Review of the Endocannabinoid System

Summary & key facts

This review describes the endocannabinoid system (ECS) as a widespread network of natural cannabinoids, cannabinoid receptors (mainly CB1 and CB2), and the enzymes that make and break those chemicals. The ECS helps shape brain development and adjusts how neurons communicate. The authors note that THC is the main psychoactive part of cannabis and can produce some schizophrenia-like symptoms in a dose-dependent way, that heavy cannabis use in adolescence is linked to higher risk of schizophrenia, and that CBD can reduce CB1 signaling in lab studies but its exact molecular targets are still unclear. The review also stresses that many ECS parts do multiple jobs and that genetic links between the

Key facts:

• The ECS is composed of endogenous cannabinoids, cannabinoid receptors, and the proteins that synthesize and degrade endocannabinoids.
• CB1 and CB2 are the best-studied cannabinoid receptors; CB1 is highly expressed in the nervous system and is especially abundant on certain GABAergic interneurons and at synaptic terminals.
• CB2 receptors are primarily found on immune cells, including microglia, and CB2 activation is generally anti-inflammatory.
• CB1 and CB2 mainly couple to inhibitory G proteins (Gi/o) and can also recruit beta-arrestins and other signaling pathways, so they influence many intracellular processes.
• THC is the main psychotropic component of cannabis and binds cannabinoid receptors; acute THC administration can reproduce some symptoms of schizophrenia in a dose-dependent manner.
• THC is a low-efficacy CB1 agonist, while the endogenous ligand 2-arachidonoyl glycerol (2-AG) and most synthetic CB1 agonists are high-efficacy agonists, which can lead to different biological effects.
• CBD can act as a negative allosteric modulator of CB1 in multiple in vitro assays and can attenuate CB1 activation by THC and endocannabinoids in some studies, but CBD's exact molecular targets are not fully known.
• The review states that heavy adolescent cannabis use is associated with an increased risk of developing schizophrenia or more severe schizophrenia later in life, but it does not claim this is the only cause.
• No coding polymorphisms in the CB1 gene (CNR1) have emerged as clear risk factors for schizophrenia, and reported noncoding variants have not been robustly replicated in follow-up studies.

Topics

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Neurotransmitter Receptor Influence on Behavior

Categories

Health Sciences Medicine Pharmacology

Tags

Antagonist Biochemistry Biology Cannabinoid Cannabinoid receptor Chemistry Delta-9-tetrahydrocannabinol Endocannabinoid system Endogeny Neuroscience Psychiatry Psychology Psychosis Receptor Synaptic plasticity