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.
ACS Pharmacology & Translational Science
July 12, 2024
Albert Dahan, Simone C Jansen, Rutger van der Schrier et al.
8 citations
The anesthetic, analgesic, and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.
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 Pharmacology & Translational Science
September 18, 2023
Richa Tyagi, Tanishka S. Saraf, Clinton E. Canal
5 citations
A psychedelic tryptamine, DPT, completely prevented sound-induced seizures in a mouse model of fragile X syndrome at a 10 mg/kg dose but not at lower doses. Although DPT activates several serotonin receptors in the lab, blocking those receptors did not stop its anti-seizure effect, nor did blocking sigma1 receptors. The anti-seizure action appears independent of DPT's psychedelic properties. However, high doses of DPT caused convulsions on their own, indicating complex, dose-dependent effects.
ACS Pharmacology & Translational Science
August 22, 2025
Devin P. Effinger, Serena S. Schalk, Jillian L. King et al.
3 citations
Microdosing involves taking psychedelics at doses too low to cause hallucinations, and is popular for supposed cognitive and emotional benefits. Psychedelics bind strongly to 5-HT 2B receptors, which can cause heart disease when chronically activated. In mice, researchers gave either serotonin or d-fenfluramine as positive controls, or low doses of LSD. Serotonin caused significant ventricular thickening at 4 and 8 weeks; d-fenfluramine caused aortic valve regurgitation at 4 weeks. No significant heart changes appeared in any LSD group. LSD, psilocybin, and norfenfluramine had similar affinity and potency at mouse and human 5-HT 2B receptors. Low-dose LSD produced substantial but short-lived receptor activation compared to d-fenfluramine. These data provide no evidence that prolonged low-dose LSD causes heart remodeling in mice.
ACS Pharmacology & Translational Science
July 16, 2025
Tobías Fernández-Borkel, Lucas F Borkel, Jaime Rojas-Hernández et al.
3 citations
A proposed randomized controlled trial aims to determine whether the subjective psychedelic experience caused by psilocybin is necessary for its antidepressant effects in treatment-resistant depression, or whether neurobiological actions alone suffice. The protocol compares three groups: psilocybin while conscious, psilocybin under propofol-induced general anesthesia (which eliminates subjective experience), and anesthesia with placebo. Clinical assessments and fMRI measures of brain connectivity will be collected. The authors hypothesize that the conscious psilocybin group will show superior improvements in depression and anxiety, and that increased brain fractal complexity and entropy will correlate with therapeutic gains. The results could clarify the causal role of conscious experience in psychedelic therapy.
ACS Pharmacology & Translational Science
May 29, 2025
Meghan Hibicke, Erik Kaadt, Emil Märcher-Rørsted et al.
3 citations
A new compound, LPH-5, acts as a potent partial agonist at the 5-HT2A receptor with high selectivity over related 5-HT2B and 5-HT2C receptors. In rats, LPH-5 induced head-twitch responses and produced both acute and persistent antidepressant-like effects. These findings suggest that selective activation of the 5-HT2A receptor alone can produce antidepressant effects, indicating that this receptor is a key component in the therapeutic action of classical psychedelics like psilocybin and LSD.
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.
ACS Pharmacology & Translational Science
December 8, 2023
Richard A Glennon, Mal Gorzata Dukat
3 citations
Alpha-ethyltryptamine (AET), a centrally acting agent known for over 75 years, was briefly marketed as an antidepressant before being withdrawn and classified as a U.S. Schedule I substance due to concerns about abuse and toxicity. Amid current interest in hallucinogenic tryptamines for treating neuropsychiatric disorders like treatment-resistant depression and anxiety, this review critically examines AET's history and argues that it may have been ahead of its time. AET possesses many antidepressant hallmarks, suggesting that its derivatives and optical isomers warrant further investigation.
ACS Pharmacology & Translational Science
October 10, 2025
Milo Moskovitz
2 citations
Music is central to psychedelic-assisted therapy, yet only three empirical studies have directly examined which music best supports treatment. A critical review finds these studies have important limitations and their findings conflict with other publications and existing recommendations. Understanding of music guidelines has not advanced much since 1970. The paper summarizes music's common impacts during therapy, reviews current knowledge on music selection and guidelines, and suggests priorities for future research.
ACS Pharmacology & Translational Science
September 11, 2025
Noelle Cataldo, John A. Razidlo, Cody J. Wenthur
2 citations
Psilocybin, a serotonergic psychedelic, enhanced fear extinction and improved extinction recall 24 hours later in male mice, regardless of whether they were stress-naïve or had been exposed to acute or chronic stress beforehand. Psilocybin transiently increased the stress hormone corticosterone in stress-naïve mice but not in previously stressed animals. The findings suggest psilocybin can promote fear extinction across different stress backgrounds, supporting its potential therapeutic relevance for disorders like PTSD where prior stress is a key factor.
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.
ACS Pharmacology & Translational Science
August 8, 2025
Kate Browne, Ewa Bałkowiec-iskra, André Elferink et al.
