View source for Psychedelic drug

{{Short description|Hallucinogenic class of psychoactive drug}}
{{Redirect|Psychedelic|other uses|Psychedelic (disambiguation)}}
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{{Psychedelic sidebar}}
[[File:Synthetic mescaline powder i2001e0151 ccby3.jpg|right|thumb|Synthetic [[mescaline]], the first psychedelic compound to be extracted and isolated<ref>{{cite web|url=http://mescaline.com/exp|title=Peyote San Pedro Cactus – Shamanic Sacraments|work=D.M.Taylor}}</ref>]]

'''Psychedelics''' are a subclass of [[Hallucinogen|hallucinogenic drugs]] whose primary effect is to trigger non-ordinary mental states (known as [[psychedelic experience]]s or "trips") and a perceived "expansion of consciousness".<ref name="Aghajanian, G 16S–23S">{{cite journal|author=Aghajanian, G|date=August 1999|title=Serotonin and Hallucinogens|journal=Neuropsychopharmacology|volume=21|issue=2|pages=16S–23S|doi=10.1016/S0893-133X(98)00135-3|pmid=10432484|doi-access=free}}</ref><ref name="psych-meditation-self">{{cite journal |last1=Millière |first1=Raphaël |last2=Carhart-Harris |first2=Robin L. |last3=Roseman |first3=Leor |last4=Trautwein |first4=Fynn-Mathis |last5=Berkovich-Ohana |first5=Aviva |title=Psychedelics, Meditation, and Self-Consciousness |journal=Frontiers in Psychology |date=2018 |volume=9 |page=1475 |doi=10.3389/fpsyg.2018.01475 |pmid=30245648 |pmc=6137697|doi-access=free }}</ref> Also referred to as '''classic hallucinogens''' or '''serotonergic hallucinogens''', the term ''psychedelic'' is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to [[psychedelia]] like [[Salvia divinorum|salvia]] and [[MDMA]], respectively.<ref name="McClure 2022">{{cite journal |title=The promises and perils of psychedelic pharmacology for psychiatry |journal=Nature Reviews Drug Discovery |year=2022 |last1=McClure-Begley |first1=Tristan D. |last2=Roth |first2=Bryan L. |volume=21 |issue=6 |pages=463–473 |pmid=35301459 |doi=10.1038/s41573-022-00421-7 |s2cid=247521633 |url=https://www.nature.com/articles/s41573-022-00421-7 |accessdate=2024-02-08 }}</ref>

Classic psychedelics generally cause specific psychological, visual, and auditory changes, and oftentimes a substantially [[altered state of consciousness]].<ref name="dmt-nde"/><ref name="Griffiths">{{cite journal | title = Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance | journal = Psychopharmacology | date = 7 July 2006 | author = R. R. Griffiths |author2=W. A. Richards |author3=U. McCann |author4=R. Jesse | volume = 187 | issue = 3 | pages = 268–283| doi=10.1007/s00213-006-0457-5 | pmid=16826400| s2cid = 7845214 }}</ref> They have had the largest influence on science and culture, and include [[mescaline]], [[Lysergic acid diethylamide|LSD]], [[psilocybin]], and [[N,N-Dimethyltryptamine|DMT]].<ref>McKenna, Terence (1992). ''Food of the Gods: The Search for the Original Tree of Knowledge A Radical History of Plants, Drugs, and Human Evolution''</ref><ref>W. Davis (1996), ''One River: Explorations and Discoveries in the Amazon Rain Forest''. New York, Simon and Schuster, Inc. p. 120.</ref>

Most psychedelic drugs fall into one of the three families of chemical compounds: [[Substituted tryptamine|tryptamines]], [[Substituted phenethylamine|phenethylamines]], or [[lysergamides]] (LSD is considered both a tryptamine and lysergamide). They act via [[Serotonin receptor agonist|serotonin 2A receptor agonism]].<ref name="Aghajanian, G 16S–23S"/><ref name="psychedelicreview.com">{{Cite web|date=2020-10-05|title=Crystal Structure of LSD and 5-HT2AR Part 2: Binding Details and Future Psychedelic Research Paths|url=https://psychedelicreview.com/crystal-structure-of-lsd-and-5-ht2ar-part-2-binding-details-and-future-psychedelic-research-paths/|access-date=2021-02-12|website=Psychedelic Science Review|language=en-US}}</ref><ref name="nichols-2018">{{cite book |last=Nichols |first=David E. |chapter=Chemistry and Structure–Activity Relationships of Psychedelics |date=2018 |title=Behavioral Neurobiology of Psychedelic Drugs |series=Current Topics in Behavioral Neurosciences |volume=36 |pages=1–43 |editor-last=Halberstadt |editor-first=Adam L. |location=Berlin |publisher=Springer |language=en |doi=10.1007/7854_2017_475 |pmid=28401524 |isbn=978-3-662-55880-5 |editor2-last=Vollenweider |editor2-first=Franz X. |editor3-last=Nichols |editor3-first=David E.}}</ref><ref name="Nichols2016">{{Cite journal |last=Nichols |first=David E. |date=2016 |title=Psychedelics |url=https://pharmrev.aspetjournals.org/content/68/2/264 |journal=Pharmacological Reviews |language=en |volume=68 |issue=2 |pages=264–355 |doi=10.1124/pr.115.011478 |issn=0031-6997 |pmc=4813425 |pmid=26841800}}</ref><ref name="McClure 2022" /> When compounds bind to serotonin [[5-HT2A receptor|5-HT<sub>2A</sub>]] receptors,<ref>{{Cite book |date=11 November 2005 |url=https://www.worldcat.org/oclc/123438340 |title=Basic neurochemistry: Molecular, cellular and medical aspects |location=Amsterdam |publisher=Elsevier Science |last=Siegel|first=George J. |isbn=978-0-08-047207-2 |edition=7th |oclc=123438340}}</ref> they modulate the activity of key circuits in the brain involved with sensory perception and cognition. However, the exact nature of how psychedelics induce changes in perception and cognition via the 5-HT<sub>2A</sub> receptor is still unknown.<ref>{{Cite journal |last1=Smigielski |first1=Lukasz |last2=Scheidegger |first2=Milan |last3=Kometer |first3=Michael |last4=Vollenweider |first4=Franz X. |date=August 2019 |title=Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects |journal=NeuroImage |url= https://linkinghub.elsevier.com/retrieve/pii/S1053811919302952 |volume=196|pages=207–215|doi=10.1016/j.neuroimage.2019.04.009|pmid=30965131|s2cid=102487343}}</ref> The psychedelic experience is often compared to non-ordinary forms of consciousness such as those experienced in meditation,<ref name="letheby-gerrans">{{cite journal |last1=Letheby |first1=Chris |last2=Gerrans |first2=Philip |title=Self unbound: ego dissolution in psychedelic experience |journal=Neuroscience of Consciousness |date=2017 |volume=3 |issue=1 |pages=nix016 |doi=10.1093/nc/nix016 |pmid=30042848 |pmc=6007152 |quote=The connection with findings about PCC deactivation in 'effortless awareness' meditation is obvious, and bolstered by the finding that acute ayahuasca intoxication increases mindfulness-related capacities.}}</ref><ref name="psych-meditation-self"/> [[mystical experience]]s,<ref name="Griffiths"/><ref name="dmt-nde">{{cite journal |last1=Timmermann |first1=Christopher |last2=Roseman |first2=Leor |last3=Williams |first3=Luke |last4=Erritzoe |first4=David |last5=Martial |first5=Charlotte |last6=Cassol |first6=Héléna |last7=Laureys |first7=Steven |last8=Nutt |first8=David |last9=Carhart-Harris |first9=Robin |title=DMT Models the Near-Death Experience |journal=Frontiers in Psychology |date=2018 |volume=9 |page=1424 |doi=10.3389/fpsyg.2018.01424 |pmid=30174629 |pmc=6107838|doi-access=free }}</ref> and [[near-death experience]]s,<ref name="dmt-nde"/> which also appear to be partially underpinned by altered default mode network activity.<ref>{{Cite journal|last1=Brewer|first1=Judson A.|last2=Worhunsky|first2=Patrick D.|last3=Gray|first3=Jeremy R.|last4=Tang|first4=Yi-Yuan|last5=Weber|first5=Jochen|last6=Kober|first6=Hedy|date=2011-12-13|title=Meditation experience is associated with differences in default mode network activity and connectivity|journal=Proceedings of the National Academy of Sciences|volume=108|issue=50|pages=20254–20259|doi=10.1073/pnas.1112029108|pmc=3250176|pmid=22114193|bibcode=2011PNAS..10820254B|doi-access=free}}</ref> The phenomenon of [[ego death]] is often described as a key feature of the psychedelic experience.<ref name="letheby-gerrans"/><ref name="psych-meditation-self"/><ref name="dmt-nde"/>

Many psychedelic drugs are illegal to possess without lawful authorisation, exemption or license worldwide under the [[Single Convention on Narcotic Drugs|UN conventions]], with occasional exceptions for religious use or research contexts. Despite these controls, [[recreational use]] of psychedelics is common.<ref name="30-million">{{cite journal|author=Krebs, Teri S|author2=Johansen, Pål-Ørjan|date=28 March 2013|title=Over 30 million psychedelic users in the United States|journal=F1000Research|volume=2|pages=98|doi=10.12688/f1000research.2-98.v1|pmc=3917651|pmid=24627778 |doi-access=free }}</ref><ref name="garcia-et-al">{{cite journal|author=Garcia-Romeu, Albert|author2=Kersgaard, Brennan|author3=Addy, Peter H.|date=August 2016|title=Clinical applications of hallucinogens: A review.|journal=Experimental and Clinical Psychopharmacology|volume=24|issue=4|pages=229–268|doi=10.1037/pha0000084|pmc=5001686|pmid=27454674}}</ref> Legal barriers have made the scientific study of psychedelics more difficult. Research has been conducted, however, and studies show that psychedelics are physiologically safe and rarely lead to addiction.<ref name="canada-commission">{{cite book|last=Le Dain|first=Gerald|title=The Non-medical Use of Drugs: Interim Report of the Canadian Government's Commission of Inquiry|date=1971|page=106|quote=Physical dependence does not develop to LSD}}</ref><ref name="Ungless 2006">{{cite journal|author1=Lüscher, Christian|author2=Ungless, Mark A.|date=14 November 2006|title=The Mechanistic Classification of Addictive Drugs|journal=PLOS Medicine|volume=3|issue=11|pages=e437|doi=10.1371/journal.pmed.0030437|pmc=1635740|pmid=17105338 |doi-access=free }}</ref> Studies conducted using psilocybin in a [[Psychotherapy|psychotherapeutic]] setting reveal that psychedelic drugs may assist with treating [[Major depressive disorder|depression]], [[alcohol addiction]], and [[nicotine addiction]].<ref name="Nichols2016"/><ref>{{cite web|title=Psychedelic psilocybin therapy for depression granted Breakthrough Therapy status by FDA|url=https://newatlas.com/psilocybin-magic-mushrooms-depression-fda-breakthrough-therapy/56928/|author=Rich Haridy|date=24 October 2018|website=newatlas.com|access-date=2019-09-27}}</ref> Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology.<ref name="bender-hellerstein-2022">{{cite journal |last1=Bender |first1=David |last2=Hellerstein |first2=David J. |title=Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research |journal=Psychopharmacology |date=2022 |volume=239 |issue=6 |pages=1907–1932 |doi=10.1007/s00213-021-06049-6 |pmid=35022823|s2cid=245906937 }}</ref><ref name="reiff-et-al-2020">{{cite journal | vauthors = Reiff CM, Richman EE, Nemeroff CB, Carpenter LL, Widge AS, Rodriguez CI, Kalin NH, McDonald WM | title = Psychedelics and Psychedelic-Assisted Psychotherapy | journal = The American Journal of Psychiatry | volume = 177 | issue = 5 | pages = 391–410 | date = May 2020 | pmid = 32098487 | doi = 10.1176/appi.ajp.2019.19010035 | s2cid = 211524704 }}</ref><ref name="tupper-et-al"/><ref name="garcia-et-al"/> A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life.<ref>{{cite web|last=Orth|first=Taylor|url=https://today.yougov.com/topics/lifestyle/articles-reports/2022/07/28/one-in-four-americans-have-tried-psychedelic-drugs|title=One in four Americans say they've tried at least one psychedelic drug|work=YouGov|date=July 28, 2022}}</ref>

