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1.
WMJ ; 123(4): 300-303, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39284091

RESUMO

INTRODUCTION: "Delta-8," or delta-8 tetrahydrocannabinol (delta-8 THC), is a cannabinoid product that is growing in popularity for recreational use across the nation. This report aims to characterize the clinical presentation of acute delta-8 ingestions presenting to the emergency department. CASE SERIES: This is a case series of 6 patients who presented to a regional network of small- and medium-volume emergency departments in northwest Wisconsin. Patient histories confirmed that all patients had delta-8 exposure. Patient ages ranged from 5 to 57 years old. Amounts ingested and routes of ingestions varied from patient to patient. The most common symptoms reported were respiratory depression, unresponsiveness, altered mental status, tachycardia, and chest pressure. CONCLUSIONS: This case series is a snapshot of the burden experienced by emergency departments because of delta-8 availability. Clinicians should maintain a high index of suspicion for delta-8 use, especially in patients with altered mental status, anxiety, or cardiac.


Assuntos
Dronabinol , Serviço Hospitalar de Emergência , Humanos , Masculino , Wisconsin , Pessoa de Meia-Idade , Feminino , Adulto , Pré-Escolar , Criança , Adolescente
2.
BMC Pulm Med ; 24(1): 449, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272060

RESUMO

BACKGROUND: Dabbing is recently getting popular among young adults. It is a new method of using the most active form of marijuana where large amounts of concentrated tetrahydrocannabinol are inhaled. Tetrahydrocannabinol is associated with a feeling of 'High' which makes the user feel joyous and relaxed. With increasing use of such techniques, dabbing becomes an important differential for evaluation of acute respiratory failure with pneumonitis especially in the adult population. CASE PRESENTATION: A Fifty-one years old Caucasian man presented to the hospital with chest pressure and shortness of breath. The patient was noted to be hypoxic, desaturating down to 82-83% on nasal cannula oxygen. Imaging revealed bilateral lung infiltrates. Patient was started on high flow oxygen, broad spectrum antibiotics and intravenous corticosteroids. The patient gradually improved and was able to come off oxygen completely. He was discharged home on prednisone taper. CONCLUSIONS: Dabbing is a newer technique which has been gaining popularity for marijuana usage. With the legalization of marijuana, newer techniques are getting popular. Our case report emphasizes the importance of keeping dabbing as a differential when a patient presents with respiratory failure and has concerns for pneumonitis. Patients might not reveal until specifically asked about their practices.


Assuntos
Dronabinol , Pneumonia , Humanos , Masculino , Pessoa de Meia-Idade , Dronabinol/efeitos adversos , Insuficiência Respiratória , Antibacterianos/efeitos adversos , Oxigenoterapia , Tomografia Computadorizada por Raios X , Dispneia/etiologia
3.
Ther Drug Monit ; 46(5): 672-680, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39235358

RESUMO

BACKGROUND: Unusually high variability in blood Δ9-tetrahydrocannabinol (THC) concentrations have been observed in subjects inhaling similar cannabis products over similar time periods when consumption is ad libitum. This makes simple gravimetric dose estimation a poor predictor of THC exposure. Population pharmacokinetic analyses of blood THC concentration versus time data are routinely used to estimate pharmacokinetic parameters. The aim of this study was to estimate the inhaled dose of THC in occasional and daily users of high potency market cannabis. METHODS: Blood THC concentrations were measured for 135 minutes from 29 participants who either smoked high concentration flower or inhaled concentrates ad libitum during a 15-minute session. Frequent blood samples were obtained over the following 135 minutes. RESULTS: The estimated central and rapidly equilibrating volumes of distribution of a 3-compartment model were 19.9 ± 1.2 and 51.6 ± 4.7 L whereas the intercompartmental clearances were 1.65 ± 0.14 and 1.75 ± 0.10 L/min, respectively. Covariate-adjusted analysis revealed that the estimated inhaled THC dose was considerably less among occasional users compared with daily users. CONCLUSIONS: Three-compartment pharmacokinetics of THC did not differ among the 3 user groups, and the early phase (first 135 minutes postinception of inhalation) kinetics were similar to those previously described after smoking low potency cannabis products. Therefore, inhaled THC dose can be estimated from pharmacokinetic data and covariate-driven adjustments can be used to estimate THC doses, based on the participant cannabis usage pattern (occasional versus daily), improving the accuracy of THC exposure estimates compared with those derived from weighed THC content alone.


