A powerpoint from my group's LSD Presentation for Psych 420

1. Lysergic ACID Diethylamide By: Holly George, Sam Irish, & Joel Vidmore

2. LSD “Educational” Video www.youtube.com/watch?v=FqGegSpMVOA

3. Myth-Conceptions of ACID Acid changes your chromosomes. Myth – It originates from a study dating back to 1967 which showed that LSD caused "chromosomal breaks“/damage to DNA. It was later proven to be false. Acid stays in your spinal cord and cracking your back can make you trip out again. Myth –Flash backs do happen but rarely, most of the time they are based on visual or auditory cues or intense emotional situations, but not due to LSD being left in the body.

4. Psych322 Review of LSD Half Life: 110min or 3-5hr Duration: 8-12hr Structurally similar to serotonin (5HT) Produced by a lower fungus (Clavicepspurpurea) that grows parasitically on rye (and other species of grain and wild grasses)

7. Dosing Human ED50: .0003-.001mg/kg Consumed most often via GI Tract Sugar Cube, Blotter, liquid, crystal Therapeutic Index (LD50/ED50) so high for humans that it hasn’t been determined! Approximation: .2mg/kg (200ug/kg) I weight 155lbs = 70.3kg = LD ~140 doses! One tsp. = 50,000 doses

8. Absorption & Biotransformation GI absorbs LSD easily and completely, thus unnecessary to inject (or occular) 80% biotransformed via liver 1-10% passes through unaltered Remainder is various biotransformed products

9. Distribution Unexpectedly, LSD has the lowestdistribution to brain Concentrated in certain centers of midbrain that regulate emotion Only 1% of theabsorbed dose makes it to the brain 1/10 grain of sand per effective dose, 1/100th gets through blood-brain barrier, meaning: 1/1000th the mass of a grain of sand of LSD in the brain is all that is necessary to elicit the INTENSE psychological effects! Concentration in body compartments at maximum 10-15min after ingestion, falls swiftly Exception: small intestine reach max concentration in 2hr

10. LSD in Animals Mouse: motor disturbances, alteration in licking behavior. Cat: Piloerection and salivation. Indication of hallucination; staring anxiously in the air. Doesn’t attack mouse, may even fear it. Fish: Unusual swimming postures Chimpanzees: caged community reacts very sensitively if a member receives LSD. “The whole cage gets in an uproar because the LSD chimpanzee no longer observes the laws of its finely coordinated hierarchical tribal order.” Spiders: Alterations in web building. Low optimum dose: webs better proportioned and exactly built than normal, higher doses webs were badly and rudimentarily made.

11. LD50 in Animals Mouse: 50-60mg/kg Rats: 16.5mg/kg Rabbit: .3mg/kg Elephant: .06mg/kg (Tusko @ .297g/500kg) Most animals die from respiratory arrest

12. Cross Tolerant with… Psilocybin/Psilocin Mescaline Congeners “MLD-42 produces in man and the Siamese fighting fish reactions that are essentially indistinguishable from those produced by LSD-25, but there are higher reaction thresholds.” (1/3 as effective in man, 1/10 in fish) BOL-148 : Some tolerance, no psychological component

13. Chemical Modifications of LSD Spatially Distinct Forms LSD = d-lysergic acid diethylamide Iso-LSD = d-isolysergic acid diethylamide L-LSD = l-lysergic acid diethylamide L-iso-LSD = l-isolysergic acid diethylamide Potency: last three show no psychic effect up to doses of .5mg (20-fold times active dose LSD)

14. Chemical Modifications, Cont. Congeners 2 ALD-52 (1-Acetyl-N,N-diethyllysergamide) Purportedly Stronger (“Orange Sunshine”) MLD-41 (1-Methyl lysergic acid diethylamide) Effects indistinguishable from LSD (1/3 potency)) BOL-148 (bromo-LSD) No Psychedelic Effects Highest activity as 5HT blocker 5HT blocking plays a role in allergic-inflammatory processes and generation of a migrain LAE-23 (monoethylamide of lysergic acid) Hydrogen atom replaces ethyl group 10 times less psychoactive as LSD Hallucinations qualitatively different: narcotic component LA-111 (lysergic acid amide) Narcotic effect > LAE-23 Naturally occurring active principle of Mexican ololiuqui

15. Effect on the Brain 5HT2 Receptor Partial Antagonist 5HT1A & 5HT1C Receptor Agonist Downregulation of 5HT2 Receptors Implications? Enhance glutamate release directly from the terminals thalamocortical inputs to layer V pyramidal cells by 5-HT2A receptor stimulation Enhance the sensory responsivity of Locus Coeruleus neurons  contributes to (via extensive cortical projection) the characteristic intensification of perceptual experience produced by these drugs

16. Non-Behavioral Effects Sweating & Chills Nausea Headache Uterine Constriction Dry Mouth Tachycardia Dilated Pupils Hyperthermia This is sympathetic nervous system response

