Did the endocannabinoid system evolve after insects?

Siberian sturgeon, bears, birds, humans and the rest of the vortices on this globe are born with cannabinoid receptors. And a system of fatty acid ligands – endocannabinoids – interact with them. If the system is removed in any of these animals, serious illness and complications ensue. Because of this, it becomes a debate as to why the small insects of this world managed to evolve without an endocannabinoid system.

John McPartland, a renowned cannabis researcher, authored studies analyzing the lack of an ECS in insects. He explained the fact that all mammalian neuroreceptors except cannabinoid receptors are found in insects. But before exclusively studying different invertebrates, McPartland studied the general evolution of cannabinoid receptors and their endogenous ligands.

The origin of fat

Life then consumes and assembles tiny molecular building blocks (ketoayl and isoprene groups) through a process known as biosynthesis. These blocks can convert into many different molecules, including terpenes, cannabinoids, and lipids.

For example, plants and insects can form long chains — with no double bonds — known as polyunsaturated fats (PUFAs). However, vertebrae cannot build these longer fat chains through enzymatic synthesis. Rather, we need to get PUFAs like omega-3 fatty acids from our diet.

All vertebrae can convert dietary omega-3 fatty acids and phospholipids into endocannabinoids, which are further metabolized in multiple pathways. And while truffles and plants can produce anandamide without cannabinoid receptors. Insects appear to produce even fewer endocannabinoids and are also completely devoid of cannabinoid receptors. In essence, the insect lipid system evolved on an entirely separate phylogenetic branch.

Evolution of endocannabinoids

Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down the endocannabinoid known as anandamide. In addition, FAAH connects all cellular organisms that contain a well-defined cell nucleus – including plants as well as fungi and animals.

Both fungi and animals contain genes that help signal the production of anandamide from other lipids. While enzymes required to break down the endocannabinoid 2-AG are exclusive to chordates and oddly reserved to some viruses.

CB1 receptors are found only in animals, including some invertebrates (invertebrates). CB2 receptors, on the other hand, were developed later and are exclusive to vertebrates. TRPV1 acquired an affinity for anandamide while GPR55 evolved within the mammalian endocannabididiome. This means that while insects are not far from a CB1 receptor/anandamide system, they instead rely on various receptors and fatty acids themselves.

Anandamide desensitizes the temperature and chemically triggered receptor known as TRPV1, but only in mammals. Plants use the canal as a means of repelling insects and other things they might eat. The affinity for anandamide at the channel may have evolved in mammals to tolerate a larger number of plant species.

Evolution when the earth was saturated with oxygen

Insects evolved during the Paleozoic, buzzing around before dinosaurs but after fish. One hypothesis is that insects evolved during this ECS-free period due to the high oxygen levels on land.

During the Paleozoic, fish swam in the ocean. At that time, however, the ocean was becoming severely depleted of oxygen. As a result, a mass extinction likely occurred that affected marine life. Eventually, true cannabinoid receptors evolved in fish, arachnids, and aquatic invertebrates. Land-dwelling insects instead avoided the system altogether.

Endocannabinoids for oxidative stress

Endocannabinoids are metabolized into an inflammatory compound called arachidonic acid, which is also broken down. The earth was rich in oxygen millions of years ago compared to today. But this very oxygen-rich environment can break down endocannabinoids into an uncoordinated team of inflammatory agents.

Insects managed to circumvent oxidative stress by avoiding the ECS entirely. But unlike whorls, they can produce polyunsaturated fatty acids. Another possibility is that marine life evolved cannabinoid receptors to survive oceanic apoxia during the Permian extinction period.

Sources

1. McPartland J, Di Marzo V, De Petrocellis L, Mercer A, Glass M. Cannabinoid receptors are absent in insects. J Comp Neurol. 2001;436(4):423-429. doi:10.1002/cne.1078
2. John M McPartland; Elizabeth Matthias; Vincenzo di Marcho; Michelle Glass (2006). Evolutionary origins of the endocannabinoid system. , 370 (none), 0-7 doi:10.1016/j.gene.2005.11.004
3. Stanley D, Kim Y. Why most insects have very low levels of C20 polyunsaturated fatty acids: The oxidative stress hypothesis. Arch Insect Biochem Physiol. 2020;103(1):e21622. doi:10.1002/arch.21622
4. Kim, Yonggyun & Stanley, David. (2021). Eicosanoid signaling in insect immunology: new genes and unsolved problems. genes 12.211.10.3390/Gene12020211.