ISSN 1948-5875
18 papers in the library · 39 citations · publishing 2023-2025
ACS medicinal chemistry letters January 9, 2025 Ram W Sabnis 7 citations
No Summary
ACS medicinal chemistry letters February 8, 2024 Navoda Jayakodiarachchi, Mallory A Maurer, Daniel C Schultz et al. 6 citations
A new set of indazole-based compounds was synthesized and tested as potent agonists of the serotonin 5-HT2 receptor subtypes. The direct indazole analogs of 5-MeO-DMT showed strong activity, but many, including the optimized compound VU6067416 (19d), also acted as potent 5-HT2B agonists, which prevented further development due to safety concerns. Computational docking studies suggest that the high potency of 19d may arise from a halogen-bonding interaction with Phe2345.38 in the 5-HT2A binding pocket. The work underscores the importance of rigorous subtype selectivity profiling for these serotonergic compounds.
ACS medicinal chemistry letters September 14, 2023 Marie Layzell, Peter Rands, Meghan Good et al. 6 citations
A deuterated analogue of DMT, called D2-DMT, has a longer half-life and slower clearance in liver cell fractions than standard DMT while maintaining a similar receptor binding profile, making it a promising candidate for extended treatment of major depressive disorder.
ACS medicinal chemistry letters June 12, 2025 Ram W Sabnis 4 citations
A new class of indole derivatives has been developed as serotonergic psychedelic agents. These compounds, along with pharmaceutical compositions containing them, are intended for use in treating psychosis, mental illness, and other central nervous system disorders. The work also describes processes for preparing these novel compounds.
ACS medicinal chemistry letters April 13, 2023 Robert B. Kargbo 4 citations
This patent describes prodrugs—compounds that are metabolically converted into active forms—of DMT, 5-MeO-DMT, and MDMA. When given to a subject, these prodrugs could potentially be used to treat neurological diseases. The disclosure outlines methods for potentially treating conditions including major depressive disorder, post-traumatic stress disorder, Alzheimer's disease, Parkinson's disease, schizophrenia, frontotemporal dementia, Parkinson's dementia, dementia, Lewy body dementia, multiple system atrophy, or substance abuse.
ACS medicinal chemistry letters November 14, 2024 Robert B. Kargbo 3 citations
Recent patents show new ways to use the psychedelic compounds 5-MeO-DMT and DMT to treat mental health disorders like depression, anxiety, and trauma-related conditions. Innovations include combining 5-MeO-DMT with mood preparation agents to improve safety and effectiveness, creating DMT prodrugs for better drug absorption and processing in the body, and designing tailored therapies for specific groups such as breastfeeding mothers. These developments offer potential new options for patients with treatment-resistant mental disorders, reflecting the growing role of psychedelics in mental health care.
ACS medicinal chemistry letters September 14, 2023 Robert B. Kargbo 3 citations
Psychoplastogens—substances that stimulate neuronal growth and enhance neural structures—may help counteract changes in synaptic connectivity and plasticity common in neurological diseases. These compounds activate key targets such as AMPA receptors, TrkB, and mTOR. Examples include ketamine, scopolamine, N,N-dimethyltryptamine, and rapastinel. Clinical trials show psychedelic psychoplastogens have antidepressant, anxiolytic, and anti-addictive effects. The patent highlights potential novel therapies for neurological disorders by modulating synaptic connections and plasticity.
ACS medicinal chemistry letters July 13, 2023 Robert B. Kargbo 2 citations
A patent describes a method for treating inflammatory or neurological disorders by administering a composition containing a subhallucinogenic dose of a substituted phenethylamine, such as those from the 2C-X family (e.g., 2C-H, 2C-I, 2C-B, or 2C-E). The dose depends on the severity of chronic inflammation: 25 mg for mild, 50 mg for moderate, and 100 mg for severe cases. The method is intended for subjects in need of treatment.
ACS medicinal chemistry letters June 12, 2025 Robert B. Kargbo 1 citation
New formulations of the psychedelic compounds DMT and 5-MeO-DMT allow injection or nasal spray delivery, bypassing the body's rapid breakdown of these drugs. These delivery methods produce fast-acting, short-lived therapeutic effects, making them suitable for controlled psychiatric treatments like depression that does not respond to standard therapies. The formulations aim to improve tolerability, ease of use, and clinical practicality.
