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Drugs and Behavior, Carl Hart, psychology, psychopharmacology

why have plants with psychoactive effects been used in religious practices all over the world?

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What is the difference between phantastica and deliriants?

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Give an example of indole hallucinogens

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Give an example of catechol hallucinogens

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Describe the relationship of LSD to the ergot fungus

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Summarize early research and evidence on LSD for use in interrogation and in psychotherapy

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What is meant by "hallucinogen persisting perception disorder"

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What is the major active ingredient of psilocybe?

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What is the major active ingredient of morning glories?

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what is the active ingredient of ayahuasca?

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What is the major active ingredient of peyote?

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What is the major active ingredient of San Pedro cactus?

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What is the major active ingredient of Amanita?

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What is the major active ingredient of Salvia divinorum?

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What is the chemical relationship among DOM, MDA, and MDMA

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compare and contrast PCP effects with those of LSD

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How do anticholinergic hallucinogens act in the brain?

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animism

-common theme in most of world's religions
-belief that animals, plants, rocks, so on derive their special characteristics from a spirit contained within the object
-hallucinogens fit into this view; if plant contains a spirit, then eating the plant transfers to that person who eats it and can give the consumer special powers/insights

shaman, medicine man/woman

-individuals who pass down knowledge of drug-containing plants, are experts on obtaining power from spirit world
-involved in origins of religion and of modern medicine

phantastica

term for hallucinogens dubbed by Lewin in 1931

Examples of phantastica drugs

Peyote
Psilocybin
LSD

psychedelic

-"mind-viewing"
-term used in the 1960s as users believed hallucinogens allowed them to see into their own minds

psychotomimetic drugs

-"mimicking psychosis"
-term for hallucinogens; implies they produce dangerous effects and a form of mental disorder, which is a controversial conclusion

entheogen, entactogen

newer terms used to describe group of drugs known as hallucinogens
-entheogen: used to describe substances (sacred mushrooms) through to create spiritual experiences
-entactogen: "to produce a touching within"; used to describe substances (MDMA) through to enhance empathetic feelings

classical phantastica

capable of altering perceptions while allowing person to remain in communication with present world
-you can be aware of both fantasy world and real world at the same time
-more purely hallucinogenic effects; do not produce much acute physiological toxicity (little danger of dying from overdose)

2 major classes of classical phantastica, grouped according to chemical structure

1) indole hallucinogens
2) catechol hallucinogens

Indole hallucinogens

-strucutre of 5-HT referred to as indole nucleus
-structure shared by LSD and psilocybin

What is LSD's claim to fame?

-d-Lysergic Acid Diethylamide
-MOST POTENT OF THE HALLUCINOGENS
-brought hallucinogens to public eye in 1960s

Where does LSD come from?

-not found in nature; synthesized from ergot alkaloids extracted from ergot fungus CLAVICEPS PURPUREA, mold that grows on grain, esp. rye and results in illness ergotism
-discovered by Dr. Albert Hofmann in Basel, Switzerland

The psychedelic '60s

1965-1975

What attracted attention to LSD?

it's potency; usually active with only .05 mg, in some people as low as .03; mescaline requires 4,000x as much to produce psychoactive effects

LSD replaced sodium pentothal, scopolamine, and amphetiamines as what?

a modern truth serum used as adjunct to psychotherapy to access "subconscious mind"

What is history of LSD research?

-discovered by Dr. Albert Hofmann in Basel, Switzerland; attracted attention bc of its potency
-initial thrust of research was related to its alleged ability to access the "subconscious mind"
-U.S. military conducted unethical experiments w/LSD & hallucinogens btwn 1950s-1960s on unwitting soldiers/civilians, most who were drug-naiive and as a result, thought they were losing their minds
-NIMH stopped its in-house LSD research on humans in 1968, stopped funding university human research on LSD in 1974
-National Cancer Institute and National Institute on Alcohol Abuse stopped psychedelic research in 1975 bc it was deemed nonproductive
-since that time, LSD research has been conducted on animals, focusing on understanding mechanism of action at neural level

True or False: drug effects are not determined by pharmacology (drug-receptor interactions) alone?
Support your answer with an example

TRUE. Other factors:
-situation in which drug use occurs
-user's level of experience with drug
-U.S. army's experimentations with hallucinogens in 1950s-1960s exquisitely illustrates this point

Timothy Leary

psychologist, popular advocate for LSD use
-conducted "experiments" on LSD and psilocybin at Harvard in early 1960s that were unethical and lacked scientific rigor
-left Harvard (fired?); started religion, League of Spiritual Discovery where LSD was the sacrament, motto "Turn on, tune in, and drop out"

when did LSD use peak?

