drugs and behaviour final

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Answer

four ways of naming drugs

chemical name, generic name, trade name and street name

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definition of drugs

as a substance that alters the physiology of the body but is not a food or nutrient

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3 ways of getting drugs to market

preclinical testing (animal testing before humans), human clinical testing (small groups of ppl being tested) and use & off label use (realizing a drug works for something else and using it for that)

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caveat

metabolic rates of animals differing - larger animals metabolize more slowly and require lower doses smaller the animal --> larger the dose

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dose response curve

small change at low dose (big effect), small change at high dose (small effect) BLUE GRAPH

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continuous variables

y axis

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ED50

Median effective dose

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LD50

median lethal dose

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purpose of ED50 and LD50

distance between them determine how safe a drug is. further LD50 is from ED50 the safer the drug is. Closer the LD50 to the ED50 the more dangerous the drug.

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Therapeutic Index

how safe drug is (ratio of LD50 and ED50) higher the number the safer the drug is LD50/ED50

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Potency

amount of drug needed to produce any given effect

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effectiveness

if the drug produces a functional response at its functional location it is effect

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drug with lower ED50

more potent, therefore you need less to acheive the same effect

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primary effect

desired effect

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side effect

any other effect that happens due to the drug

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Antagonism

one drug reduces the effect of another

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Additive

effects together - they increase the effect

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potentiation (superadditive effect)

when effect of two drugs together is greater than might be expected from their individual effects

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4 main types of parental routes

subcutaneous (arm or thigh for humans), intramuscular (into muscle), intraperitoneal (in stomach cavity not good for humans), intravenous (needle into vein right into bloodstream, usually done inside elbow).

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Other types of parental routes

intrathecal (drug into CSF not for humans), intracerebroventricular (into CSF via ventricle), intracerebral (into brain tissue)

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capillaries

small branches that have blood carried to them by arteries and away from them by veins, they pass through pores in their walls. drugs pass through their pores through diffusion.

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more capillaries ???

more rapid absorption

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diffusion

substances moving from area of high concentration to areas of low concentration

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factors that affect absorption into circulatory system

volume of blood flow (greater flow faster absorption), heat, amount of capillaries (more capillaries = faster absorption)

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problem with smoke particles

drug cannot be exhaled

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more on history of cocaine

anaestheic properties in cocaine and found it could be injected with morphine and be used as stimulant for creativity, 1860s Italians added to wine

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when did US ban cocaine

1914 used undergound but after WWII increased use

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history of amphetamines

ephedrine used in china 5,000 years ago approved in USA during WWII for narcolepsy, depression, asthma and weight loss

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chen and schmidt 1924

amphetamine - chemical structure similar to adrenalin so they used it to treat asthma

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what are amphetamines used for today

prescriptions limited to ADHD and narcolepsy

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history of cathinone (khat)

started being used around time of Alexander the Great (300 BCE) introduced in europe around 1600s

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where is cathinone popular

middle east (chew it there)

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slow absorption

oral administration (to prevent sleep and fatigue)

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fast absorption

injection, chewing of leaves (coca, khat), sniffing, smoking and inhalation of vapours

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what do the percentage of ions depend on

whether drug is weak acid or weak base, whether fluid is an acid of base, the pKA (ph at which half of molecules are ionized)

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what are the percentage of ions for psychostimulants

drugs are weak bases, pKa of 9 or 10, half are ionzed, PH of solution

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Traditional methods of absorption

incas sucked on rolled coca lead with lime from wood ash or ground shells - this increases PH of saliva and digestive tract, reduces ionization and increases absorption

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current methods of cocaine absorption

cocaine being sold as salt, crack cocaine mixed with solution of baking soda after evaporation chunks are heated and vapours are inhaled

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peak blood levels of amphetamines

after oral administration, 30 minutes

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peak blood levels of cocaine

after sniffing - 10-20 mis, after smoking uncertain but probably fast

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psychomotor stimulants distribution

cross BB barrier; concentrate in kidney, spleen and brain

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excretion of amphetamines

long half lives, depends on PH of urine. acidic drug is not reabsorbed from nephron and has a half life of 7-14 hours. basic the drug is reabsorbed from nephron and shifts to liver and has a half life of 16-34 hours

