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{{short description|General group of pharmacological agents}}

'''Hallucinogens''' are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in [[Philosophy:Thought|thought]], mood, and [[Perception|perception]] as well as other changes.<ref name="vollenweider-2001">{{cite journal |last1=Vollenweider |first1=Franz X. |title=Brain mechanisms of hallucinogens and entactogens |journal=Dialogues in Clinical Neuroscience |date=2001 |volume=3 |issue=4 |pages=265–279 |doi=10.31887/DCNS.2001.3.4/fxvollenweider |pmid=22033605 |pmc=3181663}}</ref><ref name="volgin-et-al-2019">{{cite journal |last1=Volgin |first1=Andrey D. |last2=Yakovlev |first2=Oleg A. |last3=Demin |first3=Constantin A. |last4=Alekseeva |first4=Polina A. |last5=Kyzar |first5=Evan J. |last6=Collins |first6=Christopher |last7=Nichols |first7=David E. |last8=Kalueff |first8=Allan V. |title=Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models |journal=ACS Chemical Neuroscience |date=2019 |volume=10 |issue=1 |pages=143–154 |doi=10.1021/acschemneuro.8b00433 |pmid=30252437|s2cid=52824516 }}</ref> Most hallucinogens can be categorized as either being [[Chemistry:Psychedelic drug|psychedelics]], dissociatives, or [[Chemistry:Deliriant|deliriant]]s.<ref name="volgin-et-al-2019"/>

==Etymology==
The word ''hallucinogen'' is derived from the word ''hallucination''.<ref name="merriam-webster">{{cite web |title=hallucinogen |url=https://www.merriam-webster.com/dictionary/hallucinogen |website=Merriam-Webster |access-date=31 May 2020}}</ref> The term ''hallucinate'' dates back to around 1595–1605, and is derived from the [[Social:Latin|Latin]] ''hallūcinātus'', the past participle of ''(h)allūcināri'', meaning "to wander in the mind."<ref name="dictionary-hallucinate">{{cite web |title=Hallucinate |url=https://www.dictionary.com/browse/hallucinate |website=Dictionary.com |access-date=26 June 2020}}</ref>

== Characteristics ==
Leo Hollister gave five criteria for classifying a drug as hallucinogenic.<ref name="glennon-overview">Glennon RA. Classical drugs: an introductory overview. In Lin GC and Glennon RA (eds). [http://archives.drugabuse.gov/pdf/monographs/146.pdf Hallucinogens: an update] {{webarchive|url=https://web.archive.org/web/20150723031539/http://archives.drugabuse.gov/pdf/monographs/146.pdf |date=23 July 2015 }}. National Institute on Drug Abuse: Rockville, MD, 1994.</ref><ref name="glennon-1999">{{cite journal | vauthors = Glennon RA | s2cid = 10221368 | title = Arylalkylamine drugs of abuse: an overview of drug discrimination studies | journal = Pharmacology Biochemistry and Behavior | volume = 64 | issue = 2 | pages = 251–6 | date = October 1999 | pmid = 10515299 | doi = 10.1016/S0091-3057(99)00045-3 }}</ref> This definition is broad enough to include a wide range of drugs and has since been shown to encompass a number of categories of drugs with different pharmacological mechanisms and behavioral effects.<ref name="glennon-1999"/> Richard Glennon has thus given an additional two criteria that narrow the category down to ''classical hallucinogens''.<ref name="glennon-1999"/> Hollister's criteria for hallucinogens were as follows:<ref name="glennon-overview"/><ref name="glennon-1999"/>

* in proportion to other effects, changes in thought, perception, and mood should predominate;
* intellectual or memory impairment should be minimal;
* stupor, narcosis, or excessive stimulation should not be an integral effect;
* autonomic nervous system side effects should be minimal; and
* addictive craving should be absent.

Glennon's additional criteria for classical hallucinogens are that the drugs in question must also:<ref name="glennon-1999"/>

* bind at 5-HT2 serotonin receptors; and
* be recognized by animals trained to discriminate the drug [[Chemistry:2,5-Dimethoxy-4-methylamphetamine|DOM]] from vehicle.<!--This was left here and needs to be clarified and integrated based on the source: "In contrast to Hollister's original criteria, adverse effects may predominate with some hallucinogens with this application of the term."<ref name="Nichols, David 2004"/>-->

== Nomenclature and taxonomy ==
Most hallucinogens can be categorized based on their pharmacological mechanisms as [[Chemistry:Psychedelic drug|psychedelics]] (which are [[Chemistry:Serotonin|serotonergic]]), dissociatives (which are generally antiglutamatergic), or [[Chemistry:Deliriant|deliriant]]s (which are generally [[Medicine:Anticholinergic|anticholinergic]]).<ref name="volgin-et-al-2019"/> However, the pharmacological mechanisms of some hallucinogens, such as [[Chemistry:Salvinorin A|salvinorin A]] and [[Biology:Ibogaine|ibogaine]], do not fit into any of those categories.<ref name="volgin-et-al-2019"/> Entactogens and [[Chemistry:Cannabinoid|cannabinoid]]s are also sometimes considered hallucinogens.<ref name="sherwood-prisinzano-2018">{{cite journal |last1=Sherwood |first1=Alexander M. |last2=Prisinzano |first2=Thomas E. |title=Novel psychotherapeutics – a cautiously optimistic focus on Hallucinogens |journal=Expert Review of Clinical Pharmacology |date=2018 |volume=11 |issue=1 |pages=1–3 |doi=10.1080/17512433.2018.1415755 |pmid=29224406 |pmc=6121772}}</ref> Nonetheless, while the term ''hallucinogen'' is often used to refer to the broad class of drugs covered in this article, sometimes it is used to mean only classical hallucinogens (that is, psychedelics).<ref name="Nichols, David 2004">{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacology & Therapeutics | volume = 101 | issue = 2 | pages = 131–81 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 }}</ref> Because of this, it is important to consult the definition given in a particular source.<ref name="Nichols, David 2004"/> Because of the multi-faceted [[Philosophy:Phenomenology (psychology)|phenomenology]] brought on by hallucinogens, efforts to create standardized terminology for classifying them based on their subjective effects have not succeeded to date.<ref name="hermle-kraehenmann">{{cite journal |last1=Hermle |first1=Leo |last2=Kraehenmann |first2=Rainer |title=Experimental Psychosis Research and Schizophrenia—Similarities and Dissimilarities in Psychopathology |journal=Current Topics in Behavioral Neurosciences |date=2017 |volume=36 |pages=313–332 |doi=10.1007/7854_2016_460|pmid=28444578 |isbn=978-3-662-55878-2 }}</ref>

Classical hallucinogens or psychedelics have been described by many names. David E. Nichols wrote in 2004:<ref name="Nichols, David 2004"/>

{{Quotation|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 |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>

