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Production of Tolerance to Psychosis-Producing Doses of Lysergic Acid Diethylamide - H. A. Abramson, B. Sklarofsky, M. O. Baron, N. Fremont-Smith
5HT2, 5HT1A, 5HT1C are all located in the cerebral cortex
Effects of LSD ill-defined because: 1. Media hysteria drove research dry 2. Complex drug affecting complex organism (neocortex), effects variable even in lesser animals!LSD’s main effects lie within cerebral cortex stimulation; it is a human drug.
1963 LSD first hits the streets. 1965 Owsley Stanley succeeds in synthesizing crystalline LSDSummer 1969: Orange Sunshine appears1970 Windowpane & blotter forms appears
Neurotics mental life is characterized by a more or less complete separation form causative memories and from the inner psyche. Which results in mental tension, states of fear and anxiety characterized by preoccupation with symptoms, lack of purpose and direction in life.All patients were either severe obsessional neurotics with a bad prognosis or were patients who had been ill for a considerable time and who had previously had prolonged treatment either by psychotherapy or other means without improvement.Patients were in danger of becoming permanent mental invalids, life-long neurotics or of ending their lives by suicide.Of 3 classical obsessionalnueortics, 2 recovered after an average of 40 treatmentsPatients who have been ill for up to ten years have required only a small number of treatments& unlike other treatments, LSD 25 is almost as effective in patients who have been ill for up to ten years as it is in more recent cases.Conclusion: LSD when used as an adjunct to skilled psychotherapy is of the greatest value in the obsessional and anxiety groups accompanied by mental tension.
http://www.maps.org/w3pb/new/2006/2006_Sewell_22779_1.pdfCluster headaches are often considered the most painful of all types of headaches. The disorder is categorized as either episodic, occurring for 1-week to 1-year periods interspersed with pain-free remission periods or chronic, in which the headaches occur constantly for more than a year with no remission longer than one month.Researchers searched message boards and support groups for patients who had used lsd or psilocybin treatments.Narrowed down to 53, 58% had never used the drugs prior to treatment, only 25% had used them recreationally.RESULTS: 17 of 19 users found psilocybin to be effective in aborting an attack (within 20 minutes) Only one user used LSD to abort an acute attack, but with success.29 subjects used psilocybin during a cluster period with 52% experiencing total cessation of the attacks and 41% reporting partial efficacy.5 of 6 LSD users reported cluster period termination. 4 of 5 patients were able to extend their remissions with LSDTwo of the LSD users were diagnosed with “chronic cluster headaches”. One reported no attacks for 10 days after a subhallucinogenic dose and the other reported no attacks for 2 months after a subhallucinogenic dose.Overall, 42% of the 53 subjects reported partial or complete efficacy from subhallucinogenic doses of psilocybin or LSDNo other medication has been reported to terminate a cluster period. The results are remarkable considering the low doses and number of treatments
Research began in 1959 when the interest in lsd in psychotherapy was on the riseTreated 12 children suffering from autistic-schizophreniaVarying doses were given on one or two occasions3 children showed evidence of catatonia, none of the children ate their lunchesNew bodily sensations: all but 4 of the children were observed to repeatedly stroke or move a particular area- most often the mouth or lips
Some of the negative effects of the lsd treatment were rapid mood swings, from extreme elation to extreme depressionOne hope of this study was to induce speech in previously mute children, but the hoped for change from muteness to speech did not occur.LSD studies on autism continued into the 1970s with mixed results. Many studies concluded the effects of LSD treatment were very promising and could even be considered excellent for the majority of children.Others found the promise of LSD to be short-lived with many children becoming unresponsive and immobile on the drug, which threw some doubt on its use as a therapeutic adjunct.
