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1.
Sci Adv ; 10(22): eado0077, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38809980

RESUMEN

While our understanding of the nanoscale architecture of anterograde synaptic transmission is rapidly expanding, the qualitative and quantitative molecular principles underlying distinct mechanisms of retrograde synaptic communication remain elusive. We show that a particular form of tonic cannabinoid signaling is essential for setting target cell-dependent synaptic variability. It does not require the activity of the two major endocannabinoid-producing enzymes. Instead, by developing a workflow for physiological, anatomical, and molecular measurements at the same unitary synapse, we demonstrate that the nanoscale stoichiometric ratio of type 1 cannabinoid receptors (CB1Rs) to the release machinery is sufficient to predict synapse-specific release probability. Accordingly, selective decrease of extrasynaptic CB1Rs does not affect synaptic transmission, whereas in vivo exposure to the phytocannabinoid Δ9-tetrahydrocannabinol disrupts the intrasynaptic nanoscale stoichiometry and reduces synaptic variability. These findings imply that synapses leverage the nanoscale stoichiometry of presynaptic receptor coupling to the release machinery to establish synaptic strength in a target cell-dependent manner.


Asunto(s)
Receptor Cannabinoide CB1 , Transducción de Señal , Sinapsis , Transmisión Sináptica , Animales , Transmisión Sináptica/efectos de los fármacos , Receptor Cannabinoide CB1/metabolismo , Sinapsis/metabolismo , Terminales Presinápticos/metabolismo , Ratones , Endocannabinoides/metabolismo , Endocannabinoides/farmacología , Dronabinol/farmacología
2.
J Chromatogr A ; 1727: 464994, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38759461

RESUMEN

This research aimed to support police forces in their battle against illicit drug trafficking by means of a multi-technique approach, based on gas chromatography. In detail, this study was focused on the profiling of volatile substances in narcotic Cannabis sativa L. flowering tops. For this purpose, the Scientific Investigation Department, RIS Carabinieri of Messina, provided 25 seized samples of Cannabis sativa L. The content of Δ9-tetrahydrocannabinol (THC), useful to classify cannabis plant as hemp (≤ 0.2 %) or as marijuana (> 0.2 %), was investigated. Essential oils of illicit drug samples were extracted using a microwave-assisted hydro-distillation (MAHD) system; GC-MS and GC-FID analytical techniques were used for the characterization of the terpenes and terpenoids fingerprint. Furthermore, the enantiomeric and carbon isotopic ratios of selected chiral compounds were investigated using a heart-cutting multidimensional GC (MDGC) approach. The latter exploited a combination of an apolar column in the first dimension, and a chiral cyclodextrin-based column in the second one, prior to parallel isotope-ratio mass spectrometry (C-IRMS) and MS detection. Finally, all the data were gathered into a statistical model, to demonstrate the existence of useful parameters to be used for the classification of seized samples.


Asunto(s)
Cannabis , Destilación , Flores , Cromatografía de Gases y Espectrometría de Masas , Microondas , Aceites Volátiles , Cannabis/química , Destilación/métodos , Flores/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Aceites Volátiles/análisis , Aceites Volátiles/química , Terpenos/análisis , Dronabinol/análisis , Cromatografía de Gases/métodos
3.
Ugeskr Laeger ; 186(15)2024 Apr 08.
Artículo en Danés | MEDLINE | ID: mdl-38708699

RESUMEN

In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.


Asunto(s)
Dolor Crónico , Marihuana Medicinal , Humanos , Dolor Crónico/tratamiento farmacológico , Marihuana Medicinal/uso terapéutico , Marihuana Medicinal/efectos adversos , Dronabinol/uso terapéutico , Analgésicos/uso terapéutico
4.
J Med Internet Res ; 26: e52499, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696245

RESUMEN

This study explores the potential of using large language models to assist content analysis by conducting a case study to identify adverse events (AEs) in social media posts. The case study compares ChatGPT's performance with human annotators' in detecting AEs associated with delta-8-tetrahydrocannabinol, a cannabis-derived product. Using the identical instructions given to human annotators, ChatGPT closely approximated human results, with a high degree of agreement noted: 94.4% (9436/10,000) for any AE detection (Fleiss κ=0.95) and 99.3% (9931/10,000) for serious AEs (κ=0.96). These findings suggest that ChatGPT has the potential to replicate human annotation accurately and efficiently. The study recognizes possible limitations, including concerns about the generalizability due to ChatGPT's training data, and prompts further research with different models, data sources, and content analysis tasks. The study highlights the promise of large language models for enhancing the efficiency of biomedical research.


