MECHANISM OF ACTION AND PHYSIOLOGICAL FUNCTION OF CANNABIDIOL (CBD)
The many mechanisms of action of CBD are not yet fully understood. It appears to act via several receptors and not just those of the endocannabinoid system.
1. CBD increases endocannabinoid levels: FAAH inhibitor
CBD is an inhibitor of endocannabinoid reuptake and hydrolysis. Indeed, it inhibits the FAAH enzyme which degrades anandamide, which results in an increase in the concentration of anandamide in the brain. (40)
2. CBD is a negative allosteric modulator of CB1
Unlike THC, cannabidiol has a low affinity for cannabinoid receptors . It binds to these receptors only at micromolar concentrations, acting as a low-potency agonist, inverse agonist, antagonist, or even as an allosteric modulator of the CB1 receptor. Indeed, certain effects of CBD are antagonized by inverse agonists of CB1 receptors, which suggests that this molecule can exert indirect agonism on CB1 receptors. (41)
CBD has been shown to act as a non-competitive negative allosteric modulator of the CB1 receptor, resulting in inhibition of anandamide binding to its receptors . (42)
2.1 CBD is an inverse agonist of the CB2 receptor (43)
According to some studies, CBD acts as an inverse agonist of CB2 receptors. This could partly explain its anti-inflammatory effect because such an action on CB2 receptors is responsible for inhibiting the migration of immune cells and reducing signs of inflammation.
3. CBD is an antioxidant (44)
CBD scavenges free radicals and prevents cell damage. Indeed, cannabidiol has been shown to prevent oxidative damage induced by hydrogen peroxide as well as ascorbic acid (vitamin C) or vitamin E (tocopherol). Regarding glutamate neurotoxicity, cannabidiol was more protective than these two antioxidant vitamins. CBD is therefore a powerful neuroprotective antioxidant.
4. CBD is an agonist of the vanilloid TRPV1 pain receptors (45)
The TRPV1 receptor impacts pain perception, inflammation and body temperature. Anandamide also stimulates this TRPV1 receptor. CBD directly activates vanilloid receptors, reducing the intensity of pain signals sent to the brain.
6. CBD Increases GABA Activity (46)
GABA is the main inhibitory neurotransmitter in the nervous system. CBD is an allosteric modulator of GABA (facilitates the binding of GABA to receptors), but it is also said to have an action at the level of GABAA receptors.
7. CBD is a 5-HT1A receptor agonist (47)
By directly stimulating serotonergic 5-HT1A receptors, CBD has an action on anxiety, appetite, sleep, pain perception, mood, nausea and vomiting, sexual behavior, and others. Again.
8. CBD inhibits 5-HT3A receptors (48)
Allosteric inhibition of 5-HT3A receptors contributes to its physiological roles in the modulation of nociception and vomiting mainly.
9. CBD is a GPR55 receptor antagonist (43)
There is evidence that the GPR55 receptor plays an important role in the regulation of bone metabolism, in pain control, as well as in the proliferation of tumor cells. By blocking this GRP55 receptor, CBD can help prevent osteoporosis and limit the proliferation of cancer cells.
10. CBD is a PPAR-gamma receptor agonist (49,50)
CBD may have an antiproliferative effect, which can limit tumor growth in lung cancer for example. Activation of this receptor may also help break down beta-amyloid plaques associated with Alzheimer's disease. This receptor also regulates metabolic functions such as lipid absorption or insulin sensitivity.
11. CBD is a PPAR-gamma receptor agonist (49,50)
CBD may have an antiproliferative effect, which can limit tumor growth in lung cancer for example. Activation of this receptor may also help break down beta-amyloid plaques associated with Alzheimer's disease. This receptor also regulates metabolic functions such as lipid absorption or insulin sensitivity.
12. CBD is a partial agonist of dopamine D2 receptors (51)
A study published in 2016 demonstrated that cannabidiol, like all current antipsychotics, binds to dopamine D2 receptors. It exerts a partial antagonistic action.
13. CBD is an inverse agonist of the GPR3 and GPR6 receptors (52)
Recent studies have shown that cannabidiol acts as an inverse agonist of the GPR3 and GPR6 receptors, the latter being potential therapeutic targets for Alzheimer's disease and Parkinson's disease, respectively.
Cannabidiol has therefore demonstrated effects via these different actions:
- Anti-inflammatories, analgesics (53)
- Anxiolytics, sedatives
- Anticonvulsants
- Antiemetics
- Antiproliferative, anti-apoptotic, neuroprotective
Quotes:
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