From: [lamon t g] at [u.washington.edu] (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

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 ([lamon t g] at [u.washington.edu])
"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