HaCKeRz KrOnIcKLeZ 3/HaCKeRz_KrOnIcKLeZ.iso/drugs/lsd.refs

Text File | 1996-05-06 | 20KB | 476 lines

 [...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, Hoffman, 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 <[e-mail]> [e-mail] (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: [e-mail] (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: <2qn7ak$[e-mail]>

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 ([e-mail])
"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: [e-mail] (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: <2qp7ec$[e-mail]>

In article <2qn7ak$[e-mail]> [e-mail] (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" <[e-mail]>
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: <[e-mail]>

Excerpts from netnews.alt.psychoactives: 11-May-94 Re: Interesting
LSD/Neuroph.. by Malcolm [e-mail]
> 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
[e-mail]

************ On a Trip Without a Destination (graduate school) ***********