View source for Lysergic acid diethylamide detailed information

{{drugbox |
| image = LSD-2D, 3D.png
| IUPAC_name = (6a''R'',9''R'')-''N'',''N''-diethyl-7-methyl-4,6,6a,7,8,9-<br>
hexahydroindolo-[4,3-''fg'']quinoline-9-carboxamide
| CAS_number = 50-37-3
| PubChem = 5761
| C=20 | H=25| N=3| O=1
| molecular_weight = 323.431 g/mol
| melting_point = 80
| synonyms = LSD, LSD-25, lysergide, <small>D</small>-lysergic acid diethylamide, ''N'',''N''-diethyl-<small>D</small>-lysergamide
| smiles = CN1[C@](C2=C[C@@H](C(N(CC)CC)=O)C1)([H])CC3=CNC4=C3C2=CC=C4
| elimination_half-life = 3 hours
| metabolism = hepatic
| excretion = renal
| pregnancy_category =
| pregnancy_AU = X
| pregnancy_US = X
| legal_AU = Schedule 9
| legal_CA = Schedule III
| legal_UK = Class A
| legal_US = Schedule I
| legal_status =
| routes_of_administration = [[Wiktionary:oral|Oral]], [[Wiktionary:intravenous|Intravenous]], [[Wiktionary:transdermal patch|Transdermal]]
}}
{{SI}}
{{CMG}}
__NOTOC__


==Overview==

'''Lysergic acid diethylamide''', '''LSD''', '''LSD-25''', or '''acid''', is a [[semisynthetic]] [[psychedelic drug]] of the [[ergoline]] family. Probably the most widely known psychedelic, it has been used mainly as a [[recreational drug]], an [[entheogen]], and a [[tool]] to supplement various practices for [[transcendence (philosophy)|transcendence]], including in [[meditation]], [[psychonautics]], [[art]] projects, and illicit (though at one time legal) [[psychedelic therapy]], whether self-administered or not. It is [[chemical synthesis|synthesized]] from [[lysergic acid]] derived from [[ergot]], a [[grain]] [[fungus]] that typically grows on [[rye]] and was first synthesized by [[Switzerland|Swiss]] [[chemist]] [[Albert Hofmann]]. The short form LSD comes from its early codename ''LSD-25'', which is an abbreviation for the German "Lysergsäure-diethylamid" followed by a sequential number.<ref name="problem-child" /><ref name="tihkal" />

LSD is sensitive to [[oxygen]], [[ultraviolet|ultraviolet light]], and [[chlorine]], especially in [[solution]], though its potency may last for years if it is stored away from light and moisture at low temperature. In pure form it is colorless, odorless, and mildly bitter.<ref name="tihkal" /><!-- described in this book in the part that is not online --> LSD is typically delivered orally, usually on a substrate such as absorbent [[Blotting paper|blotter paper]], a [[sugar|sugar cube]], or [[gelatin]]. In its liquid form, it can be administered by intramuscular or intravenous injection. The threshold dosage level needed to cause a psychoactive effect on humans is of the order of 20 to 30 [[kilogram#SI multiples|µg]] (micrograms).

Introduced by [[Sandoz Laboratories]] as a drug with various [[psychiatric]] uses, LSD quickly became a [[psychedelic psychotherapy|therapeutic agent]] that appeared to show great promise. However, the extra-medicinal use of the drug in [[Western world|Western society]] during the mid-twentieth century led to a political firestorm that resulted in the [[Hallucinogenic drug#Legal status and attitudes|banning of the substance]].<ref> {{cite web|url=http://www.rsc.org/chemistryworld/Issues/2006/January/LSD.asp |title=LSD: cultural revolution and medical advances |accessdate=2007-09-27 |work=Royal Society of Chemistr }}</ref> A number of organizations—including [[Beckley Foundation|the Beckley Foundation]], [[Multidisciplinary Association for Psychedelic Studies|MAPS]], [[Heffter Research Institute]] and the [[Albert Hofmann|Albert Hofmann Foundation]]—exist to fund, encourage and coordinate research into its medicinal uses.<ref> {{cite web|url=http://www.hofmann.org/ |title=The Albert Hofmann Foundation |accessdate=2007-09-27 |work=Hofmann Foundation }}</ref>

== History ==
{{main|History of LSD}}
LSD was first synthesized on [[November 16]], [[1938]] by a Swiss chemist named Dr. [[Albert Hofmann]] at the [[Sandoz Laboratories]] in [[Basel]], [[Switzerland]], as part of a large research program searching for medically useful [[ergoline|ergot alkaloid]] derivatives.<ref>Dr. Albert Hofmann[http://www.nida.nih.gov/infofacts/LSD.html];
translated from the original German (LSD Ganz Persönlich) by J. Ott. [http://www.maps.org/news-letters/v06n3/06346hof.html MAPS-Volume 6 Number 3 Summer 1996]</ref> [[Ergot]] is a fungus that, by infecting cereal grains used for making rye breads, causes [[ergotism]]. After Dr. Hofmann succeeded in synthesizing [[Ergonovine|ergobasine]] (which became the preeminent uterotonic), he began working on other [[amide]] derivatives of [[lysergic acid]]. LSD (lysergic acid diethylamide) is one of the major drugs making up the hallucinogen class of drugs.<ref>[http://www.nida.nih.gov/infofacts/LSD.html InfoFacts - LSD<!-- Bot generated title -->]</ref> Lysergic acid diethylamide, the 25th lysergic acid derivative Hofmann synthesised (hence the name LSD-25) was developed initially as a probable [[analeptic]], a [[circulatory system|circulatory]] and [[respiratory system|respiratory]] stimulant, based on its structural similarity to another known analeptic, [[nikethamide]] (nicotinic acid diethylamide). However, no extraordinary benefits of the compound were identified during animal tests (though laboratory notes briefly mention that the animals became "restless" under its effects), and its study was discontinued.<ref name="hyponichols" /> Its [[psychedelic]] properties were unknown until 5 years later, when Hofmann, acting on what he has called a "peculiar presentiment," returned to work on the chemical.<ref name="hyponichols"> {{cite web|url=http://www.erowid.org/general/conferences/conference_mindstates4_nichols.shtml |title=Hypothesis on Albert Hofmann's Famous 1943 "Bicycle Day" |accessdate=2007-09-27 |last=Nichols |first=David |date=2003-05-24 |work=Hofmann Foundation }}</ref> While re-synthesizing LSD-25 for further study on [[April 16]] [[1943]], Hofmann became dizzy and was forced to stop work. In his journal, Hofmann wrote that after becoming dizzy he proceeded home and was affected by a "remarkable restlessness, combined with a slight dizziness". Hofmann stated that as he lay in his bed he sank into a not unpleasant "intoxicated like condition" which was characterized by an extremely stimulated imagination. He stated that he was in a dreamlike state, and with his eyes closed he could see uninterrupted streams of "fantastic pictures, extraordinary shapes with intense, [[kaleidoscope|kaleidoscopic]] play of colors." The condition lasted about two hours after which it faded away.<ref> {{cite web|url=http://www.csp.org/chrestomathy/lsd_my1.html |title=LSD: My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science. |accessdate=2007-09-27 |last=Hofmann |first=Albert |date=2003-05-24 |publisher=Council on Spiritual Practices }}</ref> Hofmann had attributed the psychoactive effects he experienced to accidentally absorbing a tiny amount of LSD-25 into his skin. Three days later he would take a much larger dose in order to test its effects further; this day would later be referred to as the "Bicycle Day".<ref name="problem-child">Hofmann, Albert. ''[http://www.psychedelic-library.org/child.htm LSD—My Problem Child]'' (McGraw-Hill, 1980). ISBN 0-07-029325-2.</ref>

