Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.478
Filtrar
1.
Sci Rep ; 14(1): 14782, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926480

RESUMO

Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.


Assuntos
Cognição , Alucinógenos , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Alucinógenos/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Cognição/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Atenção/efeitos dos fármacos , Memória/efeitos dos fármacos
2.
Sci Rep ; 14(1): 14485, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914648

RESUMO

Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.


Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Hipertermia , N-Metil-3,4-Metilenodioxianfetamina , Microbioma Gastrointestinal/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Animais , Ratos , Masculino , Ácidos e Sais Biliares/metabolismo , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Ratos Sprague-Dawley , RNA Ribossômico 16S/genética , Ácido Desoxicólico/metabolismo
3.
Clin Toxicol (Phila) ; 62(5): 303-313, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38884342

RESUMO

INTRODUCTION: Acute metamfetamine toxicity is characterized by stimulant effects and neuropsychiatric disturbance, which is attenuated by gamma-aminobutyric acid type A receptor agonists including benzodiazepines. We utilized clinical registry data to examine the effect of co-exposure to a gamma-aminobutyric acid type B receptor agonist (gamma-hydroxybutyrate) in illicit drug cases with analytically confirmed exposure to metamfetamine. METHODS: The Emerging Drugs Network of Australia Victoria is an ethics board-approved prospective registry collecting clinical and analytical data (utilising blood samples) on emergency department illicit drug presentations. Comparison groups were defined by analytically confirmed exposure: lone metamfetamine, metamfetamine plus gamma-hydroxybutyrate, metamfetamine plus benzodiazepine, metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine. Cases with co-exposure to other stimulants or sedatives were excluded. RESULTS: Median metamfetamine blood concentrations were significantly greater in metamfetamine plus gamma-hydroxybutyrate (n = 153, median = 0.20 mg/L, interquartile range: 0.10-0.32 mg/L, 95 per cent confidence interval: 0.20-0.23 mg/L) and metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine (n = 160, median = 0.20 mg/L, interquartile range: 0.10-0.30 mg/L, 95 per cent confidence interval: 0.20-0.30 mg/L) positive groups compared to gamma-hydroxybutyrate negative groups including metamfetamine (n = 81, median = 0.10 mg/L, interquartile range: 0.05-0.21 mg/L, 95 per cent confidence interval: 0.09-0.18 mg/L) and metamfetamine plus benzodiazepine (n = 73, median = 0.10 mg/L, interquartile range: 0.06-0.20 mg/L, 95 per cent confidence interval: 0.09-0.20 mg/L) groups (P < 0.0004). Presenting heart rate in metamfetamine plus gamma-hydroxybutyrate cases (n = 153, median = 72 beats per minute, interquartile range: 63-86 beats per minute, 95 per cent confidence interval: 70-78 beats per minute) was significantly lower than metamfetamine plus benzodiazepine cases (n = 73, median = 84 beats per minute, interquartile range: 73-98 beats per minute, 95 per cent confidence interval: 80-90 beats per minute, P < 0.0001), and lone metamfetamine cases (n = 81, median = 110 beats per minute, interquartile range: 87-131 beats per minute, 95 per cent confidence interval: 93-120 beats per minute, P < 0.0001). Presenting temperature in metamfetamine plus gamma-hydroxybutyrate cases (median = 35.8 °C, interquartile range: 35.0-36.2 °C, 95 per cent confidence interval 35.6-35.9 °C) was significantly lower than metamfetamine plus benzodiazepine cases (median 36.2 °C, interquartile range 35.7-36.6 °C, 95 per cent confidence interval, 36.0-36.4 °C, P = 0.017), and lone metamfetamine cases (median = 36.5 °C, interquartile range: 35.8-37.1 °C, 95 per cent confidence interval: 36.2-36.7 °C, P < 0.0001). Median presenting systolic blood pressure was significantly (P ≤ 0.001) lower in benzodiazepine positive groups (metamfetamine plus benzodiazepine median = 120 mmHg, interquartile range: 109-132 mmHg, 95 per cent confidence interval: 116-124 mmHg and metamfetamine plus benzodiazepine plus gamma-hydroxybutyrate median = 124 mmHg, interquartile range: 110-137 mmHg, 95 per cent confidence interval: 120-129 mmHg). Incidence of sedation (Glasgow Coma Scale less than 9) was significantly greater in metamfetamine plus gamma-hydroxybutyrate cases (63 per cent) compared to metamfetamine plus benzodiazepine cases (27 per cent, P < 0.0001) and lone metamfetamine cases (15 per cent, P < 0.0001). Incidence of agitation was significantly lower in metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine cases (17 per cent, P < 0.0001) and metamfetamine plus gamma-hydroxybutyrate cases (34 per cent, P = 0.0004) compared to lone metamfetamine cases (58 per cent). DISCUSSION: Differences in gamma-aminobutyric acid type A and B receptor physiology may offer a gamma-aminobutyric acid type B agonist-facilitated alternative pharmacodynamic mechanism able to attenuate metamfetamine stimulant and neuropsychiatric toxicity. CONCLUSION: Metamfetamine intoxicated patients with analytically confirmed co-exposure to gamma-hydroxybutyrate had significantly reduced heart rate, body temperature and incidence of agitation compared to patients with lone metamfetamine exposure. Metamfetamine intoxicated patients with analytically confirmed co-exposure to a benzodiazepine had significantly reduced systolic blood pressure compared to patients with lone metamfetamine exposure. We hypothesize that gamma-aminobutyric acid type B receptor agonists may be beneficial in the management of acute metamfetamine toxicity.