Asunto(s)
Medios de Comunicación Sociales , Humanos , Medios de Comunicación Sociales/estadística & datos numéricos , Dronabinol/efectos adversos , Procesamiento de Lenguaje Natural
5.
PLoS One ; 19(5): e0292336, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753807

RESUMEN

BACKGROUND: In October 2019, cannabis edibles were legalized for sale in Canada for non-medical use. This move was intended to improve public safety by regulating contents (including a maximum 10 mg tetrahydrocannabinol (THC) per package) and packaging to prevent accidental ingestion or over consumption. This study aimed to explore consumer preferences for cannabis edibles to inform cannabis policy. METHODS: We explored the relative importance and trade-offs consumers make for attributes of cannabis edibles using a discrete choice experiment. Attributes included type of edible, price, THC content, cannabis taste, package information, product consistency, product recommendations, and Health Canada regulation. Participants lived in Canada, were 19 years of age or older, and purchased a cannabis edible in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analysis to assess preference sub-groups. This study was approved by the institutional ethics committee. RESULTS: Among 684 participants, the MNL model showed that potency was the most relevant attribute, followed by edible type. A two-group latent class model revealed two very distinct preference patterns. Preferences for group 1 (~65% of sample) were driven primarily by edible type, while for group 2 (~35% of sample) were driven almost entirely by THC potency. CONCLUSION: This study found that consumer preferences for ~65% of consumers of cannabis edibles are being met through regulated channels. The remaining ~35% are driven by THC potency at levels that are not currently available on the licensed market. Attracting this market segment will require reviewing the risks and benefits of restricting THC package content.


Asunto(s)
Cannabis , Conducta de Elección , Comportamiento del Consumidor , Dronabinol , Humanos , Masculino , Adulto , Femenino , Cannabis/química , Canadá , Adulto Joven , Persona de Mediana Edad , Política de Salud , Salud Pública
6.
Trials ; 25(1): 293, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693590

RESUMEN

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.


Asunto(s)
Cannabidiol , Dronabinol , Marihuana Medicinal , Neoplasias , Cuidados Paliativos , Humanos , Administración Oral , Cannabidiol/administración & dosificación , Cannabidiol/efectos adversos , Cannabidiol/uso terapéutico , Método Doble Ciego , Dronabinol/uso terapéutico , Dronabinol/administración & dosificación , Combinación de Medicamentos , Marihuana Medicinal/uso terapéutico , Marihuana Medicinal/efectos adversos , Marihuana Medicinal/administración & dosificación , Estudios Multicéntricos como Asunto , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Cuidados Paliativos/métodos , Calidad de Vida , Queensland , Ensayos Clínicos Controlados Aleatorios como Asunto , Carga Sintomática , Factores de Tiempo , Resultado del Tratamiento
7.
Sensors (Basel) ; 24(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38794042

RESUMEN

A rugged handheld sensor for rapid in-field classification of cannabis samples based on their THC content using ultra-compact near-infrared spectrometer technology is presented. The device is designed for use by the Austrian authorities to discriminate between legal and illegal cannabis samples directly at the place of intervention. Hence, the sensor allows direct measurement through commonly encountered transparent plastic packaging made from polypropylene or polyethylene without any sample preparation. The measurement time is below 20 s. Measured spectral data are evaluated using partial least squares discriminant analysis directly on the device's hardware, eliminating the need for internet connectivity for cloud computing. The classification result is visually indicated directly on the sensor via a colored LED. Validation of the sensor is performed on an independent data set acquired by non-expert users after a short introduction. Despite the challenging setting, the achieved classification accuracy is higher than 80%. Therefore, the handheld sensor has the potential to reduce the number of unnecessarily confiscated legal cannabis samples, which would lead to significant monetary savings for the authorities.


