LSD Outline I. Background A. LSD is a semi-synthetic compound derived from ergot (a rye grass fungus) B. It was first synthesized in 1938 by Albert Hoffman, a chemist at the Sandoz pharmaceutical laboratories in Basel, Switzerland. C. He created LSD-25 with the idea that it might be a circulatory and respiratory stimulant. D. After some testing, it was felt that this drug did not work as well as others, so testing was abandoned. II. Pharmacokinetics A. Routes of Administration 1. Oral - can be swallowed in pill form, taken as a liquid, or the liquid can be put on something (often paper tabs or sugar cubes). a. 1960's average dose was about 250 micrograms b. 1990's average dose is about 50 micrograms 2. Intravenous - can be injected, but this is very rarely done. 3. Intramuscularly - also rarely done B. Absorption, Distribution, Metabolism, and Excretion 1. Is easily absorbed through the gastrointestinal tract. 2. Has a high percentage of it bound to plasma, yet it is still rapidly distributed throughout the body with the main concentrations in the lungs, liver, kidneys, and brain. 3. Is lipid soluble and easily crosses the blood-brain barrier. 4. Once it is through the barrier, LSD slips into the transmission site inside nerve cells. 5. The drug affects the oldest parts of the brain first (upper end of the spinal cord, medulla oblongata, cerebrum, pineal gland, and the hypothalamus region). 6. Next it travels through the back of the brain up to the area of hearing, the cerebellum, other sense interpretive centers, and the motor areas. 7. It is metabolized in the liver and its metabolites are excreted in bile through the small intestines. 8. Only about one percent is excreted, unadulterated in the urine. a. Practically undetectable in drug tests b. Usually not tested for 9. Has a half-life of five hours III. Pharmacodynamics A. I saw in my notes that a lot of drugs we don't know how they work, LSD is one of them. B. LSD's behaves as a high affinity partial serotonin 5-HT agonist. C. It can mimic serotonin to the point where the body thinks it is serotonin and consequently shoots it across the synaptic gap. D. When LSD reaches the other side it is accepted but the it doesn't carry the message any further. E. The impulse of electricity is redirected down less familiar pathways which have not been highly conditioned. F. Depending on the presence of other molecules and its own concentration, LSD can have either agonistic or antagonistic effects on post-synaptic serotonin 5-HT(2) family receptors.(Larger amounts tend to cause antagonistic effects) G. The modulation of serotonin 5-HT behavior is probably responsible for many of the effects attributed to LSD. H. LSD also has an affinity for other nuerotransmitter receptors such as norepinephrine, dopamine, and histamine. I. It is hypothesized that LSD may modulate neural responses to these transmitters through its activity on serotonin 5-HT(1) receptors. J. Some of the cognitive effects of LSD could be attributed to the effects of brain stem innervation to areas of the brain such as the cerebral cortex and the hippocampus. K. LSD is extremely potent. 1. Effective dose - 50 micrograms 2. Lethal dose - 14,000 micrograms 3. Almost impossible to overdose a. Few cases of death reported b. When death does occur it is usually because of multiple drugs L. Tolerance to LSD develops very fast 1. Usually with three days of daily administration 2. Once tolerance is developed, administration of as much as four times the original dose had no effect. M. No evidence of addiction (long-term chronic abuse rarely develops) N. Physical Health Risks 1. Few, if any a. A report in 1967 claimed that LSD might cause genetic damage b. This report has since been debunked c. LSD has no lasting effect on genes or chromosomes 2. Use during pregnancy does not appear to harm the developing fetus (no teratogenic effect) IV. Taking LSD A. As stated before LSD is usually taken orally. B. The effects of the drug are noticeable about 30 minutes to an hour after taking it.(Some effects include: dilated pupils, increased heart rate, and tingling in the fingers and toes) C. The trip peaks two to five hours later (effects: euphoria [accompanied by smiling and laughing], visual disturbances [trails], sensory perceptual changes [pulsing walls], and cross-sensory perception [seeing sound]) D. After eight to twelve hours the trip is usually over E. A trip can be good or bad (explain bad trip - anxious, paranoid), but even a good trip can have its bad moments because feelings become intensified, the users' emotions change rapidly. F. The users' mood is likely to change depending on how they feel at various stages of the trip 1. The outcome of a trip is almost always dependent on two things a. Set - refers to the users' expectations of the drug's effects and the users' state of mind b. Setting - is the environment in which the drug is taken 2. In the case of a bad trip, the user can be brought down with Thorazine (chlorpromazine); niacin and Vitamin C have also proven to be helpful 3. Some users' may experience what is known as LSD psychosis. a. A schizophrenic-like disorder b. Those who have strong family histories of major psychosis or psychopathology are more vulnerable c. Borderline psychotic and depressed individuals are also highly vulnerable. G. A study of 5,000 LSD users', who had used the drug 25,000 times, found that 1.8 psychotic episodes per 1,000 ingestions, 1.2 attempted suicides, and .4 completed suicides (about the same ratio as non-users) H. Flashbacks - when someone relives (visual disturbances) an LSD trip (can last for a few seconds or as long as a few hours) 1. Flashbacks have been explained in many ways, but it seems that the majority of researchers feel that many people have flashbacks whether they used LSD or not. 2. Flashbacks are associated with highly emotional experiences (such as an LSD trip) 3. A person who has been raped or in a war, may have flashbacks to that experience (like those who suffer from post-traumatic stress disorder) 4. LSD flashbacks tend to happen when a person is under emotional stress or can be induced by conditions like fatigue, drunkenness, or marijuana intoxication. 