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ACS Medicinal Chemistry Letters

ISSN 1948-5875

14 papers in the library · 92 citations · publishing 2020-2026

Papers

Psilocybin Therapeutic Research: The Present and Future Paradigm

ACS Medicinal Chemistry Letters March 2, 2020 Robert B. Kargbo 48 citations

Psilocybin, the active component in magic mushrooms, may offer therapeutic benefits for conditions like major depressive disorder and addiction without the addictiveness or overdose risk of drugs such as cocaine, heroin, alcohol, and methamphetamine. The need for new treatments is urgent due to rising rates of addiction, overdose, and suicide in the United States and worldwide. Anecdotal and contemporary pharmacological reports suggest psilocybin's potential for treating mental health disorders. This Viewpoint summarizes current psilocybin therapeutic research and offers insights into future directions for scientific focus.

Microbiome–Gut–Brain Axis Modulation: New Approaches in Treatment of Neuropsychological and Gastrointestinal Functional Disorders

ACS Medicinal Chemistry Letters May 11, 2023 Robert B. Kargbo 15 citations

The gut-brain axis (GBA) is a bidirectional communication system linking the digestive system and the central nervous system through neuro-immune and hormonal pathways. The gut microbiome plays a key role in this communication, influencing mental health. This Patent Highlight describes methods to promote colonization of spore-forming bacteria in the gastrointestinal tract by administering serotonin receptor agonists, including psychedelic compounds such as psilocybin, psilocin, N,N-dimethyltryptamine, bufotenine, 5-methoxy-N,N-dimethyltryptamine, lysergic acid diethylamide, ergine, mescaline, 3,4-methylenedioxyamphetamine, and 2,5-dimethoxy-4-methylamphetamine.

5-MeO-DMT: Potential Use of Psychedelic-Induced Experiences in the Treatment of Psychological Disorders

ACS Medicinal Chemistry Letters October 21, 2021 Robert B. Kargbo 15 citations

5-MeO-DMT, a potent psychedelic, may be useful in treating psychological disorders by inducing profound experiences that facilitate therapeutic breakthroughs. The article discusses how psychedelic-induced experiences could help patients with conditions such as depression, anxiety, and addiction by promoting neuroplasticity and emotional processing. It highlights the potential of 5-MeO-DMT to produce rapid and sustained improvements in mental health, though further research is needed to understand its mechanisms and optimize therapeutic protocols. The work emphasizes the importance of set and setting in maximizing therapeutic outcomes and minimizing risks.

Tryptamines and Mental Health: Activating the 5-HT Receptor for Therapeutic Potential

ACS Medicinal Chemistry Letters September 15, 2023 Robert B. Kargbo 11 citations

Tryptamines, which activate serotonin receptors, are being investigated as potential treatments for mental health disorders. The FDA has designated psilocybin and MDMA as breakthrough therapies for conditions like treatment-resistant depression, major depressive disorder, and PTSD. Clinical trials show significant improvements in patient-reported outcomes through reductions in experiential avoidance, indicating a promising future for these compounds in mental health therapy.

Advancements in Psychoactive Alkaloid Delivery, Neuroenhancement, and Psychedelic Therapies: Exploring the Frontiers of Modern Pharmacology

ACS Medicinal Chemistry Letters May 8, 2024 Robert B. Kargbo 2 citations

Advancements in pharmacology are being made through novel delivery and application of psychoactive substances. Innovations include transdermal formulations for psychoactive alkaloids, neuroenhancement techniques to augment emotional responses, and intravenous infusion of psilocybin or psilocin for therapeutic purposes. The characterization and potential uses of crystalline forms of tryptamine derivatives are also explored. These developments represent progress in drug delivery systems, neurostimulation methods, and the therapeutic use of psychedelic compounds, potentially revolutionizing treatment for psychological and neurological disorders.

Expanding the Therapeutic Horizons of Psilocybin in Mental Health

ACS Medicinal Chemistry Letters October 15, 2024 Robert B. Kargbo 1 citation

Psilocybin, a naturally occurring psychedelic compound, shows promise as a therapeutic agent for mental health. Innovations include clinical trials targeting severe psychiatric conditions, incorporating low-dose psilocybin into dietary products for general mental well-being, and personalizing dosing for optimal treatment of depression and anxiety. These developments highlight psilocybin's versatility and potential to transform conventional mental health treatment through personalized medicine and accessible wellness applications.

