{"id":4918,"date":"2023-01-12T16:46:15","date_gmt":"2023-01-12T16:46:15","guid":{"rendered":"https:\/\/mysafesmoke.com\/psychedelics-endocannabinoids-gut-microbiota\/"},"modified":"2023-01-12T16:46:15","modified_gmt":"2023-01-12T16:46:15","slug":"psychedelics-endocannabinoids-gut-microbiota","status":"publish","type":"post","link":"https:\/\/mysafesmoke.com\/psychedelics-endocannabinoids-gut-microbiota\/","title":{"rendered":"Psychedelics, Endocannabinoids & Gut Microbiota"},"content":{"rendered":"


\n<\/p>\n

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Cannabis contains compounds that directly target cannabinoid receptors. Psychedelics like Lysergic Acid Diethylamide (LSD<\/span>) target serotonin receptors. By acting through serotonin pathways, LSD<\/span> affects endocannabinoid synthesis and function, according to a recent study published in the British Journal of Pharmacology.1<\/p>\n

The October 2022 BJP<\/span> study, featuring contributions from Dr. Vincenzo Di Marzo, Gabriella Gobbi, and several other scientists, sought to quantify serotonin and endocannabinoid-like molecules in the brains of mice that were sacrificed after a seven-day LSD<\/span> regimen. Repeated 30 microgram doses of LSD<\/span> per kilogram of body weight elicited anxiolytic and prosocial behavior. The researchers from Canada, Italy and Australia also examined how LSD<\/span> affected the microbiome of the mice after the seven-day, 30-microgram dose routine.<\/p>\n

The study noted anti-depressant and anti-anxiety effects triggered by LSD<\/span>, which altered endocannabinoid tone and affected the serotonin metabolite, kynurenic acid, without impacting the levels of serotonin or its precursor tryptophan. Increased interaction among mice and anxiolytic behavior occurred, in part, through endocannabinoid signaling and corresponded to changes in a few key families of gut bacteria. These results were seen after repeated doses of LSD<\/span>, not after a single session.<\/p>\n

LSD<\/span> Impacts Endocannabinoid Tone by Binding to Serotonin Receptors<\/h2>\n

Psilocybin, ayahuasca, mescaline, and LSD<\/span> cause a psychedelic \u201ctrip\u201d by binding to 5HT<\/span>-2A, a serotonin receptor. This is one of 14 serotonin receptors, which induce a family of enzymes known as phospholipases (PL<\/span>s). Various serotonin receptors induce different PL<\/span>s. And two compounds (agonists) that activate the same receptor can promote different enzymes.<\/p>\n

By acting through serotonin pathways, LSD<\/span> affects endocannabinoid synthesis and function.<\/p>\n

Serotonin receptors drive a symphony of endocannabinoid-producing PL<\/span>s. Previous research has shown that serotonin facilitates the release of 2-AG<\/span>, a major endocannabinoid, through a phospholipase c (PLC<\/span>)- dependent mechanism.2 LSD<\/span> and psilocin (the psychedelic metabolite of psilocybin) induce different PL<\/span> enzymes by binding to the 5-HT2A<\/span> receptor.<\/p>\n

Psilocin promotes the enzyme PLA2<\/span> via 5-HT2A<\/span>, which enables the synthesis of the lipid neurotransmitters palmitoylethanolamide (PEA<\/span>) and oleoylethanolamide (OEA<\/span>). These endocannabinoid-like signaling molecules belong to the same family as anandamide (AEA<\/span>), the other major endocannabinoid; they are anandamide\u2019s molecular cousins. But unlike anandamide, the so-called bliss molecule, PEA<\/span> and OEA<\/span> do not bind to cannabinoid receptors. They are all part of an expanded endocannabinoid system known as the endocannabinoidome (eCBome), which is intimately connected to the gut microbiome as well as a plethora of other endogenous fatty acid-derived compounds and their receptors.<\/p>\n

LSD<\/span>, unlike psilocin, does not affect the endocannabinoid-like lipid OEA<\/span>, while it insignificantly reduces PEA<\/span>. That\u2019s because LSD<\/span> binds to the 5HT<\/span>-2A receptor without promoting the PLA2<\/span> enzyme. Nor does LSD<\/span> activity at 5-HT2A<\/span> depend on PLC<\/span> synthesis, which is involved in 2-AG<\/span> release. Instead, a seven-day LSD<\/span> regimen impacts endocannabinoid tone by reducing anandamide levels in the brains of mice without affecting 2-AG<\/span> production in the hippocampus or prefrontal cortex, according to the BJP<\/span> report.<\/p>\n

<\/div>\n

LSD<\/span>\u2019s Anti-Inflammatory Properties &<\/span> the Gut Microbiome<\/h2>\n

Why does a weeklong LSD<\/span> dosing regimen reduce anandamide levels in the hippocampus region of a rodent\u2019s brain? Would a similar dosing regimen adversely deplete anandamide in the human brain?<\/p>\n

Psychedelics are known to elicit anti-inflammatory effects that are triggered by the 5-HT2A<\/span> receptor.3 It appears that the anti-inflammatory effects from a seven-day LSD<\/span> regimen would mitigate the body\u2019s requirement for anandamide production. This is because anandamide \u2013\u00a0 which is synthesized via multiple pathways and includes various enzymes but not PLC<\/span> \u2013 is created \u201con demand\u201d in response to inflammation and other forms of stress. LSD<\/span> reduces the demand for anti-inflammatory endocannabinoids by decreasing pro-inflammatory mediators.<\/p>\n

The BJP<\/span> authors note: \u201cGiven that inflammatory signaling influences gut microbiome composition, which is \u2026 altered in psychiatric disorders,\u00a0 the anti-inflammatory effects of LSD<\/span> could have a modulatory role over psychopathology-related gut bacteria.\u201d<\/p>\n

Indeed, Bifidobacterium, Ileibacterium, Dubosiella, and Rikenellaceae RC9<\/span> species increased after psychedelic treatment. Bifidobacterium, which repeated LSD<\/span> doses elevate, can amplify GABA<\/span> neurotransmitter signaling and reduce inflammation. And repeat LSD<\/span> doses further boosted a healthy ratio of two bacteria known as firmicutes and bacteroidetes. Moreover, the anti-inflammatory bacterium has been shown to improve autism and GI<\/span> symptoms.<\/p>\n

Psychedelics and serotonin sing unique symphonies in lipid synthesis through several pathways. And each molecular song embellishes a melody of biological functions. \u201cHence it is possible,\u201d the BJP<\/span> authors surmise, \u201cthat the therapeutic effects elicited by psychedelics acting via the [serotonin] system might be mediated by or result in, changes in gut microbiota composition, brain eCBome composition, or brain 5-HT<\/span> metabolism.\u201d<\/p>\n

Travis Cesorone is a writer focused on endocannabinology, psychedelics, and the scientific process. He currently runs the research-focused blog Uprooted Concepts. Copyright, Project CBD<\/span>. May not be reprinted without permission.<\/p>\n

Sources<\/h2>\n

\u00a0<\/p>\n<\/div>\n


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Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Cannabis contains compounds that directly target cannabinoid receptors. Psychedelics like Lysergic Acid Diethylamide (LSD) target serotonin receptors. 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