Source: Textbook Chapters 7–9, Lecture Notes
Tags: CNS, PNS, autonomic nervous system, sympathetic, parasympathetic, seizure, epilepsy, excitotoxicity, pharmacology, blood-brain barrier, tetrodotoxin, sedative-hypnotic, opioid, cocaine, amphetamine, psychedelic, cannabis, endocannabinoid, UC Berkeley, Brain-Mind Odyssey
Chapter 7 maps the nervous system's divisions (CNS, PNS, autonomic) and explains how too much excitation leads to seizures. Chapter 8 introduces pharmacology: how drugs cross the blood-brain barrier, block or activate channels, and the concept of therapeutic index. Chapter 9 surveys the major classes of psychoactive drugs, from caffeine and nicotine through opioids, cocaine, psychedelics, and cannabis.
Central nervous system (CNS)
Brain and spinal cord.
Peripheral nervous system (PNS)
Everything outside the CNS: sensory systems, muscles, tendons, joints.
Cranial nerves
Twelve pairs of nerves that emerge directly from the brain stem, linking the CNS and PNS.
Autonomic nervous system (ANS)
Regulates body organs and internal functions (heart rate, blood pressure, respiration, digestion). Divided into sympathetic and parasympathetic branches.
Sympathetic nervous system
"Fight or flight." Increases heart rate and blood pressure, dilates pupils and bronchioles, constricts bladder. Primary neurotransmitter: norepinephrine.
Parasympathetic nervous system
"Rest and digest." Decreases heart rate and blood pressure, constricts pupils and bronchioles, stimulates bladder. Primary neurotransmitter: acetylcholine.
Sympathomimetic
Any drug that stimulates the sympathetic nervous system.
Sympatholytic
Any drug that decreases sympathetic effects on target organs.
Parasympathomimetic
Any drug that stimulates the parasympathetic nervous system.
Parasympatholytic
Any drug that decreases parasympathetic effects.
Agonist
A molecule that binds to a neurotransmitter receptor and activates it.
Antagonist
A molecule that binds to a neurotransmitter receptor and blocks it.
Neuromuscular junction
Where ionotropic acetylcholine receptors (AChRs) mediate communication between motor nerves and skeletal muscles.
Acetylcholine (ACh)
A neurotransmitter active in both the CNS and PNS. AChRs can be ionotropic (nicotinic) or metabotropic/GPCR (muscarinic). Key enzymes: choline acetyltransferase (synthesis), acetylcholinesterase (degradation).
Monoamine neurotransmitters
A class that includes serotonin, dopamine, and norepinephrine. All are synthesised from the essential amino acid phenylalanine.
Serotonin (5-HT)
Found in raphe nuclei (brain stem clusters). Affects constriction/dilation of blood vessels. 5-HT3 receptor is a GPCR.
Dopamine
Produced in the ventral tegmentum and substantia nigra.
Norepinephrine
Produced in the locus coeruleus (brain stem). The primary sympathetic neurotransmitter.
Seizure
Runaway neural excitation in the brain. Too much excitation and insufficient inhibition triggers an explosive chain reaction. Symptoms can include aura, muscle convulsions, amnesia, and loss of consciousness.
Epilepsy
A disorder of recurring seizures. Affects about 1.1% of the US population (~3 million people). Only about two-thirds respond to medication.
Idiopathic seizure
A seizure with no identifiable cause. The majority of seizures fall into this category.
Excitotoxicity
Overexcitation of neurons by glutamate, leading to cell damage or death.
Drug
A chemical that in small amounts has a significant effect on the body.
Pharmacology
The scientific study of drugs. "Pharmakon" means both medicine and poison in Greek.
Paracelsus
Taught that all substances are poison and whether something is medicine or poison depends on the dose.
Therapeutic index (TI)
Lethal dose divided by therapeutic dose. A higher TI means a wider margin of safety.
Tetrodotoxin (TTX)
One of the most poisonous chemicals known. Found in puffer fish. Blocks voltage-gated Na+ channels. Causes numbness, muscle weakness, paralysis, death by respiratory failure. Hydrophilic, so it cannot cross the blood-brain barrier.
Blood-brain barrier (BBB)
Blood vessels in the CNS are constructed with extremely tight junctions between cells, heavily restricting passage of substances from blood into brain. Substances can cross via transporter proteins or by diffusion (gases). Hydrophilic and positively charged molecules generally cannot cross.
Local anaesthesia
Loss of sensation achieved by altering sodium channel function. Cocaine was the first local anaesthetic.
Muscarinic AChR (mAChR)
Activated by muscarine (from mushrooms), antagonised by atropine (from Atropa belladonna, deadly nightshade). Atropine crosses the BBB and has psychoactive and parasympatholytic effects. Muscarine itself cannot cross the BBB due to its positive charge.
