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The Nature of Drugs Vol. 1: History, Pharmacology, and Social Impact
The Nature of History, Pharmacology, and Social Impact, Volume 1, presents lectures from Alexander “Sasha” Shulgin’s popular course on what drugs are, how they work, how they are processed by the body, and how they affect our society. Transcribed from the original lectures recorded at San Francisco State University in 1987, The Nature of Drugs series highlights Shulgin’s engaging lecture style peppered with illuminating anecdotes and amusing asides. Ostensibly taught as an introductory course on drugs and biochemistry, these books serve as both a historical record of Shulgin’s teaching style and the culmination of his philosophy on drugs, psychopharmacology, states of consciousness, and societal and individual freedoms pertaining to their use, both medicinal and exploratory. The Nature of Drugs, Volume 1 features course lectures 1 through 8 and offers Shulgin’s view on the origin of drugs, the history of U.S. drug law enforcement, human anatomy, the nervous system, the range of drug administrations, varieties of drug actions, memory and states of consciousness, and research methods. It lays the groundwork for Shulgin’s philosophy on psychopharmacology and society. The Nature of Drugs series presents the story of humanity’s relationship with psychoactive substances from the perspective of a master psychopharmacologist and beloved luminary in the study of chemistry, pharmacology and consciousness. Audiobook The Nature of Drugs, Volume 1 audiobook contains portions of the original 1987 recordings of Shulgin himself conducting his course and interacting with his students. Those original clips are interlaced with newly recorded narration that fills in portions with more optimal audio quality.
368 pages, Hardcover
Published June 8, 2021
73 people are currently reading
868 people want to read
About the author
Alexander Shulgin
17 books313 followersAlexander "Sasha" Theodore Shulgin[1] (born June 17, 1925) was an American pharmacologist, chemist and drug developer.
Shulgin was credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and post-traumatic stress disorder. In subsequent years, Shulgin discovered, synthesized, and bioassayed over 230 psychoactive compounds. In 1991 and 1997, he and his wife Ann Shulgin authored the books PiHKAL and TiHKAL on the topic of psychoactive drugs. Shulgin discovered many noteworthy phenethylamines including the 2C* family of which 2C-T-2, 2C-T-7, 2C-E, 2C-I, and 2C-B are most well known. Additionally, Shulgin performed seminal work into the descriptive synthesis of compounds based on the organic compound tryptamine.
Shulgin was credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and post-traumatic stress disorder. In subsequent years, Shulgin discovered, synthesized, and bioassayed over 230 psychoactive compounds. In 1991 and 1997, he and his wife Ann Shulgin authored the books PiHKAL and TiHKAL on the topic of psychoactive drugs. Shulgin discovered many noteworthy phenethylamines including the 2C* family of which 2C-T-2, 2C-T-7, 2C-E, 2C-I, and 2C-B are most well known. Additionally, Shulgin performed seminal work into the descriptive synthesis of compounds based on the organic compound tryptamine.
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Displaying 1 - 13 of 13 reviews
June 10, 2022
Reviewed for Foreword Books Indies Awards.
A fairly interesting book that is a direct transcript of a professor's 1980s class on drugs. While the vast majority of this book is still relevant today in how the government views "drugs," the book suffered by being a direct transcript. Why does the reader need to read about how the instructor plans to grade tests and administer final exams? I understand that the transcriber made a choice to keep the book completely true to the professor's lecture, but I assert that the book would have been DRASTICALLY better if the transcriber had made some editorial choices to eliminate those superfluous and irrelevant sections.
A fairly interesting book that is a direct transcript of a professor's 1980s class on drugs. While the vast majority of this book is still relevant today in how the government views "drugs," the book suffered by being a direct transcript. Why does the reader need to read about how the instructor plans to grade tests and administer final exams? I understand that the transcriber made a choice to keep the book completely true to the professor's lecture, but I assert that the book would have been DRASTICALLY better if the transcriber had made some editorial choices to eliminate those superfluous and irrelevant sections.
