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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 drugs1
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)




Classification of psychedelic drugs
Classification of Psychedelic drugs produced

  • 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


  • GLUTAMINERGIC NMDAR ANT produced

    • Phencyclidine (Sernyl) (PCP)

    • Ketamine (Ketalar)

    • Dextromethorphan

  • OPIOID KAPPA R AG

    • Salvinorin A

      • from Salvia plants


Hallucinogens
hallucinogens produced

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




  • Ergot fungus
    Ergot fungus ring

    • Grew on rye (and some other grain) when weather conditions were right

    • Types of ergot poisoning


    2 types of ergot poisoning
    2 types of ergot poisoning ring

    • 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.



    Other possible examples of ergot poisoning
    Other possible examples of ergot poisoning ring

    • Joan of Arc

    • Saint Anthony’s Fire



    Other possible examples of ergot poisoning1
    Other possible examples of ergot poisoning 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.

    • Joan of Arc

    • Saint Anthony’s Fire

      • dreaded illness in the Middle Ages


    • LSD – 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.

      • 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


    • 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


    • Uses of LSD – 1953 - 1966 stuporous but restless

      • LSD used as adjunct to psychotherapy

      • possible treatment for alcoholics

      • treating cancer patients

      • possible truth serum



    • Recreational Use of LSD with 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


    • tolerance – develops very rapidly with LSD

    • 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


    • LSD experience- with LSD

      • 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




    • Psilocybin with LSD

      • long history in religious and ceremonial use

      • indole isolated by Abby Hoffman and then synthesized


    • Hoffmann analyzed seeds with LSD

    • 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


    Catecholaminelike psychedelics
    Catecholaminelike with LSD 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)


    Mescaline
    Mescaline with LSD

    • Peyote – common plant in southwest US and Mexico

    • Spineless cactus with small crown or button



    Pharmacological effects
    Pharmacological Effects beans)

    • 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)


    • Synthetic amphetamine derivatives beans)

      • 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


    Myristicin and elemicin
    myristicin beans) 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


    Glutaminergic nmdar ant
    glutaminergic beans) 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


    • PCP (phencyclidine) beans)

      • 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



    • Other PCP like drugs beans)

      • Ketamine

      • related veterinary product

      • 1999 – widespread reports of ketamine abuse resulted in ketamine receiving Schedule III designation

      • not as strong an effect as PCP


    Dextromethorphan
    dextromethorphan beans)

    • 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 -


    Salvinorin a
    Salvinorin beans) A

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


    Anticholinergic hallucinogens
    anticholinergic hallucinogens beans)

    • potato family contains all naturally occurring agents in this category

      • atropine, scopolamine

      • atropine – belladonna – active ingredient in deadly nightshade.


    Scopolamine
    scopolamine beans)

    • 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


    Ibogaine - psychoactive indole beans)

    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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