Khat, a Cultural Chewing Drug: A Toxicokinetic and Toxicodynamic Summary.

Khat () is a recreational, chewed herbal drug that has been used as a psychostimulant for centuries in East Africa and the Arabian Peninsula, namely in Somalia, Ethiopia, and Yemen. However, the growing worldwide availability of khat has produced widespread concern. The plant comprises a large number of active substances, among which cathinone, cathine, and norephedrine are the main constituents, which can be included in the group of sympathomimetics of natural origin.

Dopamine D1 receptors mediate methamphetamine-induced dopaminergic damage: involvement of autophagy regulation via the AMPK/FOXO3A pathway.

Rationale: Clinical studies have revealed that methamphetamine abuse increases risk for developing Parkinson's diseases. It is thus important to elucidate the mechanisms by which methamphetamine damages dopaminergic neurons.

Objectives: The present study was designed to elucidate the role of the dopamine D1 receptor in methamphetamine-mediated dopaminergic neuronal damage and its underlying mechanisms.

MDMA and memory, addiction, and depression: dose-effect analysis.

Rationale: ±3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that shows substantial promise as a psychotherapeutic agent. Still, there is some concern regarding its behavioral toxicity, and its dose-effect relationship is poorly understood. We previously explored the role of dose in the cognitive effects of MDMA in a systematic review of existing literature and found no evidence in animals that MDMA impairs memory at low doses (< 3 mg/kg) but mixed results at high doses (≥ 3 mg/kg).

Novel D/5-HT receptor modulators related to cariprazine with potential implication to schizophrenia treatment.

Schizophrenia is a serious mental disorder without a fully understood pathomechanism, but which involves dysregulation of neurotransmitters and their receptors. The best option for the management of schizophrenia comprises so-called multi-target ligands, similar to the third generation of neuroleptics. Dopamine type 2 receptors (DRs) are the main target in the treatment of schizophrenia, in particular for mitigation of the positive symptoms.

Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study.

With reports from Australia, Canada, USA, Hawaii and Colorado documenting a link between cannabis and congenital anomalies (CAs), this relationship was investigated in Europe. Data on 90 CAs were accessed from Eurocat. Tobacco and alcohol consumption and median household income data were from the World Bank.

Radiation Effects on Methamphetamine Pharmacokinetics and Pharmacodynamics in Rats.

Background And Objectives: Whole-body radiation exposure has been shown to alter the pharmacokinetics of certain drugs in both animal models and humans, but little is known about the effect of radiation on psychoactive medications. These drugs may have altered pharmacokinetics when administered during or after space travel or therapeutic or accidental radiation exposure, resulting in reduced efficacy or increased toxicity.

Methods: Methamphetamine was used to determine the effects of acutely administered 1, 3, and 6 Gy radiation on drug pharmacokinetics and pharmacodynamics.

Remembering Molly: Immediate and delayed false memory formation after acute MDMA exposure.

The entactogen 3,4-Methylenedioxymethamphetamine (MDMA) is increasingly being recognized for its therapeutic potential but is also widespread in nightlife settings where it may co-occur with crime. Since previous research detected impaired verbal memory during acute MDMA intoxication, understanding the drug's ramifications in an applied legal context becomes crucial. We conducted a double-blind, placebo-controlled trial to examine acute and delayed effects of MDMA (75 mg) on false memory in 60 healthy volunteers with a history of MDMA use, using three well-established false memory methods: a basic, associative word list (Deese/Roediger-McDermott (DRM)) paradigm and two applied misinformation tasks using a virtual reality crime.

Emergency department visits and trends related to cocaine, psychostimulants, and opioids in the United States, 2008-2018.

Background: Drug-related emergency department (ED) visits are escalating, especially for stimulant use (i.e., cocaine and psychostimulants such as methamphetamine).

The diagnostic utility of procalcitonin is limited in the setting of methamphetamine toxicity.

Procalcitonin (PCT) is a biomarker with greater specificity for bacterial infection than other current laboratory markers. However, PCT can also be elevated in the setting of several noninfectious conditions. A recent case report describes a patient with elevated PCT in the context of acute methamphetamine intoxication, but without evidence of infection.

Does paternal methamphetamine exposure affect the behavior of rat offspring during development and in adulthood?

Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear.

Methamphetamine, neurotransmitters and neurodevelopment.

Methamphetamine (MA), as massively abused psychoactive stimulant, has been associated with many neurological diseases. It has various potent and neurotoxic properties. There are many mechanisms of action that contribute to its neurotoxic and degenerative effects, including excessive neurotransmitter (NEU) release, blockage of NEU uptake transporters, degeneration of NEU receptors, process of oxidative stress etc.

The relationship between serum brain-derived neurotrophic level and neurocognitive functions in chronic methamphetamine users.

Methamphetamine (METH) is a highly addictive psychostimulant with serious neurotoxic effects. Given evidence indicating that brain-derived neurotrophic factor (BDNF) is associated with addictive behaviors, this study aimed to investigate the serum level of BDNF and cognitive functions in chronic METH users and healthy participants. Thirty-seven chronic METH users and 37 healthy participants were recruited in this study.

in Vitro Effect of Methamphetamine on Proliferation, Differentiation and Apoptosis of Adipose Tissue Stem Cells.

Purpose: Among abused substances, methamphetamine is a psychostimulant drug widely used recreationally with public health importance. This study investigated the effect of methamphetamine on proliferation, differentiation, and apoptosis of human adipose tissue stem cells (AdSCs).

Methods: AdSCs were isolated from human abdominal adipose tissue and were characterized for mesenchymal properties and growth kinetics.

