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Drugs and the Brain Midterm 3

Terms in this set (129)

Airplanes: Beverages and Diversions
...
Benzedrine inhaler
- a CNS stimulant
- historically an inhaler for asthma
-amphetamines clinically marketted in the form of Benzedrine pills and inhalers in 1939
Amphetamines mechanism of action (norepinephrine and dopamine)
-release norepinephrine
-release dopamine
- norepinephrine and dopamine neurotransmitter leakage via reuptake transporters
-increased activity at norepinephrine and dopamine synapses
Drug effects on reuptake transporters
- affects the central nervous system (CNS) by releasing monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin.
-Blocking the reuptake of monoamines by inhibiting the activity of monoamine transporters
-Decreasing the expression of dopamine transporters at the cell surface
-Increasing cytosolic levels of monoamines by inhibiting the activity of monoamine oxidase (MAO)
-Increasing the activity and expression of the dopamine-synthesizing enzyme tyrosine hydroxylase (TH)
ventral tegmentum
-reward/motivation (connected to nucleus accumbens)
-VTA
-in the midbrain adjacent to the substantia nigra
-one of the two major dopaminergic areas in the brain (the other being the substantia nigra)
-known for the major role it seems to play in motivation, reward, and addiction.
Medical journal advisements: meth and military
-Journals solicit pharmaceutical advertising by placing own advertisements in Medical Marketing and Media (MMM), publication aimed at pharmaceutical and other health-care manufacturers
Narcolepsy
-amphetamine type drugs used to treat narcolepsy
- chronic sleep disorder, overwhelming daytime drowsiness and sudden attacks of sleep
-difficulty staying awake
ADHD and Childhood
-attention deficit hyperactivity disorder
-characterized by inattention, hyperactivity, impulsivity
-amphetamines uses to treat symptoms of ADHD...Adderall
Obetrol and Adderall
-obetrol for weight loss, appetite suppression
- 10 mg pill = 2.5 mg amphetamine sulfate, 2.5 mg amphetamine aspartate, 2.5 mg dextroamphetamine sulfate, 2.5 dextroamphetamine saccharate

-Adderall for ADHD
- 10 mg pill= 2.5 mg amphetamine sulfate, 2.5 mg amphetamine aspartate, 2.5 mg dextroamphetamine saccharate
FDA 1997 relaxed direct to consumer advertisement
- The FDA in 1997, relaxed the earlier guidelines for TV commercials. Instead of including the "brief summary" that took up a full page in magazine ads and would take too long to explain in a TV spot, pharmaceutical companies could direct viewers to a magazine ad, an 800 number or a website
-countries where drug makers are allowed to market prescription drugs directly to consumers. The U.S. consumer drug advertising boom on television began in 1997, when the FDA relaxed its guidelines relating to broadcast media.
Amphetamines vs. Methamphetamines, routes of administration and social context
- routes of entry for amphetamines:
Oral digestive, nasal insufflation, injection, smoking
-illicit street "speed" = methamphetamine
Speed, crank, crystal meth, crystal, ice
-differences:
-MA has longer lasting and more toxic effects than A ...cuz N-methyl group that separates MA from A decreases polarity of the molecule ... better penetrates the BBB
-MA greater activity in the CNS, but has less peripheral nervous system and cardiovascular stimulation activity
-A indirectly stimulates the CNS by activating release of catecholamines preventing breakdown and storage
-MA stimulates postsynaptic catecholamine receptors
Blitzed, Drugs in the Third Reich
-book written by Norman Ohler
-claims that German soldiers used methamphetamine and that Hitler was a drug dealer
Toxic effects and withdrawal symptoms of meth
-problematic/toxic effects
Anxiety, irritability, aggression, impaired judgement, addiction, stimulant psychosis: delusions, hallucinations

- toxic/lethal effects
Cardiovascular stress and damage, heart attack, stroke, seizure, chronic psychosis

- withdrawal effects
Depressed mood, fatigue, "crash", disrupted sleep, agitation, cravings for drug
The People's Drug
-chain of drugstores based in Alexandria Virginia
-converted to CVS
Pervetin tablets
-methamphetamine popular among Nazis German soldiers in World War II
-used as a confidence booster and performance enhancer
-kept exhausted soldiers awake, no fatigue, switched off inhibitions
Patient A:
...
