PloS one
January 1, 2024
Xiaohui Wang, Zhicheng Dai, Xinying Zhu et al.
36 citations
A systematic review and meta-analysis of 11 randomized controlled trials involving 1644 breast cancer patients found that mindfulness-based stress reduction therapy, compared with standard care, significantly reduces negative emotions including perceived stress, depression, anxiety, and fear of recurrence. The therapy also improves patients' coping ability and emotional state. These findings support the use of mindfulness-based stress reduction to enhance quality of life in breast cancer patients by alleviating psychological distress.
Nature
November 5, 2025
Chenyu Yue, Nan Wang, Haojiang Zhai et al.
22 citations
Adenosine signaling is identified as the central mechanism underlying the rapid antidepressant effects of ketamine and electroconvulsive therapy (ECT). Experiments in mice using genetically encoded adenosine sensors and real-time optical recordings show that both therapies cause strong adenosine surges in mood-regulatory brain regions such as the medial prefrontal cortex and hippocampus. Disrupting A1 and A2A adenosine receptors genetically or pharmacologically abolishes the therapeutic effects, establishing adenosine's essential role. Ketamine increases adenosine by modulating cellular metabolism without causing neuronal hyperactivity. Newly developed ketamine derivatives that enhance adenosine signaling show improved antidepressant efficacy with fewer side effects. Acute intermittent hypoxia, a non-pharmacological intervention, also increases brain adenosine and produces antidepressant effects, paralleling ketamine and ECT.
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.
European journal of medicinal chemistry
January 5, 2025
Miyuan Zhang, Yuefeng Yang, Zhishuai Yang et al.
10 citations
The position of the hydroxyl group on the indole ring of psilocin analogs determines their ability to activate the 5-HT2A receptor and produce psychedelic-like effects. Analogs with the hydroxyl group at the 4th or 5th position (psilocin and bufotenine) show significantly higher agonistic activity and head-twitch responses than those with the group at the 6th or 7th position. Computer simulations reveal that the 4- and 5-position analogs form a crucial hydrogen bond with residue L229 and a stable salt bridge and hydrogen bond with residue D155, guiding them into the binding site. Analogs lacking these interactions fail to reach the orthosteric site and have poor receptor activity.
Research (Wash D C)
October 4, 2024
Miyuan Zhang, Yibo Wang, Tian-Ming Gao et al.
10 citations
Psychedelics alter sensory perceptions, disrupt self-referential thought, and can catalyze spiritual and existential experiences. As research advances, these substances are being integrated into therapeutic settings, challenging existing psychiatric models and offering new insights into consciousness and mental health. This emerging paradigm calls for careful regulation and ethical considerations, promising a more holistic approach to mental health disorders.
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.
Nature
January 28, 2026
Zheng Xu, Hongshuang Wang, Jingjing Yu et al.
5 citations
Psychedelics are being tested in over 200 clinical trials as potential treatments for psychiatric disorders, but how they work and their risks are not fully understood. The serotonin 2A receptor (5-HT2AR) is the main target of psychedelics. This study compared psychedelics with non-hallucinogenic analogues using cell and animal experiments, finding that 5-HT2AR signaling through a non-canonical Gi pathway is essential for hallucinogenic effects. Five cryo-electron microscopy structures of 5-HT2AR bound to these drugs were solved. A special contact between non-hallucinogenic analogues and the receptor biased signaling away from Gi. A derivative called DOI-NBOMe showed potent Gq-biased activity and therapeutic effects in mice without causing hallucinations. These findings reveal mechanisms of 5-HT2AR Gi signaling and guide the design of safer psychedelic-based drugs.
ACS chemical neuroscience
May 7, 2025
Hongshuang Wang, Xiaohui Wang
5 citations
Psychedelics may help treat neuropsychiatric disorders by increasing brain entropy and disrupting rigid neural patterns, which can lead to ego dissolution and profound emotional breakthroughs. This process potentially alleviates symptoms of depression, anxiety, PTSD, and addiction. However, clinical use faces challenges such as careful patient screening, managing adverse experiences, and ethical considerations, all essential for safe therapeutic integration.
ACS pharmacology & translational science
March 14, 2025
Hongyuan Li, Xiaohui Wang
5 citations
Psychedelic experiences can provide transformative perspectives on dying, potentially easing existential distress and improving quality of life for the terminally ill. Their growing recognition in palliative care, therapy, and spiritual exploration may revolutionize end-of-life care.
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.
ACS Pharmacology & Translational Science
May 15, 2025
Haojiang Zhai, Hongshuang Wang, Haohong Li et al.
3 citations
Psychedelics like psilocybin, LSD, and DMT may alter sleep architecture, particularly by influencing rapid eye movement (REM) sleep and vivid dreaming. This viewpoint suggests these substances could have therapeutic potential for sleep disorders, though their impact on sleep remains underexplored. The authors provide a perspective on how psychedelics might affect sleep phases and dreaming, opening an emerging area for sleep therapy.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
May 1, 2025
Yuanpeng Li, Hongyuan Li, Hongshuang Wang et al.
3 citations
Amphetamine-type stimulants (ATS) and their analogs can be rapidly evaluated using the roundworm Caenorhabditis elegans. In a swimming-induced paralysis assay, worms exposed to amphetamine, methamphetamine, MDMA, and their enantiomers showed distinct behavioral responses depending on their genetic makeup. The effects depended on dopaminergic and serotonergic pathways, specifically the DOP-3 and SER-4 receptors. The assay also distinguished between chiral forms of ATS, and meta-R amphetamines produced stronger effects than ortho-R and para-R analogs. This method offers a cost-effective, high-throughput way to assess the activity and toxicity of new psychoactive substances.