[Fatal serotonin syndrome induced by ecstasy consumption].

The use of amphetamines and amphetamine derivatives such as ecstasy can cause serotonin toxic syndrome, an uncommon but potentially serious adverse effect. Although most of the reported cases evolve spontaneously and favourably, in rare cases, serious complications can occur leading to the death of the patient. We report the case of a 27-year-old man admitted to our emergency department for altered consciousness with hyperthermia at 42°C after illicit drug use.

Dopamine and Methamphetamine Differentially Affect Electron Transport Chain Complexes and Parkin in Rat Striatum: New Insight into Methamphetamine Neurotoxicity.

Methamphetamine (METH) is a highly abused psychostimulant that is neurotoxic to dopaminergic (DAergic) nerve terminals in the striatum and increases the risk of developing Parkinson's disease (PD). In vivo, METH-mediated DA release, followed by DA-mediated oxidative stress and mitochondrial dysfunction in pre- and postsynaptic neurons, mediates METH neurotoxicity. METH-triggered oxidative stress damages parkin, a neuroprotective protein involved in PD etiology via its involvement in the maintenance of mitochondria.

MDMA related neuro-inflammation and adenosine receptors.

3,4-methylenedioxymethamphetamine (MDMA) is a world-wide abused psychostimulant, which has the neurotoxic effects on dopaminergic and serotonergic neurons in both rodents and non-human primates. Adenosine acts as a neurotransmitter in the brain through the activation of four specific G-protein-coupled receptors and it acts as a neuromodulator of dopamine neurotransmission. Recent studies suggest that stimulation of adenosine receptors oppose many behavioral effects of methamphetamines.

Effects of methamphetamine-induced neurotoxicity on striatal long-term potentiation.

Rationale: Methamphetamine (METH) exposure is associated with damage to central monoamine systems, particularly dopamine signaling. Rodent models of such damage have revealed a decrease in the amplitude of phasic dopamine signals and significant striatal dysfunction, including changes in the molecular, system, and behavioral functions of the striatum. Dopamine signaling through D1 receptors promotes corticostriatal long-term potentiation (LTP), a critical substrate of these striatal functions.

The Crosstalk Between Neurons and Glia in Methamphetamine-Induced Neuroinflammation.

Methamphetamine (METH), an illicit psycho-stimulant, is widely known as an addictive drug that may cause neurotoxic effects. Previous researches on METH abuse have mainly focused on neurotransmitters, such as dopamine and glutamate. However, there is growing evidence that neuroinflammation also plays an important role in the etiology and pathophysiology of brain dysfunction induced by METH abuse.

Advances in Reversal Strategies of Opioid-induced Respiratory Toxicity.

Opioids may produce life-threatening respiratory depression and death from their actions at the opioid receptors within the brainstem respiratory neuronal network. Since there is an increasing number of conditions where the administration of the opioid receptor antagonist naloxone is inadequate or undesired, there is an increased interest in the development of novel reversal and prevention strategies aimed at providing efficacy close to that of the opioid receptor antagonist naloxone but with fewer of its drawbacks such as its short duration of action and lesser ability to reverse high-affinity opioids, such as carfentanil, or drug combinations. To give an overview of this highly relevant topic, the authors systematically discuss predominantly experimental pharmacotherapies, published in the last 5 yr, aimed at reversal of opioid-induced respiratory depression as alternatives to naloxone.

The Neuroprotective Effects of the CB2 Agonist GW842166x in the 6-OHDA Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder associated with dopamine neuron loss and motor dysfunction. Neuroprotective agents that prevent dopamine neuron death hold great promise for slowing the disease's progression. The activation of cannabinoid (CB) receptors has shown neuroprotective effects in preclinical models of neurodegenerative disease, traumatic brain injury, and stroke, and may provide neuroprotection against PD.

High sensitive electrochemical methamphetamine detection in serum and urine via atom transfer radical polymerization signal amplification.

Herein we designed a highly sensitive and selective biosensor for methamphetamine (METH) detection based on aptamer recognition probe and atom transfer radical polymerization (ATRP) signal amplification strategy. In this experiment, METH aptamer and its complementary DNA strand were first attached to the electrode surface. In the presence of METH, the prioritized conjugation between METH and the aptamer will take one strand of DNA from the double-stranded DNA, so that the third segment of azide-modified DNA could be successfully modified onto the electrode surface.

Toxicological Analysis of Cases of Mixed Poisonings with Synthetic Cathinones and Other Drugs of Abuse.

Some of the most commonly used new psychoactive substances (NPSs) are synthetic cathinones (SCs). The literature increasingly indicates that SCs have a significant addictive potential and pose a high risk to human health and life. The vast majority of SC users take a number of substances simultaneously.

Short-Term Cumulative Exposure to Ambient Traffic-Related Black Carbon and Blood Pressure: MMDA Traffic Enforcers' Health Study.

Exposure to traffic-related air pollution is linked with acute alterations in blood pressure (BP). We examined the cumulative short-term effect of black carbon (BC) exposure on systolic (SBP) and diastolic (DBP) BP and assessed effect modification by participant characteristics. SBP and DBP were repeatedly measured on 152 traffic enforcers.

Peri-adolescent exposure to (meth)amphetamine in animal models.

Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs adult-initiated exposure is incomplete. We consider the existing animal research in this area for (meth)amphetamines. Established for a number of phenotypes, is lower sensitivity of peri-adolescents than adults to acute effects of (meth)amphetamines, including neurotoxic effects of binge-level exposure.