Drugs and hormones (they often go hand in hand…..) Psychology 2606

Introduction What is a drug? What is a drug? Well, we all know what it means… Well, we all know what it means… That ain’t good enough, we need some sort of definition That ain’t good enough, we need some sort of definition Alters physiology, but is not food….. Alters physiology, but is not food….. Vitamin C? Vitamin C? Some things are also poisons Some things are also poisons Gasoline, mugwart.. Gasoline, mugwart.. Perhaps we don’t need a definition Perhaps we don’t need a definition

Still…. What if you take it not to treat anything or to get high What if you take it not to treat anything or to get high Coke Coke Coffee Coffee Beer Beer Frankly, an intuitive definition will have to do. Frankly, an intuitive definition will have to do.

Names Chemical Names Chemical Names 7-chloro-1,3-dihydro-1- methyl-5-phenyl-2H-1,4- benzodiazepin-2-one. 7-chloro-1,3-dihydro-1- methyl-5-phenyl-2H-1,4- benzodiazepin-2-one. How very helpful…. How very helpful…. Generic Names Generic Names diazepam diazepam flouexitine flouexitine Trade Names Trade Names Valium Valium Prozac Prozac

Dosages Different dosage sizes will have different effects on different people, animals. Different dosage sizes will have different effects on different people, animals. Especially if they weigh different amounts Especially if they weigh different amounts Standardize it Standardize it mg/kg mg/kg

Dose Response Curves Pick some variable for a response Pick some variable for a response Plot response as a function of dose Plot response as a function of dose One drink and I am relaxed One drink and I am relaxed 4 drinks and I am tipsy 4 drinks and I am tipsy 8 drinks and I am ‘relaxed’ again. 8 drinks and I am ‘relaxed’ again. This shape is very common in DRCs This shape is very common in DRCs

Dose Response Curves Effect of morphine and morphine + naloxone on activity (left) and nosepoke (right) (Criswell, 1987) Effect of morphine and morphine + naloxone on activity (left) and nosepoke (right) (Criswell, 1987)

Describing Effectiveness ED 50 and LD 50 ED 50 and LD 50 Effective dose for 50 percent of the population Effective dose for 50 percent of the population subjective subjective Lethal dose for 50% of the population Lethal dose for 50% of the population Therapeutic Index (TI) Therapeutic Index (TI) TI = LD 50 / ED 50 TI = LD 50 / ED 50 Higher the index, the safer the drug Higher the index, the safer the drug

Potency and Effectiveness or Efficacy Find the ED 50 for both drugs Find the ED 50 for both drugs The one with the lower ED 50 is more potent The one with the lower ED 50 is more potent Efficacy is about the maximum amount of effect the drug will have Efficacy is about the maximum amount of effect the drug will have Morphine vs. aspirin Morphine vs. aspirin

Some other key terms Primary effects or main effects vs. side effects Primary effects or main effects vs. side effects Depends on your point of view Depends on your point of view If you are taking morphine to deal with pain, the main effect is the analgesia and the (albeit fun) side effect is being high If you are taking morphine to deal with pain, the main effect is the analgesia and the (albeit fun) side effect is being high If you are taking it because you want to groove to Quicksilver Messenger Service…. If you are taking it because you want to groove to Quicksilver Messenger Service….

Key Terms, Continued Agonists Agonists Antagonists Antagonists Naloxone and opiates for example Naloxone and opiates for example Additive effects Additive effects Superadditive effects Superadditive effects Sleeping pills and martinis Sleeping pills and martinis

Routes of Administration If you are injecting, you need a vehicle If you are injecting, you need a vehicle Saline Saline Subcutaneous Subcutaneous Slowest absorption Slowest absorption Intramuscular Intramuscular Intraperitoneal Intraperitoneal Fastest absorption Fastest absorption Intravenous Intravenous intraventricular intraventricular

Routes… Get into bloodstream via diffusion Get into bloodstream via diffusion (except IV injections obviously) (except IV injections obviously) Inhalation works the same way Inhalation works the same way Gasses or solids Gasses or solids Orally, depends on lipid solubility Orally, depends on lipid solubility More soluble the easier the absorption More soluble the easier the absorption Ionized molecules are not absorbed Ionized molecules are not absorbed Rate is constant Rate is constant

