 Animism  All objects derive their special characteristics from a spirit contained within objects  If a plant contains a spirit, eating the plant transfers that spirit to the person who eats it  Shaman – medicine man/woman  Specialist in harvesting and utilizing plants for medicinal properties

 Phantastica  Drugs that create a world of fantasy in our minds  Other names used over the years  Psychedelic (mind manifester)  Psychotomimetics(mimics psychosis)  Entheogen (creating spirit or divine within)  Entactogen (touching within)  Empathogen (empathy creator)  Hallucinogen (creating hallucinations)

 Classifying Hallucinogens  Chemical Structures (e.g., Indole, Catechol, Other)  Pharmacological Effects (e.g., 5-HT agonists, NMDA glutamate antagonists, anticholinergics)  Effects on Conscious Awareness (e.g., visual perception, body awareness)  Classical Phantastica  Capable of altering perceptions while allowing one to remain conscious of surroundings  Individual is simultaneously aware of both fantasy and reality  Later memory for experience is relatively clear.  They produce little acute physiological toxicity  In contrast, dissociative anesthetics and anticholinergics produce physiological toxicity and impair memory.  Two chemical classes of classical phantastica  Indole hallucinogens (Serotonin-Like)  Catechol hallucinogens (Dopamine-Like)

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 d-lysergic acid diethylamide (LSD)  Psilocybin  Mushrooms  Ololiuqui  Morning Glory seeds (lysergic acid amide)  Argyreia nervosa  Hawaiian baby woodrose seeds  Dimethyltryptamine (DMT)  Several plant substances

 LSD is not found in nature  First synthesized from grain fungus  Ergotism (St. Anthony’s fire)—Condition experienced from eating bread made from fungus infected grain  LSD discovery and early research  Synthesized in 1938 by Albert Hoffman, Sandoz  First experience from accidental absorption, 1943  Extensive medical use in U.S., 1953 to 1966  Turned over to government in 1966  Secret Army/CIA research with LSD

 Physical properties of LSD  In pure form - colorless, odorless, tasteless  Absorption from GI system rapid  Metabolism and Elimination  Half-life approx. 3 hours  > 90% is excreted within 24 hours  Subjective effects can last 2-12 hours  Cellular Tolerance develops rapidly  Repeated daily doses become ineffective within a few days  No evidence for Physical Dependence with LSD

 Acute Physiological Effects  Sympathomimetic effects  Pupil dilation, increased body temp., heart rate, and blood pressure  Parasympathetic effects  salivation and nausea  Mechanism of Action  Serotonin Agonist (5-HT 2A receptor agonist)

 Altered senses/perceptions  Synesthesia  Body distortions  Adverse Reactions  Panic  Flashbacks  Some beliefs about LSD  Creativity  Therapy

 Varieties of psychoactive mushrooms  Psilocybe mexicana  Psilocybe cubensis  Effects  Hallucinogenic effects similar to LSD  Similar autonomic effects to LSD  Cross tolerance occurs among psilocybin, LSD, and mescaline  Clinical Benefits of Entheogens  Recent studies by Griffiths et al. at Johns Hopkins.

 Dimethyltryptamine (DMT)  A short-acting hallucinogen (duration less than an hour)  Found in seeds of certain leguminous trees and prepared synthetically  No effects when taken orally, taken as snuff or smoked  Ayahuasca (vine of the soul)  Religious sacrament in South American tribes  Contains:  Banisteriopsis caapi vine (contains harmaline, an MAO inhibitor)  Psychotria viridis leaves (contains DMT)  Neither plant has psychoactive effects when ingested alone

 Mescaline (Peyote)  Structurally similar to amphetamine, but effects are more like those of LSD.  Mescaline is the most active drug in peyote; it induces intensified perception of colors and euphoria.  Effects include dilation of the pupils, increase in body temperature, anxiety, visual hallucinations, and alteration of body image, vomiting, muscular relaxation, and in very high doses may cause death.  Street samples are rarely authentic.

 Chemically related to amphetamines  Varying degrees of hallucinogenic and CNS stimulant effects  Phenylethylamines that predominantly:  Release serotonin are dominated by their hallucinogenic effects  Release dopamine are dominated by their stimulant effects

 2,5-Dimethoxy-4-methylamphetamine (DOM or STP)  3,4-Methylenedioxyamphetamine (MDA)  3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)  “Designer” amphetamines  2-CB, 2-C-T7, TMA

 Phencyclidine (PCP)  Developed as an intravenous anesthetic, but found to have serious adverse side effects.  NMDA Glutamate Antagonist  Effects differ from those of other traditional hallucinogens  It is a general anesthetic in high doses  It causes incredible strength and extreme violent behavior  Management of the severe psychological reactions requires drug therapy

 Physiological effects  Hallucinogenic effects, stimulation, depression, anesthesia, analgesia  Large doses can cause coma, convulsions, and death  Psychological effects  Feelings of strength, power, invulnerability, perceptual distortions, paranoia, violence, psychoses  Other PCP-like drugs  Ketamine  Veterinary anesthetic  Dextromethorphan at high doses  Synthetic derivative of codeine, OTC cough suppressant  Nitrous Oxide

 Belladonna  Mandrake  Henbane  Datura  These products contain the anticholinergic agents, atropine and scopolamine.

 Amanita Muscaria  Red and white speckled mushroom f ound in forests in many parts of the world  Active ingredient once thought to be muscarine, a cholinergic agonist  1960s, ibotenic acid and muscimol found in significant amounts  Muscimol is a GABA agonist: produces confusion, disorientation, sensory disturbances, muscle twitches, fatigue, sleep  Salvia Divinorum  “Magic Mint”, “Diviners sage”  Religious sacrament among Mazatec people of Oaxaca, Mexico  Only recently used in U.S. and Europe, considered legal hallucinogen, not currently listed as a controlled substance  Kappa opioid agonist

 Drug Discrimination  All hallucinogens are capable of establishing discriminative stimulus control and the discrimination appears to be specific to a particular drug’s mechanism of action.  Animals trained to discriminate LSD will generalize to other indole hallucinogens as well as mescaline, but not to catechol hallucinogens (MDMA), the dissociative anesthetics (PCP, ketamine), or the anticholinergics (atropine, scopolamine).

 Self Administration in Nonhumans  Hallucinogens that ARE self administered  MDMA, PCP, ketamine  Hallucinogens that are NOT self-administered  LSD, psilocybin, mescaline  However, a recent study showed that monkeys with a history of MDMA self-administration may self administer psilocybin and mescaline (Fantegrossi et al., 2004).