{"id":7659,"date":"2022-06-23T06:59:10","date_gmt":"2022-06-23T06:59:10","guid":{"rendered":"https:\/\/ultimatehealthreport.com\/ayahuasca-and-the-endocannabinoid-system\/"},"modified":"2022-06-23T06:59:10","modified_gmt":"2022-06-23T06:59:10","slug":"ayahuasca-and-the-endocannabinoid-system","status":"publish","type":"post","link":"https:\/\/ultimatehealthreport.com\/ayahuasca-and-the-endocannabinoid-system\/","title":{"rendered":"Ayahuasca and the Endocannabinoid System"},"content":{"rendered":"<p> <br \/>\n<\/p>\n<div property=\"content:encoded\">\n<p>Much as <span class=\"caps\">THC<\/span> exerts the majority of its psychoactive effects through the <span class=\"caps\">CB1<\/span> cannabinoid receptor, the \u201cclassic\u201d psychedelics \u2013 <span class=\"caps\">LSD<\/span>, psilocybin, mescaline, and dimethyltryptamine (<span class=\"caps\">DMT<\/span>) \u2013 are defined by activation of the serotonin 5-<span class=\"caps\">HT2A<\/span> receptor.<\/p>\n<p>Widely distributed throughout the central nervous system, 5-<span class=\"caps\">HT2A<\/span> receptors mediate a number of important processes including learning and memory, perception, inflammation, hormone regulation, and of course hallucination.<\/p>\n<p>Given the role of the endocannabinoid system (<span class=\"caps\">ECS<\/span>) as a \u201cmaster regulator\u201d of many of these functions and more, perhaps we shouldn\u2019t be surprised that 5-<span class=\"caps\">HT2A<\/span> likely manifests some of its downstream effects by altering the release and signaling of endocannabinoids.<\/p>\n<h2>Serotonin <span class=\"caps\">ECS<\/span> Crosstalk<\/h2>\n<p>A 2006 study,<sup id=\"fnref:1\">1<\/sup> coauthored by esteemed psychedelic scientist David Nichols, documents a spike in the endocannabinoid 2-<span class=\"caps\">AG<\/span>, but not in anandamide, the other major endocannabinoid, following stimulation with serotonin of 5-<span class=\"caps\">HT2A<\/span> receptors in rat brain cells. The paper concludes that \u201cneurotransmitters such as serotonin may act as regulators of endocannabinoid tone.\u201d<\/p>\n<p>Another study<sup id=\"fnref:2\">2<\/sup> two years later goes a step further by demonstrating that activation of 5-<span class=\"caps\">HT2A<\/span> in rat neurons by serotonin affects not only the release of endocannabinoids but also the expression of the <span class=\"caps\">CB1<\/span> receptor. A target of 2-<span class=\"caps\">AG<\/span>, anandamide, and <span class=\"caps\">THC<\/span> alike, this cannabinoid receptor is key to the psychoactivity of cannabis and plays a role in many cognitive and physiological processes. \u201cThese findings establish a link between serotonin signaling and endocannabinoid signaling,\u201d the authors write. \u201cIt seems likely that this mechanism could mediate many of the actions of 5-<span class=\"caps\">HT2R<\/span>s throughout the brain.\u201d<\/p>\n<aside class=\"pull-right\">\n<p>Serotonin may act as a regulator of endocannabinoid tone.<\/p>\n<\/aside>\n<p>Today, some 15 years on, two new studies from two separate research groups explore this link in human subjects following a psychedelic dose of ayahuasca, a complex brew containing <span class=\"caps\">DMT<\/span>, a 5-<span class=\"caps\">HT2A<\/span> agonist and potent psychedelic, as well as other plant compounds that may interact with the endocannabinoid system in less direct ways.<\/p>\n<p>Whether or not any clear conclusions can yet be drawn, this research represents a notable step forward in the investigation of crosstalk between these two critical neurotransmitter systems and of the physiological cascade involved in the psychedelic experience.<\/p>\n<div class=\"callout\"><\/div>\n<h2>Ayahuasca, Endocannabinoids, and Social Anxiety Disorder<\/h2>\n<p>Partially informed and inspired by these two preliminary studies, a team of researchers based in Brazil, where ayahuasca, the potent hallucinogenic plant concoction, has a long history of shamanic use, sought to answer a decidedly modern scientific question: How does ayahuasca administration affect endocannabinoid levels in healthy volunteers versus those diagnosed with social anxiety disorder?<\/p>\n<p>To learn more, the team conducted two small pilot, proof-of-concept randomized and placebo-controlled trials. In the first, 20 healthy individuals ingested a single dose of ayahuasca or placebo. In the second, 17 individuals with social anxiety disorder also received a placebo or a single (though roughly half-as-potent) serving of ayahuasca. Blood draws at baseline and 90 and 240 minutes after administration were subsequently used to analyze levels of anandamide and 2-<span class=\"caps\">AG<\/span>.<\/p>\n<aside class=\"pull-right\">\n<p>The <span class=\"caps\">ECS<\/span> is involved in mediating the physiological effects of psychedelic drugs.<\/p>\n<\/aside>\n<p>The results, published in the journal <em>Human Psychopharmacology<\/em> in February 2022,<sup id=\"fnref:3\">3<\/sup> indicate high variability in both trials, with biphasic effects observed in some cases (usually an increase followed by a decrease, though sometimes the opposite), and in others steady increases or decreases. Few findings were statistically significant; takeaways are hard to come by.