Assuntos
Oxibato de Sódio , Humanos , Feminino , Masculino , Adulto , Estimulantes do Sistema Nervoso Central , Benzodiazepinas , Adulto Jovem , Estudos Prospectivos , N-Metil-3,4-Metilenodioxianfetamina , Interações Medicamentosas , Transtornos Relacionados ao Uso de Substâncias , Sistema de Registros , Adolescente , Drogas Ilícitas , Pessoa de Meia-Idade
4.
J Med Case Rep ; 18(1): 306, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937843

RESUMO

BACKGROUND: We present a unique case of rhinolalia as the first recognizable sign of spontaneous pneumomediastinum and surgical emphysema following drug use. CASE PRESENTATION: This case presents a 17-year-old white male experiencing rhinolalia following ecstasy ingestion at a rave. Subsequent chest X-ray revealed extensive surgical emphysema, along with a continuous diaphragm sign indicative of pneumomediastinum. Computed tomography confirmed the diagnosis. The patient was managed conservatively with strict monitoring and 6 hourly electrocardiograms. Follow-up computed tomography on day 3 showed resolution of pneumomediastinum and surgical emphysema, and the patient was safely discharged. Notably, the patient experienced a temporary rhinolalia during the acute phase, which resolved spontaneously as his condition improved. CONCLUSIONS: This case underscores the importance of considering spontaneous pneumomediastinum and surgical emphysema in the differential diagnosis of young individuals presenting with acute symptoms after drug use.


Assuntos
Enfisema Mediastínico , N-Metil-3,4-Metilenodioxianfetamina , Tomografia Computadorizada por Raios X , Humanos , Masculino , Enfisema Mediastínico/induzido quimicamente , Enfisema Mediastínico/diagnóstico por imagem , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Adolescente , Enfisema Subcutâneo/induzido quimicamente , Enfisema Subcutâneo/diagnóstico por imagem , Diagnóstico Diferencial
5.
J Am Soc Mass Spectrom ; 35(7): 1480-1489, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38837752

RESUMO

The surging number of people who abuse drugs has a great impact on healthcare and law enforcement systems. Amnesty bin drug analysis helps monitor the "street drug market" and tailor the harm reduction advice. Therefore, rapid and accurate drug analysis methods are crucial for on-site work. An analytical method for the rapid identification of five commonly detected drugs ((3,4-methylenedioxymethamphetamine (MDMA), cocaine, ketamine, 4-bromo-2,5-dimethoxyphenethylamine, and chloromethcathinone)) at various summer festivals in the U.K. was developed and validated employing a single quadrupole mass spectrometer combined with an atmospheric pressure solids analysis probe (ASAP-MS). The results were confirmed on a benchtop gas chromatography-mass spectrometry instrument and included all samples that challenged the conventional spectroscopic techniques routinely employed on-site. Although the selectivity/specificity step of the validation assessment of the MS system proved a challenge, it still produced 93% (N = 279) and 92.5% (N = 87) correct results when tested on- and off-site, respectively. A few "partly correct" results showed some discrepancies between the results, with the MS-only unit missing some low intensity active ingredients (N-ethylpentylone, MDMA) and cutting agents (caffeine, paracetamol, and benzocaine) or detecting some when not present. The incorrect results were mainly based on library coverage. The study proved that the ASAP-MS instrument can successfully complement the spectroscopic techniques used for qualitative drug analysis on- and off-site. Although the validation testing highlighted some areas for improvement concerning selectivity/specificity for structurally similar compounds, this method has the potential to be used in trend monitoring and harm reduction.


