Post Mid-2

Question 1

Coffee is a ___ preparation, an infusion of complex ___ from a ___ __

Answer 1

Coffee is a botanical preparation, an infusion of complex chemicals from a plant fruit

Question 2

How are new chemicals from a plant source identified and characterized for pharmacological activity?

Answer 2

• extraction
• purification
• predictions about which chemical we are going to investigate
• characterization

Question 3

What series of experiments should psychoactive chemicals pass in order to understand the potential addictiveness of a drug?

Answer 3

• animal behaviour e.g. lever presses- drug seeking
• physiological measures
• biochemical assays

Question 4

Methylxantines resemble a ___ (-rgic) base like __ and ___

Answer 4

Methylxantines resemble a purine (-rgic) base like adenosine and guanine

Question 5

When people drink coffee, caffeine is metabolized into 3 other methylxantines which are…

Answer 5

1) Theophylline (4%)
2) Theobromine (12%)
3) Paraxanthine (84%)

Question 6

___ acid induce phase II transferases like GST and other liver enzymes

Answer 6

Chlorogenic acid induce phase II transferases like GST and other liver enzymes

Question 7

____ acid has anti-inflammatory properties on its own and it also promotes vascular health by increasing NO production

Answer 7

dihydrocaffeic acid has anti-inflammatory properties on its own and it also promotes vascular health by increasing NO production

Question 8

___ and ___ are diterpenes. They increase phase II enzymes, they induce anti-stress genes (antioxidant) but elevate cholesterol

Answer 8

Kahewol and cafestol are diterpenes. They increase phase II enzymes, they induce anti-stress genes (antioxidant) but elevate cholesterol

Question 9

___ and ___ are the most common anti-oxidant sources

Answer 9

coffee and tea are the most common anti-oxidant sources

Question 10

Caffeine is a ___ stimulant in ___ infants, ___ most commonly prescribed ___ drug after antibiotics.

It functions by inhibiting ___ which increases concentration of cAMP within ___ neurons, creating a ___ ___ in those cells.

Promotes ___ and ___ ___ in babies

Answer 10

Caffeine is a respiratory stimulant in premature infants, 2nd most commonly prescribed NICU drug after antibiotics.

It functions by inhibiting PDE4 which increases concentration of cAMP within preBotC neurons, creating a robust rhythm in those cells.

Promotes breathing and blood oxygenation in babies

Question 11

Caffeine is also used in ___ because it is a bronchodilator

Answer 11

Caffeine is also used in asthma because it is a bronchodilator

Question 12

Caffeine can be used to treat ___ in certain cases because it reduces cranial blood flow

Answer 12

Caffeine can be used to treat migraines in certain cases because it reduces cranial blood flow

Question 13

___ is the most commonly consumed psychoactive substance on the planet

Answer 13

Caffeine is the most commonly consumed psychoactive substance on the planet

Question 14

Absorption of caffeine

Answer 14

• ingestion
• small intestine is where absorption occurs
• 45 min to peak

Question 15

Distribution of caffeine

Answer 15

• amphipathic
• rapid and widely distributed- penetrates brain tissue

Question 16

Metabolism of caffeine

Answer 16

• limited or no first-pass metabolism
• CYP1A2 (demethylation reactions)
• paraxanthine: will increase blood glycerol/fatty acid via lipolysis
• theobromine: dilate vessels, increase urine volume- makes caffeine a diuretic
• theophylline: inhibit PDE, increases concentration of cAMP, relaxes smooth muscle

Question 17

Caffeine is excreted through the __

Answer 17

kidneys

Question 18

Caffeine also effects ___ release and ___ receptors

Answer 18

Caffeine also effects Ca release and GABA receptors

Question 19

AR (adenosine receptor) and PDE (phosphodiesterase) are ___ (expressed everywhere in body)

Answer 19

AR (adenosine receptor) and PDE (phosphodiesterase) are ubiquitous (expressed everywhere in body)

Question 20

Caffeine will antagonize all 3 major types of ___ .

There are 4 main sub-types of __: ___, ___, ___ and ___

___ and ___ play primary roles in caffeine effects. They are mostly pre-synaptic receptors that limit neurotransmitter release

Answer 20

Caffeine will antagonize all 3 major types of ARs (adenosine receptors).

There are 4 main sub-types of AR: A1, A2a, A2b and A3

A1 and A2a play primary roles in caffeine effects. They are mostly pre-synaptic receptors that limit neurotransmitter release

Question 21

A1 will inhibit ___ ___ and reduce cAMP levels. It will reduce ___ release, because of how neurons are wired that undergo these cellular effects it can lead to increase ___ release

Answer 21

A1 will inhibit adenylyl cyclase and reduce cAMP levels. It will reduce NT release, because of how neurons are wired that undergo these cellular effects it can lead to increase NT release

Question 22

___ will exist as pairs at rest or after they are triggered by adenosine or some other endogenous ligand. They will come together to form an active receptor complex

Answer 22

AR (adenosine receptors) will exist as pairs at rest or after they are triggered by adenosine or some other endogenous ligand. They will come together to form an active receptor complex

Question 23

Not only can AR pair with other AR but they can dock onto ___ ___ to form active signalling complexes e.g. 2A2a + 2D2

Answer 23

Not only can AR pair with other AR but they can dock onto dopamine receptors to form active signalling complexes e.g. 2A2a + 2D2

Question 24

Effects of caffeine on brain

Answer 24

• alertness, arousal, and focus
• enhanced mood, confidence and sociability
• high doses can cause anxiety
• reduced blood flow to brain
• sleep inhibited

Question 25

Effects of caffeine on heart

Answer 25

• low dose: decreased HR
• high dose: increased HR and BP

dose dependent effects that are opposite

Question 26

Effects of caffeine on lungs

Answer 26

• increased respiratory rate
• dilated bronchi

Question 27

Effects of caffeine on skin

Answer 27

• increased fat mobilizations, fatty acids, glycerol

Question 28

Effects of caffeine on bladder

Answer 28

• increased urination

Question 29

In general caffeine’s acute effects fall under ___ category. They are similar but far milder compared to __ and __

Answer 29

In general caffeine’s acute effects fall under stimulant category. They are similar but far milder compared to cocaine and amphetamines

Question 30

Caffeine increases ___, ___ and __ release

Answer 30

Caffeine increases NE, Glu and DA release

Question 31

Long-term caffeine drinkers are less likely to experience ___ ___ ___/__

Answer 31

Long-term caffeine drinkers are less likely to experience elevated heart rates/BP

Question 32

Caffeine drinkers will experience constriction in ___ ___, reducing pressure inside head, which can benefit __

Answer 32

Caffeine drinkers will experience constriction in cranial vessels, reducing pressure inside head, which can benefit headaches

Question 33

At 300+mg caffeine will increase kidney __ ___ which will promote a higher volume of urine being produced (___) and ___ (urination), at the same time the kidneys won’t reabsorb as much salt and water tends to follow salt.

Answer 33

At 300+mg caffeine will increase kidney blood flow which will promote a higher volume of urine being produced (diuretic) and micturition (urination), at the same time the kidneys won’t reabsorb as much salt and water tends to follow salt.

Question 34

Heart effects of caffeine are complicated- both ___ and __ mechanisms

___ drive from stimulant- type characteristics but also some contradictory effects in ___ tissues themselves

Some people are really sensitive to the ___ effects so they experience a bad time when they drink, so they don’t become coffee drinkers

Answer 34

Heart effects of caffeine are complicated- both peripheral and central mechanisms

Central drive from stimulant-type characteristics but also some contradictory effects in peripheral tissues themselves

Some people are really sensitive to the peripheral effects so they experience a bad time when they drink, so they don’t become coffee drinkers

Question 35

Caffeine will inhibit __ enzymes which metabolize cAMP producing high __ levels, that has an effect on __ tissue to increase ___ rates and __

Answer 35

Caffeine will inhibit PDE enzymes which metabolize cAMP producing high cAMP levels, that has an effect on heart tissue to increase contraction rates and force

Question 36

In certain blood vessels, caffeine will result in ___ of smooth muscle (__) but there is a sympathomimetic (___ effect) drive from the ___ nervous system that opposes that effect. What people actually experience is highly individual specific

Answer 36

In certain blood vessels, caffeine will result in relaxation of smooth muscle (vasodilation) but there is a sympathomimetic drive (vasoconstricting effect) from the central nervous system that opposes that effect. What people actually experience is highly individual specific

Question 37

Caffeine increases intracellular concentration of ___ by increasing activation ___ channels

Answer 37

Caffeine increases intracellular concentration of calcium by increasing activation calcium channels

Question 38

All together, caffeine is thought to increase __ capacity of ___

Answer 38

All together, caffeine is thought to increase work capacity of muscle

Question 39

Caffeine has a good ___ release in the NAc. This is likely due to blocking pre-synaptic A1 on DA-ergic VTA projecting neurons

A1 has an ___ linkage (__ linked), blocking the ___effects in a pre-synaptic terminal that would otherwise reduce NT release. So by blocking that effect you increase __ release.

At the same time, this antagonism at A1 will lead to more ___ release in the NAc

Answer 39

Caffeine has a good dopamine release in the NAc. This is likely due to blocking pre-synaptic A1 on DA-ergic VTA projecting neurons

A1 has an inhibitory linkage (Gi/o linked), blocking the Gi effects in a pre-synaptic terminal that would otherwise reduce NT release. So by blocking that effect you increase DA release.

At the same time, this antagonism at A1 will lead to more Glu release in the NAc

Question 40

Caffeine facilitates wakefulness by disrupting __.

Extracellular adenosine increases during waking until a point is reached that triggers sleep.

(1) Adenosine thought to come from metabolism of __ in neurons. As you are awake and getting through your day, you are burning more energy that leads to transient __ in adenosine outside of neurons
(2) Stimulation of __ receptors by adenosine in the hypothalamus triggers __ release
(3) __ release inhibits arousal systems
(4) Caffeine prevents adenosine binding to __ receptors (__ not released, arousal increases) = wakefulness

Answer 40

Caffeine facilitates wakefulness by disrupting adenosine.

Extracellular adenosine increases during waking until a point is reached that triggers sleep.

(1) Adenosine thought to come from metabolism of ATP in neurons. As you are awake and getting through your day, you are burning more energy that leads to transient increases in adenosine outside of neurons
(2) Stimulation of A2a receptors by adenosine in the hypothalamus triggers GABA release
(3) GABA release inhibits arousal systems
(4) Caffeine prevents adenosine binding to A2a receptors (GABA not released, arousal increases) = wakefulness

Question 41

Coffee intake may reduce risk of __ disease. Strong inverse relationship between caffeine intake and __ disease

Answer 41

Coffee intake may reduce risk of Parkinson’s disease. Strong inverse relationship between caffeine intake and Parkinson’s disease

Question 42

__ which performs the demethylation metabolic reaction of caffeine. Different polymorphisms confer fast and slow metabolism rates of caffeine.

If you have __ copies of *__ that is a fast metabolic rate for caffeine. If you have __ copy of the *__ allele that leads to a slow rate of metabolism.

Slow metabolizers show increased __-__ risk

Answer 42

CYP1A2 which performs the demethylation metabolic reaction of caffeine. Different polymorphisms confer fast and slow metabolism rates of caffeine.

If you have two copies of *1A that is a fast metabolic rate for caffeine. If you have at least one copy of the *1F allele that leads to a slow rate of metabolism.

Slow metabolizers show increased dose-dependent risk

Question 43

Tolerance for caffeine develops ___. Tolerance to cardiovascular, respiratory, sleep effects but not effects on __.

