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Nature Medicine Oct 2023This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT)... (Randomized Controlled Trial)
Randomized Controlled Trial
This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .
Topics: Humans; Stress Disorders, Post-Traumatic; N-Methyl-3,4-methylenedioxyamphetamine; Treatment Outcome; Combined Modality Therapy; Double-Blind Method
PubMed: 37709999
DOI: 10.1038/s41591-023-02565-4 -
Expert Review of Clinical Pharmacology 2023Pediatric attention-deficit disorder (ADHD) impacts a significant percentage of the population world-wide. Pharmacologic treatments have been shown to be safe and... (Review)
Review
INTRODUCTION
Pediatric attention-deficit disorder (ADHD) impacts a significant percentage of the population world-wide. Pharmacologic treatments have been shown to be safe and effective for managing symptoms. Various medication formulations exist, and new medication agents are continually approved each year.
AREAS COVERED
This article offers an overview of ADHD, an overview of both stimulant and non-stimulant medication options as well as an overview of stimulant misuse. It explores the medication mechanisms of action and side effect profiles, as well as offering an in-depth summary of the novel agents recently approved and soon-to-be approved for use in youth. PubMed and Medline were utilized. Search terms included children, adolescents, ADHD, and medication. FDA package inserts were reviewed for all medications.
EXPERT OPINION
New formulations of medications include an evening administered, extended, and delayed-release form of methylphenidate (DR/ER MPH), a methylphenidate pro-drug (serdexmethylphenidate) and an amphetamine patch. The availability of a new SNRI (selective norepinephrine reuptake inhibitor), viloxazine extended-release (VER), and the pending approval of a triple reuptake inhibitor (centanafadine) provides welcome additions to the prescriber's toolbox.
Topics: Adolescent; Humans; Child; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Amphetamine; Prodrugs
PubMed: 37587841
DOI: 10.1080/17512433.2023.2249414 -
Nature Dec 2023Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis. They recognize diverse... (Comparative Study)
Comparative Study
Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HTR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.
Topics: Animals; Humans; Mice; Amines; Amphetamine; Antipsychotic Agents; Binding Sites; Catecholamines; Cryoelectron Microscopy; GTP-Binding Proteins; Ligands; Molecular Dynamics Simulation; Mutation; Polypharmacology; Receptors, G-Protein-Coupled; Species Specificity; Substrate Specificity
PubMed: 37935376
DOI: 10.1038/s41586-023-06804-z -
The American Journal of Drug and... Sep 2023A drug concoction called tusi has emerged in Latin America and in Europe and is now beginning to acquire popularity in the United States. "Tusi" is a phonetic...
A drug concoction called tusi has emerged in Latin America and in Europe and is now beginning to acquire popularity in the United States. "Tusi" is a phonetic translation of "2C," a series of psychedelic phenethylamines. The concoction is also sometimes referred to as "pink cocaine" as it typically comes in the form of pink powder. However, despite its name, the concoction rarely contains 2C series drugs. Multiple drug checking studies have found that the majority of tusi samples contain ketamine, often combined with 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, cocaine, opioids, and/or new psychoactive substances. The tusi phenomenon complicates the drug landscape because it has the potential to confuse both people who use it and researchers alike. People using may think the drug is 2C/2C-B, and they may also be unaware that the concoction tends to consist of ketamine and a wide variety of other drugs. Unintentional exposure to its contents can lead to increased risk of adverse effects. The tusi phenomenon also has the potential to complicate drug research as unknown exposure to drugs like ketamine and MDMA will lead to underreporting of use. A combination of self-report and toxicological testing may be needed to inform the most accurate estimates of use. Both researchers and people at risk for use need to be informed about this new concoction. Drug researchers need to be cognizant about the way they query use, and people at risk for using need to be educated about the possible contents of tusi and associated dangers.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Ketamine; Hallucinogens; Methamphetamine; Cocaine; Substance-Related Disorders
PubMed: 37162319
DOI: 10.1080/00952990.2023.2207716 -
Emergency Medicine Practice Nov 2023Management of patients who are acutely intoxicated with methamphetamine (a member of the substituted amphetamine class of drugs) can be resource-intensive for most... (Review)
Review
Management of patients who are acutely intoxicated with methamphetamine (a member of the substituted amphetamine class of drugs) can be resource-intensive for most emergency departments. Clinical presentations of the methamphetamine sympathomimetic toxidrome range from mild agitation to rhabdomyolysis, acute kidney injury, seizures, and intracranial hemorrhage. High-quality evidence on how to best manage these patients is lacking, and most research focuses on symptomatic interventions to control patients' agitation and hemodynamics. This review analyzes the best available evidence on the diagnosis and management of emergency department patients with substituted amphetamine toxicity and offers best-practice recommendations on treatment and disposition.
