Research Review: What we have learned about the endocannabinoid system in developmental psychopathology

Abstract

Background: The endocannabinoid (eCB) system, the primary target of cannabis, has gained significant attention as a potential novel therapeutic approach for treating a range of psychiatric disorders characterized by dysregulation of stress, emotion, and social behavior. The use of cannabis itself as a pharmacotherapeutic in children and adolescents is limited due to various constraints, including legal status, stigma, and real or perceived negative side effects. Thus, compounds that target the eCB system without the notable unwanted effects of cannabis may offer a more viable approach for developing populations.

Methods: In this narrative review, we provide an overview of the eCB system, summarizing its function throughout development and its potential contribution to psychopathology in children and adolescents. We highlight evidence of its behavioral role and the dysregulation of this system in various psychiatric disorders. Finally, we summarize current investigations into pharmacological and nonpharmacological therapeutic interventions designed to target the eCB system.

Conclusions: The eCB system may offer an innovative target for treatments of various psychiatric disorders in child and adolescent populations. However, more research is needed to understand the nuanced developmental trajectory of this system and to determine whether existing compounds are safe and effective for use in these populations.

Keywords: 2‐arachidonoylglycerol; Endocannabinoid; anandamide; development; psychopathology.

Figure 1

Graphical representation of eCB signaling at the synapse. Stimulation of the postsynaptic neuron by the pre‐synaptic neuron leads to the synthesis of the eCB ligands anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG). These travel across the synapse in a retrograde fashion to bind to cannabinoid receptor 1 (CB1) on the pre‐synaptic neuron, inhibiting its activity. The box on the bottom right illustrates the effects of the FAAH C385A SNP and FAAH inhibitors on FAAH activity. The presence of the A allele is associated with reduced FAAH activity, resulting in higher peripheral AEA concentrations, particularly in individuals homozygous for the A allele. The highest peripheral AEA concentrations are observed when FAAH activity is pharmacologically inhibited. Figure created with Biorender.