Assuntos
Dronabinol , Humanos , Dronabinol/farmacocinética , Dronabinol/sangue , Dronabinol/administração & dosagem , Masculino , Adulto , Feminino , Administração por Inalação , Adulto Jovem , Fumar Maconha , Cannabis , Pessoa de Meia-Idade , Relação Dose-Resposta a Droga , Modelos Biológicos
4.
PLoS One ; 19(9): e0309614, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39250476

RESUMO

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of Δ9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1-2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment.


Assuntos
Dronabinol , Ilusões , Humanos , Dronabinol/farmacologia , Dronabinol/análogos & derivados , Adulto , Masculino , Feminino , Ilusões/efeitos dos fármacos , Adulto Jovem , Mãos , Estudos Cross-Over , Esquizofrenia/tratamento farmacológico , Método Simples-Cego
5.
Forensic Sci Int ; 363: 112180, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39141931

RESUMO

AIM: The aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). METHODS: Data was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either "not impaired", "mildly impaired", "moderately impaired", or "considerably impaired". RESULTS: A total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). CONCLUSION: The percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.


Assuntos
Anfetaminas , Benzodiazepinas , Dirigir sob a Influência , Dronabinol , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Humanos , Adulto , Masculino , Feminino , Benzodiazepinas/sangue , Dirigir sob a Influência/estatística & dados numéricos , Anfetaminas/sangue , Cromatografia Líquida , Dronabinol/sangue , Detecção do Abuso de Substâncias/métodos , Depressores do Sistema Nervoso Central/sangue , Etanol/sangue , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem , Bases de Dados Factuais , Toxicologia Forense
6.
Sensors (Basel) ; 24(16)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39204779

RESUMO

Cannabis is cultivated for therapeutic and recreational purposes where delta-9 tetrahydrocannabinol (THC) is a main target for its therapeutic effects. As the global cannabis industry and research into cannabinoids expands, more efficient and cost-effective analysis methods for determining cannabinoid concentrations will be beneficial to increase efficiencies and maximize productivity. The utilization of machine learning tools to develop near-infrared (NIR) spectroscopy-based prediction models, which have been validated from accurate and sensitive chemical analysis, such as gas chromatography (GC) or liquid chromatography mass spectroscopy (LCMS), is essential. Previous research on cannabinoid prediction models targeted decarboxylated cannabinoids, such as THC, rather than the naturally occurring precursor, tetrahydrocannabinolic acid (THCA), and utilize finely ground cannabis inflorescence. The current study focuses on building prediction models for THCA concentrations in whole cannabis inflorescences prior to harvest, by employing non-destructive screening techniques so cultivators may rapidly characterize high-performing cultivars for chemotype in real time, thus facilitating targeted optimization of crossbreeding efforts. Using NIR spectroscopy and LCMS to create prediction models we can differentiate between high-THCA and even ratio classes with 100% prediction accuracy. We have also developed prediction models for THCA concentration with a R2 = 0.78 with a prediction error average of 13%. This study demonstrates the viability of a portable handheld NIR device to predict THCA concentrations on whole cannabis samples before harvest, allowing the evaluation of cannabinoid profiles to be made earlier, therefore increasing high-throughput and rapid capabilities.


Assuntos
Cannabis , Dronabinol , Aprendizado de Máquina , Espectroscopia de Luz Próxima ao Infravermelho , Cannabis/química , Dronabinol/análise , Dronabinol/química , Dronabinol/análogos & derivados , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Inflorescência/química
7.
Biosens Bioelectron ; 264: 116686, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39173339

RESUMO

Cannabinoids are involved in physiological and neuromodulatory processes through their interactions with the human cannabinoid receptor-based endocannabinoid system. Their association with neurodegenerative diseases and brain reward pathways underscores the importance of evaluating and modulating cannabinoid activity for both understanding physiological mechanisms and developing therapeutic drugs. The use of agonists and antagonists could be strategic approaches for modulation. In this study, we introduce a bioelectronic sensor designed to monitor cannabinoid binding to receptors and assess their agonistic and antagonistic properties. We produced human cannabinoid receptor 1 (hCB1R) via an Escherichia coli expression system and incorporated it into nanodiscs (NDs). These hCB1R-NDs were then immobilized on a single-walled carbon nanotube field-effect transistor (swCNT-FET) to construct a bioelectronic sensing platform. This novel system can sensitively detect the cannabinoid ligand anandamide (AEA) at concentrations as low as 1 fM, demonstrating high selectivity and real-time response. It also successfully identified the hCB1R agonist Δ9-tetrahydrocannabinol and observed that the hCB1R antagonist rimonabant diminished the sensor signal upon AEA binding, indicating the antagonism-based modulation of ligand interaction. Consequently, our bioelectronic sensing platform holds potential for ligand detection and analysis of agonism and antagonism.


