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Therapeutic Drug Monitoring Apr 2020The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among...
BACKGROUND
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders, depression, or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs, such as antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.
METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.
RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamic points toward interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B also points toward such interactions, between 2C-B and prescription drugs such as antidepressants and ADHD medication.
CONCLUSIONS
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.
Topics: Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Depressive Disorder; Dimethoxyphenylethylamine; Drug Interactions; Humans; Phenethylamines; Prescription Drugs
PubMed: 32022784
DOI: 10.1097/FTD.0000000000000725 -
Neuroscience and Biobehavioral Reviews Oct 2022The relationship between amphetamine use and aggressive or violent behaviour is unclear. This review examined laboratory data collected in humans, who were administered... (Review)
Review
The relationship between amphetamine use and aggressive or violent behaviour is unclear. This review examined laboratory data collected in humans, who were administered an acute dose of amphetamine or methamphetamine, in order to investigate the link between amphetamines and aggression. It is registered with PROSPERO (CRD42019127711). Included in the analysis are data from twenty-eight studies. Behavioural and/or subjective measures of aggression were assessed in one thousand and sixty-nine research participants, with limited amphetamine-use histories, following a single amphetamine dose (0-35 mg). The available published evidence indicates that neither amphetamine nor methamphetamine acutely increased aggression as assessed by traditional laboratory measures. Future research should assess supratherapeutic amphetamine doses as well as include a broader range of multiple aggression measures, facilitating simultaneous assessment of the various components that comprise this complex, multifaceted construct.
Topics: Aggression; Amphetamine; Amphetamine-Related Disorders; Humans; Methamphetamine
PubMed: 35926727
DOI: 10.1016/j.neubiorev.2022.104805 -
Addiction Biology Sep 2022N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT agonists containing substances emerging on the illicit drug market as a replacement for...
N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p < 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.
Topics: Animals; Body Temperature Regulation; Dose-Response Relationship, Drug; Hallucinogens; Phenethylamines; Rats; Rats, Wistar
PubMed: 36001433
DOI: 10.1111/adb.13216 -
Neuroscience and Biobehavioral Reviews Mar 2023In substance use and addiction, inhibitory control is key to ignoring triggers, withstanding craving and maintaining abstinence. In amphetamine-type stimulant (ATS)... (Meta-Analysis)
Meta-Analysis Review
In substance use and addiction, inhibitory control is key to ignoring triggers, withstanding craving and maintaining abstinence. In amphetamine-type stimulant (ATS) users, most research focused on behavioral inhibition, but largely neglected the equally important subdomain of cognitive interference control. Given its crucial role in managing consumption, we investigated the relationship between interference control and chronic ATS use in adults. A database search (Pubmed & Web of Science) and relevant reviews were used to identify eligible studies. Effect sizes were estimated with random effects models. Subgroup, meta-regression, and sensitivity analyses explored heterogeneity in effect sizes. We identified 61 studies (53 datasets) assessing interference control in 1873 ATS users and 1905 controls. Findings revealed robust small effect sizes for ATS-related deficits in interference control, which were mainly seen in methamphetamine, as compared to MDMA users. The differential effects are likely due to tolerance-induced dopaminergic deficiencies (presumably most pronounced in methamphetamine users). Similarities between different ATS could be due to noradrenergic deficiencies; but elucidating their functional role in ATS users requires further/more research.
Topics: Adult; Humans; Amphetamine; Central Nervous System Stimulants; Methamphetamine; Substance-Related Disorders; Dopamine; Amphetamine-Related Disorders
PubMed: 36581170
DOI: 10.1016/j.neubiorev.2022.105020 -
The Analyst May 2021The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current...