1967-1968

LSD pharmacology
absorption (location)
metabolism (time, location)
excretion

-odorless, colorless, tasteless, one of most potent chemicals known
-absorption: rapid absorption from gastrointestinal tract, taken orally by most humans
-not selectively taken up by the brain
-metabolized: rapidly in liver-->half of LSD in blood metabolized every 3 hours
-excreted: as 2-oxy-lysergic acid diethylamide (inactive)

LSD tolerance

-tolerance develops rapidly; repeated daily doses bc ineffective in 3-4 days BUT recovery is rapid, so weekly use of same dose of LSD is possible
-cross-tolerance among LSD, mescaline, and psilocybin

Has physical dependence to LSD or any hallucinogens been demonstrated?

NO

autonomic symptoms of LSD, sympathomimetic agent,

-dilated pupils, elevated temp and blood pressure, increase in salivation

Theory of LSD's neural mechanism

works by stimulating serotonin-2A subtype of receptors (drug shaped like serotonin so it is likely it works on serotonin receptors to produce effects)

True or False: much of our knowledge about the effects of LSD and other hallucinogens is anecdotal?

True

What do most scientists agree is the most important LSD-related effect?

modification of perception, particularly visual images

synesthesia

"mixing of senses"; sounds might appear as visual images

How long does an LSD trip last?

6 to 9 hours
-can be attenuated through administration of chlorpromazine (schizophrenia medication) intramuscularly

effects of LSD

autonomic responses in first 20 min--dizzy, hot/cold--these diminish and are less focus of attention as alteration of sensations, perceptions, mood develop over next 30-40 minutes--abnormal color perception, space/time disorders, visual hallucinations
-aft 1 hr of taking, intoxication in full bloom; not until end of 2nd hour that changes occur in perception of self--center around depersonalization--feel out of body
-2 types of reactions in this stage: expansive and constricted
1) expansive: good trip--unlock insights, creativity
2) constricted: bad trip--user shows little movement, bc paranoid, exhibits feelings of persecution

Hallucinogen Persisting Perception Disorder

term in DSM-IV-TR
-individual with this disorder has not used drug recently, but has re-experienced 1+ of perceptual symptoms or "flashbacks" experienced while intoxicated, such as geometric hallucinations, intensified colors, etc.
-few cases reported

2 adverse reactions of LSD

1) "flashbacks" or Hallucinogen Persisting Perception Disorder (few cases reported)
2) panic reaction--occurs while under influence--can be dealt with by talking person through experience, or, in severe cases, administering benzodiazepine or another sedative

Does LSD increase creativity or release creativity blocked by our inhibitions?

no evidence of this

Is LSD useful in treating alcohol dependence?

no evidence

Is LSD useful in reducing pain/depression of patients with terminal cancer?

some evidence

Is LSD useful in reducing cluster headaches

some evidence

Primary active ingredient in magic mushrooms

psilocybin, an indole hallucinogen

catechol hallucinogen

mescaline

indol hallucinogens

LSD, psilocybin

Gordon Wasson

first outsider to participate in magic mushroom ceremony, wrote about experiences in 1957 Life article

most well-known psychoactive mushroom

Psilocybe mexicana

psychoactive mushroom that grows on cow dung

psilocybe cubensis; several toxic look-alikes

the hallucinogenic effects of psilocybin are similar to LSD, and the catechol hallucinogen mescaline, true or false

true

there is a cross-tolerance among LSD, psilocybin, and mescaline, true or false?

