Misc LSD Info
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[...only the conclusions of this paper are made publicly available via anonymous ftp, interested persons should visit their libraries...] (Originally printed in Journal of Psychoactive Drugs, Vol 21(1), Jan-Mar 1989). LSD and Creativity (reproduced w/o permission) ------------------ Oscar Janiger, M.D. (Department of Psychiatry, University of California, Irvine, California) Marlene Dobkin de Rios, Pd. D. (Department of Anthropology, California State University, Fullerton, California) CONCLUSION Contrary to popular belief, most artists find it possible to exercise some technical proficiency, with varying degrees of success, under the influence of LSD. This seems to improve with repeated experiences. The artistic productions are not ipso facto inferior to those performed in ordinary states of consciousness. However, in evaluating the reports and follow-up questionnaires, they are often judged by the artists to be more interesting or even aesthetically superior to their usual mode of expression. A review of the follow-up information shows that, in many instances, the artist in the series described herein felt that the LSD experience pruduced some desirable lasting change in their understanding of their work, which continued to incluence the form and direction of their artistic development. A so-called confusional or disorganized phase may represent a creative crisis in which the artis struggling, to maintain his/her traditional approach, finally reaches another level of integration and expression. These metamorphoses all contribute to the artists' convictions that they are able to create new meanings in an emergent world. It is of special interest to note that many of those elements that are universally reported under the influence of LSD are those features traditionally associated with heightened artistic creativity. The ultiamte explanation for these changes may lie in a biochemical basis of perception and/or the cultural history of the individual. **************************** Article Separation ******************************* I was reading a back copy of The Journal of Drug Issues looking at an article on additiction when I came accross annother article. A chemistry for world peace. Willam H. McGlothlin, Journal of Drug Issues, Spring 1985, 225-245. Ok so it is a twinkie title, however it is perhaps the best article I have ever read on acid. The abstract; This paper presents an argument for research into the means of altering individual attitudes, values, and communication abilities in the direction of increased social empathy, which , inturn would produce a more favorable enviroment for resolving differences and facilitate peaceful negotions between individuals and nations. It is proposed that prior research with the drug d-lysergic acid diethylamide (LSD), shows sufficient promise in producing relatively long-lasting changes in the above areas to merit further research. Furthermore, the use of LSD has been demonstrated to be quite safe _under supervisory conditions_, i.e. the guided "trip." LSD is also non-toxic and non-addictive. A brief history of psychedelic drugs is provided along with a description of thier psychological effects. Some possible modes of action are discussed. LSD and other psychedelics are seen as a possible means of tapping mental resources which are not ordinarily available, but which may be of great value to the individual and ultimately to the society. The man who wrote it is unfortunantly dead, he was a well recognized scholar with a number of awards from academia and the government. He worked for RAND for a number of years and was no brainless yammerhead (despite the twinkie title). The article is full of all kinds of interesting things, A very good brief history of LSD and other psychedelics, one of the dest descriptions of an LSD experience I have ever encountered here is part: About 30 minutes after ingesting LSD the subject normally experiences a feeling of dizziness or intoxication. One of the most common early emotional reactions is smiling and laughing, which sometimes develops into uncontrollable laughing and/or crying. With closed eyes there is a lightening of the normal gray-black expanse and almost invariably colorful and luminous geometric designs appear in the field of vision. They may change into architechtural structures which freaquently are in very saturated colors and appear to be glowing from an internal light. He goes on to discuss changes resulting from the LSD experience (almost all are beneficial), and then talks about side effects. One nifty