The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current approaches require complex sample purification strategies alongside significant analysis time. Given the high prevalence of MA within the global drug market, there remains a need for rapid, portable and alternative screening approaches appropriate for direct detection within biological matrices for employment across the forensic and clinical environments. This contribution illustrates the use of an electrochemiluminescence (ECL) strategy for the screening of MA, amphetamine (AMP) and para hydroxy-methamphetamine (pOH-MA) for such applications. The sensing system showed ideal analytical performance with linear ranges at forensically relevant concentrations of 0.1 μM to 0.5 mM for MA, 10 μM to 1 mM AMP and 10 μM to 5 mM for pOH-MA, and superb detection limits of 74.6 nM, 6 μM and 82. μM for MA, AMP and pOH-MA respectively. Furthermore, the sensor was successful in the detection of MA, AMP and pOH-AMP within human pooled serum, artificial urine and saliva, without any prior purification strategies. Here a portable ECL sensor is detailed for the successful employment of the direct screening of these amphetamine type substances and their corresponding metabolites at clinically and forensically relevant concentrations within a range of biological matrices. This approach successfully represents a strong proof-of-concept, for a novel, simple and rapid screening method with significant potential for high-throughput screening of biological samples for drug metabolites, widening the avenues where ECL sensors could be employed.
Topics: Amphetamine; Humans; Luminescent Measurements; Methamphetamine; Saliva; Substance Abuse Detection
PubMed: 33999061
DOI: 10.1039/d1an00226k -
Journal of Pharmaceutical and... May 2023A rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the targeted analysis of 75 phenethylamines...
A rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the targeted analysis of 75 phenethylamines and their derivatives from the hair matrix. The monitored classes of phenethylamines included the 2C series, D series, N-benzyl derivatives, mescaline-derived compounds, MDMA analogs, and benzodifurans. Approximately 20 mg of hair was weighed and pulverized with 0.1% formic acid in methanol by cryogenic grinding. After ultrasonication, centrifugation, and filtration, the supernatant was analyzed by LC-MS/MS operating in the scheduled multiple reaction monitoring mode. Phenethylamines and their derivatives were separated in 13 min on a biphenyl column (2.6 µm, 100 Å, 100 × 3.0 mm) using a gradient eluting mobile phase composed of 0.1% formic acid in water and acetonitrile. The developed and validated method showed good selectivity, sensitivity (LOD: 0.5-10 pg/mg and LOQ: 1-20 pg/mg), linearity (R > 0.997), accuracy and precision (< 20%), and stability. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of phenethylamines in hair from authentic forensic cases.
Topics: Chromatography, Liquid; Phenethylamines; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Hair
PubMed: 37018959
DOI: 10.1016/j.jpba.2023.115367 -
Journal of Psychopharmacology (Oxford,... Mar 2022Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or... (Review)
Review
Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or behavior are poorly understood. Controlled laboratory studies with well-defined psychological constructs are valuable to understand how these drugs manifest their therapeutic benefit. However, there are substantial methodological differences between clinical studies investigating therapeutic outcome and laboratory studies investigating the processes that might underlie the therapeutic effects. Here, we examine some of these differences using the example of 3,4-methylenedioxymethamphetamine (MDMA). We review differences in expectancies, social and physical context, participant characteristics, pharmacological factors, and outcome measures in studies with participants who do or do not have psychiatric diagnoses. We describe the challenges and opportunities in translating findings from laboratory studies to the clinic and identify ways to bridge the gap between these approaches.
Topics: Affect; Humans; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Translational Research, Biomedical
PubMed: 33944625
DOI: 10.1177/02698811211015221 -
Psychopharmacology Oct 2022Trace amine-associated receptor 1 (TAAR1) is the best-studied receptor of trace amines, a group of biogenic amines expressed at a relatively low level in the mammalian...
RATIONALE
Trace amine-associated receptor 1 (TAAR1) is the best-studied receptor of trace amines, a group of biogenic amines expressed at a relatively low level in the mammalian brain. Growing evidence suggests that TAAR1 plays a critical role in various neuropsychiatric disorders. Given that selective TAAR1 agonists were shown to produce pro-cognition and antipsychotic-like effects as well as to suppress drug use and relapse, they have been proposed to be novel treatments for mental disorders such as schizophrenia and addiction. However, the aversive effects of selective TAAR1 agonists remain largely unknown.