=== Bicycle day === 

On [[April 19]], [[1943]] Dr. [[Albert Hofmann]] intentionally ingested 250 [[micrograms|µg]] of LSD, which he hypothesized would be at most a threshold level dose, based on his research on other ergot alkaloids. Surprisingly, the substance showed a potency orders of magnitude above almost any other substance known at the time, amounting to a much heavier dose than typically given in modern therapeutic use. After ingesting the substance Hofmann found himself struggling to speak intelligibly and asked his laboratory assistant, who knew of the self-experiment, to escort him home on his bicycle, since wartime restrictions made automobiles unavailable. On the bicycle ride home, Hofmann's condition became more severe and in his journal he stated that everything in his field of vision wavered and was distorted, as if seen in a curved mirror. Hofmann also stated that while riding on the bicycle, he had the sensation of being stationary, unable to move from where he was, despite the fact that he was moving very rapidly. Once Hofmann arrived home, he summoned a doctor and asked his neighbor for milk, believing it might help relieve the symptoms. Hofmann wrote that despite his delirious and bewildered condition, he was able to choose milk as a nonspecific antidote for poisoning.<ref name="histlsd"> {{cite web|url=http://www.a1b2c3.com/drugs/lsd01.htm |title=History Of LSD |accessdate=2007-09-27 |last=Hofmann |first=Albert }}</ref> Upon arriving the attending doctor could find no abnormal physical symptoms other than extremely dilated pupils. After spending several hours terrified that his body had been possessed by a [[demon]], that his next door neighbor was a witch, and that his furniture was threatening him, Dr. Hofmann feared he had become completely insane. In his journal Hofmann said that the doctor saw no reason to prescribe medication and instead sent him to his bed. At this time Hofmann said that the feelings of fear had started to give way to feelings of good fortune and gratitude, and that he was now enjoying the colors and plays of shapes that persisted behind his closed eyes. Hofmann mentions seeing "fantastic images" surging past him, alternating and opening and closing themselves into circles and spirals and finally exploding into colored fountains and then rearranging themselves in a constant flux. Hofmann mentions that during the condition every [[Psychoacoustics|acoustic]] perception, such as the sound of a passing automobile, was transformed into [[optical]] perceptions. Eventually Hofmann slept and upon awakening the next morning felt refreshed and clearheaded, though somewhat physically tired. He also stated that he had a sensation of well being and renewed life and that his breakfast tasted unusually delicious. Upon walking in his garden he remarked that all of his senses were "vibrating in a condition of highest sensitivity, which then persisted for the entire day".<ref name="histlsd" />

=== Early research ===

Early researchers on LSD saw its potency and noticed that even in extremely small quantities it could significantly alter the mental functioning of healthy volunteers. Due to the fact that LSD could produce changes in perceptions and emotions, early researchers hypothesized that the cause of some mental illnesses, particularly schizophrenia, were due to the human body releasing small quantities of substances identical to LSD.<ref name="sgrof">{{cite book | last = Grof | first = Stanislav | authorlink = | coauthors = | title = LSD Psychotherapy | publisher = | date = | location = | pages = | url = | doi = | id = | isbn = 978-0966001945 }}</ref> Much of the research during the late 1940s dealt with this hypothesis and many LSD sessions conducted for scientific study were often termed "experimental psychoses", and this is where the terms "psychoactive" , "psychotomimetic" and "hallucinogenic" were coined to refer to such drugs. Generally these studies revolved around the attempt to block the effects of LSD with premedication, which was thought to be able to lead to medical treatments for schizophrenia. The studies showed that there was no such connection (the effects of LSD and those of schizophrenia are drastically different and have different causes and functions). Some early researchers also started to suggest that LSD could have positive effects and could be used as a treatment for patients with psychiatric illnesses. Some reports suggested that even small doses of LSD could have dramatic effects on the personalities and attitudes and even lifestyles of test subjects. Early LSD research also found evidence of the drug's ability to facilitate relief of various emotional episodes related to traumatic memories from childhood of patients.<ref name="sgrof" />

=== Government research ===

[[Image:LiquidLSD.jpg|100px|thumb|right|A solution of LSD]]

During the [[Cold War]], intelligence agencies were keenly interested in the possibilities of using LSD for [[interrogation]] and [[mind control]], as well as for large-scale [[social engineering (political science)|social engineering]]. The [[CIA]] research on LSD, most of which was done under [[Project MKULTRA]], the code name for a CIA mind-control research program, began in the 1950s and continued until the late 1960s.<ref name="CIADOD">{{cite news | first= | last= | coauthors= | title=Chapter 3: Supreme Court Dissents Invoke the Nuremberg Code: CIA and DOD Human Subjects Research Scandals | date= | publisher=[[United States Department of Energy]] | url =http://hss.energy.gov/healthsafety/ohre/roadmap/achre/chap3_4.html | work =Human Radiation Experiments | pages = | accessdate = 2007-10-04 | language = }}</ref>

Tests were also conducted by the U.S. Army Biomedical Laboratory (now known as the U.S. Army Medical Research Institute of Chemical Defense) located in the [[Edgewood Arsenal]] at [[Aberdeen Proving Grounds]]. The government would administer LSD to subjects (without consent) and then perform a battery of tests to investigate the effects of the drug on [[soldier]]s. Based on remaining publicly available records, the projects seem to have concluded that LSD was of little practical use as a mind control drug and moved on to other drugs.<ref> {{cite web|url=http://findarticles.com/p/articles/mi_m1374/is_5_59/ai_55722247 |title=Lessons Learned A Half-Century of Experimenting on Humans - U.S. Army experiments |accessdate=2007-10-04 |last=D. Moreno |first=Jonathan |date=September 1999 |work=Humanist }}</ref>

Both the CIA and the Army experiments became highly controversial when they became public knowledge in the 1970s, as the test subjects were not normally informed of the nature of the experiments, or even that they were subjects in experiments at all.<ref name="CIADOD" /> In 1961, [[Paul Robeson]] attempted suicide in a Moscow hotel room. His son claimed this was precipitated by a CIA agent who placed some synthetic hallucinogen in his drink.[http://www.democracynow.org/1999/7/6/did_the_u_s_government_drug] At least one person, an Army scientist named [[Frank Olson]] is thought by some to have committed suicide by leaping from a tall building as a result of his being unknowingly given LSD.<ref name="CIADOD" /> Frank Olson's son, Eric Olson, believes that his father was murdered by government officials and a 1994 exhumation and examination by forensic pathologists at George Washington University of the body suggested that Olson had suffered blunt trauma to the back of his head prior to falling from the building.<ref> {{cite web|url=http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2004/09/12/MNG468MM8N1.DTL |title=Son probes strange death of WMD worker He believes agents murdered employee of Army to protect government secrets |accessdate=2007-10-04 |last=Shane |first=Scott |date=2004-09-12 |work=Baltimore Sun }}</ref> Most of the MKULTRA records were deliberately destroyed in 1973. The controversy contributed to [[Gerald Ford|President Ford]]'s creation of the [[United States President's Commission on CIA activities within the United States|Rockefeller Commission]] and new regulations on [[informed consent]].<ref name="CIADOD" />The [[United Kingdom|British]] government also engaged in LSD testing; in 1953 and 1954, scientists working for [[Secret Intelligence Service|MI6]] dosed servicemen in an effort to find a "truth drug". The test subjects were not informed that they were being given LSD, and had in fact been told that they were participating in a medical project to find a cure for the [[common cold]]. One subject, aged 19 at the time, reported seeing "walls melting, cracks appearing in people's faces … eyes would run down cheeks, [[Salvador Dalí]]-type faces … a flower would turn into a slug". After keeping the trials secret for many years, MI6 agreed in 2006 to pay the former test subjects financial compensation. Like the CIA, MI6 decided that LSD was not a practical drug for mind control purposes.<ref>Rob Evans, "[http://politics.guardian.co.uk/homeaffairs/story/0,,1716708,00.html MI6 pays out over secret LSD mind control tests]". ''The Guardian'' 24 February 2006.</ref>