Advancing Next-Generation Psychedelic Therapeutics through Selective 5-HT2A Activation, Precision Aerosol Delivery, and Optimized 5-MeO-DMT Treatment Paradigms

ACS Medicinal Chemistry Letters July 10, 2026 Anna C. Renner, Robert B. Kargbo

The psychedelic therapeutics field is moving beyond classical hallucinogens to integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications describe selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds, and structured 5-MeO-DMT treatment regimens for depression. These innovations represent a convergence toward scalable, safer, and clinically practical neuropsychiatric therapies that may reshape the future of serotonergic medicine.

Molecular Diagnostics, Circuit-Calming Modulators, and Controlled Neuroplastogens: Emerging Strategies in Precision Neuropsychiatric Therapeutics

ACS Medicinal Chemistry Letters December 16, 2025 Anna C. Renner, Robert B. Kargbo

Three new approaches in neuropsychiatric therapeutics are converging: a blood test measuring FOXG1 gene expression for objective PTSD detection; benzocyclobutenyl-methylamine compounds that reduce excessive neuronal firing; and a sublingual 5-MeO-DMT formulation that promotes neuroplasticity without hallucinations. These advances link molecular diagnostics, targeted neural circuit modulation, and scalable treatments for affective disorders.

Advances in Psychedelic Therapeutics: Multimodal Iboga Analogs, EEG-Guided Psilocybin Dosing, and Optimized Harmine–DMT Formulations

ACS Medicinal Chemistry Letters December 16, 2025 Anna C. Renner, Robert B. Kargbo

Recent inventions create a framework for safer, more reliable psychedelic medicines. Simplified iboga analogs offer tunable polypharmacology, real-time EEG biomarkers personalize psilocybin dosing, and standardized harmine-DMT ratios achieve high bioavailability. These innovations improve mechanistic precision, receptor selectivity, and pharmacokinetic control.

Stabilizing Psilocybin Pharmacology and Tuning Safety with Atypical Antipsychotic Cotherapy

ACS Medicinal Chemistry Letters October 10, 2025 Anna C. Renner, Robert B. Kargbo

A new crystalline cocrystal combining psilocin and psilocybin increases drug exposure, boosts markers of neuroplasticity, and alters functional brain activity. Adding atypical antipsychotics to the treatment changes serotonin signaling, reducing safety risks linked to the 5-HT2B receptor, which is associated with heart valve problems. These chemical advances improve how the therapy works, its selectivity for desired effects, and the ability to measure its impact in lab models. Together, they offer a chemistry-based way to develop scalable psychedelic treatments that are safer for the heart and produce lasting neuroplastic changes, as shown in organoid and animal studies.

Therapeutic Divergence in 5-HT2A Agonism: Psilocybin and Phenalkylamines for Demoralization Syndrome

ACS Medicinal Chemistry Letters August 15, 2025 Robert B. Kargbo

Certain novel compounds, including psilocybin, show promise for treating psychiatric conditions through unique pharmacological actions. By modifying their chemical structure, researchers can achieve functional selectivity at serotonin (5-HT) receptors, reducing hallucinogenic effects while maintaining therapeutic benefits. The work combines receptor-level and behavioral evidence to support these compounds as rational treatments for demoralization syndrome and depression-related disorders.

Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies

ACS Medicinal Chemistry Letters April 10, 2025 Robert B. Kargbo

Psilocybin reduces phantom and residual limb pain by a clinically meaningful amount. Adaptive sensory environments (ASEs) use biosensors to guide modulation of psychological states during psychoactive therapy. This Patent Highlight reviews pharmacological findings from a psilocybin trial and discusses future integration with ASE systems to improve precision and scalability of psychedelic-assisted interventions.

Current Trends in Psychedelic Science: Integrating Modified Lysergic Acid Derivatives and Psilocybin in Modern Medicine

ACS Medicinal Chemistry Letters August 21, 2024 Robert B. Kargbo

Recent psychedelic research has produced lysergic acid derivatives with modified LSD-like effects, a psilocybin dosing method guided by ABCF1 gene expression, and new treatments for binge eating disorder. Neuroenhancement techniques that boost emotional responses are also being explored. These developments point toward personalized medicine and expanded mental health applications, signaling a transformative phase in clinical psychedelic use.

Exploring the Therapeutic Potential of Entheogens in Postoperative Cognitive Decline and Psychological Resilience

ACS Medicinal Chemistry Letters August 21, 2024 Robert B. Kargbo

A review of three patent applications examines the potential of entheogens such as psilocybin to treat cognitive decline and bolster psychological resilience in patients receiving anesthesia or sedation. The article describes proposed therapeutic mechanisms, treatment methods, and possible clinical outcomes for postoperative care. It provides an overview of this emerging approach without presenting original data or empirical findings.