Cannabinoids (CBs) have recently been approved to exert broad anti-inflammatory activities in experimental models of multiple sclerosis (MS). It has been demonstrated that these compounds could also have effects on neurodegeneration, demyelination, and autoimmune processes occurring in the pathology of MS. However, the clinical use of CBs is limited by their psychoactive effects. Among cannabinoid compounds, cannabidiol (CBD) and palmitoylethanolamide (PEA) have no psychotropic activities. We induced experimental autoimmune encephalomyelitis (EAE), a model of MS, by injecting myelin oligodendrocyte glycoprotein (MOG) to C57BL/6 mice. We assessed the effects of CBD, PEA, and co-administration of CBD and PEA on neurobehavioral scores, immune cell infiltration, demyelination, axonal injury, and the expression of inflammatory cytokines by using histochemistry methods and real-time RT-PCR. Treatment with either CBD (5mg/kg) or PEA (5mg/kg) during disease onset reduced the severity of the neurobehavioral scores of EAE. This effect of CBD and PEA was accompanied by diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression while concurrent administration of CBD (5mg/kg) and PEA (5mg/kg) was not as effective as treatment with either drug per se. These results suggest that, CBD and PEA, non-psychoactive CBs, attenuate neurobehavioral deficits, histological damage, and inflammatory cytokine expression in MOG-immunized animals. However, there is an antagonistic interaction between CBD and PEA in protection against MOG-induced disease.
Keywords: EAE; cannabidiol; cannabinoid; multiple sclerosis; palmitoylethanolamide.
Levagen+ PEA has been studied to provided targeted benefits for joint health, sports recovery, inflammation, relaxation and sleep.
20 David Briskey, Georgia Roche, Amanda Rao. The Effect of a Dispersible Palmitoylethanolamide (Levagen+) Compared to a Placebo for Reducing Joint Pain in an Adult Population – A Randomised, Double-Blind Study. International Journal of Nutrition and Food Sciences. Vol. 10, No. 1, 2021, pp. 9-13. doi: 10.11648/j.ijnfs.20211001.12
CBD and the ECS
PEA resembles CBD in that both offer anti-inflammatory and neuro-protective properties. However, CBD is not produced by the human body unlike PEA, which is endogenously produced as a direct response and repair mechanism to inflammation. PEA counteracts endotoxin-induced inflammation in cells in the same cell lineage as CBD.
1 Hartsel JA, Eades J, Hickory B, Makriyannis A.Cannabis sativa and Hemp. Nutraceuticals: Efficacy, Safety and Toxicity, pp. 735–754, 2016.
The PEA Difference
15 Hesselink, J.M.K. (2012). New targets in pain, nonneuronal cells, and the role of palmitoylethanolamide. The Open Pain Journal, 5, 12-23.
High levels of myoglobin correlate with increased muscle damage, so PEA could potentially lead to decreased muscle damage, increasing sports performance.
PEA provides many of the same benefits as CBD and removes the concern around supplements containing trace levels of THC.
The main difference is where it is sourced from. CBD, a plant cannabinoid, is sourced from hemp plants that are bred to only contain trace amounts of THC.
Endocannabinoids help to regulate mood, emotion, pleasure perception and much more. PEA may play a potential role as an antidepressant and help to reduce anxiety and stress through its ability to enhance the levels and actions of anandamide – the ‘bliss’ molecule. 10 , 11 Further, those with higher levels of PEA in their blood showed better tolerance of stress. 12
Exercise performance and recovery
Cannabinoids are a collection of chemical compounds that interact with the receptors found within the body’s own endocannabinoid system. The body naturally produces its own cannabinoids, known as endocannabinoids (‘endo’ meaning within the body) which can interact both directly and indirectly with these receptors. Cannabinoid receptors are found in tissues all over the body. The main receptors are CB1, which is found in the brain and nerves of the spinal cord, and CB2, which is found in the digestive and immune system.
Through the mechanisms described above, PEA has been shown to reduce chronic and neuropathic pain and decrease inflammation across a number of different conditions. Data pooled from 10 studies showed that PEA was associated with significantly greater pain reduction compared to control conditions. 5 , 6
While currently there is limited data around the efficacy of PEA in exercise performance and recovery, the preliminary findings of a recent trial are showing promising results.
Enhancing PEA’s absorption
PEA operates through multiple pathways and mechanisms within the body to provide its beneficial analgesic and anti-inflammatory effects. It has the ability to work both directly and indirectly within the central and peripheral nervous system.
PEA is a brilliant supplement option for professional athletes or for those who wish to completely avoid THC altogether.