==Etymology and nomenclature==
[[File:5ht2a.jpg|thumb|5-HT<sub>2A</sub> receptor]]
The term ''[[wiktionary:psychedelic|psychedelic]]'' was coined by the psychiatrist [[Humphrey Osmond]] during written correspondence with author [[Aldous Huxley]] (written in a rhyme: “To fathom Hell or soar angelic/Just take a pinch of psychedelic.”<ref>{{Cite journal |last=Tanne |first=Janice Hopkins |date=2004-03-20 |title=Humphry Osmond |journal=BMJ: British Medical Journal |volume=328 |issue=7441 |pages=713 |issn=0959-8138 |pmc=381240}}</ref>) and presented to the New York Academy of Sciences by Osmond in 1957.<ref name="tanne-osmond">{{cite journal |last1=Tanne |first1=Janice Hopkins |title=Humphrey Osmond |journal=BMJ |date=2004 |volume=328 |issue=7441 |pages=713 |doi=10.1136/bmj.328.7441.713 |pmc=381240}}</ref> It is irregularly<ref>''[[Oxford English Dictionary]]'', 3rd edition, September 2007, ''[https://www.oed.com/view/Entry/153850 s.v.]'', Etymology</ref> derived from the [[Greek language|Greek]] words ψυχή (''psychḗ'', meaning 'mind, soul') and δηλείν (''dēleín'', meaning 'to manifest'), with the intended meaning "mind manifesting" or alternatively "soul manifesting", and the implication that psychedelics can reveal unused potentials of the human mind.<ref>A. Weil, W. Rosen. (1993), ''From Chocolate To Morphine: Everything You Need To Know About Mind-Altering Drugs''. New York, Houghton Mifflin Company. p. 93</ref> The term was loathed by American [[ethnobotanist]] [[Richard Schultes]] but championed by American psychologist [[Timothy Leary]].<ref>W. Davis (1996), "One River: Explorations and Discoveries in the Amazon Rain Forest". New York, Simon and Schuster, Inc. p. 120.</ref>

Aldous Huxley had suggested his own coinage ''phanerothyme'' (Greek ''phaneroein''- "to make manifest or visible" and Greek ''thymos'' "soul", thus "to reveal the soul") to Osmond in 1956.<ref>[https://archive.org/details/mokshawritingson00aldo iia700700.us.archive.org]</ref> Recently, the term [[entheogen]] (meaning "that which produces the divine within") has come into use to denote the use of psychedelic drugs, as well as various other types of psychoactive substances, in a religious, spiritual, and mystical context.<ref name="nichols-2004">{{cite journal|author=Nichols, David E.|title=Hallucinogens|journal=Pharmacology & Therapeutics|year=2004|pages=131–81|volume=101|issue=2|pmid=14761703|doi=10.1016/j.pharmthera.2003.11.002}}</ref>

In 2004, [[David E. Nichols]] wrote the following about the nomenclature used for psychedelic drugs:<ref name="nichols-2004"/>

{{Blockquote|Many different names have been proposed over the years for this drug class. The famous German toxicologist Louis Lewin used the name phantastica earlier in this century, and as we shall see later, such a descriptor is not so farfetched. The most popular names—hallucinogen, psychotomimetic, and psychedelic ("mind manifesting")—have often been used interchangeably. ''Hallucinogen'' is now, however, the most common designation in the scientific literature, although it is an inaccurate descriptor of the actual effects of these drugs. In the lay press, the term ''psychedelic'' is still the most popular and has held sway for nearly four decades. Most recently, there has been a movement in nonscientific circles to recognize the ability of these substances to provoke mystical experiences and evoke feelings of spiritual significance. Thus, the term ''entheogen'', derived from the Greek word ''entheos'', which means "god within", was introduced by Ruck et al. and has seen increasing use. This term suggests that these substances reveal or allow a connection to the "divine within". Although it seems unlikely that this name will ever be accepted in formal scientific circles, its use has dramatically increased in the popular media and on internet sites. Indeed, in much of the counterculture that uses these substances, entheogen has replaced psychedelic as the name of choice and we may expect to see this trend continue.}}

[[Robin Carhart-Harris]] and [[Guy Goodwin]] write that the term ''psychedelic'' is preferable to ''hallucinogen'' for describing classical psychedelics because of the term ''hallucinogen''{{'}}s "arguably misleading emphasis on these compounds' hallucinogenic properties."<ref name="carhart-harris-goodwin">{{cite journal |last1=Carhart-Harris |first1=Robin |last2=Guy |first2=Goodwin |author-link2=Guy Goodwin |title=The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future |journal=Neuropsychopharmacology |date=2017 |volume=42 |issue=11 |pages=2105–2113 |doi=10.1038/npp.2017.84 |pmid=28443617 |pmc=5603818}}</ref>

While the term ''psychedelic'' is most commonly used to refer only to serotonergic hallucinogens,<ref name="Nichols2016"/><ref name="nichols-2018"/><ref name="divito-leger-2020">{{cite journal |last1=DiVito |first1=Alec J. |last2=Leger |first2=Robert F. |title=Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review |journal=Molecular Biology Reports |date=2020 |volume=47 |issue=12 |pages=9791–9799 |doi=10.1007/s11033-020-06009-x |pmid=33231817|s2cid=227157734 }}</ref><ref name="marks-and-cohen-2021">{{cite journal | vauthors = Marks M, Cohen IG | title = Psychedelic therapy: a roadmap for wider acceptance and utilization | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1669–1671 | date = October 2021 | pmid = 34608331 | doi = 10.1038/s41591-021-01530-3 | s2cid = 238355863 | doi-access = free }}</ref> it is sometimes used for a much broader range of drugs, including [[empathogen–entactogen]]s, [[dissociative]]s, and atypical hallucinogens/psychoactives such as ''[[Amanita muscaria]]'', ''[[Cannabis sativa]]'', ''[[Nymphaea nouchali]]'' and ''[[Salvia divinorum]]''.<ref name="reiff-et-al-2020"/><ref>{{cite journal |last1=Siegel |first1=Ashley N. |last2=Meshkat |first2=Shakila |last3=Benitah |first3=Katie |last4=Lipstiz |first4=Orly |last5=Gill |first5=Hartej |last6=Lui |first6=Leanna M. W. |last7=Teopiz |first7=Kayla M. |last8=McIntyre |first8=Roger S. |last9=Rosenblat |first9=Joshua D. |title=Registered clinical studies investigating psychedelic drugs for psychiatric disorders |journal=Journal of Psychiatric Research |date=2021 |volume=139 |pages=71–81 |doi=10.1016/j.jpsychires.2021.05.019 |pmid=34048997|s2cid=235242044 }}</ref> Thus, the term ''serotonergic psychedelic'' is sometimes used for the narrower class.<ref name="andersen-et-al-2020">{{cite journal |last1=Andersen |first1=Kristoffer A. A. |last2=Carhart-Harris |first2=Robin |last3=Nutt |first3=David J. |last4=Erritzoe |first4=David |title=Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies |journal=Acta Psychiatrica Scandinavica |date=2020 |volume=143 |issue=2 |pages=101–118 |doi=10.1111/acps.13249 |pmid=33125716|s2cid=226217912 }}</ref><ref name="malcolm-thomas-2022">{{cite journal |last1=Malcolm |first1=Benjamin |last2=Thomas |first2=Kelan |title=Serotonin toxicity of serotonergic psychedelics |journal=Psychopharmacology |date=2022 |volume=239 |issue=6 |pages=1881–1891 |doi=10.1007/s00213-021-05876-x |pmid=34251464|s2cid=235796130 }}</ref> It is important to check the definition of a given source.<ref name="nichols-2004"/> This article uses the more common, narrower definition of ''psychedelic''.

==Examples==
[[File:Psychs.png|thumb|From top to bottom: pills containing [[2C-B]], [[4-HO-MET]] set in [[gelatine]], and a strip of [[LSD]] tabs]]
[[File:N,N-DMT Freebase and Vape cartridge.jpg|thumb|[[Free base]] ''N'',''N''-DMT extracted from ''[[Mimosa hostilis]]'' root bark (left); vape cartridge made with freebase ''N'',''N''-DMT extract (right)]]
{{main|List of psychedelic drugs}}

