Wolff: Tobacco, Vaping, Weed

Question 1

What makes the adolescent brain more sensitive to nicotine and other risk behaviors?

Answer 1

Incomplete development of the prefrontal cortex, which drives executive function (recognizing good vs bad)

They are more vulnerable to starting drugs and becoming addicted

Question 2

What effect does nicotine have on the prefrontal cortex?

Answer 2

• Neuroplasticity is impaired – brain can’t adapt as easily
• Causes dec memory and attention
• Behavioral disturbances later in life

Question 3

What is vaping’s connection with lung injury?

What ingredient is to blame?

Answer 3

• Seems to cause acute toxic lung injury
• Collection of pneumonitis patterns: ARDS, HSN pneumonitis, interstitial pneumonia
• Vitamin E acetate = bad ingredient

Question 4

MOA of endocannabinoids

Answer 4

1. Endocannabinoids are made when intracell Ca inc
2. EC’s diffuse into the synaptic space and bind to 2 types of CB1Rs on presynaptic neurons
   
   1. Anandamide: partial agonist
   2. 2-AG: full agonist
3. Act of CB1Rs inh adenylyl cyclase –> causes hyperpol and less NT release

Question 5

How are Endocannabinoid actions terminated?

Answer 5

1. Anandimide is broken down by FAAH of post-syn cells
2. 2-AG is broken down by MAG-lipase of pre-syn cell

Question 6

Where are CB2 receptors found?

What is the endocannabinoid affinity?

Answer 6

CB2 receptors = immune cells; modulate cytokine release

Anandamide and 2-AG have higher aff for CB1 than CB2

Question 7

Dronabinol

MOA; Indication; Off-label use; AE

Answer 7

MOA = equal affinity for CB1 and CB2, but more efficacy with CB1

Indication = analgesia, appetite, ms relax, & hormonal actions

Off-label use = obstructive sleep apnea

AE = affects judgement, sedation, bloodshot eyes, depression, dizzy, tachy, hypotension, hallucinations, dry mouth, concerns for effects on intelligence in young people

Question 8

Nabilone

Indication

Answer 8

Chemotherapy induced n/v

Question 9

Conditions with evidence of cannabis efficacy

Answer 9

Question 10

Contraindications and cautions with cannabis

Answer 10

Question 11

FAAH inhibitors would….

Answer 11

Allow for less breakdown of anandamide, thus allowing for an analgesic phenotype

Question 12

CBD pharmacokinetics

Answer 12

• Significant first pass metab – oral bioavailability nearly 6%
• High distribution and builds in adipose tissue
• Extensively metab in liver by 7 CYPs
• Given orally

Question 13

What receptors does CBD affect?

Answer 13

Agonism = TRPV1, PPARg, 5-HT1A

Inverse Agonism = CB1, CB2

Question 14

When is CBD useful?

Answer 14

Epilepsy

Dravet syndrome: myoclonic seizures

Lennox-Gastaut syndrome: drop seizures