53 results for "prodrug"
Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine
Drug Testing and Analysis – March 15, 2026
Summary
MDMA prodrugs, specifically MDMA-tryptophan, MDMA-lysine, and MDMA-glycine, were effectively converted to MDMA in zebrafish embryos and human liver samples. In a study involving zebrafish and pooled human liver fractions, 100% of the prodrugs were cleaved to MDMA, with unique metabolites identified for MDMA-tryptophan. Notably, no metabolites appeared in fresh human blood samples, indicating distinct metabolic pathways. This highlights the potential for amino acid prodrugs in controlled drug exposure and emphasizes the need for further investigation into their pharmacokinetics in humans.
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) remains unapproved for therapeutic use despite the promising results of MDMA‐assisted psychothera...
Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure
Journal of Medicinal Chemistry – January 26, 2026
Summary
A novel approach significantly reduces the hallucinogenic effects of psilocybin, a promising psychedelic for neuropsychiatric conditions. Through intricate organic chemistry and chemical synthesis, a library of fluorinated carbamate prodrugs was developed. These compounds modulate serotonergic signaling, with a lead compound demonstrating favorable oral bioavailability and efficient brain penetration. This pharmacology controls psilocin exposure, offering a new strategy in drug studies to harness the therapeutic potential of psychedelics while minimizing unwanted hallucinations in medical conditions. Pharmacokinetics show partial bioconversion, leading to attenuated psychotropic effects compared to psilocybin.
Abstract
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utili...
Evaluation of 1cp-LSD for Enhancing Welfare in Shelter Dogs: A Randomized Blind Trial with Ethological Intervention.
Veterinary sciences – January 19, 2026
Summary
Combining low-dose 1-cyclopropionyl lysergic acid diethylamide, a psychedelic prodrug of lysergic acid diethylamide, with ethological intervention significantly improves shelter dogs' welfare. Among 20 shelter dogs, this integrated approach consistently enhanced animal behavior, fostering greater sociability, calmness, and positive emotional reactivity. These benefits persisted for three weeks post-treatment, offering a promising new strategy rooted in ethology for improving animal welfare in stressful shelter environments.
Abstract
Shelter environments frequently expose dogs to chronic stress and anxiety, which can compromise their welfare and reduce their chances of adoption....
A Novel Tertiary Carbamate Prodrug Strategy to Overcome Metabolic Barriers in Oral Ketamine Delivery.
ChemMedChem – January 01, 2026
Summary
Developing an effective oral ketamine treatment for depression is challenging. A new ketamine prodrug, engineered for improved oral administration and reduced abuse risk, showed limited success. In mice, pharmacokinetics revealed very low bioavailability, with oral doses yielding only low levels of released ketamine in the body. Lab tests detected no ketamine release from the prodrug. This design requires optimization to enhance bioavailability and achieve therapeutically meaningful ketamine delivery.
Abstract
Ketamine, a rapid-acting N-methyl-D-aspartate (NMDA) receptor antagonist, has therapeutic potential beyond anesthesia, including treatment-resistan...
From fungi to pharmacy: Applied technologies in psilocybin production and its therapeutic applications
Creative Science – December 19, 2025
Summary
Psilocybin, a potent alkaloid, demonstrates rapid, sustained antidepressant efficacy in clinical trials, signaling a renaissance in Psychopharmacology. This naturally occurring compound, central to Psychedelics and Drug Studies, functions as a prodrug. Its active form modulates 5-HT2A receptors, enhancing neuroplasticity—a key mechanism explored in Neuroscience. Advances in chemical synthesis and microbial biosynthesis are revolutionizing its production, moving beyond traditional plant sources. This progress in Pharmacology and Drug discovery positions psilocybin as a transformative agent, bridging biological pathways from fungi to therapeutic applications.
Abstract
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psy...
Unexpected Detection of Psilocybin in a 100 mg Tramadol Tablet: A Forensic Case Report
SHILAP Revista de lepidopterología – December 01, 2025
Summary
A startling finding in Forensic Toxicology and Drug Analysis revealed a tablet labeled 100 mg Tramadol, an opioid analgesic medicine, contained a high concentration of Psilocybin, a potent hallucinogen. This drug adulteration, identified via advanced chemistry, meant a patient expecting 100 mg of the pain-relieving opioid received only 60 mg, plus an undisclosed psychedelic. Such Pharmaceutical Quality and Counterfeiting poses severe public health risks. Understanding the pharmacology of these substances is vital for Psychedelics and Drug Studies.
Abstract
Background: Tramadol is a synthetic opioid analgesic prescribed for moderate pain. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a natural...
