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Talanta ; 236: 122863, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635245


Cannabis is currently one of the most consumed drugs in many countries. Δ9-tetrahydrocannabinol (THC) is the principal psychoactive component of this drug and is present in saliva after consumption. This paper reports a novel biomolecule-free electrochemical approach to detect an ultra-low level of THC in saliva using modified electrodes with molecules of the same analyte (THC) that are detected later via square wave voltammetry. The results from this research revealed that the electrodeposition of THC on the working electrode (sensor analyte) could highly enhance the limit of detection by improving the affinity of the THC molecules present in the sample (sample analyte) to the sensing electrode surface. Detailed descriptions about the optimization of the sensor and its performance in simple media, such as PBS, and complex media, such as simulated and real saliva, are provided. This novel and yet simple electrochemical-based sensing strategy allowed for a low limit of detection of 1.6 ng/mL THC in simulated and real saliva, distinguishing concentrations ranging from 2 to 25 ng/mL, making this technology viable for a real-world application such as roadside testing.

Cannabis , Alucinógenos , Dronabinol , Eletrodos , Saliva
Exp Neurol ; 347: 113888, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624331


3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons in primates, and reductions in markers of central serotonin axons, and axon terminals in animals. In humans, demonstration of serotonergic neurotoxicity is much more difficult to identify, and much of the research is complicated by confounding issues of polysubstance use, genetic and environmental factors and reliance on self-reports of previous drug use. We do not review the mechanisms for neurotoxicity in detail as they are covered elsewhere in this special issue. There is a large body of literature, however, which has investigated potential cognitive and neurocognitive consequences of repeated MDMA use. Here we review the literature on cognition, and neuroimaging studies that have investigated structural and functional brain changes associated with ecstasy use.

Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Alucinógenos/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Humanos
Exp Neurol ; 347: 113894, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655576


Preclinical and clinical studies indicate that 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), in addition to having abuse potential, may elicit acute and persistent abnormalities of varying severity at the central level. Importantly, neurotoxic effects of MDMA have been demonstrated in experimental animals. Accordingly, central toxicity induced by MDMA may pose a serious harm for health, since MDMA is among the substances that are used for recreational purposes by young and adult people. This review provides a concise overview of recent findings from preclinical and clinical studies that evaluated the central effects of MDMA, and the mechanisms involved in the neurotoxicity induced by this amphetamine-related drug.

Encéfalo/efeitos dos fármacos , Alucinógenos/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Síndromes Neurotóxicas , Animais , Humanos , Síndromes Neurotóxicas/etiologia
BMC Palliat Care ; 20(1): 191, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930220


BACKGROUND: Existential distress is a significant source of suffering for patients facing life-threatening illness. Psychedelic-Assisted Therapies (PAT) are novel treatments that have shown promise in treating existential distress, but openness to providing PAT may be limited by stigma surrounding psychedelics and the paucity of education regarding their medical use. How PAT might be integrated into existing treatments for existential distress within palliative care remains underexplored. METHODS: The present study aimed to elucidate the attitudes of palliative care clinicians regarding treatments for existential distress, including PAT. We recruited palliative care physicians, advanced practice nurses, and spiritual and psychological care providers from multiple US sites using purposive and snowball sampling methods. Attitudes toward PAT were unknown prior to study involvement. Semi-structured interviews targeted at current approaches to existential distress and attitudes toward PAT were analyzed for thematic content. RESULTS: Nineteen respondents (seven physicians, four advanced practice nurses, four chaplains, three social workers, and one psychologist) were interviewed. Identified themes were 1) Existential distress is a common experience that is frequently insufficiently treated within the current treatment framework; 2) Palliative care providers ultimately see existential distress as a psychosocial-spiritual problem that evades medicalized approaches; 3) Palliative care providers believe PAT hold promise for treating existential distress but that a stronger evidence base is needed; 4) Because PAT do not currently fit existing models of existential distress treatment, barriers remain. CONCLUSIONS: PAT is seen as a potentially powerful tool to treat refractory existential distress. Larger clinical trials and educational outreach are needed to clarify treatment targets and address safety concerns. Further work to adapt PAT to palliative care settings should emphasize collaboration with spiritual care as well as mental health providers and seek to address unresolved concerns about equitable access.