Sedative-hypnotic drugs
A class including alcohol, barbiturates, benzodiazepines, and general anaesthetics. Low doses produce relaxation, high doses induce sleep. They facilitate and enhance the inhibitory action of GABA at ionotropic GABA receptors, inducing Cl- flow into cells.
Opioids
Derived from or modelled on opium (from the poppy plant, Papaver somniferum). Produce relaxation, analgesia (pain relief), and euphoria. Morphine is the primary chemical constituent. Fentanyl is ~100 times more potent than morphine.
Endorphins
Endogenous opioid neurotransmitters. Molecules found in the brain that function as agonists at opioid receptors.
Cocaine
From Erythroxylum coca (South America). Blocks reuptake transporters for norepinephrine and dopamine, increasing their presence in the synaptic cleft. Produces CNS arousal. Highly addictive.
Amphetamines
Cause neurotransmitter (norepinephrine, dopamine) to leak out of the axon terminal into the synaptic cleft via the transporter. Includes drugs like Ritalin and Adderall.
Psychedelics (hallucinogens)
Intensify thoughts and feelings, ranging from awe and connection with nature to anxiety and panic. "Set and setting" are critical variables.
Mescaline
From the peyote cactus (Mexico). First psychedelic substance to be chemically identified (by Arthur Heffter).
LSD
Synthesised and first self-tested by Albert Hofmann in 1943. The most famous psychedelic drug.
Psilocybin / psilocin
Active compounds in Psilocybe mushrooms. Maria Sabina, a Mazatec healer from southern Mexico, introduced these to the wider world. Gordon Wasson wrote about the experience in Life magazine.
DMT
A powerful psychedelic. Ayahuasca combines DMT with a monoamine oxidase inhibitor.
Cannabis
Approximately 10,000 years of documented human use. THC (tetrahydrocannabinol) is the major psychoactive constituent.
Endocannabinoids
Endogenous agonists at cannabinoid (CB) receptors. Anandamide was the first to be identified. Involved in retrograde signalling (backward signalling from postsynaptic to presynaptic cell).
Caffeine
Found in coffee (Coffea arabica), tea (Camellia sinensis), cacao (Theobroma cacao), kola, guarana, and yerba mate. Functions as an adenosine receptor antagonist.
Nicotine
From tobacco (Nicotiana tabacum), native to South America. Named after Jean Nicot. Agonist at nicotinic acetylcholine receptors. CNS effects include both stimulation and relaxation. Acts on basal forebrain nuclei and midbrain pontine nuclei.
Ethanol (alcohol)
The least poisonous alcohol to the human body. Produced by fermentation. A sedative-hypnotic that enhances GABA's inhibitory action.
CNS = brain + spinal cord
PNS = sensory systems, muscles, autonomic nervous system
ANS: sympathetic (norepinephrine) vs. parasympathetic (acetylcholine)
Sympathetic ganglia = clusters of sympathetic nerve cells
Both sympathetic and parasympathetic systems use GPCRs
Heart rate: sympathetic increases, parasympathetic decreases
Blood pressure: sympathetic increases, parasympathetic decreases
Pupils: sympathetic dilates, parasympathetic constricts
Bronchioles: sympathetic dilates, parasympathetic constricts
Bladder: sympathetic constricts, parasympathetic stimulates
AChR can be ionotropic (at the neuromuscular junction, Na+ flows in, depolarization, excitatory)
AChR can also be GPCR (muscarinic receptors)
Synthesised by choline acetyltransferase
Degraded by acetylcholinesterase
Found in basal forebrain nuclei and midbrain pontine nuclei
All synthesised from the essential amino acid phenylalanine
Serotonin: raphe nuclei (brain stem)
Dopamine: ventral tegmentum, substantia nigra
Norepinephrine: locus coeruleus (brain stem)
Seizure = runaway excitation with insufficient inhibition
Causes: intense sensory stimuli, sleep deprivation, stress, head trauma, stimulant drug use, withdrawal from sedative-hypnotics
Epilepsy = recurring seizures. ~1.1% of the US population. Only ~2/3 respond to medication.