Answer 43

Tolerance for caffeine develops quickly. Tolerance to cardiovascular, respiratory, sleep effects but not effects on mood

Question 44

Withdrawal to caffeine effects

Answer 44

Headache, fatigue, decreased energy, irritability, thirst

Question 45

Dependence to caffeine develops __

Answer 45

Quickly

Question 46

A long term health risk of caffeine especially in women is __. It is due to increased calcium elimination and __ dietary Ca absorption.

Answer 46

A long term health risk of caffeine especially in women is osteoporosis. It is due to increased calcium elimination and reduced dietary Ca absorption.

Question 47

Due to central sympathomimetic/ stimulant effects of caffeine, in particular the elevation of NE, there is also an increased risk of __ __

Answer 47

Due to central sympathomimetic/ stimulant effects of caffeine, in particular the elevation of NE, there is also an increased risk of panic attacks

Question 48

Adenosine receptor antagonists may be effective __-__ due to regulating synaptic NT levels

Answer 48

Adenosine receptor antagonists may be effective anti-depressants due to regulating synaptic NT levels

Question 49

Caffeine use during pregnancy

Answer 49

• many women drink caffeine during pregnancy
• effects on the fetus are inconclusive

Question 50

What is a nootropic?

Answer 50

Cognitive enhancers

Question 51

Does caffeine improve memory?

Answer 51

Yes, seems to positively affect learning and memory. Acute doses increase two neurotropic BDNF and TrNB activation in the hippocampus. BDNF is linked to LTP(increase synaptic strength). Remembering objects was better if learning while on caffeine

Question 52

Taurine (type of __) is common in __ and __ __. Some of the effects of taurine are __, may be due to triggering glycine receptors, glycine is an inhibitory NT, so this will increase __ and reduce electrical activity. Decreased activity leads to less __.

Answer 52

Taurine (type of nootropic) is common in monster and red bull. Some of the effects of taurine are anxiolytic, may be due to triggering glycine receptors, glycine is an inhibitory NT, so this will increase IPSPs and reduce electrical activity. Decreased activity leads to less anxiety.

Question 53

Other nootropics include __-__, herbs (__ herbs __ __ and __ __, __ herb __ __)

Answer 53

Other nootropics include L-theanine, herbs (TCM herbs Ginkgo biloba and Panax ginseng, Ayurvedic herb Bacopa monnieri)

Question 54

Other nootropics that fall into category of cognitive enhancers

Answer 54

Nicotine, Amphetamines (Adderall), Ritalin, -afinil family (modafinil, adrafinil, armodafinil)

Question 55

Critical physiological purpose of nootropic drugs

Answer 55

To reduce fatigue and improve memory

Question 56

Caffeine is a non-selective ___ ___ antagonist and ___ antagonist (blocking cellular activity by taking up space on receptor site)

Answer 56

Caffeine is a non-selective adenosine receptor (AR) antagonist and phosphodiesterase (PDE) antagonist (blocking cellular activity by taking up space on receptor site)

Question 57

Forms of tobacco product

Answer 57

• cigarettes
• e-cigarettes
• cigars, cigarillos
• shisha
• smokeless e.g. chewing tobacco, snuff (dry powdered leaf or dip where you pack it into bottom lip)
• patches- more on treatment side, far less absorption but still getting enough drug to stave off withdrawal
• gum

Question 58

Electronic cigarettes ___ e-juice containing nicotine; usually ___ or __-__

Answer 58

Electronic cigarettes vaporize e-juice containing nicotine; usually glycerin or PG-based

Question 59

In electronic cigarettes there is no ___ of ___ ___, so no generation of many of the chemicals that are present in cigarette smoke like ___ . You are essentially extracting nicotine and putting it into a different medium

Answer 59

In electronic cigarettes there is no burning of plant material, so no generation of many of the chemicals that are present in cigarette smoke like tar . You are essentially extracting nicotine and putting it into a different medium

Question 60

Major marketing angle of e-ciggs

Answer 60

cleaner smoke is healthier

Question 61

Many e-ciggs contained flavours and additives that caused severe adverse effects…

E.g.
___- butter flavor, obliterates lung tissue (bronchiolitis obliterans), ‘popcorn’ lung in factory workers

___ - inducing allergic reactions

Answer 61

Many e-ciggs contained flavours and additives that caused severe adverse effects…

E.g.
Diacetyl- butter flavor, obliterates lung tissue (bronchiolitis obliterans), ‘popcorn’ lung in factory workers

Vitamin E acetate- inducing allergic reactions

Question 62

Vapour damages immune system via ___ same as cigarettes, ___ infiltrate lung tissue over time which produces a pro inflammatory environment which leads directly to long-term cancer risks

Answer 62

Vapour damages immune system via ROS same as cigarettes, macrophages infiltrate lung tissue over time which produces a pro inflammatory environment which leads directly to long-term cancer risks

Question 63

E-cigarettes cause a ‘__ ___’, similar to cigarettes

Answer 63

E-cigarettes cause a ‘throat catch’, similar to cigarettes

Question 64

One of the big differences between cigarettes and e-cigarettes is the ___ of nicotine being __ __ ___. Much ___ in e-ciggs (5-8x __ than cigarettes), which is a problem because nicotine itself will cause irritation in epithelial cells

Answer 64

One of the big differences between cigarettes and e-cigarettes is the amount of nicotine being delivered per puff. Much higher in e-ciggs (5-8x more than cigarette), which is a problem because nicotine itself will cause irritation in epithelial cells

Question 65

In hookahs water will ___ the smoke, making it ___ irritating, ___ particulates (because water will __ them out) but it is much longer sessions

Answer 65

In hookahs water will cool the smoke, making it less irritating, fewer particulates (because water will filter them out) but it is much longer sessions

Question 66

___ is the most processed, flavoured tobacco form

Answer 66

Shisha is the most processed, flavoured tobacco form

Question 67

In a hookah hot air vaporizes chemicals which produces 11x the ___ by weight compared to cigarettes. This is not good because __ robs the blood of oxygen. This will increase heart rate, ___ diseases and __/___ cancer risks

Answer 67

In a hookah hot air vaporizes chemicals which produces 11x the CO by weight compared to cigarettes. This is not good because CO robs the blood of oxygen. This will increase heart rate, lung diseases and oral/lung cancer risks

Question 68

What is smoke?

Answer 68

• particulates: nicotine, water, tar, PAHs, benzo[a]pyrene and metals
• gases: nicotine, CO, Co2, NO (key mediator of lung damage because in the blood stream it is a vasodilator but outside that it is a reactive species, it will generate radicals that damage cells), nitrosamines, ammonia, nitrites, sulfur, alcohols (when you burn alcohols you generate things like acetylaldehyde), ketones, aldehyde, hydrocarbons

Question 69

Particulate + gas =

Answer 69

aerosol

Question 70

First-hand smoke

Answer 70

inhalation of smoke directly from burning tobacco

Question 71

Second-hand smoke

Answer 71

smoke that has already been inhaled by others

Question 72

Third-hand

Answer 72

1st and 2nd-hand fumes from fingers, clothes, fabric, etc.

Question 73

Nicotine is an ___ which is the principle chemical that causes addiction. It is a competitive __ ___ (AChR) __. Both nitrogens in its structure are capable of picking up a ___ (proton) at __ pH. The uncharged form of nicotine is a ___ __.

Answer 73

Nicotine is an alkaloid which is the principle chemical that causes addiction. It is a competitive acetylcholine receptor (AChR) agonist. Both nitrogens in its structure are capable of picking up a hydrogen (proton) at low pH. The uncharged form of nicotine is a free base.

Question 74

Why does tobacco plant produce nicotine?

Answer 74

because it protects the plant from pests

Question 75

Nicotine absorption:
1. Inhalation
- controlling pH in cigarette smoke you optimize the amount of __ __ nicotine present encouraging absorption- __/__ __ molecules pass through membranes more easily
- burning generates up to ___ __ chemicals (that are not in the cig to begin with)
- 1 cigarette= contains about ___ mg nicotine, delivers __-__mg, __ mg is lethal (start causing muscle spasms)
- __, ___, __-__ __ lower bioavailability (lowering delivery of nicotine)
- art of dose: people deliver __-__ puffs/min, inhale for __ sec, delivers ___-__ micrograms nicotine/kg body weight (amount delivered to the brain), __ pack/day is optimal for brain stimulation

2. Oral (smokeless forms)
   - __-__x greater nicotine absorption, __ under plasma vs time curve
   -much ___ rate of absorption- not as much of a rush

Answer 75

Nicotine absorption:
1. Inhalation
- controlling pH in cigarette smoke you optimize the amount of free base nicotine present encouraging absorption- uncharged/free base molecules pass through membranes more easily
- burning generates up to 4000 new chemicals (that are not in the cig to begin with)
- 1 cigarette= contains about 8 mg nicotine, delivers 0.5-2mg, 60 mg is lethal (start causing muscle spasms)
- pyrolysis, filter, side-stream smoke lower bioavailability (lowering delivery of nicotine)
- art of dose: people deliver 1-2 puffs/min, inhale for 2 sec, delivers 1-2 micrograms nicotine/kg body weight (amount delivered to the brain), one pack/day is optimal for brain stimulation

2. Oral (smokeless forms)
   - 3-4x greater nicotine absorption, area under plasma vs time curve
   -much slower rate of absorption- not as much of a rush

Question 76

Distribution of nicotine:
- Blood pH is 7.4, most nicotine (70%) is in a ___ state, some (30%) is ___
-<5% is bound to __ ___
- ___, ___, ___, ___ get largest amount
- ___ gets least amount

Answer 76

Distribution of nicotine:
- Blood pH is 7.4, most nicotine (70%) is in a monoprotonated state, some (30%) is unprotonated
-<5% is bound to plasma protein
- liver, kidney, spleen, lungs get largest amount
- adipose gets least amount

Question 77

Metabolism of nicotine:
- half life = ___ hrs
- aldehyde oxidases CYP2A6 and ___ are main enzymes
- CYP2A6 mutation that slows metabolism (prolong half life) results in __ tobacco use because ___
- ___ process small amount

Answer 77

Metabolism of nicotine:
- half life = 2hrs
- aldehyde oxidases CYP2A6 and CYP2B6 are main enzymes
- CYP2A6 mutation that slows metabolism (prolong half life) results in lower tobacco use because they suffer from more of the adverse effects of nicotine intoxication instead of the euphoric effects leading to aversive responses as opposed to preferential responses
- monooxygenases process small amount

Question 78

Excretion of nicotine

Answer 78

kidneys, breast milk

Question 79

Every time ___ levels start to drop people ____.

Plasma nicotine concentration peaks in the __.

Receptors ____ over night.

___ cig is most pleasant

Answer 79

Every time plasma levels start to drop people feel the urge to go smoke again.

Plasma nicotine concentration peaks in the evening.

Receptors re-sensitize over night.

First daily cig is most pleasant

Question 80

Acute effects of nicotine are mostly ___

Answer 80

Acute effects of nicotine are mostly sympathomimetic

Question 81

NTs affected by nicotine in the brain: ___, ___, ___, ___.

When nicotine binds to ACh receptors it depolarizes cells via ___. Nicotine has a ___ affinity causing receptors to ___ (___ mechanism at high doses)

All of the effects of the NTs together: ___ heart rates/BP, __ GI movement, __ motor commands, __ and __

However, __ (from burning) can inhibit monoamine oxidases and boost NT levels- not just nicotine that is contributing to physiological effects

Answer 81

NTs affected by nicotine in the brain: ACh, DA, GABA, Glu.