Certain hallucinogens are [[Chemistry:Designer drug|designer drug]]s, such as those in the [[Chemistry:2C (psychedelics)|2C]] and [[Chemistry:25-NB|25-NB]] (NBOMe) families.<ref name="weaver-et-al-2015">{{cite journal |last1=Weaver |first1=Michael F. |last2=Hopper |first2=John A. |last3=Gunderson |first3=Erik W. |title=Designer drugs 2015: assessment and management |journal=Addiction Science & Clinical Practice |date=2015 |volume=10 |issue=1 |pages=8 |doi=10.1186/s13722-015-0024-7 |pmid=25928069 |pmc=4422150 |doi-access=free }}</ref> A designer drug is a structural or functional analog of a controlled substance (hallucinogenic or otherwise) that has been designed to mimic the pharmacological effects of the original drug while at the same time avoid being classified as illegal (by specification as a [[Chemistry:Research chemical|research chemical]]) and/or avoid detection in standard drug tests.<ref>{{cite journal | vauthors = Wohlfarth A, Weinmann W | title = Bioanalysis of new designer drugs | journal = Bioanalysis | volume = 2 | issue = 5 | pages = 965–79 | date = May 2010 | pmid = 21083227 | doi = 10.4155/bio.10.32 }}</ref>
<!-- (commented out due to lack of sources, but seems like a good outline that could be used once sources are found for it)
===Classes based on subjective effects and pharmacology===
Based on subjective effects, hallucinogens are often divided into [[Chemistry:Psychedelic drug|psychedelics]] (or classical hallucinogens), dissociatives, and [[Chemistry:Deliriant|deliriant]]s. These can be further divided by their pharmacological mechanisms (what receptors in the brain they act on). The following such a taxonomy:{{citation needed|date=May 2020}}
* ''[[Chemistry:Psychedelic drug|Psychedelics]]''
** [[Chemistry:Serotonin|Serotonergic]]s ([[Biology:5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[Biology:Agonist|agonist]]s or [[Chemistry:Serotonergic psychedelic|classical psychedelics]]) such as [[Biology:Mescaline|mescaline]] from [[Biology:Peyote|peyote]] ''(Lophophora williamsii)''
** [[Biology:Cannabinoidergic|Cannabinoidergic]]s ([[Biology:Cannabinoid receptor type 1|CB-1 receptor]] agonists or atypical psychedelics) such as THC from [[Biology:Cannabis|cannabis]] (''Cannabis'')
* ''Dissociatives''
** Antiglutamatergics ([[Chemistry:NMDA receptor antagonist|NMDA receptor antagonist]]s or classical dissociatives) such as "laughing gas" ([[Chemistry:Nitrous oxide|nitrous oxide]]) and [[Chemistry:Ketamine|ketamine]]
** [[Biology:Opioidergic|Opioidergic]]s (sometimes regarded as atypical psychedelics) (κ-Opioid receptor agonists or atypical dissociatives) such as [[Chemistry:Salvinorin A|salvinorin A]] from ''[[Biology:Salvia divinorum|Salvia divinorum]]'' and [[Chemistry:Pentazocine|pentazocine]]
* ''[[Chemistry:Deliriant|Deliriant]]s''
** [[Medicine:Anticholinergic|Anticholinergic]]s ([[Chemistry:Muscarine|muscarinic]] acetylcholine receptor antagonists or classical deliriants) such as tropane alkaloids such as [[Chemistry:Atropine|atropine]] from deadly nightshade (''[[Biology:Atropa belladonna|Atropa belladonna]]'') and [[Chemistry:Diphenhydramine|diphenhydramine]] (Benadryl)
** [[Biology:GABAergic|GABAergic]]s (sometimes regarded as atypical dissociatives) (GABA<sub>A</sub> receptor agonists, and some positive allosteric modulators of the GABA<sub>A</sub> receptor, hypnotics, or atypical deliriants) such as [[Chemistry:Muscimol|muscimol]] from fly agaric (''[[Biology:Amanita muscaria|Amanita muscaria]]'') and [[Biology:Zolpidem|zolpidem]] (Ambien)

===Classes based on chemical structure===
Hallucinogens can be divided according to their chemical structure. For instance, classical psychedelics (a subgroup of hallucinogens) can be divided according to their chemical structure as follows:{{citation needed|date=May 2020}}
* [[Chemistry:Indole|Indole]]s / [[Chemistry:Tryptamine|Tryptamine]]s such as [[Chemistry:Psilocybin|psilocybin]] from "magic" mushrooms (''[[Biology:Psilocybe|Psilocybe]]'')
** [[Chemistry:Ergoline|Ergoline]]s such as [[Chemistry:Lysergol|lysergol]] from morning glory ([[Biology:Convolvulaceae|Convolvulaceae]])
*** Lysergamides such as [[Chemistry:Lysergic acid diethylamide|LSD]] ("acid"), derived from [[Biology:Ergot|ergot]] (''[[Biology:Claviceps purpurea|Claviceps purpurea]]'')
** Beta-carbolines ([[Biology:Monoamine oxidase inhibitor|monoamine oxidase inhibitor]]s or SSRI's, specifically reversible inhibitors of monoamine oxidase A or RIMAs) such as [[Biology:Harmala alkaloid|harmala alkaloid]]s such as norharman from [[Chemistry:Ayahuasca|ayahuasca]] (''[[Biology:Banisteriopsis caapi|Banisteriopsis caapi]]'')
** Complexly substituted tryptamines such as [[Biology:Ibogaine|ibogaine]] from iboga (''[[Biology:Tabernanthe iboga|Tabernanthe iboga]]'')
* [[Biology:Phenethylamine|Phenethylamine]]s such as mescaline
-->

== Effects by type ==
=== Psychedelics (classical hallucinogens) ===
{{Main|Chemistry:Psychedelic drug}}
[[File:Ruby Slippers LSD Sheet.jpg|thumb|150px|right|One "Blotter" sheet of 900 [[Chemistry:LSD|LSD]] doses]]

Despite several attempts that have been made, starting in the 19th and 20th centuries, to define common [[Philosophy:Phenomenology (psychology)|phenomenological]] structures (i.e., patterns of experience) brought on by classical psychedelics, a universally accepted taxonomy does not yet exist.<ref name="bnsd-phenom">{{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>

A prominent element of [[Unsolved:Psychedelic experience|psychedelic experience]]s is visual alteration.<ref name="bnsd-phenom"/> Psychedelic visual alteration often includes spontaneous formation of complex flowing geometric visual patterning in the visual field.<ref name="swanson"/> When the eyes are open, the visual alteration is overlaid onto the objects and spaces in the physical environment; when the eyes are closed the visual alteration is seen in the "inner world" behind the eyelids.<ref name="swanson"/> These visual effects increase in complexity with higher dosages, and also when the eyes are closed.<ref name="swanson"/> The visual alteration does not normally constitute [[Unsolved:Hallucination|hallucination]]s, because the person undergoing the experience can still distinguish between real and internally generated visual phenomena, though in some cases, true hallucinations are present.<ref name="bnsd-phenom"/> More rarely, psychedelic experiences can include complex hallucinations of objects, animals, people, or even whole landscapes.<ref name="bnsd-phenom"/>