Assuntos
Drogas Ilícitas , Drogas Ilícitas/análise , Drogas Ilícitas/química , Espectrometria de Massas/métodos , Detecção do Abuso de Substâncias/métodos , Humanos , N-Metil-3,4-Metilenodioxianfetamina/análise , N-Metil-3,4-Metilenodioxianfetamina/química , Reprodutibilidade dos Testes , Cocaína/análise , Cocaína/química , Ketamina/análise , Ketamina/química , Pressão Atmosférica , Cromatografia Gasosa-Espectrometria de Massas/métodos , Limite de Detecção
6.
Harm Reduct J ; 21(1): 100, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783300

RESUMO

BACKGROUND: Methylenedioxymethamphetamine (MDMA) is a popular drug worldwide and use is prevalent in Aotearoa New Zealand. Although associated with some significant harms, including fatalities, MDMA is ultimately less harmful than other commonly consumed drugs. We aimed to expand the understanding of MDMA harm and harm reduction strategies from a consumer perspective so that national harm reduction efforts can be better informed. METHODS: We conducted 14 semi-structured focus group discussions including 60 people (aged 18-67, median = 21) who use MDMA in the Southern region of Aotearoa New Zealand to explore their thoughts and experiences regarding MDMA associated harm and harm reduction. Reflexive thematic analysis was conducted from a critical realist perspective. RESULTS: Five themes were generated; (1) Mindset and setting matters; (2) Looking after your body and mind, not overdoing it; (3) Other substances increase risk and harm; (4) Trusted friends and peers are protective; and (5) Valid information is key for healthy self-determination; and one subtheme 5.1) Drug checking is essential harm reduction. CONCLUSIONS: We discuss the implications for MDMA consumers and aim to inform national drug policy and the harm reduction practices of consumers and organisations, for the ultimate purpose of reducing MDMA-related harm in Aotearoa New Zealand.


Assuntos
Redução do Dano , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Nova Zelândia , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Masculino , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Idoso , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Alucinógenos/efeitos adversos
8.
Laeknabladid ; 110(5): 254-261, 2024 May.
Artigo em Islandês | MEDLINE | ID: mdl-38713560

RESUMO

MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Psicoterapia , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Resultado do Tratamento , Psicoterapia/métodos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Alucinógenos/uso terapêutico , Alucinógenos/efeitos adversos , Alucinógenos/administração & dosagem , Terapia Combinada
9.
J Forensic Sci ; 69(4): 1198-1211, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38691107

RESUMO

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Alucinógenos , Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Brasil , N-Metil-3,4-Metilenodioxianfetamina/análise , Humanos , Drogas Ilícitas/química , Drogas Ilícitas/análise , Alucinógenos/análise , Alucinógenos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Contaminação de Medicamentos , Tráfico de Drogas
10.
Trials ; 25(1): 336, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773523

RESUMO

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.


Assuntos
Afeto , Ansiedade , Alucinógenos , N-Metil-3,4-Metilenodioxianfetamina , Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Neoplasias/psicologia , Neoplasias/complicações , Ansiedade/psicologia , Método Duplo-Cego , Afeto/efeitos dos fármacos , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Alucinógenos/uso terapêutico , Resultado do Tratamento , Depressão/psicologia , Depressão/terapia , Depressão/tratamento farmacológico , Qualidade de Vida , Metilfenidato/uso terapêutico , Metilfenidato/efeitos adversos , Metilfenidato/administração & dosagem , Fatores de Tempo , Masculino , Estadiamento de Neoplasias
11.
Curr Opin Psychiatry ; 37(4): 277-281, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38726805