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excretion of cocaine

fast!!! half life of 45-75 mins depends on acidity of urine

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Agonist and amphetamine

amphetamine is an agonist that blocks DA and NE reuptake

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3 different types of monoamine transporters

dopamine transporter, norepineprine transporter, serotonin transporter

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what occurs when MA is transported into vesicle by a transporter

prevents enzymatic degradation in synapse, preserve NT for later use when an action potential occurs

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reuptake blocker (monoamines)

an example of this is cocaine. this occurs when the monoamine transporters are being blocked which leaves more monoamine in the cleft

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subtrate-releasing agent

an example of this is amphetamine. this occurs when the drug is preventing storage of MA in the vesicle, this causes a release of MA into the cell which causes a reverse action of the monoamines transporters (bringing them back to the cleft)

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where does cocaine bind to

DA transporter, NE transporter and SERTs

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where do methylphenidates bind to

DA transporters, NE transporters and high concentrations of SERTs

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where do amphetamines and methamphetamines bind to

most potent in NE transporters, then DA transporters then SERTs

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which drug acts in a similar way to cocaine

antidepressants (bcuz SNRIs block SERTs and NETs and can act on DATs)

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psychomotor stimulants behavioural effects

CNS - increased release of DA in mesolimbic and nigrostriatal system (to get high about half transporters have to be blocked) PNS- stimulants act on epinephrine synapses, result is sympathetic arousal (fight or flight)

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Anaesthetic effects of psychomotor stimultants

cocaine blocks Na+ channels, action potentials are prevented (basis for anaesthetic effects)

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basic body effects of psychomotor stimulants

increase heart rate and BP, vasodilation and bronchodilation, reduced appetite (cause feeling of fullness). Less of these effects in methamphetamine has fewer of these effects than d- or l- amphetamine

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sleep effects of psychomotor stimulants

block fatigue, increase attention, amphetamines cause insomnia (some are used to treat narcolepsy)

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subjective effects of psychomotor stimulants

improved mood, decreased fatigue, clarity in thought (felt more when blood levels are rising), acute tolerance to pleasurable effects after one use

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damage risk criteria for amphetamines

feel stimulated, like the drug, feel friendly and talkative, do not feel sluggish/fatigue

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subjective rush with amphetamines and cocaine

with iv and inhalation, very dramatic effects and often reported to have sexual component , rush followed by crash (mild depression), cocaine initial numbing sensation followed by 20-30 min high then crash

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punding

repeated behaviours (e.g., cleaning, re-sorting things, taking things apart, putting them back together)

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other things that occur during punding

people get angry if interrupted, caused by stimulation of nigrostriatal DA system

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monoamine psychosis (high doses)

looks like schizophrenia (hallucinations, delusions, paranoia; also flattened affected depression), resolves in hours to days, common symptom formication (sense that bugs are crawling under the skin)

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sensory effects of stimulants on performance

increase in visual acuity, slight improvements in auditory flicker fusion

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general effects of stimulants on performance

increased endurance, reduced fatigue

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amphetamine effects on behaviour and performance

improved reaction time, improved vigilance and attention, improved short memory, impaired divided attention, impaired performance at high doses (inflexibility, inability to change strategies, distraction and impaired judgement)

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ADHD treatments

attention improved by low dose amphetamine and methyphenidate (ritalin in US- 9% of boys, 4% of girls), stimulants increase DA and NE activity in prefrontal cortex. Improvement in attention and impulse control, better control of behaviour.

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stimulants effects on driving

twice as likely to be killed in a car accident, drifting, weaving, speeding, reduced ability in driving

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stimulants effects on sports

banned from sports due to improvements in swimming times, results for track and field sports

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stimulant effects on rats

low dose leads ton increase in locomotor and exploratory activity and in high dose increase in locomotor activity followed by SMA (head bobbing, sniffing, rearing, itching)

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stimulant effects on monkeys

SMA more complex than rats. Low dose leads to reduced consumption of food and water. High dose leads to auto-mutilation

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Dews 1985

Pigeons who take amphetamines increase responding on fixed-interval schedule (behaviour reinforced only when a certain amount of time has passed) , decreases responding on fixed ratio schedule (behaviour reinforced after a certain number of responses)

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amphetamines and dissociation

amphetamines cause dissociation (lack of memory for what was learned under influence of drug)

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discrimination in rats

they can discriminate drugs from saline, poor discrimination when mesolimbic D1/D2 receptors blocked

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sevak et al 2009

did human experiment on discriminaiton. humans could discriminate amphetamine from the placebo

