Research published in ACS Medicinal Chemistry Letters

Novel Tetrahydropyridinyl-6,6-Bicyclic Compounds as 5‑HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches.

ACS Medicinal Chemistry Letters August 13, 2026 Ram W. Sabnis, Anika R. Sabnis

Provided herein are novel tetrahydropyridinyl-6,6-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse and headaches, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.6c00430 Full text

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

High Resolution Image Download MS PowerPoint Slide The psychedelic therapeutics field continues to evolve beyond classical hallucinogens toward integrated treatment platforms that combine optimized pharmacology, drug delivery, and clinical implementation. Recent patent applications disclose selective 5-HT2A receptor activators, precision aerosol delivery technologies for psychedelic compounds,...

DOI: 10.1021/acsmedchemlett.6c00364 Aerosol Precision medicine Nanotechnology

Novel 6,5-Bicyclic Compounds as 5-HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches

ACS Medicinal Chemistry Letters July 3, 2026 Ram W. Sabnis, Anika R. Sabnis

High Resolution Image Download MS PowerPoint Slide Provided herein are novel 6,5-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse, and headaches, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.6c00354 Headaches Receptor Agonist Drug discovery +1

Novel 5,6-Bicyclic Compounds as 5-HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches

ACS Medicinal Chemistry Letters June 3, 2026 Ram W. Sabnis, Anika R. Sabnis

Provided herein are novel 5,6-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse and headaches, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.6c00270 Full text Headaches Agonist Receptor Drug +2

Novel Tricyclic Compounds as 5‑HT2A Receptor Agonists for Treating Depression, Anxiety, Substance Abuse, and Headaches.

ACS Medicinal Chemistry Letters May 7, 2026 Ram W. Sabnis, Anika R. Sabnis

Provided herein are novel tricyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse and headaches, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.6c00235 Full text

Novel Indoline Derivatives Serotonergic Psychedelic Agents as 5‑HT2A Agonists for Treating Psychosis, Mental Illness and CNS Disorders.

ACS Medicinal Chemistry Letters April 27, 2026 Ram W. Sabnis, Anika R. Sabnis

Provided herein are novel indoline derivatives serotonergic psychedelic agents as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.6c00208 Full text

Chemical Design and Pharmacokinetics Enable Precision Psychedelic Therapeutics.

ACS Medicinal Chemistry Letters January 12, 2026 Anna C. Renner, Robert B. Kargbo

Recent psychedelic patent activity highlights a strategic shift from experiential framing toward chemically and pharmacokinetically precise neurotherapeutics. Four recent patent applications collectively span solid-state control of psilocybin, exposure-shaped intramuscular and infusion-based dosing, and chemically diversified monoaminergic scaffolds with defined transporter and receptor...

DOI: 10.1021/acsmedchemlett.5c00780

From Solid-State Control to Predictive Precision: Building a Deployable Ecosystem for Psychedelic Therapeutics.

ACS Medicinal Chemistry Letters January 12, 2026 Anna C. Renner, Robert B. Kargbo

Two recent patent applications illustrate how psychedelic drug development is expanding beyond molecules and experiences toward deployable therapeutic systems. One focuses on solid-state optimization of a lysergamide analogue to ensure manufacturability and stability, while the other applies machine-learning-driven neurophysiological biomarkers to predict patient response. Together, they...

DOI: 10.1021/acsmedchemlett.5c00782

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

Emerging psychedelic therapeutics increasingly rely on mechanistic precision, receptor selectivity, and pharmacokinetic control. Recent inventions introduce simplified iboga analogs with tunable polypharmacology, real-time EEG biomarkers that individualize psilocybin dosing, and standardized harmine-DMT ratios with high bioavailability. Together, these innovations form a coherent framework for...

DOI: 10.1021/acsmedchemlett.5c00714 Full text Psilocybin Electroencephalography Hallucinogen Investigational drugs +1

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

New inventions introduce complementary advances across neuropsychiatric therapeutics: a blood-based gene-expression diagnostic centered on FOXG1 for objective PTSD detection; benzocyclobutenyl-methylamine modulators that normalize neuronal hyperexcitability; and templated-carrier sublingual 5-MeO-DMT formulations enabling controlled, nonhallucinogenic neuroplasticity. Together, these approaches...

DOI: 10.1021/acsmedchemlett.5c00716 Full text Scalability Computational biology Precision medicine Bioinformatics

Engineering the Next Generation of Psychedelic Therapeutics through Serotonergic Precision and Pharmacokinetic Control.

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

High Resolution Image Download MS PowerPoint Slide Recent patents unveil a new wave of psychedelic analogs optimized for 5-HT 2 A receptor modulation, reduced adverse effects, and tunable duration of action. By refining DMT and psilocin scaffolds through prodrug design, fluorination, and structure–activity exploration, these innovations promise safer, shorter-acting psychedelic medicines that...

DOI: 10.1021/acsmedchemlett.5c00661

Novel Psilocin Derivatives as Serotonergic Psychedelic Agents for Treating CNS Disorders

ACS Medicinal Chemistry Letters October 22, 2025 Ram W. Sabnis

High Resolution Image Download MS PowerPoint Slide Provided herein are novel psilocin derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating central nervous system (CNS) disorders, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00608 Serotonergic Serotonin Central nervous system Hallucinogen +1

Stabilizing Psilocybin Pharmacology and Tuning Safety with Atypical Antipsychotic Cotherapy

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

A crystalline cocrystal of psilocin and psilocybin enhances exposure, neuroplasticity biomarkers, and functional activity, while adjunctive atypical antipsychotics modulate serotonergic signaling to mitigate 5-HT2B-linked safety concerns. Together, these inventions advance formulation, mechanistic selectivity, and translational biomarkersoffering a chemistry-enabled path to scalable...