When nicotine binds to ACh receptors it depolarizes cells via nAChR. Nicotine has a high affinity causing receptors to inactivate (biphasic mechanism at high doses)

All of the effects of the NTs together: elevated heart rates, BP, increase GI movement, increase motor commands, focus and mood

However, acetaldehyde (from burning) can inhibit monoamine oxidases and boost NT levels- not just nicotine that is contributing to physiological effects

Question 82

CNS nAChR receptors are located in: __, ___, __

Answer 82

CNS nicotine receptors are located in: cortex, hippocampus, midbrain

Question 83

pre-synaptic triggering of nAChR (nicotinic acetylcholine receptors) will…

Answer 83

• increase glutamate release
• increase GABA (inhibiting activity/release of DA) release but the mechanism on GABA release is quickly desensitized then shut off
• increase DA release

Question 84

“Safe” additives turn bad after ___

Answer 84

burning

Question 85

Stimulation of the ___ ___ is common in first-time nicotine users

Answer 85

Stimulation of the vomiting centre is common in first-time nicotine users

Question 86

Other acute adverse effects of nicotine

Answer 86

headaches, nausea, disrupted autonomic nervous system functioning, alternating tachycardia and bradycardia

Question 87

Effects of severe intoxication of nicotine (approaching 60mg mark)

Answer 87

seizures, hypotension, respiratory depression

Question 88

nAChR (nicotinic acetylcholine receptors) in brain

Answer 88

Are heteropentameric receptors, alpha and beta subunits.

They conduct cation (Na+, Ca2+) influx to depolarize neurons.

Both pre-synaptic and post-synaptic (located on terminals and on soma).

They trigger neuromuscular activity

Question 89

Pre-synaptic nAChRs

Answer 89

increase NT release

Question 90

Post-synaptic nAChRs

Answer 90

depolarize the cell

Question 91

Eventually nAChRs inactivate if continuously exposed to ___ with __ affinity (binds and doesn’t let go)

Answer 91

Eventually nAChRs inactivate if continuously exposed to agonist with high affinity (binds and doesn’t let go)

Question 92

nAChR __ ___ affects reinforcement and reward

Answer 92

nAChR subunit composition affects reinforcement and reward

Question 93

alpha 6 containing nAChRs are involved with

Answer 93

modulating locomotor responses, not that important for releasing DA downstream

Question 94

alpha 7 containing nAChRs are responsible for __. These sub-types govern ___ release and are not inactivated.

Answer 94

facilitating glutamate release, which will trigger DA-ergic projecting VTA –> NAc neurons

These sub-types govern Glu release and are not inactivated.

Question 95

If beta 2 subunits (nAChRs) are knocked out in mice it…

Answer 95

prevents DA release and self-administration stops, plays a role in the addictive nature of nicotine

Question 96

If you apply an alpha4 beta2 receptor antagonist (turns off receptor) you will __ ___.

Answer 96

block reward

Question 97

___ nAChR are mainly expressed on DA-ergic terminals in NAc. They do not release ___ after systemic nicotine administration.

Answer 97

Alpha6-beta 2 nAChR are mainly expressed on DA-ergic terminals in NAc. They do not release DA after systemic nicotine administration.

Question 98

____ are the main functional nAChRs on VTA DA-ergic soma. When you activate these receptors on the soma that is a direct depolarization event and you are triggering ___ release downstream and ___

Answer 98

alpha4beta2 are the main functional nAChRs on VTA DA-ergic soma. When you activate these receptors that is a direct depolarization event and you are triggering DA release downstream and reinforcement

Question 99

alpha4beta2 sub-type govern ___ release and inactivate quickly (after 30-60 seconds) and for a long time (1 hour)

Answer 99

alpha4beta2 sub-type govern GABA release and inactivate quickly (after 30-60 seconds) and for a long time (1 hour)

Question 100

A single dose of nicotine injected into NAc ___ DA levels for __ min

Answer 100

A single dose of nicotine injected into NAc elevates DA levels for 80 min

Question 101

Tolerance to nicotine:
- first uses are ___ = brain regions/circuits (brainstem) for ___, ___, ___
- little or no decrease in ___ effects, ___ and ___ ___
- metabolic= ___ enzyme activity, first cig is the best
- cellular= receptor ___, affects ___
- behavioral= ___ stages experience, ___ of smoking e.g. social smoker
- nAChR expression ___, mostly ___ subtype, enhances sensitivity to nicotine effects

Answer 101

Tolerance to nicotine:
- first uses are unpleasant = brain regions/circuits (brainstem) for dizziness, nausea, sweat
- little or no decrease in heart effects, tremor and peripheral vasoconstriction
- metabolic= increased enzyme activity, first cig is the best
- cellular= receptor inactivation, affects reward
- behavioral= mindset stages experience, ritual of smoking e.g. social smoker
- nAChR expression increases, mostly alpha4beta2 subtype, enhances sensitivity to nicotine effects

Question 102

Nicotine withdrawal

Answer 102

• physiological symptoms: headache, drowsiness, insomnia, increased appetite and weight gain, GI upset
• psychological: craving, mood changes, irritability, anxiety, restlessness, depression, difficulty concentrating, poor judgement and psychomotor performance

Question 103

Nicotine dependence

Answer 103

• if you must smoke within 30 minutes of waking up, chances are you are addicted
• starts to occur within days of habit
• both physical and psychological
• quick metabolism leads to withdrawal, seek another dose to avoid symptoms
• intensely cue-driven habit: after eating, while drinking, out with friends, after sex (strong aspect of routine and habit that drive nicotine dependence)

Question 104

Long-term adverse effects of tobacco:
- cancer: lung, ___, ___
- ___ initiates cancer= intercalating agent (causing DNA damage)
-nicotine enhances ____, not ____
- inhibits apoptotic signalling by binding ___ nAChRs on ___, allow cells with damaged DNA to replicate (fail to kill themselves- nicotine helps them stay alive)

Answer 104

Long-term adverse effects of tobacco:
- cancer: lung, liver, colorectal
- benzo(a)pyrene initiates cancer= intercalating agent (causing DNA damage)
-nicotine enhances growth/metastasis, not initiation
- inhibits apoptotic signalling by binding alpha 7 nAChRs on mitochondria, can allow cells with damaged DNA to replicate (fail to kill themselves- nicotine helps them stay alive)

Question 105

Nicotine injections/patches on mice injected with cancerous cells display ___

Answer 105

Nicotine injections/patches on mice injected with cancerous cells display enhanced cancer growth

Question 106

Nicotine is NOT ____, it does not ___ cancer formation it ___ it

Answer 106

Nicotine is NOT carcinogenic, it does not initiate cancer formation it propagates it

Question 107

Nicotine accelerates ___ ___ due to peripheral vasoconstriction (decreased blood flow, lower turn over of cells, lower oxygen supply)

Answer 107

Nicotine accelerates skin aging due to peripheral vasoconstriction (decreased blood flow, lower turn over of cells, lower oxygen supply)

Question 108

Nicotine causes sexual dysfunction because of impaired ___ signaling which prevents ___

Answer 108

Nicotine causes sexual dysfunction because of impaired NO signaling which prevents erections

Question 109

Nicotine causes an increased risk of type 2 diabetes because of stressed ___ that is insensitive to ___

Answer 109

Nicotine causes an increased risk of type 2 diabetes because of stressed vasculature that is insensitive to insulin

Question 110

Other long-term adverse effects tobacco:

• cataracts, macular degeneration
• tooth ___, ___/inflamed gums (stressing microflora, proinflammatory) , ___, Crohn’s
• ___ especially in lungs
• rheumatoid arthritis, osteoporosis
• cardiovascular diseases, like ___ ___ ___ (CHD), MI, ___ __ (because of impaired epithelial cell function)
• COPD includes ___ ___ and ___ (caused by inflammation of airways covered in ___ and ash deposits, cilia function is impaired by ___ and ___ in smoke)

Answer 110

Other long-term adverse effects tobacco:

• cataracts, macular degeneration
• tooth decay, periodontitis/inflamed gums (stressing microflora, proinflammatory) , IBS, Crohn’s
• infection especially in lungs
• rheumatoid arthritis, osteoporosis
• cardiovascular diseases, like coronary heart disease (CHD), MI, ischemic stroke (because of impaired epithelial cell function)
• COPD includes chronic bronchitis and emphysema (caused by inflammation of airways covered in tar and ash deposits, cilia function is impaired by PAH and ketones in smoke)

Question 111

‘Smokers cough’ (coughing up mucus) when quitting indicates..

Answer 111

recovery of cilial function

Question 112

Second-hand smoke, non-smokers that live with smokers have ___ ___ of lung cancer, heart disease

Answer 112

Second-hand smoke, non-smokers that live with smokers have higher rates of lung cancer, heart disease

Question 113

Pregnancy and smoking:
- constriction of ___ ___, reduced ___
- may affect ___ system leading to increased addiction risk
- higher risk of __, ___ or ___, __ __ __
- __ ___ and lip risk goes up

Answer 113

Pregnancy and smoking:
- constriction of umbilical arteries, reduced oxygen
- may affect reward system leading to increased addiction risk
- higher risk of stillbirth, premature or miscarriage, low birth weight
- cleft palate and lip risk goes up

Question 114

Like safe injection sites, the goal is to provide safe nicotine to …

Answer 114

ease withdrawal and cravings

Question 115

It is very difficult to stop smoking, __% of American smokers want to quit and __% make a serious attempt, with the success rate being __%

Answer 115

It is very difficult to stop smoking, 74% of American smokers want to quit and 78% make a serious attempt, with the success rate being 6%

Question 116

3 day hump (first 3 days being the most hard to get through) correlates with nicotine ___

Answer 116

3 day hump (first 3 days being the most hard to get through) correlates with nicotine clearance

Question 117

is it harder to quit smoking or smokeless forms?

Answer 117

smokeless, higher doses and longer lasting blood nicotine concentrations

Question 118

Stopping cig smoke at 30 years old reduces the long-term health risks by __% at 45 years old reduce risk by __%, at 50 years old reduce risk by __%. Therefore, the earlier people stop, the better.

Answer 118

Stopping cig smoke at 30 years old reduces the long-term health risks by 90% at 45 years old reduce risk by 87%, at 50 years old reduce risk by 50%. Therefore, the earlier people stop, the better.

Question 119

What happens when people stop smoking:
- within 8 hours: _____
- within a week: _____
- within 9 months: ____
- within 1 year: ____
- within 5-10 years: ____
- within 15 years: ____

Answer 119

What happens when people stop smoking:
- within 8 hours: blood CO levels normalize
- within a week: heart, BP, circulation, breathing improve
- within 9 months: respiratory cilia recover
- within 1 year: CHD risk drops by 50%
- within 5-10 years: risk of stroke matches non-smokers
- within 15 years: CHD risk matches non-smokers while lung cancer risk is 50% lower than smokers

Question 120

Nicotine withdrawal must be overcome so cessation therapies offer nicotine without the ___ of ___

Answer 120

Nicotine withdrawal must be overcome so cessation therapies offer nicotine without the hazards of smoking

Question 121

Different forms of cessation therapies (for nicotine)

Answer 121

patches, gums, nasal spray, inhalers, lozenges, and e-cigs

Question 122

Gum used for nicotine cessation can cause __ __, __ __ and __ __. Patches/spray can cause __. E-cigs might be effective but the risk of __ might be high (have to do with dosages of nicotine- higher)

Answer 122

Gum used for nicotine cessation can cause bad taste, irritate throat and induce nausea. Patches/spray can cause irritation. E-cigs might be effective but the risk of reverting might be high (have to do with dosages of nicotine- higher)

Question 123

Pharmacological cessation aids for nicotine

Answer 123

• bupropion= antidepressant, nAChR antagonist, blocks the channel even when nicotine is present, DAT and NET inhibition, helps reduce cravings
• varenicline= partial nAChR agonist, compete with nicotine, reduces reward and cravings

-vaccines= methoxsalen and NicVAX are in development

Question 124

Behavioral and psychosocial cessation aids for nicotine

Answer 124

• counselling, stress management (Cortisol levels go up when people smoke)
• behavioral modification: identify and avoid risky situations e.g. don’t go to the bar that you always go to that you then smoke while drinking
• combine with pharmacological treatments
• large scale awareness campaigns

Question 125

Sedatives

Answer 125

anxiolytic drugs (relieve anxiety), cause relaxation, mild CNS depressants

Question 126

Hypnotics

Answer 126

cause drowsiness and sleep

Question 127

Drugs that have sedative- hypnotics type properties

Answer 127

Z-drugs (Ambien), orexin antagonists, melatonin agonists, anti-histamines

Question 128

Anxiety :
main chemicals that are used are ____, they are the ‘___’-___ e.g. Valium diazepam, Klonopin clonazepam

___-___:
Longer-acting drugs treat seizure disorder e.g. Phenobarbital

____:
short-acting drugs e.g. thiopental, midazolam, triazolam

Answer 128

Anxiety :
main chemicals that are used are benzos, they are the ‘aze’-pams e.g. Valium diazepam, Klonopin clonazepam

Anti-convulsants:
Longer-acting drugs treat seizure disorder e.g. Phenobarbital

Anesthesia:
short-acting drugs e.g. thiopental, midazolam, triazolam

Question 129

In general, sedatives are a more ___ class of drug that leads to ___ onset due to __ distribution.

