v 2.0 - Jul 2002
minor update May 2007, by Erowid
Erowid Note: This FAQ was not authored by Erowid. It may include out-of-date and/or incorrect information. Please check the version date to see when it was most recently revised. It appears on Erowid as part of our historical archives. For current information, see Erowid's summary pages in the substance's main vault.
- DEFINITION & INTRODUCTION
- SLANG TERMS
- DELYSID (medical fact sheet for pharmaceutical LSD)
- CAUTIONS, Real And Imagined
- DEFINITION & INTRODUCTION
- Addiction Potential (none)
- Adulterants (including the strychnine myth, manufacturing impurities, etc.)
- Bad Trips (what they are, how to avoid, what to do)
- Myths (stamps for children, staring at the sun..)
- Dangers (LSD isn't for morons...)
- Flashbacks (what they are ---post-traumatic stress syndrome)
- Insomnia (common, what to do)
- Adulterants (including the strychnine myth, manufacturing impurities, etc.)
- TOLERANCE (aquired and lost quickly (3 days) harmlessly, no withdrawal)
- BOTANY (sources in nature: mushrooms, ergot, morning glories, hawaiian baby woodrose, tropical plants)
- Ipomoea pupurea: A Naturally Occurring Psychedelic
- CHEMISTRY (structure)
- Chemistry of Seeds
- Mechanism of Action (uncertain)
Set and Setting (how to have a positive experience; lsd != beer)
Storage (keep in a cool dark dry place)
Synergies, Bad Combinations (cannabis is good, otherwise be careful)
References & Further Reading: (Recommended)
_Psychedelic Encyclopedia_ by Peter Stafford
_LSD: My Problem Child_ by Albert Hofmann
_Licit & Illicit Drugs_ (Consumer Reports)
_Storming heaven : LSD and the American dream_ by Jay Stevens
The following large (200K) file is the updated LSD FAQ incorporating various posts that I've collected since this faq first came out. There is a "Changes" section near the top. This also contains info on other tryptamine psychedelics, viz. DMT and psilocybin.
(c) 1994 The reproduction for nonprofit use of this file is encouraged.
[NB: This FAQ provided to reduce the Net's bandwidth / confusion / misinformation, as an informational resource ONLY. There are some very informed, and some very clueless people on the Net. This FAQ tries to shift the balance. The truth shall set you free, as they say.]
CHANGES Since Previous Version
- v 2.2 - May 2007 : Erowid : Minor typo correction.
- v 2.1 - Aug 2005 : Erowid : Corrected issue with cross-tolerance, which incorrectly stated cross-tolerance with DMT. Thanks to asheen.
- v 2.0 - July 2002:
- added synthesis notes, MAPS
- merged misc. files and references, organizations, the baseball story, recipes I'm not competent to judge
- added scholarly section on creativity
- include more info on related active tryptamine derivatives
- traded off half-a-decibel of signal-to-noise for wider scope
- added mycological horticultural note
- added postscript stereoimage of structure
LSD : Generic name for the hallucinogen lysergic acid diethylamide-25. Discovered by Dr. Albert Hofmann in 1938, LSD is one of the most potent mind-altering chemicals known. A white, odorless powder (EROWID NOTE : LSD generally comes in "blotter" form; small squares of paper which have been soaked in liquid LSD. It is also found as a liquid, microdot, sugar cubes, and gelatin squares, but is quite rare as a "white, odorless powder") usually taken orally, its effects are highly variable and begin within one hour and generally last 8-12 hours, gradually tapering off. It has been used experimentally in the treatment of alcoholics and psychiatric patients. [Where it showed some success.] It significantly alters perception, mood, and psychological processes, and can impair motor coordination and skills. During the 1950s and early 1960s, LSD experimentation was legally conducted by psychiatrists and others in the health and mental health professions. Sometimes dramatic, unpleasant psychological reactions occur, including panic, great confusion, and anxiety. Strongly affected by SET and SETTING. Classification: hallucinogens. Slang names: acid, sugar, L. See also appendix B. (RIS 27:211-52 entries)
-- Research Issues 26, Guide to Drug Abuse Research Terminology, available from NIDA or the GPO, page 54.
Common Drug Slang Terms
(NB: many of these refer to the carrier, ie, "Blotter" or "Sugar Cubes". Often the local names will refer to patterns printed on the blotter, eg, "Blue unicorn".):
Acid, 'Cid, Sid, Bart Simpsons, Barrels, Tabs, Blotter, Heavenly blue, "L", Liquid, Liquid A, Lucy in the sky with diamonds, Microdots, Mind detergent, Orange cubes, Orange micro, Owsley, Hits, Paper acid, Sacrament, Sandoz, Sugar, Sugar lumps, Sunshine, Tabs, Ticket, Twenty-five, Wedding bells, Windowpane, etc.
from the data sheet accompanying product:
(see also Physician's Desk Reference from mid-60's)
Delysid (LSD 25)
D-lysergic acid diethylamide tartrate
Sugar-coated tablets containing 0.025 mg. (25 ug.)
Ampoules of 1 ml. containing 0.1 mg. (100 ug.) for oral administration.
The solution may also be injected s.c. or i.v. The effect is identical with that of oral administration but sets in more rapidly.
The administration of very small doses of Delysid (1/2-2 ug./kg. body weight) results in transitory disturbances of affect, hallucinations, depersonalization, reliving of repressed memories, and mild neuro-vegetative symptoms. The effect sets in after 30 to 90 minutes and generally lasts 5 to 12 hours. However, intermittent disturbances of affect may occasionally persist for several days.
METHOD OF ADMINISTRATION
For oral administration the contents of 1 ampoule of Delysid are diluted with distilled water, a 1% solution of tartaric acid or halogen-free tap water.
The absorption of the solution is somewhat more rapid and more constant that that of the tablets.
Ampoules which have not been opened, which have been protected against light and stored in a cool place are stable for an unlimited period. Ampoules which have been opened or diluted solutions retain their effectiveness for 1 to 2 days, if stored in a refrigerator.
INDICATIONS AND DOSAGE
- Analytical psychotherapy, to elicit release of repressed material and provide mental relaxation, particularly in anxiety states and obsessional neuroses. The initial dose is 25 ug. (1/4 of an ampoule or 1 tablet). This dose is increased at each treatment by 25 ug. until the optimum dose (usually between 50 and 200 ug.) is found. The individual treatments are best given at intervals of one week.
- Experimental studies on the nature of psychoses: By taking Delysid himself, the psychiatrist is able to gain an insight in the world of ideas and sensations of mental patients. Delysid can also be used to induced model psychoses of short duration in normal subjects, this facilitating studies on the pathogenesis of mental disease.
Pathological mental conditions may be intensified by Delysid. Particular caution is necessary in subjects with a suicidal tendency and in those cases where a psychotic development appears imminent. The psycho-affective lability and the tendency to commit impulsive acts may occasionally last for some days.
Delysid should only be administered under strict medical supervision. The supervision should not be discontinued until the effects of the drug have completely worn off.
The mental effects of Delysid can be rapidly reversed by the i.m. administration of 50 mg. chlorpromazine. Literature available on request.
SANDOZ LTD., BASLE, SWITZERLAND
Printed in Switzerland.