RESUMO

PURPOSE OF REVIEW: The pace of psychedelic treatments continues to increase. Regulation and coherent clinical guidance have not been established. A philosophical divide limits effective resolution of a practice delivery quandary: is this primarily a pharmacological or psychotherapeutic intervention? RECENT FINDINGS: Lykos (formerly MAPS) has submitted its new drug application (NDA) request to the FDA for 3-4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for PTSD and is expecting a response by the summer of 2024. Australia endorsed psilocybin and MDMA for regulated use in 2023. Multiple phase II and III clinical trials are also being conducted in the United States and Europe to study the use of psilocybin. Currently, Colorado and Oregon have legalized psilocybin in different manners. In Colorado, plants containing psilocybin, ibogaine, dimethyltryptamine (DMT) and mescaline (other than peyote) are now legal to possess, share and cultivate. Guidelines for regulated treatment with psilocybin containing mushrooms are in process with service delivery to begin early in 2025. In Oregon, clients must complete a preparation session with a licensed facilitator before consuming psilocybin products at a licensed service center. A prescription is not required. It is expected that other states will follow suit with a ballot measure likely in Massachusetts this year. Additionally, in the United States, the DEA, state boards, pharmaceutical distributors, and professional liability carriers all share mounting concerns about the in-home use of compounded ketamine used as a psychedelic therapeutic via remote prescribing. SUMMARY: Psychedelic treatments are rapidly entering the mainstream of medical care delivery in the United States. Clinical guidelines are urgently needed to ensure well tolerated practice and coherent regulation. The delivery of this guidance is limited by a core philosophical disagreement. Resolution of this conflict will be needed to deliver coherent clinical guidelines. Current research and clinical experience provide a solid foundation for practical clinical guidance and the introduction of psychedelics into healthcare.


Assuntos
Alucinógenos , Alucinógenos/uso terapêutico , Humanos , Psilocibina/uso terapêutico , Psicoterapia/métodos , Estados Unidos , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico
13.
J Pharm Biomed Anal ; 244: 116139, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608509

RESUMO

This study aimed to validate a modified QuEChERS method, followed by liquid chromatography-tandem mass spectrometry, for the determination of 51 psychoactive substances and screening of 22 ones in oral fluid from electronic dance music party (EDM) attendees. Unstimulated oral fluid was collected in a polypropylene tube and stored in a glass vial at -20 ºC. The sample was extracted with acetonitrile:water and MgSO4/NaOAc, followed by cleanup with primary secondary amine and MgSO4. The effectiveness of the sample storage conditions was shown to be comparable to when the Quantisal™ buffer was used, with no substantial concentration loss (< 15%) for all the substances after up to 72 hours at -20º C. The method was satisfactorily validated, with limits of detection (LOD) and quantification (LOQ) ranging from 0.04 to 0.5 ng/mL and 0.1-1.5 ng/mL, respectively, and was applied to the analysis of 62 real samples. The main substances detected were 3,4-methylenedioxymethamphetamine (MDMA) (<0.5-829 ng/mL) and/or methylenedioxyamphetamine (MDA) (10.1 - 460.6 ng/mL), found in 27 samples, and cocaine (13.0-407.3 ng/mL) and its metabolites (benzoylecgonine 0.17-214.1 ng/mL; ecgonine methyl ester 1.8-150.1 ng/mL) in eight samples. Methamphetamine (11-439 ng/mL) was detected in eight samples, along with MDMA and MDA; eutylone was detected in two cases (4.7 and 24.1 ng/mL) reported as "ecstasy" ingestion. A comparison between self-reported drug use and results of oral fluid analysis indicated that the use of illicit substances is often underreported among EDM attendees, who are often unaware of the substances they consume.


