Anticipatory nausea (AN) is a conditioned nausea reaction experienced by chemotherapy patients upon returning to the clinic. Currently, there are no specific treatments for this phenomenon, with the classic anti-emetic treatments (e.g., ondansetron) providing no relief. The rat model of AN, contextually elicited conditioned gaping reactions in rats, provides a tool for assessing potential treatments for this difficult to treat disorder. Systemically administered drugs which elevate the endocannabinoids, anandamide (AEA) and 2-arachodonyl glycerol (2-AG), by interfering with their respective degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) interfere with AN in the rat model. We have shown that MAGL inhibition within the visceral insular cortex (VIC) interferes with acute nausea in the gaping model (Sticht et al, 2015b). Here we report that bilateral infusion of the MAGL inhibitor, MJN110 (but neither the FAAH inhibitor, PF3845, nor ondansetron) into the VIC suppressed contextually – elicited conditioned gaping and this effect was reversed by co-administration of the CB1 antagonist, AM251. These findings suggest that 2-AG within the VIC plays a critical role in the regulation of both acute nausea and AN. As there are currently no specific therapeutics for chemotherapy patients that develop anticipatory nausea, MAGL inhibition by MJN110 may be a candidate treatment.

Cannabis has been used in a medicinal context throughout recorded history and across diverse cultures to aid in the treatment of a wide array of ailments. Remarkably, clinical and preclinical investigations are only recently beginning to reveal the neurobiological mechanisms responsible for the clinically-relevant actions of cannabis that have been acknowledged by medical pharmacopeia for millennia. The therapeutic potential of cannabis-derived phytochemicals such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are currently being explored in several contexts. Experimental evidence suggests that modulation of signal transduction pathways underlying cellular excitability, as well as interactions with the endocannabinoid and serotonin systems, which modulate emotion and pain sensitivity under physiological conditions, are among the mechanisms responsible for its clinical efficacy. Interestingly, the diverse pharmacodynamic profile of CBD suggests a synergistic interaction with current first- and second-line medications used in the treatment of neuropathic pain to produce clinically meaningful therapeutic benefits. To advance understanding of the neurobiological mechanisms underlying therapeutic cannabis use in pain management and to integrate its use into modern clinical practices, it is important to understand medicinal cannabis use in historic and medical contexts. This review highlights the copious history of medical practices incorporating the use of cannabis, and discusses the potential pharmacological mechanisms responsible for its therapeutic efficacy in the management of neuropathic pain.

Many component processes of reward require appropriate serotonin (5HT) and dopamine (DA) neurotransmission within key limbic brain regions. Evidence suggests that dysregulation of 5HT and DA transmission can precipitate reward dysfunction and major depressive disorder (MDD) symptoms in genetically predisposed individuals. Various neurobiological indicators (biomarkers) of MDD have been proposed, including changes in signal transduction pathways, protein phosphorylation, and gene expression in subcortical, reward-related structures. However, these insights have yielded limited clinically relevant benefits for diagnosis, treatment, or prognosis. In addition, clinical application of identified biomarkers is often hindered by multiple factors including disease heterogeneity and symptom variability between patients. Innovative approaches including big data analytics, methodical collaboration between research programs, and reverse-translational strategies are now required to understand if particular biomarkers can be used to predict disease onset and treatment response, to stratify treatments for patient subgroups, and develop novel pharmacotherapies. This review briefly summarizes the predictive value of big data analytics in parsing the neurobiological underpinnings of MDD, with a focus on potential clinically-viable biomarkers for predictive therapies.

Historically, treatments for severe psychoses and affective disorders were nonexistent, and patients with mental disorders were transferred to asylums for public safety. This deficiency in treatment inspired the inception of somatic therapies, of which electroconvulsive therapy (ECT) was the most efficacious. This paper will outline the birth of ECT, the controversies leading to its decline, and the subsequent resurgence back into practice.