- Targeting the mechanisms underlying chronic neuroinflammation by stimulating cannabinoid receptors may be a promising therapeutic strategy.
- Palmitoylethanolamide (PEA) is a dietary cannabinoid that can reduce the impact of many neuropathological mechanisms.
- PEA’s actions are beneficial because it activates two important receptors that control inflammation and the sensation of pain.
A large variety of brain disorders associated with aging are characterized by a progressive neuronal loss, including Alzheimer’s disease and Parkinson’s disease, among others. During the past few decades, research from my laboratory on the pathological mechanism underlying these diseases has documented the critical role of long-term brain inflammation.
Under normal circumstances, an inflammatory response in the brain is a protective process that promotes neuronal regeneration. However, when sustained over many decades, inflammation predisposes specific brain regions to neurodegeneration. The brain cells that are primarily involved in this destructive inflammatory process are the microglia.
The inflammatory response may be activated through different mechanisms, such as specific mutant genes, obesity, diabetes, environmental toxins, and pro-inflammogens due to oxidative stress. Currently, there are no therapeutic agents that can effectively counteract the damaging actions of the activated microglia or even slow down the progression of these disorders.
My research has shown that targeting the mechanisms underlying chronic neuroinflammation by stimulating cannabinoid receptors may be a promising strategy. Recent studies have demonstrated that two endogenous fatty acids that are found in the brain, anandamide and palmitoylethanolamide (PEA), are also cannabinoids that can reduce the impact of many pathological mechanisms known to be involved in the neurodegenerative process. Anandamide is found naturally in cocoa powder and black truffles, while PEA is found in egg yolks, soybeans, and peanut oil. Both compounds can mimic the diverse actions of THC, the active ingredient found in cannabis products. Anandamide binds to both cannabinoid receptors and produces euphoria. In contrast, PEA does not bind well to cannabinoid receptors and has no apparent psychoactive effects.
PEA’s actions are beneficial because it activates two important receptors that control inflammation and the sensation of pain, PPAR-α and TRPV1. This dual action underlies PEA’s anti-inflammatory, antioxidant, analgesic, and neuroprotective effects. PEA is safe to consume; some countries have allowed products containing PEA to be sold as a food supplement for humans. The recommended dose is typically 600 to 1,200 milligrams per day. A recent analysis of the literature on PEA examined the clinical studies to defend this dosing regimen.
Human and animal studies have provided solid neurobiological evidence for the therapeutic benefits of PEA, particularly related to changes seen in the brains of patients with Alzheimer’s disease. PEA supplementation reduced brain inflammation, reduced the expression of amyloid protein, reduced the negative effects of tau protein in the hippocampus, and reduced glial activation. Taken together, these effects were associated with improved neuronal survival and widespread neuroprotection. PEA’s benefits were not limited to the brain; it also reduced the effects of inflammation in the gut and reduced the level of oxidative stress throughout the body.
Consistent with this view of the beneficial role of PEA, it has been shown that brain PEA levels were reduced in patients with vascular dementia and Alzheimer’s disease. An analysis of the previous studies on PEA also suggests that it has its maximal potential during the early stages of neurodegenerative diseases, stroke, and Parkinson’s disease. The evidence thus far collected in both animal and human studies is consistent with the recommendation that dietary PEA supplementation be included as a valuable adjunctive therapy to current approaches for the prevention and treatment of age-related neurogenerative diseases.
Wenk GL, Your Brain on Food: How Chemicals Control Your Thoughts and Feelings, 3rd Ed. Oxford University Press.
Colizzi M, et al (2022) Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence. Frontiers in Psychiatry, Vol 13, https://doi.org/10.3389/fpsyt.2022.1038122