Some Key Concepts from “Drugs and the Brain” – Fall 2020 – FINAL

Useful as a guide for further study; not intended as an exhaustive list.

Lecture 1 (8/27)
• history of contemporary science: began with astronomical observation
• physics -> chemistry -> biology -> neuroscience -> how to incorporate mind?
• physicalism (physical materialism), world view, reductionism
• drug, psychoactive drug
• shaman, plant medicines, allies
• reduction of plant powers to specific chemicals
• pharmacology, psychopharmacology, pharmakon
• Paracelsus
• drug-related deaths in the U.S.
• war on drugs, monetary cost and cost in human suffering
• incarceration, felony disenfranchisement

Lecture 2 (9/1)
• routes of drug entry and approximate time to reach the brain
• oral-digestive route
• liver and first-pass metabolism
• parenteral routes: intraoral (sublingual, buccal), intranasal (insufflation),
rectal, transdermal
• injection routes: IV, IM, IP, subcutaneous
• elimination of chemical compounds from the body, liver metabolism
• drug half-life or lifetime in body
• concept of blood-brain barrier
• bonding properties for H, O, N, and C
• identifying atoms in molecular structures
• molecular structures: water, ethanol
• scales in biology, sizes of molecules
• benzene ring, electrons (bonds) shared over entire molecule
• alchemy to chemistry
• periodic table
• H,O,N,C: the big 4 in composition of human body
• H2O and polarity
• hydrophobic/lipophilic molecules
• hydrophilic/lipophobic molecules
“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 1

Lecture 3 (9/3)
• macromolecules of biology: carbohydrates, fats, proteins, nucleic acids
• phospholipids and lipid-bilayer cell membrane
• amino acids and proteins
• blood-brain barrier (BBB)
• crossing the BBB: diffusion and transport
• dimensions of molecules and cells
• human brain, neurons, glia
• synapses: electrical and chemical
• neurotransmitters and neurotransmitter receptor proteins
• agonist, antagonist
• central nervous system (CNS), peripheral nervous system (PNS)
• autonomic nervous system (ANS)
• sympathetic and parasympathetic branches of ANS
• norepinephrine, acetylcholine
• sympathomimetic, sympatholytic, parasympathomimetic,, parasympatholytic
• behavioral v. molecular similarities and differences
• pupil dilation: mechanism, pharmacology
• lung airway (bronchiole) dilation: mechanism, pharmacology

Lecture 4 (9/8)
• solanaceous plant family; characteristics, examples
• food plants: tomato, potato, eggplant, chili
• Carl Linnaeus, binomial classification: family, genus, species
• alkaloid, basic nitrogen, bitter, poison
• acetylcholine receptors (AChR): muscarinic, nicotinic
• tropane alkaloids: atropine, scopolamine
• muscarinic AChR antagonists: peripheral and CNS effects
• ANS: parasympatholytic effects
• CNS: alterations in consciousness, mental confusion, hallucinations
• Atropa belladonna: deadly nightshade
• angel’s trumpet: Brugmansia
• henbane, mandrake, Datura

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 2

Lecture 5 (9/10)
• tobacco, Nicotiana tabacum
• Thanatopathia
• Pharmako/Poeia pentagram of drug classification
(based on the categories of Louis Lewin from 1924)
• history of shamanic use in the Americas
• routes of entry into the body of tobacco
• Richard Evan Schultes
• Jean Nicot
• Sir Walter Raleigh
• King James I, “A Counterblaste to Tobacco”
• Nicotiana tabacum, Nicotiana rustica
• nicotine; nicotinic acetylcholine receptors
• acute effects of tobacco/nicotine, tolerance
• cigarette consumption in 20th century USA: 1900-2000
• cigarette consumption v. lung cancer deaths 1900 - 2010
• tobacco mortality in USA
• toxic effects of tobacco use on health: cardiovascular,
carbon monoxide, smoke, fetal development, neonatal health
• second-hand smoke
• third-hand smoke
• smoking bans in USA, University of California
• smoke-free movies program (UCSF)
• vaping: glycerol, propylene glycol
• addiction
• nicotine withdrawal
• warning labels on tobacco products in and outside USA
• tobacco companies v. FDA on graphic labeling

Lecture 6 (9/15)
• attractive/rewarding/reinforcing effects of tobacco
• strategies for quitting tobacco use
• pharmacologic aids to quitting:
nicotine replacement, nAChR agonists, bupropion antidepressant
• hookah
• clove cigarettes
• 2009 US Federal law imposing additional regulation of cigarettes
“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 3

 • cigarette use (by age) trends in USA
• prevalence
• National Survey on Drug Use and Health (NSDUH)
• cigarette use v. education level
• role of vaping in decreasing use
• Monitoring the Future survey
• nicotine as an insecticide, neonicotinoid insecticides
• five most widely used psychoactive drugs
• Areca catechu: areca (betel) palm, areca (betel) nut
• Piper betle leaf, pepper family
• paan (India), doma (Bhutan)
• arecoline: muscarinic AChR agonist, PNS and CNS effects
• slaked lime = calcium hydroxide

Lecture 7 (9/17)
• ethyl alcohol, ethanol, al-kahul (chemical structure)
• fermentation, yeast (Saccharomyces cerevisiae)
• Vitis vinifera
• wine, mead, sake
• beer, ale, malt liquor
• brewing: malting, mashing, fermentation
• beer admixtures, hops (Humulus lupus)
• distillation, distilled spirits
• azeotrope
• proof
• metabolism of ethanol: ethanol -> acetaldehyde -> acetic acid
• enzymes: alcohol dehydrogenase, acetaldehyde dehydrogenase
• time course of metabolism
• blood alcohol level (BAL) or concentration (BAC)
• acute effects of alcohol and corresponding BAL
• LD-50
• therapeutic index (TI)
• prevalence of alcohol use and abuse
• economic cost of alcohol abuse
• alcohol-related motor vehicle accidents, MADD, DUI enforcement
• breathalyzer

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 4

 • NSDUH prevalence data: age groups with highest prevalence
• chronic problems associated with alcohol:
• abuse/addiction
• damage to liver,pancreas, nervous system; increased cancer risk
• teratogenic effects: fetal alcohol syndrome
• potential beneficial effects of light alcohol use
• ethanol neurochemistry:
• GABA (gamma-amino-butyric acid), glutamate, adenosine

Lecture 8 (9/22)
• sedative-hypnotic drugs
• alcohol and other sedative-hypnotic acute effects
• alcohol and other sedative-hypnotic withdrawal effects
• sedative-hypnotics all facilitate GABA (inhibitory) action
• general anesthetics (inhalation anesthetics): diethyl ether, halothane, others
• inhalants: inhalation (huffing) of petroleum distillates
• barbiturates: low TI; no longer widely prescribed medically
• continued use in lethal injection (death penalty execution)
• benzodiazepines: higher TIs; very widely used
• involvement in overdose deaths, mostly in conjunction with opioids, alcohol
• high risk of dependence: rebound anxiety and insomnia
• widespread overuse
• memory and other cognitive impairments
• possible increased risk of dementia with long-term use
• hypnotic pharmaceuticals: “z-drugs”
• sleep hygiene
• large variety of plants with sedative-hypnotic properties
• absinthe, complex distilled alcoholic herbal beverage
• wormwood: Artemisia absinthium
• large variety of terpenes and terpenoids
• history of popular use in European artistic community
• Artemisia annua: antimalarial properties
• artemesinin, Nobel Prize (2015), Tu Youyou
• thujone from wormwood, effects at GABA receptor
• history of absinthe regulation, temperance movement
• current legal status of absinthe in EU and USA

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 5

Lecture 9 (9/24)
• Food and Drug Administration (FDA)
• levels of FDA regulation of drugs
• OTC, prescription, controlled substance
• drug abuse, abuse potential, addiction
• Whiskey Tax, Whiskey Rebellion
• Harrison Narcotics Act (1914)
• 18th and 21st Amendments to US Constitution
• alcohol prohibition in the US (1920-1933)
• Volstead Act, legal definition of “intoxicating liquor”
• Harry J. Anslinger, Federal Bureau of Narcotics (created in 1930)
• Marihuana Tax Act (1937)
• Federal Controlled Substances Act (CSA) (1970)
• Drug Enforcement Administration (DEA)
• Controlled Substance Schedules: I, II, III, IV, V
• special status of Schedule I; criteria for Schedule I substance
• general idea of what kinds of drugs in the various schedules
• Uniform Controlled Substances Act (1970)
• United Nations Convention on Psychotropic Substances (1971)
• US Sentencing Commission (1984)
• Controlled Substances Analogue Act (1986)
• cannabis: federal vs. state regulations, medical marijuana laws
• 10th Amendment to US Constitution, Commerce Clause
• 2018 Farm Bill and “hemp”