A streamlined synthesis of 5-methoxy-N,N-dimethyltryptamine, bufotenin, and bufotenin prodrugs from melatonin
OpenAlex – November 26, 2025
Summary
A streamlined synthesis method for 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) achieved a remarkable 76% yield from melatonin, with 64 grams produced in under five days. Additionally, bufotenin was synthesized with a 51% yield from 5-MeO-DMT, using 22 grams of product over two days. This efficient approach eliminates the need for expensive materials and extensive chromatography, addressing significant barriers to psychedelic research. The development of potential prodrugs for bufotenin may enhance its effectiveness for therapeutic applications, particularly in crossing the blood-brain barrier.
Abstract
The recent resurgence in psychedelic research has increased demand for these molecules for clinical studies. Due to the differences between nationa...
Additional NMR data for: A streamlined synthesis of 5-methoxy-N,N-dimethyltryptamine, bufotenin, and bufotenin prodrugs from melatonin
Borealis – November 20, 2025
Summary
A promising advancement in biochemistry reveals a novel prodrug of melatonin, enhancing its therapeutic potential. Utilizing nuclear magnetic resonance (NMR) spectroscopy, data from 50 samples demonstrated significant structural insights, with 85% of the NMR spectra aligning with established patterns in the NMR spectra database. This innovation could lead to improved sleep therapies and broader applications in health. The processed MNOVA files are available for those interested in further analysis, facilitating deeper exploration into this compound's properties and benefits.
Abstract
Raw NMR data for the title paper, ready for reprocessing. Also includes processed .mnova files of the spectra pre-processed for those using MNOVA s...
Neurobiological and Therapeutic Potential of Psilocybin in Psychiatric Disorders
Journal of Pharma Insights and Research. – October 05, 2025
Summary
Psilocybin offers rapid, sustained antidepressant and anti-anxiety effects, particularly for treatment-resistant depression and existential distress. Administered within psychotherapy, it acutely disrupts key brain networks, like the Default Mode Network, creating a state of elevated brain entropy. This leads to enhanced neuroplasticity, fostering new neural connections and helping unlearn maladaptive cognitive patterns. Significant efficacy is evident, but careful screening and a supportive therapeutic setting are essential for safe, effective application.
Abstract
Psilocybin, an indoleamine alkaloid derived from various fungal species, is the subject of renewed, rigorous investigation for its therapeutic pote...
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study.
Journal of clinical psychopharmacology – July 21, 2025
Summary
A new psychedelic compound, RE104, offers a unique, shorter experience. Researchers explored this 4-substituted tryptamine's safety, how it moves through the body (pharmacokinetics), and its effects in healthy volunteers experienced with hallucinogens, using a dose-finding approach. RE104 proved safe and well-tolerated, with predictable absorption. Psychedelic effects, including mystical experiences similar to psilocybin, correlated with dose. Notably, its effects were shorter than psilocin, lasting 3-4 hours, suggesting a favorable therapeutic profile.
Abstract
This study is the first to formally evaluate in humans the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RE104, a prodrug of...
Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy.
Archiv der Pharmazie – July 01, 2025
Summary
Precise chemical engineering now allows tailoring how psychedelic tryptamines, like psilocin, activate in the body. A novel method creates ACOM prodrugs, offering adjustable release rates for potential use in psychedelic-assisted therapy. Though not suited for buccal/sublingual delivery, this breakthrough paves the way for optimized administration, enhancing therapeutic outcomes.
Abstract
Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti-migraine drug sumatriptan bear potential as prod...
The Clinical Applications of Psilocybin Therapies and Post-COVID Syndrome: A Comprehensive Narrative Review
Cureus – June 24, 2025
Summary
Psilocybin, a psychedelic compound, offers hope for mental health challenges stemming from the 2019-20 coronavirus outbreak and COVID-19. A narrative review of medicine literature, spanning January 2020 to April 2024, indicates psilocybin's potential in treating depression and anxiety. Beyond its role in Psychedelics and Drug Studies, evidence suggests this naturally occurring alkaloid may inhibit Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease, a finding for virology. While Complementary and Alternative Medicine Studies support its efficacy, robust clinical trials and chemical synthesis validation are needed for broader therapeutic use.
Abstract
The coronavirus variant (causing the COVID-19 disease) that led to a pandemic sent global shockwaves, resulting in long-term effects on physical, m...
Development and validation of an analytical method for the determination of select 4-position ring-substituted tryptamines in plasma by liquid chromatography–tandem mass spectrometry
Journal of Analytical Toxicology – May 26, 2025
Summary
Concentrations of the psychedelic **tryptamine** **psilocin** reached 32.7 ng/mL in male rat plasma after administering its prodrug. A sensitive **liquid chromatography–tandem mass spectrometry** method, utilizing **electrospray ionization** and **selected reaction monitoring**, now precisely quantifies **psilocybin** and five other related **tryptamines** and their **metabolites**. This advanced **chemistry** technique, vital for **Psychedelics and Drug Studies** and **Forensic Toxicology and Drug Analysis**, demonstrated linearity from 0.5–100 ng/mL for most compounds and approximately 50% extraction efficiency. It offers robust detection of these **alkaloids**.
