Chapter 6 LSD and Other Hallucinogens

Definition of Hallucinogen Hallucinogens distortions of perception altered sense of reality, transported to new reality also called psychedelics (“mind-expanding”) drugs produce these effects at low or moderate doses other drugs may produce hallucinations at high doses

Classifying Hallucinogens Four basic groups by pharmacology serotoninergic (5-HT systems) noradrenergic (NE systems) cholinergic (ACh systems) miscellaneous synthetic hallucinogens e.g. phencyclidine (PCP) and ketamine little resemblance to any known neurotransmitter

Classifying Hallucinogens Groups based on effects psychedelics dissociative anesthetics deliriants produce side effects that are very unpleasant therefore generally not used recreationally

Figure 6.1 Claviceps tulasne (ergot) Amanita muscaria (ibotenic acid) Atropa belladonna (atropine) Datura stramonium (atropine, scopolamine)

LSD A. is one of the most toxic of abused drugs B. was used by the CIA in experiments in the 1950s C. users show little tolerance to the drug, even if used over long periods D. like cocaine and the opiates, is abused because it is a potent activator of DA reward systems E. led to a surge in admissions to psychiatric admissionsduring its height of popularity as evidenced by DAWN statistics

Lysergic Acid Diethylamide (LSD) Lysergic acid diethylamide (LSD-25) serotonergic drug synthetically derived from ergot toxic rye fungus responsible for thousands of deaths over the centuries. LSD itself has an extremely large safety margin unclear what the LD50 is

Lysergic Acid Diethylamide (LSD) 1938 LSD synthesized by Albert Hofmann 1947 Sandoz marketed LSD (Delysid) for treating psychiatric disorders 1950s CIA experiments for use in mind control and chemical warfare given to unsuspecting enlisted men

Lysergic Acid Diethylamide (LSD) 1960s LSD popularized by Timothy Leary 1990s resurgence in LSD abuse began to reverse in 1997 Taken orally, experience lasts about 12 hours

Lysergic Acid Diethylamide (LSD) LSD experience unpredictable but certain features are commonly observed: colorful hallucinations synesthesia in which sounds often appear as visions a distortion of perceptual reality emotional swings feeling of timelessness illusory separation of mind from body

Lysergic Acid Diethylamide (LSD-25) LSD affects a subtype of serotonergic receptors 5-HT-2A receptors does not result in addiction or dependence craving is absent tolerance is extremely rapid; one dose serves to prevent abuse

Facts and Fiction about LSD LSD does not produce psychological or physical dependence induce a panic or psychotic state (providing that there is a supportive setting for taking of LSD; “set” is very important)* elevate one’s level of creativity damage chromosomes promote violent behavior LSD abuse MAY cause birth defects if used during pregnancy result in flashback experiences hallucinogen-induced persisting perceptual disorder (HPPD) * Panic attacks are much more likely if the individual has an existing psychiatric condition than if not, or if the person is unsuspecting or is emotionally troubled at the time.

8th Grade10th Grade12th Grade Lifetime***1.9%2.6%4.0% Past Year Past Month Prevalence of LSD Use Source: 2008 Monitoring the Future Survey, NIDA.

Lysergic Acid Diethylamide (LSD) LSD is classified as a Schedule I drug. LSD should be classified as a Schedule I drug.

LSD closely resembles the molecular structure of __________. A. dopamine B. serotonin C. endorphins D. acetylcholine

Other Hallucinogens Related to Serotonin Other serotonergic hallucinogens psilocybin mushrooms (0.5% psilocybin, trace psilocin) oral delivery: tea or added to foods 20 min latency, 6 hr duration lysergic acid amide (LAA) dimethyltryptamine (DMT) DMT the “businessman’s hallucinogen” often used with harmine, a MAO inhibitor ayahuaska bufotenine “bufo” is a genus of toad; toad-licking

indoleserotoninLSD psilocybinharminebufotenine

Hallucinogens Related to Norepinephrine Mescaline from crown of peyote cactus (button) used in native American religious ceremonies chemically related to norepinephrine actions at 5-HT-2A receptors are responsible hallucinogenic effects

