Serotonergic psychedelic: Difference between revisions

[[File:molecules.png|351px|thumb|right|''Psychedelic structural comparison diagram'']]

'''Serotonergic psychedelics''' (also known as '''serotonergic [[hallucinogen]]s''') are a class of [[hallucinogenic]] substances with a method of action strongly tied to modifying the normal [[neurotransmitter|neurotransmission]] of [[serotonin]]. Serotonin, which is also commonly referred to as '''5-HT''' (from '''5'''-'''h'''ydroxy-'''t'''ryptamine) is a naturally-occurring neurotransmitter which is tied to developmental, cardiovascular, gastrointestinal, and endocrine function, sensory perception, behaviors such as aggression, appetite, sex, sleep, mood, cognition, and memory, many of which have yet to be fully understood.<ref>David E. Nichols and Charles D. Nichols, Serotonin Receptors. Chemical Reviews. 2008. 108 (5), 1614-1641. https://doi.org/10.1021/cr078224o</ref>

==Method of action==

[[File:Psilocybin neural connections.jpg|315px|thumbnail|right|The diagram above demonstrates the neural connections associated with sobriety in comparison to being under the influence of psilocybin as demonstrated through the use of MRI scans. The width of the links is proportional to their weight and the size of the nodes is proportional to their strength. Note that the proportion of heavy links between communities is much higher (and very different) in the psilocybin group, suggesting greater integration<ref>Petri, G., Expert, P., Turkheimer, F., Nutt, D., Hellyer, P. J., & Vaccarino, F. (2014). Homological scaffolds of brain functional networks, 14–18. https://doi.org/10.1038/nrn2618</ref>]]

[[File:NeuroPsychDiagram.png|thumbnail|315px|right|Figure 1 - Activation of the prefrontal network and glutamate release by psychedelics. The figure shows a model in which hallucinogens, such as psilocin, lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT), increase extracellular glutamate levels in the prefrontal cortex through stimulation of postsynaptic serotonin (5-hydroxytryptamine) 2A (5-HT 2A ) receptors that are located on large glutamatergic pyramidal cells in deep cortical layers (V and VI) projecting to layer V pyramidal neurons. This glutamate release leads to an activation of AMPA (α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid) and NMDA (N-methyl-d-aspartate) receptors on cortical pyramidal neurons. in addition, hallucinogens directly activate 5-HT2A receptors located on cortical pyramidal neurons. This activation is thought to ultimately lead to increased expression of brain-derived neurotrophic factor (BDNF).<ref>Vollenweider, F. X., & Kometer, M. (2010). The Neurobiology of Psychedelic Drugs: Implications for the Treatment of Mood Disorders. Nature Publishing Group, 11(9), 642–651. https://doi.org/10.1038/nrn2884</ref>]]

[[File:Psychedelic Signal Theory.jpg|thumbnail|315px|This is an infograph hypothesizing the potential methods of action behind serotonergic psychedelics.]]

While the method of action of serotonergic psychedelics is not fully understood, serotonergic psychedelics are known to show affinities for various 5-HT receptors in different ways and levels, and may be classified by their activity at different 5-HT sub-sites, such as 5-HT_1A, 5-HT_1B, 5-HT_2A, etc.  

Many serotonergic psychedelics, such as the family of [[tryptamines]], have very strong structural similarities to serotonin itself, which partially explains the affinity for certain 5-HT sites. It is almost unanimously agreed that most serotonergic psychedelics produce their effect by acting as strong partial [[agonists]] at the 5-HT_2A receptors.{{citation needed}}

The cortico-striato-thalamo-cortical loops (also known as CSTC-loops) seem to be central to the function of psychedelics<ref>Taylor, S. B., Lewis, C. R., & Olive, M. F. (2013). The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans. Substance Abuse and Rehabilitation, 4, 29–43. https://doi.org/10.2147/SAR.S39684; [..] The overall output of the basal ganglia is predominantly via the thalamus, which then projects back to the PFC to form cortico-striatal-thalamo-cortical (CSTC) loops. [..]</ref>, which are also regulated by the serotonergic system. These control loops connect brain areas like the frontal lobe, the striatum and the thalamus; they aggregate, process and forward internal and external information.