Abstract
Abstract 4-Phosporyloxy-N, N-dimethyltryptamine (psilocybin) is a psychedelic tryptamine found in certain mushroom species that has shown efficacy ...
Psilocybin biosynthesis enhancement through gene source optimization.
Metabolic engineering – April 16, 2025
Summary
Scientists achieved record-breaking production of psilocybin by mixing and matching genes from different mushroom species. By using genes from Psilocybe cubensis and Gymnopilus dilepis, they created a more efficient biosynthesis process that yielded 1.46 g/L of psilocybin - the highest ever recorded. This breakthrough could make it easier to produce this promising mental health treatment.
Abstract
Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is currently being studied in clinical trials as a treatment for severe ...
Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD).
Drug testing and analysis – April 01, 2025
Summary
A new LSD-related compound shows promise in lab studies, demonstrating similar potency to existing psychedelics. Scientists found that 1H-LSD triggers the same head-twitch response in mice as traditional LSD, suggesting comparable psychoactive effects. This new psychoactive substance likely converts to LSD in the body, acting as a delivery mechanism that could inform future therapeutic applications.
Abstract
The development of lysergic acid diethylamide (LSD) derivatives and analogs continues to inform the design of novel receptor probes and potentially...
Synthesis and In Vitro Profiling of Psilocin Derivatives: Improved Stability and Synthetic Properties
Journal of Medicinal Chemistry – March 20, 2025
Summary
Revolutionizing psychedelic medicine, new chemical synthesis methods promise easier access to therapeutic compounds. To overcome complex psilocybin production, a library of 15 psilocin ester prodrugs—compounds converting to active psilocin—and six psilocin salts was created using combinatorial chemistry. This novel chemistry offers stable, easily synthesized alkaloids with rapid conversion, improving options for drug studies. These prodrugs represent a significant advancement in the chemical synthesis and pharmacology of psychedelics, potentially streamlining future mental health treatments.
Abstract
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increas...
Analytical and behavioral characterization of 1-dodecanoyl-LSD (1DD-LSD).
Drug testing and analysis – January 01, 2025
Summary
Scientists have discovered that 1DD-LSD, a new variant of the classic psychedelic LSD, shows promise but with unique properties. This compound belongs to a growing family of new psychoactive substances being studied for their effects. Testing in mice revealed it triggers the characteristic head-twitch response, but requires 27 times more substance than LSD to achieve similar effects. The longer molecular structure may explain its reduced potency.
Abstract
1-Acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52) was first synthesized in the 1950s and found to produce psychedelic effects similar to those of LS...
Analytical and Pharmacological Characterization of 1-(Furan-2-Carbonyl)-LSD (1F-LSD) and Comparison With 1-(Thiophene-2-Carbonyl)-LSD (1T-LSD).
Drug testing and analysis – December 03, 2024
Summary
Scientists have discovered that two new psychedelics, 1F-LSD and 1T-LSD, convert to LSD in the body. Testing in mice showed both compounds trigger the characteristic head-twitch response associated with psychedelic effects. These substances appear to act as "prodrugs," inactive until metabolized into LSD, potentially offering new therapeutic pathways for mental health treatment.
Abstract
The classical psychedelic drug (+)-lysergic acid diethylamide (LSD) continues to attract considerable multidisciplinary interest, and over the last...
Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment.
ACS medicinal chemistry letters – November 14, 2024
Summary
Naturally-occurring compounds 5-MeO-DMT and DMT show remarkable promise in treating severe mental health conditions. In controlled therapeutic settings, these substances produced rapid and significant improvements in depression and anxiety symptoms, with effects lasting weeks to months. New delivery methods and preparation techniques make treatments safer and more effective, while targeted approaches help specific groups like postpartum patients. Early results suggest these therapies could transform mental healthcare for those who haven't responded to traditional treatments.
Abstract
Recent advancements in the therapeutic use of psychedelic compounds, particularly 5-MeO-DMT and DMT, have demonstrated significant potential in tre...
Optimized psilocybin production in tryptophan catabolism‐repressed fungi
Microbial Biotechnology – November 01, 2024
Summary
A significant breakthrough in Biology and Chemistry has dramatically boosted psilocybin production, crucial for Psychedelics and Drug Studies. A mutant strain of *Aspergillus nidulans* was engineered, modifying its biochemistry to prevent tryptamine breakdown. This optimized fermentation process achieved a remarkable 10-fold increase in psilocybin yield, reaching 267 mg/L. This advance in chemical synthesis and alkaloids offers a sustainable, efficient method to produce psilocybin, a compound with high therapeutic potential for severe mental disorders.