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acute tolerance to cocaine in humans

subjective effect of improved mood, if they take too much coke (10-12 hours later) no longer improved moods. do not feel heart rate and bp effects so may risk toxic effects

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chronic tolerance in humans

some effects tolerate with time and continued administration, no tolerance for blocking sleep, sensitization

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withdrawal of stimulants

depression and lethargy, sleep problems, increased appetite, vivid dreams. chronic use leads to severe depression. begins 24 hours of stopping and mostly complete in a week. depression and appetite changes may persist for months

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cocaine self administration in humans

large quantities for a short period of time (run-abstinence cycle) enjoy mixing drugs with cocaine with heroin, benzos or hallucinogens.

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amphetamine self administration in humans

like run abstinence cycle (large quantities for a short period of time), for staying awake, high doses for euphoria (lasts 24-48 hours then big crash)

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cocaine non human animals self administration

cocaine has few withdrawal symptoms but reinforcing , lab animals will administer cocaine to point of death, binging does not occur when availability is restricted

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direct harmful effects of cocaine

liver damage, damage to mucous membranes (sniffing)

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direct harmful effects of amphetamines (short term)

confusion, restlessness, punding, stroke in some individuals

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direct and indirect harmful effects of chronic use of stimulants

heartbeat, BP (may lead to stroke), indirect effect on small blood vessels in brain; potential death of DA cells

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indirect harmful effects of cocaine

disease in IV users (hepatitis and HIV/AIDS), poor diet, lack of sleep, anti social behaviours, 6x normal death rate

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harmful effects of stimulants on reproduction

more risky sexual behaviours, high dose disrupt sexual activity, when used during pregnancy birth abnormalities and behavioural problems in kids, cocaine correlated with 10x occurence of early placental development

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cocaine overdose (caine reaction)

depends on route of administration, genetic differences caine reaction has 2 phases 1- excitement/seizure then loss of conciousness/heart failure

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3 main therapies for stimulants

behavioural, pharma (looking for non-addictive drug or one taken orally and has longer half life), immunization (in testing phase)

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why does the textbook not use the word narcotic?

negative connotation associated with older interpretations of the word, negative images of addicts

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where is opium from

poppy sap in seed pods, only available 10 days of life cycle then they are pressed into cakes and dried

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what contains opium

morphine, codeine, thebaine

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when were morphine and codeine isolated

morphine-1800s, codeine- 1830

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morphine

opium sap (10% of weight), salt form, available only by prescription

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codeine

opium sap (0.5% of weight), available in Canada in small quantities over the counter (cough or pain meds)

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hydrocodone

derived from codeine, most commonly prescribed opioid in USA, suppresses cough, relives pain and can be combined with other pain relievers, common one Vicodin

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natural opioid

morphine and codeine made from opium (from poppy)

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semi-synthetic opioids

hydrocodone, thebaine and heroin

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thebaine

occurs naturally in tiny quantities, source of oxycodone, known as percocet when combined with acetaminophen, crushed and injected (causes accidental overdose and addiction)

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heroin (diamorphine)

made by adding to morphine molecule, 10x more potent and more lipid soluble (so crosses BB barrier, gets to brain quicker)

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synthetic opioids

act same as morphine just chemically different and vary in effectiveness. many based on fetanyl molecule. examples include; methadone, fetanyl, meperidine.

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history of opium

farmed since 5000 BCE, originated in middle east, first smoked in china in 1600s, 19th century freely available in britain

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history of heroin

invented by Bayer (Germany) company that invented aspirin, discovered heroin same way, banned in US in 1920, Canada recently started prescribing heroin

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how they made aspirin

they were experimenting with acetyl groups to reduce corrosive properties of salicylic acid - aspirin

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jan 2016-march 2022

30,834 opioid toxicity deaths between jan and march 21 deaths per day mostly involved fetanyl

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how much did opioid deaths increase by over covid pandemic

91%, could be due to toxic drug supply, isolation, stress, anxiety, limited services

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what is canada doing to prevent opioid deaths

sued makers of oxycontin to cover health costs for those addicted, pushing for safe use sites during pandemic

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administration routes of cocaine

weak base so not readily absorbed by oral route, only 15% available in digestive tract and liver, advantageous oral administration allows maintenance of constant blood levels

