Midterm 2 Flashcards
Caffeine in coffee tea and soda
100 mg
50
40
Lethal dose of caffeine
200mg/kg – 100 cups
Methylxanthines
Found in 60 plants– caffeine. In coffee, tea and cocao
Yerba mate and guarana
South american drinks. Yerba–steep leaves. Guarana bre berries (2x stronger than coffee)
Dimethylxanthines
Theophylline
Theobromine – 1/10 the potency of caffeine
- Found in combination with caffeine
Main source of theobromine
Chocolate
Neural action of caffeine and methylxanthines
Competitive antagonists at adenosine receptors
Adenosine
Reduce release of other NTs and suppress neural activity. Caffeine occupies receptors and produces the opposite effect
Octopamine
Excitatory NT that increases in production and kills insects when they eat xanthines
Metabolism of caffeine
Readily absorbed by GI tract and peak effects occur within 2 hours. Metabolized 90% to completion by liver
CYP1A2
Enzyme that metabolizes caffeine, inhibited by SSRIs
Who metabolizes caffeine faster and slower
Smokers– 2x faster
Pregnancy and contraception makes it slower
4 negative effects of caffeine
Decrease appetite and quality of sleep
Relaxation of esophageal sphincters causes heart burn
Osteoperosis
Reduced fertility, more miscarriage, lower birth weight, SIDS
Caffeinism
Acute intoxication at 600mg, substance induced disorder
What % of pregnant women drink coffee
75%
What does teas contain
Caffeine and theophylline
Polyphenols
In green tea, prevents heart disease and cancer
Samovar
Russian tea urn
What does coffee contain
Only caffeiene
First methods of drinking coffee
Ethiopian goat herder– chew berries or drink fermented juice
Sultan Murad
Closed down coffee houses and threatened to toss people in rivers
Kola nut
Contains guarana and a little caffeine– 95% of caffeine is added
What does red bull contain
Taurine and caffeine
Red bull student use
12% in last week
Caffeine SA/CPP
No SA
CPP at low doses, high doses create an aversion
*NOT VERY REINFORCING
Caffeine tolerance
Tolerance shown to many effects
Dreisbach and Pfeiffer
Showed withdrawal effects of caffeine
Where did tobacco originate
Mayans
Bonsack
Invented the cigarette rolling machine in 1881
King James
Counterblaste to tobacco, refuted medical benefits of smoking
Pope urban
Banned catholics from smoking
Ibrahaim
Followed Murad, said tobacco, coffee, wine and opium were the 4 cushions on the sofa of pleasure
Czar Michael
Enforced tobacco ban with whippings
Lucy Gatson
Anti-cigarette league, Republican candidate 1920
Tobacco peak use
1964– 40% – then surgeon linked it to caner
Canadian tobacco use
Has fallen from 70-19%
Annual costs of tobacco
$17 billion in healthcare
How much earlier do smokers die
12 years younger
Incidence of smoking in people with mental disorders
41%
Posselt and Reimann
Produced nicotine in France in 1828
Pure nicotine
Oily, slightly brown or colorless, bad smell
Nicotine absorption
Absorbed 90% to completion through inhalation, only 20% of nicotine in tobacco is absorbed
Contine
Metabolite of nicotine that can be found in urine
Nicotine and urine
Diets high in alkaline reduce smoking– more basic urine
Stress increases smoking– acidic urine
– Making urine more basic increases renal absorption
Lethal dose of nicotine
60mg
Mesolimbic dopamine system
Projecting from ventral tegmental area to nucleus accumbens in pre-frontal cortex
Cholinergic receptors
Located on dopaminergic receptors, activated by nicotine
What NT does nicotine interfere with
Interferes with GABA inhibition
Cholinergic nervous system
Learning and memory in hippocampus. Rich in cannabinoid receptors
Neural action of nicotine
Reduces interference from irrelevant stimuli, improving cognition and concentration
Who has low cholinergic activity
Alzheimers
How many compounds are in a cigarette
4000
Cellular hypoxia
CO preferentially binds ot hemoglobin
Nicotine CPP and SA
Both
Nicotine tolerance
For mood effects
Mecamyaline
Blocks nicotine receptors
Rimonabant
Blocks cannabinoid recpetors
Naloxone