=== Current research ===

Today, most research with LSD involves animals or cells.  However, a few groups are exploring LSD effects in humans.  The [[Multidisciplinary Association for Psychedelic Studies]] has an eight-person study in Switzerland to see if a large dose of LSD (200 ug) is more helpful as part of psychotherapy for cancer patients than a lower dose (20 ug).  The [[Beckley Foundation]] is studying the effects of LSD on mental activity and consciousness in LSD-experienced volunteers, in order to gain insight into its reported effects on creativity and insight.<ref>The Lancet, Reviving research into psychedelic drugs 2006 367(9518):1214 [http://www.beckleyfoundation.org/bib/doc/bf/2008_Kelly_211367_1.pdf]</ref>  There has been additional interest in studying the effects of LSD on cluster headaches, although the current status of this research is uncertain.  While these studies could be criticized for being too small to lead to strong conclusions, they may represent the beginnings of renewed scientific interest into LSD.

== Dosage ==

Dosages of LSD are measured in [[kilogram#SI multiples|micrograms]] (µg), or millionths of a [[gram]]. By comparison, dosages of almost all other drugs, both recreational and medicinal, are measured in [[milligram]]s (mg), or thousandths of a gram. [[Albert Hofmann|Hofmann]] determined that an active dose of [[mescaline]], roughly 0.2 to 0.5g, has effects comparable to 100µg or less of LSD; put another way, LSD is between five to ten thousand times more active than mescaline.<ref name="problem-child" />

While a single dose of LSD may be between 100 and 500 micrograms — an amount roughly equal to one-tenth the mass of a grain of sand — threshold effects can be felt with as little as 25 micrograms.<ref name="greiner">{{cite journal | author=Greiner T, Burch NR, Edelberg R | title=Psychopathology and psychophysiology of minimal LSD-25 dosage; a preliminary dosage-response spectrum | journal=AMA Arch Neurol Psychiatry | year=1958 | pages=208–10 | volume=79 | issue=2 | id=PMID 13497365}}</ref>

Generally, the dosage that will produce a threshold psychotropic effect in humans is considered to be 20 to 30µg.<ref>Stoll, W.A. (1947). Ein neues, in sehr kleinen Mengen wirsames Phantastikum. Schweiz. Arch. Neur. 60,483.</ref><ref name="greiner" /> According to Glass and Henderson's review, black-market LSD is largely iterated though sometimes contaminated by manufacturing by-products. Typical doses in the 1960s ranged from 200 to 1000µg while street samples of the 1970s contained 30 to 300µg. By the 1980s, the amount had reduced to between 100 to 125 µg, lowering more in the 1990s to the 20–80 µg range. (Lower doses, Glass and Henderson found, generally produce fewer [[bad trip]]s.)<ref name="henderson-glass">{{cite book | author= Henderson, Leigh A.; Glass, William J. | title=LSD: Still with us after all these years | year=1994 | Jossey-Bass Inc., San Francisco | id = ISBN 978-0787943790}}</ref>

Estimates for the lethal dosage ([[LD50|LD<sub>50</sub>]]) of LSD range from between 200 µg/kg to more than 1 mg/kg of human body mass, though most sources report that there are no known human cases of such an overdose. Other sources note one report of a suspected fatal overdose of LSD occurring in November 1975 in [[Kentucky]] in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously, i.e., over 3,000 more typical oral doses of ~100 µg had been injected.<ref name="erowid-dosage">{{cite web
| url = http://www.erowid.org/chemicals/lsd/lsd_dose.shtml   
| title = LSD Vault: Dosage   
| date = [[2006-07-06]]   
| accessdate = 2007-01-31}}</ref><ref>{{cite web | url = http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&ID=1389&DocPartID=1151   
| title = LSD Toxicity: A Suspected Cause of Death   
| publisher = Journal of the Kentucky Medical Association
| accessdate = 2007-11-26
}}</ref>

[[Tusko#Tusko:_"The_elephant on LSD"|Tusko]] the elephant died shortly after being injected with 297 mg in 1962, but whether the LSD was the cause of his death is controversial.   
    
LSD is not considered addictive, in that its users do not exhibit the medical community's commonly accepted definitions of [[addiction]] and physical dependence. Rapid tolerance build-up prevents regular use, and there is cross-tolerance shown between LSD, [[mescaline]]<ref name="isbell_mescaline">{{cite journal
 | author = Wolbach AB Jr, Isbell H, Miner EJ
 | title = Cross tolerance between mescaline and LSD-25, with a comparison of the mescaline and LSD reactions
 | journal= Psychopharmacologia
 | year= 1962
 | volume = 3
 | pages= 1-14
 | url = http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=2032&DocPartID=1893
 | id = PMID 14007904
 | doi = 10.1007/BF00413101 <!--Retrieved from CrossRef by DOI bot-->
}}</ref>
and [[psilocybin]].<ref name="isbell_psilocybin">{{cite journal
 | author = Isbell H, Wolbach AB, Wikler A, Miner EJ
 | title = Cross Tolerance between LSD and Psilocybin
 | journal= Psychopharmacologia
 | year= 1961
 | volume = 2
 | pages= 147-159
 | url = http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=1979&DocPartID=1843
 | id = PMID 13717955
 | pages = E353
 | doi = 10.1007/BF00407974 <!--Retrieved from CrossRef by DOI bot-->
}}</ref> This tolerance diminishes after a few days without use and is probably caused by downregulation of [[5-HT2A receptor|5-HT<sub>2A</sub> receptors]] in the brain<!-- PMID 2803482, PMID 1969270 -->.

Adverse effects of psychotropics are often treated with fast acting [[benzodiazepine]]s like [[diazepam]] or [[triazolam]] that have calming and antianxiety effects but do not directly affect the specific actions of psychotropics. Many [[rumor]]s about [[home remedy|home remedies]] to counteract psychedelic effects are circulated, including [[sugar]], [[calcium]], orange juice, [[milk]], or [[niacin]], but none of them have been shown to be effective and they make no sense from a [[pharmacology|pharmacological]] standpoint. Theoretically, specific [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[antagonist]]s, such as [[Seroquel]], would be direct [[antidote]]s, although some anecdotal reports claim otherwise.<ref>Huxley, Aldous ''The Doors of Perception and Heaven & Hell'', Harper & Row, 1954</ref> Also, some people have reported that taking a [[SSRI]] such as [[Prozac]] or drugs that are [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] antagonists such as [[Trazodone]] will counteract the effects of LSD.