From: An Introduction to Pharmacology 3rd edition, JJ Lewis, 1964 (p 385)
These include an oxytocic action and constriction of the blood vessels of isolated vascular beds. In intact animals LSD causes a fall in blood pressure, but its adrenergic blocking potency is low.
LSD causes mydriasis in man and other species. It also causes hyperglycaemia and mydriasis, has a hyperthermic action and causes piloerection. These effects are sympathetic in nature and are abolished by ganglion blocking or adrenergic blocking agents. Parasympathetic effects include salivation, lachyrmation, vomiting, hypotension, and brachycardia [bradycardia - erowid]. Low doses stimulate respiration but larger doses depress it.
(nb: mydriasis = pupillary dilation)
Hofmann thought the diethylamide version of the lysergic acid molecule might be a respiratory stimulant... (see _LSD : My Problem Child_ by Albert Hofmann)
The "speedy" quality of unadulterated LSD is due to the pharmacological actions of LSD itself, and not necessarily due to decomposition or impurities. LSD typically causes early adrenergic effects such as sweating, nervousness, jaw grinding and insomnia which are easily confused with the side effects of amphetamine.
_The Road to Eleusius_ by Hofmann, Wasson, and Ruck.
Summary: A secret religion existed for 2,000 years in Greece (until the christians displaced it around 400 AD). The initiation was open to anyone who spoke Greek and hadn't committed murder, once in their life. After 6 month long preparatory rituals, members walked to Eleusius whereupon they underwent secret rituals. The rituals remained secret until the 1970's.
Wasson, an ethnomycological scholar and former banker (and the first white to trip on shrooms with the mexican indians) proposed the following explanation of the Eleusinian mysteries to Hofmann, an ergot-alkaloid expert chemist, and Ruck, a greek scholar:
The Secret of the ritual involved the personal visions induced by drinking the grain decoction administered to the initiates. The domestication of grains permitted the development of greek civilization; it also brought ergot fungus (of St. Anthony's fire infamy).
The thin book contains their argument for the use of the ergot fungus in Eleusinian rites, Wasson providing some background on the use of mushrooms and grains and their role in the culture; Hofmann on the psychoactivity of ergot strains; and Ruck on the mythological and cultural backround of the sect.
Evidence includes: Hofmann dosed himself with large (ergot-derived) doses of obstetric compounds to assay their hallucinogenic potential, and found them to possess such activity. The Eleusinian temple site still remains, but there is no room to view theatric performances, just rows of tripping initiates, further supporting their argument.
An interesting read, and its neat to think that the culture that more or less lead to the western industrial one had psychedelic rites. (Various greek prominant figures attended the rituals, including Plato).
CAUTIONS REAL & IMAGINED
Zero physical addiction potential. Not something that makes you want to do it again immediately.
Rarely people use it to escape in a negative way or as part of "polydrug abuse" behavior or pattern of behavior. Usually in this case other drugs are causing more harm, and the fundamental problem is a personal difficulty; the escapism/distraction is a symptom.
Several problems are associated with street drugs: their unknown purity and their unknown strength. Because of its extreme cheapness and potency, the purity of LSD in blotter form is not an issue: either it's lsd or untreated paper. The purity of powders, pills, and liquids cannot be assumed as safe. With regards to uncertain strength, the strength of hits these days is low, 100 micrograms or so. One should be careful and assume that the smallest square in a tiling of a sheet is a dose, even if a printed pattern covers several. An experienced person could judge the strength of a dose, and if it is assumed all doses on a sheet have been processed equivalently, those doses would be calibrated for others, much like anything else.
From _Psychedelic Chemistry_ by M.V.Smith, 2nd edition p 5:
"There is a great deal of superstition regarding purification of psychedelics. Actually, any impurities which may be present as a result of synthetic procedures will almost certainly be without any effect on the trip. If there are 200 micrograms of LSD in a tablet, there could only be 200 mics of impurities present even if the LSD was originally only 50% pure (assuming nothing else has been added), and few compounds will produce a significant effect until a hundred to a thousand times this amount has been ingested. Even mescaline, which has a rather specific psychedelic effect, requires about a thousand thimes this amount."
- on a piece of paper, vs. a tablet, you can't even add significant amounts of adulterants
- adulterants would cost, whereas blank paper will rip someone off just as well.
LSD itself has some "body-kinks" on some people some times. Nausea is one of them. its usually mild and transient. It also has speedlike (ie, adrenergic stimulation) effects, etc.
(It is common for the uninformed to harbor fears (e.g., about adulterants) instilled by ignorance and the current hysteria/propoganda. That's why this FAQ exists.)
[Referring to strychnine] 15 mg has been fatal, but a more typical fatal dose is on the order of 50 mg. [Another post indicates 25 mg. as the LD50] 1 mg of strychnine orally probably has no observable pharmacological effects in a typical adult. [1 mg being ten times the effective dose of LSD, by the way.]
From: Handbook of Poisoning, 10th ed, R.H. Dreisbach, M.D., PhD, Lange Med. Pub. Co. Los Altos, Ca.: strychnine is lethal in 15-30 mg amounts to adult humans. (Pure nicotine is fatal at 40 mg./person; cyanide salts are fatal at about 100 mg./person) Strychnine causes death by respitory failure, via increased spinal reflex excitability.
Actually, I think the fact that PharmChem analyzed something on the order of 2,000 LSD samples between 1972 and 1979 and never found one with strychnine in it would be better. I'm going over all their data with a toothpick and I'll get back to you on exactly what I find. It looks like the percent of LSD with strychnine in it is, however, at least under .05%. More a little later.
According to Alexander Shulgin the difinitive answer is that strychnine is neither used in the synthesis, produced by the synthesis, or a possible contaminant of the synthesis. But just look at the structures of strychnine vs Lysergic acid/LSD/etc and you should be able to understand that readily.
From "The PharmChem Newsletter" (vol 3, no 3), 1973:
Summary of Street Drug Results - 1973: "Of 189 samples of LSD quantitatively analyzed, the average dose was 67.25 ug LSD. Of the 32 samples of alleged mescaline actually containing mescaline, [...stuff about mescaline and mushrooms deleted...] It is interesting to note the low incidence of deception among the less sought after psychotomimetics LSD and PCP."
Most likely "good" acid is N-acetyl-LSD (ALD-52) [according to _Psychedelic Encyclopedia_ it produces a smoother trip and is somewhat commonly found in analysis -- references to the latter were provided]. while "speedy" acid is LSD-25. You might want to inform her that those "speedy" effects are also commonly reported side effects of legal drugs which effect the 5-HT neurotransmitter system. And ditto on the potency issue -- you'd need mg quantities of strychnine to feel anything. And what you would feel (according to descriptions I've read) does not match descriptions of LSD "speed" effects. Most significantly because strychnine muscular effects tend to fade in & out, while LSD "speed" effects are typically reported as being consistent -- and there are other qualitative differences.
"actual experience"? ... no one here is likely to post descriptions of that over the net, even in e-mail... I'm *quite* sure that some people could though...
> Well, hypothetically speaking, I bought some from her friends, and I could
> probably surrender half a hit or a whole one, maybe, in the interest of
> science. Does anyone have facilities to perform a REAL (hypothetical)
> analysis of blotter to find out exactly what's in it?
Its been done....
> > Schnoll SH Vogel WH
> > Analysis of "street drugs".
> > N Engl J Med (1971 Apr 8) 284(14):791
This reference sucks.