Blocks opiate receptors
Nicotine treatment
95% of people quit on their own but 80% relapse
NRT
Nicotine replacement therapy gets rid of withdrawal symptoms but people dont just smoke for the nicotine
Buproprion
Nicotine receptor antagonist blocks dopamine reuptake . Originally an antidepressant, 2x more effective than placebo
Varenecline
Partial nicotine agonist. Reduce stimulation and dopamine release . Most effective
Cannabinoids
60-80 chemical agents in plant. Very lipid soluble and easily passes barriers. Deposited in organs and fatty tissue
Hot/dry climate for weed
Weak fibre content and a lot of resin
Hashish (Chara)
Dried resin– THC content is 8-14%
Hash oil
Boiling hashish in a solvent– 40% THC
How did weed get to Europe
1800s– through colonization in middle east
De Tours
Noted medical uses of weed, said he fenced a bowl pf fruit
Harry Aslinger
Protested weed in the US because it was used by racial minorities
1929, 1936, 1937
Canadians made legislation and classified weed as narcotic
All states had laws
Marijuana tax act
Incidence of weed use
45% of pop
54% of undergrads
THC
Isolated and synthesized in 1964
THC absorption
Less than 50% of THC in weed can be absorbed– 5-10mg. Only 20% is absorbed by GI tract– ingested dose is 3x
THC and testosterone
Increases at low doses, impotence at high doses
Sativex
Oral THC spray for MS
Antiemetic
Reduces vomitting
THC time for effects
Peak effects in 30-60 min
Delayed matching to sample
Showed weed smokers have working memory problems
8 arm maze WM problem
Revisiting a previously baited arm– increases with weed use
8 arm maze RM problem
Visiting an arm that was never baited– forgot rules for all sessions
THC neural action
Reduces cholinergic NS activity. Damages hippocampus with reduces acetylcholine. Crucially involved in spatial learning
Substitution procedure in THC
Test drug is switched to see if it will maintain an already established drug response. THC will maintain a response, doesnt work as initial reinforcer
SA and CPP in THC
Neither
Tolerance in THC
Evidence of tolerance in animals– extreme doses required to produce it in humans.
Euphorigenic Effects
Increased firing rates of cells in VTA
Withdrawal in THC
Withdrawal in chronic use. Giving a THC antagonist or terminating use. Lasts 7-10 days
Cannabinoid Antagonists
Used to precipitate withdrawals and block rewarding effects to end self-administration
Rimonabant
Most widely used cannabinoid antagonist, originally used for obesity. Trade name Acomplia but it caused depression and anxiety
Endogenous Cannabinoid receptor system
Appetite, pain, mood, memory.
Anandamide
Cannabinoid ligand that activates the endogenous cannabinoid receptor system. Pre-synaptic and regulates release of other NT
What is THC
Exogenous cannabinoid agonist
What NTs does weed increase
Acetylcholine in hippocampus
Dopamine in VTA
What NTs do weed reduce
Glutamate
GABA
Two kinds of cannabinoid receptors
CB1–most important
CB2
What 3 places are cannabinoid receptors concentrated
Basal ganglia and cerebellum– effects movement
Frontal cortex– the high
Hippocampus– memory effects
Harmful products in weed
5x the CO
4x the tar
10x the microscopic damage
% of pregnant women that use illicit drugs
3%
– 75% of that is weed
% of people in rehab that are there for weed
16%
– 9% of recreational users become dependant
Opiate antagonists
Help treat weed addiction by reducing dopamine releasing effects – naloxone/naltrexone reduced SA
Alucinere
Wandering mid
Psychotogenics
Cause psychosis
Psychomimetics
Mimic psychosis
Psychodysleptics
Mind disrupting
Psycholytics
Mind dissolving
Hallucinogens
Found in 6000 plants. 4 categories
Cholinergics
Can be used for effects, or as a poison (protective role for plants). Cholinergic agonists and antagonists
Cholinergic NS
Learning and memory
Cholinergic agonists
Stimulate cholinergic receptors and increase activity. Amanita muscaria and ibogaine
Amanita Muscaria (Fly Agaric Mushroom)
