Cannabis and Cannabinoid Research最新文献

{"title":"Changes in Immune-Related Biomarkers and Endocannabinoids as a Function of Frequency of Cannabis Use in People Living With and Without HIV.","authors":"Conor H Murray, Marjan Javanbakht, Grace D Cho, Pamina M Gorbach, Jennifer A Fulcher, Ziva D Cooper","doi":"10.1089/can.2022.0287","DOIUrl":"10.1089/can.2022.0287","url":null,"abstract":"<p><p><b>Background:</b> Cannabis use is common among people living with HIV (PLWH). Some observational studies of PLWH have linked cannabis use to lower immune markers; however, this is yet to be confirmed. In addition, whether HIV affects the endogenous cannabinoid system has not been studied. Our objective was to examine changes in immune-related biomarkers and endocannabinoids as a function of cannabis use frequency in people living with and without HIV. <b>Materials and Methods:</b> Data were obtained from a longitudinal study of men who have sex with men living in Los Angeles with, or at risk for, HIV. By design, half were PLWH. Those eligible for the parent study were willing and able to return for follow-up every 6 months. Those eligible for inclusion in this study reported varying levels of current cannabis use at follow-up. Specifically, one visit corresponded to a period of daily use and another to a period of infrequent use (weekly, monthly, or less than monthly). Banked serum from all eligible participants was analyzed for immune-related biomarkers, endocannabinoids, and paracannabinoids. <b>Results:</b> The analysis included 36 men, 19 of whom were PLWH. PLWH reported greater lifetime methamphetamine or amphetamine use (68% vs. 0%) and current cigarette use (55% vs. 20%) than people without HIV. Serum levels of HIV-related immune biomarkers including tumor necrosis factor receptor 2 (TNFR2; <i>p</i>=0.013) and CD27 (<i>p</i>=0.004) were greater in PLWH, alongside lower anandamide (AEA) (<i>F</i>_1,34=5.337, <i>p</i>=0.027) and oleoylethanolamide (OEA) (<i>F</i>_1,34=8.222, <i>p</i>=0.007) levels relative to people without HIV. Frequency of cannabis use did not impact the serum analytes in our study. <b>Conclusions:</b> Higher levels of TNFR2 and CD27 and lower levels of AEA and OEA in PLWH underscore the role of the TNF/TNFR superfamily in HIV, while highlighting a new role for the enzymatic activity of fatty acid amide hydrolase (the enzyme that hydrolyzes AEA and OEA) in HIV. Findings that cannabis frequency did not impact the immune phenotype may not generalize to other populations of PLWH. Additional work is required to further clarify the relationship between immune markers and endocannabinoids as a function of cannabis use frequency in PLWH. ClinicalTrials.gov ID: NCT01201083.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e897-e906"},"PeriodicalIF":3.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Δ⁹-THC and CBD in Plasma, Oral Fluid, Exhaled Breath, and Urine from 23 Patients Administered Sativex.","authors":"Christopher M Melén, Magali Merrien, Agata M Wasik, Birgitta Sander, Björn Engelbrekt Wahlin, Georgios Panagiotis, Olof Beck","doi":"10.1089/can.2022.0179","DOIUrl":"10.1089/can.2022.0179","url":null,"abstract":"<p><p><b>Background:</b> Detecting the presence of Δ⁹-THC and CBD is mainly done through venous blood sampling, but other methods are becoming available. Oromucosal administration of Δ⁹-THC and CBD is less studied than inhalation, but this mode of administration is growing. In this study, we analyze samples obtained through invasive and noninvasive methods in a cohort of patients given oromucosally administered Δ⁹-THC and CBD to gain understanding in the strengths and weaknesses of the various detection methods. <b>Materials and Methods:</b> Blood, oral fluid (OF), exhaled breath, and urine were collected at several time points from 23 cannabis-naive patients after receiving a single dose of Sativex^®; dose ranges: Δ⁹-THC, 2.7-18.9 mg; CBD 2.5-17.5 mg. Detection of Δ⁹-THC and CBD was done using liquid chromatography-mass spectrometry methods. <b>Results:</b> Δ⁹-THC and CBD were present in plasma, OF, and exhaled breath in all 23 patients. The detection time of Δ⁹-THC and CBD in OF and exhaled breath was longer than in blood. Urine analysis detected the Δ⁹-THC carboxy metabolite (THC-COOH) up to 7 days after administration, also in a patient who received 8.1/7.5 mg Δ⁹-THC/CBD. <b>Conclusion:</b> Time to detection of cannabinoids in blood samples was shorter than in exhaled breath and OF. Relative ease of sample collection combined with high sensitivity makes OF and exhaled breath specimens a valuable addition when samples are handled correctly. Δ⁹-THC metabolites were detected for an unexpected long period of time in urine. EudraCT Number: 2014-005553-39. Date of registration, December 29, 2015.