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administration routes of heroin

mainly parental/inhalation; snuff, pipe, smoking, injection

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administrations of antagonists (e.g., naloxone)

parentally bcuz too slow via digestive track

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distributions of opioids in brain

concentrated in basal ganglia, amygdala and periaqueductal gray

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distributions of heroin

highly lipid soluble, goes to brain quick but cannot act there, rapidly metabolized

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excretion of morphine

10% excreted unchanged, half life is 2 hours, 90% is gone in 24 hours

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excretion of methadone

10% excreted unchanged, half life of 10-25 hours , bound to blood proteins, long action- useful as maintenance therapy

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excretion of nalaxone

completely metabolized in liver, very short half life of 1.5 hours, effects may wear off too soon

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neurophysiology history

first receptors discovered in 1973

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what were opioids derived from

polypeptides (large molecules that can be NTs or hormones)

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4 known types of opioid endorphines or enkephalins

Mu (μ), kappa (k), delta (δ) and ‘opioid receptor-like’ (ORL1)all metabotropic and release second messengers

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effects opioid endorphines have on cell

activate potassium channels, inhibit certain voltage gated calcium channels, inhibit production of cAMP second messenger and activates kinases and may alter gene expression (endocytosis)

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different types of effects of opioids

mu (agonists or antagonists), agonists or antagonists or more receptor types, some are mixed ago

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locations of cells and outcomes

mu - limbic system, thalamus, locus coeruleus, VTA, PAG, delta- limbic system, cortex, hypothalamus, Nacc, medulla, kappa- nacc, VTA, hypothalamus, thalamic

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mu receptors

where most opioids act, responsible for analgesia and sedation effects and responsible for many side effects

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naloxone opioid replacement

pure opioid antagonist at mu, delta and kappa receptors, mild effect, used to treat opioid overdose

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three important sites of actions

1 analgesia (PAG) different types of pain are relived by different types of drugs 2 reinforcement (reward path), mu receptors in VTA inhibit GABA interneurons (more DA), most reinforcing and 3 vital life function (brain stem); respiratory, vomiting etc

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opioid effects on body

vomiting nausea (first time use), constricted pupils, lower bp, constipation, reduced sex hormone, disturbed sleep patterns

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opioid subjective effects

many vivid dreams, 19th century opium oral administration produced feelings of happiness, improved vision and improved hearing. some suggests opium increased creativity. Samuel Taylor Coleridge(took combo alcohol and opium)

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opioid mood effects

initial positive feelings then negative, felt good until tolerance developed, felt worse + psychiatric symptoms after few days, relief only 30-60 mins, less social activity, more aggression

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human performance on opioids

slowed psychomotor performance and some cog performance, most tasks tolerance develops

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opioid effects on animal behaviour

low dose increase SMA, high dose decrease SMA (except in mice), low dose - increase responding, high dose - decreased responding, antagonists block effects at low dose, avoidance slow high dose, don't increase behaviour surpressed by punishment

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opioid tolerance

rapid and extensive tolerance, 3 or 4 months may increase 10 times.

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types of opioid tolerance

acute tolerance; thought due to removal of opioid receptors (endocytosis), long-term tolerance; recycling of receptors (altered sensitivity), context dependent (via learning), cross tolerance (with other mu opioids, alcohol not other drugs)

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withdrawal of opioids

never fatal, always unpleasant, starts in 6-12 hours peaks at 3 days (restless, yawning, chills, goosebumps, short breaths), then deep sleep 8-12 hours then vomiting, sweating twitching PAG INVOLVED (reduces symptoms of heroin withdrawal)

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addicted humans self administration of opioids

begins with curiousity, preoccupied with getting drug

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opioid use without doctors

56% friends/family, 80% were originally prescribed

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overdose of opioids

can kill you by depressing breathing, half of overdose deaths in US, heroin leading cause of death people with 5-10 years of expereince, laced with quinine, combining with bezo or alc or loss of tolerance (after not using or new env)

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more harmful effects of opioids

increase risk of cancer, reduced fertility, abnormal brain activation, pregnancy - withdrawal harms fetus, serious health problems, low birth weight and premature

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lifestyle and complex interactions with opioids

more accidents, more death from disease, more homicide, more suicide, more cancer deaths and add to this poor social support and poverty

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opioid treatment

detoxification (abstinence or opioid antagonist) or using methadone to help make withdrawal symptoms less bad, maintenance therapy (methadone- antagonist to heroin lasts 24 hours), antagonist therapy