== Effects ==
=== Pharmacokinetics ===

[[Image:Lsd.pdb.gif|thumb|256px|right|3D representation of an LSD molecule.]]

LSD's effects normally last from 6-12 hours depending on dosage, tolerance, body weight and age<ref name="tihkal">[[Alexander Shulgin|Alexander]] and [[Ann Shulgin]]. "[http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD]", in ''[[TiHKAL]]'' (Berkeley: Transform Press, 1997). ISBN 0-963-00969-9.</ref> - Sandoz's prospectus for "Delysid" warned: "intermittent disturbances of effect may occasionally persist for several days."<ref name="problem-child" /> Contrary to early reports and common belief, LSD effects do not last longer than significant levels of the drug in the blood. Aghajanian and Bing found LSD had an elimination half-life of 175 minutes,<ref>{{cite journal|author=Aghajanian, George K. and Bing, Oscar H. L.|url=http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf|title=Persistence of lysergic acid diethylamide in the plasma of human subjects|journal=Clin. Pharmacol. Ther.|volume=5|year=1964|pages=611–4|id=PMID 14209776}}</ref> while, more recently, Papac and Foltz reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose.<ref>{{cite journal | author=Papac DI, Foltz RL | title=Measurement of lysergic acid diethylamide (LSD) in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry | journal=J Anal Toxicol | year=1990 | pages=189-90 | volume=14 | issue=3 | id=PMID 2374410}}</ref> Notably, Aghajanian and Bing found that blood concentrations of LSD matched the time course of volunteers' difficulties with simple arithmetic problems.

=== Pharmacodynamics ===

LSD affects a large number of the [[G protein coupled receptor|G protein coupled]] [[receptor (biochemistry)|receptors]], including all [[dopamine receptor]] subtypes, all [[Adrenergic receptor|adrenoreceptor]] subtypes as well as many others. LSD binds to most [[5-HT receptor|serotonin receptor]] subtypes except for 5-HT<sub>3</sub> and 5-HT<sub>4</sub>. However, most of these receptors are affected at too low affinity to be activated by the brain concentration of approximate 10–20&nbsp;nM.<ref name="nichols">{{cite journal | author=Nichols, David E. | title=Psychotropics | journal=Pharmacology & Therapeutics | year=2004 | pages=131-81 | volume=101 | issue=2 | url=http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6318|id=PMID 14761703}}</ref> Recreational doses of LSD can affect 5-HT<sub>1A</sub>, [[5-HT2A receptor|5-HT<sub>2A</sub>]], 5-HT<sub>2C</sub>, 5-HT<sub>5A</sub>, 5-HT<sub>5B</sub>, and 5-HT<sub>6</sub> receptors. The psychotropic effects of LSD are attributed to its strong partial agonist effects at 5-HT<sub>2A</sub> receptors as specific 5-HT<sub>2A</sub> [[agonist]] drugs are psychotropics and largely 5-HT<sub>2A</sub> specific [[antagonist]]s block the psychotropic activity of LSD.<ref name="nichols" /> Exactly how this produces the drug's effects is unknown, but it is thought that it works by increasing [[glutamic acid|glutamate]] release and hence excitation in the [[Cerebral cortex|cortex]], specifically in layers IV and V.<ref>BilZ0r. "[http://www.erowid.org/psychoactives/pharmacology/pharmacology_article2.shtml The Neuropharmacology of Hallucinogens: a technical overview]". [[Erowid]], v3.1 (August 2005).</ref> In the later stages, LSD might act through [[DARPP-32]] - related pathways that are likely the same for multiple drugs including cocaine, methamphetamine, nicotine, caffeine, PCP, ethanol and morphine.<ref>{{cite journal
 | author = Svenningsson P. , Nairn A. C., Greengard P.
 | title = DARPP-32 Mediates the Actions of Multiple Drugs of Abuse.
 | journal= AAPS Journal
 | year= 2005
 | volume = 07
 | issue = 02
 | pages= E353-E360
 | doi = 10.1208/aapsj070235
 | url = http://www.aapsj.org/view.asp?art=aapsj070235
}}</ref>
One experiment studying the actions of LSD was performed by Barry Jacobs recording from electrodes implanted into cat [[Raphe nuclei]].<ref>{{cite journal
 | author = Jacobs B. L., Heym J., Rasmussen K.
 | title = Raphe neurons: firing rate correlates with size of drug response
 | journal= European Journal of Pharmacology
 | year= 1983
 | volume = 90
 | issue = 2-3
 | pages= 275-8
 | id = PMID 6873185 | doi = 10.1016/0014-2999(83)90249-2 <!--Retrieved from CrossRef by DOI bot-->
}}
</ref> Behaviorally relevant doses of LSD result in a complete blockade of action potential activity in the dorsal raphe, effectively shutting off the principal endogenous source of serotonin to the telencephalon. [[Image:LSDaffinities.GIF|thumb|right|Affinity of LSD for various receptors, averaged from data from the [[Ki Database|K<sub>i</sub> Database]]]]

Some reports indicate that although administration of [[chlorpromazine]] (Thorazine) or similar [[typical antipsychotic]] tranquilizers will not end an LSD trip, it will either lessen the intensity or immobilize and numb the patient, a side effect of the medication.<ref>{{cite journal|author=Gilberti, F. and Gregoretti, L. L.|url=http://www.maps.org/w3pb/new/1955/1955_giberti_3993_1.pdf|title=Prime esperienze di antaonismo psicofarmacologico|journal=Sistema Nervoso|volume=4|year=1955|pages=301–309}}</ref> While it also may not end an LSD trip, the best chemical treatment for a "bad trip" is an [[anxiolytic]] agent such as [[diazepam]] (Valium) or another [[benzodiazepine]]. Some have suggested that administration of [[niacin]] (nicotinic acid, [[vitamin B3]]) could be useful to end the LSD user's experience of a "bad trip".<ref>{{cite journal|author= Agnew N, and Hoffer A. L.|url=http://www.erowid.org/references/refs_view.php?A=ShowRefTopFrame&ID=3983&DocPartID=3561|title= Nicotinic acid modified lysergic acid diethylamide psychosis|journal= J. Ment. Sci.|volume=101|year=1955|pages=12| }}</ref> The nicotinic acid in [[niacin]] as opposed to [[nicotinamide]], will produce a full body heat rash, due to widening of peripheral blood vessels. The effect is somewhat akin to a [[poison ivy]] rash. Although it is not clear to what extent the effects of LSD are reduced by this intervention, the physical effect of an itchy skin rash may itself tend to distract the user from feelings of anxiety. Indeed, nicotinic acid was experienced as a stressor by all tested persons. The rash itself is temporary and disappears within a few hours. It is questionable if this method could be effective for people having serious adverse psychological reactions.