Alucinógenos , Atitude , Humanos , Cuidados Paliativos
Psychiatr Danub ; 33(4): 541-550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34928902


BACKGROUND: It is known that cannabis increases mood, decreases anxiety and causes mild euphoria, but also it can cause serious mental diseases. Previous studies showed harmful effects of cannabis and the aim of this study is to show characteristics of persons registrated because of cannabinoids abuse in Croatia in the period 2008-2018 and show effectiveness of interventions using statistic methods. SUBJECTS AND METHODS: Research data were collected based on the national Registry of Treated Psychoactive Drug Abusers in period 2008 to 2018 and included 10 533 registrated persons. Statistical analysis was performed by chi-square test and binary logistic regression. RESULTS: Results showed that men and very young people took cannabinoids more often than women and older people. There was a changing trend of registrated people in a ten-year period. The most commonly used intervention of obligatory healthcare treatment is consultation, but the difference between apstinents and people with unchanged status isn't statistically significant. The most people are referred by repressive mechanism and they are more likely to have apstinent status compared to unrepressive source of referral, with one exception - referred by the family. The highest probability of abstinence have those referred by the center for social welfare. CONCLUSIONS: Registrated people were mostly referred by repressive way, which makes question of its efficiency and prevention of long term addiction, because system like that more likely stigmatizes and punishes young people, opposite to giving support and help.

Canabinoides , Cannabis , Alucinógenos , Adolescente , Idoso , Ansiedade , Canabinoides/efeitos adversos , Croácia/epidemiologia , Humanos
JAMA ; 326(23): 2434-2435, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932084

JAMA ; 326(23): 2434, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932085

JAMA ; 326(23): 2433-2434, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932086

JAMA ; 326(23): 2435-2436, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34932081

Tijdschr Psychiatr ; 63(9): 665-672, 2021.
Artigo em Holandês | MEDLINE | ID: mdl-34647305


BACKGROUND: MDMA (ecstasy) is a relatively safe drug and induces little dependence, but is nevertheless scheduled as a hard drug (Dutch Opium Act, List 1). Concerns about MDMA-related crime, health incidents and possible inappropriate listing of MDMA on List I have led to an ongoing debate about current Dutch ecstasy policy. AIM: To develop a rational MDMA policy that takes into account all aspects related to production, sale and use of MDMA. METHOD: An interdisciplinary group of 18 experts formulates a science-based MDMA policy by assessing the expected effects of 95 policy options on 25 outcomes, including health, crime, law enforcement and finance. The optimal policy model consists of the combination of the 22 policy options with the highest total score on all 25 outcomes. RESULTS: The optimal policy model consisted of a form of regulated production and sale of MDMA, better quality management of ecstasy tablets and more intensive fight against MDMA-related organized crime. Such a policy would lead to a small increase in the prevalence of ecstasy use, but with less health damage, less MDMA-related crime, and less environmental damage. To increase practicality and political feasibility, the optimal model was slightly modified. CONCLUSION: The developed optimal model offers a politically and socially feasible set of policy instrument options, with which the placement of MDMA on List I can be revised, thereby reducing the damage of MDMA to users and society. For psychiatry, it means promoting therapeutic research and less nuisance from unnecessary stigmatization in the treatment of patients.

