Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice.

While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg/kg IP psilocybin was found to have anxiolytic-like effects in C57BL/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin's anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations. Overall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.

Neural Activity Across the Dorsolateral Prefrontal Cortex and Risk for Suicidal Ideation and Self-Injury.

The current study investigated the neural correlates of non-suicidal self-injury (NSSI) and suicidal ideation across the dorsolateral prefrontal cortex. Two-hundred ninety-six undergraduates solved anagram tasks while being monitored by a functional near-infrared spectroscopy device, and completed a questionnaire assessing behaviors and symptoms. Repeated measures analysis of variance revealed location-specific changes in neural activity based on NSSI, suicidal ideation, task type, and cognitive demand. The presence of suicidal ideation was associated with specific patterns of neural activity, modified by sex and task type. Interestingly, participants who engaged in NSSI exhibited some deactivation of the dlPFC when faced with more difficult cognitive challenges. Future research on these processes may allow for noninvasive imaging techniques to help screen risk for suicidality and NSSI.

Catalysts for change: the cellular neurobiology of psychedelics.

The resurgence of interest in the therapeutic potential of psychedelics for treating psychiatric disorders has rekindled efforts to elucidate their mechanism of action. In this Perspective, we focus on the ability of psychedelics to promote neural plasticity, postulated to be central to their therapeutic activity. We begin with a brief overview of the history and behavioral effects of the classical psychedelics. We then summarize our current understanding of the cellular and subcellular mechanisms underlying these drugs' behavioral effects, their effects on neural plasticity, and the roles of stress and inflammation in the acute and long-term effects of psychedelics. The signaling pathways activated by psychedelics couple to numerous potential mechanisms for producing long-term structural changes in the brain, a complexity that has barely begun to be disentangled. This complexity is mirrored by that of the neural mechanisms underlying psychiatric disorders and the transformations of consciousness, mood, and behavior that psychedelics promote in health and disease. Thus, beyond changes in the brain, psychedelics catalyze changes in our understanding of the neural basis of psychiatric disorders, as well as consciousness and human behavior.

Engaging, Entertaining, and Educating Under-Served and At-Risk Youth with STEM-Based Activities.

In recently constructing a curriculum for our Neuroscience major, a service-learning component was included that requires students to develop and present STEM-based activities to underserved 4th-6th grade children in an afterschool program. Though initially proposed with a primary goal of teaching children specific concepts in the field of neuroscience, efforts have gradually shifted towards simply increasing interest in, and enthusiasm for, STEM through interactive demonstrations. Most of the activities used incorporate neuroscience examples that are inherently intriguing and conceptually accessible to children. The present article briefly summarizes our experiences with enlisting college students as youth mentors, and having those students work within the community to establish a conducive setting for such a program. Insight is also offered into developing activities that might be successful for working with this particular population, including possible approaches to assessing effectiveness. Finally, specific examples for several activities are given.