factoid; Estimated rates of Major Complications Associated with LSD Attempted completed psychotic reaction suicide suicide over 48 hours experimental subjects- 0/1000 0/1000 0.8/1000 patients undergoing therapy- 1.2/1000 0.4/1000 1.8/1000 (w/o psychobabble that means like really fucking good) There are also three and a half pages of cited references which alone is worth diggin up the article. **************************** Article Separation **************************** Newsgroups: alt.drugs Distribution: world Subject: From the Merck Manual -- LSD references, etc Keywords: LSD, Lysergic Acid Amide, Lysergic Acid Summary: A couple of pages of copywrite infringement From the 11th Edition of the Merck manual, the "Centennial Edition" no less: [perhaps something to drop in the FAQ?] 5505. Lysergamide. 9,10-Didehydro-6-methylergoline- 8beta-carboxamide; lysergic acid amide; ergine. C16H17N3O; mol wt 267.32. C 71.88%, H 6.41%, N 15.72%, O 5.99%. Isoln from _Rivea_corymbosa_(L.) and from _Ipomoea_tricolor_ Cav., _Convolvulaceae_: Hofmann, Tscherter, _Experientia_ 16, 414 (1964). Prepn from lysergic acid hydrazide: Ainsworth, U.S. pat. 2,756,235 (1956 to Lilly); from lysergic acid and phosgene-dimethylformamide complex: Patelli, Bernardi, U.S. pat. 3,141,887 (1964 to Farmitalia). Microbiological production: Rutschmann, Kobel, U.S. pat. 3,219,545 (1965 to Sandoz). H. CONH2 '. / / \ / \ || | || N /\\ /\ / \ / \\ / \ / CH3 || | | \ || | | H \ // \ / \// \/ | || | || HN------- Prisms from methanol. dec 242deg. [alpha](5461)(20) + 15% (c = 0.5 in pyridine). Methanesulfonate, C7H21N3O4S, prisms from methanol + acetone, dec 232deg. Note: This is a controlled substance (depressant) listed in the U.S. code of Federal Regulations, Title 21 Part 1308.13 (1987). 5506. Lysergic Acid. 9,10-Didehydro-6-methylergoline- 8-carboxylic acid. C16H16N2O2; mol wt 268.32. C 71.62%, H 6.01%, N 10.44%, O 11.93%. Lysergic acid and isolyser- gic acid are the main cleavage products formed on alkaline hydrolysis of the alkaloids which are characteristic of ergot. Jacobs, Craig et al., _J._Biol._Chem._ 104, 547 (1934); 125, 289 (1938); 130, 399 (1939); 145, 487 (1942); _J._Org._Chem._ 10, 76 (1945). High-yield production by _Claviceps_paspali_: Arcamone et al., _Proc._Roy._Soc._ (London), _Ser._B_, 155, 26 (1961). total synthesis: Kornfeld et al., _J._Am._Chem._Soc._ 76, 5256 (1954); 78, 3087 (1956); M. Julia et al., _Tetrahedron_ _letters_ 1969, 1569; V.W. Armstrong et al., ibid. 1976, 4311; W. Oppolzer et al., _Helv._Chem._Acta_ 64, 478 (1981); R. Ramage et al., _Tetrahedron_ 37, Suppl. 9, 157 (1981); J. Rebek, D.F. Tai, _Tetrahedron_Letters_ 24, 859 (1983). Ste- reochemistry: Stoll et al., _Helv._Chem._Acta 37, 2039 (1954); Stenlake, _J._Chem._Soc._ 1955, 1626; Leeman, Fabbri, _Helv._ _Chim._Acta_ 42, 2696 (1959). Absolute configuration: Stad- ler, Hofmann, ibid. 45, 2005 (1962). H. COOH '. / / \ / \ || | || N /\\ /\ / \ / \\ / \ / CH3 || | | \ || | | H \ // \ / \// \/ | || | || HN------- Haxagonal scales, plates with one or two moles H20 from water, mp 240deg (dec). [alpha](D)(20) + 40deg (c = 0.5 in pyridine). Behaves as an acid and base, pKa 3.44, pKb 7.68. Moder- ately sol in pyridine. Sparingly sol in water and in neutral organic solvents; sol in NaOH, NH4OH, Na2CO3, and HCL solns. Slighly sol in dil H2SO4. Methyl ester, thin leaflets from benzene, mp 168deg. Note: This is a controlled substance (depressant) listed in the U.S. code of Federal Regulations, title 21 Part 1308.13 (1987). 5507. Lysergide. 9,10-Didehydro-N,N-diethyl-6-meth- ylergoline-8beta-carboxamide; N,N-diethyl-D-lysergamide; D- lysergic acid diethylamide; LSD; LSD-25; Lysergsaure Di- ethylamid. C20H25N3O; mol wt 323.42. C 74.27%, H 7.79%, N 12.99%, O 4.95%. Microbal formation by _Claviceps_pas- pali_ over the hydroxyethylamide; Arcamone et al., _Proc._ Roy._Soc._(London) 155B, 26 (1961). Partial synthesis: Stoll, Hofmann, _Helv._Chim._Acta_ 26, 944 (1943); 38, 421 (1955). Industrial prepn: Pioch; Garbrecht, U.S. pats. 2,736,728; 2,774,763 (both 1956 to Lilly); Patelli, Bernardi, U.S. pat. 3,141,887 (1964 to Farmitalia). Isotope-labeled LSD: Stoll et al., _Helv._Chim._Acta_ 37, 820 (1954). Toxicity data: E. Rothlin, _Ann._N.Y._Acad._Sci._ 66, 668 (1957). Review: Hof- fer, _Clin._Pharmacol._Ther._ 6, 183 (1965). Book: _The_Use_of_ LSD_in_Psychotherapy_and_Alcoholism_, H.A. Abramson, Ed. (Bobbs-Merrill, Indianapolis, 1967) 697 pp. / C2H5 H. CON '. / \ C2H5 / \ / \ || | || N /\\ /\ / \ / \\ / \ / CH3 || | | \ || | | H \ // \ / \// \/ | || | || HN------- Pointed prisms from benzene, mp 80-85 degs. [alpha](D)(20) + 17deg (c = 