Answer 129

In general, sedatives are a more lipophilic class of drug that leads to faster onset due to rapid distribution.

Question 130

Within the sedative class, barbiturates and benzos are categorized based on their ___ of action.

___-____ drugs are typically used as anticonvulsants, muscle relaxants, and anxiolytics

___-____ are used as pre-anesthetic sedatives or to treat insomnia

Answer 130

Within the sedative class, barbiturates and benzos are categorized based on their duration of action.

longer-acting drugs are typically used as anticonvulsants, muscle relaxants, and anxiolytics

shorter-acting are used as pre-anesthetic sedatives or to treat insomnia

Question 131

Presence of a triazole ring…

Answer 131

significantly enhances potency, because the ring allows them to bind to GABA with greater affinity. But it exposes those molecules to faster metabolic processing, causing a decrease in duration of action (short-acting).

Question 132

Longest acting to shortest acting: Alprazolam, Triazolam, Clonaezepam, Diazepam, Lorazepam

Answer 132

1) Diazepam- far fewer oxygens
2) Lorazepam
3) Clonazepam- has charged group ready for conjugation right away
4) Alprazolam- benzo
5) Triazolam

Question 133

Routes of administration for sedatives

Answer 133

oral, rectal, injection (more for clinical use)

Question 134

Absorption and distribution of sedatives

Answer 134

Benzos:
- less lipid soluble than barbiturates, absorbed more slowly, slower onset of action

barbiturates and benzos are highly bound to plasma proteins

Cross placenta

Question 135

Metabolism of sedatives:
- in the liver ___ system
- some produce ___ ___ prolonging duration of action e.g. chlordiazepoxide, diazepam
- takes ___-___ half-lives for elimination
-metabolism decreased in ___ (underdeveloped livers), __ __ (higher metabolic loads), those with liver disease, the elderly
-if drugs cross placenta it will impair electrical function in babies/ ___ ___ ___ in infants which causes the inability to ___ that can last for months= ___ ___ syndrome

Answer 135

Metabolism of sedatives:
- in the liver CYP450 system
- some produce active metabolites prolonging duration of action e.g. chlordiazepoxide, diazepam
- takes 4-5 half-lives for elimination
-metabolism decreased in infants (underdeveloped livers), pregnant women (higher metabolic loads), those with liver disease, the elderly
-if drugs cross placenta it will impair electrical function in babies/ reduced muscle tone in infants which causes the inability to nurse that can last for months= floppy infant syndrome

Question 136

GABA A receptor has __ subunits arranged around a __-conducting pore

(sedatives unit)

Answer 136

GABA A receptor has 5 subunits arranged around a chloride-conducting pore

Question 137

GABA binds between the ___ and __ subunits, Benzos bind between the __ and __ subunits

(sedatives unit)

Answer 137

GABA binds between the alpha and beta subunits, Benzos bind between the alpha and gamma subunits

Question 138

Benzos:
- bind to a site on the GABA A receptor, which increases the frequency of ___ ___ ___
- GABA receptors with benzo binding sites located in __ system, ___ ___ system and ___
- GABA receptors that control ___ do not have many benzo sites

Answer 138

Benzos:
- bind to a site on the GABA A receptor, which increases the frequency of chloride channel openings
- GABA receptors with benzo binding sites located in limbic system, reticular activating system and cortex
- GABA receptors that control respiration do not have many benzo sites

Question 139

Barbiturates:
- have a more ___ effect on GABA receptors
- when they bind, they enhance the __ of the receptor for GABA, which increases the duration of time that the ___ ___ is open, leading to neuronal ___ –> can do this even when GABA is ___ ___

Answer 139

Barbiturates:
- have a more general effect on GABA receptors
- when they bind, they enhance the affinity of the receptor for GABA, which increases the duration of time that the chloride channel is open, leading to neuronal inhibition –> can do this even when GABA is NOT present

Question 140

Benzos are ___ modulators, barbiturates are ___

Answer 140

Benzos are allosteric modulators (binds but doesn’t open the channel- they have a calming effect but not as a depressive effects as barbees), barbiturates are activators(bind and opens channel)

Question 141

Acute effects of sedatives:
- reduce ___ __, impair ___, and increase ___ and __
- reduce ___, ___, ___ and can cause ___, ___ behaviors

Answer 141

Acute effects of sedatives:
- reduce muscle tone, impair coordination, and increase sedation and sleep
- reduce anxiety, learning, memory and can cause bizarre, uninhibited behaviors

Question 142

Effect of sedatives on sleep

Answer 142

• increase total sleep time
• REM sleep and restorative deep sleep are reduced

Question 143

Common side effects of sedatives (effects they do not take sedatives for) are..

Answer 143

• drowsiness
• lethargy
• dizziness
• confusion
• reduced libido
• diminished concentration
• incoordination
• impairment of driving skills
• prevent consolidation of short-term memories (unable to be stored as long-term memory), especially when alpha subunit-containing receptors are present, can last for months
• combined with alcohol to faciliate assault

Question 144

Other dangers associated with sedatives: Effects on fetus

Answer 144

• rapid entry, increased half life due to under-developed liver
• potential increased risk of cleft palate, floppy infant syndrome, withdrawal
• no risk of major malformations
• must weigh risks of fetus against risks of the mother going off the drug

Question 145

Other dangers associated with sedatives: Drug interactions

Answer 145

• synergistic with with other depressants such as alcohol,opioids
• interact with other drugs metabolized by CYP450 system (compete for same metabolic enzyme) –> increases chances of adverse effects

Question 146

Other dangers associated with sedatives: Overdose, treated with flumazenil

Answer 146

• overdoses are relatively rare for benzos by themselves
• flumazenil is an antagonist at GABA receptors
• Barbiturates very low therapeutic index (associated with overdoses that can be treated by flumazenil)

Question 147

Tolerance of sedatives

Answer 147

• develops at different rates depending on receptor subunit shifts
• develops for sedative, hypnotic effects in days to weeks
• develops slower for anxiolytic effects (3-4 months)
• does not develop for respiratory depression
• users can require 40x original dose

Question 148

Barbiturates have both ___ and ___ mechanisms of tolerance

Answer 148

Barbiturates have both cellular and metabolic mechanisms of tolerance

Question 149

Chronic effects of sedatives

Answer 149

• associated with daytime fatigue, accidents, depression, violence, and increased overall mortality

Question 150

Withdrawal for sedatives

Answer 150

• worse with short-acting drugs (intermittent high dose schedule- e.g. take drug, effects go away, take drug again but amp up dose etc.)
• should be medically supervised due to hyperexcitability
• insomnia, anxiety, tremor, headache, confusion, and difficulty concentrating

Question 151

Dependence and addiction for sedatives

Answer 151

• both physical and psychological dependence
• benzos not as addictive as barbees

Question 152

The abuse potential for sedatives are much __ lower than other drugs. In progressive schedules, animals exert __ effort for sedatives compared to cocaine and opioid

Answer 152

The abuse potential for sedatives are much much lower than other drugs. In progressive schedules, animals exert less effort for sedatives compared to cocaine and opioid

Question 153

Another sedative that is use is GHB (Gamma-hydroxybutyric acid) - date-rape drug:

• it is made from 2 commercially available chemicals: __-__ and ___ which are uncontrolled substances
• it is a GABA __ receptor agonist: __/__ linked, inhibits __ channels, activates ___
• both a __ (produced naturally in body) and an __ __
• precursor of __, __ and __
• dose-dependent effects
• also effects __, ___, __, __
• sensation of GHB is similar to __ __
• high doses can lead to suppressed __, __, __ and ___

Answer 153

Another sedative that is use is GHB (Gamma-hydroxybutyric acid) - date-rape drug:

• it is made from 2 commercially available chemicals: gamma-butyrylactone and 1,4-butanediol both which are uncontrolled substances
• it is a GABA B receptor agonist: Gi/o linked, inhibits Ca channels, activates GIRK
• both a neurotransmitter (produced naturally in body) and an illegal drug
• precursor of GABA, Glu and Glycine
• dose-dependent effects
• also effects dopamine, acetylcholine, serotonin, opioids
• sensation of GHB is similar to alcohol inebriation
• high doses can lead to suppressed respiration, convulsions, coma and death

Question 154

Dose-dependent effects of GHB

Answer 154

• low doses of GHB have a stimulatory effects (excitatory glutamate)
• At higher doses, GHB binds to GABA receptors and can cause sedation

Question 155

Benzodiazepines exert rapid anxiolytic effects by increasing GABA (γ-aminobutyric acid)-mediated neurotransmission. However, their use in treating anxiety disorders is limited owing to the loss of control of consumption after prolonged use.

GABA A receptors containing the ___ subunit in the ventral tegmental area (VTA) underlies the addictive nature of benzodiazepines, as it activates these containing receptors and inactivates ___ release, increasing __ release

Answer 155

Benzodiazepines exert rapid anxiolytic effects by increasing GABA (γ-aminobutyric acid)-mediated neurotransmission. However, their use in treating anxiety disorders is limited owing to the loss of control of consumption after prolonged use.