December 23, 2021
Sasha Shulgin is the chemistry teacher I've longed for all my life. He makes arcane subject matter intelligible and fun. I'm more excited for the material in subsequent volumes (the class by class discussion of drugs' pharmacology and pharmacokinetics). But this first volume covers important preparatory material: What are drugs? How do they move through the body, accumulate, get converted into metabolites, excreted, etc.? What is the national and international legal history of drugs? How are clinical trials conducted? And more. He's a wealth of information ending when the course takes place (1987).
The biggest downside is the missing 35 years of recent data. Also, he's not a great political thinker, not particularly trustworthy outside of chemistry (he says things like his assertion that Francis Bacon is really Shakespeare, which was always and remains a fringe position with little to support it).
The biggest downside is the missing 35 years of recent data. Also, he's not a great political thinker, not particularly trustworthy outside of chemistry (he says things like his assertion that Francis Bacon is really Shakespeare, which was always and remains a fringe position with little to support it).
June 10, 2023
Whoever gave this book less than five stars is an asshole. Thank you Sasha Shulgin for being not only a teacher but a mentor to many. I hope you’re listening to heavenly harmonics wherever your energy may be.
May 22, 2025
pretty educational, for noobs like you
October 31, 2024
Wonderful book, what a man!! Also the context he gave these lectures, just months after MDMA was put in sched 1 makes what he says even cooler. Look forward to nr 2
January 8, 2023
This book needed a lot more editing. There was some excellent introductory material here (which was review for me), but it was interspersed with random conversations between students and Sasha, and Sasha talking about grading and class dynamics that hold no interest to the reader.
January 2, 2023
1. Intro
Betel nut - arecoline
- Receptors: Mercapto groups
- Glutathione, acetylcysteine
What is a drug? Anything that modifies the expected state of a living thing
1960 Delaney Amendment - no additives that cause cancer
- Carcinogenic - butter yellow food additive… hard to induce cancer in mammals even with carcinogenic agents
○ Story of saccharine - 2/10 rats developed because f direct implantation of capsules in their bladders.
○ Ok to add to food because it’s a drug and not a food additive
- Mutagenic - Ames test, does genetic level change
- Teratogenic - affects embryo development in utero
Acute = severe or extreme, or single occurrence vs recurring use
Chronic = repeated
Tacky = fast. Tachyphylaxis = fast guard
Eu = working normally (euthyroid)
Dys = not normal (dysthyroid)
Tonic = firm. Rigid convulsions
Clonic = alternating thrashing convulsions
Lethal = kills. LD50 - dose that kills half
ED50 - effective dose that works on half
TI (therapeutic index) = LD50/ED50. Higher the better (alcohol is only 5)
2. Origin of Drugs
Key change in evolution - ability to ask “who am I?” - consciousness
- Old man of tribe was probably 25. Known as shaman for knowledge of how to survive
MD - cure specific case of patient
PhD - find generality, not specific case
Smoking is not mentioned in the Bible. Oral or chew more accepted
3. Origin of Drugs
Methadone originally known as Dolophine - created in WWII Germany. Seeking a drug with morphine-like action, named it after Adolph hitler
Drug laws passed and are very hard to change, because in politics changing a law is the admission of a mistake
- This is why laws are so hard to change
○ As a politician or religion, you cannot admit to having made a mistake
- Used to have a law: illegal to pass through SF on the way to Sacramento to see a Marshall
○ Gave carte blanche to arrest someone for 72hrs in SF if you didn't like the way they look
Drugs have been around since the beginning of mankind
- Wrapping wounds in leaves, found that some of those leaves were impactful
- Diseases were from god, not from microbes. Origin of malaria = "mala aire". Believed it was from spirits in the air
○ Why shamans were healers during this time
- Early alchemy was the pursuit of science/healing - with a spiritual belief, 4 elements:
○ Air / earth / water / fire
§ Air/water = damp
§ Air/fire = warm
§ Earth/water = cold
§ Earth/fire = dry
○ Believed to be the search to transmutation to gold. Gold was the image of light