A number of studies by Roland R. Griffiths and other researchers have concluded that high doses of [[Chemistry:Psilocybin|psilocybin]] and other classic psychedelics trigger mystical experiences in most research participants.<ref name="Griffiths2006">{{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><ref name="barrett-et-al-2015">{{cite journal |last1=Barrett |first1=Frederick S. |last2=Johnson |first2=Matthew W. |last3=Griffiths |first3=Roland R. |title=Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin |journal=Journal of Psychopharmacology |date=2015 |volume=29 |issue=11 |pages=1182–1190 |doi=10.1177/0269881115609019 |pmid=26442957 |pmc=5203697}}</ref><ref name="5-meo-dmt-mystical">{{cite journal |last1=Barsuglia |first1=Joseph |last2=Davis |first2=Alan K. |last3=Palmer |first3=Robert |last4=Lancelotta |first4=Rafael |last5=Windham-Herman |first5=Austin-Marley |last6=Peterson |first6=Kristel |last7=Polanco |first7=Martin |last8=Grant |first8=Robert |last9=Griffiths |first9=Roland R. |title=Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study |journal=Frontiers in Psychology |date=2018 |volume=9 |page=2459 |doi=10.3389/fpsyg.2018.02459 |pmid=30574112 |pmc=6292276|doi-access=free }}</ref><ref name="johnson-et-al-2019">{{cite journal |last1=Johnson |first1=Matthew W. |last2=Hendricks |first2=Peter S. |last3=Barrett |first3=Frederick S. |last4=Griffiths |first4=Roland R. |title=Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function |journal=Pharmacology & Therapeutics |date=2019 |volume=197 |pages=83–102 |doi=10.1016/j.pharmthera.2018.11.010|pmid=30521880 |s2cid=54467870 }}</ref> Mystical experiences have been measured by a number of psychometric scales, including the [[Biography:Ralph W. Hood|Hood]] Mysticism Scale, the Spiritual Transcendence Scale, and the Mystical Experience Questionnaire.<ref name="johnson-et-al-2019"/> The revised version of the Mystical Experience Questionnaire, for example, asks participants about four dimensions of their experience, namely the "mystical" quality, positive mood such as the experience of amazement, the loss of the usual sense of time and space, and the sense that the experience cannot be adequately conveyed through words.<ref name="johnson-et-al-2019"/> The questions on the "mystical" quality in turn probe multiple aspects: the sense of "pure" being, the sense of unity with one's surroundings, the sense that what one experienced was real, and the sense of sacredness.<ref name="johnson-et-al-2019"/> Some researchers have questioned the interpretation of the results from these studies and whether the framework and terminology of mysticism are appropriate in a scientific context, while other researchers have responded to those criticisms and argued descriptions of mystical experiences are compatible with a scientific worldview.<ref name="sanders-zijlmans-2021">{{cite journal |last1=Sanders |first1=James W. |last2=Zijlmans |first2=Josjan |title=Moving Past Mysticism in Psychedelic Science |journal=ACS Pharmacology & Translational Science |date=2021 |volume=4 |issue=3 |pages=1253–1255 |doi=10.1021/acsptsci.1c00097 |pmid=34151217 |pmc=8205234}}</ref><ref name="breeksema-van-elk-2021">{{cite journal |last1=Breeksema |first1=Joost J. |last2=van Elk |first2=Michiel |title=Working with Weirdness: A Response to "Moving Past Mysticism in Psychedelic Science" |journal=ACS Pharmacology & Translational Science |date=2021 |volume=4 |issue=4 |pages=1471–1474 |doi=10.1021/acsptsci.1c00149 |pmid=34423279 |pmc=8369678}}</ref><ref name="jylkka-2021">{{cite journal |last1=Jylkkä |first1=Jussi |title=Reconciling Mystical Experiences with Naturalistic Psychedelic Science: Reply to Sanders and Zijlmans |journal=ACS Pharmacology & Translational Science |date=2021 |volume=4 |issue=4 |pages=1468–1470 |doi=10.1021/acsptsci.1c00137 |pmid=34423278 |pmc=8369668}}</ref>

Link R. Swanson divides overarching scientific frameworks for understanding psychedelic experiences into two waves. In the first wave, encompassing nineteenth- and twentieth-century frameworks, he includes model [[Medicine:Psychosis|psychosis]] theory (the [[Medicine:Psychotomimetic|psychotomimetic]] paradigm), filtration theory, and [[Philosophy:Psychoanalytic theory|psychoanalytic theory]].<ref name="swanson"/> In the second wave of theories, encompassing twenty-first-century frameworks, Swanson includes entropic brain theory, [[Integrated information theory|integrated information theory]], and predictive processing.<ref name="swanson"/> It is from the paradigm of filtration theory that the term ''psychedelic'' derives.<ref name="swanson"/> [[Biography:Aldous Huxley|Aldous Huxley]] and Humphrey Osmond applied the pre-existing ideas of filtration theory, which held that the brain filters what enters into consciousness, to explain psychedelic experiences; Huxley believed that the brain was filtering reality itself and that psychedelics granted conscious access to "[[Philosophy:Mind at Large|Mind at Large]]", whereas Osmond believed that the brain was filtering aspects of the mind out of consciousness.<ref name="swanson"/> Swanson writes that Osmond's view seems "less radical, more compatible with materialist science, and less [[Philosophy:Epistemology|epistemically]] and [[Philosophy:Ontology|ontologically]] committed" than Huxley's.<ref name="swanson"/>

=== Dissociatives ===
[[File:Salviadivinorum.jpg|thumb|175px|left|Salvia divinorum]]
''Dissociatives'' produce analgesia, amnesia and catalepsy at anesthetic doses.<ref>{{cite journal | vauthors = Pender JW | title = Dissociative anesthesia | journal = California Medicine | volume = 113 | issue = 5 | pages = 73 | date = November 1970 | pmid = 18730444 | pmc = 1501800 }}</ref> They also produce a sense of detachment from the surrounding environment, hence "the state has been designated as dissociative anesthesia since the patient truly seems disassociated from his environment."<ref>{{cite journal | vauthors = Pender JW | title = Dissociative anesthesia | journal = California Medicine Some Dissociatives Have General Depressant Effects as Well, Which is Why Doctors Prescribe Them to Sedate Patients Who Are in Pain or to Help Maintain General Anesthesia During an Operation. Common Dissociative Drugs Include: PCP (Phencyclidine) | volume = 117 | issue = 4 | pages = 46–7 | date = October 1972 | pmid = 18730832 | pmc = 1518731 }}</ref> Dissociative symptoms include the disruption or compartmentalization of "...the usually integrated functions of consciousness, memory, identity or perception."<ref>American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: American Psychiatric Association, 2000.</ref><sup>p.&nbsp;523</sup> Dissociation of sensory input can cause [[Philosophy:Derealization|derealization]], the perception of the outside world as being dream-like, vague or unreal. Other dissociative experiences include [[Philosophy:Depersonalization|depersonalization]], which includes feeling dissociated from one's personality; feeling unreal; feeling able to observe one's actions but not actively take control; being unable to associate with one's self in the mirror while maintaining rational awareness that the image in the mirror is the same person.<ref>{{cite journal | vauthors = Simeon D, Gross S, Guralnik O, Stein DJ, Schmeidler J, Hollander E | title = Feeling unreal: 30 cases of DSM-III-R depersonalization disorder | journal = The American Journal of Psychiatry | volume = 154 | issue = 8 | pages = 1107–13 | date = August 1997 | pmid = 9247397 | doi = 10.1176/ajp.154.8.1107 | s2cid = 10128404 | doi-access =  }}</ref> In a 2004 paper, Daphne Simeon offered "...common descriptions of depersonalisation experiences: watching oneself from a distance (similar to watching a movie); candid [[Unsolved:Out-of-body experience|out-of-body experience]]s; a sense of just going through the motions; one part of the self acting/participating while the other part is observing;...."<ref>{{cite journal | vauthors = Simeon D | s2cid = 18506672 | title = Depersonalisation disorder: a contemporary overview | journal = CNS Drugs | volume = 18 | issue = 6 | pages = 343–54 | year = 2004 | pmid = 15089102 | doi = 10.2165/00023210-200418060-00002 }}</ref>