GABA A receptors containing the α1 subunit in the ventral tegmental area (VTA) underlies the addictive nature of benzodiazepines, as it activates these containing receptors and inactivates GABA release, increasing DA release

Question 156

emergent view of cannabis

Answer 156

only one lineage, characterize plant by chemical profile it contains i.e. chemotypes e.g. THC and CBD (+others), the experience is chemical-dependent

Question 157

___, ___ etc. are synthesized in cannabis trichome heads

Answer 157

Phytocannabinoids, terpenes etc. are synthesized in cannabis trichome heads

Question 158

The goal of solvent or solvent-less extraction and super-critical extraction

Answer 158

high purity or a single isolated compound

Question 159

How to calculate THC % based on labelling:
E.g. pre-roll label
1 pre-roll,1g
THC 6mg/g (Total THC Per Unit: 173.0 mg/g)
CBD 0mg/g (Total CBD Per Unit: <0.7 mg/g)

Answer 159

Total THC Per Unit= 173.0 mg/g
173.0 mg/1000mg= 0.173 *100% = 17.3%

Question 160

___, __-_ and __ forms of cannabinoids are all available

Answer 160

Psychoactive, non-psychoactive and synthetic forms of cannabinoids are all available

Question 161

THC acid is the ___ form

Answer 161

psychoactive

Question 162

CBD acid is an…

Answer 162

anti-oxidant, anti-convulsant, anti-inflammatory, anti-anxiety, anti-psychotic and neuro-protective

Question 163

Personalized cultivar selection, tailor the therapeutic effect to the __ and __

Answer 163

Personalized cultivar selection, tailor the therapeutic effect to the disease and individual

Question 164

To optimize absorption of THC you…

Answer 164

decarboxylate THCA to THC by heat or pressure

Question 165

Routes of administration of cannabinoid

Answer 165

smoked- joints, pipes, bongs, vaporizers
ingested- slower onset of effect, less predictability of action, but more user control

Question 166

Cannabis vs Cigarette smoke:
- smoke is solid/liquid ___ and ___ created during combustion
- similar levels of ___, ___, ___, ___, ___, ___, ___, __
- poorer filtration of cannabis smoked, ___ irritation
- ___ and ___ when using cannabis –> because more unfiltered nature of cannabis
- Long-term effects:
= NOT __ ___ and ___
= increased risk of ___ ___ and ___

Answer 166

Cannabis vs Cigarette smoke:
- smoke is solid/liquid particulates and gases created during combustion
- similar levels of tar, CO, acetaldehyde, acetone, benzene, toulene, benzopyrene, HCN
- poorer filtration of cannabis smoked, more irritation
- toking and choking when using cannabis –> because more unfiltered nature of cannabis
- Long-term effects:
= NOT lung cancer and COPD (that is in cig smoking)
= increased risk of chronic cough and bronchitis

Question 167

Reason that cannabis does not have a link to lung cancer or COPD

Answer 167

water bongs, dabs may reduce harmful components and reduce irritation

Question 168

Terpene profiling has to do with the ___ ___

Answer 168

Terpene profiling has to do with the vape temperature e.g. CBD is associated with a vaping temperature of 180 degrees celsius, THC is associated with a temp of 157

Question 169

Absorption of cannabinoids

Answer 169

THC is very fat-soluble (lots of carbons not a lot of functional groups) and easily crosses the blood brain barrier

Question 170

Metabolism of cannabinoids

Answer 170

• liver CYP450 system
• metabolites can stay in body for days or even weeks
• long half-lives
• first-pass metabolite 11-hydroxy-delta9-THC- why ingested version is more potent than the smoked form

Question 171

Excretion of cannabinoids

Answer 171

kidneys

Question 172

The endogenous CBR(cannabinoid receptor) ligands that were identified in 1992 and 1995

Answer 172

arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG)

Question 173

CB1 (cannabinoid receptor 1) is expressed in the …

Answer 173

CNS (basal ganglia, cerebellum, hippocampus, cortex, amygdala), eye, pancreas, liver, skin, uterus and testes

Question 174

CB2 (cannabinoid receptor 2) is expressed in…

Answer 174

immune cells, spleen and tonsils

Question 175

THC mostly targets ___ explaining why it is the ___ compound

Answer 175

THC mostly targets CB1 explaining why it is the psychoactive compound

Question 176

CBD tends to target ___

Answer 176

CB2

Question 177

Acute effects of cannabis intoxication- Brain

Answer 177

• affected appetite, sex, and sleep
• inhibited memory encoding and retrieval
• impaired coordination
• enhanced sensory perception
• time seems long and drawn out
• analgesia (inability to feel pain)

Question 178

Acute effects of cannabis intoxication- Behavioral and psychological

Answer 178

• euphoria
• well-being
• talkativeness
• laughter
• relaxation
• lethargy

Question 179

Acute effects of cannabis intoxication- Immune system

Answer 179

immune function modulated/regulated

Question 180

The medicinal side of cannabis is looking mostly at __ mediated functions in the periphery things like the ___ system

Answer 180

The medicinal side of cannabis is looking mostly at CB2 mediated functions in the periphery things like the immune system

Question 181

The recreational cannabis user is going after the ___ mediated central nervous system effects

Answer 181

The recreational cannabis user is going after the CB1 mediated central nervous system effects

Question 182

Analgesia resulting from cannabis intoxication is via …

Answer 182

the CB1- mediated blockage of pain neurotransmission

Question 183

Stimulant effects of cannabis

Answer 183

• dose-dependent heart rate increase
• skin vessels dilate flushing warmth core temperature decreases
• salivary gland vessels constrict drying mouth
• eye vessels dilate leading to red, bloodshot eyes

Question 184

Energy metabolism, increased appetite and thirst via CB1/CB2 in hypothalamus, pancreas, liver

Answer 184

Energy metabolism, increased appetite and thirst via CB1 in hypothalamus, pancreas, liver

Question 185

CB1 in hypothalamus may influence…

Answer 185

• sex drive
• sperm production
• fertilization
• implantation
• fetal development
  -suckling in newborns
• modulates DA and 5-HT release

Question 186

Cellular mechanism of cannabinoid receptor signalling

Answer 186

• retrograde signaling
• cannabinoids modulate the release of other NTs because they are pre-synaptic receptors (CB1 mainly)

Question 187

Cannabinoids binds several receptors including

Answer 187

• CB1/2
• transient receptor potential cation channels e.g. TRPV1/2
• 5HT2 sub-types

Question 188

CB1 and CB2 are linked to ___

Answer 188

Gi/o

Question 189

TRPV1 and TRPV2 are ___ channels

Answer 189

Na+/Ca2+, which are linked to depolarization type stimulating type signaling

Question 190

The summary of cannabinoid signalling is ___ , there are multiple downstream __ and effects

Answer 190

The summary of cannabinoid signalling is pleiotropic , there are multiple downstream targets and effects

Question 191

Tolerance of cannabis:
- regular use of marijuana will cause __, __, __ tolerance
- __ metabolism, __ CB1 receptor expression
- reduced ___, ___, ___, ___, ___ and immune effects

Answer 191

Tolerance of cannabis:
- regular use of marijuana will cause metabolic, cellular, behavioral tolerance
- faster metabolism, reduced CB1 receptor expression
- reduced high, hypothermic, cardiovascular, analgesic, locomotor and immune effects

Question 192

Withdrawal of cannabis:
- mild __-___ (i.e. lethargy, apathy), perhaps to certain cultivars
- if withdrawal symptoms occur, they are usually __ severe
- chronic users will retain __ levels of residual metabolites but that might actually ____

Answer 192

Withdrawal of cannabis:
- mild burn-out (i.e. lethargy, apathy), perhaps to certain cultivars
- if withdrawal symptoms occur, they are usually not severe
- chronic users will retain higher levels of residual metabolites but that might actually ease withdrawal symptoms

Question 193

Dependence of cannabis

Answer 193

limited, slight psychological (mood, apathy, lethargy). Less addictive than other drugs of abuse, but can be addictive to some

Question 194

Treatment for cannabis dependence typically involves …

Answer 194

psychological approaches

Question 195

Acute adverse effects of cannabis:
- __-___: vomiting, nausea, complicated __-__ signaling (has to do with efferent signals that are ___ in nature coming from the GI tract to the brainstem –> triggers vomitting reflexes)
- higher THC impairs __, ___, concentration via hippocampal effects, also inhibits ___
- psychosis- ___, delusions of control, ___
- anxious, paranoid
- heart rhythm ___ because of stimulant type nature
- ___ contamination- especially in black market sourced cannabis

Answer 195

Acute adverse effects of cannabis:
- green-out: vomiting, nausea, complicated 5-HT signaling (has to do with efferent signals that are serotonergic in nature coming from the GI tract to the brainstem –> triggers vomitting reflexes)
- higher THC impairs learning, memory, concentration via hippocampal effects, also inhibits LTP
- psychosis- hallucinations, delusions of control, grandiosity
anxious, paranoid
- heart rhythm complications because of stimulant type nature
- pesticide contamination- especially in black market sourced cannabis

Question 196

Can a person overdose from cannabis?

Answer 196

Short answer= No, not fatally

Question 197

Volcano administration results in __ THC delivery while __ CO delivery, indicating that there are fewer pyrolytic and oncogenic chemicals present when you vape

Answer 197

Volcano administration results in similar THC delivery while reducing CO delivery, indicating that there are fewer pyrolytic and oncogenic chemicals present when you vape

Question 198

Entourage effect

Answer 198

chemical interactions with receptors enhance each others effects

Question 199

Mechanism of reinforcement:
- Increases DA levels in rats by 100%
- 8 mg of THC ___ in humans raises DA levels by 136% 45-85 min post-administration
- However, 10 mg delivered ___ induced no measurable DA increase
- Likely through ___- mediated inhibition of __ release in the VTA i.e. disinhibition of DA-ergic VTA –> NAc Neurons
- Striatal DA release by THC may underlie link to ___

Answer 199

Mechanism of reinforcement:
- Increases DA levels in rats by 100%
- 8 mg of THC inhaled in humans raises DA levels by 136% 45-85 min post-administration
- However, 10 mg delivered orally induced no measurable DA increase
- Likely through CB1- mediated inhibition of GABA release in the VTA i.e. disinhibition of DA-ergic VTA –> NAc Neurons
- Striatal DA release by THC may underlie link to schizophrenia (DA is central to schizophrenia)

Question 200

How cannabis causes bloodshot eyes

Answer 200

• noradrenaline (DA) causes narrowing of blood vessels
• anandamide (AEA) relaxes those blood vessels
• AEA is dependent on CB1 receptor and nitric oxide (NO)
• CBD induces relaxation of arteries

Question 201

Munchies in cannabis

Answer 201

result from hunger signaling, increased smell, olfaction sensitivity, increased pleasure when eating (induces DA release)

Question 202

Hunger signaling

Answer 202

• Glu-ergic inputs from cortex –> GABA-ergic internuerons in main olfactory bulb (MOB)
• GABA interneurons –> mitral neuron soma
• mitral cells –> olfactory receptor neurons

Question 203

Augmented olfaction by cannabinoids

Answer 203

• endocannabinoids naturally reduce GABA-ergic interneuron firing leading to increased transmission through mitral cells
• disinhibition of mitral neurons and increased afferent inputs to the brain hypersensitizes smell –> animals feed

Question 204

__ __ ___ and ___ __ form the centrifugal Glu-ergic inputs to the MOB

These feedback projections to the MOB is what regulates food intake via ___ signaling

Answer 204

Anterior olfactory nucleus and piriform cortex form the centrifugal Glu-ergic inputs to the MOB

These feedback projections to the MOB is what regulates food intake via CB1 signaling

Question 205

Summary of pro-appetite effects of Cannabis

Answer 205

• increased olfactory sensitivity triggers feeding
• users report greater pleasure from food
• appetite- related hormones are modulated by cannabinoids

Question 206

Anti-emetic (medication aimed to reduce nausea) activity of cannabinoids

Answer 206

• nausea and vomiting: primary signal is 5-HT3R-mediated in the medulla by afferent input from the gut
• THC inhibits 5HT release in medulla via pre-synaptic CB1
• THC binds and decreases activity of 5HT3 receptors
• CBD is an agonist in 5HT1A auto-receptors, prevents 5HT release, also antagonizes 5HT3R

Question 207

Effect of cannabis on driving

Answer 207

• mostly affects automated tasks (staying in lane) relative to attention tasks (reversing, distancing)
• doubles risk of severe injury/death
• synergistic effect when combined with alcohol, sub-effective doses create impairment

Question 208

Synthetic forms of cannabis

Answer 208

spice, K2

Question 209

Problem with synthetic forms of cannabis

Answer 209

contamination of toxins e.g. rat poisoin (brodifacoum), causes severe bleeding

Question 210

Cannabinoid detection and testing

Answer 210

• colorimetric- ELISA or dipsticks (deeper/less color= more THC)
• immunoassays, lateral flow e.g. COVID test type
• Gas chromatography mass spectrometry (GC-MS) - each peak corresponds to one chemical in a sample
• roadside screening tests are lateral flow assays, typically