OBJECTIVES
Here, we evaluated whether the selective TAAR1 full agonist RO5166017 and partial agonist RO5263397 could induce conditioned taste aversion (CTA).
RESULTS
We found that RO5166017 and RO5263397 produced significant aversions to both saccharin and NaCl taste novelty. Furthermore, RO5166017 produced CTA to saccharin in TAAR1 heterozygous knockout (taar1) and wild-type rats but not in TAAR1 homozygous knockout rats (taar1), suggesting that TAAR1 was sufficient for the taste aversive stimulus property of RO5166017.
CONCLUSIONS
Taken together, our data indicate that selective TAAR1 agonists could produce strong CTA. Our study urges careful evaluations of the aversive effects of TAAR1 agonists before translating them to clinical use for the treatment of mental disorders.
Topics: Animals; Antipsychotic Agents; Aversive Agents; Humans; Mammals; Oxazoles; Phenethylamines; Rats; Receptors, G-Protein-Coupled; Saccharin; Sodium Chloride; Taste; Taste Perception
PubMed: 36056214
DOI: 10.1007/s00213-022-06222-5 -
Journal of Forensic Sciences Jul 2023Bone samples are valuable for examining the cause of death and circumstance leading up to death when body fluids are not available for forensic toxicological analysis....
Bone samples are valuable for examining the cause of death and circumstance leading up to death when body fluids are not available for forensic toxicological analysis. Examined were heat-induced changes in methamphetamine and amphetamine concentrations in femurs removed from methamphetamine-injected mice to determine if the burned bones could be used for toxicology testing. The femurs were heated at 100°C, 300°C, or 500°C for 10 or 30 min. The tissue structure of the heated femurs was preserved at 100°C for 30 min but was destructed at higher temperatures. Methamphetamine and amphetamine were detected in femurs heated at 100°C for 10 min, 100°C for 30 min, and 300°C for 10 min (with methamphetamine and amphetamine concentrations ranging from 0.36 to 35 μg/g and 0.54 to 47 μg/g, respectively). Methamphetamine and amphetamine were detectable when heated above their decomposition temperature as a result of limited heat transfer do to protection provide by the femoral muscle. Thus, the bone could be a useful analytical sample in cases of burn-related deaths, where it is difficult to collect body fluids.
Topics: Animals; Mice; Amphetamine; Femur; Hot Temperature; Methamphetamine; Temperature
PubMed: 37149745
DOI: 10.1111/1556-4029.15263 -
Biomedical Chromatography : BMC Jul 2023The purpose of this review study was to sum up the main recent advances reported in the scientific literature about the detection of common drugs of abuse in biological... (Review)
Review
The purpose of this review study was to sum up the main recent advances reported in the scientific literature about the detection of common drugs of abuse in biological samples upon their collection by dried blood spot devices. The most recent, innovative and fully validated methods for the qualitative and/or quantitative detection of common drugs of abuse are reported, including alprazolam, clonazepam, diazepam, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methyl-enedioxyethylamphetamine, amphetamine, methamphetamine, cocaine, tetrahydrocannabinol, 6-monoacetylmorphine, morphine, codeine, hydromorphone, hydrocodone, oxycodone, noroxycodone, tramadol, methadone, buprenorphine, fentanyl, ketamine and their respective metabolites and γ-hydroxybutyric acid. Dried blood spot proved to be extremely promising for routine analysis of forensic cases, although large-scale experiments on real samples need to be performed to confirm the emerging advantages of the technique and remove the potential limitations still affecting its widespread application.
Topics: Tandem Mass Spectrometry; Substance Abuse Detection; Codeine; Methamphetamine; Amphetamine
PubMed: 36417316
DOI: 10.1002/bmc.5555