The classical dissociatives achieve their effect through blocking binding of the neurotransmitter glutamate to [[Biology:NMDA receptor|NMDA receptor]]s ([[Chemistry:NMDA receptor antagonist|NMDA receptor antagonism]]) and include [[Chemistry:Ketamine|ketamine]], [[Chemistry:Methoxetamine|methoxetamine]] (MXE), [[Chemistry:Phencyclidine|phencyclidine]] (PCP), [[Chemistry:Dextromethorphan|dextromethorphan]] (DXM), and [[Chemistry:Nitrous oxide|nitrous oxide]].<ref>{{cite journal | vauthors = Herling S, Coale EH, Hein DW, Winger G, Woods JH | s2cid = 2369250 | title = Similarity of the discriminative stimulus effects of ketamine, cyclazocine, and dextrorphan in the pigeon | journal = Psychopharmacology | volume = 73 | issue = 3 | pages = 286–91 | year = 1981 | pmid = 6787651 | doi = 10.1007/BF00422419 | hdl = 2027.42/46423 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Herling S, Woods JH | title = Discriminative stimulus effects of narcotics: evidence for multiple receptor-mediated actions | journal = Life Sciences | volume = 28 | issue = 14 | pages = 1571–84 | date = April 1981 | pmid = 6264253 | doi = 10.1016/0024-3205(81)90311-8 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/24399/1/0000669.pdf | hdl = 2027.42/24399 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Nicholson KL, Hayes BA, Balster RL | s2cid = 28576850 | title = Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys | journal = Psychopharmacology | volume = 146 | issue = 1 | pages = 49–59 | date = September 1999 | pmid = 10485964 | doi = 10.1007/s002130051087 }}</ref> However, dissociation is also remarkably administered by [[Chemistry:Salvinorin A|salvinorin A]]'s (the active constituent in ''[[Biology:Salvia divinorum|Salvia divinorum]]'' shown to the left) potent κ-opioid receptor agonism, though usually described as a very ''atypical'' dissociative.<ref>{{cite journal | vauthors = Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB| title = Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 18 | pages = 11934–9 | date = September 2002 | pmid = 12192085 | pmc = 129372 | doi = 10.1073/pnas.182234399 | bibcode = 2002PNAS...9911934R | doi-access = free }}</ref>

Some dissociatives can have [[Biology:Central nervous system|CNS]] depressant effects, thereby carrying similar risks as opioids, which can slow breathing or heart rate to levels resulting in death (when using very high doses). DXM in higher doses can increase heart rate and blood pressure and still depress respiration. Inversely, PCP can have more unpredictable effects and has often been classified as a stimulant and a depressant in some texts along with being as a dissociative. While many have reported that they "feel no pain" while under the effects of PCP, DXM and Ketamine, this does not fall under the usual classification of anesthetics in recreational doses (anesthetic doses of DXM may be dangerous). Rather, true to their name, they process pain as a kind of "far away" sensation; pain, although present, becomes a disembodied experience and there is much less emotion associated with it. As for probably the most common dissociative, [[Chemistry:Nitrous oxide|nitrous oxide]], the principal risk seems to be due to [[Medicine:Hypoxia (medical)|oxygen deprivation]]. Injury from falling is also a danger, as nitrous oxide may cause sudden loss of consciousness, an effect of oxygen deprivation. Because of the high level of physical activity and relative imperviousness to pain induced by PCP, some deaths have been reported due to the release of myoglobin from ruptured muscle cells. High amounts of myoglobin can induce renal shutdown.<ref>{{cite journal |last1=Price |first1=William A. |last2=Giannini |first2=Matthew C. |last3=Giannini |first3=A. James |s2cid=72401949 |title=Antidotal Strategies in Phencyclidine Intoxication |journal=The International Journal of Psychiatry in Medicine |volume=14 |issue=4 |pages=315–21 |year=1984 |doi=10.2190/KKAW-PWGF-W7RQ-23GN}}</ref>

Many users of dissociatives have been concerned about the possibility of NMDA antagonist [[Chemistry:Neurotoxicity|neurotoxicity]] (NAN). This concern is partly due to William E. White, the author of the DXM FAQ, who claimed that dissociatives definitely cause brain damage.<ref>White W. (1998) [http://www.erowid.org/chemicals/dxm/dxm_health1.shtml This is your brain on dissociatives] {{webarchive|url=https://web.archive.org/web/20101017095137/http://www.erowid.org/chemicals/dxm/dxm_health1.shtml |date=17 October 2010 }} (accessed 23 October 2010)</ref> The argument was criticized on the basis of lack of evidence<ref>Anderson C. (2003) [http://www.erowid.org/chemicals/dxm/dxm_health2.shtml The bad news isn't in] {{webarchive|url=https://web.archive.org/web/20081217110632/http://www.erowid.org/chemicals/dxm/dxm_health2.shtml |date=17 December 2008 }} (Accessed 23 October 2010)</ref> and White retracted his claim.<ref>White W. (2004) [http://www.erowid.org/chemicals/dxm/dxm_health3.shtml Response to "The Bad News Isn't In": Please Pass the Crow] {{webarchive|url=https://web.archive.org/web/20101017095136/http://www.erowid.org/chemicals/dxm/dxm_health3.shtml |date=17 October 2010 }} (accessed 23 October 2010)</ref> White's claims and the ensuing criticism surrounded original research by John Olney.

In 1989, John Olney discovered that neuronal vacuolation and other cytotoxic changes ("lesions") occurred in brains of rats administered NMDA antagonists, including [[Chemistry:Phencyclidine|PCP]] and [[Chemistry:Ketamine|ketamine]].<ref>{{cite journal | vauthors = Olney JW, Labruyere J, Price MT | title = Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs | journal = Science | volume = 244 | issue = 4910 | pages = 1360–2 | date = June 1989 | pmid = 2660263 | doi = 10.1126/science.2660263 | bibcode = 1989Sci...244.1360O }}</ref> Repeated doses of NMDA antagonists led to cellular tolerance and hence continuous exposure to NMDA antagonists did not lead to cumulative neurotoxic effects. Antihistamines such as diphenhydramine, barbiturates and even diazepam have been found to prevent NAN.<ref>{{cite journal | vauthors = Farber NB, Kim SH, Dikranian K, Jiang XP, Heinkel C | title = Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity | journal = Molecular Psychiatry | volume = 7 | issue = 1 | pages = 32–43 | year = 2002 | pmid = 11803444 | doi = 10.1038/sj/mp/4000912 | doi-access = free }}</ref> [[Chemistry:Lysergic acid diethylamide|LSD]] and [[Chemistry:2,5-Dimethoxy-4-bromoamphetamine|DOB]] have also been found to prevent NAN.<ref>{{cite journal | vauthors = Farber NB, Hanslick J, Kirby C, McWilliams L, Olney JW | title = Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity | journal = Neuropsychopharmacology | volume = 18 | issue = 1 | pages = 57–62 | date = January 1998 | pmid = 9408919 | doi = 10.1016/S0893-133X(97)00127-9 | doi-access = free }}</ref>

=== Deliriants ===
{{Main|Chemistry:Deliriant}}
[[File:Datura wrightii flower.jpg|175px|thumb|right|[[Biology:Datura innoxia|Datura innoxia]] in flower]]
[[File:IMG 8023 Atropa belladonna L. Single fruit.jpg|thumb|Attractive but highly toxic berry of ''Atropa belladonna'']]
[[File:Tabak P9290021.JPG|thumb|Flowers and foliage of ''[[Biology:Nicotiana tabacum|Nicotiana tabacum]]'', the cultivated tobacco]]
[[File:Fly Agaric mushroom 05.jpg|thumb|Single fruiting body of ''Amanita muscaria'']]
[[File:Nutmeg fruit seed and aril.jpg|thumb|''[[Biology:Myristica fragrans|Myristica fragrans]]'' fruit, halved, showing within the red seed (nutmeg) enclosed in its brown aril (mace)]]
Deliriants, as their name implies, induce a state of [[Medicine:Delirium|delirium]] in the user, characterized by extreme confusion and an inability to control one's actions. They are called deliriants because their subjective effects are similar to the experiences of people with delirious fevers. The term was introduced by David F. Duncan and Robert S. Gold to distinguish these drugs from [[Chemistry:Psychedelic drug|psychedelics]] and dissociatives, such as [[Chemistry:Lysergic acid diethylamide|LSD]] and [[Chemistry:Ketamine|ketamine]] respectively, due to their primary effect of causing delirium, as opposed to the more lucid states produced by the other hallucinogens.<ref>{{cite book |first1=David |last1=Duncan |first2=Robert |last2=Gold |title=Drugs and the whole person|url=https://archive.org/details/drugswholeperson00dunc|url-access=registration|date=1982|publisher=Wiley|location=New York u.a.|isbn=978-0471041207}}</ref>{{page needed|date=February 2018}}

