UNC Libraries
June 21, 2026
Verina Guirguis
Esketamine is an effective treatment for individuals with treatment-resistant depression, showing significant mood improvements shortly after administration. In a study of five participants with major depressive disorder, subjective feelings of 'Highness' increased by 31.73% and 'Happiness' by 22.75% within 15 minutes. A notable reduction in alpha power was observed, peaking at a decrease of 46.36% at 35 minutes post-administration. These changes correlate with mood fluctuations, suggesting dynamic brain network alterations during treatment.
UNC Libraries
June 5, 2026
Charlotte Rubin
Opioid use disorder involves dependence, withdrawal, and high relapse risk, but the neuroimmune mechanisms in the amygdala during withdrawal are not well understood. In adult male rats given escalating heroin doses over 10 days followed by 24-hour withdrawal, MDMA or saline was administered. Heroin-treated rats showed significant weight loss during withdrawal, confirming dependence, and MDMA did not worsen this effect. TNF-α immunoreactivity showed no effect of heroin withdrawal or MDMA in the central or basolateral amygdala, though a trend in the basolateral amygdala suggests subtle modulation by combined exposure.
UNC Libraries
May 21, 2026
Gavin Schmitz
Psychedelics are being investigated as therapeutic tools, but their brain-region-specific effects and signaling mechanisms are not fully understood. A comprehensive study of about 40 diverse psychedelic substances from the tryptamine, phenethylamine, and lysergamide classes found that all tested compounds activate the 5-HT2A serotonin receptor, while also showing serotonergic, dopaminergic, and adrenergic activity. The 5-HT2A receptor is enriched in layer V pyramidal neurons in rodent and human cortices. Electrophysiological studies identified a population of 5-HT2A receptor neurons in the prelimbic and anterior cingulate regions of the prefrontal cortex. Psilocin and a 5-HT2A-preferring compound increased firing in these neurons via a 5-HT2A- and Gαq-dependent mechanism, whereas the non-hallucinogenic LSD analog 2-bromo-LSD reduced firing in both 5-HT2A and non-5-HT2A neurons through a different mechanism.
UNC Libraries
June 12, 2024
D Mwende . Muthoni, Roth B.l
Psychedelic drugs such as psilocybin, DMT, and LSD show promise for treating neuropsychiatric diseases, with phase II trials indicating that one or two doses of psilocybin can produce significant clinical effects for depression and anxiety. This has spurred commercial interest, with nearly 60 companies exploring psychedelic treatments. While the 5-HT2A receptor is known to mediate behavioral effects, it remains unclear which aspects of its activity in the central nervous system drive therapeutic outcomes and whether these can be isolated using novel chemical probes. The article discusses controversies and consensus in this field and highlights how basic science may guide development of psychedelic-inspired medications that offer efficacy without hallucinogenic or rewarding effects.
UNC Libraries
June 12, 2024
Diberto J.f, Roth B.l
Psilocybin, a psychedelic compound, may act as a fast-acting antidepressant with lasting effects. A study in Neuron by Shao et al. (2021) demonstrates that psilocybin rapidly promotes the growth of dendritic spines in cortical layer V pyramidal neurons. This finding suggests a possible cellular basis for psilocybin's therapeutic benefits in treating depression.
UNC Libraries
June 7, 2024
Kami Kim, T Che, Ouliana Panova et al.
Psychedelics such as LSD, psilocybin, and related compounds are used recreationally and are being investigated as treatments for depression, anxiety, and substance abuse. Their therapeutic and hallucinogenic effects depend on activating the 5-HT2A serotonin receptor, but the molecular details were unclear. Using cryo-electron microscopy and X-ray crystallography, researchers determined the structures of the 5-HT2A receptor bound to a hallucinogen, LSD, and an inverse agonist. These structures reveal how the receptor interacts with Gαq protein and changes shape when activated. The findings may guide development of more selective drugs for neuropsychiatric disorders.
UNC Libraries
October 31, 2020
Adam Pigott, Bryan L. Roth, Xi‐ping Huang et al.
Replacing the ethylamine side chain of the psychedelic compounds DOI and DOB with a cyclopropylamine group produced new molecules that bind strongly to 5-HT2 family serotonin receptors. The most potent version had the (−)-(1R,2S)-configuration. However, these cyclopropane analogs also showed increased affinity for other serotonin receptor subtypes beyond 5-HT2A and 5-HT2B, making them less selective than the original compounds. At appropriate doses, they may serve as research tools for studying 5-HT2 receptor function, but their reduced selectivity for 5-HT2A receptors must be considered.
UNC Libraries
August 7, 2020
A. Pigott, X.-p. Huang, J.d. Mccorvy et al.
Replacing the ethylamine side chain of two psychedelic amphetamine derivatives, DOI and DOB, with a cyclopropylamine group produced new compounds that bind tightly to the 5-HT2 family of serotonin receptors. The most potent version had the (-)-(1R,2S)- configuration. However, these cyclopropane analogues also showed increased affinity for several other serotonin receptor subtypes beyond 5-HT2A and 5-HT2B. At appropriate doses, they may still be useful research tools for probing 5-HT2 receptor function, but their selectivity for 5-HT2A receptors is lower than that of the original compounds.
UNC Libraries
April 22, 2020
David E. Nichols
Psychedelics are psychoactive substances that alter perception, mood, and cognition, are physiologically safe, and do not cause addiction. They act as agonists at brain serotonin 5-HT2A receptors, especially on layer V neocortical pyramidal cells. Recent double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress showed unprecedented relief of anxiety and depression. Two small pilot studies also showed positive benefits for alcohol and nicotine addiction. Imaging after intravenous psilocybin and LSD revealed decreased oscillatory power in the brain's default mode network.