Lecture 10 (9/29)
• Cannabis origins and history
• camp followers, domestication of plants and animals
• plant family: Cannabaceae
• ancient history of use
• medicinal and psychoactive properties of cannabis
• routes of administration/entry
• cannabis: preparations and names
• non-psychoactive use: fiber, food
• cannabis as pharmakon
• set and setting

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 6

 • poison properties: abuse/addiction, psychosis, cognition,
motivation,short-term memory
• THC and its discovery
• cannabinoids
• Raphael Mechoulam
• cannabinoid receptors
• anandamide, endocannabinoids
• retrograde signaling at chemical synapse, neuroplasticity
• endocannabinoids vs. phytocannabinoids
• extent of endocannabinoid system in body physiology

Lecture 11 (10/1)
• THC concentrations in Cannabis
• trichromes
• pharmacokinetics of smoked/vaporized v. oral-digestive THC
• synthetic cannabinoids; toxic effects: nausea, vomiting, anxiety,
confusion, delirium, psychosis, cardiovascular stress, seizures
• phytocannabinoid entourage effects
• terpenes and terpenoids
• cannabinoid-terpene-terpenoid entourage effects
• Marinol® and Epidiolex®
• opioid overdose epidemic
• availability of medical cannabis vs. opioid use and abuse
• opium poppy: Papaver somniferum
• California poppy: Eschscholzia californica
• poppy seeds
• opium, harvesting of opium
• acute effects of opium
• routes of entry of opium: oral-digestive, smoking
• Friedrich Wilhelm Sertürner (1803)
• opiates: morphine, codeine, thebaine
• opioids: naturally-occurring, semi-synthetic, synthetic
• heroin, Bayer
• fentanyl, carfentanil

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 7

Lecture 12 (10/6)
• opioid routes of entry
• poison qualities of opioids: acute toxicity from respiratory depression
• US epidemic of opioid overdose deaths
• aggressive marketing and poor regulation of pharmaceutical opioids
• lawsuits against pharmaceutical companies
• opioid antagonist: naloxone (Narcan®)
• poison qualities of opioids: high addictive potential
• opioid withdrawal
• transition from pharmaceutical opioids to heroin (access,
cost-effectiveness)
• treatment interventions
• opioid substitution therapy
• opioid receptors
• endorphins
• neuropeptide neurotransmitters
• kratom
• opium history: India, China, 19th-century Opium Wars
• Treaty of Nanking (1842), Hong Kong

End of Material for Midterm Exam One (covering Lectures 1-12)

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Lecture 13 (10/8)
• caffeine, botanical xanthines
• acute effects of caffeine
• toxicity of caffeine
• caffeine dependence and withdrawal
• adenosine neurotransmitter, adenosine receptor
• soda, energy drinks (Red Bull®, etc.) (taurine)
• caffeine “stay-awake” pills
• Camellia sinensis
• green tea, black tea
• tea history: Buddhism in Asia, introduction to Europe
• Dutch East India Company and British East India Company
• Coffea arabica and Coffea robusta
• coffee processing: from berry to brew, fermentation, roasting
• coffee chemistry: deterioration of coffee bean
character after roasting and grinding
• history of coffee: origins, movement north into Middle East and Europe
• coffee and Islam
• coffee houses in Europe, and in London; coffee houses and politics
• coffee houses and capitalism
• Berkeley: Alfred Peet
• espresso, polyphasic nature of espresso
• drugs in wastewater
• Theobroma cacao
• theobromine, caffeine
• history of cacao: Mayan, Aztec
• processing: from cacao bean to chocolate
• Berkeley: Robert Steinberg, Scharffen Berger Chocolate
• other caffeine-containing plants: kola, guanana, guyusa, yerba mate
• caffeine in floral nectar and impact on honeybee behavior

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 9

Lecture 14 (10/15)
• cultivated coca: Erythroxylum coca
• Mama Coca: revered, sacred plant for millennia
• long history of safe oral-buccal use by indigenous peoples
• cocaine mechanism of action
• norepinephrine and dopamine reuptake, PNS and CNS effects
• toxic effects, addiction
• Sigmund Freud and cocaine
• Vin Mariani, Coca Cola
• cocaine: routes of entry
• free-base cocaine (crack)
• sentencing inequality for cocaine salt vs. crack cocaine (began in 1986)
• Fair Sentencing Act 2010
• abuse potential of cocaine
• cocaine and sugar analogy