Question 211

Sources of hallucinogens

Answer 211

• fungi:
  Claviceps purpurea fungus that produces lysergic acid (LA) which is the precursor to synthesize LSD and is active on its own
  ~200 Psilocybe, Panaelous, Conocybe spp. that produce psilocybin
  Amanita muscaria (fly agaric) produces ibotenic acid and muscimol

-animal: colorado river toad that produces bufotenin

• plants:
  ipomoea nil (morning glory) seeds that produce LA amide
  Lophophora williamsii (peyote) that produces mescaline
  Ayahuasca (made from Psychotria viridis and Banisteriopsis caapi vines) contains DMT, N,N-dimethyltryptamine, harmine, harmaline
  Anadenathera peregrine and virola trees that produce DMT and bufotenin
  Atropa belladonna, Datura, Henbane, Mandrake that produce atropine, scopolamine and hyoscyamine
  Tabernanthe iboga roots that produce ibogaine
  Myristica fragrans (nutmeg and mace) that produce myristicin and elemicin

Question 212

Chemical forms of hallucinogens

Answer 212

• indoleamine nucleus (e.g. seretonin NT)
• phenethylamine nucleus and catechol nucleus (e.g. precursor of catecholamines- DA, NE )
  nucleus helps predict which receptors it binds to
• dissociatives and deliriants e.g. ketamine, phencyclidine, ibotenic acid, muscimol, scopolamine, hysocyamine and atropine

Question 213

3 categories that hallucinogens fall into

Answer 213

1) Psychedelic (aka phantastica)- vivid sensations, altered perceptions and reality, users still responsive, communicative
2) Deliriant- vivid, maybe confusing, fantasy
3) Dissociative- analgesia, amnesia, catalepsy (seizure/loss of sensation/muscle rigidity), detached reality

Question 214

Big 3 effects of hallucinogens

Answer 214

1) Hallucination
2) Illusion
3) Delusion

Question 215

Hallucination

Answer 215

an experience involving the perception of something that may not actually be present

Question 216

Illusion

Answer 216

altered and distorted perceptions, thoughts, feelings, insights, awareness

Question 217

Delusion

Answer 217

fixed belief e.g. I am King of France, unchanged by conflicting evidence

Question 218

Trips are dependent on ____ (expectation, experience and personality) and ___

Answer 218

Trips are dependent on mindset (expectation, experience and personality) and setting

Question 219

Lower EC 50 = ___ potency
LSD (___ potency, EC 50= 100 μg) and mescaline (___ potency, EC 50= 350 μg)

Answer 219

Lower EC 50 = higher potency
LSD (highest potency) and mescaline (lowest potency)

Question 220

Administration of LSD

Answer 220

• ingested, injected, transdermal
• 10-300 μg
• blotting paper, sugar cube, gel caps, pressed tablets/microdots
  -microdosing: sub-psychedelic amounts (goal= subtly stimulate serotonergic activity in the brain)

Question 221

Distribution of LSD

Answer 221

• onset 30-90 minutes
• ~1% enters the brain
• TI>1000 (relatively safe)

Question 222

Metabolism of LSD

Answer 222

• liver
• 110-175 minutes half-life
• duration 5-12 hours (relates to high occupation time at 5HT2A receptors)

Question 223

Excretion of LSD

Answer 223

• Kidneys
• GI tract
• 1st order elimination kinetics (exponential decrease)

Question 224

Stages of LSD trips

Answer 224

1) 0-30 minutes after initial onset: physiological changes outside the brain, sympathomimetic, dizziness, nausea, muscle tremors, numbness

2) 30-120 minutes after initial onset: alteration of perceptions, familiar objects take on new appearance, time is lengthened, intense colors, patterns/textured illusions, movement in stable objects, intense sounds, smell, tastes, synesthesia

3) 3-5 hr: illusions continue, perception of self as mind/body disconnect (picture self in 3rd person perspective), distorted body appearance, deeper sense of self

Question 225

Synesthesia

Answer 225

overlapping sensations, altered perception of sensory afferent information- due to how thalamus is reacting to 5HT2A receptor triggering, auditory information is being re-routed to occipital lobe and you start to see the sound

Question 226

Psychological effects of LSD

Answer 226

-visual hallucinations and illusions
- synesthesia
- time and physical distortions
-intense emotion
- mystical, spiritual encounters
- introspection, ego dissolution (reduced defensiveness, more open)
- cognitive: inability to concentrate/focus, preoccupation with trivial thoughts, impaired judgements, communicating with God or telepathy with other animals

Question 227

Animal studies of LSD show that animals do not ___ -___ and will actually evoke effort to ___ administrations.

This is because of signalling through ___-like pathways especially in the NAc (core region)

Answer 227

Animal studies of LSD show that animals do not self -administer and will actually evoke effort to STOP administrations.

This is because of signalling through D2-like pathways especially in the NAc (core region)

Question 228

LSD is ___ it will increase BP, cause vasoconstriction, sweating and dilated pupils

Answer 228

LSD is sympathomimetic it will increase BP, cause vasoconstriction, sweating and dilated pupils

Question 229

How the stimulation of 5HT2A receptors by LSD affects LC (locus coeruleus)

Answer 229

5HT2A in other regions e.g. mPFC will project to LC. It will transform regular events into extremely novel, seemingly new encounters- instead of having preconcieved notion of object/memory of object people do not remember that and it is as if they are seeing something for the first time

Question 230

LSD is an agonist at 5-HT1A/B, 2A/B/C, 6 and 7; primarily ___

5-HT2A:
- high pre-synaptic expression in ___- perception and information processing centres
- controls ___ ___ even after a single use
- presynaptic in mPFC: Governs neuroplastic changes via ___ signaling, complementary actions by other 5-HT receptors and DA receptors
- part of the reason that LSD is not classically addictive is because of its high affinity for ___-like receptors which are coupled to __/__ which reduces some of the DA signaling in NAc <– underlies ___ ___, ___ of self-administration

Answer 230

LSD is an agonist at 5-HT1A/B, 2A/B/C, 6 and 7; primarily 2A

5-HT2A:
- high pre-synaptic expression in cortex- perception and information processing centres
- controls transcriptional programming even after a single use
- presynaptic in mPFC: Governs neuroplastic changes via glutamate signaling, complementary actions by other 5-HT receptors and DA receptors
- part of the reason that LSD is not classically addictive is because of its high affinity for D2-like receptors which are coupled to Gi/o which reduces some of the DA signaling in NAc <– underlies aversive conditioning, lack of self-administration

Question 231

LSD is very low on the __ __ scale. One exception is ___ (i.e. muscarinics)

Answer 231

LSD is very low on the abuse potential scale. One exception is deliriants (i.e. muscarinics)

Question 232

Psilocybin (shrooms/magic mushrooms):
- ___ version of LSD
- no ___, no ___ ___
- metabolized to ___ (slightly less active component) in gut and liver
- 5HT2A ___
- sympathomimetic, altered ___ and ___, hallucinations, heightened ___
- not ___, ___ tolerance

Answer 232

Psilocybin (shrooms/magic mushrooms):
- milder version of LSD
- no flashbacks, no lethal cases
- metabolized to psilocin in gut and liver
- 5HT2A agonist
- sympathomimetic, altered time and perceptions, hallucinations, heightened emotions
- not addictive, rapid tolerance

Question 233

DMT:
- ___, smoke, __
- destroyed in the gut- might treat worms, parasites
- 5HT2A/C and 1A agonist, many other receptors
- ____ tolerance
- physiological effects similar to LSD, psilocybin
- psychological effects: ________

Answer 233

DMT:
- snort, smoke, inject
- destroyed in the gut- might treat worms, parasites
- 5HT2A/C and 1A agonist, many other receptors
- no tolerance
- physiological effects similar to LSD, psilocybin
- psychological effects: intense, vivid hallucinations, emotions, introspection, connection to surrounding

Question 234

Harmine and harmaline:
- beta-carboline chemicals
- selective and reversible ___ ___-_ inhibitors (__-___)- which would otherwise breakdown NTs
-acetylcholinesterase inhibitors: may be useful in __ disease
- stimulate striatal DA release at high doses: used to treat ___ patients

Answer 234

Harmine and harmaline:
- beta-carboline chemicals
- selective and reversible monoamine oxidase-A inhibitors (MAO-A)- which would otherwise breakdown NTs
-acetylcholinesterase inhibitors: may be useful in Alzheimer’s disease
- stimulate striatal DA release at high doses: used to treat Parkinson’s patients

Question 235

Ayahuasca (DMT + beta-carbolines):
- Reason for DMT+ betacarboline combination= ___
- activates ___ and ___ brain regions
- powerful visions, intense emotion, profound introspection
- adverse effects: ___, ___

Answer 235

Ayahuasca (DMT + beta-carbolines):
- Reason for DMT+ betacarboline combination= beta-carbolines protect DMT from degradation by MAO, it enhances distribution to the brain
- activates vision and memory brain regions
- powerful visions, intense emotion, profound introspection
- adverse effects: vomiting, diarrhea

Question 236

Bufotenin:
- close chemical similarity to ___
- Common effects include drooling, heart palpitations, elevated BP, oxygen depletion, cramped muscles, blurred vision, headache, toad breath
- hallucinations likely caused by decreased ___ to __ __
- toads produce toxic ___ that leads to dysrhythmias

Answer 236

Bufotenin:
- close chemical similarity to 5-HT
- Common effects include drooling, heart palpitations, elevated BP, oxygen depletion, cramped muscles, blurred vision, headache, toad breath
- hallucinations likely caused by decreased oxygen to optic nerve
- toads produce toxic glycosides that leads to dysrhythmias

Question 237

Ibogaine:
- may block ___ circuits
- elevates glial cell-line derived neurotrophic factor (___) in midbrain
- ___ release in VTA leads to reduction in craving and drug intake
- may damage ___, cause ___ ___ ___, increase risk of ___ ___ and ___

Answer 237

Ibogaine:
- may block addiction circuits
- elevates glial cell-line derived neurotrophic factor (GDNF) in midbrain
- GDNF release in VTA leads to reduction in craving and drug intake
- may damage cerebellum, cause severe motor tremors, increase risk of heart attack and seizure

Question 238

Mescaline:
-__, 4-12 hour duration, TI __-__ (relatively high)
- vivid hallucinations, similar to ___
- toxic effects evoke ___ and vomiting
- ___ due to convulsions and respiratory arrest

Answer 238

Mescaline:
-ingested, 4-12 hour duration, TI 7-30 (relatively high)
- vivid hallucinations, similar to LSD
- toxic effects evoke nausea and vomiting
- death due to convulsions and respiratory arrest

Question 239

Nutmeg and mace
- ingested, ___, ___
- lower doses (5g) cause very ___ hallucinations, ___, confusion, ___ of ___, euphoria
- higher doses (5-30g) cause hallucinations, ___ ___, dizziness, apprehension, nausea, vomiting, unreality can persist for ___

Answer 239

Nutmeg and mace
- ingested, inhaled, insufflated
- lower doses (5g) cause very mild hallucinations, disorientation, confusion, feelings of unreality, euphoria
- higher doses (5-30g) cause hallucinations, facial flushing, dizziness, apprehension, nausea, vomiting, unreality can persist for days

Question 240

5-HT underlies ‘complex’ cognitive and emotional functions in humans e.g. language, alturism, empathy

Answer 240

5-HT underlies ‘complex’ ___ and ___ functions in humans e.g. language, alturism, empathy

Question 241

5-HT2A expression in sub-cortical nuclei may alter ___ ___ that will support a re-routing of perception, allow you to access ___ and focus your ___ on re-writing those memories

