Drugs and hormonesDrugs and hormones(they often go hand in hand…..)(they often go hand in hand…..)
Psychology 2606Psychology 2606
IntroductionIntroduction
What is a drug?What is a drug?Well, we all Well, we all knowknow what it means… what it means…That ain’t good enough, we need some sort of That ain’t good enough, we need some sort of
definitiondefinitionAlters physiology, but is not food…..Alters physiology, but is not food…..
Vitamin C?Vitamin C?
Some things are also poisonsSome things are also poisonsGasoline, mugwart..Gasoline, mugwart..
Perhaps we don’t need a definitionPerhaps we don’t need a definition
Still….Still….
What if you take it not to treat anything or What if you take it not to treat anything or to get highto get highCokeCokeCoffeeCoffeeBeerBeer
Frankly, an intuitive definition will have to Frankly, an intuitive definition will have to do.do.
NamesNames
Chemical NamesChemical Names 7-chloro-1,3-dihydro-1-7-chloro-1,3-dihydro-1-
methyl-5-phenyl-2H-1,4-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.benzodiazepin-2-one.
How very helpful….How very helpful….
Generic NamesGeneric Names diazepamdiazepam flouexitineflouexitine
Trade NamesTrade Names ValiumValium ProzacProzac
DosagesDosages
Different dosage sizes will have different Different dosage sizes will have different effects on different people, animals. effects on different people, animals.
Especially if they weigh different amountsEspecially if they weigh different amountsStandardize itStandardize itmg/kgmg/kg
Dose Response CurvesDose Response Curves
Pick some variable for a responsePick some variable for a responsePlot response as a function of dosePlot response as a function of doseOne drink and I am relaxedOne drink and I am relaxed4 drinks and I am tipsy4 drinks and I am tipsy8 drinks and I am ‘relaxed’ again.8 drinks and I am ‘relaxed’ again.This shape is very common in DRCsThis shape is very common in DRCs
Dose Response CurvesDose Response Curves
Effect of morphine and morphine + naloxone on Effect of morphine and morphine + naloxone on activity (left) and nosepoke (right) (Criswell, activity (left) and nosepoke (right) (Criswell, 1987)1987)
Describing EffectivenessDescribing Effectiveness
EDED5050 and LD and LD5050
Effective dose for 50 percent of the Effective dose for 50 percent of the populationpopulationsubjectivesubjective
Lethal dose for 50% of the populationLethal dose for 50% of the populationTherapeutic Index (TI)Therapeutic Index (TI)
TI = LDTI = LD50 50 / ED/ ED5050
Higher the index, the safer the drugHigher the index, the safer the drug
Potency and Effectiveness or Potency and Effectiveness or EfficacyEfficacy
Find the EDFind the ED5050 for both drugs for both drugs
The one with the lower EDThe one with the lower ED5050 is more is more
potentpotentEfficacy is about the maximum amount of Efficacy is about the maximum amount of
effect the drug will haveeffect the drug will haveMorphine vs. aspirinMorphine vs. aspirin
Some other key termsSome other key terms
Primary effects or main effects vs. side Primary effects or main effects vs. side effectseffectsDepends on your point of viewDepends on your point of view If you are taking morphine to deal with pain, If you are taking morphine to deal with pain,
the main effect is the analgesia and the (albeit the main effect is the analgesia and the (albeit fun) side effect is being highfun) side effect is being high
If you are taking it because you want to If you are taking it because you want to groove to Quicksilver Messenger Service….groove to Quicksilver Messenger Service….
Key Terms, ContinuedKey Terms, Continued
AgonistsAgonistsAntagonistsAntagonists
Naloxone and opiates for exampleNaloxone and opiates for exampleAdditive effectsAdditive effectsSuperadditive effectsSuperadditive effects
Sleeping pills and martinisSleeping pills and martinis
Routes of AdministrationRoutes of Administration
If you are injecting, you need a vehicleIf you are injecting, you need a vehicle SalineSaline
SubcutaneousSubcutaneous Slowest absorptionSlowest absorption
IntramuscularIntramuscular IntraperitonealIntraperitoneal
Fastest absorptionFastest absorption
IntravenousIntravenous intraventricularintraventricular
Routes…Routes…
Get into bloodstream via diffusionGet into bloodstream via diffusion (except IV injections obviously)(except IV injections obviously)
Inhalation works the same wayInhalation works the same wayGasses or solidsGasses or solids
Orally, depends on lipid solubilityOrally, depends on lipid solubilityMore soluble the easier the absorptionMore soluble the easier the absorption Ionized molecules are not absorbedIonized molecules are not absorbedRate is constantRate is constant
Distribution and MetabolismDistribution and Metabolism
Once absorbed, the drug has to get past Once absorbed, the drug has to get past the blood brain barrierthe blood brain barrier
Get across the membrane through passive Get across the membrane through passive or active transportor active transport
Protein binding stops someProtein binding stops someTaken out of blood stream by kidneys, Taken out of blood stream by kidneys,
liverliverMeasured in half lifeMeasured in half life
What affects metabolism?What affects metabolism?
