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Psychedelic Drugs

Psychedelic Drugs. Psychedelic Drugs. produce visual hallucinations and out of body experiences alterations in cortical functioning Also affect mood, thinking and physiologicalprocesses At least 90 different species of plant and many synthetic agents can produce these effects

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Psychedelic Drugs

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  1. Psychedelic Drugs

  2. Psychedelic Drugs • produce visual hallucinations and out of body experiences • alterations in cortical functioning • Also affect mood, thinking and physiologicalprocesses • At least 90 different species of plant and many synthetic agents can produce these effects • Distinguish them by the NT system that they work on (primarily)

  3. many occur in nature; other newer ones are synthetically produced • Prior to 1960 (or so) – these were primarily restricted to religious rituals and most people were not even really aware of them

  4. Most psychedelics resemble one of 4 NT • ACh, catecholamines (NE, DA) and 5HT

  5. Classification of Psychedelic drugs • ANTICHOLINERGIC • Scopolamine • CATECHOLAMINERGIC • Mescaline • DOM, MDA, DMA, MDMA (ecstasy), etc • Myristicin, elemicin • 5HT like • Lysergic acid diethylamide (LSD) • Dimethyltryptamine (DMT) • Psilocybin, psilocin, bufotenine, Ololiuqui,etc

  6. GLUTAMINERGIC NMDAR ANT • Phencyclidine (Sernyl) (PCP) • Ketamine (Ketalar) • Dextromethorphan • OPIOID KAPPA R AG • Salvinorin A • from Salvia plants

  7. hallucinogens Serotonin-like drugs – • includes lysergic acid diethylamide (LSD) • psilocybin, psilocin • dimethyltryptamine (DMT) • bufotenine • 5HT acting psychedelics produce characteristic syndrome • disturbances in thinking, illusions, elementary and complex visual hallucinations

  8. believe that these psychedelics interact with 5-HT2A receptors • LSD – agonist • DMT, bufotenine – partial agonist • ?? why doesn’t 5HT have psychotomimetic effects? What about SSRIs?

  9. naturally occurring compounds exist that resemble the indole ring • investigating therapeutic use of compounds obtained from ergot fungus • LSD belongs to class of agents called ergot alkaloids

  10. Ergot fungus • Grew on rye (and some other grain) when weather conditions were right • Types of ergot poisoning

  11. 2 types of ergot poisoning • convulsive • characterized by twisting and contorting body in pain, trembling and shaking, muscle spasms, confusions, seizures, delusions and hallucinations • gangrenous ergotism • Due to decreased blood flow, infections occur in the extremities, accompanied by burning pain and loss of extremities.

  12. explanation for witch trials….

  13. Other possible examples of ergot poisoning • Joan of Arc • Saint Anthony’s Fire

  14. On August 15, 1951 one in twenty of the 4000 inhabitants of a village in France called Pont Saint Esprit (Bridge of the Holy Spirit) went mad. They had hallucinations, writhed in agony in their beds, vomited, ran crazily in the streets and suffered terrible burning sensations in their limbs.

  15. Other possible examples of ergot poisoning • Joan of Arc • Saint Anthony’s Fire • dreaded illness in the Middle Ages

  16. LSD – • during mid 1960’s – 1970’s – LSD – • History • synthesized in 1938; • Albert Hoffman (Sandoz)- swiss chemist • looking for possible therapeutic uses of ergot fungus • early animal studies – not much • first human experience 1943 although arguments can be made for a much earlier time

  17. LSD 25 had strong uterine effect and animals became stuporous but restless • nothing of special interest – set back on shelf…… • 5 years later – made new batch and must have gotten tiny amount on fingers • tried it again under a more controlled condition using a 0.25 mg dose (10X the dose for most to show an effect) • most potent drug in existence • 10 – 300 ug

  18. Uses of LSD – 1953 - 1966 • LSD used as adjunct to psychotherapy • possible treatment for alcoholics • treating cancer patients • possible truth serum

  19. 1966- Sandoz recalled LSD and withdrew sponsorship for work with LSD • NIMH – stopped LSD research (in house) in 1968; stopped funding in 1974 • NIAAA – stopped supporting psychedelic research in 1975

  20. Recreational Use of LSD • early to mid 1960’s • Pharmacology of LSD – • drug is odorless, colorless, tasteless • extremely potent (25 – 100 ug) but no OD death reported in humans • rats – behavioral effects at 0.04 mg/kg and LD50 ~ 16 mg/kg (400X the behaviorally effective dose) • Pharmacokinetics • absorption rapid – oral route most common • ½ life ~ 3 hrs • Effect usually lasts ~ 8-12 hours • metabolized in liver

  21. tolerance – develops very rapidly • recovery is also usually rapid (so weekly use of same dose is possible) • Cross tolerance – LSD with psilocybin, mescaline • Sympathomimetic (activates sympathetic NS) and so autonomic signs are often first to appear • dilated pupils, elevated temperature, BP and salivation

