Siberian sturgeons, bears, birds, humans, and the rest of the vertebrates on this globe are born with cannabinoid receptors. And a system of fatty acid ligands— endocannabinoids — interact with them. If the system is removed from any of these animals, severe diseases and complications will occur. For this reason, it becomes a debate as to why the little insects of this world managed to evolve without an endocannabinoid system. 

John McPartland, a renowned cannabis researcher, authored studies analyzing the absence of an ECS in insects. He outlined the fact that every mammalian neuroreceptor is found within insects, except for cannabinoid receptors. But before studying different invertebrate exclusively, McPartland studied the general evolution of cannabinoid receptors and their endogenous ligands.

The origin of fat

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

As an example, plants and insects can build long chains — absent of double bonds — known as polyunsaturated fats (PUFAs). Vertebrates, however, cannot build these longer chains of fat through enzymatic synthesis. Rather, we need to obtain PUFAs, such as omega-3s, from our diet.

All vertebrates can metabolize dietary omega-3 and phospholipids into endocannabinoids, which will continue to metabolize down several paths. And while truffles and plants can produce anandamide without cannabinoid receptors. Insects appear to produce even fewer endocannabinoids and are also void of cannabinoid receptors, entirely. Essentially, the lipid system of insects evolved on an entirely separate phylogenetic branch.

Endocannabinoid evolution

Fatty acid amide hydrolase (FAAH) is an enzyme that chews up the endocannabinoid known as anandamide. Moreover, FAAH ties together all cellular organisms that contain a clearly defined nucleus — including plants as well as mushrooms and animals.

Mushrooms as well as animals contain genes that help signal the production of anandamide from other lipids. Whereas enzymes required to degrade the endocannabinoid, 2-AG, are exclusive to chordates and oddly some viruses.

CB1 receptors can only be found in animals, including some spineless creatures (invertebrate). CB2 receptors, on the hand, developed later and are exclusive to vertebrates. TRPV1 gained an affinty for anandamide while GPR55 developed within the endocannabidiome of mammals. This means that while insects are not far away from a CB1 receptor/anandamide system — they instead self-rely on different receptors and fatty acids.

Anandamide desensitizes the temperature and chemical-triggered receptor known as TRPV1, but only in mammals. Plants use the channel as a means to repel insects and other anything else that might eat them. Affinity for anandamide at the channel might have developed in mammals as a means to tolerate a greater number of plant species.

Evolving when Earth was saturated in oxygen

Insects evolved during the Paleozoic era and have been buzzing around before dinosaurs but after fish. One hypothesis states that insects evolved without an ECS due to high oxygen levels on land during the period.

Fish were swimming in the ocean during the Paleozoic. At this time, though, the ocean became heavily depleted in oxygen. As a result, a mass extinction event likely occurred that affected marine life. At some point, true cannabinoid receptors developed in fish, arachnids, and water-dwelling invertebrates. Land-dwelling insects outright avoided the system, instead.

Endocannabinoids for oxidative stress

Endocannabinoids metabolize into an inflammatory agent known as arachidonic acid, which too breaks down. The Earth was rich in oxygen millions of years ago, relative to today. But that highly oxygen-rich environment can break down endocannabinoids into an uncoordinated team of inflammatory agents.

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


  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; Isabel Matias; Vincenzo Di Marzo; Michelle Glass (2006). Evolutionary origins of the endocannabinoid system. , 370(none), 0–74. doi:10.1016/j.gene.2005.11.004 
  3. Stanley D, Kim Y. Why most insects have very low proportions 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 Unresolved Issues. Genes. 12. 211. 10.3390/genes12020211.