* [[2C-B]] (2,5-dimethoxy-4-bromophenethylamine) is a [[substituted phenethylamine]] first synthesised in 1974 by [[Alexander Shulgin]].<ref name="Shulgin 1991">{{Cite book|last=Shulgin|first=Alexander T.|url=https://www.worldcat.org/oclc/25627628|title=Pihkal : a chemical love story|date=1991|publisher=Transform Press|others=Ann Shulgin|isbn=0-9630096-0-5|location=Berkeley, CA|oclc=25627628}}</ref>{{page needed|date=January 2023}} 2C-B is both a psychedelic and a mild [[Empathogen–entactogen|entactogen]], with its psychedelic effects increasing and its entactogenic effects decreasing with dosage. 2C-B is the most well known compound in the [[2C (psychedelics)|2C family]], their [[2C-H|general structure]] being discovered as a result of modifying the structure of mescaline.<ref name="Shulgin 1991" />{{page needed|date=January 2023}}
* [[N,N-Dimethyltryptamine|DMT]] (''N'',''N''-dimethyltryptamine) is an [[indole alkaloid]] found in various species of plants. Traditionally it is consumed by tribes in South America in the form of [[ayahuasca]]. A brew is used that consists of DMT-containing plants as well as plants containing [[Monoamine oxidase inhibitor|MAOIs]], specifically [[harmaline]], which allows DMT to be consumed orally without being rendered inactive by [[monoamine oxidase]] enzymes in the digestive system.<ref name="Riba 2003">{{Cite journal|last1=Riba|first1=Jordi|last2=Valle|first2=Marta|last3=Urbano|first3=Gloria|last4=Yritia|first4=Mercedes|last5=Morte|first5=Adelaida|last6=Barbanoj|first6=Manel J.|date=July 2003|title=Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics|url=http://jpet.aspetjournals.org/lookup/doi/10.1124/jpet.103.049882|journal=Journal of Pharmacology and Experimental Therapeutics|language=en|volume=306|issue=1|pages=73–83|doi=10.1124/jpet.103.049882|pmid=12660312|s2cid=6147566|issn=0022-3565}}</ref> In the Western world DMT is more commonly consumed via the vaporisation of freebase DMT. Whereas Ayahuasca typically lasts for several hours, inhalation has an onset measured in seconds and has effects measured in minutes, being significantly more intense.<ref>{{Cite journal|last1=Haroz|first1=Rachel|last2=Greenberg|first2=Michael I.|date=November 2005|title=Emerging drugs of abuse|url=https://pubmed.ncbi.nlm.nih.gov/16227062|journal=The Medical Clinics of North America|volume=89|issue=6|pages=1259–1276|doi=10.1016/j.mcna.2005.06.008|issn=0025-7125|pmid=16227062}}</ref> Particularly in vaporised form, DMT has the ability to cause users to enter a hallucinatory realm fully detached from reality, being typically characterised by [[hyperbolic geometry]], and described as defying visual or verbal description.<ref>{{Cite journal|last1=Strassman|first1=Ruck J.|last2=Qualls|first2=Clifford R.|last3=Uhlenhuth|first3=Eberhard H.|last4=Kellner|first4=Robert|date=1994-02-01|title=Dose-Response Study of N,N-Dimethyltryptamine in Humans: II. Subjective Effects and Preliminary Results of a New Rating Scale|url=https://doi.org/10.1001/archpsyc.1994.03950020022002|journal=Archives of General Psychiatry|volume=51|issue=2|pages=98–108|doi=10.1001/archpsyc.1994.03950020022002|pmid=8297217|issn=0003-990X}}</ref> Users have also reported encountering and communicating with entitites within this hallucinatory state.<ref>{{Cite journal|last1=Davis|first1=Alan K|last2=Clifton|first2=John M|last3=Weaver|first3=Eric G|last4=Hurwitz|first4=Ethan S|last5=Johnson|first5=Matthew W|last6=Griffiths|first6=Roland R|date=September 2020|title=Survey of entity encounter experiences occasioned by inhaled N,N -dimethyltryptamine: Phenomenology, interpretation, and enduring effects|journal=Journal of Psychopharmacology|language=en|volume=34|issue=9|pages=1008–1020|doi=10.1177/0269881120916143|pmid=32345112|issn=0269-8811|doi-access=free}}</ref> DMT is the archetypal [[substituted tryptamine]], being the structural scaffold of psilocybin and – to a lesser extent – the lysergamides.
* [[Lysergic acid diethylamide|LSD]] (Lysergic acid diethylamide) is a derivative of [[lysergic acid]], which is obtained from the [[hydrolysis]] of [[ergotamine]]. Ergotamine is an [[alkaloid]] found in the fungus ''[[Claviceps purpurea]]'', which primarily infects rye. LSD is both the prototypical psychedelic and the prototypical [[Lysergamides|lysergamide]]. As a lysergamide, LSD contains both a [[Substituted tryptamine|tryptamine]] and [[Substituted phenethylamine|phenethylamine]] group within its structure. As a result of containing a phenethylamine group LSD [[Agonist|agonises]] dopamine receptors as well as serotonin receptors,<ref>{{Cite journal|date=1975-12-01|title=The dopamine receptor: Differential binding of d-LSD and related agents to agonist and antagonist states|url=https://www.sciencedirect.com/science/article/abs/pii/0024320575901186|journal=Life Sciences|language=en|volume=17|issue=11|pages=1715–1719|doi=10.1016/0024-3205(75)90118-6|issn=0024-3205|last1=Creese|first1=Ian|last2=Burt|first2=David R.|last3=Snyder|first3=Solomon H.|pmid=1207384}}</ref> making it more energetic in effect in contrast to the more sedating effects of psilocin, which is not a dopamine agonist.<ref>{{Cite journal|last1=Passie|first1=Torsten|last2=Seifert|first2=Juergen|last3=Schneider|first3=Udo|last4=Emrich|first4=Hinderk M.|date=October 2002|title=The pharmacology of psilocybin|url=http://doi.wiley.com/10.1080/1355621021000005937|journal=Addiction Biology|language=en|volume=7|issue=4|pages=357–364|doi=10.1080/1355621021000005937|pmid=14578010|s2cid=12656091}}</ref>
* [[Mescaline]] (3,4,5-trimethoxyphenethylamine) is a [[Substituted phenethylamine|phenethylamine]] alkaloid found in various species of cacti, the best-known of these being [[peyote]] (''Lophophora williamsii'') and the San Pedro cactus ([[Trichocereus macrogonus var. pachanoi|''Trichocereus macrogonus'' var. ''pachanoi'']], syn. ''[[Echinopsis pachanoi]]''). Mescaline has effects comparable to those of LSD and psilocybin, albeit with a greater emphasis on colors and patterns.<ref>{{Cite book|last=Freye|first=E.|url=https://www.worldcat.org/oclc/489218895|title=Pharmacology and abuse of cocaine, amphetamines, ecstasy and related designer drugs : a comprehensive review on their mode of action, treatment of abuse and intoxication|date=2009|publisher=Springer|isbn=978-90-481-2448-0|location=Dordrecht|oclc=489218895}}</ref>{{page needed|date=January 2023}} Ceremonial San Pedro use seems to be characterized by relatively strong spiritual experiences, and low incidence of challenging experiences.<ref>{{Cite journal |last1=Bohn |first1=Arne |last2=Kiggen |first2=Michiel H. H. |last3=Uthaug |first3=Malin V. |last4=van Oorsouw |first4=Kim I. M. |last5=Ramaekers |first5=Johannes G. |last6=van Schie |first6=Hein T. |date=2022-12-05 |title=Altered States of Consciousness During Ceremonial San Pedro Use |url=https://www.tandfonline.com/doi/full/10.1080/10508619.2022.2139502 |journal=The International Journal for the Psychology of Religion |language=en |volume=33 |issue=4 |pages=309–331 |doi=10.1080/10508619.2022.2139502 |issn=1050-8619|hdl=2066/285968 |hdl-access=free }}</ref>
* [[Psilocin]] (4-HO-[[N,N-Dimethyltryptamine|DMT]]) is the [[Dephosphorylation|dephosphorylated]] [[active metabolite]] of the [[indole alkaloid]] [[psilocybin]] and a [[substituted tryptamine]], which is produced in [[Psilocybin mushroom|over 200 species of fungi]]. Of the Classical psychedelics psilocybin has attracted the greatest academic interest regarding its ability to manifest mystical experiences,<ref>{{Cite journal|last1=Griffiths|first1=R. R.|last2=Richards|first2=W. A.|last3=McCann|first3=U.|last4=Jesse|first4=R.|date=August 2006|title=Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance|url=http://link.springer.com/10.1007/s00213-006-0457-5|journal=Psychopharmacology|language=en|volume=187|issue=3|pages=268–283|doi=10.1007/s00213-006-0457-5|pmid=16826400|s2cid=7845214|issn=0033-3158}}</ref> although all psychedelics are capable of doing so to variable degrees. [[O-Acetylpsilocin|''O''-Acetylpsilocin]] (4-AcO-DMT) is an acetylated analog of psilocin. Additionally, replacement of a methyl group at the dimethylated [[nitrogen]] with an isopropyl or ethyl group yields [[4-HO-MIPT]] and [[4-HO-MET]], respectively.<ref name="Psychedelic Science Review 2020">{{Cite web |date=2020-01-06 |title=4-HO-MiPT |url=https://psychedelicreview.com/compound/4-ho-mipt/ |access-date=2022-07-06 |website=Psychedelic Science Review |language=en-US}}</ref>

== Uses ==
=== Traditional ===
[[File:Ayahuasca prep.JPG|thumb|upright=1.15|Preparation of [[Ayahuasca]], province of [[Pastaza Province|Pastaza]], Ecuador]]
[[File:Psilocybe Mushrooms statues.jpg|thumb|upright=1.15 |Religious statues involving Psilocybe Mushrooms]]
[[File:Echinopsis pachanoi en Huaraz.jpg|thumb|upright=1.15 |''Echinopsis pachanoi'' in Peru]]
A number of frequently mentioned or traditional psychedelics such as ''[[Ayahuasca]]'' (which contains [[N,N-Dimethyltryptamine|DMT]]), [[Trichocereus macrogonus|San Pedro]], [[Peyote]], and [[Echinopsis peruviana|Peruvian torch]] (which all contain [[mescaline]]), [[Psilocybe mushrooms]] (which contain [[psilocin]]/[[psilocybin]]) and ''[[Tabernanthe iboga]]'' (which contains the unique psychedelic [[ibogaine]]) all have a long and extensive history of [[Spirituality|spiritual]], [[shamanic]] and traditional usage by [[indigenous peoples]] in various world regions, particularly in Latin America, but also [[Gabon]], Africa in the case of iboga.<ref>{{cite book |last1=Carlini |first1=E. A. |last2=Maia |first2=Lucas O. |title=Plant Toxins |chapter=Plant and Fungal Hallucinogens as Toxic and Therapeutic Agents |series=Toxinology |date=2020 |pages=1–44 |doi=10.1007/978-94-007-6728-7_6-2 |chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-94-007-6728-7_6-2 |access-date=23 February 2022 |publisher=Springer Netherlands |isbn=978-94-007-6728-7 |s2cid=239438352 |language=en}}</ref> Different countries and/or regions have come to be associated with traditional or spiritual use of particular psychedelics, such as the ancient and entheogenic use of psilocybe mushrooms by the native [[Mazatec]] people of [[Oaxaca]], Mexico<ref>{{cite web |title=History of Psychedelics: How the Mazatec Tribe Brought Entheogens to the World |url=https://psychedelictimes.com/history-of-psychedelics-how-the-mazatec-tribe-brought-entheogens-to-the-world/ |website=Psychedelic Times |access-date=23 February 2022 |date=28 October 2015}}</ref> or the use of the ayahuasca brew in the [[Amazon basin]], particularly in Peru for spiritual and physical healing as well as for religious festivals.<ref>{{Cite book|last=Ismael Eduardo Apud Peláez. |url=https://www.worldcat.org/oclc/1229544084|title=Ayahuasca: Between Cognition and Culture|date=2020|publisher=Publicacions Universitat Rovira i Virgili|isbn=978-84-8424-834-7|oclc=1229544084}}</ref> Peyote has also been used for several thousand years in the [[Rio Grande Valley]] in North America by native tribes as an [[entheogen]].<ref>{{cite journal |last1=Prince |first1=Mark A. |last2=O'Donnell |first2=Maeve B. |last3=Stanley |first3=Linda R. |last4=Swaim |first4=Randall C. |title=Examination of Recreational and Spiritual Peyote Use Among American Indian Youth |journal=Journal of Studies on Alcohol and Drugs |date=May 2019 |volume=80 |issue=3 |pages=366–370 |doi=10.15288/jsad.2019.80.366 |pmid=31250802 |pmc=6614926 }}</ref> In the [[Andes|Andean]] region of South America, the San Pedro cactus ([[Trichocereus macrogonus var. pachanoi|''Trichocereus macrogonus'' var. ''pachanoi'']], syn. ''[[Echinopsis pachanoi]]'') has a long history of use, possibly as a [[traditional medicine]]. Archaeological studies have found evidence of use going back two thousand years, to [[Moche (culture)|Moche]] culture,<ref>{{cite journal |vauthors=Bussmann RW, Sharon D |title=Traditional medicinal plant use in Northern Peru: tracking two thousand years of healing culture |journal=J Ethnobiol Ethnomed |volume=2 |issue=1 |page=47 |year=2006 |pmid=17090303 |pmc=1637095 |doi=10.1186/1746-4269-2-47 |doi-access=free }}
</ref> [[Nazca culture]],<ref>{{Cite journal |last1=Socha |first1=Dagmara M. |last2=Sykutera |first2=Marzena |last3=Orefici |first3=Giuseppe |date=2022-12-01 |title=Use of psychoactive and stimulant plants on the south coast of Peru from the Early Intermediate to Late Intermediate Period |journal=Journal of Archaeological Science |language=en |volume=148 |pages=105688 |doi=10.1016/j.jas.2022.105688 |s2cid=252954052 |issn=0305-4403|doi-access=free |bibcode=2022JArSc.148j5688S }}</ref> and [[Chavín culture]]. Although authorities of the [[Catholic Church|Roman Catholic]] church attempted to suppress its use after the Spanish conquest,<ref>{{cite book |last1=Larco |first1=Laura |title=Más allá de los encantos – Documentos sobre extirpación de idolatrías, Trujillo |chapter=Archivo Arquidiocesano de Trujillo Sección Idolatrías. (Años 1768–1771) |series=Travaux de l'IFEA |date=2008 |publisher=IFEA Instituto Francés de Estudios Andinos, Fondo Editorial de la Universidad Nacional Mayor de San Marcos |location=Lima |pages=67–87 |isbn=978-2-8218-4453-7 |url=https://books.openedition.org/ifea/4938 |access-date=April 9, 2020}}</ref> this failed, as shown by the Christian element in the common name "San Pedro cactus" – [[Saint Peter]] cactus. The name has its origin in the belief that just as St Peter holds the keys to heaven, the effects of the cactus allow users "to reach heaven while still on earth."<ref>{{Cite book |last=Anderson |first=Edward F. |year=2001 |title=The Cactus Family |location=Pentland, Oregon |publisher=Timber Press |isbn=978-0-88192-498-5 }} pp. 45–49.</ref> In 2022, the Peruvian Ministry of Culture declared the traditional use of San Pedro cactus in northern Peru as [[cultural heritage]].<ref>{{Cite web |date=2022-11-17 |title=Declaran Patrimonio Cultural de la Nación a los conocimientos, saberes y usos del cactus San Pedro |url=https://elperuano.pe/noticia/197142-declaran-patrimonio-cultural-de-la-nacion-a-los-conocimientos-saberes-y-usos-del-cactus-san-pedro |access-date=2022-12-10 |website=elperuano.pe |language=es}}</ref>