The disruption of the neurotransmitter balance causes these control loops to collapse overwhelmed, leading to the flooding of the frontal lobe with neuronal excitatory glutamate; internal and external stimuli as well as all kinds of non-conscious contents can freely move up to the cerebral cortex and appear as visions in consciousness.<ref>Vollenweider, F. X. (2001). Brain mechanisms of hallucinogens and entactogens. Dialogues in Clinical Neuroscience, 3(4), 265–79. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3181663&tool=pmcentrez&rendertype=abstract</ref><ref>[http://www.neuroculturelab.com/portfolio/edelrausch-im-labor/ Edelrausch im Labor] – ''Neuro Culture Lab'' (German)</ref> Furthermore, there is an over-activation of the locus coerlueus and thereby widespread [[norepinephrine]] secretion, causing a state of spiritual transcendence and sometimes even intense spiritual experiences.

Worth noting is that [[selective serotonin reuptake inhibitor]]s (a class of [[antidepressants]] including Paxil, Prozac, and Zoloft) can increase the dosage required for hallucinogenic effects of serotonergic psychedelics in some people based on anecdotal reports. Some users, however, have found this to be entirely untrue for them, so users who are using daily antidepressants should, at first, only attempt a common dosage.

<h3 class="panel-header">[[Lysergamide]]s[[File:book.svg|x20px|right|link=]]</h3>

<ul class="featured-table">

* [[1P-LSD]]

<div class="panel radius">

<h3 class="panel-header">[[Tryptamine]]s[[File:cogs.svg|x20px|right|link=]]</h3>

<ul class="featured-table">

<li class="featured list-item">

<h4 class="media-heading">[[Tryptamine|Base Tryptamines]]</h4>

* [[DMT]]

* [[MET]]

* [[DET]]

* [[MPT]]

* [[EPT]]

* [[DPT]]

* [[DiPT]]

* [[MiPT]]

* [[EiPT]]

* [[PiPT]]

* [[aMT]]

</li>

<li class="featured list-item">

<h4 class="media-heading">[[Substituted Tryptamine]]s</h4>

* [[4-PO-DMT]] (''Psilocybin'')

* [[4-HO-DET]] (''Ethocin'')

* [[4-HO-MiPT]] (''Miprocin'')

* [[4-HO-DiPT]] (''Iprocin'')

* [[4-HO-MPT]]

* [[4-HO-EPT]]

* [[4-HO-DPT]]

* [[4-AcO-DMT]] (''Psilacetin'')

* [[4-AcO-MET]] (''Metacetin'', ''Azomet'')

* [[4-AcO-DET]] (''Ethacetin'')

* [[4-AcO-MiPT]] (''Mipracetin'')

* [[4-AcO-MPT]]

* [[4-AcO-EPT]]

* [[5-MeO-DiPT]] (''Foxy'')

* [[5-MeO-DALT]]

* [[5-MeO-MALT]]

</li>

</div>

<div class='flex-column'>

<div class="panel radius">

<h3 class="panel-header">[[Phenethylamine]]s [[File:flask.svg|x20px|right|link=]]</h3>

<ul class="featured-table">

<li class="featured list-item">

* [[Mescaline]]

* [[Escaline]]

* [[Allylescaline]]

* [[Methallylescaline]]

* [[Proscaline]]

<li class="featured list-item">

<h4 class="media-heading">[[2C-x]] series</h4>

* [[2C-B]]

* [[2C-C]]

* [[2C-D]]

* [[2C-E]]

* [[2C-H]]

* [[2C-I]]

* [[2C-P]]

* [[2C-TFM]]

* [[2C-T-2]]

* [[2C-T-7]]