Alucinógenos , N-Metil-3,4-Metilenodioxianfetamina , Psiquiatria , Crime , Humanos , Políticas
Nat Med ; 27(10): 1687-1688, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34635858
Rev. psiquiatr. Urug ; 85(1): 63-76, oct. 2021.
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1343170


Los psicodélicos son sustancias capaces de alterar la conciencia, a través de su efecto sobre la transmisión serotoninérgica en el sistema nervioso central. En sus formas de ingesta tradicional son utilizados en rituales, con fines espirituales y medicinales. En el campo científico, dichas sustancias fueron estudiadas para posibles aplicaciones psicoterapéuticas en el período 1950-1970, y luego fueron excluidas de la investigación clínica durante las posteriores décadas. Sin embargo, desde 1990 asistimos a un «renacimiento de los estudios sobre psicodélicos¼, donde estas sustancias están siendo estudiadas en su potencial clínico para el tratamiento de distintos trastornos menta-les. El presente artículo describe y reflexiona sobre la historia de estas investigaciones en Uruguay y en el mundo, tanto en su primera etapa (1950-1970) como en su renacimiento posterior (1990-actualidad), dejando planteado un escenario en el que sea posible avanzar en el campo de las investigaciones clínicas con psicodélicos en nuestro país.

Psychedelics are substances capable of altering consciousness, through their effect on serotonergic transmission within the central nervous system. In their traditional uses, psychedelics are consumed during rituals, for spiritual and medicinal purposes. In the scientific field, these substances were studied because of their possible psychotherapeutic applications in the period 1950-1970. Afterwards, psychedelics were banned from clinical research for decades. Nevertheless, since 1990 we are witnessing a "renaissance of psychedelic studies", where these substances are being studied because of their clinical potential applications for the treatment of different mental disorders. The current article describes and analyzes the history of these research in Uruguay and in the world, both in its first stage (1950-1970) and in the present "renaissance" (1990-present). The article suggests a future scenario, where Uruguay could play a major role in the field of psychedelic research.

Humanos , Pesquisa Biomédica/tendências , Alucinógenos/história , Transtornos Mentais/tratamento farmacológico , Uruguai
Talanta ; 235: 122704, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517579


The recent discovery of the novel heptyl phytocannabinoids cannabidiphorol (CBDP) and Δ9-tetrahydrocannabiphorol (Δ9-THCP) raised a series of questions relating to the presence and abundance of these new unorthodox compounds in cannabis inflorescence or derived products. As fresh inflorescence contains mainly their acid precursors, which are not commercially available, an ad hoc stereoselective synthesis was performed in order to obtain cannabidiphorolic acid (CBDPA) and Δ9-tetrahydrocannabiphorolic acid (THCPA) to be used as analytical standards for quantitative purposes. The present work reports an unprecedented targeted analysis of both pentyl (C5) and heptyl (C7) CBD- and THC-type compounds in forty-nine cannabis samples representing four different chemotypes. Moreover, the ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry-based method was applied for the putative identification of other heptyl homologs of the most common phytocannabinoid acids, including cannabigerophorolic acid (CBGPA), cannabichromephorolic acid (CBCPA), cannabinophorolic acid (CBNPA), cannabielsophorolic acid (CBEPA), cannabicyclophorolic acid (CBLPA), cannabitriophorolic acid (CBTPA), and cannabiripsophorolic acid (CBRPA).

Canabinoides , Cannabis , Alucinógenos , Canabinoides/análise , Cromatografia Líquida , Espectrometria de Massas
Anal Methods ; 13(35): 3954-3962, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528944


A sensitive immunochemical method for identifying hallucinogenic mushrooms (magic mushrooms) is required for regulating their illicit use. We have previously generated a monoclonal antibody (mAb) that targets psilocin (Psi), the major psychoactive compound in hallucinogenic mushrooms, and developed an enzyme-linked immunosorbent assay (ELISA). However, this ELISA failed to achieve the expected low-picomole-range sensitivity, as a result of insufficient affinity of the mAb to Psi. It is recognized that haptenic antigens with a larger molecular mass tend to induce antibodies with higher affinities. Thus, we herein report a "derivatization-assisted ELISA," in which the "real analyte" Psi was determined as a "surrogate analyte," the tert-butyldimethylsilyl ether analog thereof (TBS/Psi) having a 1.6-fold greater molecular mass (Mr 318.53) than Psi. A novel mAb against TBS/Psi, prepared by immunizing mice with a TBS/Psi-albumin conjugate showed a 69-fold higher affinity to TBS/Psi residues (Ka = 3.6 × 107 M-1 as IgG) than that of our previous mAb against Psi. This mAb consequently enabled a competitive ELISA for measuring TBS/Psi with the desired sensitivity: the dose-response curve midpoint (12.1 pmol per assay) was >100-fold lower than that of the previous ELISA for determining Psi. Extracts of dried mushroom powders were mixed with TBS triflate for 30 min at room temperature, converting Psi into TBS/Psi in approximately 50% yield. The reaction mixture was then subjected to an ELISA using the anti-TBS/Psi mAb to determine TBS/Psi. Psilocybe cubensis, a species of hallucinogenic mushrooms, gave rise to positive signals, indicating the presence of Psi therein in the expected quantity, while no detectable response was observed for four kinds of edible mushrooms available in the markets.