“… in 1953 Frank Oldson jumped to his death from a New York City hotel window after he was unwittingly dosed with LSD "while attending a meeting with CIA personnel working on a test project that involved the administration of mind-bending drugs to unsuspecting Americans."““The three-day meeting had taken place in a remote area of Maryland called Deep Creek Lake and involved the LSD dosing of not just one man but several. According to The New York Times at least three participants in the meeting were given after-dinner drinks laced with a relatively small amount of LSD, about 70 micrograms. “…Starrs's exam revealed "startling results." There were no traces of LSD in Olson's corpse; there was "a highly suspicious blunt force wound" on Olson's frontal skull, most likely caused by a hammer or similar object; Olson's skull revealed "many fractures," so many that "It would not be possible unless he were on a trampoline. "“http://www.crimemagazine.com/olson.htm
“The 7000-pound bull elephant named Tusko was injected with a huge dose of LSD (297 mg) into one buttock with a dart rifle. Five minutes later, the elephant collapsed and went into convulsions.”“Twenty minutes after the initial injection of LSD… …2800 mg of chlorpromazine hydrochloride was injected into his ear over a period of 11 minutes, and only partially relieved the seizures and respiratory distress.” Sixty minutes after, “Dr. West injected Tusko with an unspecified quantity of pentobarbital sodium directly into a vein. The elephant died 1 hour and 40 minutes after the LSD had been given.”Chlorpromazine Hydrochloride – Causes dopamine receptor blockage in the central nervous system.Its used for management of manic phase of manic-depressive disorder; treatment of schizophrenia; relief of anxiety and restlessness prior to surgery; adjunct in treatment of tetanus; management of acute intermittent porphyria and severe behavioral and conduct disorders in children 1 to 12 years of age; control of nausea and vomiting; relief of intractable hiccoughs.Pentobarbital Sodium – A barbiturate used as a short-acting sedative and hypnotic.http://www.erowid.org/chemicals/lsd/lsd_history4.shtml
“Mr. A., a 20-year-old college undergraduate, completely disrobed and jumped from a window to his death while under the influence of self-administered LSD.”He complained of symptoms of anxiety and of difficulty in studying and was adjudged to be mildly or moderately disturbed…”He took LSD in the company of others, was observed to pace in and out of the room in which the others were, and, without explanation, while by himself, disrobed and took his life
Also on the drug war facts web site, there is an overdose “chapter” and it talks about Alcohol, Cannabis, Cocaine, Heroin, Methadone, Methamphetamine, and then talked about the “Bottom-Line” of drugs, however, nowhere on the page is LSD mentioned.
1 – Its hard to find accurate information.2 – It seems like deaths, involving LSD, haven’t been documented well.
Lysergic<br />ACID<br />Diethylamide<br />By: Holly George, Sam Irish, & Joel Vidmore<br />
Myth-Conceptions of ACID<br />Acid changes your chromosomes.<br />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.<br />Acid stays in your spinal cord and cracking your back can make you trip out again.<br />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.<br />
Psych322 Review of LSD<br />Half Life: 110min or 3-5hr<br />Duration: 8-12hr<br />Structurally similar to serotonin (5HT)<br />Produced by a lower fungus (Clavicepspurpurea) that grows parasitically on rye (and other species of grain and wild grasses)<br />
Dosing<br />Human ED50: .0003-.001mg/kg<br />Consumed most often via GI Tract<br />Sugar Cube, Blotter, liquid, crystal<br />Therapeutic Index (LD50/ED50) so high for humans that it hasn’t been determined!<br />Approximation: .2mg/kg (200ug/kg)<br />I weight 155lbs = 70.3kg = LD ~140 doses!<br />One tsp. = 50,000 doses<br />
Absorption & Biotransformation<br />GI absorbs LSD easily and completely, thus unnecessary to inject (or occular)<br />80% biotransformed via liver<br />1-10% passes through unaltered<br />Remainder is various biotransformed products<br />
Distribution<br />Unexpectedly, LSD has the lowestdistribution to brain<br />Concentrated in certain centers of midbrain that regulate emotion<br />Only 1% of theabsorbed dose makes it to the brain<br />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!<br />Concentration in body compartments at maximum 10-15min after ingestion, falls swiftly<br />Exception: small intestine reach max concentration in 2hr<br />
LSD in Animals<br />Mouse: motor disturbances, alteration in licking behavior. <br />Cat: Piloerection and salivation. Indication of hallucination; staring anxiously in the air. Doesn’t attack mouse, may even fear it.<br />Fish: Unusual swimming postures<br />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.”<br />Spiders: Alterations in web building. Low optimum dose: webs better proportioned and exactly built than normal, higher doses webs were badly and rudimentarily made.<br />