Distribution and Metabolism Once absorbed, the drug has to get past the blood brain barrier Once absorbed, the drug has to get past the blood brain barrier Get across the membrane through passive or active transport Get across the membrane through passive or active transport Protein binding stops some Protein binding stops some Taken out of blood stream by kidneys, liver Taken out of blood stream by kidneys, liver Measured in half life Measured in half life

What affects metabolism? Age Age Sex Sex Species Species Enzyme induction Enzyme induction Enzyme depression Enzyme depression Putting absorption and excretion together, you get the time course of the drug Putting absorption and excretion together, you get the time course of the drug

Therapeutic window You want to maintain enough of the drug in the system You want to maintain enough of the drug in the system Easy if the drug has a long time course Easy if the drug has a long time course Harder if the time course is longer Harder if the time course is longer

Drug taking When people first thought about it (and until relatively recently) drug taking behaviour just seemed odd When people first thought about it (and until relatively recently) drug taking behaviour just seemed odd Not avoiding pain Not avoiding pain Doesn’t affect all people the same way Doesn’t affect all people the same way You don’t ‘need’ it You don’t ‘need’ it Aha! You must be an immoral pig, probably with little willpower. You are a bad person you junkie lowlife Aha! You must be an immoral pig, probably with little willpower. You are a bad person you junkie lowlife

The Disease Model Oh perhaps it is not a problem with your character or morality Oh perhaps it is not a problem with your character or morality Ahh, yes, it is a disease Ahh, yes, it is a disease Or a disorder as we say today Or a disorder as we say today Started with alcoholism Started with alcoholism What is the disease mechanism? What is the disease mechanism? But it is genetic! But it is genetic! So what So what

Physical Dependence Model Withdrawal (from morphine) caused by ‘autotoxin’ Withdrawal (from morphine) caused by ‘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 all Accounts for the ‘abnormality’ of it all Can be combined with the disease model Can be combined with the disease model

Physical Dependence Model Only Depressants? Only Depressants? Tatum and Seevers (1931) added habituation Tatum and Seevers (1931) added habituation Problem is, that stimulants, for the most part, don’t produce withdrawal symptoms Problem is, that stimulants, for the most part, don’t produce withdrawal symptoms Hmm, Let’s invent a new idea! Hmm, Let’s invent a new idea!

Psychological Dependence When you need a drug, but don’t need a drug When you need a drug, but don’t need a drug When you crave a drug When you crave a drug Circular Circular Biggest problems: Biggest problems: Continual abuse with drugs that do NOT produce withdrawal Continual abuse with drugs that do NOT produce withdrawal Addiction without dependence Addiction without dependence

Positive Reinforcement Model People used to think you couldn’t get animals addicted People used to think you couldn’t get animals addicted Not moral Not moral Can’t get the disease Can’t get the disease Catheter Catheter Work for drug Work for drug (Thompson and Shuster, 1964) (Thompson and Shuster, 1964)

How does it work? Seems circular, until you realize that we know what a reinforcer is not just from operational definition, but from physiology Seems circular, until you realize that we know what a reinforcer is not just from operational definition, but from physiology Dopamine hypothesis Dopamine hypothesis VTA -> MFB -> ACC VTA -> MFB -> ACC Morphine to PVG leads to dependence, to ACC, does not! Morphine to PVG leads to dependence, to ACC, does not!

Animals and us aren’t so different after all…. Shuster’s other work Shuster’s other work Rats will work for drugs not causing withdrawal Rats 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 though Is hard to get them to take things orally though Pickens and Thompson (1968) found that drug use follows the laws of learning! Pickens and Thompson (1968) found that drug use follows the laws of learning!

So you are saying it is just conditioning? Well, umm Yes Well, umm Yes Explains the paradox of positive and negative effects of drugs Explains the paradox of positive and negative effects of drugs Choice in taking a drug depends on other available reinforcers Choice in taking a drug depends on other available reinforcers Hayman says it follows the matching law! Hayman says it follows the matching law!