Abstract
Abstract The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental diso...
Pharmacokinetics of Psilocybin, a Tryptamine Alkaloid in Magic Mushroom ( Psilocybe cubensis ): A Systematic Review
Journal of Psychoactive Drugs – September 10, 2024
Summary
Psilocybin, a Tryptamine alkaloid from traditional medicine sources, is a breakthrough therapy for major depressive disorder in Psychology. A review of 20 articles in Psychedelics and Drug Studies examined its pharmacokinetics: how the body processes it. This alkaloid, studied in Pharmacology and Chemical synthesis, acts as a prodrug, rapidly converting to psilocin. Its active form quickly peaks, with a 2-3 hour half-life, vital for Complementary and Alternative Medicine Studies.
Abstract
Psilocybin, a major indole alkaloid found in magic mushrooms (Psilocybe cubensis), has recently drawn attention as a breakthrough therapy to treat ...
Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.
Molecular psychiatry – July 01, 2024
Summary
New research reveals that natural mushroom extracts containing psilocybin may have stronger effects on brain plasticity than synthetic psilocybin alone. Scientists found that both forms increased key brain proteins, but the natural extract produced more widespread and lasting changes in brain chemistry, particularly in areas linked to learning and emotion.
Abstract
Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorde...
Reunion Neuroscience raises $103 million
C&EN Global Enterprise – May 20, 2024
Summary
A novel psychedelic drug, RE104, offers significantly shorter treatment times for mental health conditions. Unlike psilocybin therapy, which can last 6-8 hours, RE104 sessions are expected to take half that duration. This biotechnology innovation, developed by Reunion Neuroscience, recently secured $103 million to advance treatments for adjustment disorder and postpartum depression. Acting on the brain's serotonin 2A receptor, RE104 aims to boost neuroplasticity and create new neural pathways, a critical area in neuroscience and cognitive science.
Abstract
Reunion Neuroscience , a start-up focused on mental health, has raised a $103 million series A round, co-led by MPM BioImpact and the Novo Nordisk ...
RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine
ACS Chemical Neuroscience – May 17, 2024
Summary
A single 1 mg/kg dose of the novel prodrug RE104 significantly reduced immobility in rats for a week, highlighting its antidepressant potential. This serotonergic compound, developed through clever chemistry and chemical synthesis of alkaloids, is a prodrug of 4-OH-DiPT, a psychedelic with a short 2-3 hour duration. Pharmacology and neuroscience reveal RE104's glutarate moiety rapidly cleaves, yielding 4-OH-DiPT with a 40-minute half-life. This approach in drug studies offers a unique short-duration psychedelic, influencing neurotransmitter receptors and behavior, potentially reducing clinical burden.
Abstract
Results from randomized clinical trials of psilocybin in depressive disorders highlight the therapeutic potential of serotonergic psychedelic compo...
In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin
Frontiers in Psychiatry – January 08, 2024
Summary
The long-assumed chemistry of psilacetin, an unscheduled hallucinogen, is now confirmed: it acts as a prodrug for psilocin in vivo. This active metabolite, central to psilocybin's therapeutic pharmacology, was measured in C57Bl6/J mice. Psilacetin yielded approximately 70% of the psilocin exposure compared to psilocybin, which produced 10-25% higher concentrations at 15 minutes. These psychedelics and drug studies offer valuable insight, suggesting psilacetin is a viable alternative for exploring neurotransmitter receptor influence on behavior.
Abstract
Introduction The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psych...
Die subakuten Effekte des Psilocybin auf Persönlichkeit, Achtsamkeit und die Auflösung des Selbst
OpenAlex – January 01, 2024
Summary
Psilocybin significantly reduces neuroticism and anxiety, improving life satisfaction. A naturalistic study of 55 participants at psychedelic retreats revealed clear trends: reduced anxiety and neuroticism, plus improved life satisfaction, seven days post-consumption. This work in clinical psychology highlights psilocybin's profound psychological impact on personality, contributing to psychedelics and drug studies. Such findings offer new perspectives for mental health and psychiatry, informing psychotherapist practices and discussions in psychoanalysis.
Abstract
Psychedelics are a class of drugs that can occasion similar changes in conscious ex- periences mediated via the G-protein coupled Serotonin 2A rece...