1 citation
Marketing authorization applications for psychedelics in the European Union must meet the same regulatory and evidentiary standards as all other medicinal products. The European Medicines Agency identifies key knowledge gaps that complicate pivotal trial design and benefit-risk assessment, including functional unblinding, expectancy and nocebo effects, and the need to align trial populations with the intended therapeutic indication. Development programs should characterize dose-response relationships and the link between subjective experience and therapeutic response. Decisions about incorporating psychological support or psychotherapy affect trial design and conditions of use. Safety characterization requires adequately powered trials, appropriate controls, risk mitigation strategies, continuous monitoring, and ethical consideration.
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.
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.
ACS Pharmacology & Translational Science
April 14, 2026
Abhishek Gupta, Tuhin Bhattacharya, Subhamoy Pratihar et al.
Iboga alkaloids can reverse drug addiction and modulate drug tolerance, but their use is limited by severe psychedelic effects and cardiotoxicity from hERG potassium channel blockade. Researchers synthesized four modified ibogaine/ibogamine analogs (C1–C4) with a benzofuran moiety replacing the indole scaffold. Among these, the Endo-iboga analogs C2 and C4 showed notable anti-inflammatory and oxidative stress-relieving activity and improved restricted locomotor activity in a formalin-induced acute pain model in mice. C4 exhibited superior cytocompatibility (IC50 = 235 μM in C2C12 cells), no significant QTc prolongation in rat ECG tests, and the lowest hERG blockade risk (IC50 = 21.25 ± 4.89 μM). C4 acted as a potent KOR agonist and MOR antagonist, with weak 5HT2A agonist and σ1 antagonist activity, suggesting potential for acute pain management without notable cardiotoxicity.
ACS Pharmacology & Translational Science
March 13, 2026
Bo Jarrett Wood, M Frances Vest, Catharine Carfagno et al.
In male mice, chronic treatment with the SSRI fluoxetine (Prozac) reduced the head-twitch response—a behavioral sign of 5-HT2A receptor activation—caused by the psychedelic DOI, while acute fluoxetine had no effect on DOI. The reduced response reversed after a 14-day discontinuation of fluoxetine. Acute fluoxetine also weakened the efficacy (but not potency) of psilocybin, indicating that SSRI-psychedelic interactions may differ depending on the specific psychedelic compound. These results suggest that a history of SSRI use can alter sensitivity to psychedelics in a compound-specific manner, with implications for psychedelic-assisted therapy in people taking SSRIs.
ACS Pharmacology & Translational Science
September 12, 2025
Junjie Zhang, Xiubo Du, Xinying Li et al.
Controlled reductions in oxygen availability—whether through psychedelics, near-death experiences, meditation, holotropic breathwork, or hypoxia therapies—may trigger calcium signaling pathways that promote synaptogenesis and the formation of new neural circuits. This process could enable functional rerouting rather than restoring damaged connections, supporting cognitive resilience and behavioral compensation in conditions such as stroke, Alzheimer's disease, and psychiatric disorders. Terminal lucidity in late-stage dementia may be driven by transient hypoxia, highlighting the brain's latent capacity for rapid reorganization. Integrating insights from psychedelic research, hypoxia-based therapies, and neuroplasticity studies suggests a unifying framework that leverages altered oxygen homeostasis as a novel therapeutic strategy for neuropsychiatric and neurodegenerative diseases.
ACS Pharmacology & Translational Science
June 11, 2021
Justin C Strickland, Albert Garcia‐romeu, Matthew W Johnson
correction
No Summary
ACS Pharmacology & Translational Science
February 25, 2021
E. Pottie, O. Kupriyanova, Asher L. Brandt et al.
Five positional isomers of the psychedelic compound 25H-NBOMe, each differing in the placement of two methoxy groups on the phenyl ring of the phenethylamine moiety, were tested in split-nanoluciferase assays to measure their ability to recruit cytosolic proteins to the serotonin 2A receptor. Molecular docking simulations estimated which receptor residues interact with each isomer's methoxy groups. This is the first comparative evaluation of how the positioning of methoxy groups in the phenethylamine moiety of NBOMes affects functional activity at the receptor.
ACS Pharmacology & Translational Science
December 29, 2020
Justin C Strickland, A. Garcia-Romeu, Matthew W. Johnson
Psilocybin, a serotonin 2A receptor agonist, shows promise as a psychiatric treatment, but little is known about how session context ("set and setting") affects outcomes. In a study on smoking cessation, ten participants received psilocybin (20–30 mg/70 kg) in two sessions, each with a different musical genre—Western classical or overtone-based—in counterbalanced order. Mystical experience scores tended to be higher during overtone-based sessions. Six of ten participants chose overtone-based music for a third session. Biologically confirmed smoking abstinence was similar between groups, with a slight benefit for those choosing overtone-based music (66.7% versus 50%). The findings question whether Western classical music typically used in psychedelic therapy is uniquely beneficial.