Lecture 15 (10/20)
• Benzedrine inhaler
• amphetamine mechanism of action: norepinephrine and dopamine
reuptake transporters
• locus coeruelus (norepinephrine), ventral tegmentum (dopamine)
• PNS and CNS effects
• medical journal advertisements: amphetamine
• stimulant, anti-depressant, weight loss
• military stimulant use
• narcolepsy
• ADHD
• From Obetrol® to Adderall®
• direct-to-consumer marketing: FDA, 1997
• amphetamine: toxic effects, withdrawal, addiction
• amphetamine, methamphetamine: routes of entry, social context
• Blitzed: Drugs in the Third Reich
• modafinil, Provigil®, Nuvigil®
• ephedrine, pseudoephedrine
• Ephedra
• Mormon Tea
• Catha edulis, khat, qat, chat

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 10

Lecture 16 (10/22)
• characteristics of addiction
• clinical diagnostic criteria: ICD-10 and DSM-5
• high prevalence of addiction and possible social causative factors
• views of addiction: from moral shortcoming to brain disease
• James Olds: learning in rats, brain stimulation
• reward pathway: ventral tegmentum ! nucleus accumbens ! frontal cortex
• dopamine and reward
• neuroscience of addiction and quest for biological interventions
• Rat Park Experiment
• failure to pursue the study of sociocultural factors
• addiction treatment
• 12-step programs

Lecture 17 (10/27)
• mental health disorders: feeling, thinking, action
• high prevalence of mental health disorders
• mental health concern ! mental health disorder (illness)
• psychiatric mediations: prevalence of use
• psychosis, schizophrenia: symptoms, prevalence and risk
• Asian medical treatment: snakeroot (reserpine)
• phenothiazine antipsychotics
• classical antipsychotics: D2 dopamine receptor antagonists
• new-generation antipsychotics: dopamine & serotonin receptor antagonists
• dopamine hypothesis of psychosis
• depression: symptoms & prevalence
• depression as a bio-psycho-social condition
• cognitive-behavior therapy (CBT) for depression
• comparison clinical trials: CBT vs. medications
• medications: historical amphetamine
• monoamine oxidase inhibitors (MAOIs)
• tricyclic antidepressants (TCAs)
• selective serotonin reuptake inhibitors (SSRIs)
• monoamine hypothesis of depression
• monoamine brain neural circuitry: serotonin (raphe nuclei),
norepinephrine (locus coeruleus), dopamine (ventral tegmentum)
• GPCR receptors: diversity and amplification of effects (complexity!)

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 11

 • SSRIs: professional and popular enthusiasm, cosmetic psychopharmacology
• antidepressant usage by age group, duration of use
• SSRI discontinuation syndrome = withdrawal

Lecture 18 (10/29)
• FDA approval process for new drug
• preclinical investigations, rodent tests for depression
• human clinical trials: phases 1, 2, and 3
• placebo effects: double-blind, placebo-controlled, clinical trials
• efficacy of antidepressants compared to placebo
• from published data to all data
• Kirsch et al. analysis after using Freedom of Information Act
• placebo effects = belief / expectation effects
• placebo effects depend up one’s worldview (metaphysical framework)

Lecture 19 (11/3)
• placebo/expectation/holotropic effects expanded:
• surgeries, BIMAL surgery, cognitive testing, everything?
• mind-body medicine
• recent clinical studies with psychedelics
• psilocybin, LSD, MDMA, ketamine
• anxiety, depression, PTSD, addiction
• FDA “breakthrough therapy”
• history of clinical studies (1950s-1960s)
• Bill Wilson: role in AA and views on LSD
• history of study of spiritual/mystical experiences (1960s)
• psychedelic, hallucinogen, psychotomimetic, entheogen
• origin and meaning of the word “psychedelic”
• Humphry Osmond, Aldous Huxley
• characteristic effects of psychedelics on mind, pharmakon
• impact of set and setting
• psychedelic use prevalence and lack of population
negative impact on mental-health
• psychedelics are all Schedule I

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 12

Lecture 20 (11/5)
• LSD history and discovery
• Albert Hofmann
• ergot fungus, ergotamine
• LSD, potency, dose ranges, typical psychedelic dose
• early clinical research and psychiatric use
• Delysid®
• LSD history timeline
• The Doors of Perception, R. Gordon Wasson article in LIFE
• Timothy Leary, Richard Alpert (Ram Dass)
• Ken Kesey, the Merry Pranksters, Acid Tests, Tom Wolfe
• adverse effects of LSD
• LSD and “anti-establishment counterculture”
• laws against LSD and all other psychedelics