DOI: 10.1021/acsmedchemlett.5c00595

Toward Precision Psychedelic Therapies: Chemical, Computational, and Neuromodulatory Innovations.

ACS Medicinal Chemistry Letters October 9, 2025 Anna C. Renner, Robert B. Kargbo

Recent patents disclose complementary strategies to optimize psychedelic-assisted therapy. Novel psilocin prodrugs improve pharmacokinetics and stability, while digital systems enable cognitive state monitoring during treatment. Parallel advances in combining neuroplastogen drugs with transcranial electrical stimulation highlight a model-driven approach to enhance and personalize neural...

DOI: 10.1021/acsmedchemlett.5c00597

Novel Serotonergic Psychedelic Agents as 5-HT2A Agonists for Treating Psychosis, Mental Illness, and CNS Disorders

ACS Medicinal Chemistry Letters August 25, 2025 Ram W. Sabnis

High Resolution Image Download MS PowerPoint Slide Provided herein are novel serotonergic psychedelic agents as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00484 Serotonergic Serotonin Psychosis Mental illness +3

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

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

Novel phenalkylamines and tryptamines such as psilocybin demonstrate promising nontraditional pharmacological profiles for treating psychiatric syndromes. Structural modifications yield functional selectivity at 5-HT receptors, mitigating hallucinogenic risk while preserving therapeutic efficacy. This study integrates receptor and behavioral data to support phenalkylamines and psilocybin as...

DOI: 10.1021/acsmedchemlett.5c00475 Full text Psilocybin Agonism Hallucinogen Divergence linguistics +3

Novel Non-Hallucinogenic Compounds as 5‑HT2A Agonists for Treating Mental Health Disorders, Namely Depression, Anxiety, Stress Disorders, and Eating Disorders.

ACS Medicinal Chemistry Letters August 14, 2025 Ram W. Sabnis

Provided herein are novel nonhallucinogenic compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating mental health disorders, namely depression, anxiety, stress disorders and eating disorders, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00476 Full text

Novel Non-hallucinogenic Neurite Growth Compounds as 5‑HT2A Agonists for Treating Stress-Related Disorders, Namely Depression, Anxiety, and PTSD.

ACS Medicinal Chemistry Letters July 30, 2025

Provided herein are novel non-hallucinogenic neurite growth compounds as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating stress-related disorders, namely depression, anxiety, and post-traumatic stress disorder (PTSD), and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00440 Full text

Novel Tricyclic Psychedelic Psychoplastogens as 5‑HT2C Agonists for Treating Neurological Diseases.

ACS Medicinal Chemistry Letters June 29, 2025 Ram W. Sabnis

Provided herein are novel tricyclic psychedelic psychoplastogens as 5-HT2C agonists, pharmaceutical compositions, use of such compounds in treating neurological diseases, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00381 Full text

Novel Phenoxy and Benzyloxy Substituted Psychedelic Psychoplastogens as 5‑HT2C Agonists for Treating Neurological Diseases.

ACS Medicinal Chemistry Letters June 19, 2025 Ram W. Sabnis

Provided herein are novel phenoxy and benzyloxy substituted psychedelic psychoplastogens as 5-HT2C agonists, pharmaceutical compositions, use of such compounds in treating neurological diseases, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00363 Full text

Novel N‑Substituted Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders.

ACS Medicinal Chemistry Letters June 16, 2025 Ram W. Sabnis

Provided herein are novel N-substituted indole derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00346 Full text

Novel Indole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders.

ACS Medicinal Chemistry Letters June 12, 2025 Ram W. Sabnis 4 citations

Provided herein are novel indole derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00309 Full text Brain conditions Neurological Psychiatric Psychosis +6

Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy.

ACS Medicinal Chemistry Letters June 12, 2025 Robert B. Kargbo 1 citation

Innovative formulations of N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) enable parenteral and intranasal delivery, respectively. These delivery systems overcome limitations of poor bioavailability and rapid metabolism, offering rapid-onset, short-duration therapeutic effects. The compositions support controlled psychedelic interventions for psychiatric...

DOI: 10.1021/acsmedchemlett.5c00265 Full text 5-MEO-DMT Treatment-resistant depression Entheogenic treatment Hallucinogen-assisted therapy +9

Design and Evaluation of Substituted Tryptamines for Nonpsychedelic Modulation of Metabolic and Neuropsychiatric Pathways.

ACS Medicinal Chemistry Letters June 12, 2025 Robert B. Kargbo

Substituted tryptamines with selective 5-HT2A/2C activity demonstrate therapeutic promise without psychedelic effects. Two recent patent applications describe nonhallucinogenic analogs for metabolic and neuropsychiatric disorders. These agents exhibit optimized receptor selectivity, metabolic synergy, and neuroplastic potential, offering a novel chemical framework for multimodal treatment...

DOI: 10.1021/acsmedchemlett.5c00263 Full text Drug development Drug discovery Pharmaceutical research Novel compounds +8

Novel Benzofuran and Benzothiophene Psychedelic Psychoplastogens as 5‑HT2C Agonists for Treating Neurological Diseases.

ACS Medicinal Chemistry Letters June 11, 2025 Ram W. Sabnis

Provided herein are novel benzofuran and benzothiophene psychedelic psychoplastogens as 5-HT2C agonists, pharmaceutical compositions, use of such compounds in treating neurological diseases, and processes for preparing such compounds.

DOI: 10.1021/acsmedchemlett.5c00345 Full text

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