Although people of [[Western culture]] have tended to use psychedelics for either [[psychotherapeutic]] or [[Recreational drug use|recreational]] reasons, most indigenous cultures, particularly in South America, have seemingly tended to use psychedelics for more [[supernatural]] reasons such as [[divination]]. This can often be related to "healing" or health as well but typically in the context of finding out what is wrong with the individual, such as using psychedelic states to "identify" a disease and/or its cause, locate lost objects, and identify a victim or even perpetrator of [[Magic (supernatural)|sorcery]].<ref name="vice_4adngq">{{cite news |title= Psychedelics Weren't As Common in Ancient Cultures As We Think|url = https://www.vice.com/en/article/4adngq/psychedelic-drug-use-in-ancient-indigenous-cultures |access-date=January 14, 2023 |work= Vice Media |publisher=Vice |date=December 10, 2020}}</ref> In some cultures and regions, even psychedelics themselves, such as ayahuasca and the psychedelic [[lichen]] of eastern Ecuador (''[[Dictyonema huaorani]]'') that supposedly contains both [[5-MeO-DMT]] and psilocybin, have also been used by witches and sorcerers to conduct their [[Maleficium (sorcery)|malicious magic]], similarly to [[nightshade]] [[deliriants]] like ''[[brugmansia]]'' and ''[[latua]]''.<ref name="vice_4adngq"/>{{citation needed|date=January 2023}}

=== Psychedelic therapy ===
{{main|Psychedelic therapy}}
Psychedelic therapy (or psychedelic-assisted therapy) is the proposed use of psychedelic drugs to treat [[mental disorder]]s.<ref>{{Cite journal |last1=Nutt |first1=David |last2=Spriggs |first2=Meg |last3=Erritzoe |first3=David |date=2023-02-01 |title=Psychedelics therapeutics: What we know, what we think, and what we need to research |journal=Neuropharmacology |volume=223 |pages=109257 |doi=10.1016/j.neuropharm.2022.109257 |issn=0028-3908|doi-access=free |pmid=36179919 }}</ref> As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions.<ref name="marks-and-cohen-2021"/><ref name="pilecki-et-al-2021">{{cite journal |last1=Pilecki |first1=Brian |last2=Luoma |first2=Jason B. |last3=Bathje |first3=Geoff J. |last4=Rhea |first4=Joseph |last5=Narloch |first5=Vilmarie Fraguada |title=Ethical and legal issues in psychedelic harm reduction and integration therapy |journal=Harm Reduction Journal |date=2021 |volume=18 |issue=1 |pages=40 |doi=10.1186/s12954-021-00489-1 |pmid=33827588 |pmc=8028769 |doi-access=free }}</ref>

The procedure for psychedelic therapy differs from that of therapies using conventional [[psychiatric medication]]s. While conventional medications are usually taken without supervision at least once daily, in contemporary psychedelic therapy the drug is administered in a single session (or sometimes up to three sessions) in a therapeutic context.<ref name="nutt-et-al-2020">{{cite journal |last1=Nutt |first1=David |last2=Erritzoe |first2=David |last3=Carhart-Harris |first3=Robin |title=Psychedelic Psychiatry's Brave New World |journal=Cell |date=2020 |volume=181 |issue=1 |pages=24–28 |doi=10.1016/j.cell.2020.03.020 |pmid=32243793|s2cid=214753833 |doi-access=free }}</ref> The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards.<ref name="johnson-et-al-2008">{{cite journal |last1=Johnson |first1=M. W. |last2=Richards |first2=W. A. |last3=Griffiths |first3=R. R. |title=Human hallucinogen research: guidelines for safety |journal=Journal of Psychopharmacology |date=2008 |volume=22 |issue=6 |pages=603–620 |doi=10.1177/0269881108093587 |pmid=18593734 |pmc=3056407}}</ref><ref name="garcia-romeu-richards-2018">{{cite journal |last1=Garcia-Romeu |first1=Albert |last2=Richards |first2=William A. |title=Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions |journal=International Review of Psychiatry |date=2018 |volume=30 |issue=4 |pages=291–316 |doi=10.1080/09540261.2018.1486289 |pmid=30422079 |s2cid=53291327 |issn=0954-0261}}</ref> After ingesting the drug, the patient normally wears eyeshades and listens to music to facilitate focus on the psychedelic experience, with the therapeutic team interrupting only to provide reassurance if adverse effects such as anxiety or disorientation arise.<ref name="johnson-et-al-2008"/><ref name="garcia-romeu-richards-2018"/>

As of 2022, the body of high-quality evidence on psychedelic therapy remains relatively small and more, larger studies are needed to reliably show the effectiveness and safety of psychedelic therapy's various forms and applications.<ref name="bender-hellerstein-2022" /><ref name="reiff-et-al-2020" /> On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including [[major depressive disorder]],<ref name="bender-hellerstein-2022" /><ref name="romeo-et-al-2020">{{cite journal |last1=Romeo |first1=Bruno |last2=Karila |first2=Laurent |last3=Martelli |first3=Catherine |last4=Benyamina |first4=Amine |title=Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis |journal=Journal of Psychopharmacology |date=2020 |volume=34 |issue=10 |pages=1079–1085 |doi=10.1177/0269881120919957 |pmid=32448048|s2cid=218873949 }}</ref> and [[anxiety]] and depression linked to [[terminal illness]].<ref name="bender-hellerstein-2022" /><ref name="schimmel-et-al-2022">{{cite journal |last1=Schimmel |first1=Nina |last2=Breeksema |first2=Joost J. |last3=Smith-Apeldoorn |first3=Sanne Y. |last4=Veraart |first4=Jolien |last5=van den Brink |first5=Wim |last6=Schoevers |first6=Robert A. |title=Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review |journal=Psychopharmacology |date=2022 |volume=239 |issue=15–33 |pages=15–33 |doi=10.1007/s00213-021-06027-y |pmid=34812901|s2cid=244490236 |url=https://research.rug.nl/en/publications/d86d811c-a066-4d34-bc83-df904e91a765 }}</ref> The United States [[Food and Drug Administration]] has granted "breakthrough therapy" status, which expedites the assessment of promising drug therapies for potential approval,{{refn|The Food and Drug Administration describes the designation of breakthrough therapy as "a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s)."<ref name="fda-breakthrough">{{cite web |title=Breakthrough Therapy |url=https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy |publisher=United States Food and Drug Administration |access-date=27 March 2022 |archive-url=https://web.archive.org/web/20220301164346/https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy |archive-date=1 March 2022 |date=1 April 2018}}</ref>|group=note}} to psilocybin therapy for treatment-resistant depression and major depressive disorder.<ref name="marks-and-cohen-2021" />

===Recreational===
{{further|Recreational drug use#Hallucinogens}}
Recreational use of psychedelics has been common since the [[psychedelic era]] of the mid-1960s and continues to play a role in various festivals and events, including [[Burning Man]].<ref name="30-million"/><ref name="garcia-et-al"/> A survey published in 2013 found that 13.4% of American adults had used a psychedelic.<ref>{{cite journal|title=Psychedelics and Mental Health: A Population Study|journal=PLOS ONE|date=August 19, 2013|pmc=3747247|pmid=23976938|pages=e63972|volume=8|issue=8|doi=10.1371/journal.pone.0063972|author=Krebs, Teri S.|author2=Johansen, Pål-Ørjan|bibcode=2013PLoSO...863972K|doi-access=free}}</ref>

A June 2024 report by the [[RAND Corporation]] suggests psilocybin mushrooms may be the most prevalent psychedelic drug among adults in the United States. The RAND national survey indicated that 3.1% of U.S. adults reported using psilocybin in the past year. Roughly 12% of respondents acknowledged lifetime use of psilocybin, while a similar percentage reported having used [[LSD]] at some point in their lives. [[MDMA]], also known as ecstasy, showed a lower prevalence of use at 7.6%. Notably, less than 1% of U.S. adults reported using any psychedelic drugs within the past month.<ref>{{cite news |last=Goldman |first=Maya |url=https://www.axios.com/2024/06/27/psychedelics-mushrooms-rand |title=Mushrooms are the most commonly used psychedelic, study finds |work=[[Axios (website)|Axios]] |publisher= |date=2024-06-27 |accessdate=2024-06-28 }}</ref>

===Microdosing===
{{main|Psychedelic microdosing}}
Psychedelic microdosing is the practice of using sub-threshold doses ([[microdose]]s) of psychedelics in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction.<ref>{{Cite journal |last=Fadiman |first=James |date=2016-01-01 |title= Microdose research: without approvals, control groups, double blinds, staff or funding |url= https://www.researchgate.net/publication/308138461 |journal=Psychedelic Press |volume=XV }}</ref><ref>{{cite web | first = Erin | last = Brodwin | date = 30 January 2017 | url = http://www.businessinsider.com/microdosing-lsd-effects-risks-2017-1 | title = The truth about 'microdosing,' which involves taking tiny amounts of psychedelics like LSD | work = Business Insider | access-date = 19 April 2017 }}</ref> The practice of microdosing has become more widespread in the 21st century with more people claiming long-term benefits from the practice.<ref>{{cite web | first = Henrik | last = Dahl | url = http://psypressuk.com/2015/07/07/a-brief-history-of-lsd-in-the-twenty-first-century/ | title = A Brief History of LSD in the Twenty-First Century | work = Psychedelic Press UK | date = 7 July 2015 | access-date = 19 April 2017 }}</ref><ref name="Webb_2019">{{cite journal | vauthors = Webb M, Copes H, Hendricks PS | title = Narrative identity, rationality, and microdosing classic psychedelics | journal = The International Journal on Drug Policy | volume = 70 | pages = 33–39 | date = August 2019 | pmid = 31071597 | doi = 10.1016/j.drugpo.2019.04.013 | s2cid = 149445841 }}</ref>