Assuntos
Técnicas Biossensoriais , Endocanabinoides , Nanotubos de Carbono , Receptor CB1 de Canabinoide , Humanos , Endocanabinoides/metabolismo , Nanotubos de Carbono/química , Receptor CB1 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/antagonistas & inibidores , Transistores Eletrônicos , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologia , Ácidos Araquidônicos/química , Ácidos Araquidônicos/farmacologia , Canabinoides/metabolismo , Canabinoides/farmacologia , Canabinoides/química , Agonistas de Receptores de Canabinoides/farmacologia , Agonistas de Receptores de Canabinoides/química , Dronabinol/farmacologia , Dronabinol/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo
9.
Mult Scler Relat Disord ; 89: 105740, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39106541

RESUMO

BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.


Assuntos
Canabidiol , Dronabinol , Combinação de Medicamentos , Esclerose Múltipla , Espasticidade Muscular , Humanos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Canabidiol/administração & dosagem , Canabidiol/farmacologia , Dronabinol/administração & dosagem , Dronabinol/farmacologia , Método Duplo-Cego , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Adulto , Masculino , Sprays Orais , Feminino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
10.
J Chromatogr A ; 1732: 465207, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39088898

RESUMO

The adsorption of 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) by the suspended particles in sewage makes it fail to accurately monitor cannabis abuse. In this work, the model sewage sample was prepared through equivalent mixing the sewage from 10 different sewage treatment plants in Guangdong province of China and used as a comprehensive representative for investigating the adsorption and release behavior of THC-COOH on the suspended particles under different temperature and pH. The solid-liquid distribution of THC-COOH in sewage depended strongly on the adsorption and release properties which were susceptible to the temperature and pH, specially adjusting pH to 11.0 could release more than 90 % of THC-COOH from the suspended particles. By means of the kinetics models, pseudo-second-order kinetic and Weber-Morris models revealed the mechanism of adsorption and release of THC-COOH in sewage that was a relatively reversible and controllable process with multiple interactions, and then it was further confirmed by the validation experiment in a variety of actual sewage samples. According to the suggested pH, the modification of the existing detection protocol prior to high performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-TQ-MS/MS), was successfully applied to determination of THC-COOH in the stimulated positive samples, and the recoveries and RSDs were respectively 95.48-99.79 % and 4.0-5.6 %. The finding could greatly help improving the accuracy of not only the detection of THC-COOH in sewage but also the estimation data of the consumption level of cannabis in the related regions.


Assuntos
Dronabinol , Esgotos , Dronabinol/análise , Dronabinol/análogos & derivados , Dronabinol/química , Esgotos/química , Esgotos/análise , Adsorção , Concentração de Íons de Hidrogênio , Abuso de Maconha , Cinética , Detecção do Abuso de Substâncias/métodos , Cannabis/química , Temperatura , Limite de Detecção , Cromatografia Líquida de Alta Pressão/métodos , Humanos
11.
J Med Chem ; 67(16): 14574-14585, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39092992

RESUMO

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, have attracted a significant amount of attention due to their biological activities. This study identified GPR18 as the target of partial agonist CBD activating the p42/p44 MAPK pathway leading to migration of endometrial epithelial cells. Induced fit docking (IFD) showed that the affinity of THC for GPR18 is higher than that of CBD, and molecular dynamics (MD) simulations showed that CBD-GPR18 complexes at 130/200 ns might have stable conformations, potentially activating GPR18 by changing the distances of key residues in its active pocket. In contrast, THC maintains "metastable" conformations, generating a "shrinking space" leading to full agonism of THC by adding mechanical constraints in GPR18's active pocket. Steered molecular dynamics (SMD) revealed GPR18's active pocket was influenced more by CBD's partial agonism compared with THC. This combined IFD-MD-SMD method may be used to explain the mechanism of activation of partial or full agonists of GPR18.


