-
Chemical & Pharmaceutical Bulletin 2024Ephedra plants, the main components of which are ephedrine alkaloids, are used as traditional medicines in Eastern Asian countries. In this study, we isolated...
Ephedra plants, the main components of which are ephedrine alkaloids, are used as traditional medicines in Eastern Asian countries. In this study, we isolated non-ephedrine constituents from various Ephedra plant species cultivated in Japan. HPLC analysis suggested that kynurenic acid and its derivatives accumulated in a wide range of Ephedra plant species. Furthermore, a large amount of (2R,3S)-O-benzoyl isocitrate has been isolated from E. intermedia. This study suggests that Ephedra plants have diverse non-ephedrine constituents.
Topics: Ephedrine; Ephedra; Japan; Alkaloids; Chromatography, High Pressure Liquid
PubMed: 38631893
DOI: 10.1248/cpb.c24-00043 -
The Australian and New Zealand Journal... Jul 2024The Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory... (Review)
Review
OBJECTIVES
The Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory concerns and challenges for the field of psychedelic-assisted therapy. To provide clarity, we aimed to comprehensively catalogue the matters relating to psychedelic-assisted therapy that are or could be regulated.
METHODS
We conducted a desktop review of the literature and current regulatory sources, semi-structured interviews with professionals who had expertise in fields relating to psychedelic-assisted therapy and a framework analysis to generate a taxonomy of relevant regulatory matters. In relation to each matter, we further identified what type of regulation (if any) currently applies to that matter, any uncertainty as to how the matter should be addressed in clinical practice in the context of current regulation and whether there are conflicting views as to how the matter could or should be further regulated.
RESULTS
The taxonomy is structured into six main regulatory domains, three of which have a substantial proportion of matters with uncertainty or conflicting views: Service Establishment, Practitioner, and Treatment Delivery. Key examples of such matters include the location of services and facilities required, which professionals are eligible to become psychedelic therapists, and with what qualifications and experience. Matters in the remaining three domains, Patient Evaluation, Drug Supply and Service Oversight, appear by comparison relatively settled, with regulation either well-established or thought unnecessary.
CONCLUSIONS
The taxonomy provides a roadmap for health services establishing and implementing a psychedelic-assisted therapy program, or for government and other policymakers when determining areas that may require further regulation.
Topics: Humans; Hallucinogens; Australia; Psilocybin; N-Methyl-3,4-methylenedioxyamphetamine; Health Policy
PubMed: 38628079
DOI: 10.1177/00048674241240597 -
BMC Psychiatry Apr 2024Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This...
BACKGROUND
Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression.
CASE PRESENTATION
H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly.
CONCLUSION
Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.
Topics: Humans; Adolescent; Female; Venlafaxine Hydrochloride; Psychotherapy
PubMed: 38627661
DOI: 10.1186/s12888-024-05705-3 -
Translational Psychiatry Apr 2024Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain...
Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain stimulation (DBS) has shown a therapeutic potential for neuropsychological disorders, while the precise stimulation targets and therapeutic parameters for addiction remain deficient. Among the crucial brain regions implicated in drug addiction, the dorsal raphe nucleus (DRN) has been found to exert an essential role in the manifestation of addiction memory. Thus, we investigated the effects of DRN DBS in the treatment of addiction and whether it might produce side effects by a series of behavioral assessments, including methamphetamine priming-induced reinstatement of drug seeking behaviors, food-induced conditioned place preference (CPP), open field test and elevated plus-maze test, and examined brain activity and connectivity after DBS of DRN. We found that high-frequency DBS of the DRN significantly lowered the CPP scores and the number of active-nosepokes in the methamphetamine-primed CPP test and the self-administration model. Moreover, both high-frequency and sham DBS group rats were able to establish significant food-induced place preference, and no significant difference was observed in the open field test and in the elevated plus-maze test between the two groups. Immunofluorescence staining and functional magnetic resonance imaging revealed that high-frequency DBS of the DRN could alter the activity and functional connectivity of brain regions related to addiction. These results indicate that high-frequency DBS of the DRN effectively inhibits methamphetamine priming-induced relapse and seeking behaviors in rats and provides a new target for the treatment of drug addiction.
Topics: Rats; Animals; Methamphetamine; Dorsal Raphe Nucleus; Deep Brain Stimulation; Drug-Seeking Behavior; Substance-Related Disorders
PubMed: 38622130
DOI: 10.1038/s41398-024-02895-y -
Journal of Chromatography. B,... May 20243,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and...
3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography-tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5-500 ng/mL for the achiral analysis of both analytes, 0.5-1,000 ng/mL for chiral MDMA analysis, and 1-1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Stereoisomerism; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Reproducibility of Results; Linear Models; Limit of Detection; Male; Adult
PubMed: 38615429
DOI: 10.1016/j.jchromb.2024.124123 -
Scientific Reports Apr 2024Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous...
Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.
Topics: Animals; Swine; Heart Sounds; Dobutamine; Nicardipine; Hemodynamics; Phenylephrine; Propanolamines
PubMed: 38615106
DOI: 10.1038/s41598-024-59362-3 -
Journal of Ethnopharmacology Jul 2024The plants of Amaryllidaceae family, such as Amaryllis belladonna L., have been used as herbal remedies for thousands of years to address various disorders, including...
ETHNOPHARMACOLOGY RELEVANCE
The plants of Amaryllidaceae family, such as Amaryllis belladonna L., have been used as herbal remedies for thousands of years to address various disorders, including diseases that might today be identified as cancer.
AIM OF THE STUDY
The objective of this work was to evaluate the potential of three Amaryllidaceae alkaloids against four cancer cell lines.