Despite the fully legal status of several common deliriant plants, deliriants are largely unpopular as recreational drugs due to the severe, generally unpleasant and often dangerous nature of the hallucinogenic effects produced.<ref>{{cite book|last1=Grinspoon|first1=Lester|last2=Bakalar|first2=James B.|title=Psychedelic drugs reconsidered|date=1998|publisher=Lindesmith Center|location=New York|isbn=978-0964156852|edition=2. print|url-access=registration|url=https://archive.org/details/psychedelicdrugs0000grin}}</ref>{{page needed|date=February 2018}}

Typical or classical deliriants are those which are [[Medicine:Anticholinergic|anticholinergic]], meaning they [[Biology:Receptor antagonist|block]] the [[Biology:Muscarinic acetylcholine receptor|muscarinic]] [[Chemistry:Acetylcholine|acetylcholine]] [[Biology:Acetylcholine receptor|receptors]]. Many of these compounds are produced naturally by plant genera belonging to the nightshade family [[Biology:Solanaceae|Solanaceae]], such as ''[[Biology:Datura|Datura]]'', ''[[Biology:Brugmansia|Brugmansia]]'' and ''[[Biology:Latua|Latua]]'' in the [[Earth:New World|New World]] and ''[[Biology:Atropa|Atropa]]'', ''[[Biology:Hyoscyamus|Hyoscyamus]]'' and ''[[Biology:Mandragora (genus)|Mandragora]]'' in the [[Earth:Old World|Old World]].<ref>Schultes, Richard Evans; Hofmann, Albert (1979). The Botany and Chemistry of Hallucinogens (2nd ed.). Springfield Illinois: Charles C. Thomas.</ref><ref>Emboden, William, Narcotic Plants – Hallucinogens, stimulants, inebriants, and hypnotics, their origins and uses 2nd edition, revised and enlarged, pub. Macmillan Publishing Co., Inc., New York 1979, {{ISBN|0-02-535480-9}}.</ref> These tropane alkaloids are poisonous and can cause death due to [[Medicine:Tachycardia|tachycardia]]-induced heart failure and [[Medicine:Hyperthermia|hyperthermia]] even in small doses. Additionally, over-the-counter [[Chemistry:Antihistamine|antihistamine]]s such as [[Chemistry:Diphenhydramine|diphenhydramine]] (brand name Benadryl) and [[Chemistry:Dimenhydrinate|dimenhydrinate]] (brand name Dramamine) also have an anticholinergic effect.<ref>{{cite journal | last1 = Beaver | first1 = Kathleen M | last2 = Gavin | first2 = Thomas J | year = 1998 | title = Treatment of acute anticholinergic poisoning with physostigmine | journal = The American Journal of Emergency Medicine | volume = 16 | issue = 5| pages = 505–507 | doi = 10.1016/S0735-6757(98)90003-1 | pmid = 9725967 }}</ref>

Uncured tobacco is also a deliriant due to its intoxicatingly high levels of [[Chemistry:Nicotine|nicotine]].<ref>{{cite book|last1=Winter|first1=Joseph C.|title=Tobacco Use by Native North Americans: Sacred Smoke and Silent Killer|date=2000|publisher=University of Oklahoma Press|isbn=9780806132624|page=354|url=https://books.google.com/books?id=UGI4hxx6mTQC&pg=PA354|language=en}}</ref>

== History of use ==

===Traditional religious and shamanic use===
{{Main|Chemistry:Entheogen}}
Historically, hallucinogens have been commonly used in religious or [[Unsolved:Shamanism|shamanic]] rituals. In this context they are referred to as entheogens, and are used to facilitate healing, divination, communication with spirits, and coming-of-age ceremonies.<ref>{{cite book|last=Schultes|first=Richard Evans|title=Hallucinogenic Plants|others=Illustrated by Elmer W. Smith|publisher=Golden Press|location=New York|year=1976|isbn=0-307-24362-1|pages=[https://archive.org/details/hallucinogenicpl00schu_0/page/5 5, 7, 9, 102]|url-access=registration|url=https://archive.org/details/hallucinogenicpl00schu_0/page/5}}</ref> Evidence exists for the use of entheogens in [[History:Prehistory|prehistoric]] times, as well as in numerous ancient cultures, including Ancient Egyptian, Mycenaean, Ancient Greek, Vedic, Maya, Inca and Aztec cultures. The Upper Amazon is home to the strongest extant entheogenic tradition; the [[Unsolved:Urarina|Urarina]] of the Peruvian Amazon, for instance, continue to practice an elaborate system of [[Chemistry:Ayahuasca|ayahuasca]] shamanism, coupled with an animistic belief system.<ref>{{cite book|last=Dean|first=Bartholomew|date=2009|title=Urarina Society, Cosmology, and History in Peruvian Amazonia|location=Gainesville|publisher=University Press of Florida|isbn=978-0-8130-3378-5|url=http://www.upf.com/book.asp?id=DEANXS07|archive-url=https://web.archive.org/web/20110717170729/http://www.upf.com/book.asp?id=DEANXS07|archive-date=17 July 2011}}</ref>

Shamans consume hallucinogenic substances in order to induce a trance. Once in this trance, shamans believe that they are able to communicate with the spirit world, and can see what is causing their patients' illness. The Aguaruna of Peru believe that many illnesses are caused by the darts of sorcerers. Under the influence of [[Chemistry:Ayahuasca|yaji]], a hallucinogenic drink, Aguaruna shamans try to discover and remove the darts from their patients.<ref>{{cite journal|last=Brown|first=Michael Fobes|date=1988|title=Shamanism and Its Discontents|journal=Medical Anthropology Quarterly|volume=2|issue=2|pages=102–120|doi=10.1525/maq.1988.2.2.02a00020 |jstor=649156}}</ref>

In the 1970s, Frida G. Surawicz and Richard Banta published a review of two case studies where hallucinogenic drug use appeared to play a role in "delusions of being changed into a wolf" (sometimes referred to as "lycanthropy," or being a "werewolf"). They described a patient whose delusion was thought to be caused by an altered state of consciousness "brought on by LSD and strychnine and continued casual marijuana use." The review was published in the Canadian Psychiatric Association Journal. While both central cases described white male patients from contemporary Appalachia, Surawicz and Banta generalized their conclusions about a link between hallucinogens and "lycanthropy," based on historical accounts that reference myriad types of pharmacologically-similar drug-use alongside descriptions of "lycanthropes."<ref>{{cite journal|last1=Surawicz|first1=Fruda G.|last2=Banta|first2=Richard|date=November 1975|title=Lycanthropy Revisited|journal=Canadian Psychiatric Association Journal|volume=20|issue=7|pages=537–42|doi=10.1177/070674377502000706|pmid=1203837|s2cid=27654641 |doi-access=}}</ref>

