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Psychiatria Polska Oct 2022MDMA is one of the most commonly used drugs in the world. Clinical studies are currently being conducted around the world on the use of this substance in the treatment...
OBJECTIVES
MDMA is one of the most commonly used drugs in the world. Clinical studies are currently being conducted around the world on the use of this substance in the treatment of PTSD and alcoholism. However, little demographic information is available on users who use the substance for recreational purposes. The aim was to determine basic demographic and helath characteristics with validated tools.
METHODS
The authors prepared an original questionnaire on the demography of MDMA users and combined it with the General Health Questionnaire-28 (GHQ-28) and the Hospital Anxiety and Depression Scale (HADS). The survey was sent to Polish MDMA users via the Internet.
RESULTS
304 responses were received from people over 18 years of age. MDMA is widespread among young adults, in many different places of residence and regardless of gender. The users take MDMA in both pill and crystal form and very rarely test drugs bought from a dealer. Most users feel that MDMA has had a good impact on their lives.
CONCLUSIONS
MDMA is rarely used as the only psychoactive substance. MDMA users rate their health higher than people using other psychoactive substances.
Topics: Young Adult; Humans; Adolescent; Adult; N-Methyl-3,4-methylenedioxyamphetamine; Illicit Drugs; Surveys and Questionnaires; Emotions; Demography
PubMed: 37074860
DOI: 10.12740/PP/OnlineFirst/134317 -
Molecules (Basel, Switzerland) Jul 2022Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera , , and biosynthesize novel alkaloids and... (Review)
Review
Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera , , and biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer's disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including and , have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera , , and and describe their traditional and pharmacological applications.
Topics: Allium; Amaryllidaceae; Amaryllidaceae Alkaloids; Crinum; Humans; Phytochemicals; Plant Extracts
PubMed: 35889346
DOI: 10.3390/molecules27144475 -
Microbiology Spectrum Jun 2023Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota....
Gut Microbiota Taxon-Dependent Transformation of Microglial M1/M2 Phenotypes Underlying Mechanisms of Spatial Learning and Memory Impairment after Chronic Methamphetamine Exposure.
Methamphetamine (METH) exposure may lead to cognitive impairment. Currently, evidence suggests that METH exposure alters the configuration of the gut microbiota. However, the role and mechanism of the gut microbiota in cognitive impairment after METH exposure are still largely unknown. Here, we investigated the impact of the gut microbiota on the phenotype status of microglia (microglial phenotypes M1 and microglial M2) and their secreting factors, the subsequent hippocampal neural processes, and the resulting influence on spatial learning and memory of chronically METH-exposed mice. We determined that gut microbiota perturbation triggered the transformation of microglial M2 to M1 and a subsequent change of pro-brain-derived neurotrophic factor (proBDNF)-p75-mature BDNF (mBDNF)-TrkB signaling, which caused reduction of hippocampal neurogenesis and synaptic plasticity-related proteins (SYN, PSD95, and MAP2) and, consequently, deteriorated spatial learning and memory. More specifically, we found that , , , and might dramatically affect the homeostasis of microglial M1/M2 phenotypes and eventually contribute to spatial learning and memory decline after chronic METH exposure. Finally, we found that fecal microbial transplantation could protect against spatial learning and memory decline by restoring the microglial M1/M2 phenotype status and the subsequent proBDNF-p75/mBDNF-TrkB signaling in the hippocampi of chronically METH-exposed mice. Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated "specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment" pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.
Topics: Mice; Animals; Methamphetamine; Spatial Learning; Microglia; Gastrointestinal Microbiome; Memory Disorders; Phenotype
PubMed: 37212669
DOI: 10.1128/spectrum.00302-23 -
Folia Medica Cracoviensia Jul 2023Drug-abuse detection tests are becoming increasingly commonplace in patient care today and provide a rapid and effective method for identifying illicit substances.... (Review)
Review
Drug-abuse detection tests are becoming increasingly commonplace in patient care today and provide a rapid and effective method for identifying illicit substances. Occasionally, they may yield a positive result, indicating the presence of a substance, even though the individual has not consumed the suspected drug what sometimes can significantly impact both medical and legal decisions. The study outlines the substances that can lead to false-positive drug test results for amphetamines, cannabinoids, and benzodiazepines. The study's findings have revealed pivotal insights for patients receiving chronic treatment and their primary care physicians. Notably, amphetamine assays appear to be most prone to cross-reactivity with other substances. The beta-blocker group of medications, confirmed by various studies to interfere with amphetamine assays, could pose a substantial challenge in drug screening given its widespread use. Efavirenz also warrants mention, as it frequently triggers positive results for both benzodiazepine and cannabinoid assays among its users. This research helps highlight new areas for further investigation and aims to guide clinicians in their daily practice, especially when interpreting questionable positive drug-abuse test results. This comprehensive review serves as a valuable resource for clinicians to navigate false-positive scenarios effectively and maintain the highest standard of patient care.
