Psilocybin, MDMA, and ketamine have emerged as potentially effective treatments for rapid amelioration of the symptoms of mood and related psychiatric disorders. All clinical data collected so far with regard to psilocybin or MDMA, which have reported positive outcomes for treating depression, anxiety, posttraumatic stress disorder, and drug or alcohol use disorders, have involved...
Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that...
The past decade has seen a reduction in society’s perception of cannabis being of any risk or harm. However, we are in a transformational time in which cannabis’ health implications related to neurodevelopment, particularly for vulnerable populations, must challenge such perceptions of harmlessness. The combination of multiple interrelated factors — societal, political, and business — have...
A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its...
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly...
The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory...