Psychedelic/Hallucinogens - Chpt 12

1. Psychedelic/Hallucinogens- Chpt 12

2. Hallucinogen Class/structure • Serotonergic • LSD-25 • Psilocybin/Psilocin • DMT - Ayahuasca • Bufotenine (ibogaine) • Ololiuqui (oh-low-lee-oo-kee) • Morning glory seeds • Mescaline (peyote) • MDMA (ecstasy) • MDA • MDE • DOM • Myristin and Elemicin (nutmeg and mace) • Cholinergic • Muscarine • Scopolamine • Glutamatergic • PCP • Ketamine • Dextromethorphan • Opioid • Salvinorin A (Salvia)

3. Effects of Serotonergic Hallucinogens • Sympathomimetic • Visual hallucinations • Can influence perception of time, space & events • Altered consciousness • Intense emotional experiences • May produce “Expansive or Restrictive Effects”

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

5. Albert Hofmann-Discovered LSD-1943

6. LSD in the USA 1950s • Clinical usage: Psychiatric training • Military Usage: U.S. military and CIA as incapacitating agent and truth drug • U.S. government gave LSD to unsuspecting individuals to study effects

7. LSD in the USA • 1960s - popular use advocates • East Coast: Timothy Leary (clinical psychologist at Harvard) • West Coast: Ken Kesey (noted author)

8. Timothy Leary and Ken Kesey Timothy Leary LSD guru of the 1960’s-“Turn on, tune in and drop out” Advocate..Author-”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 • Early 1990s - LSD came back

10. Doses of Acid

12. Visual Hallucinations • Enhanced color perception-increased vividness/contrast emotional significance • Flickering of the visual field-Altered Perception of motion • Synesthesia- mixing of sensory qualities, Sounds can take on visual forms music may take on enhanced meaning or intensity • Form constants-

13. FORM CONSTANTS? • Visual hallucinations that are commonly experienced • 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

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

15. 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

16. Effects of LSD Effects of drug come on in about 30 min (oral or mucousal) • 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

17. 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

18. HIGH dose Effects of LSD-Tripping • 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

19. “Tripping” can be divided into four stages:

20. LSD PARTY vs. PEAK EXPERIENCES? • Many people have used hallucinogens for social/communion/party purposes..however,many claim that these substances can produce profound experiences • The Peak experience-feelings of unity, transcendence of time and space, strong positive affect, sense of reality and objectivity of the experience, sacredness, ineffability, Paradoxicality, transiency, and subsequent positive changes in attitudes and behavior.

21. Hallucinogenic drug problems ‘Bad trips’ – anxiety/panic- • - traumatizing, dark imagery, insights appalling • Usually occur in novice users, feel out of control • Generally negative set and setting are key contributing factors

22. Adverse reactions to Serotonergic Hallucinogens? • Can lead to suicide or prolonged psychotic reaction • Can usually be talked down from a bad trip • Other psychological effects sometimes experienced- depersonalization, anxious or fearful state, • disruption of logical thought.

27. 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 • mechanism unknown • can be brought on by other drugs or setting • most commonly reported in low light situations • not intrinsically dangerous and usually goes away

28. 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

29. LSD & Neurotransmission • Binds to 5-HT2A receptors • agonist effect • Increases amount of sensory information getting to cortex through excitation of the Locus Coereleus

30. TOLERANCE AND DEPENDENCE? • Very rapid tolerance – (Tachyphylaxis) nearly complete in 4 days • Tolerance acquired via down-regulation of receptors • No withdrawal syndrome • No indication from any study of either psychological or physical dependence • animals do not self-administer

31. 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

32. 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 The largest Problem relates to decisions/behaviors while intoxicated • Accidents, Suicide, Aggression/violence

33. Psilocybe Mushrooms

34. Psilocybe Mushrooms

35. Psilocybin/Psilocin • Psilocybin • “magic mushrooms” or “shrooms” • Fungi that manufactured alkaloids with hallucinogenic properties • Oral consumption • Eaten raw, boiled in water to make tea, or cooked with other foods to cover its bitter flavor • Major ingredients • Psilocybin metabolized to psilocin.

36. Psilocybin/Psilocin • Last about 6-10 hours • Less potent than LSD-25 • 5-HT2A agonist • Same basic effects as LSD • Mushrooms occasionally toxic

37. Yage’/Ayahuasca…DMT • employed for divinatory and healing purposes by peoples of the Amazonian regions of S.A., is known by a number of different names. • Supreme Court has ruled in favor of religious use of hoasca (Ayahuasca) tea (DMT) as of 2009)

38. DMT, & 5-MeOA-DMT • DMT (dimethyltryptamine) • Derived from plants (Virola Shrub)in South America • Devoid of psychoactivity when taken orally • Except with ayahauasca, “vine of the soul” • In solid powder form and smoked. • Onset of Effects is Rapid (45 sec.) but are short lasting (5-15 min.) • 5-MeO-DMT (5-methoxy-dimethyltryptamine) • “Foxy Methoxy” • Oral active synthetic DMT analog is considerably more potent

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

40. Mescaline • From the Peyote cactus • Mescal (peyote) button • Native to SW United States and N Mexico • Administration • Chewed raw or cooked and eaten • Pure powder form

41. Mescaline • 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

42. Peyote cactus-mescaline

43. Religious Use of Hallucinogens • Right to peyote ritual is protected for Native Americans

44. Peyote cactus-mescaline

45. Pharmacology of selected 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)