Pharmaceutics
March 25, 2025
Shakila Meshkat, Huda Al-Shamali, Argyrios Perivolaris et al.
22 citations
Psilocybin is rapidly converted to its active metabolite psilocin after oral intake. Psilocin reaches peak concentration in blood plasma between 1.8 and 4 hours, with maximum concentration ranging from 8.2 ng/mL in plasma to 871 ng/mL in urine, depending on dose. Its bioavailability is about 53%, and it distributes extensively into tissues, with volume of distribution between 277 and 1016 liters. Metabolism involves CYP2D6 and CYP3A4 enzymes, plus monoamine oxidase A, producing 4-hydroxyindole-3-acetic acid and 4-hydroxytryptophol. Elimination half-life ranges from 1.5 to 4 hours. These pharmacokinetics vary with dosage, route, and species, and the role of CYP enzymes indicates possible drug interactions.
Pharmaceutics
December 22, 2023
Ludivine Boudieu, Myriam Mennetrier, Pierre-Michel Llorca et al.
22 citations
Intranasal ketamine and esketamine offer a rapid onset of antidepressant effects within hours for people with major depressive disorder, particularly those with treatment-resistant depression or active suicidal thoughts. A systematic review following PRISMA guidelines found stronger evidence of efficacy for intranasal esketamine than for intranasal ketamine. The safety profile of intranasal esketamine appears acceptable, though further studies are needed; a more accurate delivery device is required for ketamine. These glutamatergic agents bypass the blood–brain barrier, potentially reducing side effects compared with intravenous administration.
Pharmaceutics
August 20, 2024
Guillaume Drevin, Maria Pena-Martin, Aurélien Bauduin et al.
4 citations
Genetic factors influence individual responses to MDMA, which is being studied for treating PTSD and substance use disorders. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been linked to cognitive and cardiovascular effects, and polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with mood disorders. However, only a few associations have been found, and many genes involved in MDMA metabolism and targets remain poorly investigated. Large-scale controlled pharmacogenomics studies are needed to optimize therapeutic use and minimize risks.
Pharmaceutics
January 8, 2026
Shiryn D Sukhram, Majandra Sanchez, Ayotunde Anidugbe et al.
Depression and diabetic neuropathy often co-occur with diabetes, worsening blood sugar control and quality of life. Ketamine and its S-enantiomer, esketamine, offer rapid antidepressant and pain-relieving effects, but diabetes-related changes and other medications may alter their effectiveness and safety. A scoping review of 11 studies (including human case reports, one randomized trial, narrative reviews, and rodent studies) found short-term improvements in treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative pain relief in gestational diabetes. Blood sugar effects varied, with both high and low blood sugar reported. Interactions with common diabetes drugs and liver enzymes (CYP3A4, CYP2B6) remain poorly studied. The authors call for dedicated pharmacokinetic and pharmacodynamic studies to guide individualized dosing in diabetes.
Pharmaceutics
June 11, 2025
Bernard Do, Luc Mallet, Maxime Annereau et al.
D-lysergic acid diethylamide (D-LSD), being investigated for alcohol use disorder, is extremely sensitive to light, which complicates formulation for clinical trials. A liquid-filled capsule formulation was developed to protect D-LSD from photodegradation while providing accurate dosing. Using liquid chromatography with ion mobility spectrometry and mass spectrometry, along with quantum chemical calculations, researchers characterized degradation products. Photostress studies showed that D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, but the capsule formulation markedly reduced these transformations under ICH-compliant conditions. Orthogonal stability profiling is essential for guiding formulation development, and this capsule approach may offer a viable, photostable platform for future clinical investigation of D-LSD.