> > Brown JK Shapazian L Griffin GD
> > A rapid screening procedure for some "street drugs" by thin-layer chromatography.
> > J Chromatogr (1972 Jan 19) 64(1):129-33
There's a LA County analysis of street drugs I've got (Clin Tox ~1984 I think) that reports LSD as being >96% pure or blank (If I remember correctly) -- the rest most likely is substitutes, but it wasn't reported in the analysis.
This is the PharmChem analysis of LSD from 1972 (vol 1, no 1) up to the time that the DEA no longer allowed them to make quantitative measurements (1974-vol 3, no 2 included). NOTE: NO STRYCHNINE! also note that PharmChem found a sample of Shrooms contaminated with Strychnine in 1972 (vol 1, no 7), and I would think it safe to assume that they also checked LSD for Strychnine.
A person on LSD who becomes depressed, agitated, or confused may experience these feelings in an overwhelming manner that grows on itself. The best solution is to remove disturbing influences, get to a safe, comforting environment, and reassure the tripper that things are alright. It may comfort those who fear that they are losing their minds to be reminded that it will end in several hours.
Authorities are fond of administering injections of anti-psychotic drugs. Recovery in the presence of authorities, in hospitals or police stations, is not pleasant. Sedatives or tranquilizers such as Valium may help reduce panic and anxiety, but the best solution is calm talking. Some claim that niacin (an over the counter vitamin supplement) can abort a trip, but this may be due to a placebo effect (niacin produces a flushing effect). Remember that odd bodily sensations are normal and not harmful.
From page 8 of Robert Anton Wilson's Sex and Drugs: A Journey Beyond Limits
"The distinction between psycholytic and psychedelic doses of LSD is used in many scientific publications but seems to be ignored by popularizers who either preach the "LSD utopia" or warn of the "decline of the West." A psycholitic does, generally 75 or 100 - or at most 200 - micrograms, causes a rush of thoughts, a lot of free association, some visualization (hallucination) and abreaction (memories so vivid that one seems to relive the experience). A psychedelic dose, around 500 micrograms, produces total but temporary breakdown of usual ways of perceiving self and world and (usually) some form of "peak experience" or mystic transcendence of ego. "Bad trips" usually occur only on psychedelic doses."
The best review of this question is Rick Strassman's "Adverse Reactions to Psychedelic Drugs: a Review of the Literature" in _J. Nerv and Mental Disease_ 172(10):577-595. He writes:
The most common adverse reaction is a temporary (less than 24 hours) episode of panic --the "bad trip". Symptoms include frightening illusions/ hallucinations (usually visual and/or auditory); overwhelming anxiety to the point of panic; aggression with possible violent acting-out behavior; depression with suicidcal ideations, gestures, or attempts; confusion; and fearfulness to the point of paranoid delusions.
Reactions that are prolonged (days to months) and/or require hospitalization are often referred to as "LSD psychosis," and include a heterogenous population and group of symptoms. Although there are no hard and fast rules, some trends have been noted in these patients. There is a tendency for people with poorer premorbid adjusment, a history of psychiatric illness and/or treatment, a greater number of exposure to psychedelic drugs (and correlatively, a great average total cumulative dosage taken over time), drug-taking in an unsupervised setting, a history of polydrug abuse, and self-therapeutic and/or peer-pressure-submission motive for drug use, to suffer these consequences.
In spite of the impressive degree of prior problems noted in many of these patients, there are occasional reports of severe and prolonged reactions occuring in basically well adjusted individuals. In the same vein, there are many instance of faily poorly adapted individuals who suffer _no_ ill effects from repeated psychedelic drug use. In fact, it has been hypothesized that some schizophrenics do not suffer adverse reactions because of their familiarity with such acute altered states. Another possibility is that there individuals may be "protected" by possible "down-regulation" of the receptors for LSD, bu the (over-)production of some endogenous compound. _Individual_ prediction of adverse reactions, therefore, is quite difficult...
Major "functional" psychosis vs. "LSD psychosis"
A diagnostic issue dealth with explicitly in only a few papers is that of LSD-precipitated major functional illnesses, e.g. affective disorders or schizophrenia. In other words, many of these so called LSD psychoses could be other illnesses that were triggered by the stress of a traumatic psychedelic drug experience. Some of the same methodological issues described earlier affect these studies, but they are, on the averagem better controlled, with more family and past psychiatric history available for comparison.
Hensala et al. compared LSD-using and non-LSD-using psychiatric inpatients. They found that this group of patients was generally of a younger age and contained more characteristically disordered individuals than the non- LSD-using group. Patients with specific diagnoses with or without LSD histories were not compared. Based on their observations, they concluded that LSD was basically just another drug of abuse in a population of frequently hospitalized individuals in the San Francisco area, and that it was unlikely that psychedelic use could be deemed etiological in the development of their psychiatric disorders.
Roy, Breakey et al., and Vardy and Kay have attempted to relate LSD use to the onset and revelopment of a schizophrenia-like syndrome. A few comments regarding this conceptual framework seem in order, before their findings are discussed. The major factor here is that of choosing schizophrenia, or in the Vardy and Kay study, schizophreniform disorders, as the comparison group. There is an implication here that LSD psychoses are comparable, phenomenologically, to schizophrenia-like disorders, and that LSD can "cause" the development of such disorders. The multiplicity of symptoms and syndromes described in the "adverse reaction" literature should make it clear that LSD can cause a number of reactions that can last for any amount of time--from minutes to, possibly, years. I believe what is being studied here is the question of the potential role of LSD in accelerating or precipitating the onset of an illness that was "programmed" to develop ultimately in a particular individual--in a manner comparable to the major physical or emotional stress that often precipitates a bona fide myocardial infarction in an individual with advanced coronary atheresclerosis. The stress did not _cause_ the heart disease; it was only the stimulus that accelerated the inexorable process to manifest illness.
In looking at the relevant studies, Breakey et al. found that schizophrenics who "used drugs" had an earlier onset of symptoms and hospitalization than non-drug-using schizophrenics, and had possibly better premorbid personal- ities than non-drug using patients (although Vardy and KAy have challenged this analysis of Breakey's data).
Bowers compared 12 first-admission patients with psychosis related to LSD use, requiring hospitalization and phenothiazines, to 26 patients hospital- ized and treated with phenothiazines with no history of drug use. Six of these controls had been previously hospitalized. Drug-induced psychotic patients were found to have better premorbib histories and prognostic indicators than the nondrug groups. There was no difference in rates of family history of psychiatric illness. However, several issues flaw this study. One is the poly-drug abusing nature of the "LSD-induced" psychotic patients, compared to the controls. The role of LSD, therefore, in causing or precipitating these symptomatic disorders, is open to dispute. The other is the lack of an adequate comparison control group, i.e. the controls were specified only as "psychotic," and did not necessarily match the LSD group in either symptoms or diagnostic classification. A follow-up study of the patients occured between 2 and 6 years later. One half did well and one half did poorly, although the lack of a control group for a follow-up in a similarly symptomatic control group makes interpretation of the data difficult.
Roy, in a somewhat different design, compared chronic schizophrenic patients (diagnosed according to DSM-III criteria) who had used LSD within the week preceding hospitalization, and found no difference in age of symptom onset or hospitalization compared to patients without a history of illicit drug use.
