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Diabetes & Metabolism Journal Dec 2020Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and... (Review)
Review
Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.
Topics: Anti-Obesity Agents; Benzazepines; Humans; Orlistat; Phentermine; Weight Loss
PubMed: 33389955
DOI: 10.4093/dmj.2020.0258 -
International Journal of Molecular... May 2021Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due... (Review)
Review
Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.
Topics: Bronchodilator Agents; Humans; Methamphetamine; Pseudoephedrine; Risk Assessment; Substance-Related Disorders
PubMed: 34067981
DOI: 10.3390/ijms22105146 -
Psychopharmacology Bulletin Jun 2021Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The... (Review)
Review
Post-traumatic stress disorder (PTSD) has become one of the most common psychiatric diagnosis in the United States specifically within the veteran population. The current treatment options for this debilitating diagnosis include trauma-focused psychotherapies along with selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI). MDMA has recently been shown as a novel therapeutic agent with promisingly results in the treatment of PTSD. MDMA is a psychoactive compound traditionally categorized as a psychedelic amphetamine that deemed a Schedule I controlled substance in the 1980s. Prior to its status as a controlled substance, it was used by psychotherapists for an array of psychiatric issues. In more recent times, MDMA has resurfaced as a potential therapy for PTSD and the data produced from randomized, controlled trials back the desire for MDMA to be utilized as an effective pharmacologic therapy in conjunction with psychotherapy..
Topics: Adult; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic; Veterans
PubMed: 34421149
DOI: No ID Found -
PloS One 2020Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.
METHODS
We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.
RESULTS
Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.
CONCLUSIONS
Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.
REGISTRATION
PROSPERO no. CRD 42015026049.
Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Modafinil; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33085721
DOI: 10.1371/journal.pone.0240584 -
CNS Drugs Apr 2020Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.
METHODS
We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.
RESULTS
Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.
CONCLUSIONS
No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Central Nervous System Stimulants; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 32185696
DOI: 10.1007/s40263-020-00711-x -
Nature Communications Aug 2023The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota...
The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.
Topics: Humans; Animals; Mice; Insulin Resistance; Metabolic Syndrome; Irritable Bowel Syndrome; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Dysbiosis; Phenethylamines; Tryptamines
PubMed: 37591886
DOI: 10.1038/s41467-023-40552-y -
Lakartidningen Oct 2020
Topics: Amphetamines; Humans; Substance Abuse Detection
PubMed: 33107582
DOI: No ID Found -
Psychopharmacology Bulletin Feb 2023This study aimed to explore the relationship between Captagon usage and the development of delusions of infidelity. The study sample; 101 male patients, was recruited... (Review)
Review
This study aimed to explore the relationship between Captagon usage and the development of delusions of infidelity. The study sample; 101 male patients, was recruited from patients admitted to Eradah Complex for Mental Health and addiction, Jeddah, Saudi Arabia, with the diagnosis of amphetamine (Captagon) induced psychosis during the period from September 2021 to March 2022. All patients underwent an extensive psychiatric interview; including interview with patients' families; a demographic sheet, a drug use questionnaire, the structured clinical interview for DSM-IV (SCID 1), routine medical investigation, and urine screening for drugs. Patients' ages ranged from 19 to 46 years old with Mean ± SD 30.87 ± 6.58. 57.4 % were single, 77.2% have finished their high school, and 22.8% had no work. Captagon using age ranged from 14-40 years old, and regular daily dose ranged from 1-15 tablet, while maximum daily dose ranged from 2-25 tablets. Twenty-six patients (25.7%) of the study group have developed infidelity delusions. A higher divorce rate was present among patients who developed infidelity delusions (53.8%) in comparison to patients who developed other types of delusions (6.7%). Infidelity delusions are common among patients diagnosed with Captagon induce psychosis, and they harmfully influence their social lives.
Topics: Humans; Male; Young Adult; Adult; Middle Aged; Adolescent; Jealousy; Schizophrenia, Paranoid; Psychotic Disorders; Amphetamine
PubMed: 36873918
DOI: No ID Found -
Molecules (Basel, Switzerland) Jan 2023A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this... (Review)
Review
A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this motif are enumerated in key therapeutic targets, listing medicinal chemistry hits and appealing screening compounds. Latest reports in discovering new bioactive 2-phenethylamines by research groups are covered too.
Topics: Chemistry, Pharmaceutical; Receptors, G-Protein-Coupled; Phenethylamines; Receptors, Dopamine D2
PubMed: 36677913
DOI: 10.3390/molecules28020855 -
Journal of Analytical Toxicology Jul 2021N-Ethylhexedrone [2-(ethyloamino)-1-phenylhexan-1-one; α-ethylaminohexanophenone (NEH)] is one of the most recent synthetic cathinones that appeared on the illegal...
N-Ethylhexedrone [2-(ethyloamino)-1-phenylhexan-1-one; α-ethylaminohexanophenone (NEH)] is one of the most recent synthetic cathinones that appeared on the illegal market in late 2015. The majority of information concerning the model of consumption of NEH and its impact on the body originates only from self-reports from gray literature websites and drug forums. There are only limited data associated with the concentrations of NEH in blood samples available in the literature. This article presents a case of fatal NEH intoxication and a method for the determination of this substance in whole blood. A 21-year-old man without any diagnosed diseases was admitted to the hospital due to disorientation, aggression and finally loss of consciousness. Hyperthermia (>41°C), tachycardia (>160 beats per minute), tachypnea (20 breaths per minute), blood pressure (110/60 mmHg) and acute kidney failure were diagnosed. After a few hours of hospitalization, the patient died. A plastic bag with a white powder was found in his underwear. Analysis of the powder by another laboratory revealed cocaine hydrochloride; however, no cocaine or its metabolites were found in the biological material upon testing in our laboratory. Therefore, re-analysis of the powder was performed, and NEH was identified. Liquid-liquid extraction followed by liquid chromatography-triple quadrupole-mass spectrometry (LC-MS/MS) analysis were used for the determination of NEH in blood. The validation parameters were as follows: calibration range 1-250 ng/mL, accuracy 106.5-109.9%, precision 3.5-6.3%, recovery 90.1-96.9%, limit of detection 0.07 ng/mL and limit of quantification 1 ng/mL. NEH was quantified in the blood at a concentration of 145 ng/mL. Additionally, amphetamine at low concentrations and 11-nor-9-karboksy-Δ9-tetrahydrokannabinol (THC-COOH) were detected. Our study provided information on the possible lethal concentration and toxidrome that clinicians can observe for NEH-intoxicated patients and can be helpful during the preparation of toxicology analysis reports for a court of law for proper data interpretation.
Topics: Amphetamine; Calibration; Chromatography, Liquid; Cocaine; Humans; Male; Tandem Mass Spectrometry; Young Adult
PubMed: 33048166
DOI: 10.1093/jat/bkaa159