Esketamine is an effective rapid-acting pharmacological intervention for treatment-resistant depression. However, the temporal dynamics of underlying brain networks associated with the improvement of depressive symptoms remain elusive. This observational study seeks to delineate alteration in network activity within 90 minutes of nasal Esketamine administration, with a focus on exploring its...
Opioid use disorder (OUD) is characterized by dependence, withdrawal, and high relapse risk, yet the neuroimmune mechanisms underlying withdrawal in the amygdala remain poorly understood. This study investigated whether 3,4-methylenedioxymethamphetamine (MDMA) modulates heroin withdrawal–induced neuroinflammation in the central amygdala (CeA) and basolateral amygdala (BLA). Adult male...
Psychedelics are seeing renewed interest due to their potential as therapeutic tools; however, despite promising clinical findings, the underlying signaling mechanisms and brain-region specific effects of psychedelics remain unclear. This dissertation first describes a comprehensive study aimed at understanding the on and off-target actions of ~40 diverse psychedelic substances representing...
Psilocybin has emerged as a potentially rapidly acting antidepressant with enduring actions. In this issue of Neuron, Shao et al. (2021) show that psilocybin quickly induces dendritic spine formation in cortical layer V pyramidal neurons. These results provide a potential cellular substrate for psilocybin's therapeutic actions.
Psychedelic drugs including psilocybin, N,Nʹ-dimethyltryptamine (DMT) and lysergic acid diethylamide (LSD) are undergoing a renaissance as potentially useful drugs for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. Notably, phase II trials have shown that psilocybin can produce statistically significant clinical effects following one or two administrations in...
Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions—both therapeutic and hallucinogenic—are not understood, although activation of...
Contemporary scholarship on mindfulness casts it as a form of purely non-evaluative engagement with experience. Yet, traditionally mindfulness was not intended to operate in a vacuum of dispassionate observation, but was seen as facilitative of eudaimonic mental states. In spite of this historical context, modern psychological research has neglected to ask the question of how the practice of...
UNC LibrariesNovember 5, 2020Melissa K. Holt, Nancy L. McCain, Jo Lynne W. Robins et al.
This article provides an overview of the mechanisms of action, evidence base, and practice of mindfulness, with an emphasis on how to easily incorporate this valuable skill into practice.
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at...
A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at...
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4- iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT 2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (-)-(1R,2S)- configuration. Screening for affinity...
Lysergic acid diethylamide (LSD), the prototypical “psychedelic,” may be unique among psychoactive substances. In the decades that followed its discovery, the magnitude of its effect on science, the arts, and society was unprecedented. LSD produces profound, sometimes life-changing experiences in microgram doses, making it a particularly powerful scientific tool. Here we sought to examine its...
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually...