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Psychedelic/Hallucinogens- Chpt 12

Psychedelic/Hallucinogens- Chpt 12. Primary effect is to produce perceptual changes & hallucinations Can influence several sensory systems, perception of time, space & events. Structure of hallucinogens.

mechelle-emerson
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Psychedelic/Hallucinogens- Chpt 12

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  1. Psychedelic/Hallucinogens- Chpt 12 • Primary effect is to produce perceptual changes & hallucinations • Can influence several sensory systems, perception of time, space & events

  2. Structure of hallucinogens • Most Hallucinogenic drugs have either a serotonin-like or a catecholamine-like structure • Serotonin-like are also known as indoleamine • LSD, psilocybin, psilocin, DMT and 5-MeO-DMT • Catecholamine-like aka phenenthylamine • mescaline • has structural similarities to NE & amphetamine Mescaline 5-HT DMT

  3. Different Types of Psychedelics-based on their neurochemical characteristics • Serotonergic • LSD • Psilocybin/Psilocin • DMT - Ayahuasca • Bufotenine • Ololiuqui (oh-low-lee-oo-kee) • Catecholamine-like • Mescaline • MDMA (ecstasy) • MDA • MDE • DOM • Myristin and Elemicin • Cholinergic • Muscarine • Scopolamine • Glutamatergic • PCP • Ketamine • Dextromethorphan • Opioid • Salvinorin A

  4. Pharmacology of Hallucinogenic Drugs • Pyschedelic effects begin within 30-90 min (oral) • LSD or mescaline trip lasts for 6-12 hrs; Psilocybin dissipates sooner • DMT effects user within seconds and dissipates in an hour or less • Depicts the typical dose range taken by recreational users (psilocybin is most potent and mescaline is the least)

  5. Physiological Responses • Activation of the sympathetic nervous system • Pupil dilation, small increases in heart rate, body temp and blood pressure • Dizziness, nausea, and vomiting

  6. Psychological Effects • State of intoxication usually called a “trip” • Trip can be divided into four stages: • Other psychological effects include depersonalization, anxious or fearful state, disruption of logical thought. • “Good trip” versus “Bad trip”: depends on dose, user’s personality, expectations, previous experiences, physical and social settings

  7. Neural mechanism • Experimental animal studies • Lack of relevant human studies • Location of critical receptors • Locus coeruleus (LC) – NE neurons • Receives/integrates input from all major sensory systems • Sends information to cortex (sensory cortex) • Activation of receptors • How does it produce sensory/cognitive distortions?

  8. Experimental receptor study • Vollenweider (1998) • Administration of antagonists • Risperidone, Ketanserin (5-HT2A + D2 DA) • Decreased drug-induced visual illusions/hallucinations • Haloperidol (Only D2 DA – Not 5-HT2A) • Completely failed to prevent hallucinogenic effects • 5-HT2A is key mediator of hallucinogenic action • Tolerance acquired via down-regulation of receptors • Very rapid tolerance – nearly complete in 4 days

  9. Receptor Activation • Serotonergic system involved in process • Perceptual and cognitive effects • High affinity for 5-HT receptor subtypes (LSD) • 5-HT1A,B,D, 5-HT2A,C, 5-HT5A, 5-HT6, 5-HT7 • LSD compared to phenyl- ethylamine drugs • Only receptors in common • 5-HT2A, 5-HT2C

  10. Two mechanism theories • Administration of hallucinogenic drugs • Aghajanian et al. (1999) • Decrease spontaneous firing, enhanced excitation • Drug intake  LC more sensitive to sensory input • Generation of hallucinations • Vollenweider et al. (2001) • Disrupt frontal cortex/striatum/thalamus circuitry • Drug intake  interfere with sensory info ‘gating’ • Information overload at cortical level

  11. Hallucinogenic drug problems • Serious drug side effects • ‘Bad trip’ – anxiety/panic • Interaction between drug, emotional state, environment • Flashbacks • Re-experience perceptual symptom long after use • Neural mechanism presently unknown • Psychotic breakdown • Most severe adverse reaction • Mental state – loss of contact with reality • Typically occurs with psychiatric disorder

  12. SerotonergicPsychdelics

  13. Serotonergic Hallucinogens • Lysergic acid diethylamide (LSD, Acid) • Psilocybin-Psilocybe mushrooms-Shrooms • Mescaline-Peyote cactus • Ergine-Morning glory • Harmaline-Ayahuasca,Yage’

  14. LYSERGIC ACID DIETHYLAMIDE (LSD) • Lysergic acid – Derived from ergot alkaloids • Ergot is a poisonous fungus that infects rye & other grains & grasses • Albert Hoffman: 1938 - synthesized #25 in series of new molecules doing ergot alkaloid chemistry • 1943 - returned to #25 making new batch & absorbed some through skin

  15. Aldous Huxley

  16. Albert Hofmann-Discovered LSD

  17. Timothy Leary and Ken Kesey

  18. Doses of Acid

  19. Effects of LSD etc... • Sympathomimetic • Visual hallucinations

  20. Visual Hallucinations • Enhanced color perception • Flickering of the visual field • Perception of motion • Synesthesia • Form constants