AgeAge SexSex SpeciesSpecies Enzyme inductionEnzyme induction Enzyme depressionEnzyme depression Putting absorption Putting absorption
and excretion and excretion together, you get the together, you get the time coursetime course of the of the drugdrug
Therapeutic windowTherapeutic window
You want to maintain enough of the drug You want to maintain enough of the drug in the systemin the system
Easy if the drug has a long time courseEasy if the drug has a long time courseHarder if the time course is longerHarder if the time course is longer
Drug takingDrug taking
When people first thought about it (and When people first thought about it (and until relatively recently) drug taking until relatively recently) drug taking behaviour just seemed oddbehaviour just seemed oddNot avoiding painNot avoiding painDoesn’t affect all people the same wayDoesn’t affect all people the same wayYou don’t ‘need’ itYou don’t ‘need’ it
Aha! You must be an immoral pig, Aha! You must be an immoral pig, probably with little willpower. You are a probably with little willpower. You are a bad person you junkie lowlifebad person you junkie lowlife
The Disease ModelThe Disease Model
Oh perhaps it is not a problem with your Oh perhaps it is not a problem with your character or moralitycharacter or morality
Ahh, yes, it is a diseaseAhh, yes, it is a diseaseOr a disorder as we say todayOr a disorder as we say today
Started with alcoholismStarted with alcoholismWhat is the disease mechanism?What is the disease mechanism?But it is genetic!But it is genetic!
So whatSo what
Physical Dependence ModelPhysical Dependence Model
Withdrawal (from morphine) caused by Withdrawal (from morphine) caused by ‘autotoxin’‘autotoxin’
Found to be lacking, but, the idea stuck. Found to be lacking, but, the idea stuck. Indeed, still VERY popular Indeed, still VERY popular Accounts for the ‘abnormality’ of it allAccounts for the ‘abnormality’ of it allCan be combined with the disease modelCan be combined with the disease model
Physical Dependence ModelPhysical Dependence Model
Only Depressants?Only Depressants?Tatum and Seevers (1931) added habituationTatum and Seevers (1931) added habituation
Problem is, that stimulants, for the most Problem is, that stimulants, for the most part, don’t produce withdrawal symptomspart, don’t produce withdrawal symptoms
Hmm, Let’s invent a new idea!Hmm, Let’s invent a new idea!
Psychological DependencePsychological Dependence
When you need a drug, but don’t need a When you need a drug, but don’t need a drugdrug
When you crave a drugWhen you crave a drugCircularCircular
Biggest problems:Biggest problems:Continual abuse with drugs that do NOT Continual abuse with drugs that do NOT
produce withdrawalproduce withdrawalAddiction without dependenceAddiction without dependence
Positive Reinforcement ModelPositive Reinforcement Model
People used to think you couldn’t get People used to think you couldn’t get animals addictedanimals addictedNot moralNot moralCan’t get the diseaseCan’t get the disease
CatheterCatheterWork for drugWork for drug
(Thompson and Shuster, 1964)(Thompson and Shuster, 1964)
How does it work?How does it work?
Seems circular, until you realize that we Seems circular, until you realize that we know what a reinforcer is not just from know what a reinforcer is not just from operational definition, but from physiologyoperational definition, but from physiology
Dopamine hypothesisDopamine hypothesisVTA -> MFB -> ACCVTA -> MFB -> ACC
Morphine to PVG leads to dependence, to Morphine to PVG leads to dependence, to ACC, does not!ACC, does not!
Animals and us aren’t so different Animals and us aren’t so different after all….after all….
Shuster’s other workShuster’s other work Rats will work for drugs not causing withdrawalRats will work for drugs not causing withdrawal Rats will work for drugs without dependence!Rats will work for drugs without dependence!
Is hard to get them to take things orally thoughIs hard to get them to take things orally though Pickens and Thompson (1968) found that drug Pickens and Thompson (1968) found that drug
use follows the laws of learning!use follows the laws of learning!
So you are saying it is just So you are saying it is just conditioning?conditioning?
