Abstract:Abstract:55--MethoxyMethoxy--N,NN,N--dimethyltryptamine dimethyltryptamine ((acronymized as acronymized as 55--MeOMeO--DMT) is a unique member of a group of naturallyDMT) is a unique member of a group of naturally--occurring psychoactive occurring psychoactive indolealkylamineindolealkylaminesubstances and substances and has been described as a prototypical entheogenhas been described as a prototypical entheogen. . It acts as a It acts as a nonselective 5nonselective 5--hydroxytryptamine hydroxytryptamine (serotonin(serotonin) agonist and causes a broad spectrum of highly interesting physiological and ) agonist and causes a broad spectrum of highly interesting physiological and psychological psychological effects. Research indicates that 5effects. Research indicates that 5--MeOMeO--DMT DMT may be synthesized in human pineal and retina, and may be synthesized in human pineal and retina, and it has it has been identified in human body fluids including urine, blood, and cerebrospinal fluid. 5been identified in human body fluids including urine, blood, and cerebrospinal fluid. 5--MeOMeO--DMT is ubiquitously present DMT is ubiquitously present in the plant kingdom and has been in the plant kingdom and has been utilised for medicinal, psychological, and spiritual purposes by utilised for medicinal, psychological, and spiritual purposes by shamans for thousands shamans for thousands of years. In additions to its phytochemical distribution, it is present in the of years. In additions to its phytochemical distribution, it is present in the skin and venom skin and venom of a single amphibian species of a single amphibian species that is endemic to the Sonoran desert. that is endemic to the Sonoran desert. Incilius Incilius alvarius:alvarius:The The Sonoran Desert toad (binomial nomenclature: Sonoran Desert toad (binomial nomenclature: Incilius alvariusIncilius alvarius) produces significant amounts of ) produces significant amounts of 55--MeOMeO--DMT DMT in its numerous parotoid glands. The salience in its numerous parotoid glands. The salience of toad of toad symbolism in symbolism in Mesoamerican iconography and Mesoamerican iconography and mythology mythology is well documented by anthropologists and is well documented by anthropologists and toadtoad--effigies effigies (with accentuated glands(with accentuated glands) are found in archaeological excavation ) are found in archaeological excavation from ancient from ancient Mayan and Aztec Mayan and Aztec cultures. cultures. Qualitative phenomenological Qualitative phenomenological effects:effects:55--MeOMeO--DMT DMT is is extremely neuroactive extremely neuroactive (4(4--10 times more potent than its relative 10 times more potent than its relative DMT but less visual), DMT but less visual), it has a fast onset (full effects almost it has a fast onset (full effects almost instantaneously present instantaneously present after administration), and a relatively after administration), and a relatively shortshort--lived action lived action (ca. (ca. 2020--50 50 minutes). minutes). Anecdotal Anecdotal evidence evidence indicates indicates that 5that 5--MeOMeO--DMT DMT expands and transforms expands and transforms consciousness consciousness inconceivably and that it inconceivably and that it has the potential to induce a has the potential to induce a temporary nontemporary non--dualistic dualistic experience of reality. In experience of reality. In other words, the dichotomy between subject and object (the observer and other words, the dichotomy between subject and object (the observer and the observedthe observed) dissipates. This phenomenon ) dissipates. This phenomenon has also been described as egohas also been described as ego--dissolution and unity dissolution and unity consciousness and it is consciousness and it is congruent with congruent with epiphanies epiphanies described in described in ancient Asian wisdom traditions (e.g., Hinduism and Buddhism). For example, the quintessential ancient Asian wisdom traditions (e.g., Hinduism and Buddhism). For example, the quintessential hinduistic/hinduistic/vvedanticedanticconcept of “concept of “AdvaitaAdvaita” ” translates from Sanskrit translates from Sanskrit into English as “notinto English as “not--two” or two” or “no second” “no second” ––a quasia quasi--mystical allmystical all--isis--one state.one state. Neurochemical receptorNeurochemical receptor--binding binding characteristics:characteristics:55--MeOMeO--DMT DMT has an exceptionally high has an exceptionally high affinity affinity for certain members of for certain members of the 5the 5--HT receptor family. Specifically, this molecule acts as a nonselective partial agonist for the 5HT receptor family. Specifically, this molecule acts as a nonselective partial agonist for the 5--HTHT1A1Aand 5and 5--HTHT2A2Areceptor subtypes. The 5receptor subtypes. The 5--HT system is associated with mood, cognition, and memory. For example, its receptors are HT system is associated with mood, cognition, and memory. For example, its receptors are located in the cerebral cortex (cognition), in the amygdala (emotions), and in the raphe located in the cerebral cortex (cognition), in the amygdala (emotions), and in the raphe nucleusnucleus. This nucleus is located in . This nucleus is located in the most primitive part of the brain, the brainstem, and its axons project widely throughout the cortex. The raphe nucleus the most primitive part of the brain, the brainstem, and its axons project widely throughout the cortex. The