Asunto(s)
Cannabis , Espectroscopía Infrarroja Corta , Cannabis/química , Cannabis/clasificación , Espectroscopía Infrarroja Corta/métodos , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Humanos , Dronabinol/análisis
8.
ACS Chem Neurosci ; 15(8): 1669-1683, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38575140

RESUMEN

The cannabinoid receptor 1 (CB1) is famous as the target of Δ9-tetrahydrocannabinol (THC), which is the active ingredient of marijuana. Suppression of CB1 is frequently suggested as a drug target or gene therapy for many conditions (e.g., obesity, Parkinson's disease). However, brain networks affected by CB1 remain elusive, and unanticipated psychological effects in a clinical trial had dire consequences. To better understand the whole brain effects of CB1 suppression we performed in vivo imaging on mice under complete knockout of the gene for CB1 (cnr1-/-) and also under the CB1 inverse agonist rimonabant. We examined white matter structural changes and brain function (network activity and directional uniformity) in cnr1-/- mice. In cnr1-/- mice, white matter (in both sexes) and functional directional uniformity (in male mice) were altered across the brain but network activity was largely unaltered. Conversely, under rimonabant, functional directional uniformity was not altered but network activity was altered in cortical regions, primarily in networks known to be altered by THC (e.g., neocortex, hippocampal formation). However, rimonabant did not alter many brain regions found in both our cnr1-/- results and previous behavioral studies of cnr1-/- mice (e.g., thalamus, infralimbic area). This suggests that chronic loss of cnr1 is substantially different from short-term suppression, subtly rewiring the brain but largely maintaining the network activity. Our results help explain why pathological mutations in CB1 (e.g., chronic pain) do not always provide insight into the side effects of CB1 suppression (e.g., clinical depression), and thus urge more preclinical studies for any drugs that suppress CB1.


Asunto(s)
Agonismo Inverso de Drogas , Piperidinas , Femenino , Ratones , Masculino , Animales , Rimonabant/farmacología , Piperidinas/farmacología , Pirazoles/farmacología , Ratones Noqueados , Encéfalo , Receptores de Cannabinoides , Receptor Cannabinoide CB1/genética , Dronabinol/farmacología
9.
Sci Rep ; 14(1): 9181, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649680

RESUMEN

The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions. Using an evidence-based approach, pharmacological investigation of CB1R agonists is timely, with the aim to provide chronically ill patients relief using well-defined and characterized compounds from cannabis. Hexahydrocannabinol (HHC), currently available over the counter in many countries to adults and even children, is of great interests to policy makers, legal administrators, and healthcare regulators, as well as pharmacologists. Herein, we studied the pharmacodynamics of HHC epimers, which activate CB1R. We compared their key CB1R-mediated signaling pathway activities and compared them to the pathways activated by Δ9-tetrahydrocannabinol (Δ9-THC). We provide evidence that activation of CB1R by HHC ligands is only broadly comparable to those mediated by Δ9-THC, and that both HHC epimers have unique properties. Together with the greater chemical stability of HHC compared to Δ9-THC, these molecules have a potential to become a part of modern medicine.


Asunto(s)
Dronabinol , Receptor Cannabinoide CB1 , Transducción de Señal , Dronabinol/farmacología , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB1/agonistas , Transducción de Señal/efectos de los fármacos , Humanos , Cannabinol/farmacología , Animales , Agonistas de Receptores de Cannabinoides/farmacología , Células HEK293 , Ratones
10.
Scand J Clin Lab Invest ; 84(2): 125-132, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619215