===Early scientific investigations===
In an 1860 book, the mycologist Mordecai Cubitt Cooke differentiated a class of drugs roughly corresponding to hallucinogens from opiates, and in 1924 the toxicologist Louis Lewin described hallucinogens in depth under the name ''phantastica''. From the 1920s on, work in psychopharmacology and [[Biology:Ethnobotany|ethnobotany]] resulted in more detailed knowledge of various hallucinogens. In 1943, Albert Hofmann discovered the hallucinogenic properties of [[Chemistry:Lysergic acid diethylamide|lysergic acid diethylamide]] (LSD), which raised the prospect of hallucinogens becoming more broadly available.<ref name="abraham-et-al-1996">{{cite journal |last1=Abraham |first1=Henry David |last2=Aldridge |first2=Andrew M. |last3=Gogia |first3=Prashant |title=The Psychopharmacology of Hallucinogens |journal=Neuropsychopharmacology |date=1996 |volume=14 |issue=4 |pages=285–298 |doi=10.1016/0893-133X(95)00136-2 |pmid=8924196|s2cid=22105326 |doi-access=free }}</ref><!--Although natural hallucinogenic drugs have been known to mankind for millennia, it was not until the early 20th century that they received extensive attention from Western [[Science|science]]. Earlier beginnings include scientific studies of [[Chemistry:Nitrous oxide|nitrous oxide]] in the late 18th century, and initial studies of the constituents of the peyote cactus in the late 19th century. Starting in 1927 with Kurt Beringer's ''Der Meskalinrausch'' (The Mescaline Intoxication), more intensive effort began to be focused on studies of psychoactive plants. Around the same time, Louis Lewin published his extensive survey of psychoactive plants, ''Phantastica'' (1928). Important developments in the years that followed included the re-discovery of Mexican [[Biology:Psilocybin mushroom|psilocybin mushroom]]s (in 1936 by Robert J. Weitlaner) and [[Biology:Turbina corymbosa|Christmas vine]] (in 1939 by Richard Evans Schultes). Arguably the most important pre-[[Social:World War II|World War II]] development was by Albert Hofmann's 1938 discovery of the semi-[[Chemistry:Chemical synthesis|synthetic]] drug LSD, which was later discovered to produce hallucinogenic effects in 1943.-->

=== Hallucinogens after World War II ===
After World War II there was an explosion of interest in hallucinogenic drugs in [[Biology:Psychiatry|psychiatry]], owing mainly to the invention of LSD. Interest in the drugs tended to focus on either the potential for [[Medicine:Psychotherapy|psychotherapeutic]] applications of the drugs (see ''psychedelic psychotherapy''), or on the use of hallucinogens to produce a "controlled [[Medicine:Psychosis|psychosis]]", in order to understand psychotic disorders such as [[Medicine:Schizophrenia|schizophrenia]]. By 1951, more than 100 articles on LSD had appeared in medical journals, and by 1961, the number had increased to more than 1000 articles.<ref name="dyck">{{cite journal |last=Dyck |first=Erika |s2cid=13894582 |year=2005 |title=Flashback: Psychiatric Experimentation With LSD in Historical Perspective |journal=The Canadian Journal of Psychiatry |volume=50 |issue=7 |pages=381–388 |doi=10.1177/070674370505000703 |pmid=16086535 |doi-access=free }}</ref>

At the beginning of the 1950s, the existence of hallucinogenic drugs was virtually unknown to the general public in the West. However this soon changed as several influential figures were introduced to the hallucinogenic experience. [[Biography:Aldous Huxley|Aldous Huxley]]'s 1953 essay ''The Doors of Perception'', describing his experiences with [[Biology:Mescaline|mescaline]], and R. Gordon Wasson's 1957 ''Life'' magazine article ("Seeking the Magic Mushroom") brought the topic into the public limelight. In the early 1960s, counterculture icons such as Jerry Garcia, [[Biography:Timothy Leary|Timothy Leary]], [[Biography:Allen Ginsberg|Allen Ginsberg]] and Ken Kesey advocated the drugs for their [[Chemistry:Psychedelic drug|psychedelic]] effects, and a large subculture of psychedelic drug users was spawned. Psychedelic drugs played a major role in catalyzing the major social changes initiated in the 1960s.<ref>{{cite book | last = Goffman | first = Ken | title = Counterculture through the Ages: From Abraham to Acid House | location = New York | publisher = Villard | date = 2004 | at = Chapters 11–13 | isbn = 978-0812974751}}</ref><ref>{{cite book | last = Lindsey | first = Brink | title = The Age of Abundance: How Prosperity Transformed America's Politics and Culture | location = New York | publisher = Collins | date = 2007 | pages = 156 | quote = ...pot and psychedelics revealed to their users wildly different visions of reality from the "straight" one everybody took for granted. ... Guided into those transcendent realms, many young and impressionable minds were set aflame with visions of radical change. ... Antiwar protesters, feminists, student rebels, environmentalists, and gays all took their turns marching to the solemn strains of "We Shall Overcome"...}}</ref> As a result of the growing popularity of LSD and disdain for the hippies with whom it was heavily associated, LSD was banned in the United States in 1967.<ref>{{cite book | last = Goffman | first = Ken | title = Counterculture through the Ages: From Abraham to Acid House | location = New York | publisher = Villard | date = 2004 | pages = 266–267 | isbn = 978-0812974751 | quote = By normative social standards, something unseemly was going on, but since LSD, the catalyst that was unleashing the celebratory chaos, was still legal [in 1966], there was little [the authorities] could do... [That year, a]cross the nation, states started passing laws prohibiting LSD. .... By their panic, as expressed through their prohibitionary legislation, the conservative forces teased out what was perhaps the central countercultural progression for this epoch.}}</ref> This greatly reduced the clinical research about LSD, although limited experiments continued to take place, such as those conducted by Reese Jones in San Francisco.<ref>{{cite journal | vauthors = Francom P, Andrenyak D, Lim HK, Bridges RR, Foltz RL, Jones RT | title = Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry | journal = Journal of Analytical Toxicology | volume = 12 | issue = 1 | pages = 1–8 | date = January–February 1988 | pmid = 3352236 | doi = 10.1093/jat/12.1.1 }}</ref>

As early as the 1960s, research into the medicinal properties of LSD was being conducted. "Savage et al. (1962) provided the earliest report of efficacy for a hallucinogen in OCD, where after two doses of LSD, a patient who suffered from depression and violent obsessive sexual thoughts experienced dramatic and permanent improvement (Nichols 2004: 164)."<ref name="Nichols, David 2004"/>

