“The endocannabinoid system, or ECS, is a group of neurotransmitters made by the body and cell receptor sites,” explains Ingegno. “The neurotransmitters look similar to exogenous cannabinoids (the ones we get from cannabis). The cell receptor sites activate when we ingest cannabis, or our body produces endocannabinoids.”
The ECS is one of the most influential systems in the human body, contributing to homeostasis or balance. The ECS influences functions as diverse as stress, appetite, energy, reproduction, pain, and sleep.
The discovery of the endocannabinoid system was surprisingly recent, dating back to the early 1990s. Again, the discovery of the ECS components was a joint effort, in which Mechoulam was instrumental. “There was no conception [of endocannabinoids],” explains Mechoulam. “We did some work and found that most probably, the plant cannabinoids act through a specific mechanism.” In the mid-1980s, Allyn Howlett discovered the CB1 receptor, and in 1993, the CB2 receptor was discovered.
Gradually, a picture of the endocannabinoid system as a network containing cannabinoid receptors, endocannabinoids, and enzymes began to form.
“Receptors don’t exist because there’s a plant out there; receptors exist because we, through compounds made in our body, activate them,” stresses Mechoulam. In 1992, after Mechoulam and his team had been looking for endogenous compounds that activate cannabinoid receptors, they identified anandamide. The endocannabinoid is responsible for engendering feelings of pleasure and bliss, leading to it being dubbed “the bliss molecule.”
The trajectory of CBD looks set to continue into the future, with diverse research on the horizon. Mechoulam is currently focusing his attention on cannabidiolic acid (CBDA), the precursor that converts to CBD over time or when exposed to heat.
“It turns out that cannabidiol acid in the studies we have undertaken so far is more potent than cannabidiol itself,” Mechoulam stated in a speech in 2019. “The chances are that slowly and to a certain extent, cannabidiol acid will prove to be parallel to cannabidiol oil in its activity because in many aspects, it’s much more active.”
Mechoulam sees cannabidiol acid slowly replacing CBD as the natural cannabidiol of importance. “We have a publication which shows that it is more potent for treating pain and depression and we have seen a few other examples,” he states. “These findings will be published over the next few years or maybe even over the next few months.”