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Hallucinogens by MacKenzie Donnelly, Lisa Martino, and Evan Hughes Hallucinogens • • • Substances whose primary effect is to cause perceptual and cognitive distortions without producing a state of toxic delirium o Most are synthesized by plants or have plant derived compounds Lysergic Acid Diethylamide (LSD), mescaline, psilcybin, dimethyltryptamine (DMT), and 5-methoxy-dimethyl-tryptamine (5-MeO-DMT) These drugs are called psychedelic by Mescaline • found the crown of the peyote cactus o • • • o mescal button or peyote button administered per os, chewed or cooked The powder can also be extracted found in Southwest United States and northern Mexico o used for religious reasons by Native Americans mainstreamed in 1953 not readily available because of high costs and lack of want Psilocybin • • • psilocybin is the main compound found in hallucinogec mushrooms o adminstered mainly per os psilocybin is converted to psilocin after ingested use of psilocybin goes back to 3500 B.C. DMT and 5-MeO-DMT • both are found in plants in South America ayahuasca drink with two different hallucinogenic plants in it o sold in powder form nad smoked o taken orally o LSD The Discovery of LSD • • First synthesized in 1938 by Albert Hofmann in Switzerland. Extracted from ergot o o • Alkaloid Produced by the fungus Claviceps purpurea Effects of ergot o o The toxicity causes ergotism; common in the Middle Ages and caused the deaths of 40,000 people in 944AD. Produces contractions of the uterus. Discovery of LSD cont. • Hofmann took lysergic acid from ergot alkaloids and combined it with other compounds. o • 25th synthesized substance was d-lysergic acid diethylamide LSD-25 LSD-25 o o Initially thought to be an analeptic. Upon reexamining the drug Hofmann underwent the world's first known LSD trip. Restlessness, dizziness, extremely stimulated imagination, dream-like state. Discovery of LSD cont. • • Hofmann later injested a small amount of synthesized LSD o Even more severe symptoms than the first time. Sandoz Pharmaceutical Company o Marketed LSD in 1947 as Delysid Helped neurotic patients uncover repressed thoughts/feelings. Administration • • PerOs Large amounts of the drug are dissolved in water o o Droplets of this water are applied to a blotter Blotters are divided into squares Uses of LSD • Psycholytic Therapy o o • Psychedelic Therapy o o • Patient underwent drug induced psycholysis. LSD first administered at low doses then dose is increased to promote the release of repressed memories and feelings. Patient given one high dose of LSD Promoted insight into patient's problems via a druginduced spiritual experience. Psychological Weapon o United States CIA ULTA Studied LSD as a mind control agent. Uses of LSD cont. • Recreational use o o • Hallucinations Altered Sensory Perception Synesthesia: combination/blending of senses • See smells, hear colors, etc. Adverse Effects o o o o o o Tremors Increased Heart Rate/Blood Pressure Neusea Sweating Dry Mouth Numbness Restrictions to LSD • 1965: Federal Law restricted research on LSD o • • Sandoz stopped distributing LSD for research purposes. 1967: LSD Banned Nationwide Now o Research has started back up MAPS (Multidisciplinary Association for Psychedelic Studies) promotes research on potential psychotherapeutic applications of hallucinogens. Psychopharmacology of Hallucinogens (insert table 14.1 on page 352) • • Depending on dose LSD and Mescaline effects begin within 30-90 minutes, and last between 6-12 hours, were as psilocybin dissipates sooner. DMT effects within seconds, and only lasts for an hour. Peaks between 5-20 minutes. LSD Responses • "Trips" (state of intoxication) has 4 main parts Onset: begins 30 minutes after taking drug. Colors intensify, patterns occur when eyes closed o Plateau: next 2 hours, time slows, more intense sensations o Peak:lasts for 2-3 hours. In another world with no time. Images appear; either good or bad trip. o Come-Down: 2-3 hours, user comes out of the hallucinogenic state, though it may take a day to feel normal. o Structure of Hallucinogenic Drugs • • • • These drugs either have a serotonin-like, (indoleamine) or catecholamine-like structure. Indoleamines o LSD, psilocybin, psilocin, DMT, 5-MeO-DMT Similar to Serotonin structures Catecholamines o Mescaline o Similar to NE, and amphetamine LSD receptor sites • • • • LSD antagonizes the action of Serotonin however they are 5-HT(subscripted 2) LSD binds to 8 different receptor subtypes, but only 5-HT(subscript 2A, and 2C) are the key receptor site for hallucinogens. No other NT is used to cause the hallucinations Complete tolerance can occur in 4 days, however there is an unknown complex system to gain this tolerance