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antipsychotics purpose

to treat schizophrenia and other psychotic disorders

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schizophrenia positive symptoms

hallucinations, delusions, paranoia, incoherent thoughts and speech

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schizophrenia negative symptoms

diminished expressiveness, lack of interest in work/social life, uncommunicative, no feelings of pleasure

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other schizophrenia symptoms

problems with learning, memory and problem solving

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brain abnormality theory behind schizophrenia

double normal size lateral and third ventricles, potentially due to loss of brain tissue volume elsewhere, loss is progressive can occur before birth, children exhibit warning signs

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1960s dopamine hypothesis schizophrenia

results from excessive DA activity in brain (3 revelevant DA systems nigrostriatal, neocortical, mesolimbic), drugs that increase DA function can cause psychosis

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Newer DA theory

due to overactivity of DA especially in D2 receptors. blocking DA does not relieve symptoms right away, slow changes may be involved, negative and cog symptoms do not improve

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most recent DA theory

excessive DA in mesolimbic pathay explains positive symptoms, lack of DA activity in mesocortical pathway explains negative symptoms

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glutamate hypothesis 1950s

synthesis of phenyclidine and ketamine, produced psychosis like symptoms, bind at GLU NMDA, PCP antagonizes with NMDA binding sites

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glutamate in relation to schizophrenia

genetic differences may predispose people to reduced glutamate activity, glutamate levels same as healthy individuals

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current view on schizophrenia

develops gradually, cog and neg symptoms first then positive, development may be explained by neural pathway changes, happens at various NT sites in brain

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proposed current schizophrenia theory

brain deterioration (moved along by synaptic pruning), deterioration results in loss of glutamate synapses (glutamate dysregulation) and glutamate no longer activates mesocortical DA neurons (neg symptoms), glutamate no longer inhibits interneurons (excit

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when were antipsychotic meds discovered

accidentally in 1950s

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how were antipsychotic meds discovered

search for anxiety treatment to prevent surgical shock (wanted to block epinephrine and Ach)

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first antipsychotic

chlorpromazine - promoted artifical hiberantion

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impact of antipsychotics

80% reduction in numbers of people in mental institutions, replaced barbiturates, electric shock and being placed in mental institution

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typical antipsychotic

developed first as dopamine antagonists (D2 blockers). Associated with motor problems and often causes non-compliance. 1/3 of ppl do not respond

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atypical antipsychotic

developed in 1975 dopamine and 5-HT antagonists EPS atypical so there are fewer motor problems. Weak affinity for D2 receptors and high affinity for D3 and D4 receptors. clozapine was first.

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third generation antipsychotics

2002- aripiprazole. modulates D2, D3 and D4 receptors. DA activity is low (prefrontal cortex) - it is an agonist and where DA activity high (mesolimbic path) it is an antagonist. Can treat positive and negative symptoms. Not better than other types.

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routes of administration for antipsychotics

treating psychosis is taken orally, for surgical treatment (sedation) is intramuscular and intravenous, in cases of non compliance, IV or depot injection

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absorption of antipsychotics

most are easily absorbed, cross BB barrier and in body fat, slowly released from body fat

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absorption of typical antipsychotics

in oil accumulate in body fat and can take weeks or months to reach steady state

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absorption of atypical antipsychotics

not in oil do not accumulate as much in body fat- peak 4-28 days

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variable effects of antipsychotics

effect of single drug varies from person to person, they are hard on the body

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side effects of typical antipsychotics

EPS,inability to stay still, tics, problems regulating temp, sun sensitivity, weight gain, heart problems, dry mouth, impaired vision, dizziness, constipation, jaundice and seizure risk clozapine - dramatically reduce white blood cell count

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side effects of atypical antipsychotics

weight gain, diabetes, increased cholesterol, heart problems, dry mouth, problems regulating temp, dizziness, nausea, cataracts

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side effects of third generation antipsychotics

far fewer side effects, mainly nausea and dizziness

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EPS (extra pyramidal signs)

looks like parkinson's disease; tremor, loss of coordination, slow movement, flat facial expression. reported in up to 40% of people who take typicals

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akathisia

restlessness, compulsive movement, protruding tongue, facial grimace. seen in 20% of people taking typical antipsychotics

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tardive dyskinesia

involuntary tics, movement in face, tongue flicking, smacking lips, symptoms are permanent (even when drug is stopped)