Mol Psychiatry
September 30, 2025
Xiubo Du, Jiantao Liu, Xiaohui Wang
2 citations
Psychedelics like psilocybin, LSD, ketamine, and DMT can alter consciousness and inspire creativity. This perspective examines how these substances interact with the concept of creation, including enhancing artistic inspiration, fostering spiritual experiences, and driving therapeutic breakthroughs. By integrating neurobiological research, clinical applications, and cultural analysis, the authors argue that psychedelics may catalyze innovative thinking and awaken creative and transformative potential. As these substances gain prominence for reshaping understanding of consciousness and psychological healing, their broader integration requires careful consideration of legal, ethical, and cultural contexts to ensure evidence-based, respectful, and responsible use.
ACS pharmacology & translational science
July 11, 2025
Cong Zhang, Yibo Wang, Xiaohui Wang
2 citations
Neuropsychiatric disorders arise from disruptions in brain network dynamics that fall along a spectrum from order to complexity to chaos. Psychedelics may work therapeutically by increasing neural entropy, breaking maladaptive patterns, and enabling network reorganization. This framework focuses on dynamic remodeling of the brain's connectome rather than static molecular fixes, proposing that controlled neural destabilization and reconnection offers a new treatment strategy for psychiatric and neurological conditions.
Natl Sci Rev
April 25, 2025
Yibo Wang, Xiaohui Wang
2 citations
The article proposes that entheogens—plant-based psychoactive substances used historically in spiritual and healing rituals—may be understood through the lens of evolutionary medicine as treatments for neuropsychiatric disorders. It argues that these compounds can address deep-seated brain mechanisms underlying conditions like depression and anxiety by resetting maladaptive neural pathways and promoting psychological flexibility. The text suggests that modern mental health challenges arise partly from mismatches between ancestral environments and contemporary lifestyles, and that entheogens offer a novel paradigm for healing by reconnecting individuals with evolved neurobiological processes. The authors indicate that this evolutionary perspective could guide clinical use and improve well-being.
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.
ACS Chemical Neuroscience
July 24, 2025
Anjian Yang, Xinyou Lv, Hongshuang Wang et al.
1 citation
This viewpoint proposes that mysticism and fundamentalism can be understood as brain network disorders, where rigid neural patterns underlie inflexible belief systems. Psychedelics such as psilocybin, LSD, and DMT may disrupt these patterns, potentially increasing cognitive flexibility and challenging dogmatic thinking. The authors suggest this modulation could have therapeutic applications for extremism and certain mental health conditions, though the argument remains theoretical and not empirically tested.
ACS Pharmacology & Translational Science
July 8, 2025
Miyuan Zhang, Haiyan Zhai, Liu Yang et al.
1 citation
Psilocin, the active metabolite of psilocybin, induces psychedelic-like behavior in male mice by activating neurons in the medial prefrontal cortex (mPFC). Using c-Fos immunofluorescent labeling, the mPFC was the only brain region among several tested that was specifically associated with the head twitch response (HTR), a behavioral marker of psychedelic activity. A picomolar dose of psilocin directly into the mPFC triggered significant HTR. Optogenetic activation of these neurons increased spontaneous HTR, while acute inhibition suppressed drug-induced HTR. The findings establish the mPFC as a critical regulator of psilocin's psychedelic effects, offering insights for improving the clinical safety and therapeutic use of psychedelics.
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.
Proceedings of the National Academy of Sciences
June 24, 2026
Yibo Wang, H Wang, C T Lin et al.
Natural hallucinogenic compounds like mescaline and psilocybin evolved independently across plants, fungi, and animals through a 'building-block' biosynthetic logic that repurposes primary metabolism. These molecules likely function as defensive agents or manipulators of herbivore and pollinator behavior, not primarily for human psychoactivity. Endogenous mammalian tryptamines appear to serve cytoprotective and stress-response roles via sigma-1 receptors, not hallucinogenic functions. Across kingdoms, these compounds converge on conserved neural targets such as serotonergic systems, making human psychoactivity an evolutionary by-product of molecules selected for ecological interactions with animals sharing deeply conserved receptor architectures.
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.
Current neuropharmacology
April 28, 2026
Hongshuang Wang, Xiaobing Li, Feng Yu et al.
Combining psychedelics with music in therapy may improve mental health outcomes by acting on specific brain mechanisms. Psychedelics like psilocybin activate 5-HT2A receptors and BDNF-TrkB signaling, increase neural plasticity, and desynchronize the default mode network, while music guides emotional processing and amplifies psychological insights. This synergy shows promise for treating depression, PTSD, and addiction. The review provides a mechanistic framework for understanding these interactions and identifies neurobiological targets for optimizing future therapeutic protocols.
Psychedelics.
October 21, 2025
Pu Jiang, Ci Lin, Xiaohui Wang
Psychedelics such as psilocybin, dimethyltryptamine, and lysergic acid diethylamide disrupt normal time perception, causing time dilation, compression, or loss of time. This opinion article integrates emerging cognitive neuroscience findings to discuss neural mechanisms behind these temporal anomalies. The authors suggest that psychedelic-induced time warps offer a new approach to studying brain correlates of the perception of the passage of time and conscious time perception. These changes may have therapeutic value for psychiatric disorders where altered time perception is central, including posttraumatic stress disorder, depression, and anxiety. Examining these time changes also highlights psychedelics' potential in shaping transformative cognitive-affective states and their clinical relevance.