A 2022 study recognized signatures of psilocybin microdosing in [[natural language]] and concluded that low amount of psychedelics have potential for application, and ecological observation of microdosing schedules.<ref>{{Cite web |last1=Chemistry |first1=University of |last2=Prague |first2=Technology |title=Recognizing signatures of psilocybin microdosing in natural language |url=https://medicalxpress.com/news/2022-09-signatures-psilocybin-microdosing-natural-language.html |access-date=2022-10-03 |website=medicalxpress.com |language=en}}</ref><ref>{{Cite journal |last1=Sanz |first1=Camila |last2=Cavanna |first2=Federico |last3=Muller |first3=Stephanie |last4=de la Fuente |first4=Laura |last5=Zamberlan |first5=Federico |last6=Palmucci |first6=Matías |last7=Janeckova |first7=Lucie |last8=Kuchar |first8=Martin |last9=Carrillo |first9=Facundo |last10=García |first10=Adolfo M. |last11=Pallavicini |first11=Carla |last12=Tagliazucchi |first12=Enzo |date=2022-09-01 |title=Natural language signatures of psilocybin microdosing |url=https://doi.org/10.1007/s00213-022-06170-0 |journal=Psychopharmacology |language=en |volume=239 |issue=9 |pages=2841–2852 |doi=10.1007/s00213-022-06170-0 |pmid=35676541 |s2cid=247067976 |issn=1432-2072}}</ref>

==Pharmacology==
{{See also|Serotonin#Psychedelics}}

While the method of action of psychedelics is not fully understood, they are known to show affinities for various 5-HT (serotonin) receptors in different ways and levels, and may be classified by their activity at different 5-HT sub-types, particularly 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>2C</sub>.<ref name="nichols-2004"/> It is almost unanimously agreed that psychedelics produce their effect by acting as strong partial [[agonist]]s at the 5-HT<sub>2A</sub> receptors.<ref name="Aghajanian, G 16S–23S"/><ref name="psychedelicreview.com"/><ref name="nichols-2018"/><ref name="Nichols2016"/> How this produces the psychedelic experience is unclear, but it is likely that it acts by increasing excitation in the cortex, possibly by specifically facilitating input from the [[thalamus]], the major relay for sensory information input to the [[Cerebral cortex|cortex]].<ref name="nichols-2004"/><ref>{{Cite news |last=Dolan |first=Eric W. |date=2023-06-02 |title=Neuroscience research sheds light on how LSD alters the brain's "gatekeeper" |url=https://www.psypost.org/2023/06/neuroscience-research-sheds-light-on-how-lsd-alters-the-brains-gatekeeper-163939 |access-date=2023-06-02 |newspaper=Psypost - Psychology News |language=en-US}}</ref> Additionally, researchers discovered that many psychedelics are potent [[psychoplastogen]]s, compounds capable of promoting rapid and sustained [[neural plasticity]].<ref name="Ly2018">{{cite journal |title=Psychedelics promote structural and functional neural plasticity |journal=Cell Reports |vauthors=Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE |year=2018 |volume=23 |issue=11 |pages=3170–3182 |doi=10.1016/j.celrep.2018.05.022 |pmid=29898390 |pmc=6082376 }}</ref><ref>{{Cite journal |last1=Vargas |first1=Maxemiliano V. |last2=Dunlap |first2=Lee E. |last3=Dong |first3=Chunyang |last4=Carter |first4=Samuel J. |last5=Tombari |first5=Robert J. |last6=Jami |first6=Shekib A. |last7=Cameron |first7=Lindsay P. |last8=Patel |first8=Seona D. |last9=Hennessey |first9=Joseph J. |last10=Saeger |first10=Hannah N. |last11=McCorvy |first11=John D. |last12=Gray |first12=John A. |last13=Tian |first13=Lin |last14=Olson |first14=David E. |date=2023-02-17 |title=Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors |journal=Science |language=en |volume=379 |issue=6633 |pages=700–706 |doi=10.1126/science.adf0435 |pmid=36795823 |pmc=10108900 |bibcode=2023Sci...379..700V |issn=0036-8075 }}</ref>

===Tryptamines===
[[File:DMT.svg|thumb|[[N,N-Dimethyltryptamine|''N'',''N''-DMT]]]]
[[Tryptamine]], along with other [[trace amine]]s, is found in the [[central nervous system]] of [[mammal]]s. It is hypothesized to play a role as a [[neuromodulator]] on classical [[monoamine neurotransmitter]]s, such as [[dopamine]], serotonin, [[norepinephrine]] and [[Adrenaline|epinephrine]]. Tryptamine acts as a non-selective [[serotonin receptor agonist]] to activate serotonin receptors, and a [[serotonin–norepinephrine–dopamine releasing agent]] (SNDRA) to release more monoamine neurotransmitter, with a preference for evoking serotonin and dopamine [[Neurotransmitter release|release]] over norepinephrine (epinephrine) release.<ref>{{Cite journal|last1=Wölfel |first1=Reinhard|last2=Graefe|first2=Karl-Heinz|date=February 1992|title=Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter|journal=Naunyn-Schmiedeberg's Archives of Pharmacology|language=en|volume=345|issue=2|pages=129–136|doi=10.1007/BF00165727|pmid=1570019|s2cid=2984583|issn=0028-1298}}</ref><ref>{{Cite journal|last1=Shimazu|first1=Seiichiro|last2=Miklya|first2=Ildikó|date=May 2004|title=Pharmacological studies with endogenous enhancer substances: β-phenylethylamine, tryptamine, and their synthetic derivatives|journal=Progress in Neuro-Psychopharmacology and Biological Psychiatry|language=en|volume=28|issue=3|pages=421–427|doi=10.1016/j.pnpbp.2003.11.016|pmid=15093948|s2cid=37564231}}</ref><ref>{{Cite journal|last1=Blough|first1=Bruce E.|last2=Landavazo|first2=Antonio|last3=Partilla|first3=John S.|last4=Baumann|first4=Michael H.|last5=Decker|first5=Ann M.|last6=Page|first6=Kevin M.|last7=Rothman|first7=Richard B.|date=2014-06-12|title=Hybrid Dopamine Uptake Blocker–Serotonin Releaser Ligands: A New Twist on Transporter-Focused Therapeutics|journal=ACS Medicinal Chemistry Letters|language=en|volume=5|issue=6|pages=623–627|doi=10.1021/ml500113s|issn=1948-5875|pmc=4060932|pmid=24944732}}</ref> Psychedelic tryptamines found in nature include psilocin, [[Dimethyltryptamine|DMT]], 5-MeO-DMT, and tryptamines that have been synthesized in the laboratory include [[4-HO-MET]],<ref>{{Cite web |title=4-HO-MET |url=https://thedrugclassroom.com/video/4-ho-met/ |access-date=2022-07-31 |website=The Drug Classroom |language=en-US}}</ref> [[4-HO-MiPT]],<ref name="Psychedelic Science Review 2020" /> and [[5-MeO-DALT]].<ref>{{Cite book|last=Shulgin, Alexander T. (Alexander Theodore)|url=https://www.worldcat.org/oclc/38503252|title=Tihkal : the continuation|date=1997|publisher=Transform Press|others=Shulgin, Ann.|isbn=0-9630096-9-9|edition=1st|location=Berkeley, CA|pages=|oclc=38503252}}</ref>

[[File:Mescaline Structural Formula.svg|thumb|Mescaline]]

===Phenethylamines===
[[Phenethylamine]] is also a trace amine but to a lesser extent acts as a [[neurotransmitter]] in the human central nervous system (CNS). Phenethylamine instead regulates monoamine neurotransmission by binding to [[trace amine-associated receptor 1]] (TAAR1), which plays a significant role in regulating [[neurotransmission]] in dopamine, norepinephrine, and serotonin [[neuron]]s in the CNS and inhibiting [[vesicular monoamine transporter 2]] (VMAT2) in monoamine neurons.<ref>{{Cite journal|last=Miller|first=Gregory M.|date=2010-12-16|title=The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity|journal=Journal of Neurochemistry|volume=116|issue=2|pages=164–176|doi=10.1111/j.1471-4159.2010.07109.x|pmid=21073468|pmc=3005101|issn=0022-3042}}</ref><ref>{{Cite journal|last=Grandy|first=Gina|date=2020-04-23|title=Guest editorial|journal=Gender in Management|language=en|volume=35|issue=3|pages=257–260|doi=10.1108/GM-05-2020-238|issn=1754-2413|doi-access=free}}</ref> When VMAT2 is inhibited monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms.<ref>{{Cite journal|last1=Little|first1=Karley Y.|last2=Krolewski|first2=David M.|last3=Zhang|first3=Lian|last4=Cassin|first4=Bader J.|date=January 2003|title=Loss of Striatal Vesicular Monoamine Transporter Protein (VMAT2) in Human Cocaine Users|journal=American Journal of Psychiatry|language=en|volume=160|issue=1|pages=47–55|doi=10.1176/appi.ajp.160.1.47|pmid=12505801|issn=0002-953X}}</ref> Mescaline is a naturally occurring psychedelic [[Alkaloid|protoalkaloid]] of the [[substituted phenethylamine]] class.

===Lysergamides===
[[File:Lysergsäurediethylamid (LSD).svg|thumb|Lysergic acid diethylamide (LSD)]]
[[Amide]]s of [[lysergic acid]] are collectively known as [[lysergamides]], and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine [[Receptor (biochemistry)|receptors]]. The structure of lysergamides contains the structure of both tryptamines and phenethylamines. [[LSD]] (Lysergic Acid Diethylamide) is one of many lysergamides. A wide range of lysergamides have emerged in recent years, inspired by existing scientific literature. Others, have appeared from chemical research.<ref>{{Cite journal |last1=Brandt |first1=Simon D. |last2=Kavanagh |first2=Pierce V. |last3=Westphal |first3=Folker |last4=Stratford |first4=Alexander |last5=Odland |first5=Anna U. |last6=Klein |first6=Adam K. |last7=Dowling |first7=Geraldine |last8=Dempster |first8=Nicola M. |last9=Wallach |first9=Jason |last10=Passie |first10=Torsten |last11=Halberstadt |first11=Adam L. |date=2020-04-20 |title=Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1-cyclopropanoyl- d -lysergic acid diethylamide (1CP-LSD) |journal=Drug Testing and Analysis |volume=12 |issue=6 |language=en |pages=812–826 |issn=1942-7603 |doi=10.1002/dta.2789 |pmid=32180350 |pmc=9191646 |s2cid=212738912 |url=https://researchonline.ljmu.ac.uk/id/eprint/12478/1/DTA-20-0053.R1_accepted_uncorrected.pdf}}</ref> [[1P-LSD]] is a [[Derivative (chemistry)|derivative]] and [[Functional analog (chemistry)|functional analogue]] of LSD and a [[Homologous series|homologue]] of [[ALD-52]]. It modifies the LSD molecule by adding a [[Propionic acid|propionyl group]] to the nitrogen atom of LSD's [[Indole ring|indole]].<ref>{{Cite journal |last1=Grumann |first1=Christina |last2=Henkel |first2=Kerstin |last3=Brandt |first3=Simon D. |last4=Stratford |first4=Alexander |last5=Passie |first5=Torsten |last6=Auwärter |first6=Volker |date=2020 |title=Pharmacokinetics and subjective effects of 1P-LSD in humans after oral and intravenous administration |journal=Drug Testing and Analysis |language=en |volume=12 |issue=8 |pages=1144–1153 |doi=10.1002/dta.2821 |pmid=32415750 |issn=1942-7611 |doi-access=free}}</ref>