§ One of 8 metals known
○ Seeking "gold" that could be drunk in the search for immortality
§ The 5th element - origin of the word "quintessential"
Up, Down, Stars - cuneiform classification by the Feds for stimulants, depressants, and hallucinogens
4 & 5. Plumbing of the Human Body
Ontogeny - origin of being
Phylogeny - origin of the individual
Blood circulation takes about 1min
- From first IV to detection is 1min
- Takes 2-3min / 2-3 passes to smooth out concentration
- Heart pumps 5-6L or blood/min
Most drugs are basic - acidic environment of stomach doesn’t absorb. Needs to bass to small intestine that is basic (alcohol does absorb in stomach)
- Artery - high pressure, has pump
- Vein - low pressure, no pump. Muscle and tissue return to heart
- Hepatic portal system: 1.5L/min of the body’s 6L of blood
○ From small intestine to liver
○ 70-90% metabolism of drugs in the liver. Then to the brain in 15s
- Bypass the liver to get a drug to the brain
- Heart: veins into right atrium, deoxygenated blood pumped by right ventricle to lungs. Oxygenated blood back to left atrium, out left ventricle. 3 main outlets:
○ Brain
○ Heart: coronary arteries to tissues and organs
○ Gut
Oral: 30-60mins from stomach to intestine, then pretty fast
- Some drugs only become active after metabolized in liver “prodrugs”
- Goal of metabolism by the liver - to make more soluble, so can be excreted by kidneys instead of stored in tissues past fatty barriers (partitioning)
- Partition coefficient = ratio of drug dissolved in blood - fatty tissue
- Oxidation, or increasing ionizability
IV: less than a minute to get to brain
Inhalation: few seconds to get to brain
Arterial injection: immediate
- IV and arterial injection are lumpy. Absorption is not immediately consistent across all 5L of blood, like ink droplet in water. Whack! 5mg/ml blood passed to brain then suddenly 100mg/ml
Dosage: most people have the same # of receptor sites, regardless of body weight —> uniform dose for adults
Excretion: if not by kidneys in water
- Stool for materials never absorbed
- Vía expiration through lungs. Methylene chloride as a lipophilic solvent - exhaled out while drug left in body
○ Volume of distribution - how much of drug stays in blood vs. Passes into tissues. Higher = longer half life
○ 200L means that 1/40 is in blood (5L * 40 to clear)
- Perspiration through skin
- Insoluble compounds clog capillaries - most notably retinas (why eyes get cloudy)
Renal excretion impacted by urine acidity. Nicotine + acidic urine becomes an ionized salt that is water soluble.
- If de-ionized, nicotine doesn’t excrete as much and gets reabsorbed
- Clearance: amount of blood needed to clear out the drug. Measure of liver efficiency
Neuroreceptors
Afferent (A) - towards CNS. Anything from outside the brain to feed sensory signals
- Telereceptors (from outside the body, senses)
- Enteroreceptors (from inside the body, eg blood sugar)
- Proprioreceptors
Efferent (E) - nerves and systems going out of cns for motor control
- Telepathy
- Voluntary
- Involuntary
Autonomic nervous system drugs. Mimetic = imitate, lytic = cut
1) Sympathetic agonists / sympathomimetic
- Amphetamine: dilation, stimulation. Stimulants of blood flow, cerebral circulation
2) Sympathetic antagonists / sympatholytic
- Clonidine: constriction. MAOi’s - lower sympathetic system
3) Parasympathetic agonists / parasympathomimetic
- Physostigmine: pin-point pupil
4) Parasympathetic antagonists / parasympatholytic
- Atropine: extreme dilation. Blind, dry, hot, red, mad
Sympathomimetic - activates sympathetic, same effect as parasympatholytic that inhibits parasympathetic
- Sympathetic action is dilated, so eyes will respond to light
- Parasympathetic is constricted, so eyes will not respond to light
Acetylcholine and NE major players for autonomic nervous system
- 5HT and DA for CNS
Synapses: 200 micron gap, 20m/s transmission
- -70mV negative potential allows for conduction, due to Ca2+ outside of neurons and K+ ions in the neurons
- Neurochemicals destroyed in the pre-synaptic neuron by MAO and COMT in the synaptic cleft
○ Monoamine oxidase in neuron
○ Catechol-O-methyl transferase out of neuron
Neurotransmitters are destroyed after transmission
- Refractory period so they can regenerate
- If destruction is inhibited, transmission is stronger
- Without refractory period, neurotransmitters become fatigued and become unresponsive