Assuntos
Canabidiol , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas G , Canabidiol/farmacologia , Canabidiol/química , Canabidiol/metabolismo , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Dronabinol/farmacologia , Dronabinol/química , Dronabinol/metabolismo , Dronabinol/análogos & derivados , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Movimento Celular/efeitos dos fármacos , Feminino
12.
Talanta ; 280: 126770, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39208678

RESUMO

Monitoring various biomarkers in saliva samples emerges as a dynamic and non-invasive method. However, the high viscosity of saliva presents a distinct challenge when integrating paper-based platforms for on-site analysis. In addressing this challenge, we introduced the capillary-driven microfluidic paper-based analytical devices (µCD-PAD) designed for user-friendly and simultaneous detection of ethanol and tetrahydrocannabinol (THC) in saliva without a sample preparation step. Employing a colorimetric approach, we quantified both analytes. Synthetic salivas of varying viscosity flowed seamlessly to the detection zone without needing a sample preparation step, and no impact on colorimetric detection due to viscosity was observed (RSD <5 %). Within 10 min after the solution reached the detection zone, the device produced a homogeneous color signal, easily analyzed by a smartphone camera. To extend the application for determination to cover a legal limit concentration of ethanol and concentration of salivary THC even 24 h after marijuana consumption, the detection time of 30 min was optimized. Moreover, a saliva sample containing both analytes was used to demonstrate the capability of the developed device to detect ethanol and THC simultaneously. No cross-talk between ethanol and THC occurred and showed recovery in the 98-102 % for ethanol and 95-105 % for THC with acceptable accuracy. This developed device exhibits excellent potential for forensic applications, providing a user-friendly, cost-effective, and real-time screening tool for detecting ethanol and THC in saliva.


Assuntos
Colorimetria , Dronabinol , Etanol , Papel , Saliva , Smartphone , Dronabinol/análise , Saliva/química , Etanol/análise , Colorimetria/métodos , Colorimetria/instrumentação , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Detecção do Abuso de Substâncias/métodos , Detecção do Abuso de Substâncias/instrumentação
13.
Forensic Sci Int Genet ; 73: 103123, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39173341

RESUMO

Cannabis sativa, a globally commercialized plant used for medicinal, food, fiber production, and recreation, necessitates effective identification to distinguish legal and illegal varieties in forensic contexts. This research utilizes multivariate statistical models and Machine Learning approaches to establish correlations between specific genotypes and tetrahydrocannabinol (Δ9-THC) content (%) in C. sativa samples. 132 cannabis leaves samples were obtained from legal growers in Piedmont, Italy, and illegal drug seizures in Turin. Samples were genetically profiled using a 13-loci STR multiplex and their Δ9-THC content was detected through quantitative GC-MS analysis. This study aims to assess the use of supervised classification modelling on genetic data to distinguish cannabis samples into legal and illegal categories, revealing distinct clusters characterized by unique allele profiles and THC content. t-distributed Stochastic Neighbor Embedding (t-SNE), Random Forest (RF) and Partial Least Squares Regression (PLS-R) were executed for the machine learning modelling. All the tested models resulted effective discriminating between legal samples and illegal. Although further validation is necessary, this study presents a novel forensic investigative approach, potentially aiding law enforcement in significant marijuana seizures or tracking illicit drug trafficking routes.


Assuntos
Cannabis , Dronabinol , Cromatografia Gasosa-Espectrometria de Massas , Aprendizado de Máquina , Cannabis/genética , Cannabis/química , Marcadores Genéticos , Humanos , Repetições de Microssatélites , Folhas de Planta/química , Folhas de Planta/genética , Genótipo , Análise dos Mínimos Quadrados , Itália
14.
Histochem Cell Biol ; 162(5): 363-372, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39110194

RESUMO

The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague-Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.