=== Physical ===

Physical reactions to LSD are highly variable and may include the following: [[uterus|uterine]] contractions, [[hypothermia]], fever, elevated levels of [[blood sugar]], [[goose bumps]], increase of heart rate, jaw clenching, perspiration, [[Mydriasis|pupil-dilation]], [[saliva]] production, [[mucus]] production, [[sleep]]lessness, [[paresthesia]], [[Euphoria (emotion)|euphoria]], [[hyperreflexia]], [[tremor]]s and [[synesthesia]]. LSD users report numbness, weakness, trembling, and nausea.<ref>{{cite journal |author=Schiff PL |title=Ergot and its alkaloids |journal=American journal of pharmaceutical education |volume=70 |issue=5 |pages=98 |year=2006 |pmid=17149427 |doi=}}</ref> LSD was studied in the 1960s by Eric Kast as an [[analgesic]] for serious and chronic [[pain]] caused by [[cancer]] or other major trauma.<ref>{{cite journal | author=Kast, Eric | title=Attenuation of anticipation: a therapeutic use of lysergic acid diethylamide | journal=Psychiat. Quart. | year=1967 | pages=646-57 | volume=41 | issue=4 | id=PMID 4169685 | url=http://www.maps.org/w3pb/new/1967/1967_kast_3881_1.pdf | doi = 10.1007/BF01575629 <!--Retrieved from CrossRef by DOI bot-->}}</ref> Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional [[opiate]]s while being much longer lasting (pain reduction lasting as long as a week ''after'' peak effects had subsided). Kast attributed this effect to a decrease in anxiety. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of the [[Psychedelic drug|psychedelic]] [[tryptamine]] [[psilocybin]] on [[anxiety]] in terminal cancer patients.

Furthermore, LSD has been used as a treatment for [[cluster headache]]s, an uncommon but extremely painful disorder. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic."<ref>Dr. Goadsby is quoted in "[http://www.maps.org/research/cluster/psilo-lsd/ Research into psilocybin and LSD as cluster headache treatment]", and he makes an equivalent statement in [http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s42434.htm an ''Health Report'' interview] on Australian [[Radio National]] (9 August 1999). Pages accessed [[2007-01-31]].</ref> Although the phenomenon has not been formally investigated, case reports indicate that LSD and [[psilocybin]] can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various [[ergoline]]s, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study, testing the effectiveness of both LSD and psilocybin was planned at [[McLean Hospital]], although the current status of this project is unclear. A 2006 study by McLean researchers interviewed 53 cluster-headache sufferers who treated themselves with either LSD or psilocybin, finding that a majority of the users of either drug reported beneficial effects.<ref name="sewell-etal2006">{{cite journal | last=Sewell | first=R. A. | coauthors=Halpern, J. H.; Pope, H. G. Jr. | title=Response of cluster headache to psilocybin and LSD | journal=Neurology|date=[[2006-06-27]] | volume=66 | issue=12 | pages=1920–2
| doi= 10.1212/01.wnl.0000219761.05466.43
| accessdate=2006-07-18 }}</ref> Unlike attempts to use LSD or [[MDMA]] in [[psychotherapy]], this research involves non-psychological effects and often sub-psychedelic dosages; therefore, it is plausible that a respected medical use of LSD will arise.<ref>Summarized from "[http://www.maps.org/research/cluster/psilo-lsd/ Research into psilocybin and LSD as cluster headache treatment]" and [http://www.clusterbusters.com/ the Clusterbusters website]. Pages accessed [[2007-01-31]].</ref>

=== Psychological ===

LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, depending on factors such as previous experiences, state of mind and environment, as well as dose strength. They also vary from one trip to another, and even as time passes during a single trip. An LSD trip can have long term psychoemotional effects; some users cite the LSD experience as causing significant changes in their personality and life perspective. Widely different effects emerge based on what has been called ''[[set and setting]]''; the "set" being the general mindset of the user, and the "setting" being the physical and social environment in which the drug's effects are experienced.

[[Timothy Leary]] and [[Richard Alpert]] considered the chemical to be of potentially beneficial application in psychotherapy. If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant than if he or she is in a comfortable environment and has a relaxed, balanced and open mindset.

Some psychological effects may include an experience of radiant colors, objects and surfaces appearing to ripple or "breathe," colored patterns behind the eyes, a sense of time distorting (time seems to be stretching, repeating itself, changing speed or stopping), crawling geometric patterns overlaying walls and other objects, morphing objects, a sense that one's thoughts are spiraling into themselves, loss of a sense of identity or the ego (known as "[[ego death]]"), and powerful, and sometimes brutal, psycho-physical reactions interpreted by some users as reliving their own birth.<ref name="sgrof"/><ref>{{cite web
|author     = The Good Drugs Guide
|title      = LSD psychedelic effects
|url        = http://www.thegooddrugsguide.com/lsd/psychedelic.htm
|accessdate = 2008-03-03}}</ref>

Many users experience a dissolution between themselves and the "outside world".<ref name="linton-langs">Linton, Harriet B. and Langs, Robert J. "[http://www.maps.org/w3pb/new/1962/1962_linton_2052_1.pdf Subjective Reactions to Lysergic Acid Diethylamide (LSD-25)]". ''Arch. Gen. Psychiat.'' Vol. 6 (1962): 352–68.</ref> This unitive quality may play a role in the spiritual and religious aspects of LSD. The drug sometimes leads to disintegration or restructuring of the user's historical personality and creates a mental state that some users report allows them to have more choice regarding the nature of their own personality.

Some experts hypothesize that drugs such as LSD may be useful in psychotherapy, especially when the patient is unable to "unblock" repressed subconscious material through other psychotherapeutic methods,<ref>Cohen, S. (1959). The therapeutic potential of LSD-25. ''A Pharmacologic Approach to the Study of the Mind,'' p251–258.</ref> and also for treating alcoholism. One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"<ref>{{cite journal | author=Chwelos N, Blewett D.B., Smith C.M., Hoffer A. | title=Use of d-lysergic acid diethylamide in the treatment of alcoholism | journal=Quart. J. Stud. Alcohol | year=1959 | pages=577-90 | volume=20 | id=PMID 13810249}}</ref> presumably by forcing the user to face issues and problems in that individual's psyche. Many believe that, in contrast, other drugs (such as [[alcohol]], [[heroin]], and [[cocaine]]) which are used to [[escapism|escape]] from reality, LSD is seen as more of an introspective experience. Studies in the 1950s that used LSD to treat alcoholism professed a 50% success rate,<ref>Maclean, J.R.; Macdonald, D.C.; Ogden, F.; Wilby, E., "LSD-25 and mescaline as therapeutic adjuvants." In: Abramson, H., Ed., ''The Use of LSD in Psychotherapy and Alcoholism,'' Bobbs-Merrill: New York, 1967, pp. 407–426; Ditman, K.S.; Bailey, J.J., "Evaluating LSD as a psychotherapeutic agent," pp.74–80; Hoffer, A., "A program for the treatment of alcoholism: LSD, malvaria, and nicotinic acid," pp. 353–402.</ref> five times higher than estimates near 10% for [[Alcoholics Anonymous]].<ref>Minogue, S. J. "Alcoholics Anonymous." ''The Medical Journal of Australia'' May 8 (1948):586–587.</ref> 

Some LSD studies were criticized for methodological flaws, and different groups had inconsistent results. Mangini's 1998 paper reviewed this history. He concluded that the efficacy of LSD in treating alcoholism remains an open question.<ref>{{cite journal | author=Mangini M | title=Treatment of alcoholism using psychedelic drugs: a review of the program of research | journal=J Psychoactive Drugs | year=1998 | pages=381-418 | volume=30 | issue=4 | id=PMID 9924844}}</ref> Dr Abram Hoffer referred to Mangini's paper as "a good review of the literature" but said that, in common with many other scientists, the author has failed to grasp the important point that psychedelic therapy is a ''therapeutic'' experience.