Topics: Humans; Amphetamine; Substance Abuse Detection
PubMed: 37903383
DOI: 10.24425/fmc.2023.145917 -
British Journal of Pharmacology Sep 2022Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by... (Review)
Review
Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Amphetamine; Animals; Antimanic Agents; Dextroamphetamine; Mania; Rats; Ultrasonics; Vocalization, Animal
PubMed: 33830495
DOI: 10.1111/bph.15487 -
The International Journal of... Aug 2021Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine...
BACKGROUND
Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.
METHODS
The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.
RESULTS
Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.
CONCLUSIONS
These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.
Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Central Nervous System Stimulants; Discrimination Learning; Interoception; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saimiri; Synthetic Cathinone
PubMed: 33909067
DOI: 10.1093/ijnp/pyab017 -
Biology Letters Nov 2022Bodyguard manipulation is a behavioural manipulation in which the host's behaviour is altered to protect the inducer's offspring from imminent biotic threats. The... (Review)
Review
Bodyguard manipulation is a behavioural manipulation in which the host's behaviour is altered to protect the inducer's offspring from imminent biotic threats. The behaviour of a post-parasitoid-egressed host resembles a quiescence state with a characteristic reduction in motor activities like feeding, locomotion, respiration, and metabolic rate. Yet, they respond aggressively through a defensive response when disturbed, which ensures better fitness for the parasitoid's offspring. The behavioural changes in the parasitized host appear after the parasitoid egression. Several hypotheses have been proposed to elucidate how the parasitized host's behaviour is manipulated for the fitness benefits of the inducers, but the exact mechanism is still unknown. We review evidence to explain the behavioural changes and their mechanism in the parasitized hosts. The evidence suggests that parasitoid pre-pupal egression may drive the host to stress-induced sleep. The elevated octopamine concentration also reflects the stress response in the host. Given the theoretical links between the behavioural and the physiological changes in the post-parasitoid-egressed host and stress-induced sleep of other invertebrates, we suggest that behavioural studies combined with functional genomics, proteomics, and histological analyses might give a better understanding of bodyguard manipulation.
Topics: Animals; Sleep; Respiration; Octopamine; Locomotion; Pupa
PubMed: 36448293
DOI: 10.1098/rsbl.2022.0280 -
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 -
PloS One 2023Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks.
METHODS
Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy.
RESULTS
We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006).
CONCLUSION
The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences.
CLINICAL TRIAL REGISTRATION NUMBER
CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
Topics: Humans; Dextroamphetamine; Caffeine; Healthy Volunteers; Dopamine; Australia; Amphetamine; Double-Blind Method
PubMed: 37440493
DOI: 10.1371/journal.pone.0287538 -
Molecular Pharmacology Oct 2021The drugs salmeterol, formoterol, and salbutamol constitute the frontline treatment of asthma and other chronic pulmonary diseases. These drugs activate the 2-adrenergic...
The drugs salmeterol, formoterol, and salbutamol constitute the frontline treatment of asthma and other chronic pulmonary diseases. These drugs activate the 2-adrenergic receptors (2-AR), a class A G protein-coupled receptor (GPCR), and differ significantly in their clinical onset and duration of actions. According to the microkinetic model, the long duration of action of salmeterol and formoterol compared with salbutamol were attributed, at least in part, to their high lipophilicity and increased local concentrations in the membrane near the receptor. However, the structural and molecular bases of how the lipophilic drugs reach the binding site of the receptor from the surrounding membrane remain unknown. Using a variety of classic and enhanced molecular dynamics simulation techniques, we investigated the membrane partitioning characteristics, binding, and unbinding mechanisms of the ligands. The obtained results offer remarkable insight into the functional role of membrane lipids in the ligand association process. Strikingly, salmeterol entered the binding site from the bilayer through transmembrane helices 1 and 7. The entry was preceded by membrane-facilitated rearrangement and presentation of its phenyl-alkoxy-alkyl tail as a passkey to an access route gated by F193, a residue known to be critical for salmeterol's affinity. Formoterol's access is through the aqueous path shared by other 2-AR agents. We observed a novel secondary path for salbutamol that is distinct from its primary route. Our study offers a mechanistic description for the membrane-facilitated access and binding of ligands to a membrane protein and establishes a groundwork for recognizing membrane lipids as an integral component in the molecular recognition process. SIGNIFICANCE STATEMENT: The cell membrane's functional role behind the duration of action of long-acting β2-adrenergic receptor (β2-AR) agonists such as salmeterol has been a subject of debate for a long time. This study investigated the binding and unbinding mechanisms of the three commonly used β2-AR agonists, salmeterol, formoterol, and salbutamol, using advanced simulation techniques. The obtained results offer unprecedented insights into the active role of membrane lipids in facilitating access and binding of the ligands, affecting the molecular recognition process and thus their pharmacology.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Binding Sites; Cell Membrane; Delayed-Action Preparations; Formoterol Fumarate; Humans; Molecular Docking Simulation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Salmeterol Xinafoate
PubMed: 34334369
DOI: 10.1124/molpharm.121.000285