Vardy and Kay, in an elegant study with a 3- and 5- year follow-up period, demonstrated that patients hospitalized for a schizophrenic picture that developed within two weeks of LSD use (patients with other diagnoses were explicitly excluded form comparisons with non-drug-using schizophrenics) were "fundamentally similar to schizophrenics in geneology, phenomenology, and course of illness (165, p. 877). Pre- morbid adjustment, age of onset of symptoms and hospitalization, family history of psychosis or suicide, and most cognitive features were also equal between groups. Family histories of alcohol abuse were markedly great in the LSD group.
I believe these data, taken as a whole, limited as they are in terms of comparing subgroups (i.e. LSD-using vs. non-LSD-using) of "schizophrenia- like" disorders, point towar, at most, a possible precipitory role in the development of these disorders, in a non specific and not etiologically related manner.
LSD does not form "crystals" that reside in the body to be "dislodged" later, causing flashbacks. LSD is a crystalline solid (though it is unlikely that one would ever have enough to be visible to the naked eye) but it is easily water soluble, thus cannot form bodily deposits. Furthermore, it is metabolized and excreted in hours. The bogus "loosened crystal" description in not necessary to explain flashbacks, which are psychological phenomena (see FLASHBACKS).
LSD does not cause chromosome damage.
In Science 30 April 1972, Volume 172 Number 3982 p. 431-440 there was an article by Norman I. Dishotsky, William D. Loughman, Robert E. Mogar and Wendell R. Lipscomb titled "LSD and Genetic Damage - Is LSD chromosome damaging, carcinogenic, mutagenic, or teratogenic?". They reviewed 68 studies and case reports published 1967-1972, concluding "From our own work and from a review of literature, we believe that pure LSD ingested in moderate doses does not damage chromosomes in vivo, does not cause detectable genetic damage, and is not a teratogen or carcinogen in man."
Well, there's the study by Sidney Cohen which was cited here recently, Journal of Nervous and Mental Disease, 130, 1960. The following is from Jay Stevens' Storming Heaven: "Cohen surveyed a sample of five thousand individuals who had taken LSD twenty-five thousand times. He found and average of 1.8 psychotic episodes per thousand ingestions, 1.2 attempted suicides, and 0.4 completed suicides. 'Considering the enormous scope of the psychic responses it induces,' he concluded, 'LSD is an astonishingly safe drug.'"
Some urban legends: I've heard two "stories" about people blinding themselves on "drugs". One was revealed as a hoax by the person who perpetrated it (apparently it was intended to "illustrate" the dangers of LSD), another is trotted out by anti-drug speakers at high schools:
- Staring at the Sun: Seven people on LSD stared at the sun and lost 90% of their reading vision. See Erowid's LSD Myth Page
- Plucking Out Eyeballs: A teenager arrested while on LSD plucked out his eyeballs in his jail cell, and felt no pain. This may come from Fear & Loathing in Las Vegas where the main character, Duke, reads about a similar episode involving PCP. See Erowid's LSD Myth Page.
There is an occasionally circulated fake warning from some police department about LSD-laced "tattoos" or stickers (the "blue star tattoo" story) being given to children. This probably originated with some hick cop or ignorant and panicky parent not understanding some children-cartoon (eg, mickey mouse in sorcerer's garb) printed on a sheet of blotter.
Purely psychological hazards, not harmful to body. May release latent psychosis or exacerbate depression, leading to irrational behavior. There is also a danger of foolish or incautious behavior, e.g, misjudging distances or thinking one can fly. Physical overdose is not a hazard, though one may easily ingest more than one may be able to handle psychologically.
Because the "LSD psychosis" is not distinguishable from non-drug-induced psychosis, we have reasonable evidence to conclude that LSD was not the sole cause of psychosis. Instead, it would seem that the drug brought on the problems in vulnerable individuals. Interestingly, the rate of parental alcoholism was found to be much higher in LSD patients than in other patients or in the general population by one study (Vardy and Kay, Arch-Gen-Psych, 1983 40(8): 877-83).
Lethal (toxic) doses of LSD are conservatively several tens of thousands of times as much as a normal dose, making it (in the toxic sense) one of the safest drugs known. See section on Pharmacology for description of bodily side-effects.
The LD50 for psilocybin (active ingredient in mushrooms) is 275 mg/kg i.v. in mice. Of course, it would take lots more p.o. to kill someone.
The reported LD50 values for LSD are 46, 16.5, 0.3 mg/kg I.V. for mice, rats, and rabbits, respectively. Again, it's hard to accurately translate these numbers to oral values.
Note that an average human dose is 0.001 mg/kg, ie, 1 microgram/kg, ie, 1 part per billion by weight.
Never take any drugs while pregnant. Best to be prudent.
Quoted without permission from 'Licit and Illicit Drugs,' written by Edward M. Brecher and the editors of Consumer Reports. ISBN: 0-316-15340-0
A simple explanation of LSD flashbacks, and of their changed character after 1967, is available. According to this theory, almost everybody suffers flashbacks with or without LSD. Any intense emotional experience--the death of a loved one, the moment of discovery that one is in love, the moment of an automobile smashup or of a narrow escape from a smashup--may subsequently and unexpectedly return vividly to consciousness weeks or months later. Since the LSD trip is often an intense emotional experience, it is hardly surprising that it may similarly "flash back."
"Post-traumatic stress disorder has been commonly associated with war veterans, but it also affects victims of disasters and violence... Experts estimate that 1% of the population suffers from the disorder."
---LA Times, Feb 18 1992, p A3, "Journey For Better Life Hell For Some Women."
Can smoking marijuana induce a flashback?
Also are you more likely to suffer flashbacks from having a bad trip?
Apparently yes and yes. The following is reproduced without permission from Lester Grinspoon and James B. Bakalar, "Psychedelic Drugs Reconsidered," Basic Books, Inc. New York, 1979. pp. 159-163. I highly recommend this book, and if you find it please buy me one too.
I typed this in a while ago and didn't type in the references at the time (slap!). If you want them i'll see what i can do. Typos are mine.
... Studies of flashbacks are hard to evaluate because the term has been used so loosely and variably. On the broadest definition, it means the transitory recurrence of emotions and perceptions originally experienced while under the influence of a psychedelic drug. It can last seconds or hours; it can mimic any of the myriad aspects of a trip; and it can be blissful, interesting, annoying, or frightening. Most flashbacks are episodes of visual distortion, time distortion, physical symptoms, loss of ego boundaries, or relived intense emotion lasting a few seconds to a few minutes. Ordinarily they are only slightly disturbing, especially since the drug user usually recognizes them for what they are; they may even be regarded lightheartedly as "free trips." Occasionally they last longer, and in a small minority of cases they turn into repeated frightening images or thoughts. They usually decrease quickly in number and intensity with time, and rarely occur more than a few months after the original trip.
A typical minor and pleasant flashback is the following:
... Frequently afterward there is a momentary "opening" ("flash" would be too spastic a word) when for maybe a couple of seconds an area one is looking at casually, and indeed unthinkingly, suddenly takes on the intense vividness, composition, and significance of things seen while in the psychedelic condition. This "scene" is nearly always a small field of vision -- sometimes a patch of grass, a spray of twigs, even a piece of newspaper in the street or the remains of a meal on a plate.