  21. Form Constants • Lattice Pattern

  22. Form Constants • Lattice Pattern • Tunnel/Vortex

  23. Form Constants • Lattice Pattern • Tunnel/Vortex • Spiral Explosion

  24. Visual Hallucinations • Enhanced color perception • Flickering of the visual field • Perception of motion • Synesthesia • Form constants

  25. Form Constants • Lattice Pattern • Tunnel/Vortex • Spiral Explosion

  26. Effects of LSD etc... • Sympathomimetic • Visual hallucinations • Altered consciousness • Tolerance (but no dependence)

  27. Adverse Effects: Myth & Reality • Birth defects/chromosome damage • Myth! • Acute Psychotic Reactions (Bad Trips) • Fairly Common • Use 7 times and legally insane • Myth! • Residual Psychosis • Rare; not certainly related to LSD

  28. Adverse Effects: Myth & Reality • Flashbacks • Fairly common among heavy users • For some people, flashbacks are constant • Rare, but true: hallucinogen persisting perception disorder • Stored in spine? • Myth—Causes of flashbacks unclear

  29. LSD in the USA Came to U.S. in 1950s in two ways: • Clinical usage: Supplied to psychologists and psychiatrists • encouraged their taking drug • Military Usage: U.S. military and CIA as incapacitating agent and truth drug • U.S. government gave LSD to unsuspecting individuals to study effects

  30. LSD in the USA • 1960s - popular use advocates • East Coast: Timothy Leary (clinical psychologist at Harvard) • West Coast: Ken Kesey (noted author) • graduate student in California got dose in psychology study • shortly after this goes to work in psychiatry • year later, writes One Flew Over The Cuckoo's Nest

  31. LSD in the USA • Spread through country with huge publicity until peak 1968 to 1972 • Schedule I in 1968 • Stuffy politicians didn’t know what to do because LSD was used by white, middle to upper class, college students • Early 1990s - LSD came back

  32. LSD & Neurotransmission • Binds to 5-HT2A receptors • agonist effect • Increases amount of sensory information getting to cortex through overriding filter mechanisms • This is how the drug influences perception, especially for vision

  33. Pharmacology of LSD Pharmacological Effects • Effects heavily dependent on dose taken • not just intensity of effects, but type of effects • Low doses = mild perceptual alterations • comparable to effects of marijuana use, but greater clarity

  34. Effects of LSD High Doses • progression through mental and emotional experiences • 6-12 hrs duration • Each trip unique, highly dependent upon setting and personal expectations • Can alter subjects’ emotional feelings during trip by experimenter’s previous behavior • warm and supportive or suspicious and nonsupportive

  35. Effects of LSD Effects of drug come on in about 30 min • first signs are autonomic activation • followed by overt behavioral signs - loosening of emotional inhibitions • giddiness, laughter for no reason • mood euphoric and expansive, but labile mood swings notable • abnormal color sensations, luminescence • colors reported as more brilliant

  36. Effects of LSD • space and time disorders • added depth with loss of perspective - up/down altered • close in space influenced more than distant • general slowing of time reported

  37. LSD Hallucinations • gratings, latticework, honeycomb, chessboard, • tunnels, funnels, alleys, cones, vessels, and spirals • can be present with eyes open or closed • involve bright light in center with figures moving in from periphery • forms appear to move in depth and take on color shades, red common • Sounds can take on visual forms • music may take on enhanced meaning or intensity

  38. LSD & Bad Trips • Psychological impact - traumatizing, imagery dark, insights appalling • Usually occur in novice users, feel out of control • Generally negative set and setting are key contributing factors • Can lead to suicide or prolonged psychotic reaction • Can usually be talked down from a bad trip

  39. LSD & Flashbacks Spontaneous recurrence of trip after period of normalcy • can occur after long periods of abstinence • more common after multiple high dose use • prolonged afterimages for days and weeks after • tripping mechanism unknown • can be brought on by other drugs or setting • most commonly reported in low light situations • not intrinsically dangerous and usually go away

  40. Psilocybin/Psilocin • Magic Mushrooms, Liberty Caps • Central America and northwestern U.S. • Last about 6-10 hours • Need a lot to get same effect as LSD • 5-HT2A agonist • Same basic effects as LSD • Mushrooms occasionally toxic

  41. Psilocybe Mushrooms-psilocybin

  42. Psilocybe Mushrooms-psilocybin

  43. Psilocybin, DMT, & 5-MeO-DMT • Psilocybin • “magic mushrooms” or “shrooms” • Fungi that manufactured alkaloids with hallucinogenic properties • Per os • Eaten raw, boiled in water to make tea, or cooked with other foods to cover its bitter flavor • Major ingredients • Psilocybin and related compound psilcon, the actual psychoactive agent psilocybin is converted to

  44. Psilocybin, DMT, & 5-MeO-DMT (cont’d) • DMT (dimethyltryptamine) • Derived from plants in South America • Devoid of psychoactivity when taken orally • Except with ayahauasca, “vine of the soul” • Vines contribute to alkaloids called β-carbolines • Hypothesized to inhibit the enzyme monoamine oxidase which breaks down DMT • In solid powder form and smoked • 5-MeO-DMT (5-methoxy-dimethyltryptamine) • “Foxy Methoxy” • Oral active synthetic DMT analog

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