RESUMEN

This study investigated the effects of hexahydrocannabinol (HHC) and other unclassified cannabinoids, which were recently introduced to the recreational drug market, on cannabis drug testing in urine and oral fluid samples. After the appearance of HHC in Sweden in 2022, the number of posts about HHC on an online drug discussion forum increased significantly in the spring of 2023, indicating increased interest and use. In parallel, the frequency of false positive screening tests for tetrahydrocannabinol (THC) in oral fluid, and for its carboxy metabolite (THC-COOH) in urine, rose from <2% to >10%. This suggested that HHC cross-reacted with the antibodies in the immunoassay screening, which was confirmed in spiking experiments with HHC, HHC-COOH, HHC acetate (HHC-O), hexahydrocannabihexol (HHC-H), hexahydrocannabiphorol (HHC-P), and THC-P. When HHC and HHC-P were classified as narcotics in Sweden on 11 July 2023, they disappeared from the online and street shops market and were replaced by other unregulated variants (e.g. HHC-O and THC-P). In urine samples submitted for routine cannabis drug testing, HHC-COOH concentrations up to 205 (mean 60, median 27) µg/L were observed. To conclude, cannabis drug testing cannot rely on results from immunoassay screening, as it cannot distinguish between different tetra- and hexahydrocannabinols, some being classified but others unregulated. The current trend for increased use of unregulated cannabinols will likely increase the proportion of positive cannabis screening results that need to be confirmed with mass spectrometric methods. However, the observed cross-reactivity also means a way to pick up use of new cannabinoids that otherwise risk going undetected.


Asunto(s)
Drogas Ilícitas , Detección de Abuso de Sustancias , Humanos , Detección de Abuso de Sustancias/métodos , Drogas Ilícitas/orina , Drogas Ilícitas/análisis , Suecia , Dronabinol/orina , Dronabinol/análisis , Dronabinol/análogos & derivados , Cannabis/química , Saliva/química , Cannabinoides/orina , Cannabinoides/análisis , Cannabinol/análisis , Cannabinol/orina , Reacciones Cruzadas , Inmunoensayo/métodos
11.
Addict Behav ; 155: 108029, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38593597

RESUMEN

BACKGROUND: Recent cannabis use (RCU) exerts adverse effects on the brain. However, the effect of RCU on structural covariance networks (SCNs) is still unclear. This retrospective cross-sectional study aimed to explore the effects of RCU on SCNs in young adults in terms of whole cerebral cortical thickness (CT) and cortical surface area (CSA). METHODS: A total of 117 participants taking tetrahydrocannabinol (RCU group) and 896 participants not using cannabis (control group) were included in this study. All participants underwent MRI scanning following urinalysis screening, after which FreeSurfer 5.3 was used to calculate the CT and CSA, and SCNs matrices were constructed by Brain Connectivity Toolbox. Subsequently, the global and nodal network measures of the SCNs were computed based on these matrices. A nonparametric permutation test was used to investigate the group differences by Matlab. RESULTS: Regarding global network measures of CT, young adults with RCU exhibited altered small-worldness (P = 0.020) and clustering coefficient (P = 0.031) compared to controls, whereas there were no significant group differences in terms of SCNs constructed with CSA. Additionally, SCNs based on CT and CSA displayed abnormal nodal degree, nodal efficiency, and nodal betweenness centrality in vital brain regions of the triple network, including the dorsolateral and ventrolateral prefrontal cortex, and anterior cingulate cortex. CONCLUSION: The effects of RCU on brain structure in young adults can be detected by SCNs, in which structural abnormalities in the triple network are dominant, indicating that RCU can be detrimental to brain function.


Asunto(s)
Dronabinol , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto Joven , Estudios Transversales , Estudios Retrospectivos , Adulto , Uso de la Marihuana , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Red Nerviosa/diagnóstico por imagen , Adolescente , Grosor de la Corteza Cerebral
12.
Int J Mol Sci ; 25(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38674023