Ephedrine/Pseudoephedrine
- stimulants which have become so abused you now have to ask the pharmacist for these OTC drug... restricted OTC
-related plant derived stimulants
-ephedra
-amphetamine molecule with an OH group that keeps it from crossing the BBB and affects norepinephrine and dopamine
2005 FDA ban
-FDA bans enrofloxacin use in poultry
-decided to ban the use of the antibiotic enrofloxacin in poultry because of the risk that it promotes drug-resistant bacteria that can be harmful to humans
OH vs carboxylic vs methyl groups for BBB
...
Ephedra, Chinese ephedra, ma huang
-A substance derived from a shrub like plant used as a stimulant as energy enhances for athletic performance and a weight-loss agent
-Main ingredient in oral asthma medication, used for allergies, nasal congestion, asthma and bronchitis
-ephedra sinica
Mormon Tea
-ephedrine containing plants that are sympathomimetics and mild stimulants containing ephedrine
Long term effects of amphetamines and antidepressants
-psychosis and delusions
-feelings of paranoia and hostility
-cardiovascular problems
-reduction of cognitive ability
-breakdown of muscle and malnutrition
Catha edulis, khat, qat, chat
Khat a cathinone containing plant, chemically similar to ephedrine and amphetamine, native to Africa
coca leaves
-leaves that cocaine come from
-leaves chewed with or without calcium carbonate to neutralize the HCL promotes.
-used in rituals of natives in South America ... taking roasted coca leaf preparation mixed with calcium carbonate
Somalia Civil War
-ongoing civil war
-conflict over a Coke plant that was installed
Drug schedules
Cocaine- schedule 2 drug
Sunset garden guide
-book about plants and gardening in the West
Erythroxylum coca
coca plant
Performance enhancing substance
Mama Coca
-long history of use in South America, brewed as a tea, leaves are chewed with or without calcium carbonate to neutralize the HCL promotes. Plant of worship
-wakefulness and stamina
-reduced appetite
-leaves are nutritious
-medicinal properties
USA and the war against the coca plant
-coca eradication a strategy promoted by the US government starting in 1961 as part of its "War in Drugs" to eliminate the cultivation of coca
Coca, coffee and divinations
-divinations: the practice of seeking knowledge of the future or the unknown by supernatural means
Albert Niemann
-German chemist who isolated cocaine in 1860.
Sulfur mustard
-mustard gas
-A clear, yellow, or amber oily liquid with a faint, sweet odor of mustard or garlic that can be dispersed in an aerosol form. It causes blistering of exposed skin.
-chemical warfare
Cocaine mechanism of action
-indirect sympathetic agonist - catecholamine uptake inhibitor
-blocks presynaptic reuptake transporters for norepinephrine, dopamine and serotonin
Sigmund Freud and cocaine
-Freud interested in its local anesthesia, abilities, them it's stimulating ability
-promoted its use for depression, anxiety, addiction
-stimulant psychosis
-lost his finger, addicted to morphine, Freud broke his addiction with cocaine
Cocarettes, Vin Mariani and tooth pain
-cocarettes: cigarette made with coca and tobacco leaves
-Vin Mariani: cheap wind containing cocaine, heavily marketed with sexy ads, became very popular in the late 19th and early 20th centuries
-tooth pain: cocaine tooth drops in a pharmaceutical advertisement in 1885 ... considered a possible local anesthesia... prolonged use if cocaine can actually cause tooth decay and teeth grinding
Post 1903 Coca-Cola
-by 1903, tpublic opinion had turned against the widely used and abused narcotic, leading the Coca-Cola Company's then-manager, Asa Griggs Candler, to remove nearly all cocaine from the company's beverages
cocaine routes of administration
-oral-digestive
-oral-buccal
-nasal insufflation
-injection
-vaporization/smoking

ALL routes of entry can be dangerous
Risks of toxic effects greater for more rapid routes of entry
Calcium carbonate mix
-CaOH2 calcium hydroxide (lime)
-neutral "free base" form at basic pH
-ionized form at acidic pH
-improved oral-buccal absorption
Free-base cocaine (crack)
-A technique for ingesting cocaine in which the pure cocaine basic alkaloid is chemically separated from processed cocaine, vaporized by heat from a flame, and inhaled through a pipe.