{{Quotation|The critics of psychedelic therapy have not taken this into account. Thus the Toronto studies studied the drug. They made no attempt whatever to induce a psychedelic experience. I saw at least two of the patients many years after they had been treated in Toronto and they told me that it was the most horrible experience they had ever had. It was in fact a true psychotomimetic experience and probably reproduced delirium tremens more than anything else. Not surprisingly their patients did not do well. They gave them 800 micrograms which is too heavy, gave them a barbiturate in advance to prevent convulsions, tied them to the bed so that they could not run away, and had sitting with them a psychologist who wrote notes all the time and did not interact with the patients.|Abram Hoffer M.D, Ph.D, FRCP|''[http://www.hofmann.org/Reviews/Alcoholism.html Comments on the article Treatment of Alcoholism Using Psychedelic Drugs]''}}

Many notable individuals have commented publicly on their experiences with LSD. Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to [[psychiatric]] treatment in the 1950s and 60s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

==== Sensory / perception ====

LSD causes expansion and altered experience of [[sense]]s, [[emotion]]s, [[memory|memories]], [[time]], and [[awareness]] for 6 to 14 hours, depending on dosage and tolerance. LSD does typically not produce real [[hallucination]]s as the [[deliriant]]s do. Generally beginning within thirty to ninety minutes after ingestion, the user may experience anything from subtle changes in perception to overwhelming [[cognitive shift]]s. Changes in auditory and visual perception are typical.<ref name="linton-langs" /><ref>{{cite journal 
| author=Katz MM, Waskow IE, Olsson J 
| year=1968 
| title=Characterizing the psychological state produced by LSD 
| journal=J Abnorm Psychol 
| volume=73 
| issue=1 
| pages=1-14 
| id=PMID 5639999 | doi = 10.1037/h0020114 <!--Retrieved from CrossRef by DOI bot-->
}}</ref> Visual effects include the illusion of [[motion aftereffect|movement of static surfaces]] ("walls breathing"), [[after image]]-like trails of moving objects ("tracers"), the appearance of moving colored geometric patterns (especially with closed eyes), an intensification of colors and brightness ("sparkling"), new textures on objects, blurred vision, and shape suggestibility. Users commonly report that the inanimate world appears to animate in an unexplained way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.<ref>See, ''e.g.,'' Gerald Oster's article "[http://www.maps.org/w3pb/new/1966/1966_oster_3875_1.pdf Moiré patterns and visual hallucinations]". ''Psychedelic Rev.'' No. 7 (1966): 33–40.</ref> Many of the basic visual effects resemble the [[phosphene]]s seen after applying pressure to the eye and have also been studied under the name "[[form constant]]s". The auditory effects of LSD include [[Echo (phenomenon)|echo]]-like distortions of sounds, a mixing of all sounds which makes it harder to discern distinct sounds, the feeling that what you're hearing is your thought, a general intensification of the experience of music, and an increased discrimination of instruments and sounds. Higher doses often cause intense and fundamental distortions of sensory perception such as [[synaesthesia]], the experience of additional spatial or temporal dimensions, and temporary dissociation.

==== Spiritual ====

LSD is considered an [[entheogen]] because it can catalyze intense spiritual experiences where users feel they have come into contact with a greater spiritual or cosmic order. Some users report insights into the way the mind works, and some experience long-lasting changes in their life perspective. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Dr. [[Stanislav Grof]] has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the secret mystical texts of ancient civilizations.<ref name="Grof1979">{{cite book | last = Grof | first = Stanislav | authorlink = Stanislav Grof | coauthors = Joan Halifax Grof| title = Realms of the Human Unconcious (Observations from LSD Research) | publisher = Souvenir Press (E & A) Ltd|date=1979| location = London| pages = 13-14| url = http://www.csp.org/chrestomathy/realms_of3.html| doi = | id = | isbn = 0 285 64882 9}}</ref>

Such experiences under the influence of LSD have been observed and documented by researchers such as [[Alan Watts]], [[Timothy Leary]] and Stanislav Grof. For example, Walter Pahnke conducted the Good Friday [[Marsh Chapel Experiment]] in 1962 under Leary's supervision, performing a [[double blind]] experiment on the administration of psilocybin to volunteers who were students in religious graduate programs, ''e.g.,'' divinity or theology.<ref>Video of the experiment can be viewed [http://www.yoism.org/?q=node/52 here].</ref> That study provided evidence that psychotropics may induce mystical religious states.<ref>Pahnke, Walter N., ''[http://www.erowid.org/entheogens/journals/entheogens_journal3.shtml Drugs and Mysticism]: An Analysis of the Relationship between Psychedelic Drugs and the Mystical Consciousness''. A thesis presented to the Committee on Higher Degrees in History and Philosophy of Religion, Harvard University, June 1963. Cited in Masters, R.E.L., & Houston, Jean., ''The Varieties of Psychedelic Experience'' (Turnstone Books, 1973).</ref>

==== Potential risks of LSD use ====

LSD is generally considered nontoxic; it may temporarily impair the ability to make sensible judgments and understand common dangers, thus making the user more susceptible to accidents and personal injury.

There is also some indication that LSD may trigger a [[fugue state|dissociative fugue]] state in individuals who are taking certain classes of [[antidepressants]] such as [[lithium salt]]s and [[Tricyclic antidepressant|tricyclics]]. In such a state, the user has an impulse to wander, and may not be aware of his or her actions, which can lead to physical injury.<ref name="lsd-antidepressants">"[http://www.erowid.org/chemicals/lsd/lsd_health3.shtml LSD and Antidepressants]" (2003) via [[Erowid]].</ref> [[Selective serotonin reuptake inhibitor|SSRIs]] are believed to interact more benignly, with a tendency to noticeably reduce LSD's subjective effects.<ref>Kit Bonson, "[http://www.erowid.org/chemicals/maois/maois_info4.shtml The Interactions between Hallucinogens and Antidepressants]" (2006).</ref> Similar and perhaps greater reductions have also been reported with [[MAOI]]s.<ref name="lsd-antidepressants" />

As Albert Hofmann reports in ''LSD – My Problem Child,'' the early pharmacological testing Sandoz performed on the compound (before he ever discovered its psychoactive properties) indicated that LSD has a pronounced effect upon the mammalian [[uterus]]. Sandoz's testing showed that LSD can stimulate uterine contractions with efficacy comparable to [[Ergoline#Lysergic acid amides|ergobasine]], the active uterotonic component of the [[ergot]] fungus (Hofmann's work on ergot derivatives also produced a modified form of ergobasine which became a widely accepted medication used in [[obstetrics]], under the trade name [[Ergoline#Lysergic acid amides|Methergine]]). Therefore, LSD use by pregnant women could be dangerous and is [[contraindication|contraindicated]].<ref name="problem-child" />

