Psychedelics

1. Psychedelics CHAPTER 12

2. Psychedelic/Hallucinogens • Called by many different names • Psychotogens • Psychotomimetics • Psychedelics • Primary effect is to produce perceptual changes & hallucinations • Can influence several sensory systems, perception of time, space & events

3. Different Types of Psychedelics • Serotonergic • LSD • Psilocybin/Psilocin • DMT - Ayahuaca • Bufotenine • Ololiuqui • Catecholamine-like • Mescaline • MDMA (ecstasy) • MDA • MDE • DOM • Myristin and Elemicin • Cholinergic • Muscarine • Scopolamine • Glutamatergic • PCP • Ketamine • Dextromethorphan • Opioid • Salvinorin A

4. SerotonergicPsychdelics

5. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. DMT • Dimethyltriptamine • 5-HT2A agonist • Alkaloid • Often smoked • Main ingredient in Ayahuasca • Same effects as LSD

20. Bufotenine • Dimethyl-serotonin • A product of abnormal serotonin breakdown • Like LSD and others • Can occur in urine of people with psychiatric disorders • Psychosis • Paranoia • Depression

21. Ololiuqui • Substance found in morning glory seeds • Similar to LSD • Significant nausea, vomiting and cramping

22. Tolerance/Dependence • Not significant producers of tolerance or dependence • No withdrawal either • People and animals do not self-administer • Problems related to the things people do while under the influence • Accidents • Suicide • Aggression/violence • Toxic reactions

23. Catecholamine-likePsychedelics

24. Mescaline • Active drug in peyote • Structurally similar to NE • However, most of the effect is mediated by our friend, the 5-HT2A agonist action • Legal for members of the Native American Church

25. Ecstasy • MDMA (methylene-dioxy-methamphetamine) • Synthesized in 1912 • Structurally related to amphetamines • Sympathomimetic • Weak in altering perceptual functions • But strong effects on emotions - empathogen • Used in combo with psychotherapy

26. Pharmacodynamics Monoamine neurotransmission • increase synaptic DA and 5-HT • blocks 5-HT transporter • enters neuron and causes release of 5-HT

27. Ecstasy Effects • Stimulant effects typically noted shortly after ingestion • increased heart rate • increased blood pressure • dry mouth • decreased appetite • increased alertness • elevated mood • jaw clenching

28. Subjective Effects • euphoria • increased physical and emotional energy • heightened sensual awareness • subjective feeling of increased closeness or enhanced communication Cognitive Effects • memory loss Ecstasy Effects

29. X Tox • Malignant hyperthermia and dehydration • Idiopathic toxic response (not common but nasty) • Renal failure • Rhabdomyolysis – disintegration of muscle tissue • Street X is even more of a problem because it’s not always X or may have other drugs

30. X Tox • Potent neurotoxin • 1-2 times street dose • depletes forebrain 5-HT (not DA) • Kills the transporter receptor (SSRI) • Degeneration of 5-HT terminals • Fine axons from dorsal raphe • Can get 30% loss with single injection • Up to 80% with repeated injections • Can induce psychiatric disturbance in vulnerable individuals. Treatment refractory depression

31. MDMA & MDA neurotoxicity 5-HT immunoreactive fibers in rat parietal cortex PCA MDA Normal 9.9

32. Squirrel monkeys 18 mo post-trtmt Control 5-HT immuno- reactivity Caudate Hippocampus Neocortex MDMA McCann et al. (1997)

33. What is PMA? • Paramethoxy-amphetamine • "Death" "Mitsubishi Double Stack" "Killer" "Red Mitsubishi" • Substitute for MDMA • Cheaper to make • Slower, longer effects • More hallucinogenic • Incidence of toxic side effects much higher than MDMA (narrow safety margin)

34. Designer Psychedelics • DOM, MDA, DMA, MDE, TMA, AMT, 5MeO-DIPT • All structurally related to mescaline and methamphetamine; therefore MDMA. • MDA is a metabolite of MDMA. May be responsible for much of the MDMA effect.

35. Myristin and Elemicin • Found in nutmeg and mace • Structurally similar to mescaline • Significant nausea and vomiting • The sick usually limit use

36. GlutamatergicPsychedelics Dissociative Anesthetics

37. Phencyclidine • PCP • NMDA receptor antagonist • Blocks the function of glutamate • Used as an analgesic and anesthetic • Can be administered by any route • Oddly enough, animals self-administer (euphoria) • Induces amnesia and true psychosis • Hallucinations, paranoia, agitation, dissociation • Higher doses lead to stupor, coma seizures, death • A perfect example of a Schedule I drug

38. Ketamine • Special K • Very similar to PCP, not as powerful • Liquid, but can be powdered for snorting or smoking • But just as dumb, stupid, useless and unsafe • Another perfect example of a Schedule I drug

39. Subjective Effects of PCP/Ketamine • Sensations of light coming through the body and/or colorful visions • Complete loss of time sense • Bizarre distortions of body shape or size • Altered perception of body consistency • Sensations of floating or hovering in space • Feelings of leaving one’s body • Visions of spiritual or supernatural beings • Emotions ranging from euphoria to hositlity Dalgarno & Shewan (1996)

40. Dextromethorphan • Active ingredient in most OTC cough medicine • NMDA receptor blockade at high doses • Mostly teenage males abuse it • Like PCP and K at 20-30 X OTC dose • Coricidin –Bad news

41. CholinergicHallucinogens

42. Muscarine/Muscimol • Found in mushrooms (Amanita Muscaria) • Muscimol is a GABAA agonist • Trance-like, dreamy state with dreamlike illusions • Like Ambien • Muscarine is an Acetylcholine agonist (muscarinic receptors) • Not psychotropic • Peripheral effects: sweating, limb twitching, seizure activity

43. Found in – Atropa belladonna, DaturaStramonium, Henbane Acetylcholine receptor (muscarinic) antagonists • Dissociatives that induces delirium , hallucinations, and amnesia • Classic anti-cholinergic symptoms • Hot as hell • Dry as a bone • Mad as a hatter • Blind as a bat • Red as a beet Used in the treatment of motion sickness & to dilate pupils during eye-exams. Atropine & Scopolamine

44. Comes from a plant in the mint family • Salvia Divinorum • Affinity for kappa opioid receptors • Agonist action • Like LSD and psilocybin • Fresh leaves are chewed and left in mouth • Dried leaves smoked • Not effective if taken orally • Most potent, but not most powerful, of all naturally occurring hallucinogens • It’s still legal, but not likely for long Opioid Hallucinogen - Salvinorin A