- Esterase destroys acetylcholine to allow neuron time to regenerate (rebalance K+)
Stimulants increase release of NE
- Enter the cleft and fit in post-synaptic neuron
- Inhibit MAO
- Inhibit reuptake of NE
- More NE in pre-synaptic neuron and in the cleft
Depressants decrease NE in the cleft
- Block re-uptake of epinephrine
6. Drug action
Drugs are organizing or disorganizing
- Given to Ill or well people
Maintain state = inoculation / vaccination
Suppress symptoms = Tylenol for headache, insulin, most prescriptions
Eliminate symptoms = chemotherapy, treatment of Hashimoto / thyroid
Generate symptoms = anesthesia, or psychedelics for mental wellness
Babies cns is all screwed up
- At birth can swim, have very strong grip, toes curl down
- 3 days later all changes
- Half-life of caffeine is 20 days - unable to metabolize yet
Irrational mixtures = dosing combination that is wrong for an individual but selected because it’s best on average. Not tailored
Louis Lewin - brought peyote to west from Mexico in the 1880s
- Arthur Hefftrr was the one who synthesized mescaline
- 1820’s people had ether parties
- Then nitrous parties
- Lewin had the first classification system
Excitantia - uppers or stimulants
- Caffeine, ephedra, khat (khat does not store well)
Inebriantia - cause intoxication
- Alcohol
- Do not vomit if unconscious, has taken a hydrocarbon (gets Into lungs), or caustic (causes more damage in way out, neutralize with acid), or a convulsant (will trigger the whole convulsant system)
Hypnotica - depressant of CNS
- Sedative = quieting down
- Hypnotic = going to sleep
- Some barbiturates and tranquilizers, scopolamine (dreamlike state with amnesia)
Euphorica - quiets physical and emotional pain, dulls senses
- Heroin, morphine
Phantastica - makes more aware, amplifies senses
- Most known as psychedelic, psychotimimetic, psychodysleptic
- 5HT (indole) and DA (phenethylamine)
7. Memory and states of consciousness
Temporal lobes - memory storage
- Aphasia - have complete knowledge of what you wish to say except the one word
Mesmer and hypnotism - animal magnetism studied as a science, but did not talk about placebo effect
Pavlov and the 1921 flood that killed 90% of his dogs in their cages in Leningrad. Surviving dogs no longer conditioned - expected death and didn’t receive it, would not salivate at the bell but instead bite people when they heard a bell. Brainwashing
Schizophrenia - no center. Ability to have perfect recall of all memories, so can draw cause and effect to every trigger. Saw that bird fly by, so might be a sign of danger since last time I saw a bird fly by…
Simplest form of chemical transformation in the body is the addition/removal of a methyl group - deepest area of study for so many years
- Almost all neurotransmitters (especially CNS/ANS) are inactivated by methylation
- Methionine is the compound most active in methylation
- Take serotonin, and in the pineal gland it methylates - add an acetyl group --> melatonin (also add an ester)
-
- Melatonin in the pH and salinity of the body forms into a derivative of harmaline
-
○ McIsaac who was director of University of Texas Psychiatry program was convinced that methoxyharmalan was the source of depression, and scoured car accident victims to sample their pineal gland for presence of harmaline. Did not find and committed suicide
8. Research
All about the purpose of research - to disprove a hypothesis, not prove it.
- Impossible to prove
- Possible to have 99 tests that do not disprove - absence of evidence is not the evidence of absence
Chemist vs pharmacologist - Best way to Test a sweetener? Dip a moist finger in the powder and taste it
- Example of dimoxamime at Bristol labs. Believed to be an antidepressant. Company spent half a year seeking a translational animal model
- This was all for fda process, but before agreeing to do animal studies every person on the board of directors tried it (never told the fda)
”I don’t care how many animal tests you have; the human is the experimental animal that discovers most drugs.”
-
Betel nut - arecoline
- Receptors: Mercapto groups
- Glutathione, acetylcysteine
What is a drug? Anything that modifies the expected state of a living thing
1960 Delaney Amendment - no additives that cause cancer
- Carcinogenic - butter yellow food additive… hard to induce cancer in mammals even with carcinogenic agents
○ Story of saccharine - 2/10 rats developed because f direct implantation of capsules in their bladders.
