Cannabinoids

Question 1

Cannabinoid receptor history

Answer 1

1964 - toxic oil (-)-∆9-THC structure
1681 - stereoselectivity between cis/trans isomers response
1986 - synthesis analogues (CP55,940)
1988 - ability to inhibit cAMP formation and competes with analogues (use radioligand, CB1 = receptor)
1990 - isolate CB1 = GPCR, presynaptic terminals, inhibits cAMP, THC is partial agonist
1993 - CB2 in tonsils and immune cells

Question 2

Endocannabinoids

Answer 2

Anadamide, 2-AG, ∆-9-THC, JWH-018, SR141716A
Act on CB1 and CB2
Synthesised on demand from integral membrane phospholipids
Move in adipossomes and via AITs (anandamide intracellular transporters)

Question 3

Cannabinoid receptors

Answer 3

CB1 and CB2
GPCRs - Gi/o, decrease AC, AMP, Ca2+, K+ channels
Inhibitory but depends on which neurotransmitter is being effected

Question 4

2-AG

Answer 4

Synthesised from phospholipid by DAGL a/B, broken down by ABDH6/12 to arachidonate

Question 5

Anadamide

Answer 5

Synthesised from phospholipid by NATs broken down by FAAH

Question 6

Target CB1

Answer 6

Dronabinol - synthetic THC, treat CINV, AIDS weight loss
Nabilone - THC analogue, treat CINv
Nabiximols - 1:1 THC:CBD, spacticity
Rimonabant - inverse agonist, obesity, withdrawn
FAAH inhibitors in trial - withdrawal, pain, schizophrenia, bipolar disorder

Question 7

Clinical trial concerns

Answer 7

Not done well, doses too high
FAAH off target effects?

Question 8

Medicinal cannabis regulations

Answer 8

Need quality and standards
-contamination, storage, active ingredients concentrations, labelling
Doctors must prescribe within scope of practice, if not approved for that contraindication must go through MoH and specialist
Hasn’t been approved through medsfae

Question 9

Oral THC

Answer 9

Very active metabolite, although less reaches the blood, it still has a high effect

Question 10

Phytocannabinoids

Answer 10

From cannabis plant
CBD - not an agonist at CB1, slight inverse agonist at CB2, CYP2D6, ion channels among potential targets

Question 11

Medicinal cannabis

Answer 11

Dose of THC/CBD
Meta-analysis = small to very small improvement in pain and sleep (10%), adverse effects of dizziness etc
May use if standard care is not effective
IASP study of pain - inadequate reporting can not support or refute