5. Studies have estimated that about 28 percent of LSD users experience flashbacks V. History A. April 16, 1943 - Hoffman accidentally ingests LSD-25 He felt restless and slightly dizzy, his imagination was active, and he "perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors." B. April 19, 1943 - Hoffman deliberately ingests 250 micrograms of LSD-25 This is how he described his experience in his notes: The following were the most outstanding symptoms: vertigo; visual disturbances; the faces of those around him appeared as grotesque, colored masks; marked motoric unrest, alternating with paralysis; an intermittent heavy feeling in the head, limbs, and entire body; dry, constricted sensation in the throat; feeling of choking; clear recognition of his condition, in which state I observed... that I shouted half insanely or babbled incoherent words. Occasionally he felt as if he were out of his body. He also writes about how acoustic perceptions were transformed into optical effects. When he woke up the next day he felt "perfectly well". C. 1947 - Sandoz begins marketing LSD-25 to European research institutions D. 1949 - LSD introduced to the U.S. E. 1950's-ealry 1960's - Research done on the effects of LSD Experimentation was legally conducted by psychiatrists and others in the health and mental professions. In the data sheet which accompanied the LSD sent to psychiatrists, it stated that by taking the drug himself, "the psychiatrist is able to gain insight in the world of ideas and sensations of mental patients. LSD did show some success in the treatment of alcoholics and psychiatric patients. F. Early 1950's-1963 - MKULTRA: CIA mind control Starting in the early 1950's the CIA began studying LSD. They were intrigued by the drug, and hoped that they could use it to disorient and manipulate certain foreign leaders. They also believed that they could use LSD as a kind of truth serum. The experiments that the CIA conducted were often done on unwitting subjects, most often prisoners or patrons of brothels set up and run by the agency. Two way mirrors were installed so researchers could observe the drug's effects. Some people volunteered for these studies and in one case seven volunteers were given LSD for 77 straight days. (No tolerance?) Much of the information on MKULTRA was destroyed by the CIA in 1972, so there may be other cases of inhumane treatment of subjects. In the late 1970's James Thornwell sued the government for $10 million because they gave him the drug and tortured him to obtain information. In 1980 he was awarded $650,000. The movie Conspiracy Theory, particularly Mel Gibson's character, is loosely based on the MKULTRA experiments. G. 1960 - Harvard's Timothy Leary establishes the Psychedelic Research Project Along with Richard Alpert they study the effects of LSD, mainly on prison inmates. H. 1963 - LSD begins to appear on the streets; Leary is fired from Harvard for his personal use of LSD (coins the phrase Turn on, Tune in, and Drop out) I. 1965-66 - Acid Tests (California) During these two years Acid Tests were sponsored by Ken Kesey and the Merry Pranksters. At these tests, which were kind of like a dance/concert, people were given cups of Kool-Aid spiked with LSD. There was music, usually performed by the Grateful Dead, light shows, and all kinds of strange devices to play with. Tom Wolfe's book The Electric Kool-Aid Acid Test was based on these events. J. 1966 - Sandoz stops production and distribution; Government bans LSD K. June 20, 1970 -Dock Ellis of the Pittsburgh Pirates pitches a no-hitter while on LSD Not thinking he was pitching that day, Dock Ellis took some LSD while at home. After seeing the newspaper, he saw that he was scheduled to pitch and went to the game. His first pitch bounced two feet in front of the plate and he almost fell down after throwing it. But once he got going, his control was excellent. And he pitched the rest of the game without giving up a hit. L. 1975 - Last National Institute of Mental Health projects using LSD in human subjects ends M. 1986 - Federal mandatory minimums go into effect for LSD If the accused seller is convicted in a Federal court, the penalties are usually harsh. Minimum Mandatory sentences are based not on the amount of LSD but on the weight of the LSD and its carrier. For example, selling 100 doses of liquid LSD would result in a sentence of 10 to 18 months, with parole likely. Selling the same number of doses of LSD on blotter paper would result in a sentence of 5-1/2 to 16 years with no parole possible, if the LSD were on sugar cubes the sentence could be as long as 40 years. The same standards apply for possession. In NJ, the penalty, depending on weight, can range from a few months to 5 years for selling or possession. N. 1987 - LSD use begins to rise (Raves, Grateful Dead new popularity) O. 1989 - Less than 100 people in prison for LSD P. 1993 - After a tripling of the D.E.A.'s LSD task force the number of people imprisoned on LSD charges is almost 2,000. The DEA focused, for the most part, on travelling fans of the Grateful Dead. Q. 1997 - 13.6 percent of high school seniors had experimented with LSD at least once in their lifetimes compared to the twenty year low in 1986, when the figure was only 7.2 percent.