Assuntos
Dronabinol , Frutose , Intestino Delgado , Ratos Sprague-Dawley , Animais , Dronabinol/farmacologia , Frutose/farmacologia , Ratos , Masculino , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Intestino Delgado/efeitos dos fármacos , Dieta
15.
J Pharm Biomed Anal ; 251: 116422, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39197204

RESUMO

Cannabis sativa L. is a plant belonging to the Cannabaceae family known primarily for its recreational use due to the psychoactive properties of Δ9-tetrahydrocannabinol (THC). Despite this, several compounds belonging to the category of phytocannabinoids have shown in recent years a number of potentially promising therapeutic effects that have increased the interest in the pharmaceutical field towards this plant. However, the content of these compounds is very variable and influenced by different factors, such as growing conditions and time of the year. An indication of the status and age of Cannabis samples is provided by the content of CBN, a minor phytocannabinoid and degradation product of other phytocannabinoids, including THC. In this research work an innovative, solid state analytical approach has been developed to observe and evaluate the variations in the content of two phytocannabinoids (CBN and CBD) in Cannabis-derived products over time. In order to simulate the ageing of the Cannabis samples, an artificially accelerated ageing procedure has been developed and optimised by using high temperatures. The analyses were carried out using an innovative ATR-FTIR method for solid state analysis, enabling direct analysis of a solid sample without any pretreatment phase. This study has allowed the development of an innovative analytical approach for the evaluation of the age and state of conservation of Cannabis samples and may be a useful tool both in the industrial, pharmaceutical and forensic fields.


Assuntos
Canabinoides , Cannabis , Cannabis/química , Canabinoides/análise , Canabinoides/química , Dronabinol/análise , Dronabinol/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Estabilidade de Medicamentos , Extratos Vegetais/química , Extratos Vegetais/análise , Fatores de Tempo , Canabidiol/análise , Canabidiol/química
16.
Nervenarzt ; 95(9): 781-796, 2024 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-39134752

RESUMO

Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly.


Assuntos
Abuso de Maconha , Humanos , Abuso de Maconha/epidemiologia , Abuso de Maconha/diagnóstico , Alemanha/epidemiologia , Classificação Internacional de Doenças , Adulto , Dronabinol/efeitos adversos , Estudos Transversais , Colaboração Intersetorial , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/diagnóstico
17.
BMJ Ment Health ; 27(1)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39182921

RESUMO

BACKGROUND: The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual's effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting. METHODS: Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration. RESULTS: CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr<0.05) but not 600 mg dosage. Declining AEA was observed with Δ9-THC at 10 mg (-1.3-fold) and 20 mg (-1.4-fold) but restored to baseline levels by 160 min. CBD+Δ9-THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response. CONCLUSION: CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ9-THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.


Assuntos
Ácidos Araquidônicos , Canabidiol , Relação Dose-Resposta a Droga , Dronabinol , Endocanabinoides , Etanolaminas , Voluntários Saudáveis , Alcamidas Poli-Insaturadas , Humanos , Endocanabinoides/sangue , Ácidos Araquidônicos/sangue , Ácidos Araquidônicos/administração & dosagem , Canabidiol/administração & dosagem , Canabidiol/sangue , Adulto , Masculino , Alcamidas Poli-Insaturadas/sangue , Alcamidas Poli-Insaturadas/administração & dosagem , Etanolaminas/administração & dosagem , Etanolaminas/sangue , Dronabinol/sangue , Dronabinol/administração & dosagem , Dronabinol/farmacocinética , Feminino , Adulto Jovem , Administração Oral , Pessoa de Meia-Idade , Amidas , Ácidos Palmíticos
18.
Tokai J Exp Clin Med ; 49(3): 128-132, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39182181

RESUMO

A 20-year-old man was brought to the emergency room with chief complaints of dysarthria and vomiting after placing several drops of an inhalation liquid containing hexahydrocannabiphorol (HHCP) under his tongue. During ambulance transport, the patient had a post-vomiting convulsion that lasted approximately 1 minute. Upon arrival at the hospital, he was agitated, had dysarthria to the extent that he was in danger of falling from the stretcher, and was having visual hallucinations. Blood tests showed acidosis and a high lactic acid concentration. The patient was urgently admitted to the hospital with a diagnosis of acute poisoning and was started on supplemental intravenous fluids. The patient was able to communicate from the second day, started eating on the third day, finished receiving supplemental fluids on the fourth day, and was discharged from the hospital on the fifth day. HHCP was not illegal in Japan at the time and was distributed mainly through mail order. Clinical information on HHCP is lacking, but this case shows that the drug causes health problems. Although HHCP has been regulated by law in Japan since January 2024, clinicians and the general public should be aware that similar cases may occur in the future.