true

Good Friday experiement

1963: Walter Pahnke conducted experiment to investigate the ability of psilocybin to induce meaningful religious experiences
-20 Christian theological seminary students assigned to 2 groups--1 received psilocybin, the other nicotinic acid as "placebo"
-students attended Good Friday service following administration
-Psilocybin occasioned mystical experience, where nicotinic acid did not
-compromising features: participants explicitly told they would be taking psilocybin, and it was conducted in group setting which compromised blinding procedures and influenced findings

Roland Griffiths and colleagues

used rigorous double-blind study to investigate acute (7 hours) and longer term (2 months) mood-altering and psychological effects of psilocybin (30 mg) relative to methylphenidate (active placebo)
-psilocybin found to increase mystical experience

ololiuqui

seeds of morning glory plant Rivea corymbosa
-have several active alkaloids as well as d-lysergic acid amide
-about 1/10th as active as LSD

active ingredient in psilocybe mushrooms

psylocybin

DSM: 5 points
-history of use?
-active ingredient of what?
-how do you use?
-effects?
-unique characteristic?

-dimethyltryptamine (DMT); never been widely used in the U.S., but on worldwide basis, it is one of the most important, naturally occurring hallucinogenic compounds, it occurs in many plants
-active ingredient in Cohoba snuff
-normally ineffective when taken orally (bc MAO enzyme breaks it down quickly); usually snuffed, smoked, or taken by injection
-effects brief, no matter how it is used
-ONLY hallucinogen to which tolerance to its psychological effects DOES NOT develop

Ayahuasca

"vine of the soul" --used for brew made from 2 vines containing harmaline and DMT
-harmaline inhibits MAO from breaking down DMT, which allows the plants together to be used as psychoactive religious sacrament

catechol hallucinogens

-based on catechol nucleus structure of NE and DA

catecholamine neurotransmitters

NE and DA
"Colleen NE Doyle"

peyote

a type of hallucinogenic cactus (catechol hallucinogen)

what is the primary active agent in peyote cactus?

mescaline

What psychoactive agent is used in religious ceremonies of Native American Church?

peyote

active ingredient in San Pedro cactus

mescaline
-contains less than half the amount of mescaline the Peyote cactus does; use associated with more adverse side effects than desired hallucinogenic experience

pharmacology of mescaline
-absorbtion
-blood-brain barrier
-metabolism
-excretion

-absorbed readily if taken orally
-poorly passes blood-brain barrier (which is why high doses are required)
-maximum concentration in brain after 30 to 120 minutes; about half removed from body in 6 hours
-most excreted unchanged in urine; metabolites are not psychoactive

does tolerance develop more quickly in mescaline or LSD?

LSD; it develops more slowly in mescaline
-there is cross-tolerance between them

True or False? Catechol hallucinogens act on NE and DA receptors?

FALSE! Although their structure is similar to NE and DA neurotransmitters, they act indirectly on the serotonin 2A receptor

True or False? large group of synthetic hallucinogens is chemically related to amphetamines?

True; MDMA, MDA, DOM are structurally similar to meth and amphetamine structures

MDMA

also called ecstacy or XTC

effects of MDMA are more similar to what drug than those of classical hallucinogens?

amphetamine and methamphetamine; increases sociability and euphoria, decreases appetite and sleep

anecdotal adverse affect of MDMA?

-"Suicide tuesday"--substantial release of 5-HT followed by marked reduction in NT leads to drop in mood
-No hard evidence

potential negative consequence of MDMA based on animal research?

large doses of MDMA given to lab animals can destroy 5-HT neurons; relevance and related findings for human recreational use is unclear

MDMA is what schedule drug

Schedule I; recreational use is prohibited

MDA

"love drug"; appears to produce effects similar to MDMA, though there is yet to be scientific study comparing 2 drugs

DOM

2,5-dimethoxy-4-methylamphetamine
-called STP on streets in 60s and 70s for "serenity, tranquility,and peace"
-actions/effects similar to mescaline and LSD

2-CB and 2-C-T7

phenylethylamines; chemical cousins to amphetamine series of hallucinogens; share rave scene with MDMA

deliriants

class of hallucinogens that have somewhat more of a tendency to produce mental confusion and loss of touch with reality

PCP, "Sernyl"

-phencyclidine, originally developed as an anesthetic; has hallucinogenic properties
-good anesthetic for monkeys, in humans it is medically safe but has psychologically troubling results so it was never marketed for human use; "dissociative anaesthetic"
-used for "tranquilizer guns" to immobilize stray, wild, or dangerous zoo animals
-market name "Sernyl"

ketamine (ketalar) or "special k"

-dissociative anesthetic used in humans for 40 years
-causes hallucinations and delirium in 12% of patients
-known as party drug as "special k"; media attention caused DEA to add to Schedule III controlled substances in 1999

True or False? OTC cough suppressant can produce dissoative-type hallucinations?