Starting in the mid-20th century, psychedelic drugs have received extensive attention in the Western world. They have been and are being explored as potential therapeutic agents in treating [[Medicine:Alcoholism|alcoholism]],<ref>{{cite journal |url=http://eurekaselect.com/111921/article |title=Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin |journal=Current Drug Abuse Reviews |date=28 February 2013 |volume=6 |issue=1 |pages=17–29 |access-date=1 July 2013 |url-status=live |archive-url=https://web.archive.org/web/20131013230857/http://eurekaselect.com/111921/article |archive-date=13 October 2013 |last1=Michael |first1=P. Bogenschutz |doi=10.2174/15733998113099990002 |pmid=23627783 }}</ref> and other forms of drug [[Medicine:Addiction|addiction]].<ref>{{cite journal |url=http://eurekaselect.com/111918/article |title=Editorial (Hot Topic: The Potential of Psychedelics as a Preventative and Auxiliary Therapy for Drug Abuse) |journal=Current Drug Abuse Reviews |date=28 February 2013 |volume=6 |issue=1 |pages=1–2 |access-date=1 July 2013 |url-status=live |archive-url=https://web.archive.org/web/20131013230825/http://eurekaselect.com/111918/article |archive-date=13 October 2013 |last1=Hector |first1=Vargas-Perez |last2=Rick |first2=Doblin |doi=10.2174/18744737112059990023 |pmid=23773089 }}</ref><ref>{{cite journal |url=http://eurekaselect.com/111922/article |title=Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada |journal=Current Drug Abuse Reviews |date=28 February 2013 |volume=6 |issue=1 |pages=30–42 |access-date=26 December 2013 |url-status=live |archive-url=https://web.archive.org/web/20131018003441/http://www.eurekaselect.com/111922/article |archive-date=18 October 2013 |last1=Gerald |first1=Thomas |last2=Philippe |first2=Lucas |last3=n. |first3=Rielle Capler |last4=Kenneth |first4=W. Tupper |last5=Gina |first5=Martin |doi=10.2174/15733998113099990003 |pmid=23627784 }}</ref><ref>{{cite journal |url=http://eurekaselect.com/111920/article |title=Ibogaine in the Treatment of Substance Dependence |journal=Current Drug Abuse Reviews |date=28 February 2013 |volume=6 |issue=1 |pages=3–16 |access-date=1 July 2013 |url-status=live |archive-url=https://web.archive.org/web/20131013230814/http://eurekaselect.com/111920/article |archive-date=13 October 2013 |last1=Thomas |first1=Kingsley Brown |doi=10.2174/15672050113109990001 |pmid=23627782 }}</ref>

== Legal status and attitudes ==
In the United States, classical hallucinogens (psychedelics) are in the most strictly prohibited class of drugs, known as Schedule 1 drugs.<ref name="Nichols, David 2004"/> This classification was created for drugs that meet the three following characteristics: 1) they have no currently accepted medical use, 2) there is a lack of safety for their use under medical supervision, and 3) they have a high potential for abuse.<ref name="Nichols, David 2004"/> However, pharmacologist David E. Nichols argues that hallucinogens were placed in this class for political rather than scientific reasons.<ref name="Nichols, David 2004"/> In 2006, Albert Hofmann, the chemist who discovered [[Chemistry:Lysergic acid diethylamide|LSD]], said he believed LSD could be valuable when used in a medical rather than recreational context, and said it should be regulated in the same way as [[Biology:Morphine|morphine]] rather than more strictly.<ref>{{cite news | url=https://query.nytimes.com/gst/fullpage.html?res=9505E3DB153FF934A35752C0A9609C8B63&sec=&pagewanted=2 | work=The New York Times | title=The Saturday Profile; Nearly 100, LSD's Father Ponders His 'Problem Child' | first=Craig S. | last=Smith | date=7 January 2006 | access-date=22 May 2010 | url-status=live | archive-url=https://web.archive.org/web/20110520182244/http://query.nytimes.com/gst/fullpage.html?res=9505E3DB153FF934A35752C0A9609C8B63&sec=&pagewanted=2 | archive-date=20 May 2011 | df=dmy-all }}</ref>

The Netherlands previously allowed psilocybin mushrooms to be sold, but in October 2007 the Dutch government moved to ban their sale following several widely publicized incidents involving tourists.<ref>{{Cite news |url=http://news.bbc.co.uk/2/hi/europe/7041961.stm |title=Netherlands bans magic mushrooms |work=BBC |date=12 October 2007 |access-date=13 November 2016 |url-status=live |archive-url=https://web.archive.org/web/20161113191144/http://news.bbc.co.uk/2/hi/europe/7041961.stm |archive-date=13 November 2016 }}</ref> In November 2020, Oregon became the first U.S. state to both decriminalize psilocybin and legalize it for therapeutic use, after Ballot Measure 109 passed.<ref>{{Cite web|last=Naftulin|first=Julia|date=4 November 2020|title=Oregon has become the first state to legalize 'magic' mushrooms for therapeutic use. Here's what that means.|url=https://www.businessinsider.com/oregon-first-ever-state-to-legalize-psilocybin-for-therapeutic-use-2020-11|access-date=27 May 2021|website=Business Insider|language=en-US}}</ref>

==Effects==
===Relationship between long-term use and mental illness===
No clear connection has been made between psychedelic drugs and organic brain damage. However, [[Medicine:Hallucinogen persisting perception disorder|hallucinogen persisting perception disorder]] (HPPD) is a diagnosed condition wherein certain visual effects of drugs persist for a long time, sometimes permanently,<ref>{{cite journal |last1=Halpern |first1=John H. |last2=Lerner |first2=Arturo G. |last3=Passie |first3=Torsten |title=A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD |journal=Behavioral Neurobiology of Psychedelic Drugs |series=Current Topics in Behavioral Neurosciences |date=2018 |volume=36 |pages=333–360 |doi=10.1007/7854_2016_457|pmid=27822679 |isbn=978-3-662-55878-2 }}</ref> although the underlying cause and pathology remains unclear.<ref>{{cite journal |last1=Ford |first1=Hannah |last2=Fraser |first2=Clare L. |last3=Solly |first3=Emma |last4=Clough |first4=Meaghan |last5=Fielding |first5=Joanne |last6=White |first6=Owen |last7=Van Der Walt |first7=Anneke |title=Hallucinogenic Persisting Perception Disorder: A Case Series and Review of the Literature |journal=Frontiers in Neurology |date=6 May 2022 |volume=13 |pages=878609 |doi=10.3389/fneur.2022.878609 |pmid=35599738 |pmc=9120359 |doi-access=free }}</ref>

A large epidemiological study in the U.S. found that other than personality disorders and other substance use disorders, lifetime hallucinogen use was not associated with other mental disorders, and that risk of developing a hallucinogen use disorder was very low.<ref>{{cite journal | vauthors = Shalit N, Rehm J, Lev-Ran S | title = Epidemiology of hallucinogen use in the U.S. results from the National epidemiologic survey on alcohol and related conditions III | journal = Addictive Behaviors | volume = 89 | pages = 35–43 | pmid = 30245407 | doi = 10.1016/j.addbeh.2018.09.020 | year = 2019 | s2cid = 52821352 }}</ref>

A 2019 systematic review and meta-analysis by Murrie et al. found that the transition rate from a diagnosis of hallucinogen-induced [[Medicine:Psychosis|psychosis]] to that of [[Medicine:Schizophrenia|schizophrenia]] was 26% (CI 14%-43%), which was lower than cannabis-induced psychosis (34%) but higher than amphetamine (22%), opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up. In comparison, the transition rate for brief, atypical and not otherwise specified psychosis was found to be 36%.<ref>{{cite journal |last1=Murrie |first1=Benjamin |last2=Lappin |first2=Julia |last3=Large |first3=Matthew |last4=Sara |first4=Grant |title=Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis |journal=Schizophrenia Bulletin |date=16 October 2019 |volume=46 |issue=3 |pages=505–516 |doi=10.1093/schbul/sbz102 |pmid=31618428 |pmc=7147575 |doi-access=free }}</ref>