RESUMEN

Cisplatin and other platinum-derived chemotherapy drugs have been used for the treatment of cancer for a long time and are often combined with other medications. Unfortunately, tumours often develop resistance to cisplatin, forcing scientists to look for alternatives or synergistic combinations with other drugs. In this work, we attempted to find a potential synergistic effect between cisplatin and cannabinoid delta-9-THC, as well as the high-THC Cannabis sativa extract, for the treatment of HT-29, HCT-116, and LS-174T colorectal cancer cell lines. However, we found that combinations of the high-THC cannabis extract with cisplatin worked antagonistically on the tested colorectal cancer cell lines. To elucidate the mechanisms of drug interactions and the distinct impacts of individual treatments, we conducted a comprehensive transcriptomic analysis of affected pathways within the colorectal cancer cell line HT-29. Our primary objective was to gain a deeper understanding of the underlying molecular mechanisms associated with each treatment modality and their potential interactions. Our findings revealed an antagonistic interaction between cisplatin and high-THC cannabis extract, which could be linked to alterations in gene transcription associated with cell death (BCL2, BAD, caspase 10), DNA repair pathways (Rad52), and cancer pathways related to drug resistance.


Asunto(s)
Cannabis , Cisplatino , Neoplasias Colorrectales , Dronabinol , Extractos Vegetales , Transcriptoma , Humanos , Cisplatino/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Dronabinol/farmacología , Cannabis/química , Extractos Vegetales/farmacología , Transcriptoma/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos/farmacología , Células HT29 , Perfilación de la Expresión Génica/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Apoptosis/efectos de los fármacos
13.
CNS Drugs ; 38(5): 375-385, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38597988

RESUMEN

BACKGROUND: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER: NCT02560545.


Asunto(s)
Dolor Crónico , Neuralgia , Humanos , Masculino , Dronabinol/farmacología , Dronabinol/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Encéfalo , Método Doble Ciego , Estudios Cruzados
14.
J Photochem Photobiol B ; 254: 112902, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38569457

RESUMEN

The effect of low artificial Ultraviolet (UV) on the DNA methylation remains controversial. This study addresses how differential photoperiods of UV radiation affect the biochemical and molecular behaviors of Cannabis indica cell suspension cultures. The cell suspensions were illuminated with the compact fluorescent lamps (CFL), emitting a combination of 10% UVB, 30% UVA, and the rest visible wavelengths for 0, 4, 8, and 16 h. The applied photoperiods influenced cell morphological characteristics. The 4 h photoperiod was the most effective treatment for improving biomass, growth index and cell viability percentage while these indices remained non-significant in the 16 h treatment. The methylation-sensitive amplified polymorphism (MASP) assay revealed that the UV radiation was epigenetically accompanied by DNA hypermethylation. The light-treated cells significantly displayed higher relative expression of the cannabidiolic| acid synthase (CBDAS) and delta9-tetrahydrocannabinolic acid synthase (THCAS) genes about 4-fold. The expression of the olivetolic acid cyclase (OAC) and olivetol synthase (OLS) genes exhibited an upward trend in response to the UV radiation. The light treatments also enhanced the proline content and protein concentration. The 4 h illumination was significantly capable of improving the cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) concentrations, in contrast with 16 h. By increasing the illumination exposure time, the activity of the phenylalanine ammonia-lyase (PAL) enzyme linearly upregulated. The highest amounts of the phenylpropanoid derivatives were observed in the cells cultured under the radiation for 4 h. Taken collective, artificial UV radiation can induce DNA methylation modifications and impact biochemical and molecular differentiation in the cell suspensions in a photoperiod-dependent manner.


Asunto(s)
Cannabinoides , Cannabis , Cannabis/genética , Cannabis/química , Cannabinoides/farmacología , Dronabinol/farmacología , Metilación de ADN , Rayos Ultravioleta , Proliferación Celular
15.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38673788

RESUMEN

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids. CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions. THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential. In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN). The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways. The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.