-improved oral-buccal absorption
Anti-Drug Abuse Act of 1986
Created a 100 to 1 sentencing disparity for crack vs. powder cocaine possession
Sentencing inequality for cocaine
-Fair Sentencing Act of 2010
-sentencing disparity - 18:1
Body packers
People swallowing bags of cocaine and then pooping them out in order to recover the drugs, but if the bag break instantaneous overdose and death
Abuse potential of cocaine
-extremely high abuse potential when you extract out the active components and make it available in pure white powder form
Characteristics of addiction
-defined as an inability to control ones use which almost always causes adverse consequences often associated with withdrawal
20th century view of addiction
"Good people don't smoke marijuana"
- addiction= a moral failure, something disfunctional about people who let themselves get out of control with substance use
-a lot of addiction in media fueled by racism
View of addiction now: a brain disease
-addiction a multi-faceted psychological social factors, takes attention off of addiction as a "disorder"
-however idea that addiction is a brain disease had been elevated past what research can support
James Olds Experiment
His 1954 experiment, discovered the pleasure center of the brain; He put the rat in a box and stimulated its brain whenever the rat approached a certain corner. He expected the rat to stay out of that corner, but instead he observed the rat was "coming back for more," acting as though the brain stimulation was pleasurable and in the limbic system. Further research showed that stimulation of areas in the limbic system produced pleasure in humans, too; Hypothalamus stimulated and dopamine released
-discovery of reward-reinforcement pathway
Reward pathway and drugs of abuse
Cocaine, amphetamine, morphine and other euphorigenic chemicals
Dopamine and reward
Most abused drugs increase dopamine levels in the nucleus accumbens
rat park experiment
-James Olds
transcranial magnetic stimulation (TMS)
-electro shock therapy for depression
Treatment of addiction
-breaking the cycle
-creating new lifestyles, social support networks, recreational activities, stress reduction skills, restoration of reward system, unlearn behaviors, practice new behaviors
Psychiatric mediations: prevalence of use
-17% US adults take prescribed psychiatric meds
-84% for long term use
Psychosis, schizophrenia: symptoms, prevalence and risk
-psychosis: impairment in "reality testing" ... delusions, hallucinations
-schizophrenia= chronic, gen population 1 % prevalence, genetic factors also environmental factors
Ex: schizophrenic aunt 3%, parent, sibling 10%, both parents 50%, twin 50%
Phenothiazine Antipsychotics
-chlorpromazine (Thorazine) France (1952) and US (1954)
-a new class of phenothiazine antipsychotics
Classical Antipsychotic Drugs
-treats positive symptoms, tardive dsykinesia
- all classic antipsychotics are D2 dopamine receptor antagonists
-drug that binds and inhibits/blocks the activation of dopamine
New Generation antipsychotics: dopamine and seratonin receptor antagonists
- new gen psychotics are dopamine and seratonin receptor antagonists
Dopamine Hypothesis of psychosis
-Psychosis is due to excess of dopamine neuronal activity in the mesolimbic-mesocortical pathways
-psychosis related to excess activity in particular dopamine receptors
Too much amphetamine/cocaine can lead to psychosis
Depression: symptoms and prevalence
-major depression prevalence:
Lifetime: 17%
Current: 5%
-symptoms: a bio-psycho-social phenomenon
- feelings: mood, interests, pleasures
-thoughts: guilt, suicidal ideation
-actions: eating
-somatic: sleep
Monoamine Oxidase Inhibitors (MAOIs)
-antidepressant medications that increase the amount of monoamine neurotransmitter in synapses
-1950s iproniazid, isocarboxazide (Marpian) ... MAOI breaks down/inactivates dopamine/serotonin
Tricyclic Antidepressants (TCAs)
-Antidepressants that increase the action of neurotransimtters by blocking their removal (reuptake) from the synapses (spaces between nerve cells).