(Cohen 1970, pp. 114-115)
Here are two more troublesome examples:
For about a week I couldn't walk through the lobby of A-entry at the dorm without getting really scared, because of the goblin I saw there when I was tripping.
(Pope 1971, p. 93)
A man in his late twenties came to the admitting office in a state of panic. Althought he had not taken any drug in approximately 2 months he was beginning to re-experience some of the illusory phenomena, perceptual distortions, and the feeling of union with the things areound him that had previously occurred only under the influence of LSD. In addition, his wife had told him that he was beginning to "talk crazy," and he had become frightened ... He was concerned lest LSD have some permanent effect on him. He wished reassurance so that he could take it again. His symptoms have subsided but tend to reappear in anxiety-provoking situations.
(Frosch et al. 1965, p. 1237)
Flashbacks are most likely to occur under emotional stress or at a time of altered ego functioning; they are often induced by conditions like fatigue, drunkenness, marihuana intoxication, and even meditative states. Falling asleep is one of those times of consciousness change and diminished ego control; an increase in the hypnagogic imagery common at the edge of sleep often follows psychedelic drug use and can be regarded as a kind of flashback. Dreams too may take on the vividness, intensity, and perceptual peculiarities of drug trips; this spontaneous recurrence of psychedelic experience in sleep (often very pleasant) has been called the high dream (Tart 1972). Marihuana smoking is probably the most common single source of flashbacks. Many people become more sensitive to the psychedelic qualities of marihuana after using more powerful drugs, and some have flashbacks only when smoking marihuana (Weil 1970). In one study frequency of marihuana use was found to be the only factor related to drugs that was correlated with number of psychedelic flashbacks (Stanton et al. 1976).
How common flashbacks are said to be depeds on how they are defined. By the broad definition we have been using, they occur very often; probably a quarter or more of all psychedelic drug users have experienced them. A questionanaire survey of 2,256 soldiers (Stanton and Bardoni 1972), leaving the definition to the respondents, revealed that 23 percent of the men who used LSD had flashbacks. In a 1972 survey of 235 LSD users, Murray P. Naditch and Sheridan Fenwick found that 28 percent had flashbacks. Eleven percent of this group (seven men in all) called them very frightening, 32 percent called them somewhat frightening, 36 percent called them pleasant, and 21 percent called them very pleasant. Sixty-four percent said that their flashbacks did not disrupt their lives in any way; 16 percent (4 percent of the whole LSD-using group) had sought psychiatric help for them (Naditch and Fenwick 1977). In a study of 247 subjects who had taken LSD in psychotherapy, William H. McGlothlin and David O. Arnold found 36 cases of flashbacks, only one of which was seriously disturbing (McGlothlin and Arnold 1971). McGlothlin, defining flashbacks narrowly for clinical purposes as "repeated intrusions of frightening images in spite of volitional efforts to avoid them" (McGlothlin 1974b, p. 291), estimates that 5 percent of habitual psychedelic users have experienced them.
There are few studies on the question of who is most susceptible. In 1974, R. E. Matefy and R. Krall compared psychedelic drug users who had flashbacks with those who did not, and found no significant differences in their biographies or on personality tests. The main causes of flashbacks were stress and anxiety. About 35 percent found them more or less pleasant, and the same proportion thought they could control them. Most accepted them as an inevitable part of their lives as members of the psychedelic fraternity and did not want help from psychiatry (Matefy and Krall 1974). Naditch and Fenwick found that the number of flashbacks, both pleasant and unpleasant, was highly correlated with the number and intensity of bad trips and the use of psychedelic drugs as self-prescribed psychotherapy. Those who enjoyed flashbacks and those who were frightened by them did not differ significantly on tests of ego functioning.
A case seen in an outpatient setting in the late sixties illustrates the kind of set and setting that may create flashback problems. PQ was a thirty-six-year-old single man who entered therapy because of depression and anxiety. He was a heavy drinker who was passive, slovenly, and spent most of his time in bed. Just before taking to alcohol and his bed he had failed in an attempt to parlay a gift from his wealthy father into a fortune on the stock market. Despite a remarkable incapacity for insight, during a year in psychotherapy he managed to give up alcohol and start a promising business. But his anxiety continued, and in order to allay it he had to keep himself very busy wheeling and dealing. Imitating his father, a successful self-made man who had married a woman twenty years younger than himself, PQ dated only women under the age of nineteen. Being attractive to young women was so imporant to him that much of his time was spent in the company of teenagers. During business hours he would wear a conservative three-piece suit and drive a new sedan, but when he was with his young friends he would wear a leather jacket and drive a motorcycle. Anxiety and fears of inadequacy dominated both of these lives. Several months after therapy began, during a weekend in a small resort town, his young friends decided to take LSD, and he felt obliged to dissemble his fears and join them; it was his first and only trip. He felt a panic he had never known before; he thought that he was losing his mind and going "out of control." His friends were so concerned that they took him to a small hospital, where he was given chlorpromazine and after six hours released in their care. The next day he had a flashback that lasted one or two hours and was almost as frightening as the original experience. Flashbacks continued for six months, their frequency, duration, and severity eventually diminishing to the point where it was difficult for him to determine whether they were related to the LSD trip or merely an intensification of his usual anxiety. In fact, the patient described the flashbacks as being like very much enhanced anxiety episodes. Even several years after this experience, when he became very anxious, he was reminded of the trip and these flashbacks. He denied that these experiences had any perceptual or cognitive aspect; both during the LSD trip and later, the only symptom was panic. There is no question that the nature of his trip was influenced by the unfortunate set and setting. It is a matter of speculation what part his underlying chronic anxiety played in the development and form of the flashback phenomena.
Several explanations for flashbacks have been proposed. One is that the drug has lowered the threshold for imagery and fantasy and made them less subject to voluntary control; in another version of this explanation, flashbacks are caused by a heightened attention to certain aspects of immediate sensory experience suggested by drug trips and reinforced by the community of drug users. Something more seems to be needed to account for repeated fearful relivings of sequences from past drug trips, and these have been explained as similar to traumatic neuroses precipitated by fright: disturbing unconscious material has risen to consciousness during the drug trip and can be neither accepted nor repressed. For example, D. F. Saidel and R. Babineau (1976) have reported a case of recurrent flashbacks -- three years of blurring images and auditory distortions, with some anxiety and confusion -- which they regard as a neurosis founded on the patient's problems with his career and his relationship to his mother. (See also Horowitz 1969; Shick and Smith 1970; Heaton 1975.) Another explanation treats the flashback as an example of recall associated with a particular level of arousal. (Fischer 1971). In this conception the memory of an experience is best retrieved when the rate of mental data-processing is the same as it was during the original experience -- in other words, when the state of consciousness in similar. Therefore, psychedelic experiences are likely to be recalled and relived when the ego's sorting and control of sensory information is disturbed by drugs, stress, or the state of half-sleep.
For a critique of flashback studies, see Stanton et al. 1976
Insomnia occurs frequently after the trip. A mild, over-the-counter sleeping aid can help, and these antihistamines do not produce adverse interactions. Also, some people like to consume a small amount of alcoholic beverage to "smooth the jitteries". The usual precautions about sleeping aids if alcohol has been consumed apply of course.
Aquired rapidly, within 3 days. Tolerance dissipates equally rapidly, without withdrawal, craving, or symptoms of addiction.
