Cannabidiol
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4 sources
🧬 Receptor activity
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| D(2) dopamine receptor | — | Ki 0.066 nM | CHEMBL | TargetD(2) dopamine receptor Action— AffinityKi 0.066 nM SourceCHEMBL |
| Cytochrome P450 1A1 | — | Ki 150 nM | CHEMBL | TargetCytochrome P450 1A1 Action— AffinityKi 150 nM SourceCHEMBL |
| Cannabinoid receptor 1 | — | Ki 151 nM | CHEMBL | TargetCannabinoid receptor 1 Action— AffinityKi 151 nM SourceCHEMBL |
| Cytochrome P450 3A5 | — | Ki 190 nM | CHEMBL | TargetCytochrome P450 3A5 Action— AffinityKi 190 nM SourceCHEMBL |
| Cannabinoid receptor 2 | — | Ki 230 nM | CHEMBL | TargetCannabinoid receptor 2 Action— AffinityKi 230 nM SourceCHEMBL |
| Equilibrative nucleoside transporter 1 | — | Ki 250 nM | CHEMBL | TargetEquilibrative nucleoside transporter 1 Action— AffinityKi 250 nM SourceCHEMBL |
| Cytochrome P450 2B6 | — | Ki 690 nM | CHEMBL | TargetCytochrome P450 2B6 Action— AffinityKi 690 nM SourceCHEMBL |
| Cytochrome P450 2C19 | — | Ki 790 nM | CHEMBL | TargetCytochrome P450 2C19 Action— AffinityKi 790 nM SourceCHEMBL |
| Cytochrome P450 3A4 | — | Ki 1000 nM | CHEMBL | TargetCytochrome P450 3A4 Action— AffinityKi 1000 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2C | — | Ki 1100 nM | CHEMBL | Target5-hydroxytryptamine receptor 2C Action— AffinityKi 1100 nM SourceCHEMBL |
| Mu-type opioid receptor | — | Ki 1300 nM | CHEMBL | TargetMu-type opioid receptor Action— AffinityKi 1300 nM SourceCHEMBL |
| Kappa-type opioid receptor | — | Ki 2300 nM | CHEMBL | TargetKappa-type opioid receptor Action— AffinityKi 2300 nM SourceCHEMBL |
| Cytochrome P450 2D6 | — | Ki 2420 nM | CHEMBL | TargetCytochrome P450 2D6 Action— AffinityKi 2420 nM SourceCHEMBL |
| Cytochrome P450 1A2 | — | Ki 2690 nM | CHEMBL | TargetCytochrome P450 1A2 Action— AffinityKi 2690 nM SourceCHEMBL |
| D(1A) dopamine receptor | — | Ki 2700 nM | CHEMBL | TargetD(1A) dopamine receptor Action— AffinityKi 2700 nM SourceCHEMBL |
| Histamine H3 receptor | — | Ki 3100 nM | CHEMBL | TargetHistamine H3 receptor Action— AffinityKi 3100 nM SourceCHEMBL |
| Alpha-2B adrenergic receptor | — | Ki 3200 nM | CHEMBL | TargetAlpha-2B adrenergic receptor Action— AffinityKi 3200 nM SourceCHEMBL |
| Sigma intracellular receptor 2 | — | Ki 3400 nM | CHEMBL | TargetSigma intracellular receptor 2 Action— AffinityKi 3400 nM SourceCHEMBL |
| Cytochrome P450 1B1 | — | Ki 3630 nM | CHEMBL | TargetCytochrome P450 1B1 Action— AffinityKi 3630 nM SourceCHEMBL |
| Alpha-2C adrenergic receptor | — | Ki 3700 nM | CHEMBL | TargetAlpha-2C adrenergic receptor Action— AffinityKi 3700 nM SourceCHEMBL |
| Cytochrome P450 2C9 | — | Ki 5600 nM | CHEMBL | TargetCytochrome P450 2C9 Action— AffinityKi 5600 nM SourceCHEMBL |
| Delta-type opioid receptor | — | Ki 6400 nM | CHEMBL | TargetDelta-type opioid receptor Action— AffinityKi 6400 nM SourceCHEMBL |
| Cytochrome P450 3A7 | — | Ki 12300 nM | CHEMBL | TargetCytochrome P450 3A7 Action— AffinityKi 12300 nM SourceCHEMBL |
| Cytochrome P450 2C11 | — | Ki 20700 nM | CHEMBL | TargetCytochrome P450 2C11 Action— AffinityKi 20700 nM SourceCHEMBL |
| L-lactate dehydrogenase A chain | — | Ki 24000 nM | CHEMBL | TargetL-lactate dehydrogenase A chain Action— AffinityKi 24000 nM SourceCHEMBL |
| Cytochrome P450 2A6 | — | Ki 55000 nM | CHEMBL | TargetCytochrome P450 2A6 Action— AffinityKi 55000 nM SourceCHEMBL |
| Steroid 17-alpha-hydroxylase/17,20 lyase | — | Ki 124000 nM | CHEMBL | TargetSteroid 17-alpha-hydroxylase/17,20 lyase Action— AffinityKi 124000 nM SourceCHEMBL |
Mechanism of action
The exact mechanism of action of CBD and THC is not currently fully understood. However, it is known that CBD acts on cannabinoid (CB) receptors of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems, including the brain. The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood. More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect CBD-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect CBD-induced anti-inflammatory processes. CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric regulation of a receptor is achieved through the modulation of the activity of a receptor on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects.
Pharmacodynamics
Although the exact mechanism and magnitude of effects of THC and CBD are not fully understood, CBD has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity. This wide variety of effects is likely due to it's complex pharmacological mechanisms. In addition to binding to CB1 and CB2 receptors of the endocannabinoid system, there is evidence that CBD activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH).
Pharmacokinetics
Half-life
The CBD component of sublingual Sativex was found to have a half life (t1/2) of 1.44hr, while buccal Sativex was found to have a half life (t1/2) of 1.81hr.
Absorption
Following a single buccal administration, maximum plasma concentrations of both CBD and THC typically occur within two to four hours. When administered buccally, blood levels of THC and other cannabinoids are lower compared with inhalation of smoked cannabis. The resultant concentrations in the blood are lower than those obtained by inhaling the same dose because absorption is slower, redistribution into fatty tissues is rapid and additionally some of the THC undergoes hepatic first pass metabolism to 11-OH-THC, a psycho-active metabolite. The CBD component of sublingual Sativex was found to have a Tmax of 1.63hr and a Cmax of 2.50ng/mL, while buccal Sativex was found to have a Tmax of 2.80hr and a Cmax of 3.02ng/mL.
Elimination from plasma is bi-exponential with an initial half-life of one to two hours. The terminal elimination half-lives are of the order of 24 to 36 hours or longer. Sativex is excreted in the urine and faeces.
Cannabinoids are distributed throughout the body; they are highly lipid soluble and accumulate in fatty tissue. The release of cannabinoids from fatty tissue is responsible for the prolonged terminal elimination half-life.
Metabolism
THC and CBD are metabolized in the liver by a number of cytochrome P450 isoenzymes, including CYP2C9, CYP2C19, CYP2D6 and CYP3A4. They may be stored for as long as four weeks in the fatty tissues from which they are slowly released at sub-therapeutic levels back into the blood stream and metabolized via the renal and biliary systems. The main primary metabolite of CBD is 7-hydroxy-cannabidiol.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.