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Cannabinoid Clinic: Anandamide

Welcome to Cannabinoid Clinic, an education project powered by Higher Learning LV. This series provides cannabis and hemp industry professionals with easily digested cannabinoid profiles that ask little of your time—but provide plenty of science-based information.

There are two categories of cannabinoids: Phytocannabinoids and endocannabinoids. Phytocannabinoids are those produced by cannabis/marijuana/hemp, while endocannabinoids are made by the human body. This series covers both.

Anandamide molecular structure

What is Anandamide?

Anandamide (also known as N-arachidonoylethanolamine or AEA) was first isolated and identified in 1992 by two independent research teams: The same Israeli researcher who isolated and synthesized delta-9 tetrahydrocannabinol (THC) in the mid-1960s, Raphael Mechoulam, and NIMH researchers William Devane and Lumir Hanus. Anandamide is one of two major endogenous (internally produced) cannabinoids that includes 2-AG.

"Anandamide is one of two major endogenous (internally produced) cannabinoids that includes 2-AG."

This endocannabinoid functions in a similar manner to THC. In fact, delta-9 THC mimics anandamide. It is theorized that those who may suffer deficient levels of anandamide due to an imbalance in or problems with their endocannabinoid system may gain benefit from supplementation with THC because it provides many of the same benefits as the anandamide made by our own bodies. When researchers refer to THC as a mimetic phytomolecule, it is because of this mechanism.

Anandamide Fast Facts

  • Role: Regulation of the ECS

  • Biosynthetic pathway: n/a

  • Psychoactivity: Psychoactive (mood control)

  • Acidic precursor: n/a

  • Boiling point: n/a

  • Medical benefits: Reduced inflammation, neuroprotection, etc. Similar to THC.

Anandamide Medicinal Benefits

Anandamide is intimately involved in a long list of bodily functions involving the ECS, including sleep, appetite, sex drive, mood, cognitive processes, metabolic rate and energy level, and immune function—among others. Interestingly, anandamide is produced outside of the human body by a few plant species, including truffles (the winter black variety) and cacao.

According to a February 2015 study entitled "Truffles Contain Endocannabinoid Metabolic Enzymes and Anandamide" that was published in the journal Phytochemistry, "truffles contain the major metabolic enzymes of the ECS, [but] do not express the most relevant endocannabinoid-binding receptors [CB1 and CB2]."

"Anandamide is produced outside of the human body by a few plant species, including truffles (the winter black variety) and cacao."

However, students should avoid embracing the urban legend that chocolate contains "feel good chemicals" like anandamide and that its consumption may benefit those who suffer depression or other mood disorders. The levels of anandamide produced by cacao and found in dark chocolate are believed to be too low to affect a consumer's psychological state via an improvement of mood. Reported the 2015 book Chocolate and Health: Chemistry, Nutrition, and Therapy, "It is unlikely that chocolate's anandamide level could actively trigger a psychological response."

Also of note: Cacao produces two chemicals that are similar to anandamide that synergistically interact with the ECS to prevent the metabolic breakdown of anandamide. This results in increased bioavailability and greater potency than would be achieved by anandamide acting in isolation.

The potency amplification and mood improvement resulting from the synergistic interplay of these three molecules manufactured by cacao may result in true mood improvement—and help explain the craving that some humans experience for dark chocolate and the emergence of the urban legend surrounding chocolate's ability to positively affect mood.

A March 2015 study entitled "FAAH Genetic Variation Enhances Fronto-amygdala Function in Mouse and Human" that was published in the journal Nature Communications investigated the ability of anandamide to diminish or erase fear-based memories, making it of potential therapeutic value in the treatment of trauma-related conditions such as Post-traumatic Stress Disorder and social anxiety. "Our results demonstrated enhanced fear extinction in human and mouse carriers," reported the study, including "reduced levels of...anxiety."

"Our data suggest that...elevated [anandamide]...reduces stress, anxiety, and fear."

A February 2019 study entitled "Upregulation of Anandamide Hydrolysis in the Basolateral Complex of Amygdala Reduces Fear Memory Expression and Indices of Stress and Anxiety" that was published in The Journal of Neuroscience explored the ability of anandamide to reduce anxiety. "Our data suggest that...elevated [anandamide]...reduces stress, anxiety, and fear." The research uncovered "new insights on the mechanisms by which...endocannabinoid signaling regulates emotional behavior."

The study found a direct relationship between anandamide levels and emotional behavior and identified the areas of the brain in which this mechanism occurs. "Our results indicate that the ability of anandamide signaling to regulate emotional behavior is nonlinear and may involve actions at distinct neuronal populations, which could be influenced by the basal level of anandamide."

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