Quantification of psilocin in human whole blood using liquid chromatography–tandem mass spectrometry (LC–MS/MS)
Journal of Forensic Sciences – December 22, 2023
Summary
Psilocybin, an **alkaloid** from magic mushrooms, shows therapeutic promise, yet quantifying its active form, psilocin, in **whole blood** has been challenging. A new **chemistry** method, vital for **pharmacokinetics** and **forensic toxicology and drug analysis**, now accurately measures psilocin. This **Liquid chromatography–mass spectrometry** technique, employing **tandem mass spectrometry**, achieved over **89% recovery** efficiency and a linearity range of **0.7–200 ng/mL**. This advance significantly aids **Psychedelics and Drug Studies**, providing crucial data for understanding these compounds, whether from **chemical synthesis** or natural sources.
Abstract
Abstract There has been burgeoning interest in psilocybin‐use for the treatment of various neurological and neurodegenerative diseases. Psilocybin ...
Novel Psilocin Prodrugs with Altered Pharmacological Properties as Candidate Therapies for Treatment-Resistant Anxiety Disorders
Journal of Medicinal Chemistry – November 20, 2023
Summary
The prolonged hallucinogenic effects of psilocybin, a potent psychedelic prodrug, often limit its use for anxiety and other psychological conditions. This duration stems from its active metabolite, psilocin. To address this, new chemical synthesis and pharmacology efforts created 28 novel prodrugs. These compounds, identified through comprehensive drug studies, exhibit altered pharmacokinetics and reduced pharmacological exposure compared to psilocybin. This chemistry breakthrough could maintain the therapeutic benefits for anxiety without the extended hallucinogen experience, offering a significant advance in psychedelics.
Abstract
The psychedelic prodrug psilocybin has shown therapeutic benefits for the treatment of numerous psychiatric conditions. Despite positive clinical e...
Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract
OpenAlex – July 20, 2023
Summary
Natural psilocybin mushroom extracts demonstrate superior brain benefits compared to synthetic versions. In male mice, a hallucinogen-rich mushroom extract significantly boosted four key synaptic proteins across four brain regions, indicating enhanced neuroplasticity, lasting 11 days. In contrast, chemically synthesized psilocybin showed more limited effects, impacting only two proteins in two areas. This suggests the full mushroom's complex chemistry, relevant to drug studies and chemical synthesis of alkaloids, offers a distinct neurotransmitter receptor influence on behavior. This difference is vital for understanding psychedelics.
Abstract
Abstract Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatri...
Novel psilocin prodrugs with altered pharmacological properties as candidate therapies for treatment-resistant anxiety disorders
OpenAlex – May 18, 2023
Summary
Psilocybin, a natural hallucinogen, offers significant promise as medicine for severe depression and anxiety. However, its prolonged psychedelic effects (up to 6 hours) limit widespread use. Through advanced chemical synthesis, 28 novel prodrugs of psilocin were engineered. Biochemical analysis revealed 15 effectively released psilocin in vitro. Subsequent pharmacology studies in mice showed these prodrugs reduced overall psilocin exposure, with no detectable levels after 24 hours, unlike psilocybin. Critically, five of these compounds maintained potent psychedelic activity, and two provided long-term anxiety relief. This work in psychedelics and drug studies identifies new compounds for shorter-duration therapy.
Abstract
Abstract The psychedelic compound psilocybin has shown therapeutic benefit in the treatment of numerous psychiatric diseases. A recent randomized c...
Orally Active Forms of DMT, 5-MeO-DMT, and Long-Acting MDMA for the Treatment of Neuropsychiatric Disorders.
ACS medicinal chemistry letters – April 13, 2023
Summary
Breakthrough compounds could revolutionize mental health treatment by making powerful psychedelic medicines orally effective and longer-lasting. These modified versions of DMT and MDMA are designed to activate in the body, potentially offering new hope for treating depression, PTSD, and neurodegenerative conditions like Alzheimer's and Parkinson's disease.
Abstract
This Patent Highlight describes derivatives of DMT, 5-MeO-DMT, and MDMA that are metabolically converted to biologically active analogs. When these...
Direct Quantitation of Psilocybin and Psilocin by One-Dimensional 1H and 31P qNMR in a revived Greek specimen of Psilocybe cyanescens
Planta Medica – December 01, 2022
Summary
Psilocybin, a powerful secondary metabolite from specific fungi, is a prodrug that transforms into its active metabolite, psilocin, within the body. This unique biology is now central to numerous Psychedelics and Drug Studies, exploring its chemistry for treating conditions like Major Depressive Disorder and Alcohol Use Disorder. The growing therapeutic interest, including Complementary and Alternative Medicine Studies, highlights a critical need for rigorous investigation and quantification of these substances, encompassing their chemical synthesis, alkaloids, and stereochemistry.
Abstract
The genus Psilocybe of Basidiomycota includes more than two hundred species of mushroom-forming fungi, which are widely known for the production of...
Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice
ACS Pharmacology & Translational Science – November 02, 2022
Summary
Only specific tryptamines, like the tertiary amine psilocybin, act as potent psychedelics. In drug studies, psilocybin and its active form psilocin, an agonist at the 5-HT receptor, induced psychedelic-like head twitches in mice (ED50 0.11-0.29 mg/kg). Other related tryptamines, despite their chemistry showing nanomolar affinity for serotonin receptors, lacked this hallucinogen effect. This pharmacology highlights how subtle chemical differences in these compounds dictate their neurotransmitter receptor influence on behavior, revealing critical insights for future psychedelic research.
Abstract
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug...
N,N‐Diformylmescaline: A novel analogue of mescaline detected in Queensland
Drug Testing and Analysis – October 17, 2022
Summary
N,N-Diformylmescaline, a new mescaline analogue, was identified in two seizures in Australia. A three-step synthesis from 3,4,5-trimethoxyphenylacetic acid revealed challenges in purifying the compound due to its instability. Analysis showed that under acidic and basic conditions, it degraded to N-formylmescaline, ultimately breaking down to mescaline when exposed to hydrochloric acid over time. This suggests that N,N-diformylmescaline may act as a prodrug for mescaline. The study included detailed data on purification techniques and stability assessments using chromatography and molecular sensors.
Abstract
Abstract N,N ‐Diformylmescaline, a novel analogue of mescaline, has recently been detected in Australia in two unrelated seizures. To confirm the i...
Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines
ACS Omega – July 05, 2022
Summary
Aeruginascin-related quaternary tryptamines, synthesized through chemical methods, surprisingly showed no affinity for receptors mediating psychedelic effects. Through precise characterization, six new alkaloid analogues were explored in drug studies. While lacking 5-HT2A activity, several quaternary tryptammonium compounds strongly targeted the serotonin transporter (SERT). Three analogues displayed sub-micromolar affinity for SERT (370-890 nM), inhibiting serotonin uptake in rat brain tissue from 0.31-3.5 μM. This chemistry offers novel templates for exploring SERT-selective actions, distinct from psychedelics.
Abstract
Aeruginascin (4-phosphoryloxy-N,N,N-trimethyltryptammonium) is an analogue of psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) that has been ide...
Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P‐AL‐LAD
Drug Testing and Analysis – May 07, 2022
Summary
A novel psychedelic, 1P-AL-LAD, acts as a prodrug, converting to AL-LAD as its primary metabolite through in vitro human liver microsome chemistry. This metabolism is crucial for its in vivo hallucinogen effects. In animal studies, 1P-AL-LAD induced head twitches with an ED50 of 491 nmol/kg, nearly three times less potent than AL-LAD (174.9 nmol/kg). This pharmacology suggests its stereochemistry allows for metabolism, including hydroxylation, before activating receptors like lysergic acid diethylamide or psilocybin. Fourteen metabolites were observed, highlighting complex drug studies.
Abstract
Abstract Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important too...
Receptor binding profiles and behavioral effects of psilocybin analogs
The FASEB Journal – May 01, 2022
Summary
A compelling finding reveals psilacetin, a synthetic psilocybin analog, acts as a potent hallucinogen with potential intrinsic psychedelic activity, not merely as a prodrug. *In vivo* studies in male mice, using doses from 0.03 to 3 mg/kg, showed psilocin most potent for head twitch responses, followed by psilacetin and psilocybin. This pharmacology suggests psilacetin converts to psilocin, yet its direct agonist action at 5-HT2A receptors (nM affinities) is significant. An antagonist blocked these effects, clarifying 5-HT2A receptor influence on behavior and advancing understanding of these alkaloids' stereochemistry.
Abstract
4‐phosphorloxy‐ N,N ‐dimethyltryptamine (psilocybin) is a naturally occurring psychedelic compound that is being investigated in clinical studies i...
Assessment of Bioactivity‐Modulating Pseudo‐Ring Formation in Psilocin and Related Tryptamines
ChemBioChem – April 28, 2022
Summary
Psilocin, a potent psychedelic tryptamine, profoundly alters consciousness, unlike its close chemical cousin bufotenin. This critical difference stems from a unique intramolecular force: a hydrogen bond forming a pseudo-ring in psilocin's specific molecular arrangement. This fundamental chemistry, vital for understanding psychedelics and drug studies, allows a higher number of uncharged psilocin molecules to cross the blood-brain barrier. Such nuances in chemical synthesis and alkaloids' structural chemistry dictate their neurotransmitter receptor influence on behavior. Psilocybin acts as a prodrug for psilocin, highlighting its therapeutic promise.
Abstract
Abstract Psilocybin ( 1 ) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin ( 2 , 4‐hydroxy‐ N , N ‐dimethyltr...
Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?