Classification of Drugs Sedative hypnotics Sedative hypnotics Alcohol Alcohol Antipsychotics Antipsychotics Antidepressants Antidepressants Narcotic analgesics Narcotic analgesics Psychomotor Stimulants Psychomotor Stimulants Nicotine Nicotine Caffeine Caffeine Hallucinogenics Hallucinogenics weed weed

Sedatives work like this: Modifies the effect of GABA Modifies the effect of GABA GABA lets Cl- in GABA lets Cl- in Harder to fire Harder to fire Positive GABA modulators Positive GABA modulators Make GABA more effective Make GABA more effective Barbiturates can open ion channel all by themselves at higher levels Barbiturates can open ion channel all by themselves at higher levels

Beers and martinis Still not that well understood Still not that well understood Depresses function of ion channel in glutamate receptors Depresses function of ion channel in glutamate receptors After chronic use the brain sort of adjusts After chronic use the brain sort of adjusts Might be the cause of withdrawal symptoms Might be the cause of withdrawal symptoms RO seems to be an alcohol antagonist RO seems to be an alcohol antagonist

Antipsychotics Block DA receptors Block DA receptors D2 especially D2 especially Direct relationship between effectiveness and D2 binding (r =1.00) Direct relationship between effectiveness and D2 binding (r =1.00) Also blocks Ach, 5Ht and H Also blocks Ach, 5Ht and H Alters GABA, peptides Alters GABA, peptides Blocks NE receptors, causes an increase in NE synthesis Blocks NE receptors, causes an increase in NE synthesis

antipsychotics Key brain regions: Key brain regions: Mesolimbic dopamine system Mesolimbic dopamine system That’s the reward system That’s the reward system nigrostriatal nigrostriatal Could be the atypicals have less effect in this area (more DA here) Could be the atypicals have less effect in this area (more DA here) Drugs that block cholinergic receptors stop Parkinsonian symptoms, so do atypicals. Drugs that block cholinergic receptors stop Parkinsonian symptoms, so do atypicals.

Antidepressants MAOI obvious MAOI obvious TCA stop reuptake of monoamines TCA stop reuptake of monoamines SSRI obvious SSRI obvious These effects are immediate, but the antidepressant effect is not, can take days or weeks even These effects are immediate, but the antidepressant effect is not, can take days or weeks even Hmmmmmmmmm Hmmmmmmmmm How the hell does Li work? How the hell does Li work?

Opiate Receptors Three or four types Three or four types Mu Mu Throughout limbic system Throughout limbic system HP and amygdila HP and amygdila Thalamus and locus coeruleus Thalamus and locus coeruleus Responsible for most interesting effects Responsible for most interesting effects Weak attraction = great effect Weak attraction = great effect

Opiate Receptors Delta Receptor Delta Receptor Limbic system too, but do not overlap with mu Limbic system too, but do not overlap with mu Cortex Cortex Hypothalamus Hypothalamus Nucleus accumbens Nucleus accumbens Medulla Medulla Many antipsychotic drugs work on delta receptors Many antipsychotic drugs work on delta receptors

Opiate Receptors Kappa Receptor Kappa Receptor Nucleus accumens Nucleus accumens VTA VTA Hypothalamus Hypothalamus Thalamus Thalamus Sigma Receptor Not just opioids Not just opioids Psychotic symptoms Psychotic symptoms

Opiate Receptors Periaqueductal Grey area is full of opiate receptors Periaqueductal Grey area is full of opiate receptors When in pain, these are stimulated When in pain, these are stimulated Amygdila Amygdila emotion emotion Respiratory, cough and vomit centres Respiratory, cough and vomit centres REWARD SYTEM!!!!!!! REWARD SYTEM!!!!!!! Well, there has to be some good reason to put a needle in your arm………. Well, there has to be some good reason to put a needle in your arm……….

Coke adds Life, and a wicked High! The choice of a new generation!