raphe nucleus produces the majority of the brains serotonin. Ergo, when it is stimulated by 5produces the majority of the brains serotonin. Ergo, when it is stimulated by 5--MeOMeO--DMT it causes extensive serotonergic DMT it causes extensive serotonergic activation throughout many neural networks of the brain. Moreover, 5activation throughout many neural networks of the brain. Moreover, 5--HT receptors are present in the hypothalamus HT receptors are present in the hypothalamus which connects the which connects the central nervous central nervous system to the endocrine system. It has been convincingly argued that 5system to the endocrine system. It has been convincingly argued that 5--MeOMeO--DMT DMT causes the hypothalamus to release large amounts of oxytocin via causes the hypothalamus to release large amounts of oxytocin via the pituitary the pituitary gland. This gland. This increase in oxytocinergic increase in oxytocinergic activity might activity might explain why the qualitative description of explain why the qualitative description of 55--MeOMeO--DMTs DMTs phenomenology oftentimes include phenomenology oftentimes include words words like like “love”, “unity”, and “connectedness“love”, “unity”, and “connectedness”.”.Accumulating Accumulating evidence indicates that 5evidence indicates that 5--MeOMeO--DMT is an endogenous ligand of the DMT is an endogenous ligand of the Trace amineTrace amine--associated receptors (associated receptors (TAARsTAARs), a class of G protein), a class of G protein--coupled receptors that were recently discovered in 2001. It coupled receptors that were recently discovered in 2001. It has been hypothesized that the has been hypothesized that the TAARsTAARsare involved in sensory perception. Moreover, the are involved in sensory perception. Moreover, the TAARsTAARshave been associated have been associated with pathological neuroadaptations associated with prolonged exposure to drugs (e.g., alcohol or cocaine addiction). with pathological neuroadaptations associated with prolonged exposure to drugs (e.g., alcohol or cocaine addiction). Consequently, this might explain 5Consequently, this might explain 5--MeOMeO--DMTs apparent effectiveness in addiction treatment. That is, because 5DMTs apparent effectiveness in addiction treatment. That is, because 5--MeOMeO--DMT is able to target these receptors it might be able to regulate the DMT is able to target these receptors it might be able to regulate the pathological neurological pathological neurological adaptions caused by adaptions caused by addiction. addiction. Furthermore, Furthermore, 55--MeOMeO--DMT has been found to match the sDMT has been found to match the s11receptor and it has been shown to have antireceptor and it has been shown to have anti--inflammatory effects. inflammatory effects. The effects of 5The effects of 5--MeOMeO--DMT on the dopaminergic system are currently controversial and more DMT on the dopaminergic system are currently controversial and more research research is clearly needed to elucidate its mechanisms of action. is clearly needed to elucidate its mechanisms of action. 55--MeOMeO--DMT DMT as an as an entheogen:entheogen:An entheogen is a chemical substance An entheogen is a chemical substance used in a religious, shamanic, or spiritual used in a religious, shamanic, or spiritual contexts contextsthat that has has the the potential potential to produce profound to produce profound psychopsycho--spiritual spiritual changes. The etymology of the neologism changes. The etymology of the neologism “entheogen” “entheogen” is isderived from the ancient Greek and translates into derived from the ancient Greek and translates into “generating “generating the divine within“. the divine within“. 55--MeOMeO--DMT is a prototypical DMT is a prototypicalrepresentative of an representative of an entheogenicentheogenicsubstance. For instance, it is substance. For instance, it is a ceremonial sacrament a ceremonial sacrament (Eucharist) (Eucharist) of the Church of the of the Church of theTree of Life. Research focusing on 5Tree of Life. Research focusing on 5--MeOMeO--DMT might provide impetus for the emergence of a new neuroscientific DMT might provide impetus for the emergence of a new neuroscientificparadigm which goes by the name “paradigm which goes by the name “neurotheologyneurotheology”. It has been proposed by Efrain C. ”. It has been proposed by Efrain C. AzmitiaAzmitiathat “that “the ability of these the ability of thesedrugs to induce a feeling of closeness to God is a special property of the indoles and this property is attributed to drugs to induce a feeling of closeness to God is a special property of the indoles and this property is attributed toactivation of the cortical 2A serotonin receptoractivation of the cortical 2A serotonin receptor” (” (AzmitiaAzmitia, 2012, 2012).).HoweverHowever, , systematic scientific research systematic scientific research is currently is currentlylegally highly legally highly restricted due to the irrational restricted due to the irrational generic Class A status generic Class A status of of psychoactive psychoactive tryptamines (i.e., tryptamines (i.e., “Psychoactive “PsychoactiveSubstances Substances Act” Act” which reached which reached Royal Assent Royal Assent in January 2016).in January 2016). Christopher B. Germann More information: http://www.cognovo.eu/christopher-germann#5meo-dmtmail@christopher-germann.dechristopher.germann@plymouth.ac.ukMore information: http://www.cognovo.eu/christopher-germann#5meo-dmt