-have 3 rings in molecular structure
-1950s, doxepin, imipramine
Monoamine hypothesis of depression
-depression is caused by insufficient activity of monoamine neurotransmitter systems in the brain, especially serotonin
-predicts the underlying basis of depression is a depletion in the levels of serotonin, norepinephrine, and dopamine in the central nervous system
Monoaminergic brain circuitry
GPCR receptors:diversity and amplification
-GPCR receptors -> 5HT, dopamine -> diversity and amplification
SSRIs: professional and popular enthusiasm, cosmetic psychopharmacology
-selective serotonin reuptake inhibitors: the 1980s
-Prozac 1989
-professional enthusiasm: massive advertising to physicians: listening to Prozac (1989) cosmetic psychopharmacology
-popular enthusiasm: in 1997 FDA allows direct-to-consumed advertising of prescription medicines... massive advertising to consumers caused even more popular enthusiasm
-other new generation antidepressants: trazodone, Wellbutrin, cymbatta
Antidepressant usage by age group, duration of use
-highest in age groups 40-59 and 60 and over
-highest in females
-lowest in 12-19 age group
FDA approval process
-preclinical investigations: human clinical trials
-human clinical trials: to be considered for approval, new drug must demonstrate statistical significance over and above the placebo effect
Phase 1: safety
Phase 2: efficacy (small sample)
Phase 3: efficacy, safety (larger sample), placebo control, double-blind
Placebo: an inert substance or condition ... placebo is Latin "to please"
-rodent testing of antidepressant drugs:
Tail suspension test, forced swim test, = antidepressants promote prolonged mobility... idea was that the rat gave up because it was depressed and rats on anti-depressants would struggle longer/ "have hope"
Efficacy of antidepressants compared to placebo
-used ALL clinical trial data submitted to the FDA
-antidepressant drugs found not superior to placebo for a mild and moderate depression
-for severe depression: small statistically significant but not clinically significant effect
-YOU CANNOT REPLACE MEDICATION WITH PLACEBO AND EXPECT EFFICACY ... REQUIRES A SHIFT IN WORLDVIEW A DEEP PARADIGM SHIFT
SSRI discontinuation syndrome
-withdrawal from anti-depressants
-symptoms: nausea, headache, dizziness, irritability, lethargy, nightmares, tingling and shock-like sensations, depression, anxiety
-the best way to quit antidepressants is VERY slowly
Basic needs for mental and physical health
-Eat, move, sleep
-do not stop taking your anti-depressant medicine
Addiction as a behavioral condition
-inability to control use
-adverse consequences
-often associated with withdrawal
- a biological-psychological- social factor
12 step program: AAA
-A social support network, guidelines for recovery from addiction
-Step One: Acceptance, We admit we are powerless over alcohol and that our lives have become unmanageable
-12 steps: cultivation and practice of honesty, hope, trust, courage, integrity, humility, love, repair, and reconciliation in relationships, perseverance, service to others
-Bill Wilson: Founder of AAA in 1935, supported LSD psychotherapy sessions in the 1950#
Aldous Huxley and Humphry Osmond
-correspondence with Humphrey Osmond in 1956
-psychosis wasn't really their main feature
-Osmond psychiatrist who coined the word psychedelic to drugs he introduced Huxley to
-Huxley proposed the term phanerothyme...phaneros= visible, thymos= (soul/mind)
Origin and meaning of the term psychedelic
-psychedelic= mind revealing, term coined by Humphrey Osmond in 1956 in correspondence with Aldous Huxley
-psyche= spirit/ life breath/ soul/ mind
-deloun= to show/ make manifest/ reveal
-Delos= visible, clear
-hallucinogens: producing hallucinations (perceptions in the absence of an eternal stimulus)
-hallucinari= to wander in the mind
-genesis= to bring into existence/ creation/ generate
-psychotomimetics= mimicking psychosis
-entheogen= generating god within
Psychedelic effects on the mind
-heightened awareness:
external sensory output
internal thoughts and feelings
increased emotional consent to everything
-alterations of sensory perception: motion, multiple visual images, distortions of perspective, hallucinations, synesthesia
-dreamlike imagery and feelings
-loosening of psychological defenses
unconsciousness material brought into awareness
beneficial for therapeutic work
Anxiety and panic may occur
-pharmakon
Set and setting
