Cannabis And Plant-derived Cannabinoids

Question 1

What are phytocannabinoids?

Answer 1

Plant derived cannabinoids - a lot of active chemicals in cannabis plant

Question 2

Long history with cannabis (6)

Answer 2

used as medicine several thousand years ago China, India, Persia, Assyria

1839: Pain, spasms, convulsions =queen vic

1964: THC

Alcohol-containing tincture of cannabis as licensed medicine in UK until early 1970s

1989-93: CB1 + CB2

1992-95: AEA, 2-AG (endo cannabinoids)

Question 3

2 main constituents in cannabis - (3)

Answer 3

Psychoactive: THC (1964)
Non-psycho: CBD (1934) - doesn’t activated cannabinoid r’s

strains = % of each
Cannabis sativa: THC > CBD
Cannabis indica: CBD > THC

Question 4

3 different types of cannabinoids (3)

Answer 4

• Plant-derived cannabinoids (or phytocannabinoids) – naturally occurring, found in plants
• Synthetic cannabinoids – not found in nature
• Endogenous cannabinoids – naturally occurring, produced by our body

Question 5

CB1 and CB2 receptors (5)

Answer 5

GPCR: Gi/o coupled

2 separate genes of each - 44% homology

both activated by THC + endo cann.

diff pharm profile: range of agonist that bind + potency of agonist differ

Widespread expression of both receptors : CB1= high density in brain (psychoactive THC = high affinity of THC to CB1)

Question 6

CB1 receptor signalling (5)

Answer 6

• Gi and Go
• Signalling downstream of CB1 activation:
• Inhibition of adenylyl cyclase = red. cAMP
• Inhibition of voltage-gated Ca2+ channels
• Activation of inwardly rectifying K+ channels (both = cells less excited)
• Activation of MAP kinases
• Longer-term changes: gene expression etc

CB1: primarily in neurons
CB2: primarily in immune cells

Question 7

Presynaptic CB1 receptors MoA (3)

Answer 7

highly expressed in neurones

primarily pre-synaptic

1) THC binds to CB1 - Gi/Go sig. cascade
2) indirectly activates K+ channels or inhibit Ca2+ = inc. efflux = less +ve
3) = red. neurotransmitter release = INHIBITORY

Question 8

CB1 receptors in the central nervous system (4)

Answer 8

linked to reward pathway

CB1 inhibits glutamatergic transmission in nucleus accumbens

CB1 – often found in GABAergic interneurons

Reduced inhibitory input = increase firing rate of dopaminergic neurons in VTA and nucleus accumbens?

Question 9

effects:

Answer 9

red. memory, cognition, etc. based of its expression in the brain

Question 10

CB1 neurotransmission proof (3)

Answer 10

• Involve a range of neurotransmitters: glutamate, GABA, dopamine, acetylcholine, noradrenaline, CGRP
• Evidence from brain slices and animals/tissues with intact innervation
• Modulate functions in the brain, cardiovascular and respiratory system, gut motility etc

Question 11

Cannabis effects through CB2? (6)

Answer 11

THC is also a partial agonist at CB2

CB2: Primarily in immune cells (e.g. macrophages &lymphocytes)

• Anti-inflammatory
• Immunosuppressive
• Analgesic
• Peripheral vs central CB2
• Atherosclerosis
• Microglia; neuroinflammation; neurodegeneration

Question 12

Other pharmacologically active constituents in
cannabis (6)

Answer 12

CBDV, CBV, CBL, CBGV, CBCV, CBGM

Question 13

The other pharm active components in cannabis Pharm:

Answer 13

• CB1/CB2 receptors
• 5-HT1A receptors
• Transient Receptor Potential Vanilloid receptor
  (TRPV1)
• Ca2+ channels
• Peroxisome proliferator-activated receptor (PPAR)
• Enzymes for endocannabinoid degradation (FAAH)
• Others?

Question 14

Renewed medicinal
use?

Answer 14

THC: partial agonist for CB1 and CB2

synthetic CB r agonists are >100c potent than THC (found in (il)legal highs) - VERY DANGEROUS

Question 15

Nabilone (Casamet) uses (3)

Answer 15

Synthetic analogue of THC
* Marketed since 1983
* suppression of nausea and vomiting during chemotherapy
* (and anorexia in AIDS patients)

= munchies

Question 16

Sativex use in MS (3)

Answer 16

Standardized cannabis extract (GW Pharmaceuticals)

THC: CBD 1:1 - provides best results
- pain control in MS
- maybe motor control MS in long term
- spray under tongue
- doesn’t give high

Question 17

Cannabidiol - not psychoactive (4)

Answer 17

• Epilepsy use potentially - where other drugs don’t work - reduces seizures in some kids
• Cannabis oil on prescription?
• Cannabidiol oil?
• Epidiolex (cannabidiol) for seizures associated w/ Lennox-Gastaut syndrome or Dravet syndrome in USA

Question 18

Legislation and regulation (4)

Answer 18

Cannabis is a controlled drug under Misuse of Drugs Act 1971 (Misuse of Drugs Regulations Act 2001, Schedule 1)

• Since 2018, cannabis oil with <0.2% THC can be licensed and may be prescribed by a specialist hospital doctor.
• Cannabidiol products, if advertised for medical purposes, are regulated by Medicines and Healthcare products Regulatory Agency)
• Epidiolex (cannabidiol) for seizures associated with Lennox- Gastaut syndrome or Dravet syndrome

Question 19

Summary (4)

Answer 19

• THC activates brain CB1 to induce psychoactive effects
• Cannabis is more than THC. E.g. CBD is also pharmacologically active.
• Phytocannabinoids act on cannabinoid receptors and others
• CBR and phytocannabinoids can modulate a range of body functions and thus offer therapeutic potentials