Treatment targets: voltage-gated Na+/Ca2+/K+ channels (reduce excitability), GABA receptors, glutamate receptors, cannabinoids
Severe cases: severing the corpus callosum (rare), excision of epileptogenic brain tissue
Excitotoxicity: glutamate overexcitation causes neuronal damage
Action potential propagates to the axon terminal
Voltage-gated Ca2+ channels open
Calcium triggers exocytosis of neurotransmitter vesicles
Neurotransmitter binds postsynaptic (and some presynaptic) receptors
Inactivation via reuptake or enzymatic degradation
"Pharmakon" = medicine and poison
Paracelsus: all substances are poison, the dose determines the effect
Therapeutic index (TI) = lethal dose / therapeutic dose
Example: botulinum toxin, therapeutic dose 5 mg, lethal dose 100 mg, TI = 20
Found in puffer fish and some other marine animals (serves as protection)
Blocks voltage-gated Na+ channels
Symptoms: numbness, muscle weakness, paralysis, death by respiratory paralysis
Hydrophilic, so it cannot cross the BBB
Extremely tight cell junctions in CNS blood vessels
Regular body blood vessels have small gaps; brain vessels do not
Substances cross via transporter proteins or diffusion (gases only)
Positively charged molecules (e.g. muscarine, tubocurarine) are blocked
Muscarine (from mushrooms) activates muscarinic AChRs
Atropine (from Atropa belladonna, deadly nightshade) antagonises muscarinic AChRs
Atropine crosses the BBB → psychoactive and parasympatholytic effects
Muscarine cannot cross BBB (positive charge)
Atropine also affects the eye: sphincter muscles constrict the pupil, radial muscles dilate it
Saxitoxin: causes paralytic shellfish poisoning (PSP)
Batrachotoxin: disrupts voltage-gated Na+ channel function (from poison frogs)
Adenosine receptor antagonist
Adenosine normally: slows heart rate, opens blood vessels, decreases neuronal excitability
Caffeine blocks these effects → stimulation
Agonist at nicotinic AChRs
CNS effects: stimulation and relaxation, focused attention
Named after Jean Nicot (French)
Ethanol = least poisonous alcohol, produced by fermentation
All sedative-hypnotics (alcohol, barbiturates, benzodiazepines, general anaesthetics) enhance GABA's inhibitory action at ionotropic GABA receptors → Cl- flows in
Low dose: relaxation. High dose: sleep/unconsciousness.
First general anaesthetic was essentially whiskey
Barbiturates: first synthetic drug class, used for anxiety and insomnia
Friedrich Wilhelm Sertürner: isolated morphine from opium, showed purified form is more potent
Opium from poppy plant (Papaver somniferum), known as the "joy plant"
Extracted from unripe seed pods
Effects: relaxation, analgesia, euphoria
Morphine: primary active constituent
Heroin: semi-synthetic opioid
Fentanyl: synthetic, ~100x more potent than morphine
Endorphins: endogenous opioid neurotransmitters (brain's own opioid agonists)
British East India Company historically traded enormous quantities of opium
From Erythroxylum coca (South America)
Blocks reuptake transporters for norepinephrine and dopamine
Effects: CNS arousal, increased NT in synaptic cleft
First local anaesthetic
Can cause psychosis
Cause neurotransmitter to leak from axon terminal into synaptic cleft via transporter (reverse transport)
Increase norepinephrine and dopamine in the cleft
Examples: Ritalin, Adderall
Set and setting are critical to the experience
Mescaline: from peyote cactus (Mexico), first psychedelic chemically identified (Arthur Heffter)
LSD: synthesised by Albert Hofmann (1943), most famous psychedelic
Psilocybin/psilocin: from Psilocybe mushrooms. Maria Sabina (Mazatec healer, southern Mexico) introduced them. Gordon Wasson wrote about the experience in Life magazine.
DMT: powerful psychedelic. Ayahuasca = DMT + an MAO inhibitor.
LSD has shown efficacy in treating certain illnesses
~10,000 years of human use (also as hemp)
THC is the major psychoactive constituent
Anandamide: the first identified endogenous agonist at cannabinoid (CB) receptors
Endocannabinoid system uses retrograde signalling (postsynaptic → presynaptic)
Caffeine (coffee, tea, cacao, kola, yerba mate)
Alcohol
Nicotine (tobacco)
Arecoline (areca nut)
THC (cannabis)
Plants are extraordinary chemical factories
⚠️ Know the sympathetic vs. parasympathetic comparison: neurotransmitters (norepinephrine vs. acetylcholine), effects on heart rate, blood pressure, pupils, bronchioles, and bladder.
⚠️ Agonist vs. antagonist: be able to define each and give examples (e.g. nicotine is an agonist at nicotinic AChRs; atropine is an antagonist at muscarinic AChRs; caffeine is an antagonist at adenosine receptors).
⚠️ Sympathomimetic, sympatholytic, parasympathomimetic, parasympatholytic: be able to define and give examples.
⚠️ Therapeutic index = lethal dose / therapeutic dose. Higher TI = safer drug.
⚠️ TTX: know what it blocks (voltage-gated Na+ channels), its symptoms, and why it cannot cross the BBB (hydrophilic).
⚠️ Blood-brain barrier: understand why some drugs cross (lipophilic, uncharged) and others cannot (hydrophilic, positively charged).
⚠️ Sedative-hypnotics enhance GABA at ionotropic receptors, inducing Cl- influx. This is how alcohol, barbiturates, benzodiazepines, and general anaesthetics all work.
⚠️ Cocaine blocks reuptake of norepinephrine and dopamine. Amphetamines cause reverse transport (NT leaks out). Different mechanisms producing related effects.
⚠️ Know the endogenous systems: endorphins (opioid receptors), anandamide (cannabinoid receptors). Retrograde signalling for endocannabinoids.
⚠️ Seizures = too much excitation, not enough inhibition. Epilepsy = recurring seizures. Excitotoxicity = glutamate overexcitation.
Q: What neurotransmitter is used by the sympathetic nervous system, and what is used by the parasympathetic?
A: Sympathetic uses norepinephrine. Parasympathetic uses acetylcholine.
Q: Define agonist and antagonist, with one example of each.
A: An agonist binds to a receptor and activates it (e.g. nicotine at nicotinic AChRs). An antagonist binds and blocks the receptor (e.g. atropine at muscarinic AChRs).
Q: What is the therapeutic index, and how is it calculated?
A: Therapeutic index = lethal dose / therapeutic dose. A higher value means a greater safety margin between the effective dose and a lethal dose.
Q: How does tetrodotoxin work, and why does it not affect the brain directly?
A: TTX blocks voltage-gated sodium channels, preventing action potentials in peripheral nerves. It is hydrophilic and cannot cross the blood-brain barrier.
Q: What property must a substance have to cross the blood-brain barrier by diffusion?
A: It must be lipophilic (non-polar, fat-soluble) or be a gas. Hydrophilic and positively charged molecules are generally excluded.
Q: How do sedative-hypnotic drugs produce their effects?
A: They facilitate and enhance the inhibitory action of GABA at ionotropic GABA receptors, increasing Cl- flow into cells (hyperpolarization), which reduces neural excitability.
Q: What is the difference between cocaine's and amphetamine's mechanisms of action?
A: Cocaine blocks reuptake transporters for norepinephrine and dopamine, keeping more NT in the synaptic cleft. Amphetamines cause NT to leak out of the axon terminal into the cleft via reverse transport through the transporter.
Q: What are endorphins?
A: Endogenous opioid neurotransmitters found in the brain. They are the body's own agonists at opioid receptors and produce effects similar to opioid drugs (pain relief, euphoria).
Q: What is excitotoxicity?
A: Damage or death of neurons caused by excessive excitation from glutamate. This is relevant to seizures and other neurological conditions.
Q: What is retrograde signalling in the context of endocannabinoids?
A: Endocannabinoids signal backwards, from the postsynaptic cell to the presynaptic cell, modulating neurotransmitter release. This is the opposite of the normal direction of synaptic signalling.
Q: Name three causes of seizures discussed in the course.
A: Intense sensory stimuli, sleep deprivation, stress, physical head trauma, stimulant drug use, or withdrawal from sedative-hypnotic drugs (any three).
Q: Who was Maria Sabina?
A: A Mazatec healer from a small mountain village in southern Mexico who introduced Psilocybe mushroom use to the wider world. Gordon Wasson documented the experience in Life magazine.
CNS, PNS, autonomic nervous system, sympathetic, parasympathetic, norepinephrine, acetylcholine, cranial nerves, sympathomimetic, sympatholytic, parasympathomimetic, parasympatholytic, agonist, antagonist, neuromuscular junction, nicotinic AChR, muscarinic AChR, atropine, muscarine, Atropa belladonna, monoamine, serotonin, dopamine, norepinephrine, phenylalanine, raphe nuclei, ventral tegmentum, substantia nigra, locus coeruleus, seizure, epilepsy, idiopathic seizure, excitotoxicity, glutamate, GABA, pharmacology, Paracelsus, therapeutic index, tetrodotoxin, TTX, puffer fish, blood-brain barrier, BBB, local anaesthesia, cocaine, saxitoxin, batrachotoxin, sedative-hypnotic, alcohol, ethanol, barbiturate, benzodiazepine, general anaesthesia, GABA receptor, opioid, opium, morphine, heroin, fentanyl, endorphin, opioid receptor, amphetamine, Ritalin, Adderall, reuptake, reverse transport, psychedelic, hallucinogen, mescaline, peyote, LSD, Albert Hofmann, psilocybin, psilocin, Maria Sabina, DMT, ayahuasca, cannabis, THC, endocannabinoid, anandamide, retrograde signalling, caffeine, adenosine, nicotine, tobacco, set and setting