LD50 in Animals<br />Mouse: 50-60mg/kg<br />Rats: 16.5mg/kg<br />Rabbit: .3mg/kg<br />Elephant: .06mg/kg (Tusko @ .297g/500kg)<br />Most animals die from respiratory arrest<br />
Cross Tolerant with…<br />Psilocybin/Psilocin<br />Mescaline<br />Congeners<br />“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)<br />BOL-148 : Some tolerance, no psychological component<br />
Chemical Modifications of LSD<br />Spatially Distinct Forms<br />LSD = d-lysergic acid diethylamide<br />Iso-LSD = d-isolysergic acid diethylamide<br />L-LSD = l-lysergic acid diethylamide<br />L-iso-LSD = l-isolysergic acid diethylamide<br />Potency: last three show no psychic effect up to doses of .5mg (20-fold times active dose LSD)<br />
Chemical Modifications, Cont.<br />Congeners 2<br />ALD-52 (1-Acetyl-N,N-diethyllysergamide)<br />Purportedly Stronger (“Orange Sunshine”)<br />MLD-41 (1-Methyl lysergic acid diethylamide)<br />Effects indistinguishable from LSD (1/3 potency))<br />BOL-148 (bromo-LSD)<br />No Psychedelic Effects<br />Highest activity as 5HT blocker<br />5HT blocking plays a role in allergic-inflammatory processes and generation of a migrain<br />LAE-23 (monoethylamide of lysergic acid)<br />Hydrogen atom replaces ethyl group<br />10 times less psychoactive as LSD<br />Hallucinations qualitatively different: narcotic component<br />LA-111 (lysergic acid amide)<br />Narcotic effect > LAE-23<br />Naturally occurring active principle of Mexican ololiuqui<br />
Effect on the Brain<br />5HT2 Receptor Partial Antagonist<br />5HT1A & 5HT1C Receptor Agonist<br />Downregulation of 5HT2 Receptors<br />Implications?<br />Enhance glutamate release directly from the terminals thalamocortical inputs to layer V pyramidal cells by 5-HT2A receptor stimulation<br />Enhance the sensory responsivity of Locus Coeruleus neurons contributes to (via extensive cortical projection) the characteristic intensification of perceptual experience produced by these drugs<br />
Subjective Effects<br />Hallucinations as distortions of reality<br />As opposed to intensification of reality<br />Closed & Open eye visuals<br />Kaleidoscopic & Geometric patterns<br />Cross Modal experience (Synaesthesia) <br />Evokes strong emotional reaction<br />Time Distortion<br />Ego-death/transcendence<br />Repetitive/looping thought patterns<br />Rapid Mood Shifts<br />Extremely stimulated imagination<br />“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<br />
Hofmann’s “Peculiar Presentiment”<br />Hofmann was researching a medicament to facilitate uterine contractions & aid in obstetrics.<br />Intended circulatory and respiratory stimulant (analeptic)<br />Years later wanted to look into LSD-25 again, maybe missed something.<br />“The feeling that this substance (LSD-25) could possess properties other than those established in the first investigations"<br />
First LSD Experience<br />While re-synthesizing Hofmann is assumed to have absorbed LSD in an undetermined way<br /> "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."<br />
Second LSD Experience<br />Hofmann intentionally ingested 250ug<br />Wartime: Bicycled home<br />External world became stranger & stranger<br />When home, “room had changed”<br />Objects had different form, color, and significance<br />Inanimate objects become ‘alive’<br />Heaven Hellish Heaven<br />Colloquially known as “Bicycle Day”<br />
What is the LSD experience?<br />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)<br />"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<br />
Doors of Perception<br />"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<br />Aldous Huxley’s “Doors of Perception” 1953 <br />Account of his first Mescaline experience (4/10g)<br />Evoked a response akin to religious, mystical, and psychotic experience<br />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.<br />Mescaline is not necessary but helpful, especially so for the intellectual who is immersed in words & symbols<br />The person who has this mystical experience will be transformed for the better.<br />Huxley later had an LSD experience that was deemed more profound than his mescaline trip from Doors of Perception!<br />
Government Intervention<br />Oct. 6, 1966: LSD made illegal in California<br />Oct. 24, 1968: Staggers-Dodd Bill, LSD possession is banned federally<br />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.<br />
Treatment of Obsessional Neurosis<br />N= 36 neurotics<br />Ranged from 2 to 58 treatments <br />20 received previous psychotherapy<br />14 recovered<br />3 showed moderate improvement<br />2 did not improve<br />1 too early to asses<br />Almost as effective in patients who have been ill for up to 10 years <br />Sandison, R. A. & Spencer, A. M. (1953). The therapeutic value of lysergic acid diethylamide in mental illness.<br />