Lecture 21 (11/10)
• Albert Hofmann, psilocybin, psilocin
• ololiuqui, Richard Schultes, morning glories
• Albert Hofmann, lysergic acid amide (LSA)
• ergot fungi symbiosis
• Eleusinian Mysteries
• San Pedro cactus, peyote cactus
• history of ceremonial use
• impact of Spanish conquest
• Native American Church (1918)
• Employment Division, State of Oregon vs Al Smith, US Supreme Court (1990)
• Religious Freedom Restoration Act, US Congress (1993)
• American Indian Religious Freedom Act Amendment, US Congress (1994)
• mescaline, Arthur Heffter
• John Symthies and Humphry Osmond, biochemical theory of schizophrenia (1952)

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 13

Lecture 22 (11/12)
• Gordon Wasson, Oaxaca
• teonanacatl = flesh of god, Richard Schultes
• Maria Sabina
• Albert Hofmann, psilocybin, psilocin
• diversity of Psilocybe mushrooms
• ancient mushroom rock art
• know the risk of deadly poisonous mushrooms
• Harvard psilocybin project
• Walter Pahnke, Good Friday experiment
• end of research 1970s

Lecture 23 (11/17)
• end of research 1970s, re-initiation of research ~1990
• psilocybin and mystical experiences: Johns Hopkins (2006)
• measuring “mystical experience”
• psilocybin and anxiety and depression related to terminal illness, FDA Phase II
• psilocybin and depression, FDA Phase III clinical trial
• classical psychedelics
• dimethyltryptamine (DMT), tryptophan
• enzymes: aromatic-amino-acid decarboxylase, N-methyl transferase
• Amazonian jungle, shamanic ritual: epená snuff from Virola
• actions of monoamine oxidase (MAO) on DMT
• ayahuasca = “vine of the soul/spirit”
• Banisteriopsis caapi, harmine, harmaline
• Psychotria viridis
• ayahuasca-based syncretic religions: Santo Daime & União do Vegetal (UDV)
• Supreme Court, USA v. UDV (2006)
• DMT in human body?
• DMT meme

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 14

Lecture 24 (11/19)
• Tabernanthe iboga
• Bwiti rite-of-passage ritual and iboga plant
• ibogaine
• classical psychedelics as 5HT2A serotonin receptor agonists
• G-protein coupled receptors (GPCRs)
• neuroplasticity and psychedelics
• Alexander “Sasha” Shulgin
• mescaline chemical derivatives
• mescaline and alpha-methyl mescaline
• serotonin and alpha-O-dimethyl serotonin
• post-Shulgin synthetics and the dangers of the illicit market
• MDMA and its differences from classical psychedelics
• MDMA recreational use and name “ecstasy” - schedule I
• positive and negative effects of MDMA
• MDMA neurochemistry: serotonin release
• MDMA phase 3 clinical trials for PTSD

Lecture 25 (11/24)
• Salvia divinorum: origins and ritual use
• salvinorin A, kappa-opioid receptors
• receptor specificity: salvinorin A versus LSD
• dissociative anesthetics: phencylidne (PCP) and ketamine
• dissociative anesthetic versus general anesthetic
• surgical uses of ketamine
• exploration of antidepressant effects
• IV infusion and expense of sessions
• esketamine, patent, intranasal administration, FDA approval
• large placebo effect?
• enormous expense, no psychotherapy
• the future: ketamine-assisted psychotherapy?

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 15

Lecture 26 (12/1)
• southern California cave painting representing Datura and
suggesting ritual use
• soma, Rig Veda
• nitrous oxide, N2O
• overdose and non-overdose drug mortality
• ritual structure loss and expansive commodification
• pervasive mental illness: systemic causes
• gaming, internet, and social media addictions
• screen time and depression link
• development of available psychedelic therapy: MDMA, psilocybin, ketamine
• proliferation of companies planning to market psychedelic medicines and
psychedelically-assisted therapy
• tension in the field: commodification and profit versus open science
• how to maintain ritual and respect
• investigating consciousness, William James
• mind, brain, and body

Midterm Exam Two (covering Lectures 13-26)

“Drugs and the Brain” Fall 2020 Key Concepts FINAL - 16