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antipsychotics effects on sleep

no changes in sleep cycle, can be sedating and can lengthen sleep

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typical antipsychotic effects on behaviour

described as unpleasant, chlorpromazine; confusion, difficulty concentrating, dejection, anxiety, irritability, feeling tired. haloperidol; restless and having difficulty moving

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is atypical or typical antipsychotics effects more unpleasant

typical

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antipsychotics effect on performance

potential impairment in attention due to sedative effects, impairment of attention

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animals and antipsychotics

avoid antipsychotics

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other uses for antipsychotics

prevent nausea and vomiting , pre surgical sedatives, treats huntington's disease, tourette's, tardive dsykinesia

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major depressive episode

feeling of sadness, loss of appetite, anhedonia (no interest in normal activities), lack of energy, guilt, sleep problems, suicidal ideation

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major depressive disorder

same as depressive episodes symptoms just do not go away

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dysthymic disorder

chronic mild depression

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history of depression

since early greek civilization, 13-17% will experience, women double likelihood of having depression in life time

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depression for males vs females

male= 12% in lifetime, feel tired and irritable. females= 24% in lifetime, feel sad and guilty

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suicide and depression

5x more risk for suicide. females attempt more, males suceed more

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original monoamine theory

depression caused by reduced activity in 5HT, NE and DA, drugs that deplete monoamines cause depression, depleting 5HT cause depression

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problems with monoamines theory

antidepressants act on monoamines but relief may not be felt for weeks or months, only affects mood in some ppl (with family history of depression)

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additions to monoamine theory

norephineprine and 5HT dysregulated in depression, 5HT, NE & DA may influence other systems, second messenger systems, hormones and immune system all can increase risk of depression. depression complex disorder

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updates on monoamine theory

low levels of 5HT, low levels of tryptohan, low levels of tryptophan metabolite, decreased numbers of 5HT transporter reuptake proteins, abnormalities in number and function of 5HT receptors

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glucocoricoid theory of depression

hypothalamic-pituitary-adrenal axis (HPA), stress response in hypothalamus leads to activation of pituitary and release of cortisol from adrenal cortex, cortisol travels to hippocampus, amygdala, prefrontal cortex, buildup cortisol - increase risk depre

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interaction monoamine & glucocoticoid processes

connections from amygdala to 5HT & NE in midbrain & hindbrain - overexcite override prefron cortex, high levels stress - reduce 5HT hippocampus, adrenalectomy - upregulation 5HT receptors

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what do antidepressants do

increase number of cortical receptors, improves feedback and ultimately lowers level of stress hormone, normalization happens before person feels relief, if normalization does not occur person relapses

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first generation antidepressants

monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs)

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second generation antidepressants

more recent many different chemical structures. includes selective serotonin inhibitors (SSRIs)

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third generation antidepressants

includes both 5HT and NE reuptake inhibitors (SNRIs)

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Monoamine oxidase inhibitors (MAOIs)

first one 1950s. originally tuberculosis med. fell out of favour, supposedly, caused liver damage, ineffective (correct dose neither r true) newer ones available

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tricyclic antidepressants (TCAs)

discovered accidentally during research on antipsychotics, thought to be safer than MAOIs - so replaced them, block reuptake transporter proteins 5HT NE act on NT system many side effects

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second generation antidepressants

first SSRI 1987 (prozac) slightly different than TCAs- fewer side effects, treat anxiety

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third generation antidepressants

SNRI enhanced NE activity and reduce symptoms of fatigue, do not alter Ach so fewer side effects

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first generation antis and monoamines

block enzyme activity and breaks free floating monoamines (NE, DA and 5HT) 2 types of enzymes MAO-A (degrades all 3 types) MAO-B (degrades DA)

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second generation antis and monoamines

SSRI block reuptake transporter for 5HT, cause buildup of 5HT in synapse, act only on 5HT but everywhere, delayed effect on these drugs

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third generation antis and monoamines

block reuptake of 5HT, NE and sometimes DA, some modified to induce sedation

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main antidepressant actions

monoamine oxidase inhibitors, tricyclics, second generation; selective serotonin reuptake inhibitors

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absorption of antidepressants

all the drugs have similar absorption, TCA peak in blood 1-3 hours, SSRIs/SNRIs peak at 4-8 hours, first pass metabolism in liver/digestive tract

