The endocannabinoid system (ECS) is a complex network of molecules and receptors that plays a significant role in maintaining balance and regulating physiological processes within many organisms. A central question in biology is whether this intricate system, particularly its cannabinoid receptors, is universally present across all animal species.
Understanding Cannabinoid Receptors
Cannabinoid receptors, primarily CB1 and CB2, are specialized proteins that receive signaling molecules known as endocannabinoids. CB1 receptors are abundantly found in the brain and central nervous system, influencing functions such as mood, memory, and appetite. CB2 receptors are more commonly located in immune cells and peripheral tissues, where they modulate inflammation and immune responses.
The ECS, comprising these receptors, their endocannabinoid ligands like anandamide and 2-arachidonoylglycerol (2-AG), and the enzymes that synthesize and degrade them, helps maintain bodily equilibrium. The ECS is widespread, identified in various species from primitive organisms like the freshwater Hydra to vertebrates such as fish, birds, and mammals. Its prevalence highlights its importance in regulating fundamental biological processes.
Animals Identified Without Receptors
While the endocannabinoid system is found in most animal groups, certain species lack cannabinoid receptors. Insects are a notable example. Research has shown that common fruit flies (Drosophila melanogaster), western honey bees (Apis mellifera), water striders (Gerris marginatus), fall armyworm moths (Spodoptera frugiperda), and darkling beetles (Zophobas atratus) do not possess CB1 or CB2 receptors.
The absence of these receptors in insects is a significant finding in comparative neurobiology. Scientific investigations, including genetic sequencing, have not identified orthologs for human cannabinoid receptors in insect genomes. Laboratory experiments confirm this, as insect tissues do not show specific binding to synthetic cannabinoid ligands or activation of G-proteins associated with these receptors.
Beyond insects, some primitive invertebrates also lack these receptors. Sponges (Porifera) do not exhibit cannabinoid binding. Certain cnidarians, such as the sea anemone (Actinothoe albocincta), also lack specific cannabinoid receptors.
Physiological Differences and Adaptations
The absence of cannabinoid receptors in animals like insects raises questions about how they manage physiological functions typically regulated by the ECS. One hypothesis suggests insects lack these receptors because they produce minimal arachidonic acid, a precursor for endocannabinoid synthesis.
Despite lacking typical CB1 and CB2 receptors, some invertebrates still exhibit responses to cannabinoids, suggesting alternative regulatory mechanisms. For instance, the nematode C. elegans, while lacking traditional cannabinoid receptors, shows changes in appetite when exposed to cannabinoids. This indicates other molecular pathways or receptor types may mediate cannabinoid-like signaling in these organisms.
This suggests that while the canonical ECS is absent, these animals have evolved distinct biochemical pathways to regulate processes such as feeding, locomotion, and other behaviors. Studying these alternative systems provides insights into the diverse strategies life has developed to maintain internal balance.