Journal of Xenobiotics – February 07, 2022
Summary
Psilocybin, a potent hallucinogen present in over 200 mushroom species, is showing profound promise in modern psychiatry. Synthesized in 1957, early clinical observations suggested its therapeutic potential for anxiety, mood disorders, and addiction. Despite its 1970 scheduling, renewed interest in chemical synthesis and alkaloids has propelled recent psychology and drug studies. Contemporary medicine now provides robust evidence for psilocybin's efficacy in treating conditions like pathological anxiety and addiction. This complementary and alternative medicine approach, often involving a psychotherapist, represents a significant advance.
Abstract
Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. In 1957, Dr. Hofmann identified and ...
Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1‐valeroyl‐d‐lysergic acid diethylamide (1V‐LSD)
Drug Testing and Analysis – November 27, 2021
Summary
1-Valeroyl-LSD (1V-LSD), a new derivative of lysergic acid diethylamide, shows significant promise as a psychedelic. In a study involving various analytical techniques, 1V-LSD demonstrated a median effective dose of 373 nmol/kg in inducing the head-twitch response in mice, about one-third the potency of traditional LSD (132.8 nmol/kg). This suggests that 1V-LSD may act as a prodrug, potentially converting to LSD in the body. Further exploration of its pharmacology could illuminate its therapeutic and recreational applications.
Abstract
Abstract The psychopharmacological properties of the psychedelic drug lysergic acid diethylamide (LSD) have attracted the interest of several gener...
Psilocybin for Treating Psychiatric Disorders: Is it a Psychonaut Legend or a Promising Therapeutic Perspective?
Preprints.org – June 28, 2021
Summary
Psilocybin, a potent hallucinogen from over 200 mushroom species, is re-emerging in modern Psychiatry. Identified via chemical synthesis and alkaloids research in 1957, this compound, now central to Psychedelics and Drug Studies, was scheduled in 1970. However, Complementary and Alternative Medicine Studies in Psychology and Medicine now suggest significant therapeutic potential. A psychotherapist's perspective indicates it may effectively address pathological Anxiety, Mood disorders, and Addiction, offering a new outlook. This shift provides a fresh perspective on mental health.
Abstract
Psychedelics extracted by plants have been used in religious, spiritual and mystic practices for millennia. In 1957, Dr. Hofmann have identified an...
Psilocybin in the treatment of obsessive-compulsive disorder: What do we know so far?
European Psychiatry – April 01, 2021
Summary
Promising findings suggest psilocybin, a potent hallucinogen, may offer relief for obsessive-compulsive disorder. One open-label clinical trial observed acute reductions in obsessive-compulsive symptoms, sparking interest across psychology and psychiatry. This initial data is encouraging for medicine and clinical psychology, prompting further rigorous clinical trials. These investigations aim to solidify psilocybin's potential in mental health research topics, exploring new therapeutic avenues for psychotherapists and advancing psychedelics and drug studies.
Abstract
Introduction Psilocybin is a naturally occurring plant alkaloid in mushrooms and a prodrug of psilocin. It is a serotonin receptor (5-HT2A) agonist...
Psilacetin derivatives: fumarate salts of the methyl–ethyl, methyl–allyl and diallyl variants of the psilocin prodrug
Acta Crystallographica Section E Crystallographic Communications – January 08, 2021
Summary
The precise molecular architecture of psychedelic compounds is fundamental to medicinal chemistry. Chemical synthesis revealed the solid-state structures of three psilacetin derivative salts. All three molecules undergo protonation, forming salts with fumaric acid or its derivatives. For instance, 4-AcO-DALT forms a two-to-one fumarate salt with a co-crystallized fumaric acid molecule. Extensive hydrogen bond networks stabilize their unique stereochemistries. This fundamental chemistry advances drug studies on alkaloids, offering insights for understanding various receptors, like nicotinic acetylcholine receptors.
Abstract
The solid-state structures of the salts of three psilacetin derivatives, namely, 4-acetoxy- N -ethyl- N -methyltryptammonium (4-AcO-MET) hydrofumar...
Investigation of the Structure–Activity Relationships of Psilocybin Analogues
ACS Pharmacology & Translational Science – December 14, 2020
Summary
Psychedelic drug studies reveal that 4-acetoxy tryptamines, often from chemical synthesis, likely function as prodrugs *in vivo*. This pharmacology means the body converts them into active hallucinogen metabolites. Examining 17 different tryptamines, including psilocybin analogs, showed *O*-acetylation reduced *in vitro* 5-HT2A receptor potency by 10-20 fold. Yet, *in vivo* effects were similar. These tryptamines act as full or partial agonists at serotonin 5-HT receptors, influencing behavior through neurotransmitter receptor activation. Their chemistry confirms their classification as potent psychedelics.
Abstract
The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogen...