<\/p>\n<p>\u201cConsidering the results of both tests together, it seems that in social anxiety disorder patients, ayahuasca increased [anandamide] levels from baseline to 90 minutes after its intake, reducing them below baseline levels at the 240-minute time-point,\u201d the authors summarize, adding: \u201cThe study may have been underpowered due to the small sample, and it is possible that statistically significant differences could be observed if the sample was larger.\u201d<\/p>\n<p>Interestingly, not only were the results mixed and unaligned with preclinical findings, but they were also inconsistent with earlier findings from the same team. In a short case report published as a letter to the editor in the <em>Journal of Clinical Psychopharmacology<\/em> in 2018,<sup id=\"fnref:4\">4<\/sup> the researchers describe measuring endocannabinoid levels in the blood of a single healthy, 34-year-old male both before and 90 and 240 minutes after ayahuasca intake. The result? For anandamide, a steady decline below baseline; for 2-<span class=\"caps\">AG<\/span>, a slight decrease followed by a sharper increase.<\/p>\n<div class=\"callout\"><img fetchpriority=\"high\" decoding=\"async\" typeof=\"foaf:Image\" class=\"img-responsive\" src=\"https:\/\/www.projectcbd.org\/sites\/projectcbd\/files\/styles\/related_content_popout\/public\/field\/image\/psychedelic-therapy-.png?itok=5XKMjFij\" width=\"670\" height=\"350\" alt=\"\" data-pagespeed-url-hash=\"1885494249\" onload=\"pagespeed.CriticalImages.checkImageForCriticality(this);\"\/><\/div>\n<h2>More on Ayahuasca\u2019s Molecular Pathways<\/h2>\n<p>For those counting along \u2013 that\u2019s four different studies drawing four different conclusions. And here is a fifth: another study, published in the May 2022 issue of <em>Biomedicine and Pharmacotherapy<\/em>,<sup id=\"fnref:5\">5<\/sup> in which plasma samples were collected from 23 healthy regular users of ayahuasca in the Netherlands before and after consumption.<\/p>\n<p>The scope of this study was far broader than those discussed above, as the Spain-based researchers measured levels of a long list of metabolic markers including amino acids, hormones, neurotransmitters, and a dozen endocannabinoids including anandamide, 2-<span class=\"caps\">AG<\/span>, and lesser-known compounds like <span class=\"caps\">DHEA<\/span>, <span class=\"caps\">OEA<\/span>, 2-<span class=\"caps\">OG<\/span>, 2-<span class=\"caps\">LG<\/span>, <span class=\"caps\">LEA<\/span>, and <span class=\"caps\">DEA<\/span>. But as far as the two primary endocannabinoids go, the researchers observed that ayahuasca consumption increased levels of anandamide and decreased levels of 2-<span class=\"caps\">AG<\/span>.<\/p>\n<p>While this is essentially the exact opposite of what was observed in the Brazilian team\u2019s 2018 case study, it doesn\u2019t make much sense to compare the two given their different designs. Nor does it really make sense to attempt to stack any of the human studies up against the early preclinical work because of the exponentially greater complexity involved in administering a complex botanical brew to humans versus straight serotonin to rat brain cells in vitro.<\/p>\n<p>What we can glean thus far from all the conflicting data is this: The endocannabinoid system is modified through activation of the same cell receptor targeted by classic psychedelics, and the <span class=\"caps\">ECS<\/span> is somehow involved in mediating the physiological effects of these powerful drugs. And that sounds like an avenue worth exploring more.<\/p>\n<hr\/>\n<p><em>Nate Seltenrich, an independent science journalist based in the San Francisco Bay Area, covers a wide range of subjects including environmental health, neuroscience, and pharmacology. Copyright, Project <span class=\"caps\">CBD<\/span>. May not be reprinted without permission.<\/em><\/p>\n<hr\/>\n<h2>Footnotes<\/h2>\n<p>\u00a0<\/p>\n<\/div>\n<p><br \/>\n<br \/><a href=\"https:\/\/www.projectcbd.org\/ayahuasca-and-endocannabinoid-system\" target=\"_blank\" rel=\"noopener\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Much as THC exerts the majority of its psychoactive effects through the CB1 cannabinoid receptor, the \u201cclassic\u201d psychedelics \u2013 LSD, psilocybin, mescaline, and dimethyltryptamine (DMT) [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":7660,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/posts\/7659"}],"collection":[{"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/comments?post=7659"}],"version-history":[{"count":0,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/posts\/7659\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/media\/7660"}],"wp:attachment":[{"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/media?parent=7659"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/categories?post=7659"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ultimatehealthreport.com\/wp-json\/wp\/v2\/tags?post=7659"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}