Northern hemisphere Bright red cap with white dots Vikings Flies in milk Drink pee to get high Many unpleasant side effects
What does the amanita muscaria contain
Ibotenic acid
Muscimole
Ibotenic acid
Metabolized to muscazone
Ibogaine
Gabon hunters chew yellow root for stimulating effect that lasts up to 30 hours
Street cure
Ibogaine was sold over the counter for fatigue, people realized you could take a lot and trip out and heroin addicts thought it was healing– ibogaine treatment centres
Schedule 1 drug
High potential for abuse, lack of safety, no medical use
Cholinergic antagonists
Block cholinergic receptors to reduce activity. Atropa belladonna, Datura stramonium, Henbane, Mandrake
Atropa Belladonna
Potato in Europe, north africa and asia. Bell shaped purple flower with berries produces atropine. No repeated recreational use
Atropine
Alkaloid thought to be an aphrodisiac– 1831
Side effects of atropine
Rapid heart beat, loss of balance, uncontrollable movements
Atropine doses
Low– arousal
High– Sedative effects, pleasant trip
Really high– Bad trips– line is very thin
Datura Stramonium
Jamestown weed, stink weed. White/purple trumpet flower with thorny fruit pod with seeds. Used to fortify weed and opium in far east
3 cholinergic blockers in Datura Stramonium
Atropine
Scopolamine
Hyoscyamine
Datura stramonium and witches
Atropine and scopolamine produce sensation of flying
Datura/atropa cigarettes
Legal in Canada until the 60s for bronchodilation
Datura dose
Moderate– 10-20 seeds
50 seeds to hallucinate
Henbane
Strong smelling herb in northern hemisphere with purple veined yellow flowers and hairy leaves. Medieval orgies
2 components of henbane
Scopolamine
Hyoscyamine
Mandragora Officinarum
Potato from europe, africa, asia. Used in potions and as an aphrodisiac. Low doses it is a depressant, higher doses cause hallucination
2 components of mandrake
Atropine
Scopolamine
5 Seratogenic hallucinogens
LSD Psilocybin DMT Bufotenine Foxy
LSD synthesized
Hoffman in 1938
Lysergic acid derived from…
Ergot: Parasitic fungus on grains. Causes vasoconstriction and uterus tone
Minimal dose of LSD
50 micrograms
Osmond
Canadian coined term psychadelic
Leary/Alpert
Did research at Harvard and gave out LSD to students
LSD legal until
1966 when it was classified as schedule 1
LSD use
Peak in 60s– 18%
now lifetime use for taking any hallucinogen is 15%
LSD metabolism
Readily absorbed by GI tract, easily crosses blood-brain and placental barriers. Results last 5-12 hours
First effects of LSD
Caused by activation of sympathetic NS
Object trials
Perceptual residue of objects moving across vision
Form constants
Close eyes and see shapes and patterns
LSD flashbacks
33% of users, possibly response to drug cues
Hallucinogen Persisting Perception Disorder
Recurrent and distressing flashbacks in 4% of users
LSD brain changes
Enduring neuroplastic change in occipital cortex
LD50 of LSD
14mg– 300x the minimal dose
LSD tolerance
All seratogenics produce tolerance in a couple days. Cross-tolerance for psilocybin and mescaline
LSD neural action
Agonist to pre-synaptic seratogenic receptors. Supress firing of neurons in raphe nuclei. AND blocks post-synaptic receptors and antagonizes effects
ARAS
Ascending Reticular Activation System– LSD interferes with filtering sensory information, end up with distortions
Lysergic Acid Amide
1/10 the potency of LSD but naturally occuring– ergot, hawaiian woodrose, sleepy grass, acemonium fungus
Psilocybin
Shrooms native to central america. Eat them or drink brew. More euphoric and visual, less emotional and less bd trips
Isolated shrooms
Hoffman in 1958
Shrooms doses
4-8mg for effect, 15 for hallucinations. Lasts 2-6 hours
Psilocin
Converted in body, more lipid soluble. active agent in shrooms
Shrooms tolerance
Tolerance and cross-tolerance displayed
Dimethyltryptamine
Virola or pergrina plants of South America. Reddish bark is inhaled, injected or eaten
DMT synthesized
1931– hallucinogenic effects found in 1956
Business Mans psychadelic
DMT only lasts 10-60 min