Assuntos
Limite de Detecção , Psicotrópicos , Saliva , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Humanos , Psicotrópicos/análise , Saliva/química , Cromatografia Líquida/métodos , Detecção do Abuso de Substâncias/métodos , Masculino , Adulto , Drogas Ilícitas/análise , N-Metil-3,4-Metilenodioxianfetamina/análise , Espectrometria de Massa com Cromatografia Líquida
14.
Artigo em Inglês | MEDLINE | ID: mdl-38615429

RESUMO

3,4-Methylenedioxymethamphetamine (MDMA) is an entactogen with therapeutic potential. The two enantiomers of MDMA differ regarding their pharmacokinetics and pharmacodynamics but the chiral pharmacology of MDMA needs further study in clinical trials. Here, an achiral and an enantioselective high performance liquid chromatography-tandem mass spectrometry method for the quantification of MDMA and its psychoactive phase I metabolite 3,4-methylenedioxyamphetamine (MDA) in human plasma were developed and validated. The analytes were detected by positive electrospray ionization followed by multiple reaction monitoring. The calibration range was 0.5-500 ng/mL for the achiral analysis of both analytes, 0.5-1,000 ng/mL for chiral MDMA analysis, and 1-1,000 ng/mL for chiral MDA analysis. Accuracy, precision, selectivity, and sensitivity of both bioanalytical methods were in accordance with regulatory guidelines. Furthermore, accuracy and precision of the enantioselective method were maintained when racemic calibrations were used to measure quality control samples containing only one of the enantiomers. Likewise, enantiomeric calibrations could be used to reliably quantify enantiomers in racemic samples. The achiral and enantioselective methods were employed to assess pharmacokinetic parameters in clinical study participants treated with racemic MDMA or one of its enantiomers. The pharmacokinetic parameters assessed with both bioanalytical methods were comparable. In conclusion, the enantioselective method is useful for the simultaneous quantification of both enantiomers in subjects treated with racemic MDMA. However, as MDMA and MDA do not undergo chiral inversion, enantioselective separation is not necessary in subjects treated with only one of the enantiomers.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Espectrometria de Massas em Tandem , Humanos , N-Metil-3,4-Metilenodioxianfetamina/sangue , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/química , Estereoisomerismo , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Modelos Lineares , Limite de Detecção , Masculino , Adulto
15.
Psychiatry Res ; 335: 115886, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574699

RESUMO

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.


Assuntos
Alucinógenos , Transtornos Mentais , N-Metil-3,4-Metilenodioxianfetamina , Transtorno Obsessivo-Compulsivo , Humanos , Alucinógenos/efeitos adversos , Psilocibina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Dietilamida do Ácido Lisérgico/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico
16.
J Anal Toxicol ; 48(4): 226-234, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38613438

RESUMO

A novel analytical method was developed for the simultaneous quantification of the R/S-enantiomers of amphetamine, methamphetamine, MDA and MDMA in hair samples using liquid chromatography-tandem mass spectrometry (LC-MS-MS). This method involved a straightforward derivatization step with dansyl chloride and the use of a chiral column, enabling the separation and quantification of all eight enantiomers in a single analysis. The method exhibited excellent linearity across a concentration range of 0.03-3.00 ng/mg for each enantiomer. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 6% and 9%, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated high sensitivity, with limits of detection (LOD) below 8 pg/mg and limits of quantification (LOQ) below 19 pg/mg for all analytes. Extraction recovery exceeded 79%, and matrix effects were minimal for all analytes. Processed sample stability evaluations revealed consistent results with deviations below 11% for all analytes. Application of the method to 32 authentic human hair samples provided valuable insights into amphetamine use patterns, allowing differentiation between medical amphetamine consumption and illicit use based on enantiomeric composition. Additionally, the method detected co-use of methamphetamine, MDA or MDMA in some samples, highlighting its applicability in drug monitoring and real-life case scenarios within a forensic institute. This innovative analytical approach offers a sensitive and selective method for enantiomeric differentiation of amphetamine, methamphetamine, MDA and MDMA in human hair samples, providing a valuable tool for forensic and clinical investigations.


Assuntos
Anfetamina , Cabelo , Limite de Detecção , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Humanos , Cabelo/química , Anfetamina/análise , Anfetamina/química , N-Metil-3,4-Metilenodioxianfetamina/análise , N-Metil-3,4-Metilenodioxianfetamina/química , Metanfetamina/análise , Detecção do Abuso de Substâncias/métodos , Estereoisomerismo , Cromatografia Líquida , Reprodutibilidade dos Testes
17.
J Chin Med Assoc ; 87(5): 538-549, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587377

RESUMO

BACKGROUND: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. METHODS: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. RESULTS: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. CONCLUSION: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.