Treatment of Cluster Headaches<br />N= 53 diagnosed with cluster headaches<br />58% had never used LSD or psilocybin<br />5 of 6 LSD users reported termination<br />22% reported partial or complete efficacy from sub-hallucinogenic doses of LSD or psilocybin<br />One dose of LSD vs. ~3 of psilocybin<br />Sewell, R. A. & Pope, H. G. Jr. (2006). Response of cluster headache to psilocybin and LSD. Neurology 2006. 66, 1920-1922.<br />
Treatment of Autism<br />10 boys, 2 girls (5 yrs. 11 mo.- 11 yrs. 10 mo.)<br />Sessions of 50, 100, or 200 micrograms<br />Positive results:<br />Increased physical contact<br />Disappearance of physical mannerisms<br />Development of new bodily sensations<br />Improved play behaviors<br />Increased social responsiveness<br />Decrease in stereotyped movements<br />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.<br />
Treatment of Autism (cont.)<br />Negative results:<br />Rapid mood swings<br />Increased anxiety<br />Auditory and visual hallucinations<br />No improvement of speech<br />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.<br />
Treatment of Alcoholism @4:03<br />http://www.youtube.com/watch?v=-bafNxQDUmo<br />
Treatment of Color Blindness<br />Case studies from erowid.org:<br />“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.” <br />“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.”<br />
What Some Attribute to LSD<br />The Mysterious Death of CIA Scientist Frank Olson<br />
What Some Attribute to LSD<br />Tusko the Elephant - 1962<br />
What Some Attribute to LSD<br />Tusko the Elephant - 1962<br />Questions<br />Was LSD was the cause of the fatality?<br />Did Jolly West acted irresponsibly and unscientifically? <br />Was the Thorazine (chlorpromazine) more likely to be the direct cause of death?<br />Were there any additional drugs administered which were not reported in the article?<br /> Did Jolly West have had ulterior motives in his work because of his interests in the potential mind-control and warfare uses of LSD?<br />http://www.erowid.org/chemicals/lsd/lsd_history4.shtml<br />
What Some Attribute to LSD<br />Suicide During an LSD Reaction – 1967<br />MR. A + Disturbed + LSD + Window<br />Keeler, M. H., Reifler, C. B. (1967). Suicide During an LSD Reaction. American Journal of Psychiatry, 123, 884-885.<br />
What Some Attribute to LSD<br />Death of 20 Year old Diane Linkletter – 1969<br /> “… 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)”<br />Art Linkletter became a strong voice against drug use, continually attributing his daughters death to her LSD use.<br />http://www.nytimes.com/2010/01/08/books/08book.html<br />
What Some Attribute to LSD<br />Teen Faces Charges in Death -October 16, 2004<br />“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.”<br />“Gloria Discerni, 18, of Cottage Grove, Ore., died Friday after an apparent LSD overdose put her in a coma Tuesday night.”<br />http://journalstar.com/news/local/article_e09b5805-fb49-5700-bbff-9e90b28d10ed.html<br />
What Some Attribute to LSD<br />Teen Faces Charges in Death -October 16, 2004<br />“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.)”<br />http://journalstar.com/news/local/article_e09b5805-fb49-5700-bbff-9e90b28d10ed.html<br />
What Some Attribute to LSD<br />According to DrugWarFacts.Com<br />In 2000, it was reported the annual causes of death in the US as:<br />Tobacco 435,000<br />Poor Diet and Physical Inactivity 365,000<br />Alcohol 85,000<br />Microbial Agents 75,000<br />Toxic Agents 55,000<br />Motor Vehicle Crashes 26,347<br />Adverse Reactions to Prescription Drugs 32,000<br />Suicide 30,622<br />Incidents Involving Firearms 29,000<br />Homicide 20,308<br />Sexual Behaviors 20,000<br />All Illicit Drug Use, Direct and Indirect 17,000<br />Non-Steroidal Anti-Inflammatory Drugs Such As Aspirin 7,600<br />Marijuana 0<br />
What Some Attribute to LSD<br />“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.“<br />http://www.sigep.org/documents/lsd-fact-sheet.pdf<br />
What Some Attribute to LSD<br />Discovery of Double Helix DNA Structure by Francis Crick<br />“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.”<br />http://www.miqel.com/entheogens/francis_crick_dna_lsd.html<br />
What Some Attribute to LSD<br />Invention of PCR by Dr. Kerry Mullis in 1983<br />Polymerase Chain Reaction - a method to start and stop DNA polymerase enzyme activity at specific points along a single strand of DNA.<br />Invention of Shareware by Bob Wallace<br />Shareware – a tool used to provide free software to users who in turn may purchase it.<br />Videos:<br />www.youtube.com/watch?v=wibQv5aebZs<br />http://www.youtube.com/watch?v=Ku3jz_NGUfU<br />