Cross-tolerance has been reported with some other indole-hallucinogens such as Psilocybin, but this document erroneously reported cross-tolerance with N,N-DMT, which is not likely and has not been shown.
Lysergic compounds appear in ergot, a fungal parasite of cereal grains; morning glory and hawaiian baby wood rose seeds; psychedelic tryptamines also occur in psilocybe mushrooms, in some south american trees and the poison glands of the cane toad. (Mescaline is not in this chemical family).
"Indole Alkaloids In Plant Hallucinogens" Richard Evans Schultes, PhD. Journal of Psychedelic Drugs Vol.8(No.1) Jan-Mar 1976
"The main constituent of the seeds of Rivea corymbosa is ergine or d-lysergic acid amide. Minor alkaloids present are the related d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine and lysergol. The seeds of Ipomoea violacea have a similar composition, but instead of lysergol, they have ergometrine (ergonovine). Later, very minor amounts of two alkaloids ergometrinine and penniclavine - were found in I. violacea by chromatography. the total alkaloid content of the seeds of Ipomoea viloacea is approximately five times as great as that of the seeds of Rivea corymbosa: 0.06% in the former; 0.012% in the latter. This difference in the alkaloid content explains why Indians employ smaller doses of seeds of the Ipomoea than of the Rivea.
"Ethnopharmacology and Taxonomy of Mexican Psychodysleptic Plants"
Jose Luis Diaz M.D.
Journal of Psychedelic Drugs Vol. 11(1-2) Jan-Jun 1979
Seeds of various Morning Glories contain
Glucosides: turbicoryn [apparently in Turbina corymbosa only]
called Tlitlitzen (Aztec word for "The Divine Black One") to the Aztecs, Black is a "hot" color, a property of psychotropics associated with light
"The Botanical and Chemical Distribution of Hallucinogens"
Richard Evans Schultes, PhD.
Journal of Psychedelic Drugs Vol.9(No.3) Jul-Sep 1977
"I. violacea, often referred to by it's synonyms I. rubro-caerulea and I. tricolor, is represented in horticulture by a number of "varieties," such as: Heavenly Blue, Pearly Gates, Flying Saucers, Wedding Bells, Summer Skies, and Blue Stars - all of which contain the hallucinogenic ergot alkaloids."
>In the Journal of Psychoactive Drugs, 1980, there is an article
>on an ergot derivative used in obstetrics which is an hallucinogen.
>Although the dose required is ten times the ED50 (.2 mg) no
>significant ill effects were reported.
>I believe the name of this drug is methyl ergovine(?) The drug
>without the methyl group is supposed to be more effective. It
>was (is?) a Sandoz drug, for those with a PDR.
Ergonovine and methylergonovine are both oxytocic agents: they increase uterine tone and are used (rarely) to assist in delivery and (more frequently) to stop post-partum uterine hemorrhage. Less frequently, they can be used to abort a migraine headache. If they have any hallucinogenic effects, it is certainly a well-kept secret.
I would be quite concerned about taking 10x the therapeutic dose of a drug like ergonovine, since it can cause arterial spasm and precordial distress even in healthy persons, and intense vasoconstriction and gangrene can follow from an overdose. These are not drugs to fool around with.
Another related drug, 1-methyl-methylergonovine, or methysergide (Sansert), is used in migraine prophylaxis, and is claimed to have LSD-like actions when high doses are taken. The methyl group on the indole nitrogen reduces the drug's vasoconstrictive actions. Chronic, uninterrupted use of the drug causes a fibrosis of the heart valves and the lungs.
"Burger's Medicinal Chemistry" Fourth Edition, Volume III
Chapter: "Hallucinogens" Alexander Shulgin
Composition, % of total alkaloids present ========================================= Compound R. corymbosa I. violacea =============== ================ ====================== Ergine (LA-111) 54, 48 58, 10-16, 5-10 Isoergine 17, 35 8, 18-26, 9-17 Ergometrine 8 Elymoclavine 4 4 Chanoclavine 4 4 Lysergol 4 Total Alkaloids .012, .04 .06, .04-.08, .02-.04 (% of dry weight of seeds)
IPOMOEA PURPUREA: A NATURALLY OCCURRING PSYCHEDELIC
Charles Savage, Willis W. Harman and James Fadiman
>From "Altered States of Consciousness, A Book of Readings"
edited by Charles Tart BF311.T28
Of the naturally occurring plant alkaloids used in ancient and modern religious rites and divination one of the least studied is ololiuqui. The earliest known description of its use is by Hernandez, the King of Spain's personal physician, who spent a number of years in Mexico studying the medicinal plants of the Indians and "accurately illustrated ololiuqui as a morning glory in his work which was not published until 1651" (Schultes, 1960). In his words, "When a person takes ololiuqui, in a short time he loses clear reasoning because of the strength of the seed, and he believes he is in communion with the devil" (Alacon, 1945). Schultes (1941) and Wasson (1961) have reported in detail on the religious and divinatory use of two kinds of morning-glory seeds, Rivea corymbosa and Ipomoea violacea, among the Mazatec and Zapotec indians. The first of these is assumed to be the ololiuqui of the ancient Aztecs.
In 1955 Osmond described personal experiments with Rivea corymbosa seeds and reported that the effects were similar to those of d-lysergic acid diethylamide (LSD-25). He suggested (1957) that the word psychedelic (meaning mind-manifesting) be used as a generic term for this class of substances to refer to their consciousness-expanding and psychotherapeutic function as contrasted with the hallucinogenic aspect. In 1960 Hofmann reported that he had isolated d-lysergic acid amide (LA) and d-isolysergic acid amide from the seed of both Rivea corymbosa and Ipomoea violacea. LA is very similar to LSD in its psychological and physiological manifestations but is reported to have about one twentieth the psychological effectiveness of LSD (Cerletti & Doepfner, 1958).
The work of these investigators led us to a preliminary study of the psychedelic properties of species of Ipomoea which are commonly found within the continental United States. The seeds of Ipomoea purpurea, the common climbing morning glory, resemble the seeds of Ipomoea violacea and have been found to have similar psychedelic properties. Recent analysis by Taber et al. (1963) has verified that LA is present in the varieties used and is probably the primary active agent.
The effects of the seeds of Ipomoea purpurea (varieties Heavenly Blue and Pearly Gates) in a total of 45 cases are summarized below. The subjects are all normally functioning adults and the majority had previous experience with LSD. The onset of effects is about half an hour after the seeds have been chewed and swallowed and they last from five to eight hours.
Low Dose, 20-50 Seeds (11 Subjects)
This dosage rarely produces any visual distortions, although with eyes closed there may be beginning imagery. Restlessness, evidenced by alternating periods of pacing about and lying down, may be present. There tends to be a heightened awareness of objects and of nature, and enhanced rapport with other persons. A feeling of emotional clarity and of relaxation is likely to persist for several hours after other effects are no longer noticeable.
Medium Dose, 100-150 Seeds (22 Subjects)
In this range the effects resemble those reported for medium-dose (75-150 micrograms) LSD experiences, including spatial distortions, visual and auditory hallucinations, intense imagery with eyes closed, synaesthesia and mood elevation. These effects, which occur mainly during the period of 1 to 4 hours after ingestion, are typically followed by a period of alert calmness which may last until the subject goes to sleep.