Agaricales , Alucinógenos , Psilocybe , Animais , Ensaio de Imunoadsorção Enzimática , Camundongos
J Pharm Biomed Anal ; 206: 114346, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34537622


Cannabis sativa L. is a plant known all over the world, due to its history, bioactivity and also social impact. It is chemically complex with an astonishing ability in the biosynthesis of many secondary metabolites belonging to different chemical classes. Among them, cannabinoids are the most investigated ones, given their pharmacological relevance. In order to monitor the composition of the plant material and ensure the efficacy and safety of its derived products, extraction and analysis of cannabinoids play a crucial role. In this context, in addition to a conventional separation method based on HPLC with UV/DAD detection, a new strategy based on a non-separation procedure, such as 13C-qNMR, may offer several advantages, such as reduced solvent consumption and simultaneous acquisition of the quali/quantitative data related to many analytes. In the light of all the above, the aim of this work is to compare the efficiency of the above-mentioned analytical techniques for the study of the main cannabinoids in different samples of cannabis inflorescences, belonging to fibre-type, recreational and medical varieties. The 13C-qNMR method here proposed for the first time for the quantification of both psychoactive and non-psychoactive cannabinoids in different cannabis varieties provided reliable results in comparison to the more common and consolidated HPLC technique.

Canabinoides , Cannabis , Alucinógenos , Canabinoides/análise , Cromatografia Líquida de Alta Pressão , Extratos Vegetais
Drug Alcohol Depend ; 227: 108998, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482037


BACKGROUND: As cannabis legalization spreads, so do concerns about potential harms from use during pregnancy. Legalization may facilitate improved patient-provider interactions about cannabis use. Yet little is known about pregnant people's discussions of cannabis use with healthcare providers in an environment where recreational cannabis is legal. METHODS: In May-August 2019, we conducted semi-structured in-depth interviews with 33 pregnant or postpartum people in California who used cannabis during pregnancy, and explored their discussions with healthcare providers about their cannabis use. We audio-recorded and transcribed interviews, and conducted thematic analysis using inductive and deductive methods. RESULTS: Participants were diverse by age, race/ethnicity, and socio-economic position. Most reported daily cannabis use, both before and during pregnancy. Most participants did not disclose their cannabis use to their prenatal care providers, due to fears of being reported to child protective services (CPS), or fears of provider judgment. Participants reported that few providers initiated any discussions about cannabis use in pregnancy with them; some participants interpreted this omission as tacit endorsement of cannabis use in pregnancy. When participants and providers did discuss cannabis use in pregnancy, participants heard a wide range of sometimes-conflicting health messages, as well as some legal threats. CONCLUSIONS: This study documents notable deficits in patient-provider interactions about cannabis. Pregnant patients' fears of being reported to CPS and separated from their children for cannabis use persist despite cannabis legalization. Providers' role as potential reporters to CPS appears to pose a significant barrier to comprehensive, compassionate counseling and education on cannabis use in pregnancy.

Cannabis , Alucinógenos , Criança , Humanos , Legislação de Medicamentos , Período Pós-Parto , Gravidez , Cuidado Pré-Natal