Effects of psychedelic drugs varies with difference in set and setting
Set: mental and physical state of the user: intentions, expectations, prior experience, personality, and current state of mind
Setting: environment in which uses occur
Albert Hoffman's Discovery of LSD
-synthesized by Albert Hoffman in Sandoval Libraries, Basel, Switzerland, 1938
-resynthesis and discovery of psychoactive properties by Hofmann in April 1943
-landmark event in the history of neuroscience
-derivative of an alkaloid (ergotamine) found in Claviceps purpurea (ergot), a fungus that grows on rye and other cereal grains
-exploring derivatives for ergotamines vasoconstrictive properties, for use in the treatment of headache, postpartum bleeding, stimulation of uterine muscle contractions for induced labor
Ergotomime, ergot fungus
A vasoconstrictor
-fungus may contain various psychoactive alkaloids such as LSD, lysergic acid hydroxethylamide and other toxic alkaloids
-outbreaks of ergot poisoning have happened throughout history... associated with consumption of flour, bread, beer made from ergot infected grain
Dose and route of administration of LSD
-effects are dose dependent... range from mild perceptual distortions to profound emotionally-charged mystical experiences
-intention the most important thing... determined everything else
-oral digestive absorption ... blotter paper, pill or tablet, liquid, sugar cube, gelatin ...
-historically LSD was pure ... however myth that it is commonly laced with strychnine, PCP, methamphetamine ,
Typical psychedelic dose
50-300 micrograms
Threshold dose
10 micrograms
Illicit market dose
65 micrograms
Early clinical research and psychiatric use
-in 1950s-60s: clinical research in the treatment of addiction, psychosis and other mental illness
Delysid
-LSD
-produced and distributed free of charge by Sandoz for clinical research during the 1950s
LSD History Timeline
The Doors of Perception, R. Gordon Wasson article in Life
-book by Aldous Huxley published in 1954, elaborates on his psychedelic experience under the influence of mescaline... LSD goes to the public
- LIFE magazine: May 13th, 1957 "The Discovery of Mushrooms that Cause Strange Visions: Seeking the magic mushroom ... written by R. Gordon Wasson
Timothy Leary, Richard Alpert (later Ram Dass), and the Harvard group
- researched LSD in the early 1960s
-wrote social dimensions of personality
-Ph.D. in Psychology from UC Berkeley in 1950
-labeled the "most dangerous man in America" by president Nixon in 1974 ... arrested for bringing small amount of cannabis across the border from Mexico into Texas
Ken Kesey, The Merry Pranksters and the Acid Test, and Tom Wolfe
-San Francisco Bay Area Acid Tests in the early 1960s... expanding recreational use
-Ken Kesey wrote: one flew over the cuckoos nest/ sometimes a Great Notion
-Tom Wolfe: The Elctric Kool-Aid Acid Test in 1968
Adverse effects of LSD
-mid to late 1960s: adverse effects of LSD exaggerated and demonized by the media
-somatic toxicity is low: TI is VERY high
-dangerous behavior while intoxicated
-anxiety, panic, "bad trip"
-Too much from the psyche too soon
-creation or exacerbation of long-term cognitive/emotional problems
-anxiety, depression, psychosis
-flashbacks
-powerful memories, positive or negative
Eleusininan Mysteries
-Ancient Greek
-infrequent (annual, maybe once in a lifetime?) ritual offered to individuals in certain strata of society
-flourished for many centuries
-possibly involved used of psychedelic plants or fungi ... hypothesis: ingested ergot alkaloids from fungi on grain
Psilocybin, psilocin
-psilocybin: 4- phosporyloxy-N, N-dimethyltryptamine
-psilocin: 4-hydroxy-N, N-dimethyltryptamine
-found in numerous species of Mushrooms which grow throughout the world
-ex: psilocybe cubensis, psilocybe cyanescens, psilocybe semilanceata
teonanacatl, 'flesh of god'
-best documented history is of the native pre-Columbian peoples of Latin America
-teonanacatl: "sacred mushroom" or "flesh of the gods" in Nahuatl, language of the Aztecs
-described in writings of the Spanish from the 1500s - 1600s
Marina Sabina (1894-1985)
-a shaman/curandera
-lived in the Sierra Mazateca
- practice based on the use of Psilocybe Mushrooms
-involved in 1955 mushroom ritual documented in a major article with photographs in Life Magazine
-brought knowledge of this heretofore secret ritual use into the world
Classical psychedelics
-LSD, psilocybin, DMT, mescaline ...
