emilyrk39+-+Log

Emily Krantz Research Paper Log

=Abstract=
 * structure, metabolism, reception, structural affinity to receptors, flashbacks, bad trips, and a couple case studies

=Introduction=
 * Ancient Greece where for 2000 years the Greek drink kykeon
 * Albert Hoffmann ‘as I lay in a dazed condition with eyes closed there surged up from me a succession of fantastic rapidly changing imagery of a striking reality and depth, alternating with a vivid kaleidoscopic display of colors.’
 * Robert Kennedy, a United States Senator promoted LSD use stating ‘it can be very helpful in our society if used correctly’

=Molecular Structure of LSD=
 * Single crystal analysis of LSD reveals that LSD is a monoclinic crystal. The hydrogen atoms were located by difference syntheses using isotropic thermal parameters. While the non-hydrogen atoms were located using anisotropic thermal parameters. A water molecule is present in crystallization which forms hydrogen bonds to oxygen atoms of the benzoate molecules. (Baker, 1972)
 * The C5 and C8 atoms are asymmetric which allows for four isometries which are d and l-LSD and d and l-isolysergic acid dietylamide. The d-LSD is primarily described in this paper due to the fact that this isomer is the only isomer with psychoactive properties. (Baker, 1972)
 * LSD’s hallucinogenic capabilities are suggested to be attributed to the structural conformation. (Baker, 1972)

=Metabolism of LSD= Half Life
 * For monkeys, the biological half-life of LSD was found to be about 100 minutes, while cats were 130 minutes and mice were only 7 minutes. (Axelrod, 1957)
 * Using human plasma results indicate that there was a steep decline then a leveling off of the plasma levels after 30 minutes, then a gradual decline until after 8 hours there was minimal amounts of LSD-25 present in the plasma. The half-life was calculated after plotting on a semi-log plot and was discovered to be 175 minutes. (Aghajanian, 1964)
 * Another study on Humans The results of this study, conducted in 1990 on one male where blood was collected 10,30,60 minutes, and 2,3,4,6,8.12 and 24 hours after consumption, indicated a longer half-life than the previous study of 5.1 hours. (Papac, 1990)

Metabolic Pathways
 * metabolic pathways for LSD transformation using rats. It was proposed that it could potentially involve N-demethylation which results in norLSD and formaldehyde. An indole ring was suggested to form from oxidation and lysergic acid was proposed to form from hydrolysis. (Axelrod, 1957)
 * Radioactive Metabolites Canezin Study
 * discovery of a new metabolite di-hydroxy-LSD in the human liver chromosomes
 * It was discovered that the liver tissue is where the metabolic change occurs because ti was the only tissue that metabolized the drug.
 * The half-life of radioactivity in the blood was found to be 20 minutes. The radioactive material was most abundant in the G.I. track, of which 60%-80% was found in the bile after 3 hrs
 * radioactive material, LSD and, all LSD metabolites were apparent in all male reproductive tissues. In late terms of pregnancy, LSD was apparent in the fetus after 5 minutes in concentrations of .5% which indicated placental transfer of the drug to the fetus.

=Interaction with Receptors=
 * 5HT2 receptor had 100 times higher attraction for the 5HT2 receptor than the 5HT1C.
 * LSD was suggested to act as a dopamine agonist
 * When rats were dosed with .32mg/kg doses of LSD It failed to block at least 20% of conditioned avoidance responding.

=Structural Conformation of LSD effect on 5HT Reception=


 * The nitrogen apparent in the indoles therefore plays an important part in the affinity to that receptor.
 * mathematical model made to represent hallucinogenic properties of tryptamines. Didn’t work on LSD. But worked on 9,10 di-hydro-LSD the difference is bond length. Which leads to question if bond length presents a reason for hallucinogenic properties.
 * amide binding region was determined to be an important factor that determines the ability for LSD to have hallucinogenic properties.

=The Bad Trip=
 * United Kingdom Survey to doctors in the 1960s who used LSD clinically
 * EROWID recollection of a bad trip

=Flashbacks=
 * Horowitz study. Patient’s describing flashbacks
 * study for flashbacks conducted on 31 people with varying LSD backgrounds

=Case Study=
 * treating alcoholics with LSD
 * Only 23 of the 69 patients maintained abstinence up to the six month follow up.

=Case Study=
 * autistic children to increase vocalization