0.5 in pyridine). uv max (ethanol): 311 nm (E(1 cm)(1%) 257). LD50 in mice, rats, rabbits (mg/kg): 46, 16.5, 0.3 i.v. (Rothlin). D-Tartrate, C46H64N6O10, solvated, elongated prisoms from methanol, mp 198-200deg. [alpha](D)(20) + 30 deg. Soluble in water. Caution: This is a controlled substance (hallucinogen) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.11 (1987). USE: In biochemical research as an antagonist to serotonin. Has been used experimentally as adjunct in study and treat- ment of mental disorders. NOTES: Not guaranteed to be free from typos. Underlines are supposed to be italic (ie book/journal titles, etc) Alpha, beta, and deg are the greek letters and the degree symbol [alpha](D)(20) means a greek letter in  followed by a subscript and then a superscript (I don't know *WHAT* this actually is) The chemical structures are almost exactly what the Merck manual has drawn. Almost nothing was lost in the conversion to ASCII. [if you wanted to get really technical, the lower hydrogen atom in all of the structures should be coming out, and have a thick line] ============================================================================= In article <1992Dec8.firstname.lastname@example.org> email@example.com (Christian Wernstedt) writes: > > Has anyone any comments on this? Is it common that people experiencing >a bad trip resort to violence against him/herselves or people around? Any >anecdotes, statistical info or just scientific references would be of >benefit to get a clearer picture. > A followup to my earlier reply. Two refrences from the bibliograpy of Intoxication, Ronald SIEGEL BARTER, J. T and REITE, M. 1969. "Crime and LSD: The Insanity Plea." American Journal of Psychiatry 126:113-19. REICH, R and HEPPS, R. B. 1972. "Homicide During a Psychosis Induced by LSD." Journal of American Medical Association 219:869-71 From Siegel's Intoxication (p 240): The cases of Jeffery and Harold, who killed people after having taken LSD, are presented. "Cases like Harold's tend to confuse the issue of intoxication and violence. Violent people are often intoxicated but the violence is usually rooted in the personality, not the drug." mark ============================================================================= From: Lamont Granquist Newsgroups: alt.drugs,alt.psychoactives Subject: Interesting LSD/Neuropharm/Psychopathology Articles (improving alt.drugs SNR) Date: 10 May 1994 05:50:12 GMT Message-ID: <firstname.lastname@example.org> In a valiant attempt to improve the SNR on alt.drugs... And i'd like to note that all my rants for the past 2 years on the pre-synaptic mechanism of action of LSD on the dorsal and median raphe 5-HT neurons were, apparently, all fucked. =) Apparently this theory was shot down in 1981 by Trulson et al. (Brain Res 215:275-293). The current dogma is that "classic hallucinogens" are 5-HT2 post-synaptic agonists.... Pierce + Peroutka have a mini-review of the mechanism of action of classic hallucinogens in their introduction. I also found "Study of the extraction of LSD from illicit blotters for HPLC determination." J-Forensic-Sci. Sep 1993. 38(5):1105-1110. But it was off at the bindery so i couldn't read the article... Psychopathology Abraham-HD, Aldridge-AM. "Adverse consequences of lysergic acid diethylamide." Addiction. Vol 88:1327-1334. 1993. Overview of acute effects, prolonged psychoses and post-hallucinogen perceptual disorder (PHPD). Biased somewhat towards trying to find problems with LSD and doesn't address the methodological considerations in the studies they cite. Interesting because it clearly states that LSD is not an in vivo clastogen, either weakly or not mutagenic, not teratogenic and not oncogenic (clastogen = breaks chromosomes, mutagen = causes DNA mutations, teratogenic = birth defects, oncogenic = causes cancer) -- and this got by the editors at Addictions. Neuropharmacology Shen-Y, Monsma-FJ, Metcalf-MA, Jose-PA, Hamblin-MW, Sibley-DR, "Molecular Cloning and Expression of a 5-Hydroxytryptamine7 serotonin Receptor Subtype." Journal of Biological Chemistry. Vol 268(24):18200-18204. 25 Aug 1993. Discovery of a 5-HT7 receptor which has a high affinity for LSD (KD = 4.9 +/- 0.78 (n = 5) nM; Bmax = 5-15 pmol/mg protein). Also displays a high affinity for tricyclic antipsychotic and antidepressant agents. It is located primarily in the limbic and cortical regions of the brain. Pierce-PA, Peroutka-SJ. "Antagonist Properties of d-LSD at 5-Hydroxytryptamine2 Receptors." Neuropsychopharmacology. Vol 3(5-6):503-508. 