17. Subjective Effects Hallucinations as distortions of reality As opposed to intensification of reality Closed & Open eye visuals Kaleidoscopic & Geometric patterns Cross Modal experience (Synaesthesia) Evokes strong emotional reaction Time Distortion Ego-death/transcendence Repetitive/looping thought patterns Rapid Mood Shifts Extremely stimulated imagination “Despite the mass of published reports, definitive evidence is generally lacking, particularly with regard to the subjective and behavioral effects both during and subsequent to the LSD induced State.” - Robert E. Mogar, Current Status and Future Trends in Psychedelic (LSD) Research. J. human Psychol., Vol. 2, 1965, pp. 147-166

18. Subjective Effects @ 2:00 www.youtube.com/watch?v=yHkTnHR12I0&feature=related

19. Hofmann’s “Peculiar Presentiment” Hofmann was researching a medicament to facilitate uterine contractions & aid in obstetrics. Intended circulatory and respiratory stimulant (analeptic) Years later wanted to look into LSD-25 again, maybe missed something. “The feeling that this substance (LSD-25) could possess properties other than those established in the first investigations"

20. First LSD Experience While re-synthesizing Hofmann is assumed to have absorbed LSD in an undetermined way "Last Friday, April 16, 1943, I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home, being affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away."

21. Second LSD Experience Hofmann intentionally ingested 250ug Wartime: Bicycled home External world became stranger & stranger When home, “room had changed” Objects had different form, color, and significance Inanimate objects become ‘alive’ Heaven  Hellish  Heaven Colloquially known as “Bicycle Day”

22. What is the LSD experience? Activity evoked by LSD similar to Mescaline (peyotlby the Aztecs) but novel in its high activity (5,000 – 10,000 times more active) & high specificity (aimed at human psyche) "The psychic effects of LSD, which are produced by such minimal quantities of material, are too meaningful and too multiform to be explained by toxic alterations of brain functioning. If LSD acted only through a toxic effect on the brain, then LSD experiences would be entirely psychopathological in meaning, without any psychological or psychiatric interest. ” - Albert Hofmann, LSD: My Problem Child

23. Doors of Perception "If the doors of perception were cleansed every thing would appear to man as it is, infinite. For man has closed himself up, till he sees all things through narrow chinks of his cavern.” - William Blake, The Marriage of Heaven and Hell Aldous Huxley’s “Doors of Perception” 1953 Account of his first Mescaline experience (4/10g) Evoked a response akin to religious, mystical, and psychotic experience Claims: Urge to transcend self is universal‘Healthier doors’ than alcohol & cigarettes are neededIdeally, self-transcendence should be found in religion, but this doesn’t seem feasible. Mescaline is not necessary but helpful, especially so for the intellectual who is immersed in words & symbols The person who has this mystical experience will be transformed for the better. Huxley later had an LSD experience that was deemed more profound than his mescaline trip from Doors of Perception!

24. Government Intervention Oct. 6, 1966: LSD made illegal in California Oct. 24, 1968: Staggers-Dodd Bill, LSD possession is banned federally Oct. 27, 1970: The Comprehensive Drug Abuse Prevention and Control Act passed. Part II is Controlled Substance Act (CSA) placing most known hallucinogens in Schedule I, including LSD.

25. Treatment of Obsessional Neurosis N= 36 neurotics Ranged from 2 to 58 treatments 20 received previous psychotherapy 14 recovered 3 showed moderate improvement 2 did not improve 1 too early to asses Almost as effective in patients who have been ill for up to 10 years Sandison, R. A. & Spencer, A. M. (1953). The therapeutic value of lysergic acid diethylamide in mental illness.

26. Treatment of Cluster Headaches N= 53 diagnosed with cluster headaches 58% had never used LSD or psilocybin 5 of 6 LSD users reported termination 22% reported partial or complete efficacy from sub-hallucinogenic doses of LSD or psilocybin One dose of LSD vs. ~3 of psilocybin Sewell, R. A. & Pope, H. G. Jr. (2006). Response of cluster headache to psilocybin and LSD. Neurology 2006. 66, 1920-1922.

27. Treatment of Autism 10 boys, 2 girls (5 yrs. 11 mo.- 11 yrs. 10 mo.) Sessions of 50, 100, or 200 micrograms Positive results: Increased physical contact Disappearance of physical mannerisms Development of new bodily sensations Improved play behaviors Increased social responsiveness Decrease in stereotyped movements Sigafoos, J., Green, V., Edrisinha, C., & Lancioni, G. (2007). Flashback to the 1960s: LSD in the treatment of autism. Developmental Neurorehabilitation, 10(1), 75-81.

28. Treatment of Autism (cont.) Negative results: Rapid mood swings Increased anxiety Auditory and visual hallucinations No improvement of speech Sigafoos, J., Green, V., Edrisinha, C., & Lancioni, G. (2007). Flashback to the 1960s: LSD in the treatment of autism. Developmental Neurorehabilitation, 10(1), 75-81.