==Psychedelic experiences==
{{main|Psychedelic experience}}
Although several attempts have been made, starting in the 19th and 20th centuries, to define common [[Phenomenology (psychology)|phenomenological]] structures of the effects produced by classic psychedelics, a universally accepted taxonomy does not yet exist.<ref>{{Cite book|last1=Preller|first1=Katrin H.|title=Behavioral Neurobiology of Psychedelic Drugs|last2=Vollenweider|first2=Franz X. |date=2016|publisher=Springer Berlin Heidelberg|isbn=978-3-662-55878-2|editor1=Adam L. Halberstadt |editor2=Franz X. Vollenweider |editor3=David E. Nichols |volume=36|location=Berlin, Heidelberg|pages=221–256|chapter=Phenomenology, Structure, and Dynamic of Psychedelic States |series=Current Topics in Behavioral Neurosciences|doi=10.1007/7854_2016_459|pmid=28025814}}</ref><ref name="swanson">{{Cite journal |last=Swanson|first=Link R.|date=2018-03-02|title=Unifying Theories of Psychedelic Drug Effects|journal=Frontiers in Pharmacology |volume=9 |pages=172|doi=10.3389/fphar.2018.00172|pmid=29568270|pmc=5853825|issn=1663-9812|doi-access=free}}</ref> At lower doses, features of psychedelic experiences include sensory alterations, such as the warping of surfaces, shape suggestibility, pareidolia and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes or [[form constants]] are common as well. Higher doses often cause intense and fundamental alterations of sensory (notably [[Visual perception|visual]]) perception, such as [[synesthesia]] or the experience of additional spatial or temporal dimensions.<ref>{{cite journal|author1=Luke, David|title=Rock Art or Rorschach: Is there More to Entoptics than Meets the Eye?|journal=Time and Mind|date=28 November 2013|volume=3|issue=1|pages=9–28 |doi=10.2752/175169710x12549020810371|s2cid=144948636}}</ref> Tryptamines are well documented to cause classic psychedelic states, such as increased [[empathy]], visual distortions (drifting, morphing, breathing, melting of various surfaces and objects), auditory hallucinations, ego dissolution or [[ego death]] with high enough dose, mystical, [[transpersonal]] and spiritual experiences, autonomous "[[entity]]" encounters, time distortion, [[closed eye hallucination]]s and complete detachment from reality with a high enough dose.<ref>{{Cite journal |last=Berry |first=Mark D.|date=July 2004|title=Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators |journal=Journal of Neurochemistry|volume=90|issue=2|pages=257–271|doi=10.1111/j.1471-4159.2004.02501.x |pmid=15228583 |s2cid=12126296 |issn=0022-3042|doi-access=free}}</ref> [[Luis Eduardo Luna|Luis Luna]] describes psychedelic experiences as having a distinctly [[gnosis]]-like quality, and says that they offer "learning experiences that elevate consciousness and can make a profound contribution to [[personal development]]."<ref name="luna-peru">{{cite journal |last1=Luna |first1=Luis Eduardo |title=The concept of plants as teachers among four mestizo shamans of Iquitos, northeastern Peru |journal=Journal of Ethnopharmacology |date=1984 |volume=11 |issue=2 |pages=135–156 |doi=10.1016/0378-8741(84)90036-9 |pmid=6492831 |url=http://home.iscte-iul.pt/~fgvs/Luna_plants.pdf |access-date=10 July 2020}}</ref> Czech psychiatrist [[Stanislav Grof]] studied the effects of psychedelics like LSD early in his career and said of the experience, that it commonly includes "complex [[Revelation|revelatory]] [[Epiphany (feeling)|insights]] into the nature of existence… typically accompanied by a sense of certainty that this knowledge is ultimately more relevant and 'real' than the perceptions and beliefs we share in everyday life."{{citation needed|date=January 2023}} Traditionally, the standard model for the [[Subjective experience|subjective]] phenomenological effects of psychedelics has typically been based on LSD, with anything that is considered "psychedelic" evidently being compared to it and [[Lysergic acid diethylamide#Effects|its specific effects]].<ref>{{cite journal |last1=Nichols |first1=David E. |title=Psychedelics |journal=Pharmacological Reviews |date=April 2016 |volume=68 |issue=2 |pages=264–355 |doi=10.1124/pr.115.011478|pmid=26841800 |pmc=4813425 }}</ref>

During a speech on his 100th birthday, the inventor of LSD, [[Albert Hofmann]] said of the drug: "It gave me an inner joy, an [[Open-mindedness|open mindedness]], a gratefulness, open eyes and an internal sensitivity for the miracles of creation... I think that in human evolution it has never been as necessary to have this substance LSD. It is just a tool to turn us into what we are supposed to be."<ref>{{cite magazine |url=https://www.wired.com/science/discoveries/news/2006/01/70015?currentPage=2 |title=LSD: The Geek's Wonder Drug? |magazine=Wired |date=16 January 2006 |access-date=29 April 2008}}</ref> With certain psychedelics and experiences, a user may also experience an "[[afterglow (drug culture)|afterglow]]" of improved mood or perceived mental state for days or even weeks after ingestion in some cases.<ref>{{cite journal | vauthors = Majić T, Schmidt TT, Gallinat J | title = Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences? | journal = Journal of Psychopharmacology | volume = 29 | issue = 3 | pages = 241–53 | date = March 2015 | pmid = 25670401 | doi = 10.1177/0269881114568040 | s2cid = 16483172 }}</ref><ref>{{Cite journal |last=Evens |first=Ricarda |last2=Schmidt |first2=Marianna Elisa |last3=Majić |first3=Tomislav |last4=Schmidt |first4=Timo Torsten |date=2023-05-29 |title=The psychedelic afterglow phenomenon: a systematic review of subacute effects of classic serotonergic psychedelics |journal=Therapeutic Advances in Psychopharmacology |volume=13 |pages=20451253231172254 |doi=10.1177/20451253231172254 |issn=2045-1253 |pmid=37284524 |pmc=10240558}}</ref> In 1898, the English writer and intellectual [[Havelock Ellis]] reported a heightened perceptual sensitivity to "the more delicate phenomena of light and shade and color" for a prolonged period of time after his exposure to mescaline.<ref>{{cite news |last1=Hanson |first1=Dirk |title=When the Trip Never Ends |url=https://dana.org/article/when-the-trip-never-ends/ |work=Dana Foundation |date=29 April 2013 }}</ref> Good trips are reportedly deeply pleasurable, and typically involve intense joy or euphoria, a greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe.<ref name="erowid-faq">{{cite web | vauthors = Honig D | url = http://www.erowid.org/chemicals/lsd/lsd_faq.shtml | title = Frequently Asked Questions | archive-url = https://web.archive.org/web/20160212232436/https://www.erowid.org/chemicals/lsd/lsd_faq.shtml | archive-date = 12 February 2016 | work = [[Erowid]] }}</ref><ref name="PMID6054248">{{cite journal | vauthors = McGlothlin W, Cohen S, McGlothlin MS | title = Long lasting effects of LSD on normals | journal = Archives of General Psychiatry | volume = 17 | issue = 5 | pages = 521–32 | date = November 1967 | pmid = 6054248 | doi = 10.1001/archpsyc.1967.01730290009002 | url = http://www.maps.org/w3pb/new/1967/1967_mcglothlin_4655_1.pdf | url-status = dead | archive-url = https://web.archive.org/web/20110430020912/http://www.maps.org/w3pb/new/1967/1967_mcglothlin_4655_1.pdf | archive-date = April 30, 2011 }}</ref> Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation.<ref name="cdasa">{{cite web|url=http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html#h-30 |title=Controlled Drugs and Substances Act |access-date=December 15, 2013 |publisher=Canadian Department of Justice |year=1996 |author=Canadian government |website=Justice Laws |url-status=dead |archive-url=https://web.archive.org/web/20131215170432/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html |archive-date=December 15, 2013 }}</ref> While it is impossible to predict when a bad trip will occur, one's mood, surroundings, sleep, [[Drinking#Hydration and dehydration|hydration]], social setting, and other factors can be controlled (colloquially referred to as "[[set and setting]]") to minimize the risk of a bad trip.<ref name=MedlinePlus>{{citation|title=Substance use – LSD | vauthors = Rogge T |date=21 May 2014|access-date=14 July 2016|publisher=MedlinePlus, U.S. National Library of Medicine|url=https://medlineplus.gov/ency/patientinstructions/000795.htm|url-status=live|archive-url=https://web.archive.org/web/20160728004220/https://medlineplus.gov/ency/patientinstructions/000795.htm|archive-date=July 28, 2016|df=mdy-all}}</ref><ref name=CESAR>{{citation|title=LSD |author=CESAR |publisher=Center for Substance Abuse Research, University of Maryland |date=29 October 2013 |access-date=14 July 2016 |url=http://www.cesar.umd.edu/cesar/drugs/lsd.asp |url-status=dead |archive-url=https://web.archive.org/web/20160715071823/http://www.cesar.umd.edu/cesar/drugs/lsd.asp |archive-date=July 15, 2016 }}</ref> The concept of "set and setting" also generally appears to be more applicable to psychedelics than to other types of hallucinogens such as deliriants, hypnotics and dissociative anesthetics.<ref>{{cite journal |last1=Garcia-Romeu |first1=Albert |last2=Kersgaard |first2=Brennan |last3=Addy |first3=Peter H. |title=Clinical applications of hallucinogens: A review. |journal=Experimental and Clinical Psychopharmacology |date=August 2016 |volume=24 |issue=4 |pages=229–268 |doi=10.1037/pha0000084|pmid=27454674 |pmc=5001686 }}</ref>

Classic psychedelics are considered to be those found in nature like psilocybin, DMT, mescaline, and LSD which is derived from naturally occurring ergotamine, and non-classic psychedelics are considered to be newer analogs and derivatives of pharmacophore lysergamides, tryptamine, and phenethylamine structures like [[2C-B]]. Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three major families have subjectively different qualities in the "feel" of the experience, which are difficult to describe. Some compounds, such as 2C-B, have extremely tight "dose curves", meaning the difference in dose between a non-event and an overwhelming disconnection from reality can be very slight. There can also be very substantial differences between the drugs; for instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics.<ref name="Nichols2016"/>

==Potential adverse effects==
{{see also|Bad trip|Trip sitter}}

Despite the contrary perception of much of the public, psychedelic drugs are not addictive and are physiologically safe.<ref name="canada-commission"/><ref name="Ungless 2006"/><ref name="Nichols2016"/> As of 2016, there have been no known deaths due to [[Drug overdose|overdose]] of LSD, psilocybin, or mescaline.<ref name="Nichols2016"/>

Risks do exist during an unsupervised psychedelic experience, however; [[Ira Byock]] wrote in 2018 in the ''[[Journal of Palliative Medicine]]'' that psilocybin is safe when administered to a properly screened patient and supervised by a qualified professional with appropriate set and setting. However, he called for an "abundance of caution" because in the absence of these conditions a range of negative reactions is possible, including "fear, a prolonged sense of dread, or full panic." He notes that driving or even walking in public can be dangerous during a psychedelic experience because of impaired [[hand-eye coordination]] and [[Fine motor skill|fine motor control]].<ref name="byock-2018">{{cite journal |last1=Byock |first1=Ira |author-link1=Ira Byock |title=Taking Psychedelics Seriously |journal=Journal of Palliative Medicine |date=2018 |volume=21 |issue=4 |pages=417–421 |doi=10.1089/jpm.2017.0684 |pmid=29356590 |pmc=5867510}}</ref> In some cases, individuals taking psychedelics have performed dangerous or fatal acts because they believed they possessed superhuman powers.<ref name="Nichols2016"/>