High Dose, 200-500 Seeds (12 Subjects)
In this range the first few hours may resemble the medium-dose effects described above. However, there is usually a period during which the subjective states are of a sort not describable in terms of images or distortions, states characterized by loss of ego boundaries coupled with feelings of euphoria and philosophical insight. These seem to parallel the published descriptions of experiences with high doses (200-500 micrograms) of LSD given in a supportive, therapeutic setting as reported by Sherwood et al. (1962).
All the subjects who had previous experience with LSD claimed the effects of the seeds were similar to those of LSD. Transient nausea was the most commonly reported side effect, beginning about one half hour after ingestion and lasting a few minutes to several hours. Other reported side effects not commonly found with LSD were a drowsiness or torpor (possibly due to a glucoside also present in the seeds) and a coldness in the extremities suggesting that the ergine content of the seeds may be causing some vascular constriction. (If this is the case, there may be some danger of ergot poisoning resulting from excessive dosages of the seeds.) The only untoward psychic effect was a prolonged (eight hours) disassociative reaction which was terminate with chlorpromazine [Thorazine]. The possibility of prolonged adverse reactions to the psychological effects of the seeds is essentially the same as with LSD, and the same precautions should be observed (Cohen & Ditman, 1963).
Additional Notes: Ipomoea purpurea is sold as the "Heavenly Blue" variety of morning glory. "Ipomoea tricolor" is the trade name used for that variety. It is identical with the species of morning glory described above.
The seeds must be chewed or ground in order to be effective. Soaking the ground seeds in water for several hours, filtering out the grounds, and then drinking only the water portion of the mixture can reduce some of the stomach-upset symptoms if such occur.
Unpleasant LSD and morning glory trips can be smoothed out or even stopped by taking niacin (in the form of nicotinic acid, vitamin B-3 or "niacin"). Vitamin C has been shown to reduce the incidence of paranoia and prevent depletion of the vitamin from the adrenal glands during LSD trips.
There have been reports that commercially available packets of morning glory seeds from some distributors are coated with fungicides or other chemicals to increase shelf life or discourage the practice of eating them. Seeds from plants grown in one's own garden will be safe as long as you do not spray them with insecticides.
The last few notes about Niacin and Vitamin C are based on a paperback edition of Hoffer & Osmonds "The Psychedelics"
It's pretty clear that the latin names of this plant are somewhat confused (which is typical). Ipomoea purpurea, Ipomoea tricolor, Ipomoea violacea and Ipomoea rubro-caerulea are all the same plant.
The other variety of morning glory, "Ololiuhqui" has at least two Latin names as well: Turbina corymbosa, and Rivea corymbosa.
"Recreational use of Ergoline Alkaloids from Argyreia Nervosa"
William E. Shawcross
Journal of Psychedelic Drugs Vol. 15(4) Oct-Dec 1983
lysergic acid diethylamide _is_ lysergic acid diethylamide (or... N,N-diethyl-D-lysergamide or... 9,10-Didehydo-N,N-diethyl-6-methylergoline-8B-carboxamide).
Only one stereoisomer (the d-) is psychoactive. Thus, racemic (l/d 50-50 mix) lsd shows half the potency of the dextro form. In synthesis it is possible to recover the l-form for the lysergic acid.
Lysergic Acid Diethylamide is LSD rather than LAD because the German word for acid is saeure (sp).
LSD-25 Lysergic acid O CH2-CH3 O || / || || / || -C--N C---OH | \ | | \ | |___ CH2-CH3 |___ / \ / \ / \ / \ << N---CH3 << N---CH3 \\ / \\ / \\____/ \\____/ / \ / \ / \ / \ < > < > // \ / // \ / // \_____/ // \_____/ | || || | || || | || || | || || | || || | || || \\ /\ / \\ /\ / \\ / \ / \\ / \ / N N H HErgot is a product of the fungus Claviceps purpurea. The bio-active ingredients of ergot are all derivatives of lysergic acid. LSD is a semisynthetic derivative of lysergic acid. Thus LSD is an "ergot"-like substance.
CHEMISTRY AND EFFECT OF THE SEEDS
The Hawaiian baby woodrose entered the drug scene in 1965 with the publication of a paper in "Science" entitled "Ergoline Alkaloids in Tropical Wood Roses" by Hylin and Watson. The wide circulation of this journal assured thorough dissemination of the information they presented. They wrote, "The possible health and legal problems associated with the presence of similar compounds in commercially cultivated plants led us to examine the ornamental wood roses, Ipomoea tuberosa and Argyreia nervosa, both common Hawaiian crops that have assumed commerical importance as components of [the] dried tropical flower industry." Comparing the seeds of these two plants with those of the morning glory varieties Pearly Gates and Heavenly Blue, they found the following yield of alkaloids (mg of alkaloid/g of seed material):
Heavenly Blue 0.813
Pearly Gates 0.423
I. tuberosa [None]
A. nervosa 3.050
The seed of A. nervosa is the best plant source of ergoline alkaloids discovered; it contains approximately 3 mg of alkaloidal material per gram of seed. Approximately one-eighth of this is lysergamide.
Hylin and Watson found the major alkaloidal constituents in A. nervosa seeds to be ergine (780 mcg/g of fresh seed) and isoergine and penniclavine (555 mcg).
[Note: Argyreia nervosa has NO history of shamanic use as a hallucinogen]
This is an excerpt from the article cited :
There's no record of Argyreia being used as an hallucinogen in India, but it was used externally as some kind of skin medicine. There's been speculation that Argyreia might have been a component of "Soma", but there's no evidence for that, apparently. Because there's not a long history of human usage of Argyreia, it may be that there are glycosides not mentioned here that take effect at higher doses or might cause stomach upset, tachycardia etc. The article mentioned intestinal complaints in one or two cases at higher experimental doses.
MECHANISM OF ACTION:
(Note: the mechanism of action of LSD and other psychedelics is uncertain.)
From Watson SJ. Hallucinogens and other psychotomimetics: biological mechanisms.
In: Barchas JD, Berger PA, Cioranello RD, Elliot GR (eds.). Psychopharmacology from theory to practice.
Oxford: Oxford University Press, 1977.
"The current thesis of the effect of indole hallucinogens on 5-hydroxytrypamine might be stated as follows: LSD acts to preferentially inhibit serotonergic cell firing and seems to spare postsynaptic serotnergic receptors. This preference is shared by other simillar hallucinogens but in a limited fashion. Nonhallucinogenic analogs of LSD show no preference. These results suggest that there are two different steric conformation of serotonergic receptors, one of which has higher affinity for LSD than the other. In general, 5-ht is an inhibitory transmitter; thus, when its activity is decreased, the next neuron in the chain is freed from inhibition and becomes more active. Since serotnergic systems appear to be intimately involved int eh control of sensation, sleep, attention, and mood, it may be possible to explain the actions of LSD and other hallucinogens by their disinhibition of these critical systems.
There is also evidence for interaction with dopaminergic systems.
LSD acts as a 5HT autoreceptor agonist in the raphe nucleus. These autoreceptors are typically considered to be 5HT1As. It also acts as a 5HT2 agonist, which is thought to be the main site of hallucinogenic activity. It's probably best called a a mixed 5HT2/5HT1 receptor partial agonist.