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excretion of MAOIs

short half life 2-4 hours,

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excretion of TCAs

half life of 24 hours

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excretion of second & third generation

half life of 15-25 hours

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are antidepressants effective

most effective for ppl who are severely depressed, often have to try several before finding one that works for them. 60-70% expereience relief, placebo effects high

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MAOIs side effects

tremors, weight gain, dry mouth, postural hypotension, insomnia or sedation, breaks down tyramine in food (cheese, beer, wine, chocolate), can cause cheese effect - serious condition in which BP rises may cause internal bleeding, serotonin syndrome

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tricyclic side effects

fluid retention, constipation, dry mouth, dizziness, low BP, weight gain, reduced seizure threshold, can cause nightmares and can cause heart attack

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SSRI and third generation effects

SSRI; nausea, headache, nervousness agitation, gastro problems, weight lose, vivid dreams, insomnia third generation; increase appetite, weight gain, gastro problems, may cause sedation

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subjective and behavioural effects of antidepressants

feeling of apathy, no euphopria, driving and other vigilance tasks are affected by TCAs, personality changes (questionable)

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tolerance and withdrawal of antidepressants

TCAs have to be gradually withdrawn can include restlessness and anxiety, SSRIs; anxiety, headache, fatigue and others and SNRIs; serious withdrawals, psychiatric symptoms

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other treatments for depression instead of antidepressants

herbal treatments (lavender, chamomile); not large effect, electroconvulsive therapy, deep brain stimulation, transcranial magnetic stimulation, exercise, CBT, psychotherapy (reduce cortisol), hallucinogens

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female cannabis plant

shorter with more leaves

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2 species of cannabis plant

cannabis sativa and cannabis indica

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history of cannabis

native to central asia, grown in europe for medicine, 19th century used to treat psychiatric and neurological disorders, 1970 no medical potential, strong potential for abuse

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cannabinoids

main ingredient delta-9-tetrahydrocannabinol, anything that binds to endocannabinoid receptor

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phytocannabinoids

from plant

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endocannabinoids

endogenous to body, are triggered when one consumes cannabis. THC effects of cannabis (psychoactive effects)

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synthocannabinoid

synthesized made in lab, legal and illegal varieties, some treat anorexia associated with AIDS

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THC

psychoactive and appetite inducing

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CBD

non psychoactive and may be therapeutic

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oral administration of cannabis

lipid soluble, slow absorption, first-pass metabolism in the liver, peak of effects in 1-3 hours

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inhalation of cannabis

normal smoking 10-25% of cannabinoids to lungs (all absorbed)

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cannabis vaporizers

heats plants - safer because cannabinoids vaporize at lower temp than tar/carcinogens

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cannabis distribution

highly lipid soluble so distributed to fat concentrations in lungs, kidneys, only 1% concentrated in brain

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cannabis excretion

metabolism mainly in liver, delta-9-THC is converted to 11-hydroxy-delta-9-THC, CBD and CBN interact with THC slows metabolism in liver

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THC half life

biphasic half life; drop in first 30 mins followed. by 20-30 hour half life

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cannabis neurpharmacology

receptors found in 1990s two receptors CB1 (in CNS), CB2 (found in immune system and some in brain)

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where cannabis acts in brain

cerebellum (movement), hippocampus (memory) and maybe mesolimbic DA system (via opioids)

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effects of moderate dose of cannabis

bloodshot eyes, drooping eyelids, dry mouth/thirst, hunger (3 hours after use), altered perceptions & good feelings, increased heart rate, drowsiness, high dose cause sleep disturbance

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medical uses of cannabis

glaucoma, helps reduce nausea with chemo, reduces muscle spasms, improves subjective pain ratings

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cannabis effects on human behaviours

euphoria, hilarity, placid dreaminess, avoid physical activity, sensory distortions, loss of sensitivity to pain, experience time as passing more quickly, long term use associated with reduction in hippocampal volume, no effect on creativity

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cannabis tolerance

fairly rapid 5-6 days in animals, down regulation in CB1 receptors

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cannabis withdrawal

not severe in animals or humans in humans appetite change, restlessness, craving

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synthetic cannabis toxic effects

more dangerous agitation, confusion, psychosis, paranoia

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cannabis gateway theory

more cannabis use associated with use of other drugs, no causal relationship

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some harmful effects of cannabis

high doses - panic attack, may accelerate schizophrenia occurs in people who already may be vulnerable, effects may be permanent on developing brain

