Treatment with CBD

CBD against inflammation

Receptors involved in inflammation

The following endocannabinoid receptors are involved in inflammation:
  • CB1 cannabinoid receptor:
    • while CBD itself does not bind to the CB1 receptor, its metabolic forms do.
  • CB2 cannabinoid receptor:
    • One CBD metabolic form binds very strongly to CB2
  • A2A receptors:
    • They down-regulate over-reactive immune cells, and thus protect tissues from damage due to inflammation
    • CBD indirectly activates A2A receptors (by blocking those agents that block A2A)
    • In acute lung injury in mice model, 20 mg/kg CBD promoted the migration of neutrophils (white blood cells helping fight off tissue damage and infections) into the lungs
    • In animal models, CBD limited the harmful effect of intensified immune response by decreasing the invasion of white blood cells into the brain and thereby prevented irreversible tissue damage.

Watch this 8:05 minute video by PhysioPathoPharmaco: “The Inflammatory Response”

  • CB2/5HT1A heterodimerization:
    • CB2 can bind to the serotonin receptor 5HT1A. This is called heterodimerization – meaning two different things bind into one joint (pun absolutely intended) thing.
    • When CB2 is joined with 5HT1A, then CBD has very strong neuroprotective effect
  • TRPV1 receptor:
    • CBD is a very strong TRPV1 agonist (meaning: it promotes the function of the other)
    • In animal studies, 25 mg/kg CBD rapidly decreased liver inflammation through TRVP1 activation
  • GPR55 receptor:
    • CBD is a strong GPR55 receptor antagonist (meaning: it blocks the function of the other)

Signaling by CBD

CBD is involved in the communication between cells (also called: cellular signaling). There are molecules called messengers that trigger a range of cellular actions, such as cell division and proliferation, migration, survival and natural cell death (apoptosis).
  • Arachidonic acid – a messenger in cell communication:
    • Both CBD and THC considerably stimulate the release of arachidonic acid in human cells
    • CBD is about 5 times more potent than THC in this process
    • This is the rank order of six cannabinoids in arachidonic acid regulation: CBD >> CBCy > THC = CBCR = CBN >> CBG 
    • In this pathway, CBD is the most effective anti-inflammatory agent
  • Cyclooxygenase (COX) – and enzyme involved in communication
    • THC enhances COX-1 activity, while CBD had very little effect on it
    • CBD had a twice as potent stimulating effect on COX-2 as THC
    • The mechanism is not exactly known, but these animal models suggest that CBD acts mainly through COX-2

Watch this 1:18 minute animation by McGraw-Hill Animations about Ca++ channels

  • Cytokines – molecules involved in cell signaling
    • CBD reduces cytokines synthesis
    • 10 mg/kg CBD reduced gene expression and protein production of cytokines by 50%
    • CBD was both efficacious (had strong effect) and safe in these animal experiments
    • The effect was independent of the CB1 and CB2 receptors
  • Intracellular Ca++ levels
    • An increase of Ca++ ions is associated with increased presence of mastocytes (migrating white blood cells)
    • CBD increases the level of Ca++ in cells
    • This is the rank order of cannabinoids in Ca++ regulation: THCV > CBD > carvacrol > THCVA > CBGV > CBC > CBG > THC > CBGA > CBDV > CBN > CBDA = THCA

Gene expression and translation of genes into proteins

CBD effects the regulation of genes, even more than THC, because it:

  • blocks oxidative stress
  • suppresses genes that regulate inflammatory responses
  • inhibits the genes for autoimmune responses

Watch this 2:41 minute animation video about gene expression and translation

CBD against inflammation

  • Anti-arthritic effects
    • Pro-inflammatory cytokines (such as TNF-α and IL-1β) are present in high concentrations in arthritis
    • 25 mg/kg of CBD in mouse models reduced TNF-α production and concentration
  • Edema and hyperalgesia
    • CBD administration in animal models reduced levels of prostaglandins and free radicals
    • Edema (swelling) and hyperalgesia (increased sensitivity to pain probably due to tissue and nerve damage) benefited from CBD administration
  • Ear inflammation
    • Both CBD and THC and their metabolites reduced ear inflammation in animal models
  • Inflammatory bowel disease (IBD)
    • CBD reduced inflammation in animal models of IBD
    • This is surprising, because the mechanism was through DB1, and CBD does not well bind to CB1
    • CBD might affect CB1 indirectly
  • Colitis
    • In animal models, CBD was administered either orally (20 mg/kg), rectally (20 mg/kg), or intraperitoneally (into the body cavity, 10 mg/kg)
    • Oral CBD was not effective, but both rectal and intraperitoneal administration resulted in reduced extent of colitis
  • Type I diabetic cardiomyopathy
    • CBD alleviated myocardial dysfunction, cardiac fibrosis, oxidative/nitrosative stress, inflammation, cell death, and interrelated signaling pathways
    • Inflammation and oxidative stress are important in many human illnesses, so these results are promising for other conditions as well
  • Other conditions that are due to inflammation that may benefit from CBD:
    • Pneumococcal meningitis
    • Demyelinating pathologies
    • Hepatic ischemia-reperfusion injury (liver failure after transplantation)
    • Sepsis-related encephalitis
    • Autoimmune encephalomyelitis
    • Inflammatory lung diseases

Treatment with a combination of THC and CBD

Increasing evidence suggests that a combination of THC and CBD is much more effective than only one of these cannabinoids alone.  This is especially true for the diseases of the central nervous system.  The following conditions have benefited from such entourage effect:

  • Alzheimer’s disease
  • Huntington’s disease

Reference

Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg Med Chem. 2015 Apr 1;23(7):1377-85.

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