ACS medicinal chemistry letters May 8, 2025 Robert B. Kargbo 1 citation
DMT produces fast-acting antidepressant effects, but its use is limited by acute side effects like high blood pressure and rapid heart rate. This work describes coformulations of DMT with short-acting beta-blockers or nitrates that are matched to DMT's pharmacokinetics. These combinations reduce peripheral cardiovascular risks without interfering with the central therapeutic effects, potentially enabling safer psychedelic therapy for vulnerable populations.
ACS medicinal chemistry letters August 8, 2024 Robert B. Kargbo 1 citation
Ketamine, originally an anesthetic, is now used for depression and chronic pain but causes side effects like hallucinations and dizziness from rapid blood concentration spikes. Recent patents describe new delivery methods: subcutaneous injections, ketamine conjugates with other molecules, and dual-release formulations combined with aspirin. These innovations aim to improve how the drug is absorbed and processed in the body, potentially enhancing therapeutic outcomes and safety.
ACS medicinal chemistry letters January 11, 2024 Robert B. Kargbo 1 citation
Psychedelic compounds such as ketamine and LSD promote neuronal growth by activating AMPA receptors, TrkB, and mTOR, acting as psychoplastogens. The prefrontal cortex exerts top-down control over brain regions involved in motivation, fear, and reward, contributing to therapeutic effects. These compounds enhance synaptic plasticity and neurogenesis, producing antidepressant effects, and modulate fear circuits to provide anxiolytic properties. They also disrupt addictive patterns and promote neuroplasticity, showing promise as anti-addictive agents. This exploration reveals new opportunities for treating major depressive disorder, anxiety, and addiction.
ACS medicinal chemistry letters June 12, 2025 Robert B. Kargbo
New non-hallucinogenic compounds based on substituted tryptamines show promise for treating metabolic and neuropsychiatric disorders by selectively targeting 5-HT2A/2C receptors. Two recent patent applications describe analogs that avoid psychedelic effects while offering optimized receptor selectivity, potential metabolic benefits, and the ability to promote neuroplasticity. These agents represent a novel chemical framework for multimodal treatment strategies in brain disorders and metabolic health.
ACS medicinal chemistry letters April 10, 2025 Robert B. Kargbo
Advancements in psychedelic therapeutics, tryptamine derivatives, neuroplastic modulators, and AI-powered machine-learning platforms are opening new possibilities in precision medicine. These innovations target neurological and psychiatric disorders, chronic pain, and computational accessibility through receptor modulation, targeted delivery, and simplified AI integration. They promise transformative solutions for patient care and technological development.
ACS medicinal chemistry letters April 10, 2025 Robert B. Kargbo
Psychedelics and artificial intelligence both alter cognitive frameworks, disrupt rigid thinking, and boost neuroplasticity, which may help treat depression, PTSD, and addiction. By relaxing neural filters, they induce altered states of consciousness that challenge how reality is perceived. This viewpoint examines the neurobiological mechanisms behind these effects and considers how AI could enhance psychiatric treatments.
ACS medicinal chemistry letters February 13, 2025 Robert B. Kargbo
Combining monoamine antidepressants with short-duration psychedelics like DMT and psilocybin, alongside AI-driven behavioral tracking, may offer rapid and sustained improvements for treatment-resistant depression and anxiety. AI-enhanced monitoring uses motion tracking and machine learning to quantify outcomes in animal models, speeding drug development. These approaches aim to personalize psychiatric care.
ACS medicinal chemistry letters December 12, 2024 Robert B. Kargbo
Psychedelic compounds like psilocybin and psilocin show therapeutic promise for neurological and psychiatric disorders, but their clinical use is limited by poor bioavailability, rapid metabolism, and stability issues. This Patent Highlight reviews recent innovations in drug delivery systems and psilocin analogs, including controlled-release systems, ester analogs, and acetal/ketal derivatives. These patents present novel approaches to improving stability, bioavailability, and efficacy, potentially leading to more effective treatments for depression, chronic pain, and neurodegenerative diseases.
ACS medicinal chemistry letters March 14, 2024 Robert B. Kargbo
Recent innovations in neurostimulation, psychedelic therapy, and brain function optimization are advancing personalized brain therapy. Methods for altering brain states include AI-driven non-invasive neurostimulation. The therapeutic potential of N-isopropyl tryptamines and tryptamine derivatives is examined, alongside psilocybin and psilocin crystalline forms for mental health and central nervous system disorders. These diverse approaches are compared for their mechanistic insights and therapeutic implications, contributing to neuroscience and mental health.