○ Ok to add to food because it’s a drug and not a food additive
- Mutagenic - Ames test, does genetic level change
- Teratogenic - affects embryo development in utero
Acute = severe or extreme, or single occurrence vs recurring use
Chronic = repeated
Tacky = fast. Tachyphylaxis = fast guard
Eu = working normally (euthyroid)
Dys = not normal (dysthyroid)
Tonic = firm. Rigid convulsions
Clonic = alternating thrashing convulsions
Lethal = kills. LD50 - dose that kills half
ED50 - effective dose that works on half
TI (therapeutic index) = LD50/ED50. Higher the better (alcohol is only 5)
2. Origin of Drugs
Key change in evolution - ability to ask “who am I?” - consciousness
- Old man of tribe was probably 25. Known as shaman for knowledge of how to survive
MD - cure specific case of patient
PhD - find generality, not specific case
Smoking is not mentioned in the Bible. Oral or chew more accepted
3. Origin of Drugs
Methadone originally known as Dolophine - created in WWII Germany. Seeking a drug with morphine-like action, named it after Adolph hitler
Drug laws passed and are very hard to change, because in politics changing a law is the admission of a mistake
- This is why laws are so hard to change
○ As a politician or religion, you cannot admit to having made a mistake
- Used to have a law: illegal to pass through SF on the way to Sacramento to see a Marshall
○ Gave carte blanche to arrest someone for 72hrs in SF if you didn't like the way they look
Drugs have been around since the beginning of mankind
- Wrapping wounds in leaves, found that some of those leaves were impactful
- Diseases were from god, not from microbes. Origin of malaria = "mala aire". Believed it was from spirits in the air
○ Why shamans were healers during this time
- Early alchemy was the pursuit of science/healing - with a spiritual belief, 4 elements:
○ Air / earth / water / fire
§ Air/water = damp
§ Air/fire = warm
§ Earth/water = cold
§ Earth/fire = dry
○ Believed to be the search to transmutation to gold. Gold was the image of light
§ One of 8 metals known
○ Seeking "gold" that could be drunk in the search for immortality
§ The 5th element - origin of the word "quintessential"
Up, Down, Stars - cuneiform classification by the Feds for stimulants, depressants, and hallucinogens
4 & 5. Plumbing of the Human Body
Ontogeny - origin of being
Phylogeny - origin of the individual
Blood circulation takes about 1min
- From first IV to detection is 1min
- Takes 2-3min / 2-3 passes to smooth out concentration
- Heart pumps 5-6L or blood/min
Most drugs are basic - acidic environment of stomach doesn’t absorb. Needs to bass to small intestine that is basic (alcohol does absorb in stomach)
- Artery - high pressure, has pump
- Vein - low pressure, no pump. Muscle and tissue return to heart
- Hepatic portal system: 1.5L/min of the body’s 6L of blood
○ From small intestine to liver
○ 70-90% metabolism of drugs in the liver. Then to the brain in 15s
- Bypass the liver to get a drug to the brain
- Heart: veins into right atrium, deoxygenated blood pumped by right ventricle to lungs. Oxygenated blood back to left atrium, out left ventricle. 3 main outlets:
○ Brain
○ Heart: coronary arteries to tissues and organs
○ Gut
Oral: 30-60mins from stomach to intestine, then pretty fast
- Some drugs only become active after metabolized in liver “prodrugs”
- Goal of metabolism by the liver - to make more soluble, so can be excreted by kidneys instead of stored in tissues past fatty barriers (partitioning)
- Partition coefficient = ratio of drug dissolved in blood - fatty tissue
- Oxidation, or increasing ionizability
IV: less than a minute to get to brain
Inhalation: few seconds to get to brain
Arterial injection: immediate
- IV and arterial injection are lumpy. Absorption is not immediately consistent across all 5L of blood, like ink droplet in water. Whack! 5mg/ml blood passed to brain then suddenly 100mg/ml
Dosage: most people have the same # of receptor sites, regardless of body weight —> uniform dose for adults
Excretion: if not by kidneys in water
- Stool for materials never absorbed
- Vía expiration through lungs. Methylene chloride as a lipophilic solvent - exhaled out while drug left in body
○ Volume of distribution - how much of drug stays in blood vs. Passes into tissues. Higher = longer half life
○ 200L means that 1/40 is in blood (5L * 40 to clear)
- Perspiration through skin
- Insoluble compounds clog capillaries - most notably retinas (why eyes get cloudy)
Renal excretion impacted by urine acidity. Nicotine + acidic urine becomes an ionized salt that is water soluble.