I don't know of its effects on dopamine. Wouldn't be surprised if it has 'em; the systems aren't really functionally separable. The DA effects wouldn't be necessary for hallucinogenic activity, I'd bet.
(From Snyder, "Drugs and the Brain", 1986, Sci Am Books Inc., Reprinted w/o permission, blah, blah, blah... )
In more recent studies, Aghajanian has focused not on the serotonin neurons of the raphe nuclei but on the norepinephrine neurons of the locus coeruleus. As we saw in Chapter 6, the locus coeruleus cell bodies give rise to axons that ramify all over the brain and provide the majority of the norepinephrine neuronal input in most brain regions. Amphetamine releases norepinephrine from these nerve terminals by diplacing the norepinephrine from the neurotransmitter storage vesicles. Presumably, the overall influence of amphetamine on brain function is therefore somewhat different than what occurs when the locus coeruleus fires rapidly. The amphetamine-induced seepage of norepinephrine out of nerve terminals probably elicts a milder type of activation than does the repetitive and presumably more robust ejection of norepinephrine that occurs with rapid firing of the locus coeruleus. Drug-induced changes in animal behavior support this conceptual model. Amphetamine elicits behavioral activation, represented by the rats or mice running about the cage. In contrast, electrical stimulation of the locus coeruleus produces a more dramatic startle response. It is difficult to observe a rat and make inferences about what the animal is feeling, but rats in whom the locus coeruleus has been stimulated seem to go into a state of panic. They stare about, hyper-responsive to all stimuli in the enviornment, whether visual, auditory, or tactile.
Rats show the same hyper-responsiveness to environmental-stimuli--jumping abruptly at the sound of fingers snapping or in response to a puff of air in the face--when they have been treated with a psychedelic drug. And as you will recall, hyper-responsiveness to sensory stimuli of all modalities is just what one observes in humans under the influence of psychedelic drugs. At- tracted by the similarity between the behavior of rats on LSD and their reac- tion to stimulation of the locus coeruleus, Aghajanian embarked in 1980 upon a series of studies to evaluate how psychedelic drugs affect the locus coeruleus. He showed that any kind of sensory stimulation--sight, sound, smell, taste, or tactile sensation--speeds up the firing of locus coeruleus neurons in rats, and that the accelerated firing is greatly enhanced by treating the animals with LSD or mescaline. In contrast, nonpsychedelic drugs, such as amphetamines and antidepressants, fail to exert this effect. Moreover, the LSD analogue methysergide, which has no psychedelic effects in humans, is correspondingly ineffective in enhancing the reactivity of locus coeruleus neurons to sensory stimulation. Although psychedelic drugs increase the response of locus coeruleus cells to sensory stimulation, they do not cause the neurons to fire spontaneously in the absence of such stimulation. Moreover, directly applying LSD or mescaline to locus coeruleus neurons does not enhance the neurons' reponse to sensory stimulation. We must therefore conclude that the effect of psychedelic drugs on sensory stimulation is indirect--the drugs presumably interact with a different set of neurons that in turn make direct contact with the locus coeruleus. What is particularly fascinating about Aghajanian's findings is how nicely they correspond to what we know about the effects of psychedelic drugs in humans, and how readily they explain the way psychedelic drugs accentuate all our sensory perceptions. The locus coeruleus is a funneling mechanism that integrates all sensory input. Viewed in this way, the observations of Aghajanian can explain synesthesia. If the locus coeruleus lumps all types of sensory messages--from sights, sounds, tactile pressures, smells, tastes--into a generalized excitation system within the brain, one can readily appreciate that stimulation of the locus coeruleus will cause the drug user to feel that sensations are crossing the boundaries between different modalities.
Aghajanian's research may also illuminate how LSD influences the user's sense of self. The greatly accelerated firing of the locus coeruleus presumably provokes a powerful, patterned release of norepinephrine from nerve terminals throughout the brain. As we discussed earlier, the consequent alerting action would be much more pronounced than what occurs with the far more gradual leaking out of norepinephrine produced when amphetamine displaces the transmitter from the storage vesicles. This extremely enhanced level of alert- ness might possibly account for the "transendent" mental state produced by psychedelic drugs. In other words, in a state of such heightened awareness, the drug user may become conscious of an "inner self" to which he or she is normally oblivious.
Did that answer any of your questions? Probably not, but I thought it was interesting.
P.S. Snyder has tripped before =)
>"If there's no documentation, you can't tell bugs from features." ---C.P.
>> >>When ingested into the human body, LSD act as 5-HT (Serotonin) autoreceptor
>>inhibitor, thus it is a 5-HT agonist. LSD increases the level of active 5-HT
>>molecules by disaffecting their autoreceptors (a safeguard type feature in the
>>brain which reduces levels of certain neurotransmitter and the like).
That "thus" in the first sentence should be an "and." I'm not certain what "disaffecting" should be (autoreceptors' only true loyalty is to the laws of chemistry & physics) for the second sentence to be true.
The autoreceptors in question are 5-HT1As. 5-HT2s, which are not autoreceptors and which hallucinogens agonize, seem to be the more important ones for hallucinogenic activity. Hallucinogens need not affect 1As directly (some definitely don't). However, 5-HT2 receptor activation seems to facilitate presynaptic 1A function (such that, for example, hallucinogen use produces rapid 5-HT2 downregulation which, in turn, decreases 5-HT1A function). So hallucinogens would inhibit autorecetpor activity, but not necessarily directly.
>LSD also has effects on 5-HT1C receptors, and its not entirely sure what the
>specific receptor mechanism is -- there's also the question of why the
>psychological effects seem to last much longer than the presence of the LSD
>molecule. One thing that is fairly sure is that LSD shuts down the firing of
>the seratonin neurons in the raphe, though.
It is difficult to separate 1Cs from 2s because of their great similarity. However, hallucinogens seem to be all 2 & 1C agonists. Molecules which (like LSD) are partial 2 agonists, and which (unlike LSD) are 1c antagonists are not hallucinogenic.
I believe that the effects of DOI (and probably LSD) on firing in the raphe nucleus are not blocked by 5-HT2 antagonists (like ketanserin), implying that these effects are not mediated by 5-HT2 receptors. Oddly enough, ritanserin (which antagonizes 2 and 1C) doesn't block 'em either. That's kind of mysterious to me.
> 5-HT has been implicated in
>>certain behaviors, notably dreaming and sleep, which explains the hallucinatory
>>effect. We are in effect dreaming while completely awake and aware.
>Actually, a better explanation is the increased firing of the locus coereleus
>by its disinhibition due to the neurons in the raphe slowing down (since you
>are inhibiting an inhibitory neuron the result is excitation...). The l.c.
>has been associated with being a "sensory highway" in the brain, and has also
>been associated with feelings of anxiety, and theorized that its invovled
>with depression. My guess is that the hallucinations and stimulatory effects
>of LSD come from potentiating the l.c., while the effect on the 5-HT neurons
>in the raphe is responsible for its entheogenic effect on the mind.
This isn't the full story since this decrease in firing (in the raphe) is still produced by hallucinogens even after chronic treatment with hallucinogens. Since tolerance does develop to hallucinogens, we would have expected to see it in the firing. Of course, rate of firing and amount of 5-HT released _are_ two different things. Besides, tolerance may occur via another route.
[Reminder: FYI only, consult your shamans & attorneys etc., you are self-responsible, regardless of what anyone asserts.]