Psilocybin-induced states of mind share features with states experienced in [[psychosis]], and while a causal relationship between psilocybin and the onset of psychosis has not been established as of 2011, researchers have called for investigation of the relationship.<ref name="van-amsterdam-et-al">{{cite journal |last1=van Amsterdam |first1=Jan |last2=Opperhuizen |first2=Antoon |last3=van den Brink |first3=Wim |date=2011 |title=Harm potential of magic mushroom use: A review |journal=Regulatory Toxicology and Pharmacology |volume=59 |issue=3 |pages=423–429 |doi=10.1016/j.yrtph.2011.01.006 |pmid=21256914}}</ref> Many of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context.<ref>{{Cite journal|last1=Schlag|first1=Anne K|last2=Aday|first2=Jacob|last3=Salam|first3=Iram|last4=Neill|first4=Jo C|last5=Nutt|first5=David J|date=2022-02-02|title=Adverse effects of psychedelics: From anecdotes and misinformation to systematic science|journal=Journal of Psychopharmacology|volume=36|issue=3|pages=258–272|doi=10.1177/02698811211069100|pmid=35107059|pmc=8905125|issn=0269-8811}}</ref> A [[population study]] on associations between psychedelic use and mental illness published in 2013 found no evidence that psychedelic use was associated with increased prevalence of any mental illness.<ref>{{cite journal|author1=Krebs, Teri S.|author2=Johansen, Pål-Ørjan|author3=Lu, Lin|title=Psychedelics and Mental Health: A Population Study|journal=PLOS ONE|date=19 August 2013|volume=8|issue=8|pages=e63972|doi=10.1371/journal.pone.0063972|pmid=23976938|pmc=3747247|bibcode=2013PLoSO...863972K|doi-access=free}}</ref>

Using psychedelics poses certain risks of re-experiencing of the drug's effects, including flashbacks and [[hallucinogen persisting perception disorder]] (HPPD).<ref name="van-amsterdam-et-al" /> These non-psychotic effects are poorly studied, but the permanent symptoms (also called "endless trip") are considered to be rare.<ref>{{cite journal |last1=Baggott |first1=M. J. |last2=Coyle |first2=J. R. |last3=Erowid |first3=E. |last4=Erowid |first4=F. |last5=Robertson |first5=L. C. |date=1 March 2011 |title=Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire |journal=Drug and Alcohol Dependence |volume=114 |issue=1 |pages=61–67 |doi=10.1016/j.drugalcdep.2010.09.006 |pmid=21035275}}</ref>

[[Serotonin syndrome]] can be caused by combining psychedelics with other serotonergic drugs, including certain antidepressants, opioids, CNS stimulants (e.g. MDMA), [[5-HT receptor|5-HT<sub>1</sub>]] agonists (e.g. [[triptan]]s), herbs and others.<ref>{{cite journal|author=Bijl D |title=The serotonin syndrome |journal=Neth J Med |volume=62 |issue=9 |pages=309–13 |date=October 2004 |pmid=15635814 |quote= Mechanisms of serotonergic drugs implicated in serotonin syndrome... Stimulation of serotonin receptors... LSD}}</ref><ref>{{Cite web |url= https://www.drugwise.org.uk/amt/ |title=AMT |date=2016-01-03 |website=DrugWise.org.uk |language=en-gb |access-date=2019-11-18}}</ref><ref>{{Cite report |title=Alpha-methyltryptamine (AMT) – Critical Review Report |date=20 June 2014 |publisher=World Health Organisation – Expert Committee on Drug Dependence |publication-date=2014-06-20 |url=https://legal-high-inhaltsstoffe.de/sites/default/files/uploads/amt.pdf |access-date=2019-11-18}}</ref><ref name=Boy2005>{{cite journal | vauthors = Boyer EW, Shannon M | title = The serotonin syndrome | journal = The New England Journal of Medicine | volume = 352 | issue = 11 | pages = 1112–20 | date = March 2005 | pmid = 15784664 | doi = 10.1056/NEJMra041867 | url = http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | archive-url = https://web.archive.org/web/20130618053344/http://toxicology.ucsd.edu/art%203%20serotonin%20syndrome.pdf | url-status = live | archive-date = 2013-06-18 | author-link2 = Michael Shannon (pediatrician) }}</ref>

Serotonergic psychedelics are [[agonist]]s not only of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] but also of the serotonin [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]] and other [[serotonin receptor]]s.<ref name="TagenMantuanivanHeerden2023">{{cite journal | vauthors = Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R | title = The risk of chronic psychedelic and MDMA microdosing for valvular heart disease | journal = J Psychopharmacol | volume = 37 | issue = 9 | pages = 876–890 | date = September 2023 | pmid = 37572027 | doi = 10.1177/02698811231190865 | url = }}</ref><ref name="RouaudCalderHasler2024">{{cite journal | vauthors = Rouaud A, Calder AE, Hasler G | title = Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins | journal = J Psychopharmacol | volume = 38 | issue = 3 | pages = 217–224 | date = March 2024 | pmid = 38214279 | pmc = 10944580 | doi = 10.1177/02698811231225609 | url = }}</ref> A potential risk of frequent repeated use of serotonergic psychedelics is [[cardiac fibrosis]] and [[valvular heart disease|valvulopathy]] caused by 5-HT<sub>2B</sub> receptor activation.<ref name="TagenMantuanivanHeerden2023" /><ref name="RouaudCalderHasler2024" /> However, single high doses or widely spaced doses (e.g., months) are widely thought to be safe and concerns about cardiac toxicity apply more to chronic [[psychedelic microdosing]] or very frequent use (e.g., weekly).<ref name="TagenMantuanivanHeerden2023" /><ref name="RouaudCalderHasler2024" /> [[Binding selectivity|Selective]] 5-HT<sub>2A</sub> receptor agonists that do not activate the 5-HT<sub>2B</sub> receptor or other serotonin receptors, such as [[25CN-NBOH]], [[DMBMPP]], and [[LPH-5 (drug)|LPH-5]], have been developed and are being studied.<ref name="MärcherRørstedJensenKristensen2021">{{cite journal | vauthors = Märcher Rørsted E, Jensen AA, Kristensen JL | title = 25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor | journal = ChemMedChem | volume = 16 | issue = 21 | pages = 3263–3270 | date = November 2021 | pmid = 34288515 | doi = 10.1002/cmdc.202100395 | url = }}</ref><ref name="DuanCaoWang2024">{{cite journal | vauthors = Duan W, Cao D, Wang S, Cheng J | title = Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants | journal = Chem Rev | volume = 124 | issue = 1 | pages = 124–163 | date = January 2024 | pmid = 38033123 | doi = 10.1021/acs.chemrev.3c00375 | url = }}</ref><ref name="Peplow2024">{{cite journal | last=Peplow | first=Mark | title=Next-generation psychedelics: should new agents skip the trip? | journal=Nature Biotechnology | volume=42 | issue=6 | date=2024 | issn=1087-0156 | doi=10.1038/s41587-024-02285-1 | pages=827–830 | quote=Another problem is that some classical psychedelics are also agonists of the 5-HT2B receptor, which is expressed in heart tissue and can cause long-term cardiac problems. Kristensen’s company Lophora aims to solve that with its lead compound LPH-5, a phenylethylamine derivative with an extra molecular ring that makes it less flexible. LPH-5 has a 60-fold higher selectivity for 5-HT2A over 5-HT2B.}}</ref> Selective 5-HT<sub>2A</sub> receptor agonists are expected to avoid the cardiac risks of 5-HT<sub>2B</sub> receptor activation.<ref name="Peplow2024" />

==Potential therapeutic effects==
{{further|Psychedelic therapy}}
[[File:Johns Hopkins psilocybin session room-SessionRm 2176x.jpg|thumb|Psilocybin session at Johns Hopkins]]

Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline.<ref name="tupper-et-al">{{Cite journal|last1=Tupper|first1=Kenneth W.|last2=Wood|first2=Evan|last3=Yensen|first3=Richard|last4=Johnson|first4=Matthew W.|date=2015-10-06|title=Psychedelic medicine: a re-emerging therapeutic paradigm|journal=CMAJ: Canadian Medical Association Journal|volume=187|issue=14|pages=1054–1059|doi=10.1503/cmaj.141124|issn=0820-3946|pmc=4592297|pmid=26350908}}</ref> During the 1950s and 1960s, lack of [[informed consent]] in some scientific trials on psychedelics led to significant, long-lasting harm to some participants.<ref name="tupper-et-al"/> Since then, research regarding the effectiveness of psychedelic therapy has been conducted under strict ethical guidelines, with fully informed consent and a pre-screening to avoid people with psychosis taking part.<ref name="tupper-et-al"/> Although the history behind these substances has hindered research into their potential medicinal value, scientists are now able to conduct studies and renew research that was halted in the 1970s. Some research has shown that these substances have helped people with such mental disorders as [[obsessive-compulsive disorder]] (OCD), [[post-traumatic stress disorder]] (PTSD), alcoholism, depression, and [[cluster headaches]].<ref name="garcia-et-al"/>

It has long been known that psychedelics promote neurite growth and [[neuroplasticity]] and are potent [[psychoplastogen]]s.<ref>{{cite journal|last1=Jones|first1=K.A.|last2=Srivastave|first2=D.P.|last3=Allen|first3=J.A.|last4=Roth|first4=B.L.|last5=Penzes|first5=P.|title=Psychedelics Promote Structural and Functional Neural Plasticity|journal=Proc Natl Acad Sci U S A|date= 2009|volume=106|issue=46|pages=19575–19580|doi=10.1073/pnas.0905884106|pmid=19889983|pmc=2780750|doi-access=free}}</ref><ref>{{cite journal|last1=Yoshida|first1=H.|last2=Kanamaru|first2=C.|last3=Ohtani|first3=A.|last4=Senzaki|first4=K.|last5=Shiga|first5=T.|title=Subtype specific roles of serotonin receptors in the spine formation of cortical neurons in vitro|journal=Neurosci Res.|date=2011|volume=71|issue=3|pages=311–314|doi=10.1016/j.neures.2011.07.1824|pmid=21802453|hdl=2241/114624|s2cid=14178672|url=https://tsukuba.repo.nii.ac.jp/record/25719/files/NR_71-3.pdf |hdl-access=free}}</ref><ref>{{cite journal|last1=Ly|first1=Calvin|last2=Greb|first2=Alexandra C.|last3=Cameron|first3=Lindsay P.|last4=Wong|first4=Jonathan M.|last5=Barragan|first5=Eden V.|last6=Wilson|first6=Paige C.|last7=Burbach|first7=Kyle F.|last8=Soltanzadeh Zarandi|first8=Sina|last9=Sood|first9=Alexander|last10=Paddy|first10=Michael R.|last11=Duim|first11=Whitney C.|last12=Dennis|first12=Megan Y.|last13=McAllister |first13=A. Kimberley|last14=Ori-McKenney|first14=Kassandra M.|last15=Gray|first15=John A.|last16=Olson|first16=David E.|title=Psychedelics Promote Structural and Functional Neural Plasticity|journal=Cell Reports|date=June 2018|volume=23|issue=11|pages=3170–3182 |doi=10.1016/j.celrep.2018.05.022|pmid=29898390|pmc=6082376|doi-access=free}}</ref> There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits.<ref>{{Cite journal|last1=de Vos|first1=Cato M. H.|last2=Mason|first2=Natasha L.|last3=Kuypers|first3=Kim P. C.|date=2021|title=Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics|journal=Frontiers in Psychiatry|volume=12|pages=1575|doi=10.3389/fpsyt.2021.724606|pmid=34566723|pmc=8461007|issn=1664-0640|doi-access=free}}</ref><ref>{{Cite journal |last1=Calder |first1=Abigail E. |last2=Hasler |first2=Gregor |date=2022-09-19 |title=Towards an understanding of psychedelic-induced neuroplasticity |journal=Neuropsychopharmacology |volume=48 |issue=1 |language=en |pages=104–112 |doi=10.1038/s41386-022-01389-z |pmid=36123427 |pmc=9700802 |s2cid=252381170 |issn=1740-634X|doi-access=free }}</ref> Psychedelics have also been shown to have potent anti-inflammatory activity and therapeutic effects in animal models of inflammatory diseases including asthma,<ref>{{cite journal|last1=Nau|first1=F.|last2=Miller|first2=J.|last3=Saravia|first3=J.|last4=Ahlert|first4=T.|last5=Yu|first5=B.|last6=Happel|first6=K.I|last7=Cormier|first7=S.A|last8=Nichols|first8=C.D.|title=Serotonin 5-HT₂ receptor activation prevents allergic asthma in a mouse model |journal= American Journal of Physiology. Lung Cellular and Molecular Physiology|date=2015|volume=308|issue=2|pages=191–198 |doi=10.1152/ajplung.00138.2013|pmid=25416380|pmc=4338939}}</ref> and cardiovascular disease and diabetes.<ref>{{cite journal|last1= Flanagan |first1=T.W.|last2= Sebastian |first2=M.N.|last3= Battaglia|first3=D.M.|last4= Foster |first4=T.P.|last5= Maillet |first5=E.L.|last6= Nichols|first6=C.D.|title= Activation of 5-HT2 Receptors Reduces Inflammation in Vascular Tissue and Cholesterol Levels in High-Fat Diet-Fed Apolipoprotein E Knockout Mice|journal=Sci. Rep. |date=2019|volume=9|issue=1|pages=13444–198 |doi=10.1038/s41598-019-49987-0|pmid=31530895|pmc=6748996|bibcode=2019NatSR...913444F|doi-access=free}}</ref>