</li>

<li class="featured list-item">

<h4 class="media-heading">[[DOx]] series</h4>

* [[DOB]]

* [[DOC]]

* [[DOET]] (''DOE'')

* [[DOI]]

* [[DOPR]]

* [[DOM]]

</li>

<li class="featured list-item">

<h4 class="media-heading">[[25x-NBOMe]]s</h4>

* [[25B-NBOMe]]

* [[25C-NBOMe]]

* [[25D-NBOMe]]

* [[25I-NBOMe]]

* [[25N-NBOMe]]

</li>

<li class="featured list-item">

<h4 class="media-heading">Others</h4>

* [[TMA-2]]

* [[TMA-6]]

* [[Bk-2C-B|ßk-2C-B]]  

* [[2C-B-FLY]]

* [[Bromo-DragonFLY]]

</li>

</div>

<div class='flex-column'>

<div class="panel radius">

<h3 class="panel-header">[[Entheogen]]s [[File:users.svg|x20px|right|link=]]</h3>

<li class="featured list-item">

* [[Ayahuasca]]

* [[Syrian Rue]]

* [[Yopo]]

* [[Hawaiian Baby Woodrose]]

* [[Morning Glory]]

</li>

<li class="featured list-item">

<h4 class="media-heading">[[beta-Carboline|β-Carbolines]]</h4>

* [[Harmaline]]

* [[Harmine]]

* [[Tetrahydroharmine]]

</li>

</div>

<div class="panel radius">

<h3 class="panel-header">Others[[File:cogs.svg|x20px|right|link=]]</h3>

<ul class="featured-table">

<li class="featured list-item">

* [[5-MeO-DiBF]]

* [[Efavirenz]]

</li>

</ul>

</div>

</div>

*[[Subjective effects index]]

* Nichols, D. E. (2016). '''''Psychedelics.''''' Pharmacological reviews, 68(2), 264-355. https://doi.org/10.1124/pr.115.011478

* Geyer, M. A., Nichols, D. E., & Vollenweider, F. X. (2009). '''''Serotonin-related psychedelic drugs.''''' https://doi.org/10.1016/b978-008045046-9.01160-8

* Nichols, C. D., & Sanders-Bush, E. (2001). '''''Serotonin receptor signaling and hallucinogenic drug action'''''. Heffter Rev Psychedelic Res, 2, 73-79. https://web-beta.archive.org/web/20170110205041/https://heffter.org/docs/hrireview/02/chap5.pdf

* Halberstadt, A. L. (2015). '''''Recent advances in the neuropsychopharmacology of serotonergic hallucinogens.''''' Behavioral Brain Research, 277, 99–120. https://doi.org/10.1016/j.bbr.2014.07.016  

* Winter, J. C., Fiorella, D. J., Timineri, D. M., Filipink, R. A., Helsley, S. E., & Rabin, R. A. (1999). '''''Serotonergic receptor subtypes and hallucinogen-induced stimulus control'''''. Pharmacology Biochemistry and Behavior, 64(2), 283-293. http://doi.org/10.1016/S0091-3057(99)00063-5.

* Nichols, D. E. (2004). '''''Hallucinogens.''''' Pharmacology & therapeutics, 101(2), 131-181.

===Specific Examples===

* Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). '''''The Pharmacology of Lysergic Acid Diethylamide: A Review''''', 14, 295–314. https://doi.org/10.1111/j.1755-5949.2008.00059.x

* Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., … Nutt, D. J. (2016). '''''Neural correlates of the LSD experience revealed by multimodal neuroimaging.''''' Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1518377113

* Tylš, F., Páleníček, T., & Horáček, J. (2014). '''''Psilocybin–summary of knowledge and new perspectives.''''' ''European Neuropsychopharmacology'', 24(3), 342-356. http://doi.org/10.1016/j.euroneuro.2013.12.006.

<references/>

[[Category:Psychedelic]][[Category:Psychoactive substance]]