Harmaline
Drink it with DMT when taken orally to block MAO metabolism
Bufotenine
Fish,plants and toads. Snuff containing DMT. Strong sympathetic arousal limits atractiveness
Cyanosis
Skin turns blue when you trip on toads
5-MeO-DIPT
Foxy/Fake ecstasy. Tryptamine type, lasts 3-6 hours
Seratogenic SA
Seratogenics do not produce SA, some will actually try and prevent dose
Phenethylamine Hallucinogens
Norepinephrine and methylated amphetamines cause sympatheic arousal
Mescaline
Norepinephrine type alkaloid in peyote cactus. Causes un pleasant hangovers after. Exert effects similarly to seratogenics
Mescaline isolation
Heffer in 1896, Synthesized by Spath in 1918
Mescaline metabolism
Readily absorbed by GI tract but passes poorly through blood-brain barrier
Mescaline dose
3mg/kg for stimulation
5mg/kg for hallucinations
3 appropriate doses that are undistinguishable
Peyote, shrooms and acid
Mescaline tolerance
Tolerance and cross tolerance
Peyote use
Dropped from 17% -4%
DOM/STP
Synthesized as an appetite suppressant . Associated with more bad trips
DOM/STP dose
10 mg produces hallucinations lasting 16-25 hours
MDA
Metabolite of MDMA. Street name EVE. Originally made in 1910 for appetite suppression, anti-depressant and parkinson. More like a hallucinogen than an amphetamine
MDA dose
60-160 mg lasts 8-12 hours
Merck
Made MDMA as an appetite suppressant in 1914
MDMA dose
50-200 mg lasts 4-6 hours – well absorbed by GI tract
Sasafras tree
Contains safrole which can easily be converted to MDA
Neural action of MDMA
Release serotonin and block reuptake, release dopamine
Myristicin/Elemicin
Found in fruit of myristica fragrans. Nut meg is the dried sees, mace is the seed coat. Weak even at high doses so you vommit for 2 hours then get a little high
SA and CPP in methylated amphetamines
Both
PCP/K
Dissociative anesthetics causing detachment at low doses and anesthesia at high doses. Bind to sigma opiate receptors
Neural action of PCP/K
Act as antagonists on NMDA glutamate receptors. Glutamate opens ion channel and drug attaches inside to suppress glutamate activity and increase dopamine
PCP/K SA and CPP
SA but no CPP
PCP dose
1-10mg lasts 4-6 hours– LD50 is 2-5x that
PCP bad trips
80% of users
PCP tolernace
No tolerance or physical dependance
Ketamine
Less side effects than PCP and only lasts 2 hours– more useful model of schizophrenia
Dextromethorphan
Cough syrup– stimulates sigma opiate receptors and blocks NMDA receptors. Same action as PCP/K but less potent
Cough syrup dose
400 mg for hallucinations
Salvia Divinorum
Mint plant in Mexico. Equal potency to shrooms. Chew smoke or make tea
Ethenogens
Plants that produce a religious experience
Salvinorin A
Active ingredient exerts agonistic action on opiate receptors
Thujone
Found in sage and wormwood and used to make absinthe in france
Thujone neural action
GABA antagonist and acts on serotonin receptors
Volatile hydrocarbons
Solvents with medical use – 20% use in mexican street kids, 1% here
Anesthetic gas
Increase GABA inhbition and glycine, reduce effectiveness of NMDA receptors for glutamate
Glycine
Inhibitory NT
Gas SA and CPP
Some SA but no CPP
Ether
Lullius distilled alcohol and sulphuric acid together – sweet vitrol
Hoffman drops
3 parts alcohol, 1 ether
Chloroform
Synthesized in 1831, similar effects but more potent than ether
Nitrous Oxide
Discovered by Priestly in 1776. Peak use in 60s but use is increasing now.
NO gas damage
Hypoxia and inactivation of B12 dependant enzyme
System involved with analgeisc effects of gas
Endrogenous Opiate system– opiate antagonists block effects
Solvent
Toluene has greatest risk. Correlated with APP
Neural Action of solvents
Activates mesolimbic dopamine reward system
CPP and SA in solvents
Both– no tolerance or withdrawal
3 nitrites
Amyl
Butyl
Isobutyl
Nitrites
Yellow, flammable liquid with fruity odour
When were nitrites synethesized for medical use
1867
Amyl
Angina pain, antidote to cyanide poisoning
Poppers
Butyl and isobutyl in sex drug
