New Insights Into the Neural Consequences of Synthetic Cannabinoids During Adolescence: The Critical Role of Reelin at Prefrontal Synapses

The recreational use of synthetic cannabinoids (SCs) has increased markedly in recent years, with a particularly high prevalence among young people. Originally designed to mimic the effects of Δ9-tetrahydrocannabinol (THC), the main psychotomimetic compound in cannabis, SCs have proliferated in the illicit drug market under the generic term “new psychoactive substances”. This heterogeneous group of substances often exhibits a higher binding affinity for the CB1 cannabinoid receptor (CB1R) than THC, which acts as a partial agonist at CB1Rs. Additionally, SCs interact with other components of the endocannabinoid system, potentially resulting in distinct pharmacological effects and diverse toxicity profiles. These characteristics make SCs unsuitable for medical use because they have a high potential for abuse and addiction, which poses significant challenges for human dosing. Reports of acute intoxications, hospitalizations, and, in some cases, fatalities, particularly coinciding with the general trend toward the appearance of increasingly potent SCs, underscore the global public health concern posed by these substances.