Pharmacokinetics and subjective effects of 1P‐LSD in humans after oral and intravenous administration
Drug Testing and Analysis – May 16, 2020
Summary
Oral administration of 1P-LSD, a non-controlled psychedelic, results in nearly 100% bioavailability of LSD in the body, confirming its role as a prodrug. In two human volunteers, 100 µg of 1P-LSD was given orally and intravenously. Biochemical analysis revealed that oral doses exclusively yielded LSD, which had a terminal elimination half-life of approximately 6.4 hours. This pharmacology suggests 1P-LSD converts entirely to LSD, influencing neurotransmitter receptors and behavior. Subjective effects were comparable to LSD, with 5D-ASC scores higher after oral administration, offering insights for medicine and drug studies.
Abstract
Abstract 1‐Propanoyl‐lysergic acid diethylamide (1P‐LSD) appeared as a non‐controlled alternative to LSD a few years ago. Although evidence is begi...
Prodrugs of New Psychoactive Substances (NPS): A New Challenge.
Journal of forensic sciences – May 01, 2020
Summary
Many substances are designed to be inactive until the body converts them into active compounds. This mechanism creates a new forensic challenge with 'prodrugs' of new psychoactive substances (NPS). For instance, compounds like 1-propanoyl-lysergic acid diethylamide (1p-lsd), 2cb-aminonitrile (2c-b-an), or psilacetin, complicate detection by releasing their active forms only after metabolism. Recognizing these evolving prodrugs is crucial for accurate forensic and toxicological analysis, enhancing our ability to identify them effectively.
Abstract
The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medi...
Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)
Drug Testing and Analysis – March 16, 2020
Summary
1CP-LSD, a new lysergamide, shows potential as a psychoactive substance, acting similarly to LSD. In tests with C57BL/6 J mice, it induced a head-twitch response with an effective dose of 430 nmol/kg, comparable to 1P-LSD's 350 nmol/kg. Detailed analysis utilized techniques like mass spectrometry and chromatography, revealing that 1CP-LSD may degrade into LSD when incubated with human serum. This suggests it could function as a prodrug for LSD, highlighting the intricate chemistry behind psychedelics derived from plant and fungal interactions.
Abstract
Abstract Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recen...
Bis(4-acetoxy-N,N-dimethyltryptammonium) fumarate: a new crystalline form of psilacetin, an alternative to psilocybin as a psilocin prodrug
Acta Crystallographica Section E Crystallographic Communications – May 31, 2019
Summary
Unlocking the precise **stereochemistry** of **psychedelics** like psilacetin is vital for advanced **drug studies**. **Crystallography** reveals this **alkaloid** derivative, a product of **chemical synthesis**, forms a distinct structure. A **protonated** psilacetin **ion**, featuring an **indole** group, connects with a fumarate **ion** via multiple **hydrogen bond** interactions. Specifically, **ammonium** and indole hydrogen atoms bond with fumarate oxygen atoms. This intricate **chemistry** creates infinite one-dimensional chains, providing fundamental insights into its molecular architecture.
Abstract
The title compound (systematic name: bis{2-[4-(acetyloxy)-1 H -indol-3-yl]ethan-1-aminium} but-2-enedioate), 2C 14 H 19 N 2 O 2 + ·C 4 H 2 O 4 2− ,...
Production Options for Psilocybin: Making of the Magic
Chemistry - A European Journal – July 16, 2018
Summary
Psilocybin, a potent hallucinogen from "magic mushrooms," shows remarkable promise as a therapeutic for depression and anxiety, transforming its role in Psychedelics and Drug Studies. To meet anticipated demand, significant progress illuminates its biosynthesis. This enables efficient enzymatic in vitro and heterologous in vivo production, complementing existing Chemical synthesis of alkaloids. Such advancements in Pharmacology are crucial for ensuring scalable access to this valuable compound as its therapeutic potential expands.
Abstract
Abstract The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4‐phosphoryloxy‐ N , N ‐dime...
Horizontal gene cluster transfer increased hallucinogenic mushroom diversity
Evolution Letters – February 27, 2018
Summary
The potent hallucinogen psilocybin is produced by diverse Agaricales mushrooms via horizontal gene transfer. Scientists uncovered the psilocybin gene cluster in three mushroom genomes, demonstrating how this biological mechanism spread the chemical synthesis capability across fungal lineages. This ecological adaptation likely provides a fitness advantage, potentially altering invertebrate behavior by affecting their biology, including neural structures like mushroom bodies. This work in fungal biology and applications informs psychedelics and drug studies, advancing alkaloid research for new neuropharmaceuticals.
Abstract
Abstract Secondary metabolites are a heterogeneous class of chemicals that often mediate interactions between species. The tryptophan-derived secon...