  22. LSD experience- • mostly visual/perceptual changes • altered sense of time • synethesia – mixing of senses • depersonalization • typical lasts 6 – 9 hours • Adverse Reactions • panic reaction • flashbacks • quite variable and unpredictable

  23. Bufo Marinus, also known as the cane toad,

  24. skin and glandular secretions • toad secretions have been used since ancient time……

  25. Psilocybin • long history in religious and ceremonial use • indole isolated by Abby Hoffman and then synthesized

  26. Hoffmann analyzed seeds • found several active alkaloids as well as d-lysergic acid amide • dangers: pesticides, substances coated on seeds in US; coatings on seeds can cause nausea, vomiting, headaches, increased BP, probably need 100s for species common in US • Morning Glory Seeds Heavenly Blue

  27. Catecholaminelike Psychedelics • NE and DA receptors important site of action for a large group of psychedelic drugs structurally similar to catechol NT and amph • differ from nt by one or more methoxy group (-OCH3) • exert amphetaminelikepsychostimulantactioons; can enhance energy, endurance, sociability and sexual arousal • psychedelic actions probably due to augmentation of 5HT neurotransmissions (5HT2A)

  28. Mescaline • Peyote – common plant in southwest US and Mexico • Spineless cactus with small crown or button

  29. mescal buttons (not mescal liquour from agave cactus, mescal beans) • dates back 5000 or more years • Aztecs • used in spiritual ceremonies (Native American Church) • Members of Native American Church exempt from federal criminal penalities for religious use (predates CSA)

  30. Pharmacological Effects • mescaline identified in 1918 • pharmacokinetics: • mescaline rapidly absorbed orally • levels increased in brain 1-2 hrs • acute psychotomimetic state 3.5 – 4 hrs • effects can persist for ~ 10 hrs • does not appear to be metabolized • imaging studies – hyperfrontal pattern of activity (right hemisphere)

  31. Synthetic amphetamine derivatives • large group of synthetic hallucinogens chemically related to amphetamines; • structurally related to mescaline and methamphetamine • exs. DOM –dimethyoxymethamphetamine • 100X more potent than mescaline (but less potent than LSD) • high incidence of OD – use not common – toxic • MDMA – Ecstasy- methlenedioxymethamphetamine • potent and selective serotonin neurotoxin • neurotoxic – issues re raves

  32. myristicin and elemicin • nutmeg and mace • common household spices • ingestion of large amounts – confusion disorientation, impending doom, depersonalization • structural resemblance to mescaline • many unpleasant side effects including vomiting, nausea and tremors • if people try it once – they don’t usually try again

  33. glutaminergic NMDAR ant • PCP (phencyclidine) • developed as an IV anesthetic- Sernyl – Parke Davis • monkey studies suggested that it was a good analgesic but did not produce muscle relaxation OR sleep – • a dissociative anesthetic • several patients were unmanageable as they emerged from the anesthetic; • studies showed patients becoming angry or uncooperative; reduction in sensitivity to pain in combination could contribute to violent behavior

  34. PCP (phencyclidine) • few reports of intense visual experiences and many more reports of body image changes • reports of disorganized thinking, suspiciousness and lack of cooperation • Recreational Use of PCP • early 1970’s – PCP crystals sprinkled onto oregano, parsley, etc and sold as marijuana • can be made inexpensively and relatively easily • PCP receptor – discovered in 1979 • appears to antagonize GLU • endogenous ligand – as yet unknown

  35. Other PCP like drugs • Ketamine • related veterinary product

  36. Other PCP like drugs • Ketamine • related veterinary product • 1999 – widespread reports of ketamine abuse resulted in ketamine receiving Schedule III designation • not as strong an effect as PCP

  37. dextromethorphan • an analgesic and a drug of abuse • common ingredient in more than 140 OTC cough suppressants • high doses produce hallucinations • highest age group for abuse potential -

  38. Salvinorin A • from salvia plant (magic mint, diviner’s sage, Sally-d)

  39. anticholinergic hallucinogens • potato family contains all naturally occurring agents in this category • atropine, scopolamine • atropine – belladonna – active ingredient in deadly nightshade.

  40. scopolamine • ACh antagonist – • comes from belladona (Deadly nightshade) • Jamestown weed, jimsonweed, stinkweed, devil’s apple, moonflower, mandrake • scopolamine containing plants have been used and misused for centuries • Professional and amateur poisoners used deadly nightshade as a source of poison

  41. Ibogaine - psychoactive indole alkaloid from roots of Tabernanthe iboga Howard Lotsof- Preclinical data reduces self- administration of both cocaine and morphine, as well as attenuates symptoms of morphine WD mechanism of anti-addictive action of ibogaine not well defined NMDA R antagonist; kappa agonist; mAChR activity has hallucinogenic effects in humans

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