Well, umm YesWell, umm YesExplains the paradox of positive and Explains the paradox of positive and
negative effects of drugsnegative effects of drugsChoice in taking a drug depends on other Choice in taking a drug depends on other
available reinforcersavailable reinforcersHayman says it follows the matching law!Hayman says it follows the matching law!
Classification of DrugsClassification of Drugs Sedative hypnoticsSedative hypnotics AlcoholAlcohol AntipsychoticsAntipsychotics AntidepressantsAntidepressants Narcotic analgesicsNarcotic analgesics Psychomotor StimulantsPsychomotor Stimulants NicotineNicotine CaffeineCaffeine HallucinogenicsHallucinogenics weedweed
Sedatives work like this:Sedatives work like this: Modifies the effect of Modifies the effect of
GABAGABA GABA lets Cl- inGABA lets Cl- in
Harder to fireHarder to fire
Positive GABA Positive GABA modulatorsmodulators
Make GABA more Make GABA more effectiveeffective
Barbiturates can open Barbiturates can open ion channel all by ion channel all by themselves at higher themselves at higher levelslevels
Beers and martinisBeers and martinis
Still not that well understoodStill not that well understoodDepresses function of ion channel in Depresses function of ion channel in
glutamate receptors glutamate receptors After chronic use the brain sort of adjustsAfter chronic use the brain sort of adjustsMight be the cause of withdrawal Might be the cause of withdrawal
symptomssymptomsRO 15-4513 seems to be an alcohol RO 15-4513 seems to be an alcohol
antagonistantagonist
AntipsychoticsAntipsychotics
Block DA receptorsBlock DA receptorsD2 especiallyD2 especiallyDirect relationship between effectiveness and Direct relationship between effectiveness and
D2 binding (r =1.00)D2 binding (r =1.00)Also blocks Ach, 5Ht and HAlso blocks Ach, 5Ht and HAlters GABA, peptidesAlters GABA, peptidesBlocks NE receptors, causes an increase in Blocks NE receptors, causes an increase in
NE synthesisNE synthesis
antipsychoticsantipsychotics
Key brain regions:Key brain regions:Mesolimbic dopamine systemMesolimbic dopamine system
That’s the reward systemThat’s the reward system
nigrostriatalnigrostriatalCould be the atypicals have less effect in this area Could be the atypicals have less effect in this area
(more DA here)(more DA here)Drugs that block cholinergic receptors stop Drugs that block cholinergic receptors stop
Parkinsonian symptoms, so do atypicals.Parkinsonian symptoms, so do atypicals.
AntidepressantsAntidepressants
MAOI obviousMAOI obviousTCA stop reuptake of monoaminesTCA stop reuptake of monoaminesSSRI obviousSSRI obviousThese effects are immediate, but the These effects are immediate, but the
antidepressant effect is not, can take days antidepressant effect is not, can take days or weeks evenor weeks evenHmmmmmmmmmHmmmmmmmmm
How the hell does Li work?How the hell does Li work?
Opiate ReceptorsOpiate Receptors
Three or four typesThree or four typesMu Mu
Throughout limbic systemThroughout limbic system HP and amygdilaHP and amygdila
Thalamus and locus coeruleusThalamus and locus coeruleusResponsible for most interesting effectsResponsible for most interesting effectsWeak attraction = great effectWeak attraction = great effect
Opiate ReceptorsOpiate Receptors
Delta ReceptorDelta ReceptorLimbic system too, but do not overlap with muLimbic system too, but do not overlap with muCortexCortexHypothalamusHypothalamusNucleus accumbensNucleus accumbensMedullaMedullaMany antipsychotic drugs work on delta receptorsMany antipsychotic drugs work on delta receptors
Opiate ReceptorsOpiate Receptors
Kappa ReceptorKappa ReceptorNucleus accumensNucleus accumensVTAVTAHypothalamusHypothalamusThalamusThalamus
Sigma ReceptorSigma ReceptorNot just opioidsNot just opioidsPsychotic symptomsPsychotic symptoms
Opiate ReceptorsOpiate Receptors
Periaqueductal Grey area is full of opiate Periaqueductal Grey area is full of opiate receptorsreceptors When in pain, these are stimulatedWhen in pain, these are stimulated
AmygdilaAmygdila emotionemotion
Respiratory, cough and vomit centresRespiratory, cough and vomit centres REWARD SYTEM!!!!!!!REWARD SYTEM!!!!!!!
Well, there has to be some good reason to put a Well, there has to be some good reason to put a needle in your arm……….needle in your arm……….
Coke adds Life, and a wicked Coke adds Life, and a wicked High! The choice of a new High! The choice of a new
generation!generation!