True; dextromethorphan at very high doses can produce hallucinogenic effects

angel dust

street name for PCP sprinkled on plant material (i.e. oregano, parsley, alfalfa sold to unsuspecting youngsters as marijuana)

In late 1970s, what was the most common cause of drug-induced visits to the hospital emergency rooms?

PCP

restraint techniques on PCP users can be __________

ineffective; because they are anesthetized, so pain does not have as much of an effect
-is this much different from alcohol intoxicated arrest?

Rodney King and PCP

L.A.P.D. were videotaped beating Rodney King; said during trial they used such force because they believed King might have been "dusted"--under the influence of PCP--and there are gruesome legends of PCP users being impervious to pain

What receptor does PCP act on?

SIGMA
-previously Sigma was thought to be a subtype of opiate receptor, however, cyclazocine (some opiate activity, also reported to produce hallucinations) binds well to sigma, but morphine, nalozone, and other opiates do not;
THEREFORE, sigma receptor is better characterized as being selective for PCP, ketamine, and other similar drugs, rather than a type of opiate receptor

anticholinergic hallucinogens

-potato family contains all naturally occurring anticholinergic hallucinogens
-occupy acetylcholine receptor site but do not activate it; effect is to block muscarinic cholinergic neurons including parasympathetic system

what 3 characteristics separate anticholinergic hallucinogens from indole and catechol hallucinogens?

1) clouding of consciousness
2) no memory for period of intoxication
3) absence of vivid sensory effects

belladonna

anticholinergic hallucinogen
atropine is active ingredient of "nightshade"; used as poison and to dilate pupils
-reports that it can give sensation of flying to users; associated with witches and witchcraft

mandrake

anticholinergic hallucinogen
contains all 3 anticholinergic alkaloids
-close association w/love and lovemaking in Bible

Henbane

anticholinergic hallucinogen
highly poisonous substance

Datura

anticholinergic hallucinogen
-contains 3 alkaloids under discussion: atropine, scopolamine, hyoscyamine
-Chinese used to treat colds and nervous disorders; associated with Buddha
-associated with worship of Shiva in India and used in love potions
-used by Algonquin Indians in adolescent search for identity (known as Jamestown weed or Jimsonweed)

what is a medical use of anticholinergic hallucinogens?

-used to treat Parkinson's disease before introduction of L-dopa
-still widely used to treat pseudoparkinsonism produced by antipsychotic drugs

amanita muscaria musroom

-one of the most common poisonous mushrooms found in forests in many parts of the world
-associated with India's religion, "food of the gods" and Christianity's "tree of life"

2 active ingredients in amanita

-ibotenic acid
-muscimol: more potent than ibotenic acid; acts as antagonist at GABA receptors; results in confusion, disorientation in time and place, etc.
-drying of amanita mushroom promotes transformation of ibotenic acid to muscimol

salvia divinorum

member of mint family; translated as "diviner's sage"
-used in religious ceremonies, recently used as substitute for marijuana
-not currently listed as controlled substance in U.S.; used as legal hallucinogen
-effects last for up to an hour
-active ingredient is Salvinorin A; binds selectively to kappa opioid receptor where it acts as agonist; nearly as potent as LSD, in that an effect human dose is as little as 200 micrograms

True or False? LSD enhances emotionality, so real world is seen differently and is responded to with great emotion?

TRUE
-not only does it alter perceptual processes, it enhances emotionality

PCP produces ________ changes in body perception and __________ visual effects than LSD

PCP produces MORE changes in body perception and FEWER visual effects than LSD

Anticholinergic hallucinogens have been used recreationally, medically, and spiritually, as well as_____________________

poisons

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