Synthetic cannabinoids and their impact on neurodevelopmental processes

Cannabinoids comprise a broad group of psychoactive substances that activate endogenous cannabinoid (EC) receptors (ie, CB₁R and CB₂R), altering neurotransmitter release in the brain. The importance of their regulatory role in different biological processes has prompted the development of synthetic cannabinoids (SCs), substantially more potent than tetrahydrocannabinol (THC, the main psychoactive substance of cannabis). Although SCs were primarily designed given their therapeutic applications, their recreational use has become a major public health concern due to several reports of severe intoxications and deaths. SCs have favored increased popularity over recent years due to their intensified psychoactive effects, compared with THC, turning regular cannabis users into SCs. Among cannabinoid users (mainly young people), pregnant women and women of child-bearing potential (WoCBP) comprise particular risk groups, due to the potential onset of neurodevelopment disorders in the offspring (eg, schizophrenia and autism spectrum disorders). Understanding the role played by cannabinoids, and the potential action of emerging SCs in the regulation of the neuronal function, especially during neuronal development, thus assumes critical relevance. Here, we review the mechanistic regulation of neuronal processes, namely during neuronal development, by the endocannabinoid system. Most important, we further develop on the potential of SCs to modulate such mechanisms and subsequently disrupt proper neurodevelopment.