Peyote, San Pedro cactus, mescaline, Heffter
-mescaline: 3,4,5, trimethoxyphenethylamine
-found in several species of cacti of the Americas
-peyote cactus: Lophophora williamsii
-San Pedro cactus: Echinopsis pachanoi
closely related to the Peruvian torch cactus: echinopsis peruvianus
-first psychedelic substance to be chemically indemnified from a plant by Arthur Heffter from peyote cactus, Germany 1897
-dosage: 300-500 mg of sulphate salt, less of chloride salt
6-12 peyote "buttons"
Length of trip: 6+ hours
Native American Church (1918)
- peyote has a long history of spiritual use by native Americans from Mexico and later North America
-Native American Church peyote ceremonial sacrament
uses peyote exclusively for Sacrament Ceremony ... may contribute to an increase in mental performance
Employment Division, State of Oregon vs. Al Smith - US Supreme Court 1990
-court case that held that the state could deny unemployment benefits to a person fired for violating a state prohibition on the use of peyote/illicit drugs, even though the use of the drug was part of religious ritual
-court upheld decision to deny unemployment benefits by two native Americans who were dismissed from drug counseling jobs because they tested positive for peyote ... ingested drug in religious ceremony
US Congress- Religious Freedom Restoration Act 1993
-federal Law that endured that interests in religious freedom are protected
1994 US Congress: American Indian Religious Freedom Act Amendment
-provided protected use of peyote as a sacrament in traditional religious ceremonies
Dimethyltryptamine (DMT), tryptophan
-hallucinogenic present in large variety of plant species throughout the world.
-long history of use in the Amazonia
-must be taken by parenteral routes, bypassing the digestive system, insufflation of dry snuff made from plants w DMT
-can be smoked or injected but not traditional routes of administration... rapid onset, duration 15-30 minutes
-tryptophan: essential amino acid that helps body make proteins... body changes it into serotonin
Actions monoamine oxidase on DMT
-cannot take DMT orally because of efficient oxidation, (producing non-Psychoactive compounds) by the enzyme MAO in digestive system
-it won't be effective if you eat it because enzyme MAO make it inactive
Enzymes: aromatic-amino-acid decarboxylase, N-methyl transferase
-Aromatic: a pyridoxine-dependent enzyme that decarboxylates L-DOPA and 5-hydroxytryptophan to make dopamine and serotonin
-N-methyl transferase: one of two enzymes involved in metabolism of histamine along w diamine oxidase
Amazonian jungle, shamanic ritual: Epena snuff from Virola
-long history of use in DMT
-insufflation of a dry snuff made from plants containing DMT
-Virola: epena snuff from bark
-Anadenanthera peregrina: cohoba and yopo snuffs from seeds
-Amazonian tribal peoples long ago discovered a way of preparing DMT that makes it orally active
Ayahuasca = "vine of the soul/spirit"
-Ayahuasca: Banisteriopsis caapi
-Ay brew (aka yagé)... other plant mixtures sometimes present
-Ay vine (now known to contain MAOIs, harmine and harmaline)
-plant containing DMT... psychotria viridis or Diplopterys cabrerana
ayahuasca-based religions
-tribal ayahuasca use in Brazil has migrated into cities and syncretic spiritual practices ...combining elements of Christianity, other indigenous religious practices and ayahuasca) founded
-two major faiths: Santo Daime and União do Vegetal (UDV)
-Santo Daime: use, within a ritual context, the sacramental enteogen beverage known as ayahuasca, liturgical religion, which consists in sharing the sacramental tea in appropriate dates
-União do Vegetal: "the union of the plants", drink ayahuasca tea
Supreme Court 2006 USA vs. UDV
-UDV petitioned federal court to prevent government from interfering with UDV's use of hoasca used during religious ceremonies that contains a drug prohibited by the Controlled Substances Act
-argued Religious Freedom Restoration Act, prohibits substantial imposition on religious practices in the absence of a compelling government interest, established their right to use hoasca.