===Effects on the brain===
Different classes of hallucinogens have different pharmacological mechanisms of action.<ref name="volgin-et-al-2019"/><ref name="nichols-2018">{{Citation |last=Nichols |first=David E. |title=Chemistry and Structure–Activity Relationships of Psychedelics |date=2018 |url=https://doi.org/10.1007/7854_2017_475 |work=Behavioral Neurobiology of Psychedelic Drugs |pages=1–43 |editor-last=Halberstadt |editor-first=Adam L. |series=Current Topics in Behavioral Neurosciences |volume=36 |place=Berlin, Heidelberg |publisher=Springer |language=en |doi=10.1007/7854_2017_475 |pmid=28401524 |isbn=978-3-662-55880-5 |access-date=5 March 2022 |editor2-last=Vollenweider |editor2-first=Franz X. |editor3-last=Nichols |editor3-first=David E.}}</ref> Psychedelics are [[Biology:5-HT2A receptor#Agonists|5-HT<sub>2A</sub> receptor agonists]] ([[Chemistry:Serotonin|serotonin]] 2A receptor agonists).<ref name="nichols-2016">{{Cite journal |last=Nichols |first=David E. |date=2016-04-01 |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="nichols-2018"/>

LSD, mescaline, psilocybin, and PCP are drugs that cause hallucinations, which can alter a person's perception of reality. LSD, mescaline, and psilocybin cause their effects by initially disrupting the interaction of nerve cells and the neurotransmitter serotonin.<ref name="drugabuse.gov">"DrugFacts: Hallucinogens – LSD, mescaline, Psilocybin, and PCP." Drugabuse.gov. National Institute on Drug Abuse, n.d. Web. 13 April 2014. <http://www.drugabuse.gov/publications/drugfacts/hallucinogens-lsd-mescaline-psilocybin-pcp{{Dead link|date=January 2020 |bot=InternetArchiveBot |fix-attempted=yes }}>.</ref> It is distributed throughout the brain and spinal cord, where the serotonin system is involved with controlling of the behavioral, perceptual, and regulatory systems. This also includes mood, hunger, body temperature, sexual behavior, muscle control, and sensory perception. Certain hallucinogens, such as PCP, act through a glutamate receptor in the brain which is important for perception of pain, responses to the environment, and learning and memory.
Thus far, there have been no properly controlled research studies on the specific effects of these drugs on the human brain, but smaller studies have shown some of the documented effects associated with the use of hallucinogens.<ref name="drugabuse.gov"/>

===Psychotomimetic paradigm===
While early researchers believed certain hallucinogens mimicked the effects of schizophrenia, it has since been discovered that some hallucinogens resemble endogenous psychoses better than others. PCP and ketamine are known to better resemble endogenous psychoses because they reproduce both positive and negative symptoms of psychoses, while psilocybin and related hallucinogens typically produce effects resembling only the positive symptoms of schizophrenia.<ref>{{cite journal | vauthors = Vollenweider FX, Geyer MA | s2cid = 230298 | title = A systems model of altered consciousness: integrating natural and drug-induced psychoses | journal = Brain Research Bulletin | volume = 56 | issue = 5 | pages = 495–507 | date = November 2001 | pmid = 11750795 | doi = 10.1016/S0361-9230(01)00646-3 }}</ref> While the serotonergic psychedelics (LSD, psilocybin, mescaline, etc.) do produce subjective effects distinct from NMDA antagonist dissociatives (PCP, ketamine, dextrorphan), there is obvious overlap in the mental processes that these drugs affect and research has discovered that there is overlap in the mechanisms by which both types of psychedelics mimic psychotic symptoms.<ref>{{cite journal | vauthors = Aghajanian GK, Marek GJ | s2cid = 13040014 | title = Serotonin model of schizophrenia: emerging role of glutamate mechanisms | journal = Brain Research. Brain Research Reviews | volume = 31 | issue = 2–3 | pages = 302–12 | date = March 2000 | pmid = 10719157 | doi = 10.1016/S0165-0173(99)00046-6 }}</ref><ref>{{cite journal | vauthors = Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA, Nomikos GG, Greengard P | s2cid = 84901005 | title = Diverse psychotomimetics act through a common signaling pathway | journal = Science | volume = 302 | issue = 5649 | pages = 1412–5 | date = November 2003 | pmid = 14631045 | doi = 10.1126/science.1089681 | bibcode = 2003Sci...302.1412S }}</ref><ref>{{cite journal |last1=Tsapakis |first1=E. M. |title=Glutamate and psychiatric disorders |journal=Advances in Psychiatric Treatment |volume=8 |issue=3 |pages=189–97 |year=2002 |doi=10.1192/apt.8.3.189|doi-access=free }}</ref> One double-blind study examining the differences between DMT and [[Chemistry:Ketamine|ketamine]] hypothesized that ''[[Chemistry:Serotonergic psychedelic|classically psychedelic]]'' drugs most resemble paranoid schizophrenia while ''dissociative'' drugs best mimicked catatonic subtypes or otherwise undifferentiated schizophrenia.<ref name="ketamine-dmt">{{cite journal | vauthors = Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, Kovar KA | title = Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers | journal = Pharmacopsychiatry | volume = 38 | issue = 6 | pages = 301–11 | date = November 2005 | pmid = 16342002 | doi = 10.1055/s-2005-916185 | s2cid = 28653940 }}</ref> The researchers stated that their findings supported the view that "a heterogeneous disorder like schizophrenia is unlikely to be modeled accurately by a single pharmacological agent."<ref name="ketamine-dmt"/>

==Chemistry==
Classical hallucinogens (psychedelics) can be divided into three main chemical classes: tryptamines (such as [[Chemistry:Psilocin|psilocin]] and DMT), ergolines (such as [[Chemistry:Lysergic acid diethylamide|LSD]]), and phenethylamines (such as [[Biology:Mescaline|mescaline]]).<ref name="nichols-2018"/> Tryptamines closely resemble [[Chemistry:Serotonin|serotonin]] chemically.<ref name="nichols-2018"/>

==See also==
* [[Unsolved:Closed-eye hallucination|Closed-eye visualization]]
* [[Chemistry:DOx|DOx]]
* [[Chemistry:Hallucinogenic plants in Chinese herbals|Hallucinogenic plants in Chinese herbals]]
* [[Unsolved:Out-of-body experience|Out-of-body experience]]
* Psychedelia
* [[Unsolved:Psychedelic experience|Psychedelic experience]]
* [[Philosophy:Psychonautics|Psychonautics]]
* Psychopharmacology
* [[Philosophy:Visual perception|Visual perception]]

==References==
{{Reflist|30em}}

== Further reading ==
* Ann & Alexander Shulgin: PIHKAL (Phenethylamines I Have Known And Loved), a Chemical Love Story
* Ann & Alexander Shulgin: TIHKAL (Tryptamines I Have Known And Loved), the Continuation
* Charles S. Grob, ed.: Hallucinogens, a reader
* Winkelman, Michael J., and Thomas B. Roberts (editors) (2007).''Psychedelic Medicine: New Evidence for Hallucinogens as Treatments'' 2 Volumes. Westport, CT: Praeger/Greenwood.

== External links ==
* [http://www.erowid.org/ Erowid] is a web site dedicated entirely to providing information about psychoactive drugs, with an impressive collection of trip reports, materials collected from the web and usenet, and a bibliography of scientific literature.
* [http://www.maps.org/ Multidisciplinary Association for Psychedelic Studies] is a nonprofit research and educational organization which carries out clinical trials and other research in order to assess the potential medicinal uses of psychedelic drugs and develop them into medicines.
* [http://www.psychonautwiki.org PsychonautWiki]{{Dead link|date=November 2023 |bot=InternetArchiveBot |fix-attempted=yes }} is a wiki dedicated to documenting psychoactive drugs and their subjective effects, with an emphasis on hallucinogens and novel psychoactives. The site hosts experience reports, tutorials, and a curated collection of articles.

{{Major Drug Groups}}
{{Drug use}}
{{Hallucinogens}}
{{Cannabinoids}}
{{Entactogens}}

[[Category:Hallucinations]]

{{Sourceattribution|Hallucinogen}}