1990. Argues that LSD is a 5-HT2 receptor antagonist and that this tends to rule out the notion that classic hallucinogens work via a 5-HT2 agonist mechanism. Suggests that LSD might be a 5-HT1A or, more likely, 5-HT1C agonist -- although the role of the 5-HT2A receptor subtype is not at present well known. Glennon-RA. "Do Classical Hallucinogens Act As 5-HT2 Agonists or Antagonists?" Neuropsychopharmacology. Vol 3(5-6):509-517. 1990. This is a rebuttal to Pierce and Peroutka's article in the same issue. It argues that LSD is a high-affinity, low-efficacy, nonselective 5-HT agonist, aka a dirty, partial agonist. Thus compared with high-efficacy agonists LSD would exhibit relative antagonist effects. Also, 5-HT1 sites have been shown to behave functionally as 5-HT2 antagonists, particularly 5-HT1A receptors. LSD's non-selective ("dirty") affinity for 5-HT receptors, and in particular 5-HT1A receptors, could explain other evidence which was offered in support of the 5-HT2 antagonist theory, and would explain certain biphasic dose/response curves that LSD has. The author does, however, conclude by noting that the 5-HT1C site may also (or alternatively) play a role in hallucinogenic activity, and that it should be explored. -- Lamont Granquist "And then the alien anthropologists - Admitted they were still perplexed - But on eliminating every other reason - For our sad demise - They logged the only explanation left - This species has amused itself to death" -- Roger Waters ============================================================================= From: email@example.com (Malcolm Gillies) Newsgroups: alt.drugs,alt.psychoactives Subject: Re: Interesting LSD/Neuropharm/Psychopathology Articles (improving alt.drugs SNR) Date: 11 May 1994 00:04:28 GMT Message-ID: <firstname.lastname@example.org> In article <email@example.com> Lamont Granquist writes: > Shen-Y, Monsma-FJ, Metcalf-MA, Jose-PA, Hamblin-MW, Sibley-DR, > "Molecular Cloning and Expression of a 5-Hydroxytryptamine7 > serotonin Receptor Subtype." Journal of Biological Chemistry. > Vol 268(24):18200-18204. 25 Aug 1993. > [...] > Pierce-PA, Peroutka-SJ. "Antagonist Properties of d-LSD at > 5-Hydroxytryptamine2 Receptors." Neuropsychopharmacology. Vol > 3(5-6):503-508. 1990. > [...] > Glennon-RA. "Do Classical Hallucinogens Act As 5-HT2 Agonists or > Antagonists?" Neuropsychopharmacology. Vol 3(5-6):509-517. > 1990. > [...] Lamont, you have to note that 5-HT receptor nomenclature is in a bit of a state of flux at the moment. 1993's 5-HT2 receptor is not necessarily the same as 1990's 5-HT2 receptor. There is also some discrepancy between the nomenclature used by those with a more molbio perspective, and those approaching from a more classical pharmacological perspective (i.e. 5-HT7 is not accepted nomenclature by most pharmacologists). Defining the exact pharmacological actions of LSD will probably not be possible until 5-HT receptor has properly settled down. Note that there may be issues of significant inter-species variation here as well (rat != human). Malcolm -- Funk not only moves, it can re-move, dig? -- P-FUNK ============================================================================= From: "Charles D. Nichols"
Newsgroups: alt.psychoactives,alt.drugs Subject: Re: Interesting LSD/Neuropharm/Psychopathology Articles (improving alt.drugs SNR) Date: Fri, 13 May 1994 09:50:24 -0400 Message-ID: Excerpts from netnews.alt.psychoactives: 11-May-94 Re: Interesting LSD/Neuroph.. by Malcolm Gillies@cs.su.oz > Defining the exact pharmacological actions of LSD will probably not be > possible until 5-HT receptor has properly settled down. Note that there > may be issues of significant inter-species variation here as well > (rat != human). > > Malcolm You've got a point there. There are 5HT receptors in worms, insects such as Drosophila, all the way through to humans. The 'homologous' version of a particular receptor may only have 60% identity from species to species. So if you figgure what's specifically going on in one system it may be different in another, although the global model of what's going on probably (usually) holds. Given that genetics (creating transgenics with mutant receptors and such) are difficult to nearly impossible in 'higher' animals such as rats and humans it may be necessary to study these receptors in a more genetically tractable animal such as Drosophila before we really can know how drugs like this are interacting with the receptors. Chuck ************************************************************************** Chuck Nichols Carnegie-Mellon University Department of Biological Sciences firstname.lastname@example.org ************ On a Trip Without a Destination (graduate school) ***********