Cannabinoids

Question 1

What are terpines?

Answer 1

A class of hydrocarbons with carbon skeletons derived from the basic isoprene unit

Question 2

What are cannabinoids?

Answer 2

Chemically, they are C21 terpenophenols obtained from the plant Cannabis Sativa L.

Question 3

What are the three classifications of cannabinoids?

Answer 3

1) phytocannabinoids
2) Endocannabinoids
3) Synthetic cannabinoids

Question 4

What can decarboxylate THC?

Answer 4

Light or heat

Question 5

How does THC show its psychoactive/hallucinogenic properties?

Answer 5

Acts as an agonist on the CB1 receptor in the brain

Question 6

What is the major therapeutic application of cannabinoids?

Answer 6

Chronic pain, (chemotherapy induced) N/V, anorexia and epilepsy

Question 7

What are some examples of synthetic cannabinoids?

Answer 7

Dronabinol –> trans isomer of THC

Nabilone –> trans isomer of THC and racemic

Question 8

What Health Canada schedule are cannabinoids in?

Answer 8

Schedule 2, controlled substances

Question 9

What are the chemical constituents of cannabinoids?

Answer 9

more than 450 chemical constituents

> 60 cannabinoids

Question 10

When was the recreational use of cannabis legalized in Canada?

Answer 10

Oct 2018

Question 11

What are the classifications of cannabinoids?

Answer 11

1) Phytocannabinoids
2) Endocannabinoids
3) Synthetic cannabinoids

Question 12

What are the non-psychoactive cannabinoids? What is the mildly psychoactive cannabinoid?

Answer 12

Non-psychoactive = THCA, CBDA & CBD

Psychoactive = CBN

Question 13

Can cannabinoids cause addiction or depenence?

Answer 13

Yes

Question 14

What is the ring system contained in cannabinoids?

Answer 14

Benzopyran ring system (tricyclic terpenoids)

Question 15

Can synthetic cannabinoids penetrate the CNS?

Answer 15

Yes, Dronabinol and nabilone are highly lipophilic and can penetrate the CNS

Question 16

Do cannabinoids used in therapy go through first pass metabolism? What is their oral bioavailability?

Answer 16

Yes, they go through extensive first pass effect in the liver/gut

Oral bioavailability = poor

Question 17

What are the AEs of dronabinol, cannabinol, and nabilone?

Answer 17

Nausea, sedation, dry mouth, euphoria, cognitive impairment, ataxia, headache, allergic reactions, addiction potential

Question 18

What do cannabinoids bind to and where are these receptors found? How similar are these receptors?

Answer 18

CB1 and CB2 receptors; these are G-protein coupled receptors present in the CNS and PNS

These receptors exhibit ~44% amino acid sequence similarity

Question 19

Phytocannabinoids are agonists for which receptors?

Answer 19

delta9-THC, CBN, CBD and CB

Question 20

What metabolizes cannabinoids?

Answer 20

CYP2C9
2C19
CYP3A4
UGT - UDP glucuronosyltransferase

Question 21

What receptors/enzymes can cannabinoids inhibit?

Answer 21

CYP3A4
2B6
2C9
2D6

Question 22

The different metabolism, inhibition, induction of enzymes suggest what about cannabinoids?

Answer 22

Potential drug-drug interactions during co-administration of other drugs that either induce or inhibit CYP enzymes

Question 23

Where are CB1 and CB2 receptors found?

Answer 23

CB1 = brain

CB2 = predominantly present in PNS

Question 24

What are the SAR considerations for cannabinoids?

Answer 24

• changing methyl group of ring C to ketones/alcohols increases CB affinity
• OH group on the A ring increases CB affinity
• the longer the chain on the A ring increases CB affinity

(look at the picture of THC to figure out what I’m talking about)