Topics: Humans; Methamphetamine; Emergency Service, Hospital; Amphetamine
PubMed: 37877728
DOI: No ID Found -
Journal of Veterinary Emergency and... 2024To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis.
OBJECTIVE
To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis.
CASE SUMMARY
A 3-year-old female neutered mixed breed dog initially presented with neurological signs suspected to be secondary to LDX toxicosis. The dog was treated as typical for amphetamine toxicoses but developed severe respiratory and cardiovascular signs throughout their hospitalization. The progression of the cardiopulmonary signs led to cardiopulmonary arrest, for which CPR was unsuccessful. Postmortem examination exhibited severe hemorrhage throughout multiple organ systems. Toxicology testing confirmed the presence of unaltered LDX and its metabolite, amphetamine.
NEW OR UNIQUE INFORMATION PROVIDED
This is the first case report documenting a severe progression of clinical signs and postmortem examination findings in a case of confirmed LDX toxicosis in a dog. Although the patient did not survive treatment, postmortem examination and microscopic evaluation of tissues allowed visualization of the extent of systemic pathophysiology. With prompt treatment, the prognosis of amphetamine toxicosis in dogs is generally considered good; however, this case report demonstrates a severe case in which even prompt and appropriate treatment did not prevent mortality. This suggests a need to establish negative prognostic indicators for which to monitor in cases of amphetamine toxicosis. Finally, this report is also unique in the fact that the LDX toxicosis was confirmed using a toxicological analysis technique not previously described clinically in dogs.
Topics: Humans; Female; Dogs; Animals; Lisdexamfetamine Dimesylate; Central Nervous System Stimulants; Dextroamphetamine; Attention Deficit Disorder with Hyperactivity; Treatment Outcome
PubMed: 38412018
DOI: 10.1111/vec.13370 -
Emergency Medicine Clinics of North... Feb 2024Physiologic and psychological effects of substance use are common occurrences. They may be the proximate purpose of the exposure or related to an unintended... (Review)
Review
Physiologic and psychological effects of substance use are common occurrences. They may be the proximate purpose of the exposure or related to an unintended complication. Acute short-term exposure effects may not be the same as long-term effects. These effects are mediated by different receptors they act on and the homeostatic changes that occur due to repeat exposure. We review in this article the physiologic and psychological effects from exposure to commonly encountered drugs, ethanol, sedative hypnotics, cocaine, amphetamines, marijuana, opioids, nicotine, hydrocarbons (halogenated and non-halogenated), and nitrous oxide.
Topics: Humans; Substance-Related Disorders; Ethanol; Hypnotics and Sedatives; Cocaine; Amphetamines
PubMed: 37977754
DOI: 10.1016/j.emc.2023.06.022 -
Ugeskrift For Laeger Jan 2024This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was...
This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was associated with an increase in abdominal pressure during defaecation and the other occurred during treatment with methylphenidate. Based on the published 43 cases, risk factors include male sex, increased intraabdominal pressure or increased vascular pressure. Methylphenidate most likely increased the blood pressure, and dissections of other arteries have been described during treatment with this and the similar drug amphetamine.
Topics: Humans; Male; Amphetamine; Blood Pressure; Celiac Artery; Methylphenidate; Splenic Artery; Adult
PubMed: 38235724
DOI: 10.61409/V07230468