Assuntos
Dronabinol , Humanos , Masculino , Adulto Jovem , Administração por Inalação , Dronabinol/administração & dosagem , Dronabinol/análogos & derivados , Vômito/induzido quimicamente , Doença Aguda , Japão , Hidratação , Cannabis
19.
J Psychiatr Res ; 177: 90-95, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38991269

RESUMO

INTRODUCTION: Attentional bias (AB) is believed to be an important factor in the development and maintenance of both opioid use disorder (OUD) and chronic pain. Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), produce analgesic effects via processes that are potentially relevant to AB and is commonly used by persons with OUD. This exploratory study investigated if THC influences AB towards pain and opioid cues individuals with OUD. METHODS: Using a within-subject, crossover design, 27 adults receiving methadone were randomly assigned to receive single doses of oral THC (10 mg, 20 mg administered as dronabinol) or placebo across three, 5-h sessions. During each session, a visual probe task was used to measure AB to pain and opioid cues at baseline and 120 min post-THC administration. RESULTS: Mixed-effects models examined main effects of THC dose, time, and their interaction across all participants; findings were then stratified by methadone dose (low dose <90 mg/day and high dose ≥90 mg/day). Among individuals receiving high doses of methadone, a significant interaction was observed such that AB towards opioids increased following 10 mg THC administration and decreased following 20 mg THC administration. Additionally, participants receiving low doses of methadone showed significant increases in the variability of opioid-related AB post THC administration. CONCLUSION: We provide preliminary evidence showing that THC may cause dose-dependent effects on selective attention for opioid cues among methadone patients. These results underscore the need for further clinical investigation into the effects of cannabinoids and other substances with potential analgesic and addictive properties among persons with OUD.


Assuntos
Viés de Atenção , Estudos Cross-Over , Dronabinol , Transtornos Relacionados ao Uso de Opioides , Humanos , Dronabinol/farmacologia , Dronabinol/administração & dosagem , Masculino , Feminino , Adulto , Viés de Atenção/efeitos dos fármacos , Viés de Atenção/fisiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Metadona/administração & dosagem , Metadona/farmacologia , Adulto Jovem , Dor/tratamento farmacológico , Pessoa de Meia-Idade , Método Duplo-Cego , Relação Dose-Resposta a Droga , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Sinais (Psicologia)
20.
Am J Physiol Heart Circ Physiol ; 327(3): H701-H714, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39028280

RESUMO

Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, remains a schedule I substance, thus safety data regarding the effects on the cardiovascular and prenatal health are limited. Importantly, there is evidence showing prenatal cannabis exposure can negatively impact fetal organ development, including the cardiovascular system. THC can cross the placenta and bind to cannabinoid receptors expressed in the developing fetus, including on endothelial cells. To understand the impact of prenatal THC exposure on the fetal cardiovascular system, we used our rhesus macaque model of prenatal daily edible THC consumption. Before conception, animals were acclimated to THC (2.5 mg/7 kg/day, equivalent to a heavy medical cannabis dose) and maintained on this dose daily throughout pregnancy. Fetal tissue samples were collected at gestational day 155 (full term is 168 days). Our model showed that in utero THC exposure was associated with a decreased heart weight-to-body weight ratio in offspring, warranting further mechanistic investigation. Histological examination of the fetal cardiac and vascular tissues did not reveal any significant effect of THC exposure on the maturity of collagen within the fetal heart or the aorta. Total collagen III expression and elastin production and organization were unchanged. However, bulk RNA-sequencing of vascular cells in the umbilical vein, umbilical artery, and fetal aorta demonstrated that THC alters the fetal vascular transcriptome and is associated with upregulated expression of genes involved in carbohydrate metabolism and inflammation. The long-term consequences of these findings are unknown but suggest that prenatal THC exposure may affect cardiovascular development in offspring.NEW & NOTEWORTHY Prenatal cannabis use is increasing and despite the public health relevance, there is limited safety data regarding its impact on offspring cardiovascular health outcomes. We used a translational, nonhuman primate model of daily edible Δ-9-tetrahydrocannabinol (THC) consumption during pregnancy to assess its effects on the fetal cardiovascular system. THC-exposed fetal vascular tissues displayed upregulation of genes involved in cellular metabolism and inflammation, suggesting that prenatal THC exposure may impact fetal vascular tissues.


Assuntos
Dronabinol , Matriz Extracelular , Macaca mulatta , Transcriptoma , Animais , Dronabinol/toxicidade , Gravidez , Feminino , Transcriptoma/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Coração Fetal/efeitos dos fármacos , Coração Fetal/metabolismo
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