Alcohol

Question 1

Mechanism of Action of alcohol

Answer 1

• positive modulation of GABAA
  receptor function
• negative modulation of AMPA and
  NMDA receptor function
• general CNS depression

Question 2

Mechanism of Action of alcohol ?

Answer 2

• positive modulation of GABAA
  receptor function
• negative modulation of AMPA and
  NMDA receptor function
• general CNS depression

Question 3

what is the effect of chronic alcohol exposure

Answer 3

Downregulation of GABA A receptor function

Question 4

what is the mechanism of alcohol tolerance

Answer 4

• subunit switch (e.g. 𝝰4)
  (cross-tolerance to other
  positive modulators)
• increased internalization
• altered phosphorylation
• uncoupling of the GABA /
  ethanol sites

Question 5

what are the ethanol receptors

Answer 5

Glycine receptor
BK channel

Question 6

what are the alcohol withdrawal symptoms

Answer 6

minor withdrawal symptoms
seizures
delirium tremens
hallucination

Question 7

what are the Pharmacological therapy for alcohol use disorder

Answer 7

Diazepam
Acamprosate
Naltrexone

Question 8

how does Diazepam work

Answer 8

• benzodiazepine that is used to treat anxiety and convulsions
• approved for acute alcoholic withdrawal: symptomatic relief of acute
  agitation, tremor, and impending acute delerium tremens

Question 9

how does Acamprosate work

Answer 9

• dissociates into acetylhomotaurine and calcium
• homologue of GABA
• action not fully understood; restores the excitatory / inhibitory balance
  in the brain
• indicated for maintenance of abstinence from alcohol

Question 10

how does Naltrexone work

Answer 10

• long-acting opioid receptor antagonist (𝝻,𝝹,𝝳)
• action not fully understood; endogenous opioid system may be involved

Question 11

how does

Answer 11

As an antagonist at the 𝝻 opioid receptor,
naltrexone may reduce the urge to consume
alcohol through two mechanisms:
* Suppression of alcohol-mediated
𝝱-endorphin stimulation of dopamine
neurons in the nucleus accumbens
* Reduction of 𝝱-endorphin disinhibition of
the tonic inhibition of dopamine cells by
GABAergic neurons in the ventral
tegmental area

Question 12

How does Naltrexone reduce the urge to consume alcohol

Answer 12

As an antagonist at the 𝝻 opioid receptor,
naltrexone may reduce the urge to consume
alcohol through two mechanisms:
* Suppression of alcohol-mediated
𝝱-endorphin stimulation of dopamine
neurons in the nucleus accumbens
* Reduction of 𝝱-endorphin disinhibition of
the tonic inhibition of dopamine cells by
GABAergic neurons in the ventral
tegmental area

Question 13

what is cannabis

Answer 13

delta9-tetrahydrocannabinol
(Δ9-THC)

Question 14

how is the Δ9-THC concentrations in declining order:

Answer 14

flowering tops -> bracts -> leaves -> stems -> roots -> seeds

Question 15

which cannabinoid is Psychoactive, Less Psychoactive, Not Really Psychoactive

Answer 15

Psychoactive (i.e., activation of CB1 receptors)
* Δ9-THC
Less Psychoactive
* Cannabichromene
Not Really Psychoactive (not active at CB1 or CB2 receptors)
* Cannabinol
* Cannibidiol

Question 16

compare Pharmacokinetics of the cannabinoid

Answer 16

inhalation: Fast acting and early onset
- In blood within seconds
- 10-35% of THC in blood

ingestion;
- Slow acting and late onset
- Passes through the liver

Question 17

what are the behavioral effects of the cannabinoid

Answer 17

Subjects may have a form of disinhibition in that there is an inclination
to increase motor activity, and behavior is impulsive. However,
paradoxically, even the simplest tasks appear to require enormous
effort&raquo_space;»» Motor activity & impulsivity is up. Effort & coordination is down.

Question 18

what are the Problematic effects of Cannabinoid

Answer 18

• Forgetfulness (working memory tasks)
• Poor concentration
• Motor coordination impairment
• Poor sense of time
• Reaction time slower
• Some anxiety or paranoia

Question 19

what are the common withdrawal symptoms of cannabinoids

Answer 19

Common Symptoms
Decreased Appetite
Irritability
Nervousness/Anxiety
Anger
Restlessness
Sleep Difficulty/Strange Dreams

Question 20

how is the dopamine level after the THC withdrawal

Answer 20

Dopamine levels
are down during
withdrawal from
chronic THC

Question 21

what are the The ‘endocannabinoids’

Answer 21

1. Anandamide
2. 2-arachidonyl glycerol (2-AG)

Question 22

How do Endocannabinoids work

Answer 22

Agonists at CB1 and CB2

Question 23

how does CB1 work

Answer 23

• Expressed in the CNS (cerebral cortex, hippocampus, caudate putamen,
  basal ganglia, cerebellum)
• Located on presynaptic terminals (thus, modulate neurotransmitter release)

Question 24

how does CB2 work

Answer 24

• Very low expression
  in the CNS
• Predominantly located
  in the periphery

Question 25

what is Endocannabinoids: Mechanism of Action

Answer 25

Retrograde second messenger signalling to provide negative feedback

Question 26

What are CB1 and CB2 receptors coupled with

Answer 26

Both CB1 and CB2 receptors are GPCRs that are coupled with Gi/o (inhibitory)

Question 27

what is the signalling consequences of receptor activation

Answer 27

decreased function
of adenylate cyclase
- increased function
of GIRK K + channels
- decreased function
of voltage-gated
Ca2+ channels
This all acts to
hyperpolarize the local
membrane potential
and decrease
neurotransmitter release

Question 28

how annabinoids contribute to the reward pathway

Answer 28

Cannabinoids can activate the inhibitory CB1 receptor on GABAergic neurons
to disinhibit the VTA dopaminergic neurons —> increased DA release

Question 29

what is the Acute THC reward pathway

Answer 29

• increased DA neuron firing in the VTA
• increased DA release in the nucleus accumbens and prefrontal cortex
  (mesolimbic and mesocortical dopamine pathways)
• increased content for tyrosine hydroxylase (DA synthesizing enzyme)
• increased DA synthesis
  (CB1 receptor)

Question 30

what is the Chronic THC reward pathway

Answer 30

• altered GLU and GABA signalling onto VTA DA neurons (below)
• decreased DA synthesis and release in response to a rewarding stimulus
• increased D2 receptor availability in postsynaptic neurons
• morphological alterations to dendrites