Pharmacology of Cannabis/Cannabinoids

Question 1

Explain the legal status of natural and synthetic cannabinoids.

Answer 1

Federal law permits the cultivation and sale of hemp not marijuana
Hemp and industry hemp refer to the strain of cannabis plant that is grown for agricultural products such as textiles, seeds, and oils
Marijuana is illegal to grow and distribute;
Cannabis remains schedule I under federal controlled substance act
Legalization of hemp production has allowed the production and promotion of other cannabinoids - now hemp and hemp-derived products, including CBD oil are legal
synthetic marijuana use is widespread, though illegal; agents are more potent than THC

Question 2

FDA approved cannabinoid drugs

Answer 2

Marinol (Dronabinol)
Nabilone (Cesamet)

Question 3

Marinol

Answer 3

• Synthetic Δ9-THC in sesame oil
• Schedule III
• Counter loss of appetite
• Tachycardia, red eyes

Question 4

Nabilone

Answer 4

• THC mimetic
• Schedule II
• Anti-emetic
• Chronic pain (Off Label): Fibromyalgia, Multiple Sclerosis

Question 5

Cannabidiol (CBD) Pharmacology and Use

Answer 5

• Low affinity for CB receptors
• May antagonize THC @ CB1
• Promiscuous effects on ECS
• Lacks euphoric effects
• CBD oil with <0.3% THC legal in IN
• Most common reported use is for pain
• Sold in many forms: oral, topical, cosmetic,
  edibles, vaporizers
• FDA approved drug for seizure disorder
  CBD products are unregulated and of unknown and variable quality

Question 6

CBD approved for rare seizure disorders

Answer 6

Dravet Syndrome
Lennox-Gastaut Syndrome

Question 7

Differentiate hemp and marijuana based on ∆9− THC content.

Answer 7

Hemp: contains 0.3% of less of tetrahydrocannabinol (THC)
Marijuana: contains 15-20% of tetrahydrocannabinol (THC)

Question 8

Describe the clinical effects associated with cannabis ingestion.

Answer 8

Acute cannabis intoxication: perceptual, affective, physical, cognitive

Question 9

Perceptual

Answer 9

Temporal slowing
Auditory, visual, or tactile illusions
De-personalization

Question 10

Affective

Answer 10

Euphoria
Disinhibition
Anxiety
Emotional lability

Question 11

Physical

Answer 11

Tachycardia
Postural hypotension
Conjunctival injection
Dry mouth
Increase appetite

Question 12

Cognitive

Answer 12

Suspiciousness or paranoid ideation
Impaired judgement
Impaired reaction time
Impaired attention

Question 13

Name the 4 key components of the endocannabinoid system and where ∆9−THC acts on this system.

Answer 13

• Receptors (CB1 & CB2)
• Ligands (Anandamide [AEA] and 2-AG)
• Transporter (EMT, endocannabinoid membrane transporter)
• Enzymes (fatty acid amide hydrolase, FAAH; mono-glycerol lipase, MAGL; diacyl glycerol lipase, DAG) - involved in synthesis and degradation
  THC is a partial agonist at CB1R, while synthetic cannabinoids are full agonists

Question 14

Endocannabinoids and phytocannabinoids serve as

Answer 14

retrograde regulators of neurotransmission, inhibiting release of GABA and glutamine
work as part of feedback loop to decrease signaling that comes from gabaergic + glutamergic innervation into DA

Question 15

CB1 expression in brain is higher than

Answer 15

CB2 receptor expression
* Brain CB1&raquo_space; CB2
* Low levels respiratory centers of brainstem
* <resp. depression, coma
* CB2 on glia

Question 16

CB2 expression in periphery is higher than

Answer 16

CB1 receptor expression
* Periphery: CB2&raquo_space; CB1 - don’t get the significant psychological effects
CB2
* Lymphocytes: B-Cells; T-Cells - part of inflammatory response
CB1
* Liver: Increase lipogenesis
* Upregulated in liver fibrosis

Question 17

Summarize the association of heavy cannabis use with mental health disorders.

Answer 17

• Extremely difficult to prove and controversial.
• Growing evidence for association with several disorders, cause and effect not established.
  Risk factors and pathway to psychosis: age of use onset and potency appear to be key determinants

Question 18

Describe the symptoms and management of cannabinoid hyperemesis syndrome.

Answer 18

Diagnostic Criteria:
* Cyclic vomiting/abdominal pain
* Presentation after prolonged,
excessive use
* Relief by sustained cessation
* May be associated with pathological bathing (hot showers/baths)
Treatment:
* Cannabis cessation
* Benzodiazepines
* Haloperidol
* Capsaicin cream (abdomen)

Question 19

Mechanism of Capsaicin for Cannabinoid Hyperemesis Syndrome

Answer 19

1. substance P activates neurokinin-1 receptors (NK-1R) in the medullary vomiting center of the CNS causing nausea and vomiting
2. activation of transient receptor potential vanilloid-1 (TRPV-1) receptor by heat, capsaicin, or acidic conditions causes depletion of substance P
3. Chronic cannabis use causes desensitization and downregulation of TRPV-1 receptors
4. topical capsaicin applied to the abdomical area provides multiple mechanism of sx releif