly, John R.; Clarke, Gerard; Harkin, Andrew; Corr, Sinéad C.; Galvin, Stephen; Pradeep, Vishnu; Cryan, John F.; O’Keane, Veronica; Dinan, Timothy G.

doi:10.1016/j.ijchp.2022.100349

Cited by 11 publications

(7 citation statements)

References 295 publications

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“…The findings of the current study are promising, as significant alteration of the gut microbiome may provide a possible explanation as to why psilocybin users report a reduction of depressive symptoms after treatment ( Chen et al, 2023 ; Meccia, Lopez & Bagot, 2023 ). It has been proposed that psychedelics may affect gut microbiome to influence their treatment responses ( Kelly et al, 2023 ; Kuypers, 2019 ). To our knowledge, the current study is the first study that investigated the effects of the tryptamines, psilocybin and norbaeocystin, on gut microbe populations.…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly likely, since 5-HT 2A receptors are an essential component of the gut-brain axis ( Fiorica-Howells et al, 2002 ). Although gut microbiome has been proposed as a potential mechanism that psychedelics act upon ( Kelly et al, 2023 ; Kuypers, 2019 ), no prior studies have investigated the effects of any psychedelics on gut microbe populations. Norbaeocystin is structurally similar to psilocybin and is also found in Psilocybe mushrooms.…”

Section: Introductionmentioning

confidence: 99%

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Effect of oral tryptamines on the gut microbiome of rats—a preliminary study

Xu,

Kiss,

Jones

et al. 2024

PeerJ

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Background Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota. Methods To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition. Results We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria. Conclusion and Implications These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of oral tryptamines on the gut microbiome of rats—a preliminary study

Xu,

Kiss,

Jones

et al. 2024

PeerJ

View full text Add to dashboard Cite

show abstract

“…For example, ketamine and psilocybin are emerging treatments for depression that do not act through monoaminergic mechanisms. These drugs appear to have beneficial effects on inflammation and gut-brain axis functioning [201][202][203]. Likewise, psychobiotics may have antidepressant, anti-inflammatory, and neuroprotective effects, and may be useful both in improving treatment outcomes in MDD and in reducing the long-term risk of neurodegeneration [152,204].…”

Section: The Paradox Resolved: Why Do Antidepressants Fail To Signifi...mentioning

confidence: 99%

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Rajkumar

2024

Explor Neuroprot Ther

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Depression is a known risk factor for dementia. Antidepressants are the most commonly used treatment for this condition, and are effective in at least half to two-thirds of cases. Extensive evidence from in vitro and animal models suggests that antidepressants have anti-inflammatory and neuroprotective properties. These effects have been shown to reduce the oxidative damage, amyloid aggregation, and expression of pro-inflammatory genes associated with animal models of neurodegenerative disorders. However, longitudinal research in humans has shown that antidepressants do not protect against dementia, and may even be associated with a risk of cognitive deterioration over time in older adults. The contrast between two sets of findings represents a paradox of significant clinical and public health significance, particularly when treating depression in late life. This review paper attempts to resolve this paradox by critically reviewing the medium- and long-term effects of antidepressants on peripheral immune-inflammatory responses, infection risk, gut microbiota, and neuroendocrine responses to stress, and how these effects may influence the risk of neurodegeneration. Briefly stated, it is possible that the peripheral actions of antidepressant medications may antagonize their beneficial effects against neuroinflammation. The implications of these findings are then explored with a particular focus on the development and testing of multimodal neuroprotective and anti-inflammatory treatments that could reduce the risk of Alzheimer’s and related dementias in patients suffering from depression.

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“…In Figure 3 , Kelly et al illustrate how the microbiota–gut–brain (MGB) axis may modulate responses to psychedelic therapy, acting as a biofeedback system [ 52 ]. Initial MGB activity could help identify individuals more likely to benefit from such therapy.…”

Section: Microbiome and Psychedelic Interactionmentioning

confidence: 99%

Microbiome: The Next Frontier in Psychedelic Renaissance

Kargbo

2023

JoX

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The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome—the ecosystem of microorganisms in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut–brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy’s effectiveness. By integrating insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

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Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis

Cited by 11 publications

References 295 publications

Effect of oral tryptamines on the gut microbiome of rats—a preliminary study

Effect of oral tryptamines on the gut microbiome of rats—a preliminary study

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Microbiome: The Next Frontier in Psychedelic Renaissance

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