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….