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types of hallucinogens

classic hallucinogens; lysergic acid amide (LSD), psilocybin, MDMA (ecstasy), ketamine, dextromenthorphan

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sources of classic hallucinogens

LSD- morning glory seeds and ergot fungus grains, psilocybin - mushrooms

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sources of other hallucinogen

toad, vines, plants, nutmeg, mace

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pre LSD history

Ergotism (sickness from ingesting grains that have been infected) causes hallucinations, delirium and feeling of excessive warmth during middle ages (500-1500 CE)

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LSD history

Albert Hoffman 1940 accidentally ingested and had the first trip. they thought it could be used to treat mental disorders because it looked similar to serotonin

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Timothy Leary

Psych prof at harvard experimented with psilocybin in Mexico thought hallucinogens could lead to great psychic improvement

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history of psilocybin

Aztecs (14th century) used in religious ceremonies

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administration of LSD

oral gel tabs effective at 20-80 µg for intense visuals 200 µg takes effect in about 30-60 mins mostly metabolized by liver felt for about 12 hours

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administration of psilocybin

oral in dried form

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hallucinogens and the CNS

LSD - serotonin receptor agonist only at certain receptor subtypes. Psilocybin also agonist but at more serotonin receptor subtypes

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Locus coeruleus and hallucinogens

drugs can surpress also enhance response to novelty

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cortex and hallucinogens

drugs act on glutamate to increase duration of action potentials esp prefrontal cortex

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raphe nuclei and hallucinogens

inhibits 5 HT release

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phantasticant perceptual effects

effect of hallucinogens means feeling as though expereience is significant (emotionally or to world events), enhaced expereince of music and art

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etactogenic and empathogenic

insight into one's own feelings and mind and insight leading to empathy with others

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Tolerance of hallucinogens

rapid 1-3 days, sensitivity then develops

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withdrawal symptoms of hallucinogens

none

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harmful effects of hallucinogens

designer versions can be dangerous, psychedelic crisis, flashbacks

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History of MDMA

synthesized by Merck 1914

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administration of MDMA

oral administration ~100mg, effects felt in about half an hour and peak in an hour or 2, half life of 8 hours and effects can persist for days

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excretion of MDMA

either in urine or being metabolized to MDA

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neuropharmacology of MDMA

prevents reuptake of DA, NE and 5HT, in humans increases levels of serotonin, stimulant and euphoric effects related to increased DA transmission, empathy due to enhanced release of oxytocin, heavy use - higher cortisol

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effects of MDMA on non human animals

rats; increased locomotor activity, increase in anxiety, avoidance behaviours impairment of object recognition memory monkeys; increased locomotor activity, more social grooming behaviour

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effects of MDMA on humans

low dose- effects like cannabis, high associated with social inhibition, openess, self-confidence, emotional warmth, empathy, energy and euphoria, rapid tolerance

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acute withdrawal of MDMA

'crash' associated with lethargy, irritability, depression, insomnia and memory problems

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MDMA effects on body

short term - pupil dilation, headache, teeth grinding heavy use - tachycardia (HR over 100 beats per min) can cause hyperthermia in warm env, excercising extra sweat brain swelling '

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Neurotoxic effects of DA on mice

degeneration of axon terminals in nigro-striatal DA path early life (adolescent) exposure leads to greater vulnerability later on

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Neurotoxic effects of DA on humans

effects on DA less obvious; future Parkinson's disease may be result

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Neurotoxic effects of 5HT on humans

can lead to impulsivity, problems with memory, emotion and cognition

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Neurotoxic effects of 5HT on monkeys

damages serotonin neurons in many brain regions - damage persists for 7 years in some species of monkeys

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history of ketamine

synthesized in 1960 - mainly used by veterinarians

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administration of ketamine

oral liquid or capsule but can be inhaled from power. effects only last about an hour

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neuropharmacology of ketamine

blocking glutamate receptive, therefore glutamate is ineffective

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behavioural effects of ketamine

usual dose- sedation, tingling, numbness, euphoria, feeling of floating date rape drug high dose- psychosis, catatonic excitation, sudden mood change

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more effects of ketamine

some will be injured if they do not feel pain, in rats kills fetus

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lethal dose ketamine

40x usual dose

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dextromethorphan

synthetic cough supressant - found in cold and cough drugs very large doses blocks NMDA receptors increases 5HT (should not b taken w antidepressants) rapid tolerance

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