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: 1. Onset – 30 min to 1 hour visual effects begin 2. Plateau – next 2 hours sense of time slows, visual effects intensify 3. Peak – after about 3 hrs and lasts 2-3 hours Each trip unique, highly dependent upon setting and personal expectations “In another world”, synesthesia 4. Come down – 2 hours May take up until next day to feel normal again

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-HT 2A + D 2 DA) – Decreased drug-induced visual illusions/hallucinations Haloperidol (Only D 2 DA – Not 5-HT 2A ) – Completely failed to prevent hallucinogenic effects 5-HT 2A 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-HT2 A 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

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-HT2 A 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-HT2 A 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) DrugRoute of Admin Typical Dose Range LSDOral.05-.10 mg PsilocybinOral10-20 mg MescalineOral200-500 mg DMTSmoking20-50 mg