ABM300

ABM300 is a novel, brain-penetrant small molecule allosteric modulator of the cannabinoid receptor 1 (CB1). Specifically characterized as a CB1 positive allosteric modulator (PAM)-antagonist (or negative allosteric modulator, NAM), ABM300 binds to an allosteric site on the CB1 receptor normally occupied by cholesterol. It increases orthosteric agonist binding affinity while simultaneously blocking agonist-induced downstream signaling pathways, including G-protein activation, β-arrestin2 recruitment, and cAMP inhibition. Developed by researchers at the University of Toronto, ABM300 has demonstrated preclinical efficacy in rodent models of hyperdopaminergia (such as GluN1-knockdown and dopamine transporter knockout mice), where it significantly dampens amphetamine-induced dopamine release and reduces psychosis-like behaviors and psychomotor hyperactivity without causing the typical adverse effects (such as anxiety or cannabimimetic effects) associated with orthosteric CB1 antagonists or inverse agonists.