Asunto(s)
Cannabinoides , Humanos , Cannabinoides/uso terapéutico , Cannabinoides/farmacología , Animales , Cannabis/química , Endocannabinoides/metabolismo , Endocannabinoides/uso terapéutico , Cannabidiol/uso terapéutico , Cannabidiol/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Dronabinol/uso terapéutico , Dronabinol/farmacología
16.
Chem Commun (Camb) ; 60(39): 5205-5208, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38652014

RESUMEN

This work developed an aptamer-dye complex as a label-free ratiometric fluorescence sensor for rapid analysis of THC and its metabolite in sewage samples. Integrated with a portable fluorescence capture device, this sensor exhibited excellent sensitivity with visualization of as low as 0.6 µM THC via naked-eye observation, and THC analysis can be accomplished within 4 min, which would be a complementary tool for quantifying THC in sewage samples to estimate cannabis consumption.


Asunto(s)
Aptámeros de Nucleótidos , Dronabinol , Colorantes Fluorescentes , Aguas del Alcantarillado , Aptámeros de Nucleótidos/química , Dronabinol/análisis , Dronabinol/química , Colorantes Fluorescentes/química , Aguas del Alcantarillado/análisis , Aguas del Alcantarillado/química , Espectrometría de Fluorescencia , Técnicas Biosensibles
17.
Biomolecules ; 14(4)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38672512

RESUMEN

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.


Asunto(s)
Benzoxazinas , Cannabidiol , Supervivencia Celular , Dronabinol , Linfoma no Hodgkin , Morfolinas , Naftalenos , Humanos , Perros , Cannabidiol/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dronabinol/farmacología , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/patología , Benzoxazinas/farmacología , Naftalenos/farmacología , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Endocannabinoides/farmacología , Endocannabinoides/metabolismo
18.
J Anal Toxicol ; 48(4): 197-203, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38581658

RESUMEN

11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH) is the most frequently detected illicit drug metabolite in the military drug testing program. An increasing number of specimens containing unresolved Δ8-THCCOOH prompted the addition of this analyte to the Department of Defense drug testing panel. A method was developed and validated for the quantitative confirmation of the carboxylated metabolites of Δ8- and Δ9-THC in urine samples utilizing automated pipette tip dispersive solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Analytes were separated isocratically over an 8.5-min runtime and detected on an MS-MS equipped with an electrospray ionization source operated in negative mode. A single point calibrator (15 ng/mL) forced through zero demonstrated linearity from 3 to 1,000 ng/mL. Intra- and inter-day precision were ≤9.1%, and bias was within ±14.1% for Δ8-THCCOOH and Δ9-THCCOOH. No interferences were found after challenging the method with different over-the-counter drugs, prescription pharmaceuticals, drugs of abuse and several cannabinoids and cannabinoid metabolites, including Δ10-THCCOOH. Urine specimens presumptively positive by immunoassay (n = 2,939; 50 ng/mL Δ9-THCCOOH cutoff) were confirmed with this analytical method. Δ8-THCCOOH and Δ9-THCCOOH were present together above the 15 ng/mL cutoff in 33% of specimens. However, nearly one-third of the specimens analyzed were positive for Δ8-THCCOOH only. This manuscript describes the first validated automated extraction and confirmation method for Δ8- and Δ9-THCCOOH in urine that provides adequate analyte separation in urine specimens with extreme isomer abundance ratios.


Asunto(s)
Dronabinol , Extracción en Fase Sólida , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Dronabinol/análogos & derivados , Dronabinol/orina , Humanos , Detección de Abuso de Sustancias/métodos , Cromatografía Liquida , Reproducibilidad de los Resultados , Drogas Ilícitas/orina , Límite de Detección , Isomerismo , Cromatografía Líquida con Espectrometría de Masas
19.
J Anal Toxicol ; 48(4): 235-241, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38581662