Assuntos
Dextrometorfano , N-Metil-3,4-Metilenodioxianfetamina , Recompensa , Proteínas da Membrana Plasmática de Transporte de Serotonina , Animais , Masculino , Ratos , Dextrometorfano/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Tomografia por Emissão de Pósitrons , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
18.
Sci Adv ; 10(17): eadl6554, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38657057

RESUMO

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.


Assuntos
Empatia , Proteínas dos Microfilamentos , N-Metil-3,4-Metilenodioxianfetamina , Núcleo Accumbens , Optogenética , Serotonina , Animais , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Empatia/efeitos dos fármacos , Serotonina/metabolismo , Camundongos , Masculino , Comportamento Animal/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Transtorno Autístico/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
19.
Perspect Biol Med ; 67(1): 155-165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662070

RESUMO

Psychedelics, including psilocybin, and other consciousness-altering compounds such as 3,4-methylenedioxymethamphetamine (MDMA), currently are being scientifically investigated for their potential therapeutic uses, with a primary focus on measurable outcomes: for example, alleviation of symptoms or increases in self-reported well-being. Accordingly, much recent discussion about the possible value of these substances has turned on estimates of the magnitude and duration of persisting positive effects in comparison to harms. However, many have described the value of a psychedelic experience with little or no reference to such therapeutic benefits, instead seeming to find the experience valuable in its own right. How can we make sense of such testimony? Could a psychedelic experience be valuable even if there were no persisting beneficial effects? If so, how? Using the concept of psychological richness, combined with insights from the philosophy of aesthetics and the enhancement literature, this essay explores potential sources of value in the acute subjective experience, apart from the value derived from persisting beneficial effects.


Assuntos
Alucinógenos , Humanos , Alucinógenos/uso terapêutico , Estado de Consciência/efeitos dos fármacos , Psilocibina/uso terapêutico , N-Metil-3,4-Metilenodioxianfetamina
20.
J Anal Toxicol ; 48(5): 380-387, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38613441

RESUMO

The general use of cocaine is increasing in recent years, while the trend for 3,4-methylenedioxymethamphetamine (MDMA) is less clear. The relationship between blood concentrations and impairment is poorly understood, which complicates interpretation. The aims of this study were to report prevalence and blood concentrations of cocaine and MDMA in drugged drivers, and to investigate the relationship between blood concentrations and impairment. Samples of whole blood were collected from apprehended drivers in the period 2000-2022, and a clinical test of impairment (CTI) was simultaneously performed. The samples were initially analyzed for cocaine and MDMA using gas chromatography-mass spectrometry (until 2009 and 2012, respectively), and later using ultra-high-performance liquid chromatography-tandem mass spectrometry. Overall, cocaine was detected in 2,331 cases and MDMA in 2,569 cases. There were 377 and 85 mono cases of cocaine and MDMA, respectively. In the mono cases, the median cocaine concentration was 0.09 mg/L (range: 0.02-1.15 mg/L), and 54% of the drivers were clinically impaired. The median MDMA concentration was 0.19 mg/L (range: 0.04-1.36 mg/L), and 38% were clinically impaired. There was a statistically significant difference in the median cocaine concentration between drivers assessed as not impaired (0.07 mg/L) and drivers assessed as impaired (0.10 mg/L) (P = 0.009). There was also a significant effect of the blood concentration of cocaine (adjusted odds ratio [aOR] = 6.42, 95% confidence interval [CI] = 1.13-36.53, P = 0.036) and driving during the evening/night-time (aOR = 2.17, 95% CI = 1.34-3.51, P = 0.002) on the probability of being assessed as impaired on the CTI. No significant differences were found for MDMA. Many drivers are not assessed as impaired on a CTI following cocaine or especially MDMA use. For cocaine, a relationship between blood concentrations and impairment was demonstrated, but this could not be shown for MDMA.


Assuntos
Cocaína , Dirigir sob a Influência , N-Metil-3,4-Metilenodioxianfetamina , Detecção do Abuso de Substâncias , N-Metil-3,4-Metilenodioxianfetamina/sangue , Humanos , Cocaína/sangue , Detecção do Abuso de Substâncias/métodos , Masculino , Cromatografia Gasosa-Espectrometria de Massas , Adulto , Espectrometria de Massas em Tandem , Feminino , Cromatografia Líquida de Alta Pressão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...