29. Treatment of Alcoholism @4:03 http://www.youtube.com/watch?v=-bafNxQDUmo

30. Treatment of Color Blindness Case studies from erowid.org: “Since I have tripped, I have visited the optometrist once and got 8 out of 15 numbers right in the colorblindness test when before I would only get 3 at the most.” “I am at the extreme end of the colorblindness scale… Yet under the influence of LSD, my color perceptions began to heighten… steadily I began to notice, for the first time a difference in appearance between the leaves of a tree and its bark.”

31. What Some Attribute to LSD The Mysterious Death of CIA Scientist Frank Olson

32. What Some Attribute to LSD Tusko the Elephant - 1962

33. What Some Attribute to LSD Tusko the Elephant - 1962 Questions Was LSD was the cause of the fatality? Did Jolly West acted irresponsibly and unscientifically? Was the Thorazine (chlorpromazine) more likely to be the direct cause of death? Were there any additional drugs administered which were not reported in the article? Did Jolly West have had ulterior motives in his work because of his interests in the potential mind-control and warfare uses of LSD? http://www.erowid.org/chemicals/lsd/lsd_history4.shtml

34. What Some Attribute to LSD Suicide During an LSD Reaction – 1967 MR. A + Disturbed + LSD + Window Keeler, M. H., Reifler, C. B. (1967). Suicide During an LSD Reaction. American Journal of Psychiatry, 123, 884-885.

35. What Some Attribute to LSD Death of 20 Year old Diane Linkletter – 1969 “… Diane Linkletter, the daughter of the television and radio personality Art Linkletter, jumped from a window to her death while on LSD…(an autopsy later found no evidence of the drug in her body)” Art Linkletter became a strong voice against drug use, continually attributing his daughters death to her LSD use. http://www.nytimes.com/2010/01/08/books/08book.html

36. What Some Attribute to LSD Teen Faces Charges in Death -October 16, 2004 “Cameron James Jester, 18…told investigators he gave the woman about 10 doses of the hallucinogen in a drink and then let her have some of his drink, which also had about the same number of droplet-sized doses.” “Gloria Discerni, 18, of Cottage Grove, Ore., died Friday after an apparent LSD overdose put her in a coma Tuesday night.” http://journalstar.com/news/local/article_e09b5805-fb49-5700-bbff-9e90b28d10ed.html

37. What Some Attribute to LSD Teen Faces Charges in Death -October 16, 2004 “Police are awaiting toxicology results to determine if the drug was actually LSD or if Discerni had taken any medications or had any other medical conditions which might have contributed to her death. (Updated 9.22.06: Toxicology reports later showed it was a designer drug.)” http://journalstar.com/news/local/article_e09b5805-fb49-5700-bbff-9e90b28d10ed.html

38. What Some Attribute to LSD According to DrugWarFacts.Com In 2000, it was reported the annual causes of death in the US as: Tobacco 435,000 Poor Diet and Physical Inactivity 365,000 Alcohol 85,000 Microbial Agents 75,000 Toxic Agents 55,000 Motor Vehicle Crashes 26,347 Adverse Reactions to Prescription Drugs 32,000 Suicide 30,622 Incidents Involving Firearms 29,000 Homicide 20,308 Sexual Behaviors 20,000 All Illicit Drug Use, Direct and Indirect 17,000 Non-Steroidal Anti-Inflammatory Drugs Such As Aspirin 7,600 Marijuana 0

39. What Some Attribute to LSD “In 1999, according to (DAWN) Medical Examiner data, LSD was mentioned in 5 deaths by medical examiners reporting to DAWN. Of these 5 deaths, three were male and two were female. All deceased were white and under the age of 25. Reasons for the deaths were accidental/unexpected, and other/unknown.“ http://www.sigep.org/documents/lsd-fact-sheet.pdf

40. What Some Attribute to LSD Discovery of Double Helix DNA Structure by Francis Crick “told a fellow scientist that he often used small doses of LSD then an experimental drug used in psychotherapy to boost his powers of thought. He said it was LSD, not the Eagle's warm beer, that helped him to unravel the structure of DNA, the discovery that won him the Nobel Prize.” http://www.miqel.com/entheogens/francis_crick_dna_lsd.html

41. What Some Attribute to LSD Invention of PCR by Dr. Kerry Mullis in 1983 Polymerase Chain Reaction - a method to start and stop DNA polymerase enzyme activity at specific points along a single strand of DNA. Invention of Shareware by Bob Wallace Shareware – a tool used to provide free software to users who in turn may purchase it. Videos: www.youtube.com/watch?v=wibQv5aebZs http://www.youtube.com/watch?v=Ku3jz_NGUfU

42. Inventions @ 9:25 www.youtube.com/watch?v=wibQv5aebZs

43. Inventions (cont) www.youtube.com/watch?v=Ku3jz_NGUfU&feature=related