- If de-ionized, nicotine doesn’t excrete as much and gets reabsorbed
- Clearance: amount of blood needed to clear out the drug. Measure of liver efficiency
Neuroreceptors
Afferent (A) - towards CNS. Anything from outside the brain to feed sensory signals
- Telereceptors (from outside the body, senses)
- Enteroreceptors (from inside the body, eg blood sugar)
- Proprioreceptors
Efferent (E) - nerves and systems going out of cns for motor control
- Telepathy
- Voluntary
- Involuntary
Autonomic nervous system drugs. Mimetic = imitate, lytic = cut
1) Sympathetic agonists / sympathomimetic
- Amphetamine: dilation, stimulation. Stimulants of blood flow, cerebral circulation
2) Sympathetic antagonists / sympatholytic
- Clonidine: constriction. MAOi’s - lower sympathetic system
3) Parasympathetic agonists / parasympathomimetic
- Physostigmine: pin-point pupil
4) Parasympathetic antagonists / parasympatholytic
- Atropine: extreme dilation. Blind, dry, hot, red, mad
Sympathomimetic - activates sympathetic, same effect as parasympatholytic that inhibits parasympathetic
- Sympathetic action is dilated, so eyes will respond to light
- Parasympathetic is constricted, so eyes will not respond to light
Acetylcholine and NE major players for autonomic nervous system
- 5HT and DA for CNS
Synapses: 200 micron gap, 20m/s transmission
- -70mV negative potential allows for conduction, due to Ca2+ outside of neurons and K+ ions in the neurons
- Neurochemicals destroyed in the pre-synaptic neuron by MAO and COMT in the synaptic cleft
○ Monoamine oxidase in neuron
○ Catechol-O-methyl transferase out of neuron
Neurotransmitters are destroyed after transmission
- Refractory period so they can regenerate
- If destruction is inhibited, transmission is stronger
- Without refractory period, neurotransmitters become fatigued and become unresponsive
- Esterase destroys acetylcholine to allow neuron time to regenerate (rebalance K+)
Stimulants increase release of NE
- Enter the cleft and fit in post-synaptic neuron
- Inhibit MAO
- Inhibit reuptake of NE
- More NE in pre-synaptic neuron and in the cleft
Depressants decrease NE in the cleft
- Block re-uptake of epinephrine
6. Drug action
Drugs are organizing or disorganizing
- Given to Ill or well people
Maintain state = inoculation / vaccination
Suppress symptoms = Tylenol for headache, insulin, most prescriptions
Eliminate symptoms = chemotherapy, treatment of Hashimoto / thyroid
Generate symptoms = anesthesia, or psychedelics for mental wellness
Babies cns is all screwed up
- At birth can swim, have very strong grip, toes curl down
- 3 days later all changes
- Half-life of caffeine is 20 days - unable to metabolize yet
Irrational mixtures = dosing combination that is wrong for an individual but selected because it’s best on average. Not tailored
Louis Lewin - brought peyote to west from Mexico in the 1880s
- Arthur Hefftrr was the one who synthesized mescaline
- 1820’s people had ether parties
- Then nitrous parties
- Lewin had the first classification system
Excitantia - uppers or stimulants
- Caffeine, ephedra, khat (khat does not store well)
Inebriantia - cause intoxication
- Alcohol
- Do not vomit if unconscious, has taken a hydrocarbon (gets Into lungs), or caustic (causes more damage in way out, neutralize with acid), or a convulsant (will trigger the whole convulsant system)
Hypnotica - depressant of CNS
- Sedative = quieting down
- Hypnotic = going to sleep
- Some barbiturates and tranquilizers, scopolamine (dreamlike state with amnesia)
Euphorica - quiets physical and emotional pain, dulls senses
- Heroin, morphine
Phantastica - makes more aware, amplifies senses
- Most known as psychedelic, psychotimimetic, psychodysleptic
- 5HT (indole) and DA (phenethylamine)
7. Memory and states of consciousness
Temporal lobes - memory storage
- Aphasia - have complete knowledge of what you wish to say except the one word
Mesmer and hypnotism - animal magnetism studied as a science, but did not talk about placebo effect
Pavlov and the 1921 flood that killed 90% of his dogs in their cages in Leningrad. Surviving dogs no longer conditioned - expected death and didn’t receive it, would not salivate at the bell but instead bite people when they heard a bell. Brainwashing
Schizophrenia - no center. Ability to have perfect recall of all memories, so can draw cause and effect to every trigger. Saw that bird fly by, so might be a sign of danger since last time I saw a bird fly by…
