Anandamide: The Bliss Molecule

The endocannabinoid system (ECS) is a lipid signaling network that maintains homeostasis in the body and plays an essential role in many cognitive and physiological processes, including mood, inflammation, pain, appetite, and pre-and postnatal development.  The ECS is comprised of endogenous cannabinoid ligands (endocannabinoids), including anandamide (AEA) and 2-arachidonoylglycerol (2-AG), CB1/2 receptors (and others), transporters, and various biosynthetic and metabolizing enzymes. AEA and 2-AG participate in the body's ECS by binding to cannabinoid receptors, CB1 and CB2, the same receptors that THC acts on.

Because of its involvement in the mechanisms of reward and feelings of euphoria, as well as its potential role in the treatment of several health conditions, AEA has been the most studied among the endocannabinoids to date. “Anandamide” comes from the Sanskrit word “ananda” (internal bliss), which emphasizes the interesting role of AEA as an endogenous cannabis-like substance self-delivered by the brain.

HOW DOES DIET AFFECT THE ECS?

Diet can play a significant role in modulating the ECS. For example, certain foods contain AEA.  Other foods can bolster the ECS by stimulating CB1 and CB2 receptors, enhancing endocannabinoids’ and cannabinoids’ overall effects.  In other cases, foods can influence the production of enzymes involved in the metabolism of endocannabinoids and cannabinoids.  Moreover, stress can have detrimental effects on the ECS.  For example, rodents exposed to chronic stress exhibit increased levels of fatty acid amide hydrolase (FAAH), the enzyme that degrades AEA, resulting in a significant decrease in AEA levels in the brain and associated brain dysfunction (PMID: 35276827).

SUPERFOODS

Theobroma cacao, literally translated as “cacao, food of the gods,” is a superfood that possesses many therapeutic properties. It contains several “happy brain” chemicals such as theobromine, phenylethylamine, tryptophan, and small amounts of anandamide.  While the levels of anandamide are not considered physiologically significant, cacao indirectly engages the ECS by deactivating FAAH resulting in higher anandamide levels in the brain.  Cacao also enhances the effects of THC by inhibiting its metabolism through this same mechanism.

The highly sought-after delicacy, black truffles, also contain AEA.  Although truffles don’t contain endocannabinoid receptors, it’s theorized that evolution might play a role in the presence of AEA. Animals do have endocannabinoid receptors, and AEA could provide a positive reward to the animals that eat the truffles, encouraging them to seek out more, and spreading the spores.

There has been growing scientific interest to identify suitable FAAH inhibitors to enhance AEA levels in the brain to treat several health conditions such as depression, chronic pain and neurological diseases.  Animal studies show that the administration of FAAH inhibitors increase endogenous levels of AEA and extend the duration of AEA’s biological effect, making it an exciting potential therapeutic strategy.

Several foods have been identified that exhibit FAAH-inhibiting activity.  For example, piperine, a major component in the superfood, black pepper, is one such food (PMID: 34364309).  Piperine was also shown to exert antidepressant-like activity and exert a cognition-enhancing effect by regulating the metabolism of other neurotransmitters in animal studies.

Moreover, the polyphenol, kaempferol, has been identified as a potent FAAH inhibitor (PMID: 35276827).  Kaempferol is present in a variety of plant foods including beans, broccoli cabbage, grapes, tomatoes and citrus.  Consumption of these kaempferol-rich foods can increase AEA levels and also enhance the effects of THC.

Black pepper and other superfoods such as cinnamon, lavender, clove and rosemary contain beta-caryophyllene (βCP), a terpene that has received incredible attention due to its ability to bind to the Δ9-THC binding site of CB2, the cannabinoid receptor found predominantly in the immune system. βCP is also a major terpene found in various cannabis cultivars.  Activation of the CB2 receptor is considered a potential therapeutic strategy for the treatment of inflammation, pain, and mood disorders (PMID: 18574142), — benefits also associated with the above-mentioned spices.  Animal studies also support the antidepressant effects of βCP (PMID: 31862467, PMID: 30864870).

Extra-virgin olive oil (EVOO) is naturally rich in polyphenolic compounds, which are a family of molecules known for their antioxidant, anti-inflammatory, neuroprotective and anti-obesity properties.  Studies by Vago et al. found that olive oil upregulates CB1 gene expression (PMID: 35276827), highlighting the idea that EVOO enhances the uptake of THC, making it a desirable base for the formulation of cannabis tinctures.