Answer 241

5-HT2A expression in sub-cortical nuclei may alter functional connectivity that will support a re-routing of perception, allow you to access memories and focus your attention on re-writing those memories

Question 242

Plant-derived anti-cholinergics

Answer 242

Mandragora officinarum (mandrake), atropa belladonna (nightshade), datura stramonium (datura), hyoscyamus niger (henbane)

Question 243

Mandragora officinarum (mandrake):
- low doses:
-high doses:

Answer 243

Mandragora officinarum (mandrake):
- low doses: relieves anxiety, induces sleep
-high doses: causes hallucinations, amnesia, muscular paralysis

Question 244

All plant-derived anti-cholinergics contain

Answer 244

3 primary tropane alkaloids atropine, scopolamine and hyoscyamine

Question 245

Anti-cholinergics will block muscarinic AChRs (AChR is used in parasympathetic system) causing …

Answer 245

dilated pupils, increased heart rate, dry secretions (esp. mouth)

Question 246

Anti-cholinergics:
- produce hallucinations, but don’t remember it
- physiological effects: ______
- can be ___- rapid heart rate, hyperthermia, asphyxia
- it has parasympatholytic effects (i.e. reducing activity of parasympathetic system)
- usually no ___

Answer 246

Anti-cholinergics:
- produce hallucinations, but don’t remember it
- physiological effects: elevates heart rate, dry mouth, lack of perspiration, constipation, difficulty urinating
- can be fatal- rapid heart rate, hyperthermia, asphyxia
- usually no euphoria

Question 247

Dissociatives:
- ___ (phencyclidine) and ___ which are anaesthetics
- ___ ___, ___ ___
- completely removed from reality, ___
- produce reinforcement in animal models, unique amongst hallucinogens but _____

Answer 247

Dissociatives:
- PCP (phencyclidine) and ketamine which are anaesthetics
- Amanita muscaria, Saliva divinorum
- completely removed from reality, detached
- produce reinforcement in animal models, unique amongst hallucinogens but not due to augmented DA release in the NAc

Question 248

PCP (phencyclidine):
- inhaled, ___ a cigarette in ___-___ and smoke it
- ___, ___, or ___ (hardcore users)
- duration 4-8 hours, TI 10-15
- diverse effects dependent on ___
- blocks ___ in cortex and hippocampus
- increased synthesis and release of ___ causing agitation, stimulation, locomotor activity
- delirium, confusion, paranoia, impaired ___ may last for days or weeks (most likely due to cellular tolerance of NMDA receptors)

Answer 248

PCP (phencyclidine):
- inhaled, dip a cigarette in free-base and smoke it
- ingested, insufflated, or injected (hardcore users)
- duration 4-8 hours, TI 10-15
- diverse effects dependent on dose
- blocks NMDARs in cortex and hippocampus
- increased synthesis and release of DA causing agitation, stimulation, locomotor activity
- delirium, confusion, paranoia, impaired memory may last for days or weeks (most likely due to cellular tolerance of NMDA receptors)

Question 249

Dose dependent effects of PCP at 5mg, 10mg and >20mg

Answer 249

5mg:
- anaesthetic, analgesic, stimulant, depressant, convulsant, hallucinogen

10mg:
- muscle rigidity, loss of pain sensitivity, agitation, mood swings, combative (wanting to fight), sympathomimetic, visual/auditory hallucinations, detachment

> 20 mg: toxic dose
- convlusions, respiratory failure, coma, death

Question 250

Ketamine:
- ingested, ___, ___, ___
- 15-20 minute onset, 35-60 minute duration
- same effects as PCP, ___ acting
- Blocks ___ in cortex and hippocampus
- increase synthesis and release of ___ causing agitation, stimulation, locomotor activity

Answer 250

Ketamine:
- ingested, inhaled, insufflated, injected
- 15-20 minute onset, 35-60 minute duration
- same effects as PCP, shorter acting
- Blocks NMDARs in cortex and hippocampus
- increase synthesis and release of DA causing agitation, stimulation, locomotor activity

Question 251

What happens as a result of ketamine and PCP blocking NMDARs ion channels?

Answer 251

it will affect Glu, NE, DA, ACh and 5-HT NTs

Question 252

Dependence on PCP and Ketamine

Answer 252

• moderate risk, mildly reinforcing but no DA increases in the NAc
• PCP self-administration in animal models
• mostly psychological, very slight physical dependence
• Ketamine dependence is liked to access not neurochemistry e.g. someone in vet clinic steals ketamine

Question 253

Adverse effects of PCP and Ketamine (vitamine K)

Answer 253

• psychosis and analgesia lead to damaging behaviors: attempting ‘superhuman’ feats
• ketamine cystitis: arrest bladder cell growth, cause cell death, causes blood urine, pain, incontinence (leaking urine by accident)
• long-term users experience memory loss, speech problems, delusional thinking

Question 254

Amanita muscaria:
- ingested, onset 30-90 minutes, duration up to ___ hours
- withdrawal ___, ___, ___ can last for days
- active chemical is excreted ___ in urine
- alter ___ ___, euphoria, dizziness, vivid hallucinations
- muscle twitches, sweat, salivation, constructed pupils, lowered BP
- Muscimol is ___ agonist responsible for most effects
- Ibotenic acid binds ___
- Fatal dose is around ___ mushroom caps

Answer 254

Amanita muscaria:
- ingested, onset 30-90 minutes, duration up to 12 hours
- withdrawal headaches, amnesia, sleepiness can last for days
- active chemical is excreted unchanged in urine
- alter body perception, euphoria, dizziness, vivid hallucinations
- muscle twitches, sweat, salivation, constructed pupils, lowered BP
- Muscimol is GABAA R agonist responsible for most effects
- Ibotenic acid binds NMDARs
- Fatal dose is around 15 mushroom caps

Question 255

Salvia divinorum:
- inhaled, ___; 15-120 minute duration
- mild alteration of ___ to __ ___ trip
- vivid visuals, sensory and time disturbances, detachment and ___ through time
- nausea, ___ ___, chills
- very high dose can cause ___ lesions

Answer 255

Salvia divinorum:
- inhaled, chewed; 15-120 minute duration
- mild alteration of consciousness to full psychedelic trip
- vivid visuals, sensory and time disturbances, detachment and floating through time
- nausea, slurred speech, chills
- very high dose can cause brain lesions

Question 256

New psychoactive substances (NPSes)

Answer 256

chemical alteration of existing hallucinogens

Question 257

2-C drugs:
- 5HT receptor agonists
- produce hallucinations, ___ effects
- adverse effects: ___, ___ ___, lethal (because designed drug it is more severe)

Answer 257

2-C drugs:
- 5HT receptor agonists
- produce hallucinations, stimulant effects
- adverse effects: seizure, extremity rigidity, lethal (because designed drug it is more severe)

Question 258

Bromo-dragonFLY:
- ___
- duration ___-___ ___
- binds 5-HT1 and __ receptors
- severe vasoconstriction via alpha adrenergic receptors
- similar effects to LSD
- ___ therapeutic window, several ___ ___ have been reported

Answer 258

Bromo-dragonFLY:
- benzodifuran
- duration 1-3 days
- binds 5-HT1 and 2A receptors
- severe vasoconstriction via alpha adrenergic receptors
- similar effects to LSD
- narrow therapeutic window, several overdose deaths have been reported

Question 259

N-benzyl-oxy-methyl (NBOM) drugs:
- several ‘N-bomb’ derivatives, __-__-__ is most common
-___ 5HT2A agonists

Answer 259

N-benzyl-oxy-methyl (NBOM) drugs:
- several ‘N-bomb’ derivatives, 2C-I-NBOM is most common
-potent 5HT2A agonists

Question 260

Designer drugs, include several evolving classes of ____. They resemble the ___ + ___ ring feature of MDMA

Answer 260

Designer drugs, include several evolving classes of stimulants. They resemble the amphetamine + methylene ring feature of MDMA

Question 261

___ ___, more commonly known as bath salts, are drugs that contain one or more human-made chemicals related to ___, a stimulant found in the ___ plant.

Answer 261

Synthetic cathinones, more commonly known as bath salts, are drugs that contain one or more human-made chemicals related to cathinone, a stimulant found in the khat plant

Question 262

Source of bath salts

Answer 262

khat plant

Question 263

Bath salts resemble __ ___ __

Answer 263

epsom salt crystals- why it is known as “bath salt”

Question 264

Bath salts are collectively known as __- ___ amphetamines. __ reduces lipophilicity, reduces transport across BBB.

The most common bath salt is 4-___

The nucleus present in cathinone = ___

Answer 264

Bath salts are collectively known as beta- ketonated amphetamines. Ketone reduces lipophilicity, reduces transport across BBB.

The most common bath salt is 4-methylmethcathinone

The nucleus present in cathinone = phenethylamine

Question 265

3M’s refers to…

Answer 265

the 3 synthetic cathinones (mephedrone, methylone, MDPV) that are active agents in bath salts

Question 266

Recreational effects of 3Ms/bath salts

Answer 266

• sympathomimetic effects, high energy
• euphoria
• arousal
  -MDPV is stimulant at low doses, induces bizarre behaviors at high doses

Question 267

Physiological mechanisms of 3Ms:
- euphoria via elevated __ __
- increased ___ and __ in NAc of rats
- striatal __ elevations cause locomotor activity increases in mice and rats
- sympathomimetic (via __, ___, ___ increases): agitation, hyperthermia, tachypnea (rapid breathing), tachycardia (rapid heart rate), hypertension, cardiac arrest
- hyperthermia leads to ___ (muscles breaking down), ___ ___ (myoglobin that is supposed to be in muscle cells will get to kidney and shut them down)
-___, ___, __ ___ and ___ ___ are most common adverse effects

Answer 267

Physiological mechanisms of 3Ms:
- euphoria via elevated NAc DA
- increased DA and 5HT in NAc of rats
- striatal DA elevations cause locomotor activity increases in mice and rats
- sympathomimetic (via DA, NE, 5HT increases): agitation, hyperthermia, tachypnea (rapid breathing), tachycardia (rapid heart rate), hypertension, cardiac arrest
- hyperthermia leads to rhabdomyolysis (muscles breaking down), kidney failure (myoglobin that is supposed to be in muscle cells will get to kidney and shut them down)
-hyperthermia, hypertension, cardiac arrest and serotonin syndrome are most common adverse effects

Question 268

The cellular mechanism of the 3Ms withOUT pyrrolidine ring (i.e. mephedrone and methylone)

Answer 268

1) Bind DAT, SERT, NET
2) Enter terminals via SERT
3) Interact with TAAR
4) Leak cytoplasmic NT stores, reverse transporter, inhibit VMAT
5) Mephedrone and methylone stimulate non-exocytotic release of DA, 5HT, NE

Question 269

The cellular mechanism of the 3Ms WITH pyrrolidine ring i.e. MDPV

Answer 269

blocks transporters does not reverse transporters- does not enter terminals because of its size. It is a potent DAT/NET blocker, weaker SERT activity

Question 270

IC 50 represents…

Answer 270

concentration of drug required to block 50% of uptake

Question 271

A lower IC 50= more/less potent

Answer 271

more potent

Question 272

A DAT/SERT of 806 means that MDPV is 806x more potent at ___ compared to ___, predict MDPV to have high abuse potential

Answer 272

A DAT/SERT of 806 means that MDPV is 806x more potent at DATs compared to SERTs, predict MDPV to have high abuse potential

Question 273

Structure-activity relationship i.e. what kind of structure of 3Ms produce highest activity at DAT?