Initial studies in the 1960s and 70s raised concerns that LSD might produce genetic damage or developmental abnormalities in fetuses. However, these initial reports were based on ''in vitro'' studies or were poorly controlled and have not been substantiated. In studies of [[chromosome|chromosomal]] changes in human users and in monkeys, the balance of evidence suggests no significant increase in chromosomal damage. For example, studies were conducted with people who had been given LSD in a clinical setting.<ref name="dishotsky">{{cite journal | author=Dishotsky NI, Loughman WD, Mogar RE, Lipscomb WR | title=LSD and genetic damage | journal=Science | year=1971 | pages=431-40 | volume=172 | issue=982 | id=PMID | url=http://www.maps.org/w3pb/new/1971/1971_dishotsky_5148_1.pdf | doi = 10.1126/science.172.3982.431 <!--Retrieved from CrossRef by DOI bot-->}}</ref> [[White blood cell]]s from these people were examined for visible chromosomal abnormalities. Overall, there appeared to be no lasting changes. Several studies have been conducted using illicit LSD users and provide a less clear picture. Interpretation of these data is generally complicated by factors such as the unknown chemical composition of street LSD, concurrent use of other [[psychoactive drug]]s, and diseases such as [[hepatitis]] in the sampled populations. It seems possible that the small number of genetic abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD.<ref name="dishotsky" />

=== Flashbacks and HPPD ===

"[[Flashback (psychological phenomenon)|Flashbacks]]" are a reported psychological phenomenon in which an individual experiences an episode of some of LSD's subjective effects long after the drug has worn off — sometimes weeks, months, or even years afterward. Flashbacks can incorporate both positive and negative aspects of LSD trips.  Flashbacks have proven difficult to study and are no longer officially recognized as a psychiatric syndrome.  However, colloquial usage of the term persists and usually refers to any drug-free experience reminiscent of psychedelic drug effects, with the typical connotation that the episodes are of short duration.  

No definitive explanation is currently available for these experiences. Any attempt at explanation must reflect several observations: first, over 70 percent of LSD users claim never to have "flashed back"; second, the phenomenon does appear linked with LSD use, though a causal connection has not been established; and third, a higher proportion of psychiatric patients report flashbacks than other users.<ref name="abrahart">{{cite web
| url = http://www.maps.org/research/abrahart.html
| title = A Critical Review of Theories and Research Concerning Lysergic Acid Diethylamide (LSD) and Mental Health
| author = David Abrahart
|date=1998
| accessdate = 2007-02-02}}</ref> Several studies have tried to determine how likely a user of LSD, not suffering from known psychiatric conditions, is to experience flashbacks. The larger studies include Blumenfeld's in 1971<ref>{{cite journal | author=Blumenfield M | title=Flashback phenomena in basic trainees who enter the US Air Force | journal=Military Medicine | year=1971 | pages=39-41 | volume=136 | issue=1 | id=PMID 5005369}}</ref> and Naditch and Fenwick's in 1977,<ref>{{cite journal | author=Naditch MP, Fenwick S | title=LSD flashbacks and ego functioning | journal=Journal of Abnormal Psychology | year=1977 | pages=352-9 | volume=86 | issue=4 | id=PMID 757972 | doi = 10.1037/0021-843X.86.4.352 <!--Retrieved from CrossRef by DOI bot-->}}</ref> which arrived at figures of 20% and 28%, respectively.  

Although flashbacks are not recognized as a medical syndrome, there is a potentially related syndrome in which LSD-like visual changes are persistent and cause clinically significant impairment or distress. This syndrome is called [[hallucinogen persisting perception disorder|Hallucinogen Persisting Perception Disorder]] (HPPD), though not truly hallucinogenic, a [[Diagnostic and Statistical Manual of Mental Disorders|DSM-IV]] diagnosis. Several scientific journal articles have described the disorder.<ref>See, for example, {{cite journal | author=Abraham HD, Aldridge AM | title=Adverse consequences of lysergic acid diethylamide | journal=[[Addiction (journal)|Addiction]] | year=1993 | pages=1327-34 | volume=88 | issue=10 | id=PMID 8251869}}</ref>  HPPD differs from flashbacks in that it is persistent and apparently entirely visual (although mood and anxiety disorders are sometimes diagnosed in the same individuals).

A recent review suggests that [[hallucinogen persisting perception disorder|HPPD]] (as defined in the DSM-IV) is rare and affects only a distinctly vulnerable subpopulation of users.<ref>{{cite journal | author=Halpern JH, Pope HG Jr | title=Hallucinogen persisting perception disorder: what do we know after 50 years? | journal=Drug Alcohol Depend | year=2003 | pages=109-19 | volume=69 | issue=2 | id=PMID 12609692 | doi = 10.1016/S0376-8716(02)00306-X <!--Retrieved from CrossRef by DOI bot-->}}; {{cite journal | author=Halpern JH | title=Hallucinogens: an update | journal=Curr Psychiatry Rep | year=2003 | pages=347-54 | volume=5 | issue=5 | id=PMID 13678554 | doi = 10.1007/s11920-003-0067-4 <!--Retrieved from CrossRef by DOI bot-->}} [http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6224]</ref>  However, it is possible that the prevalence of HPPD is underestimated because it can only be diagnosed in a person who admits to their health care practitioner that they have used psychotropics.<ref>[http://www.cpdd.vcu.edu/Pages/Meetings/Meetings_PDFs/2006abstractbook.pdf. Baggott et al. (2006) Prevalence of chronic flashbacks in hallucinogen users: a web-based questionnaire]</ref> 

There is no consensus regarding the nature and causes of HPPD (or flashbacks). Given that some symptoms have environmental triggers, it may represent a failure to adjust visual processing to changing environmental conditions.  There are no explanations for why only some individuals develop HPPD.  Explanations in terms of LSD physically remaining in the body for months or years after consumption have been discounted by experimental evidence.<ref name="abrahart" /> Some say HPPD is a manifestation of [[post-traumatic stress disorder]], not related to the direct action of LSD on brain chemistry, and varies according to the susceptibility of the individual to the disorder. Many emotionally intense experiences can lead to flashbacks when a person is reminded acutely of the original experience. However, not all published case reports of HPPD appear to describe an anxious hyper-vigilant state reminiscent of post-traumatic stress disorder. Instead, some cases appear to involve only visual symptoms.<ref name="abrahart" />

=== Psychosis ===

There are some cases of LSD inducing a [[psychosis]] in people who appeared to be healthy prior to taking LSD. This issue was reviewed extensively in a 1984 publication by [[Rick Strassman]].<ref>{{cite journal | author=Strassman RJ | title=Adverse reactions to psychedelic drugs. A review of the literature | journal=J Nerv Ment Dis | year=1984 | pages=577-95 | volume=172 | issue=10|id=PMID 6384428}}</ref> In most cases, the psychosis-like reaction is of short duration, but in other cases it may be chronic. It is difficult to determine if LSD itself induces these reactions or if it triggers latent conditions that would have manifested themselves otherwise. The similarities of time course and outcomes between putatively LSD-precipitated and other psychoses suggests that the two types of syndromes are not different and that LSD may have been a nonspecific trigger. Several studies have tried to estimate the prevalence of LSD-induced prolonged psychosis arriving at numbers of around 4 in 1,000 individuals (0.8 in 1,000 volunteers and 1.8 in 1,000 psychotherapy patients in Cohen 1960;<ref>{{cite journal|author=Cohen, Sidney|url=http://www.maps.org/w3pb/new/1960/1960_cohen_1848_1.pdf|title=Lysergic Acid Diethylamide: Side Effects and Complications|journal=Journal of Nervous and Mental Disease|volume=130|issue=1
| pages=30–40|month=January|year=1960|id=PMID 13811003}}</ref> 9 per 1,000 psychotherapy patients in Melleson 1971).<ref>{{cite journal|author=Malleson, Nicholas|url=http://www.maps.org/w3pb/new/1971/1971_malleson_5136_1.pdf|title=Acute Adverse Reactions to LSD in Clinical and Experimental Use in the United Kingdom|journal=Brit. J. Psychiat.|volume=118|pages=229–30|id=PMID 4995932|issue=543|year=1971}}</ref>

== Chemistry ==

[[Image:LSD isomers.png|thumb|240px|The four possible isomers of LSD. Only LSD is psychoactive.]]

