Informed High - Becoming Informed about Cannabis

What Are Anandamide and 2-AG?

Disclaimer: My Rationale for Understanding the Science


Not everyone loves learning the scientific specifics, but lucky for you I do. And what I like to do with this information is gather it up, trim the fat, translate the jargon, and present it to you. Everything I explain has a point. I want you to experience an Informed High. I want to help create informed consumers making informed decisions.



What Are Anadamide and 2-AG?


1992, the year Clinton was elected, NAFTA was signed, Reservoir Dogs and Aladdin released. It was also the year that Raphael Mechoulam and his team discovered Anandamide. Anandamide is also known by the long name, N-arachidonoylethanolamine, and the much shorter AEA.


I emphasized that this discovery in the year 1992 to highlight just how recent this occurred. During the years around this date, scientists had just discovered Cannabinoid Receptors and the Endocannabinoids System in the human body. The second Endocannabinoid that we will also discuss is 2-Arachidonoylglycerol (2-AG), a compound discovered around the same time.



Cannabinoid Receptors


Refer to my full post for further details (Cannabinoid Receptors). Briefly, CB1 Receptors are found primarily in the central nervous system (but also in the peripheral nervous system). They are involved in tone-setting and activity regulation between various areas of the nervous system. CB2 Receptors are found throughout the peripheral nervous system, the gastrointestinal system, and the central nervous system (less densely than CB1 Receptors). CB2 Receptors are involved in immune system regulation and neuronal signal transmission.





Both of the following compounds are Endocannabinoids, which means the body naturally creates than in association with Cannabinoid Receptors and the Endocannabinoid System. This cannabinoid neuromodulatory system was discovered through research into AEA and then 2-AG. To repeat, AEA and 2-AG are produced by our bodies; these exact substances are not found in the Cannabis plant or any Cannabis product.


Endocannabinoids as a broad category, play a role in appetite, movement, learning, the perception of pain, immune responses, inflammation, neuroprotection, mood, insulin sensitivity, fat and energy metabolism, and other vital processes. A very long list of important functions for this critical system in the evolution of humans.




What is Anandamide (AEA)?


Anandamide, also known as AEA or N-arachidonoylethanolamine, was the first cannabinoid-like neurotransmitter discovered by Mechoulam and his colleagues. The word Anada is Sanskrit for bliss, joy, or delight. AEA was the first brain metabolite (a substance made within our central nervous system) shown to act upon central CB1 Cannabinoid Receptors


AEA was reported as potently and selectively inhibition the growth of human breast cancer cells, in vitro, in the lab (in vitro = in glass). De Petrocellis and colleagues reported this finding in 1998. These effects were not a result of poisoning (toxicity) or forced death of cells (apoptosis), instead due to a reduction in the growth and replication stage of the associated cells.



Anandamide Chemical Structure



The Role of AEA


AEA has been shown to impair working memory in rats (working memory involve current memory processes, like trying to remember a new phone number, not remember an old song, for example). It is thought to be involved in the regulation of eating and sleeping, relief of pain, and the neural generation of motivation and pleasure.


  • In the Cardiovascular system, AEA induces hypotension and bradycardia (low blood pressure and slow heart rate)
  • In the eye, AEA lowers ocular blood pressure (ocular = eyeball)
  • In the Gastrointestinal and Urinary tracts, AEA inhibits smooth muscle contraction (nonvoluntary muscles that line these tracts and are involved in their functioning)
  • In the human body, AEA may impact the action of steroid hormones (growth and repair hormones)
  • In the brain, AEA affects the HPA (hypo-thalamo-pituitary-adrenal) axis through CB1 regulatory action. The HPA axis is the stress response system including the central nervous system (brain and spinal cord) and endocrine system (glands and hormones)



What is 2-Arachidonoylglycerol (2-AG)?


2-AG was discovered earlier, but was first described around 1994-1995. 2-AG acts upon CB1 and CB2 Receptors (immune functions). The reported effects on CB1 receptors is minimal, with the CB2 receptors appearing to be the primary target.



2-AG Chemical Structure



AEA and 2-AG and the Immune System


Both of these compounts have an affect on lymphocyte and macrophage function. Very briefly, lymphocytes and macrophages are involved with immune responses, and the actual work of finding and destroying pathogens (like a police force going around killing potential criminals inside our bodies).



AEA and 2-AG, the Unusual Neuromodulators


These compounds are unusual neuromodulators in the human body (Neuromodulator are messangers within the nervous system and regulate functioning). This is because they work via retrograde signaling. While most neurotransmitters are created in a presynaptic cell (sending cell) and send across the synaptic gap to the postsynaptic cell (receiving cell).


These endocannabinoids, however, are made on demand in the postsynaptic neuron (receiving cell) and sent back across the synapse to tell the presynaptic cell (sending cell) to tone it down or speed it up



AEA and 2-AG, the Great Equalizers


We can not understand how AEA and 2-AG are involved in maintaining and restoring balance (homeostasis) through their regulatory role in the human body. They inhibit nerve cells that firing too intensely and disinhibit nerve cells that are firing too sluggishly. Sort of like a soundboard equalizer, which reduce the highs and the lows to create a more even and harmonious sound.





AEA and 2-AG and the Master Tone Setter


The Endocannabinoid system is considered to be the Master-tone setter. This tone-setting function is impacted by the natural presence and functions of AEA and 2-AG. We know that the functions of THC and CBD produce similar (if not identical) effects in human cells.



So What does this have to do with Cannabis?


Cannabimimetic was a term used to describe AEA and 2-AG. This is important because of the natural Phytocannabinoids produced by the Cannabis plant mimic effects of the naturally occurring AEA and 2-AG. In other words, the Cannabis compounds THC and CBD produce similar or identical effects as AEA and 2-AG, respectively.


AEA is mimicked in the human body by the Phytocannabinoid  THC. This means that THC impacts the same cells and same processes as the naturally occurring AEA. The effects of 2-AG are duplicated by CBD.




DISCLAIMER: The content on this website is not intended to substitute for professional medical advice, diagnosis, or treatment. Always seek professional medical assistance with any questions you may have regarding your health. Never disregard medical advice or postpone seeking medical help due to any content on this website.




De Petrocellis, L., Melck, D., Palmisano, A., Bisogno, T., Laezza, C., Bifulco, M., & Di Marzo, V. (1998). The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc. Natl. Acad. Sci., 95, p. 8375-8380.


Cervantes, J. (2015). The Cannabis Encyclopedia: The definitive guide to cultivation & consumption of medical Marijuana. Van Patten Publishing, USA.


Clarke, R. C., & Merlin, M. D. (2013). Cannabis: Evolution and ethnobotany. University of California Press, California, USA. ISBN-13: 978-0520292482.


Madras, B. K. (2015). Update of cannabis and its medical use. Retrieved from: [PDF].


Arnold Warkentin

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