Answer 273

those with larger carbon tails and a pyrrolidine <– explains why MDPV has highest activity at DAT/able to block it and block its reuptake of DA releasing DA instead

Question 274

Mechanisms of 3M reinforcement:
- 3M bath salts bind ___
- ___ and ___ enter terminals, displace DA into synapse and ___ DAT
- ___ does not enter terminals

Answer 274

Mechanisms of 3M reinforcement:
- 3M bath salts bind DAT
- Mephedrone and methylone enter terminals, displace DA into synapse and reverse DAT
- MDPV does not enter terminals

Question 275

Adverse effects of bath salts on behavior at high doses

Answer 275

• violence, homicidal combative behavior, self-mutilation, excited delirium syndrome (ExDS)
• panic attacks, paranoia, suicidal thoughts, confusion, psychosis

Question 276

Cathinone fatal case reports:

Symptoms are related to surge in levels of dopamine, noradrenaline and serotonin in the periphery and include: ______

Answer 276

hyperthermia (indicated as primary problem in several deaths- many users take off clothes), leads to rhabdomyolysis, kidney failure, tachycardia (sometimes followed by bradychardia), hyperternsion, chest pain, panic attacks, paranoia, suicidal thoughts, confusion, psychosis

Question 277

Other adverse effects of 3Ms

Answer 277

• water intoxication = hyponatremia
• increased cranial pressure caused tonsillar herniation of cerebellum (cerebellum to be pushed through skull)
• pressure on medulla lead to respiratory depression, cardiac arrest

Question 278

Tolerance, withdrawal and dependence of bath salts/3Ms:

• Rhesus monkeys show ___ self-administration for __ with MDPV and alpha-PVP compared to cocaine and meth
  -rats display ___ drug-taking behavior when given free access to MDPV (rapid mechanisms of tolerance)
  -mephedrone causes ___ in mice and rats
• altogether, bath salts appear to have a very ___ abuse potential

Answer 278

Tolerance, withdrawal and dependence of bath salts/3Ms:

• Rhesus monkeys show higher self-administration for longer with MDPV and alpha-PVP compared to cocaine and meth (REALLY high abuse potential since cocaine and meth are on the top of the abuse spectrum)
  -rats display escalating drug-taking behavior when given free access to MDPV (rapid mechanisms of tolerance)
  -mephedrone causes CPP in mice and rats
• altogether, bath salts appear to have a very high abuse potential

Question 279

Categories of PEDs (performance enhancing drugs)

Answer 279

anabolic/androgenic steroids (AAS) and hormones

Question 280

____ are the major PEDs (performance enhancing drugs). They are based off ___ ___ nucleus. They are altered to ___ ___ ___

Answer 280

AAS are the major PEDs (performance enhancing drugs). They are based off testosterone steroid nucleus. They are altered to enhance muscle building- increase muscles, mass and decrease fat

Question 281

Type 1 AAS (anabolic/androgenic steroids):
- ___
- ____ half-lives
- hydrolyzed to ____
- aromatized to ____ by aromatase

Answer 281

Type 1 AAS (anabolic/androgenic steroids):
- esters
- prolonged half-lives
- hydrolyzed to testosterone
- aromatized to estrogens by aromatase

Question 282

Type 2 AAS (anabolic/androgenic steroids):
- __-__-testosterone (nandrolone) derivatives
- ___ half-lives
- ___ androgenic effects
- 80% ___ aromatization compared to type 1

Answer 282

Type 2 AAS (anabolic/androgenic steroids):
- 19-nor-testosterone (nandrolone) derivatives
- prolonged half-lives
- reduced androgenic effects
- 80% less aromatization compared to type 1

Question 283

Type 3 AAS (anabolic/androgenic steroids):
- ___-___ derivatives
- greatly ____ liver metabolism- prolongs action
- ___ converted to estrogen
- ____ anabolic effects

Answer 283

Type 3 AAS (anabolic/androgenic steroids):
- 17alpha-alkyl derivatives
- greatly reduced liver metabolism- prolongs action
- not converted to estrogen
- increased anabolic effects

Question 284

Best type AAS for body builders?

Answer 284

type 3

Question 285

Administration of AAS:
- ____: increasing doses followed by decreasing dose
- ___: using multiple steroids
- ____: alternating periods of use, co-ordinated with training or testing schedules - why the best anti-doping policies are random
- certain users e.g. ____ may take 100-1000x therapeutic doses

Answer 285

Administration of AAS:
- pyramiding: increasing doses followed by decreasing dose
- stacking: using multiple steroids
- cycling: alternating periods of use, co-ordinated with training or testing schedules - why the best anti-doping policies are random
- certain users e.g. bodybuilders may take 100-1000x therapeutic doses

Question 286

Distribution of AAS

Answer 286

• lipophilic because of ring structures
• rapid
• muscle
• widespread

Question 287

Metabolism of AAS

Answer 287

• liver
• first-pass metabolites
• low bioavailability (slowly absorbed)

Question 288

Absorption of AAS

Answer 288

• injection intramuscular
• ingestion
• topical

Question 289

Excretion of AAS

Answer 289

• kidney 90%
• other 10% e.g. GI tract

Question 290

Mechanisms of AAS action

Answer 290

• anabolic steroids bind androgen receptor
• higher concentrations cause additional receptor binding e.g. estrogen receptors
• drug-receptor complexes translocate to nucleus, bind specific DNA sequences
• activates gene transcription mRNA production, make new protein e.g. to build muscle
• steroids shift stem cells towards muscle cell differentiation, as opposed to adipose cell

Question 291

Mechanism(s) of reinforcement

Answer 291

• many users report euphoria
• may come from increased beta-endorphin levels which decrease GABA release onto VTA DA-ergic neurons
• when steroids modulate GABA A receptors, DA-ergic mesolimbic neurons increase firing rate

Question 292

AAS produce massive weight ____, virtually all ___

Answer 292

AAS produce massive weight gains, virtually all muscle

Question 293

When treated with AAS animals showed..

Answer 293

• increased number of myonuclei (drive maintenance of cells)
• increased muscle fibre cross-sectional area (increase area=increase force)

Question 294

Cellular ‘____’ allows rapid muscle building after period of inactivity- mice with steroid treatment have quicker muscle recovery after taking a break

Answer 294

Cellular ‘memory’ allows rapid muscle building after period of inactivity

Question 295

Cellular mechanisms of action: Trenbolone (an androgen)
- ___-___ derivative of testosterone
- not a substrate for ___ ___-___(testosterone) nor ___ (estrogen)
- induces ____ effects without unwanted effects
- reverses expression of ____ (cause muscle to digest self) genes
- increases expression of ____ genes (helps with muscle growth)

Answer 295

Cellular mechanisms of action: Trenbolone (an androgen)
- 19-nor derivative of testosterone
- not a substrate for 5 alpha-reductase nor aromatase
- induces myotrophic effects without unwanted effects
- reverses expression of atrophic (cause muscle to digest self) genes
- increases expression of anabolic genes

Question 296

Tolerance of AAS

Answer 296

• even after a single dose
• presence of steroids inhibits their own production-negative feedback

Question 297

Withdrawal of AAS

Answer 297

depression, mood swings, fatigue, headache, insomnia, lack of energy, no appetite, body dissatisfaction

Question 298

Dependence of AAS

Answer 298

• 30% of users become dependent
• more likely at higher doses
• mostly psychological due to cycle length

Question 299

Long-term health risks of AAS:
- steroid receptors are present in ___ ___ e.g. ___ and ___
- lack of knowledge of __ __ and ___ genes are turned on
- activation of other genes leads to ___, ___ side effects
- ___ blood pressure, cholesterol, and heart abnormalities
- “___” rage: increased aggression, anger, rage especially in dependent users, psychosis and depression also occur more frequently, __ __ and ___ and ___ receptors can bind endogenous neurosteroids

Answer 299

Long-term health risks of AAS:
- steroid receptors are present in multiple tissues e.g. muscle and brain
- lack of knowledge of how many and which genes are turned on
- activation of other genes leads to unwanted, dangerous side effects
- increased blood pressure, cholesterol, and heart abnormalities
- “roid” rage: increased aggression, anger, rage especially in dependent users, psychosis and depression also occur more frequently, GABA A and NMDA and 5HT receptors can bind endogenous neurosteroids

Question 300

AAS long-term effect on anterior hypothalamus (AH)

Answer 300

• activation of D2 in AH results in aggression and violence in animal models
• moderate doses in adolescence increases D2 expression in AH
• arginine vasopressin is excitatory and potentiates aggression, while 5HT is inhibitory and decreases aggression
• steroid exposure enhances vasopressin, reduces 5-HT effects

Question 301

AH (anterior hypothalamus)

Answer 301

aggression centre

Question 302

___ is a common effect reported by steroid abusers this is because abuse is linked to reduced ___-___ ___ ___ (___) which correlates with ___ behaviours. ___ also stimulates neuronal growth in hippocampus

Answer 302

Depression is a common effect reported by steroid abusers this is because abuse is linked to reduced brain-derived neurotrophic factor (BDNF) which correlates with depressed behaviours. BDNF also stimulates neuronal growth in hippocampus

Question 303

Clinical steroids are __ and ___ detected

Answer 303

Clinical steroids are safe and easily detected

Question 304

Designer steroids

Answer 304

• modified by clandestine labs
• undetectable
• no one knows the mechanisms, long-term effects

Question 305

How are steroid samples tested?

Answer 305

• usually urine, tested for known metabolites
• can run HPLC, ELISA, GC-MS

Question 306

Cycle of addiction

Answer 306

1) Initial drug use: genetics (impulsivity), mood (depression), environment (early life trauma)

2)Acute drug experience (euphoria, analgesia, anxiolytic, antidepressant)

3) Drug withdrawal (opposite effects of acute drug use, unpleasant symptoms can drive craving and relapse)

4) chronic drug experience (neurological adaptations, tolerance to positive effects of drug and natural rewards, loss of prefrontal cortical control of drug behaviors- compulsive drug seeking)

Question 307

behavioral interventions for addiction

Answer 307

CBT (cognitive behavioral therapy), contingency management interventions/motivational incentives, counselling/therapeutic communities

Question 308

CBT (cognitive behavioral therapy)

Answer 308

a talk-based psychosocial intervention administered by a licensed psychologist. Aims to develop non-drug coping strategies to triggers

Question 309

Contingency management interventions/ motivational incentives

Answer 309

individuals are rewarded (money) for evidence of positive behavioral change e.g. clean urine drug screens

Question 310

Counselling/therapeutic communities

Answer 310

alcoholics anonymous, narcotics anonymous etc.

Question 311

Pros and cons to narcotics anonymous and alcohol anonymous

Answer 311

pros:
- connects people seeking treatment to a community of non-users
- de-stigmatizes drug use
- can connect users with medical interventions
- free (low barrier of access)

cons:
- no medical interventions
- religious undertones can be off-putting for some
- abstinence only

Question 312

2 pharmacological intervention drug classes

Answer 312

1. block the positive effects of the drug: drug no longer rewarding, no longer desire/drive to continue using
2. make withdrawal easier: try to restore hedonic balance, ability to feel pleasure in normal life things not related to drug

Question 313

Drug withdrawal

Answer 313

• certain drugs induce lethal withdrawal symptoms e.g. alcohol
• other drugs induce long-term withdrawal that are unpleasant and promote continued drug use e.g. nicotine, opioids
• treatment of withdrawal symptoms can help maintain drug abstinence and may be a necessary step to safely and effectively stop drug use
• treatment involves treatment with a drug that targets the same receptor as the drug of abuse, but with safer therapeutic profile

Question 314

NRT (nicotine replacement therapy)

Answer 314

• provides nicotine by means other than tobacco (gum, patches, vaping)
• alleviates side effects of nicotine withdrawal and reduces drug cravings
• increases success of quitting by 55%
• side effects similar to tobacco e.g. dry mouth, headaches
• probably safe for long term use (better than tobacco), minimal studies done on long term effects