1cP-LSD: Difference between revisions - PsychonautWiki Archive

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The [[psychedelic]] effects are thought to primarily come from its efficacy at the 5-HT2A receptors distributed throughout the brain. 1cP-LSD also likely displays binding activity at a wide range of [[monoamine]] receptors, such as those for [[dopamine]] and [[norepinephrine]]. However, there is currently no data to support these claims.

Most serotonergic psychedelics are not significantly dopaminergic, and ~~1-cP~~-LSD is therefore atypical in this regard. The agonism of the D2 receptor may contribute to its psychoactive effects in humans.<ref>Marona-Lewicka D, Thisted RA, Nichols DE (July 2005). "Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis". ''Psychopharmacology''. '''180''' (3): 427–35. doi:10.1007/s00213-005-2183-9. <nowiki>PMID 15723230</nowiki>. S2CID 23565306.</ref> 1cP-LSD binds to most serotonin receptor subtypes except for the 5-HT3 and 5-HT4 receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.<ref>Nichols DE (February 2004). "Hallucinogens". ''Pharmacology & Therapeutics''. '''101''' (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. <nowiki>PMID 14761703</nowiki>.</ref> Recreational doses can affect 5-HT1A (Ki=1.1nM), 5-HT2A (Ki=2.9nM), 5-HT2B (Ki=4.9nM), 5-HT2C (Ki=23nM), 5-HT5A (Ki=9nM [in cloned rat tissues]), and 5-HT6 receptors (Ki=2.3nM).

Most serotonergic psychedelics are not significantly dopaminergic, and 1cP-LSD is therefore atypical in this regard. The agonism of the D2 receptor may contribute to its psychoactive effects in humans.<ref>Marona-Lewicka D, Thisted RA, Nichols DE (July 2005). "Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis". ''Psychopharmacology''. '''180''' (3): 427–35. doi:10.1007/s00213-005-2183-9. <nowiki>PMID 15723230</nowiki>. S2CID 23565306.</ref> 1cP-LSD binds to most serotonin receptor subtypes except for the 5-HT3 and 5-HT4 receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.<ref>Nichols DE (February 2004). "Hallucinogens". ''Pharmacology & Therapeutics''. '''101''' (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. <nowiki>PMID 14761703</nowiki>.</ref> Recreational doses can affect 5-HT1A (Ki=1.1nM), 5-HT2A (Ki=2.9nM), 5-HT2B (Ki=4.9nM), 5-HT2C (Ki=23nM), 5-HT5A (Ki=9nM [in cloned rat tissues]), and 5-HT6 receptors (Ki=2.3nM).

1cP-LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins.<ref>Chen Q, Tesmer JJ (January 2017). "A Receptor on Acid". ''Cell''. '''168''' (3): 339–341. doi:10.1016/j.cell.2017.01.012. PMC 5520807. <nowiki>PMID 28129534</nowiki>.</ref> A crystal structure of 5-HT2B bound to 1cP-LSD reveals an extracellular loop that forms a lid over the diethylamide end of the binding cavity which explains the slow rate of unbinding from serotonin receptors.<ref>UNC Health Care (January 26, 2017). "This is LSD Attached to a Brain Cell Serotonin Receptor (Update)". ''Phys.org''.</ref>

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 The [[psychedelic]] effects are thought to primarily come from its efficacy at the 5-HT<sub>2A</sub> receptors distributed throughout the brain. 1cP-LSD also likely displays binding activity at a wide range of [[monoamine]] receptors, such as those for [[dopamine]] and [[norepinephrine]]. However, there is currently no data to support these claims.
-Most serotonergic psychedelics are not significantly dopaminergic, and 1-cP-LSD is therefore atypical in this regard. The agonism of the D<sub>2</sub> receptor may contribute to its psychoactive effects in humans.<ref>Marona-Lewicka D, Thisted RA, Nichols DE (July 2005). "Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis". ''Psychopharmacology''. '''180''' (3): 427–35. doi:10.1007/s00213-005-2183-9. <nowiki>PMID 15723230</nowiki>. S2CID 23565306.</ref> 1cP-LSD binds to most serotonin receptor subtypes except for the 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.<ref>Nichols DE (February 2004). "Hallucinogens". ''Pharmacology & Therapeutics''. '''101''' (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. <nowiki>PMID 14761703</nowiki>.</ref> Recreational doses can affect 5-HT<sub>1A</sub> (K<sub>i</sub>=1.1nM), 5-HT<sub>2A</sub> (K<sub>i</sub>=2.9nM), 5-HT<sub>2B</sub> (K<sub>i</sub>=4.9nM), 5-HT<sub>2C</sub> (K<sub>i</sub>=23nM), 5-HT<sub>5A</sub> (K<sub>i</sub>=9nM [in cloned rat tissues]), and 5-HT<sub>6</sub> receptors (K<sub>i</sub>=2.3nM).
+Most serotonergic psychedelics are not significantly dopaminergic, and 1cP-LSD is therefore atypical in this regard. The agonism of the D<sub>2</sub> receptor may contribute to its psychoactive effects in humans.<ref>Marona-Lewicka D, Thisted RA, Nichols DE (July 2005). "Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis". ''Psychopharmacology''. '''180''' (3): 427–35. doi:10.1007/s00213-005-2183-9. <nowiki>PMID 15723230</nowiki>. S2CID 23565306.</ref> 1cP-LSD binds to most serotonin receptor subtypes except for the 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.<ref>Nichols DE (February 2004). "Hallucinogens". ''Pharmacology & Therapeutics''. '''101''' (2): 131–81. doi:10.1016/j.pharmthera.2003.11.002. <nowiki>PMID 14761703</nowiki>.</ref> Recreational doses can affect 5-HT<sub>1A</sub> (K<sub>i</sub>=1.1nM), 5-HT<sub>2A</sub> (K<sub>i</sub>=2.9nM), 5-HT<sub>2B</sub> (K<sub>i</sub>=4.9nM), 5-HT<sub>2C</sub> (K<sub>i</sub>=23nM), 5-HT<sub>5A</sub> (K<sub>i</sub>=9nM [in cloned rat tissues]), and 5-HT<sub>6</sub> receptors (K<sub>i</sub>=2.3nM).
 cP-LSD is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins.<ref>Chen Q, Tesmer JJ (January 2017). "A Receptor on Acid". ''Cell''. '''168''' (3): 339–341. doi:10.1016/j.cell.2017.01.012. PMC 5520807. <nowiki>PMID 28129534</nowiki>.</ref> A crystal structure of 5-HT<sub>2B</sub> bound to 1cP-LSD reveals an extracellular loop that forms a lid over the diethylamide end of the binding cavity which explains the slow rate of unbinding from serotonin receptors.<ref>UNC Health Care (January 26, 2017). "This is LSD Attached to a Brain Cell Serotonin Receptor (Update)". ''Phys.org''.</ref>