==Surrounding culture==
[[File:Jefferson Airplane photo 1967.JPG|thumb|upright|[[Psychedelic rock]] band [[Jefferson Airplane]] in 1967]]
{{main|Psychedelia}}
Psychedelic culture includes manifestations such as [[psychedelic music]],<ref name=Hicks2000>{{cite book |last1=Hicks |first1=Michael |title=Sixties Rock: Garage, Psychedelic, and Other Satisfactions |date=15 January 2000 |publisher=University of Illinois Press |location=Chicago, IL |isbn=0-252-06915-3 |pages=63–64}}</ref> [[psychedelic art]],<ref name="krippner">{{cite journal |last1=Krippner |first1=Stanley |title=Ecstatic Landscapes: The Manifestation of Psychedelic Art |journal=Journal of Humanistic Psychology |date=2017 |volume=57 |issue=4 |pages=415–435 |doi=10.1177/0022167816671579|s2cid=151517152 }}</ref> [[psychedelic literature]],<ref name="Dickins-2013">{{cite journal |last1=Dickins |first1=Robert |title=Preparing the Gaia connection: An ecological exposition of psychedelic literature 1954-1963 |journal=European Journal of Ecopsychology |date=2013 |volume=4 |pages=9–18 |citeseerx=10.1.1.854.6673 |url=http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.854.6673&rep=rep1&type=pdf |access-date=7 January 2021}}</ref> [[psychedelic film]],<ref name="gallagher-2004">{{cite journal |last1=Gallagher |first1=Mark |title=Tripped Out: The Psychedelic Film and Masculinity |journal=Quarterly Review of Film and Video |date=2004 |volume=21 |issue=3 |pages=161–171 |doi=10.1080/10509200490437817|s2cid=191583864 }}</ref> and psychedelic [[Music festival|festivals]].<ref name=StJohn>St John, Graham. [https://dj.dancecult.net/index.php/dancecult/article/view/270 "Neotrance and the Psychedelic Festival."] ''Dancecult: Journal of Electronic Dance Music Culture,'' '''1'''(1) (2009).</ref> Examples of psychedelic music would be rock bands like the [[Grateful Dead]], [[Jefferson Airplane]] and [[The Beatles]]. Many psychedelic bands and elements of the psychedelic subculture originated in San Francisco during the mid to late 1960s.<ref>{{Cite web |url=https://experiments.californiahistoricalsociety.org/what-was-the-trips-festival/|title=The Trips Festival explained|first=Adam |last=Hirschfelder|date=Jan 14, 2016|website=Experiments in Environment: The Halprin Workshops, 1966–1971}}</ref>

==Legal status==
{{See also|Legal status of psilocybin mushrooms|Psilocybin decriminalization in the United States|Legal status of ayahuasca by country}}
Many psychedelics are classified under Schedule I of the United Nations [[Convention on Psychotropic Substances]] of 1971 as drugs with the greatest potential to cause harm and no acceptable medical uses.<ref name="rucker-2015">{{cite journal |last1=Rucker |first1=James J. H. |title=Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential |journal=British Medical Journal |date=2015 |volume=350 |pages=h2902 |doi=10.1136/bmj.h2902|pmid=26014506 |s2cid=46510541 }}</ref> In addition, many countries have analogue laws; for example, in the United States, the [[Federal Analogue Act]] of 1986 automatically forbids any drugs sharing similar chemical structures or chemical formulas to prohibited substances if sold for human consumption.<ref>{{cite web |title=U.S.C. Title 21 – FOOD AND DRUGS |url=https://www.govinfo.gov/content/pkg/USCODE-2011-title21/html/USCODE-2011-title21-chap13.htm |website=www.govinfo.gov |access-date=28 February 2022}}</ref>

In July 2022, though, under the United States Food and Drug Administration, the drug psilocybin was on track to be approved of as a treatment for depression, and MDMA as a treatment for post-traumatic stress disorder.<ref>{{Cite journal |last=Harrington |first=Anne |date=2023-11-01 |title=Mental Health's Stalled (Biological) Revolution: Its Origins, Aftermath & Future Opportunities |url=https://direct.mit.edu/daed/article/152/4/166/118242/Mental-Health-s-Stalled-Biological-Revolution-Its |journal=Daedalus |language=en |volume=152 |issue=4 |pages=166–185 |doi=10.1162/daed_a_02037 |issn=0011-5266|doi-access=free }}</ref>

U.S. states such as Oregon and Colorado have also instituted decriminalization and legalization measures for accessing psychedelics<ref>{{cite web |title=Pot Prohibition Continues Collapsing, and Psychedelic Bans Could Be Next |url=https://reason.com/2022/11/09/pot-and-psychedelics-rack-up-wins-at-the-ballot-box/|date=November 9, 2022}}</ref> and states like New Hampshire are attempting to do the same.<ref>{{cite web |title=New Hampshire Lawmakers File Psilocybin And Broader Drug Decriminalization Bills For 2022 |url=https://www.marijuanamoment.net/new-hampshire-lawmakers-file-psilocybin-and-broader-drug-decriminalization-bills-for-2022/|date=December 29, 2021}}</ref> J.D. Tuccille argues that increasing rates of use of psychedelics in defiance of the law are likely to result in more widespread legalization and decriminalization of access to the substances in the United States (as has happened with [[alcohol (drug)|alcohol]] and [[cannabis (drug)|cannabis]]).<ref>{{cite web|last=Tuccille|first=J.D.|url=https://reason.com/2022/08/03/scofflaws-lead-the-way-to-legalizing-psychedelic-drugs/|title=Scofflaws Lead the Way To Legalizing Psychedelic Drugs|work=Reason|access-date=18 January 2023|date=3 August 2022}}</ref>

==See also==
{{div col|colwidth=30em}}
* [[Aztec use of entheogens]]
* [[Bwiti]]
* [[Cognitive liberty]]
* [[Concord Prison Experiment]]
* [[Designer Drugs]]
* [[Dissociative drug]]
* [[Deliriant]]
* [[Drug harmfulness]]
* [[Entheogenic drugs and the archaeological record]]
* [[Entheogenics and the Maya]]
* [[Hallucinogenic fish]]
* [[Hallucinogenic plants in Chinese herbals]]
* ''[[Hamilton's Pharmacopeia]]''
* [[History of lysergic acid diethylamide]]
* [[Ibogaine]]
* [[List of designer drugs]]
* [[List of psychedelic drugs]]
* [[List of psychedelic plants]]
* [[Marsh Chapel Experiment]]
* [[Morning glory]]
* [[Mystical psychosis]]
* ''[[PiHKAL]]''
* {{annotated link|Psychedelia (film)|''Psychedelia''}}
* [[Research chemical]]
* [[Serotonergic cell groups]]
* [[Serotonin syndrome]]
* ''[[Tabernanthe iboga]]''
* ''[[TiHKAL]]''
* [[Trip killer]]
{{div col end}}

===Categories===
{{See also for drug classes defined by psychological effects|Psychedelic drugs}}

== Notes ==
{{Reflist|1|group=note}}

== References ==
{{reflist|30em}}

==Further reading==
* {{cite book |last1=Echard |first1=William |title=Psychedelic Popular Music: A History through Musical Topic Theory |date=2017 |publisher=Indiana University Press |location=Bloomington, IN |doi=10.2307/j.ctt1zxxzgx |isbn=978-0-253-02645-3}}
* {{Cite book|title=Behavioral Neurobiology of Psychedelic Drugs|date=2018|publisher=Springer|isbn=978-3-662-55878-2|editor-first=Adam L.|editor-last=Halberstadt |editor2=Franz X. Vollenweider |editor3=David E. Nichols |volume=36|location=Berlin, Heidelberg}}
* {{cite book |last1=Jay |first1=Mike |title=Mescaline: A Global History of the First Psychedelic |date=2019 |publisher=Yale University Press |location=New Haven, CT |doi=10.2307/j.ctvgc61q9 |isbn=978-0-300-25750-2|s2cid=241952235 }}
* {{cite book |last1=Letheby |first1=Chris |title=Philosophy of Psychedelics |date=2021 |publisher=Oxford University Press |location=Oxford |isbn=978-0-19-884312-2|doi=10.1093/med/9780198843122.001.0001}}
* {{cite book |last=Richards |first=William A. |title=Sacred Knowledge: Psychedelics and Religious Experiences |date=2016 |publisher=Columbia University Press |location=New York |isbn=978-0-231-54091-9}}
* {{cite book |last=Siff |first=Stephen |title=Acid Hype: American News Media and the Psychedelic Experience |date=2015 |publisher=University of Illinois Press |location=Champaign, Illinois |isbn=978-0-252-09723-2}}
* Winstock, Ar; Timmerman, C; Davies, E; Maier, Lj; Zhuparris, A; Ferris, Ja; Barratt, Mj; Kuypers, Kpc (2021). ''[https://www.globaldrugsurvey.com/wp-content/uploads/2021/03/GDS2020-Psychedelics-report.pdf Global Drug Survey (GDS) 2020 Psychedelics Key Findings Report]''.

== External links ==

{{commons category|Psychedelics}}
{{wiktionary|psychedelic}}[https://psychedelictimes.com/psychedelic-timeline/ Psychedelic Timeline] by Tom Frame, Psychedelic Times{{Major Drug Groups}}
{{Drug use}}
{{Hallucinogens}}
{{Serotonin receptor modulators}}

[[Category:Drug classes defined by psychological effects]]
[[Category:5-HT2A agonists]]
[[Category:Hallucinations]]
[[Category:Psychedelic drugs| ]]