-UDV won
Ayahuasca tourism impacts on Amazonians
-westerners flocked to the Amazon to get a taste of ayahuasca
- popularized as mind-blowing, life-altering, universe-opening ...
-cultural appropriation
-as ayahuasca has become more popular ... pseudo shamans have sprung up ... rituals have lost their original power and the ceremonies are adapted to appeal to foreigners ... has become commercialized/exploited
-some locals altered original traditions to conform to foreign-constructed image as a selling tactic ... betrays the authenticity of their culture
"Good Friday Experiment" 1962, Walter Pahnke and Timothy Leary
-designed by Pahnke in 1962 to determine if psilocybin could elicit religious/spiritual experiences in theology students in a religious setting
-wrote his doctoral thesis on the results of the study under the auspices of his advisors Timothy Leary and Richard Alpert (Ram Dass)
-double-blind experiment: gave 10 theology students 10 mg of psilocybin during a Good Friday church service, 90% of students in the psilocybin group reported religious or mystical experiences
experiments: mystical type psilocybin experiences
...
Dock Ellis No-Hitter
-baseball player who pitched a No-Hitter on LSD ... played an entire baseball game while tripping on LSD
Morning Glory
-LSA: lysergic acid amide close chemical cousin to LSD
-found in seeds of some species in of morning glory ... family Convolvulaceae
-contains components similar to LSD
ololiuqui and lysergic acid amide
-morning glory seeds Ololiuqui in Nahuatl language of the Aztecs ... meaning "round thing"
-contain LSA
Convolvulaceae
-the morning glory family
Tabernanthe iboga root
-ibogaine
-root bark of the west African iboga plant
-ritual use in Gabon, Africa
-chemical ibogaine isolated and identified in 1901
-classical psychedelics effects
-5HTR (serotonin) agonist, SSRI, NMDA-Glur antagonist, mu-opioid agonist, kappa opioid agonist
-anti-addiction properties ... for opioids
-higher risk of toxicity than other classical psychedelics... cardiovascular stress, cardiac arrhythmia, death
Bwiti adolescent rite-of-passage-ritual and iboga root
-initiates adolescent into adulthood
-use the root ... induce powerful state of consciousness
Ibogaine and opioid addiction
-ibogaine therapy for opioid addiction
Classical psychedelics as 5HT2A serotonin receptor agonists
-psychedelics promote structural and functional neural plasticity ... enhance synapse changing effects
-classical and 5HT2A serotonin receptor agonists ... serotonergic nerve fibers emerging from the raphe nuclei in the brainstem innervate the entire brain
GPCRS
-serotonin receptors are GPCRS
Plasticity and psychedelics
-promote structural and functional neural plasticity
Salvia divinorum route of administrative
-"sage of divination"
-for shamanic use: oral-buccal, fresh leaves are chewed and held in mouth
Native location of Salvia
-Sierra Mazateca mountains
Salvinorin A
-Active compound in the hallucinogenic plant Salvia divinorum; acts as a kappa- receptor agonist.
-major identified psychoactive component in Salvia
-not an alkaloid
-binds with high specificity to kappa-opioid receptor and nothing else
Current psychedelic science
-psilocybin entering Phase III, FDA clinical trials for depression and anxiety
-MDMA entering Phase III FDA clinical trials for PTSD
MDMA differences from classical
Alexander "Sasha" Shulgin
-1965: re-synthesized and tested by chemist Alexander "Sasha" Shulgin... Berkeley Graduate
-wrote first publication on MDMA in humans
MDMA recreational use and name "ecstasy"-Schedule I
-1980s: recreational use and media attention, introduction of the name "ecstasy" figured out its fun to take this and go dancing
Positive effects of MDMA
Negative effects of MDMA
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