Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects.

With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Fatty acid-binding protein 7 gene deletion promotes decreases in brain cannabinoid type 1 receptor binding.

Fatty acid-binding protein 7 (FABP7) aids in the intracellular transport of endogenous cannabinoids and is involved in regulating the stress response system. This study examined the role of FABP7 in chronic stress exposure through the binding of CB1 receptors. Adult male FABP7 and FABP7 mice were treated with the unpredictable chronic mild stress (UCMS) procedure.

Time course of kratom effects via ecological momentary assessment, by product type, dose amount, and assayed alkaloid content.

Background And Aims: Using ecological momentary assessment (EMA), we undertook a natural experiment wherein kratom-product variability was a tool to assess kratom dose-response relationships based on product form and alkaloid level.

Methods: Between July-November 2022, 357 US kratom consumers (56.6 % male, 90.

Multiple-Dose Pharmacokinetics and Safety of Mitragynine, the Major Alkaloid of Kratom, in Rats.

This study reports the steady-state pharmacokinetic parameters for mitragynine and characterizes its elimination in male and female rats. Four male and female rats were dosed q12h with 40 mg/kg, and orally administered mitragynine for 5 and 6 days, respectively. Using a validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, the plasma concentrations of mitragynine, its metabolites (7-hydroxymitragynine, 9-hydroxycorynantheidine, and mitragynine acid), and a non-CYP oxidation product (3-dehydromitragynine) were determined at various time points.

Perinatal nicotine vaping exposure induces pro-myofibroblastic phenotype in rat bone marrow-derived mesenchymal stem cells.

Perinatal nicotine exposure via tobacco smoking results in increased proclivity to chronic lung disease (CLD); however, the underlying molecular mechanisms remain incompletely understood. We previously demonstrated that in addition to nicotine's direct effects on the developing lung, there are also adverse molecular alterations in bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to lung injury repair. Whether perinatal nicotine exposure via electronic-cigarette (e-cig) vaping also adversely affects BMSCs is unknown.

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds.

Multimodal imaging analyses of dosed tissue samples can provide more comprehensive insights into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multimodal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging.

Explorations of Agonist Selectivity for the α9* nAChR with Novel Substituted Carbamoyl/Amido/Heteroaryl Dialkylpiperazinium Salts and Their Therapeutic Implications in Pain and Inflammation.

There is an urgent need for nonopioid treatments for chronic and neuropathic pain to provide effective alternatives amid the escalating opioid crisis. This study introduces novel compounds targeting the α9 nicotinic acetylcholine receptor (nAChR) subunit, which is crucial for pain regulation, inflammation, and inner ear functions. Specifically, it identifies novel substituted carbamoyl/amido/heteroaryl dialkylpiperazinium iodides as potent agonists selective for human α9 and α9α10 over α7 nAChRs, particularly compounds , , and .

Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid.

Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed.

Formation of multiple ion types during MALDI imaging mass spectrometry analysis of Mitragyna speciosa alkaloids in dosed rat brain tissue.

Mitragyna speciosa, more commonly known as kratom, has emerged as an alternative to treat chronic pain and addiction. However, the alkaloid components of kratom, which are the major contributors to kratom's pharmaceutical properties, have not yet been fully investigated. In this study, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry was used to map the biodistribution of three alkaloids (corynantheidine, mitragynine, and speciogynine) in rat brain tissues.

A multi-modal image fusion workflow incorporating MALDI imaging mass spectrometry and microscopy for the study of small pharmaceutical compounds.

Multi-modal imaging analyses of dosed tissue samples can provide more comprehensive insight into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multi-modal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging.

Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats.

Kratom and cannabidiol products are used to self-treat a variety of conditions, including anxiety and pain, and to elevate mood. Research into the individual pharmacokinetic properties of commercially available kratom and cannabidiol products has been performed, but there are no studies on coadministration of these products. Surveys of individuals with kratom use history indicate that cannabidiol use is one of the strongest predictors of both lifetime and past month kratom use.

Microbiome and Otic Quinolone Levels Following Tympanoplasty Assessed by Gelatin Sponge Analysis.

Objective: To determine if absorbable gelatin sponge (AGS) can be used to assess the posttympanoplasty microbiome and otic antibiotic exposure.

Study Design: Prospective.

Setting: Tertiary hospital.

Effects of kratom on driving: Results from a cross-sectional survey, ecological momentary assessment, and pilot simulated driving Study.

Objectives: Despite widespread kratom use, there is a lack of knowledge regarding its effects on driving. We evaluated the self-reported driving behaviors of kratom consumers and assessed their simulated-driving performance after self-administering kratom products.

Methods: We present results from: 1) a remote, national study of US adults who regularly use kratom, and 2) an in-person substudy from which we re-recruited participants.

DR5 disulfide bonding as a sensor and effector of protein folding stress.

New agents are needed that selectively kill cancer cells without harming normal tissues. The TRAIL ligand and its receptors, DR5 and DR4, exhibit cancer-selective toxicity, but TRAIL analogs or agonistic antibodies targeting these receptors have not received FDA approval for cancer therapy. Small molecules for activating DR5 or DR4 independently of protein ligands may bypass some of the pharmacological limitations of these protein drugs.

Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars.

An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations.

Introduction: Kratom () has generated substantial clinical and scientific interest as a complex natural product. Its predominant alkaloid mitragynine and several stereoisomers have been studied for activity in opioid, adrenergic, and serotonin receptors. While awaiting clinical trial results, the pre-clinical evidence suggests a range of potential therapeutic applications for kratom with careful consideration of potential adverse effects.

Responses to a "Typical" Morning Dose of Kratom in People Who Use Kratom Regularly: A Direct-Observation Study.

Introduction: Use of kratom has outpaced systematic study of its effects, with most studies reliant on retrospective self-report.

Methods: We aimed to assess acute effects following kratom use in adults who use regularly, and quantify alkaloids in the products, urine, and plasma. Between July and November 2022, 10 adults came to our clinic and orally self-administered their typical kratom dose; blinding procedures were not used.

Synthesis of α3β4 Nicotinic Acetylcholine Receptor Modulators Derived from Aristoquinoline That Reduce Reinstatement of Cocaine-Seeking Behavior.

Growing evidence suggests that inhibition of the α3β4 nicotinic acetylcholine receptor (nAChR) represents a promising therapeutic strategy to treat cocaine use disorder. Recently, aristoquinoline (), an alkaloid from , was identified as an α3β4-selective nAChR inhibitor. Here, we prepared 22 derivatives of and evaluated their ability to inhibit the α3β4 nAChR.

Commercial Delta-8 THC Products: an Analysis of Content and Labeling.

Introduction: ∆-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid and structural isomer of ∆-9 THC that is technically legal under United States Federal law. Commercial ∆-8-THC products being sold are currently unregulated. This study aims to (1) describe the advertising and labeling of Δ-8 THC retail products; (2) compare the advertised amount of Δ-8 THC for each product to that found during independent laboratory analysis; and (3) evaluate the presence and amount of other cannabinoids in those products.

FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice.

Fatty acid binding protein 5 (FABP5) interacts with the endocannabinoid system in the brain via intracellular transport of anandamide, as well as Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. Previous work has established the behavioral effects of genetic deletion of FABP5, but not in the presence of THC. The present study sought to further elucidate the role of FABP5 on the pharmacokinetic and behavioral response to THC through global deletion.