Alzheimer´s
CBD may have anti-inflammatory properties through activation of PPARγ. In addition, CBD stimulates neurogenesis and may therefore counteract neurodegeneration at multiple levels (Esposito et al., 2011).
In cultured astrocytes, Aβ1-42 reduced cell viability and PPARγ expression and increased cellular inflammation and anti-oxidant capacity. Specific CB1 stimulation (with WIN55,212-2, a synthetic analog of THC) prevented all these effects and increased cellular viability (Aguirre-Rueda et al., 2015).
Autism
In a rat model of autism (Valproic Acid model), GPR55, PPARα and PPARγ were reduced in several brain regions involved in higher cognitive functions (frontal cortex and hippocampus) (Kerr et al., 2013)
Functional Gastro-Intestinal Disorders
Apart from CB1 and CB2, there is evidence for the involvement of PPARγ and TRPV1 in Crohn’s Disease (de Fontgalland et al., 2014; Schicho and Storr, 2014).
In the LPS mouse model of colitis, 10 mg/kg i.p. CBD decreased reactive gliosis, mast cell and macrophage recruitment, TNFα expression and intestinal apoptosis. In ulcerative colitis patient rectal biopsies also reduced reactive gliosis, at least partially through PPARγ (De Filippis et al., 2011)
Hypoxic-ischemic encephalopaty
Activation of PPAR-γ receptor showed behavioral recovery and microglial supression in a model of stroke (Yu et al., 2015). CBD mechanisms would involve the modulation of excitotoxicity, oxidative stress and inflammation through CB2, 5HT1A, Adenosine A2A and PPAR-γ receptors (Castillo et al., 2010; Hind et al., 2015; Pazos et al., 2012, 2013)
cancer
Lung Cancer
In cancer cell lines (A549 and H460) and human metastatic lung cancer cells CBD induced apoptosis via COX-2 and PPARγ. In A549-xenografted mice CBD caused tumor regression (Ramer et al., 2013).
multiple sclerosis
Regarding treatment of MS with sativex, the effects of CBD were PPARγ-mediated whereas THC signaling was CB1/2 dependent (Feliú et al., 2015).
Parkinson´s
In human neuroblastoma cells, THC, but not CBD was found to be neuroprotective. Neuroprotection was mediated by PPARγ (Carroll et al., 2012)
Psoriasis
CBD and CBG do not function through classical CB receptors and none of the phytocannabinoids depended on TRPV1 for their effect (in contrast to endocannabinoid function below), but PPARγ and GPR55 may be involved in the effect of cannainoids in Psoriasis (Wilkinson and Williamson, 2007).
psychosis and schizophrenia
PPAR-γ receptor has also been related to schizophrenia (Costa et al., 2013; Liu et al., 2014).
References:
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Carroll, C.B., Zeissler, M.-L., Hanemann, C.O., and Zajicek, J.P. (2012). Δ9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease. Neuropathol. Appl. Neurobiol. 38, 535–547.
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Ramer, R., Heinemann, K., Merkord, J., Rohde, H., Salamon, A., Linnebacher, M., & Hinz, B. (2013). COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human Lung Cancer cells. Molecular cancer Therapeutics, 12(1), 69-82. https://doi.org/10.1158/1535-7163.MCT-12-0335
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Wilkinson, J.D., and Williamson, E.M. (2007). cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of Psoriasis. J. Dermatol. Sci. 45, 87–92.
Yu, S.-J., Reiner, D., Shen, H., Wu, K.-J., Liu, Q.-R., and Wang, Y. (2015). Time-Dependent Protection of CB2 Receptor Agonist in stroke. PloS One 10, e0132487.