Simplest form of chemical transformation in the body is the addition/removal of a methyl group - deepest area of study for so many years
- Almost all neurotransmitters (especially CNS/ANS) are inactivated by methylation
- Methionine is the compound most active in methylation
- Take serotonin, and in the pineal gland it methylates - add an acetyl group --> melatonin (also add an ester)
-
- Melatonin in the pH and salinity of the body forms into a derivative of harmaline
-
○ McIsaac who was director of University of Texas Psychiatry program was convinced that methoxyharmalan was the source of depression, and scoured car accident victims to sample their pineal gland for presence of harmaline. Did not find and committed suicide
8. Research
All about the purpose of research - to disprove a hypothesis, not prove it.
- Impossible to prove
- Possible to have 99 tests that do not disprove - absence of evidence is not the evidence of absence
Chemist vs pharmacologist - Best way to Test a sweetener? Dip a moist finger in the powder and taste it
- Example of dimoxamime at Bristol labs. Believed to be an antidepressant. Company spent half a year seeking a translational animal model
- This was all for fda process, but before agreeing to do animal studies every person on the board of directors tried it (never told the fda)
”I don’t care how many animal tests you have; the human is the experimental animal that discovers most drugs.”
-
August 26, 2025
This book covered an interesting spectrum of subjects. There is the organic chemistry - heavy at times. There is discussion of legal history (in the US) and the way in which societal attitudes have changed over time. There is also a neat diversion into the business side of drug research. One aspect that I wish had been taken up too briefly was the anthropology - how other societies, from medieval Europe to hunter/gatherers have regarded and handled drugs.
Several reviewers have remarked that the retention of the student/teacher interaction in this presentation was inappropriate. I understand their objection, but I was mostly glad to see it. Professor Shugin was a captivating lecturer, and by including this material we get to see his egalitarian attitude - which played a role in his attitudes toward drugs - in practice.
Several reviewers have remarked that the retention of the student/teacher interaction in this presentation was inappropriate. I understand their objection, but I was mostly glad to see it. Professor Shugin was a captivating lecturer, and by including this material we get to see his egalitarian attitude - which played a role in his attitudes toward drugs - in practice.
August 21, 2021
An interesting and enjoyable transcription of lectures given by Sasha at SFSU, though only the first part of the semester is provided in volume 1. It doesn't really get into any particulars of the substances for which he is famous, though presumably those will come in future volumes. The course wasn't necessarily scoped for hard scientists, and it is probably accessible even if you don't have a strong (or any) orgo/biochem background. Notably there are intermittent "dirty pictures" that get into some of the chemistry. Overall, there isn't much in here that you wouldn't get in any comparable undergrad course, but the conversational tone of the lectures and Sasha's excitement/passion come through. Definitely worth having for the historical significance alone, if you're into that sort of thing.
September 21, 2024
Great book! Keen for volume 2. Shulgin speaks clearly this book is for anyone with an interest in pharmacology of psychedelics
January 25, 2022
These are transcripts from a course Shulgin gave at UCSF. This first volume is introductory material on drugs, pharmacology, and neurobiology. I'm looking forward to Vol 2 which will go into individual psychoactive compounds.
February 7, 2023
Wonderful lecture series. He explains things similar to the way Feynman did. He uses jargon as a tool, rather than a bludgeon.
September 13, 2022
In my view every person who stands to gain immensely - even if their knowledge of a good bit of this they're competent with, nevertheless - are: any person interested in this topic and all its related issues and, most certainly, educators.
Displaying 1 - 13 of 13 reviews