Advanced science (Weinheim, Baden-Wurttemberg, Germany)
April 2, 2025
Cong Lin, Xiaoxuan Zhou, Mingqi Li et al.
14 citations
In a mouse model of inflammation-induced depression, S-ketamine (S-KET) reduced depressive-like behaviors and lowered pro-inflammatory factors in the medial prefrontal cortex, while R-ketamine (R-KET) did not. S-KET bound directly to the protein SIRT2 at the Q167 residue, enhancing its interaction with NF-κB subunit p65, which reduced acetylation and suppressed pro-inflammatory gene expression. Experiments using RNA interference, a SIRT2 inhibitor (AK-7), and pharmacological blockade confirmed that SIRT2 is essential for these effects. The findings indicate that SIRT2 mediates the therapeutic actions of S-KET, suggesting a target for treating inflammation-associated depression.
ACS Pharmacology & Translational Science
March 7, 2025
Shuai Hu, Cong Lin, Hongshuang Wang et al.
8 citations
Psychedelics such as psilocybin and MDMA show promise for treating anorexia nervosa by disrupting maladaptive neural circuits, enhancing cognitive flexibility, and facilitating emotional processing. Early studies report reductions in symptoms and improvements in psychological well-being, particularly for patients unresponsive to conventional therapies like cognitive-behavioral therapy and pharmacotherapy. However, further research is needed to establish long-term safety, efficacy, and clinical integration, and to address legal, ethical, and safety challenges.
Mol Neurodegener
October 12, 2024
Cong Lin, Xiubo Du, Xiaohui Wang
6 citations
This perspective piece explores two unusual phenomena that may offer new insights into Alzheimer's disease: terminal lucidity—unexpected moments of mental clarity shortly before death in people with severe dementia—and paradoxical lucidity, similar brief episodes not linked to dying. The authors also discuss the potential of psychedelic compounds to induce such lucid states, suggesting these phenomena could challenge current assumptions about irreversible cognitive decline and point toward novel therapeutic avenues. The paper synthesizes existing observations and hypotheses rather than presenting new empirical data, arguing that investigating these transient cognitive improvements might reveal underlying neural mechanisms and treatment targets.
ACS Pharmacology & Translational Science
February 10, 2025
Xue Wang, Cong Lin, Xiaohui Wang
5 citations
Psychedelics like LSD, psilocybin, and MDMA may enhance pro-social behaviors in people with autism spectrum disorders by altering brain circuits involved in social cognition. The viewpoint discusses potential mechanisms underlying these effects, such as increased neuroplasticity and changes in serotonin receptor activity. While direct evidence in ASD populations is limited, the authors suggest that these compounds could offer new therapeutic avenues for improving social interaction and communication deficits. The paper calls for further research to explore the safety and efficacy of psychedelic-assisted therapy for autism, emphasizing the need for controlled clinical trials.
ACS chemical neuroscience
July 9, 2025
Xue Wang, Fan Jun, Cong Lin et al.
4 citations
Classic psychedelics and the gut microbiome influence each other through 5-HT2A receptor signaling, neuroplasticity, and microbial metabolism. Psychedelics may alter the composition of gut bacteria, while the microbiome can affect how well these compounds work. The authors propose using microbiome-informed approaches, such as probiotics or dietary changes, to tailor and improve psychedelic treatments for mental health conditions.
Biological Psychiatry
February 1, 2026
Jin Zhang, Cong Lin, Xinyou Lv et al.
1 citation
Classic psychedelics like psilocybin, LSD, and DMT modulate neuroplasticity and metaplasticity in the adult brain beyond their transient psychotropic effects. They activate serotonin 5-HT2A receptors and signaling cascades involving CaMKII, ERK, mTOR, and BDNF pathways, inducing synaptogenesis, dendritic spine remodeling, and immediate early gene transcription. The brain's extracellular matrix, particularly perineuronal nets (PNNs), regulates synaptic stability and is a key target of psychedelic action. Psychedelics transiently disrupt ECM integrity by loosening PNNs, reopening critical periods of plasticity and restoring circuit flexibility. These ECM-mediated metaplastic effects appear essential for sustained therapeutic outcomes in psychedelic-assisted therapy for depression, PTSD, addiction, and potentially neurodegenerative diseases.
Molecular Psychiatry
July 10, 2026
Cong Lin, Xiaohui Wang
Classic psychedelics like LSD, psilocybin, DMT, and mescaline, as well as the antidepressant ketamine, can cause lasting changes in brain function and behavior beyond their immediate effects. This review examines how these substances may influence epigenetic regulation—changes in gene activity that do not alter the DNA sequence itself—through mechanisms such as DNA methylation, histone modifications, and non-coding RNA dynamics. The authors propose that psychedelics also affect metabolic pathways, altering the availability of key molecules like acetyl-CoA and SAM, which in turn may impact gene expression and synaptic connectivity. Understanding these processes could help explain how short-term psychedelic exposure leads to sustained therapeutic benefits and guide the development of new treatments for neuropsychiatric conditions.
ACS pharmacology & translational science
June 12, 2026
Tianshu Zhang, Cong Lin, Xiaohui Wang
Classic serotonergic psychedelics like LSD, psilocybin, and DMT show promise for treating neuropsychiatric disorders but are limited by first-pass metabolism, erratic pharmacokinetics, and off-target effects. Advanced delivery systems—including transdermal and microneedle patches, intranasal sprays, sublingual films, and injectable formulations—along with molecular strategies such as prodrugs and selective receptor bias, bypass hepatic metabolism, enable precise control over onset and duration, and minimize peripheral activation. Preclinical and early clinical evidence indicates gains in bioavailability, half-life extension, and conversion of fleeting effects into manageable windows, offering a path to safer, patient-centered therapies despite regulatory and trial-design challenges.