Coke etcCoke etc
Transmitter LeakageTransmitter LeakageCA + 5HtCA + 5Ht
Increase in amount releasedIncrease in amount releasedEcstasy does this with 5HtEcstasy does this with 5Ht
Block reuptakeBlock reuptakeCoke does this onlyCoke does this only
In PNS E is releasedIn PNS E is released
CaffeineCaffeine
Like alcohol, we don’t know!Like alcohol, we don’t know!Might block adenosineMight block adenosine
Neuromodulator that inhibits firingNeuromodulator that inhibits firingSo, caffeine disinhibits?So, caffeine disinhibits?High doeses block benzodiazipine receptorsHigh doeses block benzodiazipine receptors
nicotinenicotine
There are nicotine receptors in:There are nicotine receptors in:CortexCortexBasal gangliaBasal gangliaVentral tegmental areaVentral tegmental areaNucleus accumbensNucleus accumbens
That’s the Reward system folksThat’s the Reward system folks
EffectsEffects
PNS EffectsPNS EffectsTremorsTremors InhibitionInhibition
Seems odd, disinhibitionSeems odd, disinhibitionConstriction of blood vesselsConstriction of blood vessels
There are CNS effects too:There are CNS effects too:Reward systemReward systemRelease of NE, E, DA 5HtRelease of NE, E, DA 5Ht
StimulantStimulant
You look cool and grown up if you You look cool and grown up if you smokesmoke
If it is a stimulant, why do people smoke to If it is a stimulant, why do people smoke to relax?relax? Nesbitt’s ParadoxNesbitt’s Paradox
Physical act of smoking?Physical act of smoking? Withdrawal?Withdrawal? Could be due to nicotine receptors in GABA systemCould be due to nicotine receptors in GABA system
LSD and other 5Ht like drugsLSD and other 5Ht like drugs
About a 110 minute half lifeAbout a 110 minute half lifeMagic Mushrooms are similarMagic Mushrooms are similar
psilocybinpsilocybinTimothy Leary started out with these, Tune In, Timothy Leary started out with these, Tune In,
Turn on, Drop outTurn on, Drop outMorning Glory SeedsMorning Glory SeedsHarmineHarmineBufotenine (toad licking!)Bufotenine (toad licking!)
NE and Ach like drugs and a NE and Ach like drugs and a few others….few others….
MDMAMDMA STPSTP MescalineMescaline Nutmeg!Nutmeg! MandrakeMandrake Deadly nightshadeDeadly nightshade PCP (Angel Dust)PCP (Angel Dust) Special KSpecial K
How do I know the red you see How do I know the red you see is the same as the red I see?is the same as the red I see?
Radioactive LevonantradolRadioactive Levonantradol (syntehtic cannabinoid)(syntehtic cannabinoid)
Group in the next lab found a gene that Group in the next lab found a gene that coded for a receptor sitecoded for a receptor site
The maps matched!The maps matched!Science is coolScience is cool
So, where are the receptors for So, where are the receptors for THC?THC?
CortexCortex HippocampusHippocampus CerebellumCerebellum Basal gangliaBasal ganglia Spinal cordSpinal cord BrainstemBrainstem HypothalamusHypothalamus Spleen!Spleen!
Conclusions about drugsConclusions about drugs
Drugs are funDrugs are funConditioning is a great explanationConditioning is a great explanationCan you handle the truth?Can you handle the truth?Don’t mix science and moralityDon’t mix science and morality
HormonesHormones
Chemicals that target certain organs, and Chemicals that target certain organs, and brain regionsbrain regions
Secreted by glandsSecreted by glandsHomeostasisHomeostasisReproductionReproductionstressstress
Hypothalamus sends releasing factors to Hypothalamus sends releasing factors to pituitarypituitary
Pituitary tells glands to make and release Pituitary tells glands to make and release hormoneshormones
Hormones enter cellsHormones enter cellsTurn on genesTurn on genesProteins madeProteins made
Let’s talk about sexLet’s talk about sex
Hormones that isHormones that isTestosterone contributes to male spatial Testosterone contributes to male spatial
superiority on testssuperiority on testsProgesterone and estradiol, low levels, Progesterone and estradiol, low levels,
females do better on spatial tasks, higher females do better on spatial tasks, higher levels, not so good, but verbal superiority levels, not so good, but verbal superiority shows upshows up
I am so stressedI am so stressed
Brain recognizes stressorBrain recognizes stressorEpinephrine and cortisolEpinephrine and cortisolOne turns stuff on, one turns stuff offOne turns stuff on, one turns stuff offCortisol levels controlled by HpCortisol levels controlled by HpToo much damages HpToo much damages HpSo….So….