2,5-dimethoxy-4-methylampetamine (DOM) more euphoric, less hallucinogenic than LSD may produce “amphetamine psychosis” with prolonged use Hallucinogens Related to Norepinephrine DOM DOM and MDMA synthetic variations of the amphetamine molecule MDMA (Ecstasy) popular club drug neurotoxic to 5-HT neurons

synthetic, taken orally in tablet or capsule form (3,4 methylenedioxymethamphetamine (MDMA) structurally similar to 5-HT blocks 5-HT, NE reuptake may also enter terminals via 5-HT transporter MDMA Hallucinogens Related to Norepinephrine

MDMA (Ecstacy, XTC, etc) Sometimes used in combination with other drugs e.g. LSD, psilocybin, marijuana, ketamine

Hallucinogens Related to Norepinephrine MDMA (Ecstacy, XTC, etc) mental stimulation emotional warmth enhanced sensory perception increased physical energy. Has been used in psychotherapy for its empathy-enhancing effects PTSD, other anxiety disorder Popular club drug

Hallucinogens Related to Norepinephrine MDMA (Ecstacy, XTC, etc) nausea chills sweating teeth clenching muscle cramping blurred vision hyperthermia

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Hallucinogens Related to Norepinephrine 2,5-dimethoxy-4-methylampetamine (DOM) more euphoric, less hallucinogenic than LSD slower onset than LSD, effects last 7-24 hours like LSD, DOM is a 5-HT-2A partial agonist may produce “amphetamine psychosis” with prolonged use DOM

Your text includes DOM and MDMA as hallucinogens often classified as stimulants potent effects on NE and DA reuptake, much like “classical” stimulants arousal effects are much greater than those of psychedelics. Hallucinogenic effects much milder than those of true psychedelics Hallucinogens Related to Norepinephrine

dopamine norepinephrine mescaline MDMADOM amphetamine

Mescaline is derived from __________. A. psilocybin mushrooms B. the bark of a South American tree C. substances created in a laboratory D. the peyote cactus

Toxicity of MDMA (Ecstasy) involves __________. A. hyperthermia B. dehydration C. agitation and confusion D. all of the above

Hallucinogens Related to Acetylcholine Anticholinergic (ACh antagonist) hallucinogens block muscarinic ACh receptors cause extreme confusion, temporary psychosis “deliriants” amnesia autonomic effects include blurred vision extreme dilation of pupils rapid heart rate all of which are unpleasant to the user preclude becoming drugs of abuse.

Hallucinogens Related to Acetylcholine Sources include deadly nightshade (belladonna) mandrake roots henbane seeds datura family (jimsonweed) involved in sorcery and witchcraft since the Middle Ages (“hexing drugs”) combination of atropine, scopolamine, and/or hyoscyamine

Phencyclidine and Ketamine dissociative anesthetics NMDA (glutamate) receptor antagonists hallucinogenic properties make them unsuitable for use in humans ketamine is a standard component of a commonly used veterinary anesthetic Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum Salvinorin A (Salvia divinorum) analgesic as well as hallucinogenic properties selective κ -opioid receptor agonist

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum PCP (angel dust) 1950s developed as an anesthetic 1960s appeared as a psychedelic street drug developed a reputation for adverse reactions aggression, acute schizophrenia-like behaviors lost favor 1970s reappeared smokable forms alone or in combination with marijuana

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum PCP (angel dust) snorted, smoked duration of effect, 4-6 hrs Chronic Effects memory loss difficulties with speech and thinking depression weight loss Addictive—users engage in drug-seeking Symptoms may persist up to one year after stopping PCP abuse.

The principal reason anticholinergic drugs have little or no street appeal is that they produce __________. A. nausea and headaches B. powerful hallucinations C. a feeling of flying out of control D. amnesia

© Copyright 2011, Pearson Education, Inc. All rights reserved. Table 6.2

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum Ketamine popular club drug produces a dream-like intoxication inability to move or feel pain amnesia potentially hazardous depression in breathing

Miscellaneous Hallucinogens: Phencyclidine (PCP), Ketamine, and Salvia divinorum Salvia divinorum Mexican leafy herb smoked chewed brewed as a tea Hallucinogenic effects short-lived (1 min onset, 30 sec duration) altered visual perception, perception of reality mood and body sensations emotional swings feelings of detachment individual experimentation, not a club drug