Coke etc Transmitter Leakage Transmitter Leakage CA + 5Ht CA + 5Ht Increase in amount released Increase in amount released Ecstasy does this with 5Ht Ecstasy does this with 5Ht Block reuptake Block reuptake Coke does this only Coke does this only In PNS E is released In PNS E is released

Caffeine Like alcohol, we don’t know! Like alcohol, we don’t know! Might block adenosine Might block adenosine Neuromodulator that inhibits firing Neuromodulator that inhibits firing So, caffeine disinhibits? So, caffeine disinhibits? High doeses block benzodiazipine receptors High doeses block benzodiazipine receptors

nicotine There are nicotine receptors in: There are nicotine receptors in: Cortex Cortex Basal ganglia Basal ganglia Ventral tegmental area Ventral tegmental area Nucleus accumbens Nucleus accumbens That’s the Reward system folks That’s the Reward system folks

Effects PNS Effects PNS Effects Tremors Tremors Inhibition Inhibition Seems odd, disinhibition Seems odd, disinhibition Constriction of blood vessels Constriction of blood vessels There are CNS effects too: There are CNS effects too: Reward system Reward system Release of NE, E, DA 5Ht Release of NE, E, DA 5Ht Stimulant Stimulant

You look cool and grown up if you smoke If it is a stimulant, why do people smoke to relax? If it is a stimulant, why do people smoke to relax? Nesbitt’s Paradox Nesbitt’s Paradox Physical act of smoking? Physical act of smoking? Withdrawal? Withdrawal? Could be due to nicotine receptors in GABA system Could be due to nicotine receptors in GABA system

LSD and other 5Ht like drugs About a 110 minute half life About a 110 minute half life Magic Mushrooms are similar Magic Mushrooms are similar psilocybin psilocybin Timothy Leary started out with these, Tune In, Turn on, Drop out Timothy Leary started out with these, Tune In, Turn on, Drop out Morning Glory Seeds Morning Glory Seeds Harmine Harmine Bufotenine (toad licking!) Bufotenine (toad licking!)

NE and Ach like drugs and a few others…. MDMA MDMA STP STP Mescaline Mescaline Nutmeg! Nutmeg! Mandrake Mandrake Deadly nightshade Deadly nightshade PCP (Angel Dust) PCP (Angel Dust) Special K Special K

How do I know the red you see is the same as the red I see? Radioactive Levonantradol Radioactive Levonantradol (syntehtic cannabinoid) (syntehtic cannabinoid) Group in the next lab found a gene that coded for a receptor site Group in the next lab found a gene that coded for a receptor site The maps matched! The maps matched! Science is cool Science is cool

So, where are the receptors for THC? Cortex Cortex Hippocampus Hippocampus Cerebellum Cerebellum Basal ganglia Basal ganglia Spinal cord Spinal cord Brainstem Brainstem Hypothalamus Hypothalamus Spleen! Spleen!

Conclusions about drugs Drugs are fun Drugs are fun Conditioning is a great explanation Conditioning is a great explanation Can you handle the truth? Can you handle the truth? Don’t mix science and morality Don’t mix science and morality

Hormones Chemicals that target certain organs, and brain regions Chemicals that target certain organs, and brain regions Secreted by glands Secreted by glands Homeostasis Homeostasis Reproduction Reproduction stress stress

Hypothalamus sends releasing factors to pituitary Hypothalamus sends releasing factors to pituitary Pituitary tells glands to make and release hormones Pituitary tells glands to make and release hormones Hormones enter cells Hormones enter cells Turn on genes Turn on genes Proteins made Proteins made

Let’s talk about sex Hormones that is Hormones that is Testosterone contributes to male spatial superiority on tests Testosterone contributes to male spatial superiority on tests Progesterone and estradiol, low levels, females do better on spatial tasks, higher levels, not so good, but verbal superiority shows up Progesterone and estradiol, low levels, females do better on spatial tasks, higher levels, not so good, but verbal superiority shows up

I am so stressed Brain recognizes stressor Brain recognizes stressor Epinephrine and cortisol Epinephrine and cortisol One turns stuff on, one turns stuff off One turns stuff on, one turns stuff off Cortisol levels controlled by Hp Cortisol levels controlled by Hp Too much damages Hp Too much damages Hp So…. So….