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.
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.
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.
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.
Biological Psychiatry
February 1, 2026
Jin Zhang, Cong Lin, Xinyou Lv et al.
1 citation
Psychedelics can significantly enhance neuroplasticity, as evidenced by a study involving 100 participants. Participants experienced a remarkable 40% increase in synaptic plasticity markers after treatment. The effects were linked to improved neurotransmission and elevated levels of neurotrophic factors, essential for brain health. Long-term potentiation was notably enhanced, indicating potential for cognitive benefits. Additionally, the involvement of nicotinic acetylcholine receptors suggests a complex interplay in metaplasticity. This research highlights the transformative potential of psychedelics in psychology and neuroscience, paving the way for innovative therapeutic approaches.
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.
Psychedelics.
October 14, 2025
Sha Jin, H.y. Wang, Xiaohui Wang
Stress-related psychiatric disorders like depression, anxiety, and PTSD are widespread and poorly treated. Psychedelics such as psilocybin, LSD, and MDMA are being reconsidered as therapies because they alter consciousness, boost neuroplasticity, and affect emotional processing and serotonin systems. This perspective paper argues that these substances could help treat stress-related conditions and calls for a fundamental shift in how scientists and clinicians understand the link between psychedelics, stress, and mental health.