MATERIAL AND METHODS
The alkaloids lycorine, 1-O-acetylcaranine, and montanine were evaluated in vitro against colon adenocarcinoma cell line (HCT-116) and breast carcinoma cell lines (MCF-7, MDAMB231, and Hs578T). Computational experiments (target prediction and molecular docking) were conducted to gain a deeper comprehension of possible interactions between these alkaloids and potential targets associated with these tumor cells.
RESULTS
Montanine presented the best results against HCT-116, MDAMB231, and Hs578T cell lines, while lycorine was the most active against MCF-7. In alignment with the target prediction outcomes and existing literature, four potential targets were chosen for the molecular docking analysis: CDK8, EGFR, ER-alpha, and dCK. The docking scores revealed two potential targets for the alkaloids with scores similar to co-crystallized inhibitors and substrates: CDK8 and dCK. A visual analysis of the optimal docked configurations indicates that the alkaloids may interact with some key residues in contrast to the other docked compounds. This observation implies their potential to bind effectively to both targets.
CONCLUSIONS
In vitro and in silico results corroborate with data literature suggesting the Amaryllidaceae alkaloids as interesting molecules with antitumoral properties, especially montanine, which showed the best in vitro results against colorectal and breast carcinoma. More studies are necessary to confirm the targets and pharmaceutical potential of montanine against these cancer cell lines.
Topics: Humans; Amaryllidaceae Alkaloids; Molecular Docking Simulation; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; MCF-7 Cells; Amaryllidaceae; HCT116 Cells; Computer Simulation; Phenanthridines; Isoquinolines
PubMed: 38614259
DOI: 10.1016/j.jep.2024.118154 -
Journal of Analytical Toxicology Jun 2024The general use of cocaine is increasing in recent years, while the trend for 3,4-methylenedioxymethamphetamine (MDMA) is less clear. The relationship between blood...
The general use of cocaine is increasing in recent years, while the trend for 3,4-methylenedioxymethamphetamine (MDMA) is less clear. The relationship between blood concentrations and impairment is poorly understood, which complicates interpretation. The aims of this study were to report prevalence and blood concentrations of cocaine and MDMA in drugged drivers, and to investigate the relationship between blood concentrations and impairment. Samples of whole blood were collected from apprehended drivers in the period 2000-2022, and a clinical test of impairment (CTI) was simultaneously performed. The samples were initially analyzed for cocaine and MDMA using gas chromatography-mass spectrometry (until 2009 and 2012, respectively), and later using ultra-high-performance liquid chromatography-tandem mass spectrometry. Overall, cocaine was detected in 2,331 cases and MDMA in 2,569 cases. There were 377 and 85 mono cases of cocaine and MDMA, respectively. In the mono cases, the median cocaine concentration was 0.09 mg/L (range: 0.02-1.15 mg/L), and 54% of the drivers were clinically impaired. The median MDMA concentration was 0.19 mg/L (range: 0.04-1.36 mg/L), and 38% were clinically impaired. There was a statistically significant difference in the median cocaine concentration between drivers assessed as not impaired (0.07 mg/L) and drivers assessed as impaired (0.10 mg/L) (P = 0.009). There was also a significant effect of the blood concentration of cocaine (adjusted odds ratio [aOR] = 6.42, 95% confidence interval [CI] = 1.13-36.53, P = 0.036) and driving during the evening/night-time (aOR = 2.17, 95% CI = 1.34-3.51, P = 0.002) on the probability of being assessed as impaired on the CTI. No significant differences were found for MDMA. Many drivers are not assessed as impaired on a CTI following cocaine or especially MDMA use. For cocaine, a relationship between blood concentrations and impairment was demonstrated, but this could not be shown for MDMA.
Topics: N-Methyl-3,4-methylenedioxyamphetamine; Humans; Cocaine; Substance Abuse Detection; Driving Under the Influence; Male; Gas Chromatography-Mass Spectrometry; Adult; Tandem Mass Spectrometry; Female; Chromatography, High Pressure Liquid
PubMed: 38613441
DOI: 10.1093/jat/bkae024 -
International Journal of Molecular... Apr 2024Salinity is an environmental stress that severely impacts rice grain yield and quality. However, limited information is available on the molecular mechanism by which...
Salinity is an environmental stress that severely impacts rice grain yield and quality. However, limited information is available on the molecular mechanism by which salinity reduces grain quality. In this study, we investigated the milling, appearance, eating and cooking, and nutritional quality among three japonica rice cultivars grown either under moderate salinity with an electrical conductivity of 4 dS/m or under non-saline conditions in a paddy field in Dongying, Shandong, China. Moderate salinity affected rice appearance quality predominantly by increasing chalkiness rate and chalkiness degree and affected rice eating and cooking and nutritional quality predominantly by decreasing amylose content and increasing protein content. We compared the expression levels of genes determining grain chalkiness, amylose content, and protein content in developing seeds (0, 5, 10, 15, and 20 days after flowering) of plants grown under saline or non-saline conditions. The chalkiness-related gene was up-regulated and was repressed. The genes and which determine amylose content, were downregulated, while protein-content-associated genes and were upregulated by salinity in the developing seeds. These findings suggest some target genes that may be utilized to improve the grain quality under salinity stress conditions via gene-pyramiding breeding approaches.
Topics: Oryza; Amylose; Plant Breeding; Salt Stress; Seeds; Calcium Carbonate; Edible Grain; Methamphetamine
PubMed: 38612852
DOI: 10.3390/ijms25074042 -
International Journal of Molecular... Mar 2024Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children....
Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81-1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41-0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability.
Topics: Adult; Child; Humans; Bile; Chromatography, Liquid; Luminescence; Reproducibility of Results; Tandem Mass Spectrometry; Drug Overdose; Amphetamines
PubMed: 38612632
DOI: 10.3390/ijms25073825