LSD is an [[ergoline]] derivative. It is commonly produced from reacting [[diethylamine]] with an activated form of [[lysergic acid]]. Activating reagents include [[phosphoryl chloride]]<ref name="synth1">{{cite journal 
| title = Stereoselective LSD-like Activity in a Series of <small>D</small>-Lysergic Acid Amides of (''R'')- and (''S'')-2-Aminoalkanes
 | author = Aaron P. Monte, Danuta Marona-Lewicka, Arthi Kanthasamy, Elaine Sanders-Bush, and David E. Nichols. 
 | journal = J. Med. Chem.
 | volume =  38
 | issue = 6
 | pages = 958 - 966
 | year = 1995
 | doi =10.1021/jm00006a015}}</ref> and [[peptide coupling reagent]]s.<ref name="synth2">{{ cite journal 
 | title = Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)
 | author = Nichols, D. E.; Frescas, S.; Marona-Lewicka, D.; Kurrasch-Orbaugh, D. M. 
 | journal = J. Med. Chem.
 | volume =  45
 | issue = 19
 | pages = 4344-4349
 | year = 2002
 | doi = 10.1021/jm020153s}}</ref> Lysergic acid is made by alkaline [[hydrolysis]] of lysergamides like [[ergotamine]], a substance derived from the [[ergot]] [[fungus]] on [[rye]], or, theoretically, from [[ergine]] (lysergic acid amide, LSA), a compound that is found in [[morning glory]] (''Ipomoea tricolor'') and [[hawaiian baby woodrose]] (''Argyreia nervosa'') seeds. LSD is a [[chirality (chemistry)|chiral]] compound with two [[stereocenter]]s at the [[carbon]] atoms C-5 and C-8, so that theoretically four different [[optical isomerism|optical isomers]] of LSD could exist. LSD, also called (+)-<small>D</small>-LSD, has the [[absolute configuration]] (5''R'',8''R''). The C-5 [[isomer]]s of lysergamides do not exist in nature and are not formed during the synthesis from <small>D</small>-lysergic acid. However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of [[base (chemistry)|base]]. Non-psychoactive iso-LSD which has formed during the synthesis can be removed by [[chromatography]] and can be isomerized to LSD. A totally pure salt of LSD will emit small flashes of white light when shaken in the dark.<ref>{{cite web   
 | url=http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml
 | title=Erowid Online Books : "TIHKAL" - #26 LSD-25
 |accessdate=2007-11-12
 |format=
 |work=}}</ref> LSD is strongly [[fluorescent]] and will glow bluish-white under [[UV light]].

=== Stability ===

"LSD," writes the chemist [[Alexander Shulgin]], "is an unusually fragile molecule."<ref name="tihkal" /> It is stable for indefinite amounts of time ''if'' stored, as a solid salt or dissolved in water, at low temperature and protected from air and light exposure. Two portions of its molecular structure are particularly sensitive, the carboxamide attachment at the 8-position and the [[covalent bond|double bond]] between the 8-position and the [[aromatic hydrocarbon|aromatic ring]]. The former is affected by high [[pH]], and if perturbed will produce isolysergic acid diethylamide (iso-LSD), which is biologically inactive. If water or alcohol adds to the double bond (especially in the presence of light), LSD converts to "lumi-LSD", which is totally inactive in human beings, to the best of current knowledge. Furthermore, [[chlorine]] destroys LSD molecules on contact; even though chlorinated tap water typically contains only a slight amount of chlorine, because a typical LSD solution only contains a small amount of LSD, dissolving LSD in tap water is likely to completely eliminate the substance.<ref name="tihkal" />

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.<ref>{{cite journal | author=Li Z., McNally A. J., Wang H., Salamone S. J.
 | url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9788528&dopt=Abstract
 | title=Stability study of LSD under various storage conditions.
 | journal=J. Anal. Toxicol.
 | volume=22
 | issue=6
 | pages=520–5
 | month=October
 | year=1998
 | id=PMID 9788528
 | url = http://www.jatox.com/abstracts/1998/october/226mcn.htm}}</ref>
The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 °C for up to 4 weeks. After 4 weeks of incubation, a 30% loss in LSD concentration at 37 °C and up to a 40% at 45 °C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of [[EDTA]].

== See also ==

* [[Mind at Large]]
* [[ALD-52]]
* [[Bogle-Chandler case]], deaths mistakenly attributed to LSD overdoses
* [[Drug_urban_legends#Urban_legends_about_LSD|Urban legends about LSD]]
* [[Entheogen]]
* [[Psychedelic psychotherapy]]
* [[United States v. Stanley]], US Supreme Court case
* Related [[chemistry|chemical]] compounds: [[ergoline]]s, [[Ergine|LSA]], [[psilocybin]], [[Dimethyltryptamine|DMT]], [[serotonin]]
* [[The Sixties|The 60s]]
* [[Methysergide]] and [[Sumatriptan]] - Prescription drugs closely related to LSD which treats migraine headaches.

== References ==
{{reflist|2}}

== Further reading ==

* Stevens, Jay. ''Storming Heaven: LSD And The American Dream'' ([http://www.sunrisedancer.com/radicalreader/includes/inc_hitting.asp?iLink=6])
* Marks, John. ''The Search for the Manchurian Candidate: The CIA and Mind Control'' (1979), 0-8129-0773-6
* Grof, Stanislav. ''LSD Psychotherapy''. (April 10, 2001)
* Lee, Martin A. and Bruce Shlain. ''Acid Dreams: The Complete Social History of LSD: The CIA, the Sixties, and Beyond'' [http://www.sunrisedancer.com/radicalreader/includes/inc_hitting.asp?iLink=3]

== External links ==
{{Wikinews|Drug website surveys LSD users and culture}}
* [http://www.erowid.org/chemicals/lsd/lsd.shtml Erowid -> LSD Information]
* [http://leda.lycaeum.org/?ID=10 The Lycaeum Archive -> LSD]
* [http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml TIHKAL entry for LSD]
* [http://www.sci-con.org/2003/06/the-neurochemistry-of-psychdelic-experiences/ The Neurochemistry of Psychedelic Experience], ''Science & Consciousness Review''
* [http://www.maps.org/research/cluster/psilo-lsd/ Current LSD Research – MAPS]
* [http://www.lsd.info International 3 day conference on LSD in Basel]
* [http://www.talktofrank.com/drugs.aspx?id=192 Talk to Frank]UK government anti-drug site on LSD
* [http://ahp.yorku.ca/?p=97 Scholarly bibliography on the histories of LSD use]

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[[Category:Incapacitating agents]]
[[Category:Light-sensitive chemicals]]
[[Category:LSD|LSD]]
[[Category:Lysergamides]]
[[Category:Mind control]]
[[Category:Novartis]]
[[Category:Psychedelics]]
[[Category:Serotonin receptor agonists]]
[[Category:Withdrawn drugs]]

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