RESUMEN

Hexahydrocannabinol (HHC) was first reported in the EU in May 2022. HHC has three chiral carbon atoms, but only (6aR,9R,10aR)-HHC (9R-HHC) and (6aR,9S,10aR)-HHC (9S-HHC) have been encountered in HHC products. The aim of this study was to develop and validate a method for the quantitative analysis of 9R-HHC, 9S-HHC, 11-OH-9R-HHC, 9R-HHC-COOH, 9S-HHC-COOH and 8-OH-9R-HHC. In addition, an objective was to investigate the immunochemical cross-reactivity. Blood samples from driving under the influence of drugs (DUID) cases screened positive for cannabis using enzyme-linked immunoadsorbent assay (ELISA) and confirmed negative for tetrahydrocannabinol (THC), 11-hydroxy-THC and THC-COOH were reanalyzed with a newly validated HHC method to investigate the presence of HHC and metabolites. The LC-MS-MS method was validated for matrix effects, lower limit of quantification (LLOQ), calibration model, precision, bias and autosampler stability. Cross-reactivity on an ELISA method was investigated separately for 9R-HHC-COOH and 9S-HHC-COOH at a concentration range between 5 and 200 ng/mL. The cross-reactivity was found to be 120% for 9R-HHC-COOH and 48% for 9S-HHC-COOH. In the LC-MS-MS method, 9R-HHC-COOH, 9S-HHC-COOH and 11-OH-9R-HHC showed matrix effects <25% at both concentrations, while 8-OH-9R-HHC, 9R-HHC and 9S-HHC matrix effects exceeded 25% at both concentrations but showed good precision (<10% for both inter and intra day) and low bias (<6%) in the further validation. The LLOQ was investigated and established at 0.2 ng/mL for all analytes except the carboxylated metabolites that had an LLOQ of 2.0 ng/mL. The upper LOQ was 20 and 200 ng/mL, respectively. Reanalysis of cases (n = 145) confirmed HHC and metabolites in 32 cases (22%). It was determined that the major metabolite in blood after administration of HHC was 9R-HHC-COOH followed by 11-OH-9R-HHC and that presumptive positive cases are caught by the routine ELISA screening for cannabis.


Asunto(s)
Dronabinol , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Dronabinol/sangre , Dronabinol/análogos & derivados , Detección de Abuso de Sustancias/métodos , Conducir bajo la Influencia , Ensayo de Inmunoadsorción Enzimática , Reproducibilidad de los Resultados , Límite de Detección , Cromatografía Liquida
20.
Behav Pharmacol ; 35(4): 161-171, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38660819

RESUMEN

Cannabis is a pharmacologically complex plant consisting of hundreds of potentially active compounds. One class of compounds present in cannabis that has received little attention are terpenes. Traditionally thought to impart aroma and flavor to cannabis, it has become increasingly recognized that terpenes might exert therapeutic effects themselves. Several recent reports have also indicated terpenes might behave as cannabinoid type 1 (CB1) receptor agonists. This study aimed to investigate whether several terpenes present in cannabis produce discriminative stimulus effects similar to or enhance the effects of Δ 9 -tetrahydrocannabinol (THC). Subsequent experiments explored other potential cannabimimetic effects of these terpenes. Rats were trained to discriminate THC from vehicle while responding under a fixed-ratio 10 schedule of food presentation. Substitution testing was performed with the CB receptor agonist JWH-018 and the terpenes linalool, limonene, γ-terpinene and α-humulene alone. Terpenes were also studied in combination with THC. Finally, THC and terpenes were tested in the tetrad assay to screen for CB1-receptor agonist-like effects. THC and JWH-018 dose-dependently produced responding on the THC-paired lever. When administered alone, none of the terpenes produced responding predominantly on the THC-paired lever. When administered in combination with THC, none of the terpenes enhanced the potency of THC, and in the case of α-humulene, decreased the potency of THC to produce responding on the THC-paired lever. While THC produced effects in all four tetrad components, none of the terpenes produced effects in all four components. Therefore, the terpenes examined in this report do not have effects consistent with CB1 receptor agonist properties in the brain.


Asunto(s)
Cannabis , Dronabinol , Terpenos , Animales , Terpenos/farmacología , Ratas , Dronabinol/farmacología , Masculino , Cannabinoides/farmacología , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/metabolismo , Indoles/farmacología , Naftalenos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Ratas Sprague-Dawley , Relación Dosis-Respuesta a Droga , Aprendizaje Discriminativo/efectos de los fármacos , Discriminación en Psicología/efectos de los fármacos
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