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e839-e846"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9427325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Cannabis sativa</i> L. from Seized Drug Material: <i>In Vitro</i> Germination and Establishment.","authors":"Alessandra Moraes Pedrosa, Thaís Teixeira Valério Caetano, Camila Moreno Lopes de Andrade, Mateus Moreira Bernardes, Bruna Cristina Alves, Vinícius Belo, Joaquim Maurício Duarte-Almeida, Vanessa C Stein","doi":"10.1089/can.2022.0305","DOIUrl":"10.1089/can.2022.0305","url":null,"abstract":"<p><p><b>Background:</b> With the expansion of the cannabis-derived product market, there is a growing need for seedling development to produce raw material for pharmaceutical applications and medicinal research. However, cannabis cultivation is illegal in many countries, and legal producers do not sell cannabis seeds in these countries. In Brazil, cannabis is still illegal, and the only way to obtain access to cannabis plants for research or as medicine is through importation, which is costly and requires authorization from the National Health Surveillance Agency (ANVISA), or from material seized by the police from drug trafficking. <b>Methods:</b> Therefore, since cannabis seeds obtained from drug trafficking have never been tested regarding their viability and use in <i>in vitro</i> cultivation, the aim of this study was to analyze the <i>in vitro</i> establishment of cannabis from seeds derived from Brazilian drug trafficking seizures that were provided by the police to investigate seed disinfestation procedures and further multiplication of nodal segments, with the purpose of obtaining material for medicinal research in the country. Seeds were subjected to four disinfestation treatments. <b>Results:</b> The best disinfestation treatment consisted in submerging the seeds in a 2 g·L^-1 Captan^® solution for 30 min before following the standard procedure with 70% ethanol for 30 sec and then 20 min in 2.5% sodium hypochlorite. The <i>in vitro</i> establishment of cannabis from seeds originating from Brazilian drug trafficking seizures was successful. The germination rate ranged from 10% to 90% according to the sample material. Non-brick weed, which consisted of dry leaves, stalks, and flowers, was more suitable for seed extraction and germination. Clones originating from BW4b showed the best development results compared with others. <b>Conclusions:</b> This is the first report of <i>in vitro</i> cannabis use in Brazil and opens great prospects for future work on its cultivation and research for medicinal applications in the country without relying on seed importation.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e924-e932"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41117354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effect of a Pharmaceutical Extract of Cannabis with High Content on CBD Against Rotenone in Primary Cerebellar Granule Cell Cultures and the Relevance of Formulations.","authors":"Carolina Echeverry, Analía Richeri, Jimena Fagetti, Gaby F Martínez, Federico Vignolo, Giselle Prunell, Leticia Cuñetti, Marcela Martínez Busi, Sandra Pérez, Verónica Sánchez de Medina, Carlos Ferreiro, Cecilia Scorza","doi":"10.1089/can.2022.0289","DOIUrl":"10.1089/can.2022.0289","url":null,"abstract":"<p><p><b>Introduction:</b> Preclinical research supports the benefits of pharmaceutical cannabis-based extracts for treating different medical conditions (e.g., epilepsy); however, their neuroprotective potential has not been widely investigated. <b>Materials and Methods:</b> Using primary cultures of cerebellar granule cells, we evaluated the neuroprotective activity of Epifractan (EPI), a cannabis-based medicinal extract containing a high level of cannabidiol (CBD), components like terpenoids and flavonoids, trace levels of Δ9-tetrahydrocannabinol, and the acid form of CBD. We determined the ability of EPI to counteract the rotenone-induced neurotoxicity by analyzing cell viability and morphology of neurons and astrocytes by immunocytochemical assays. The effect of EPI was compared with XALEX, a plant-derived and highly purified CBD formulation (XAL), and pure CBD crystals (CBD). <b>Results:</b> The results revealed that EPI induced a significant reduction in the rotenone-induced neurotoxicity in a wide range of concentrations without causing neurotoxicity <i>per se</i>. EPI showed a similar effect to XAL suggesting that no additive or synergistic interactions between individual substances present in EPI occurred. In contrast, CBD did show a different profile to EPI and XAL because a neurotoxic effect <i>per se</i> was observed at higher concentrations assayed. Medium-chain triglyceride oil used in EPI formulation could explain this difference. <b>Conclusion:</b> Our data support a neuroprotective effect of EPI that may provide neuroprotection in different neurodegenerative processes. The results highlight the role of CBD as the active component of EPI but also support the need for an appropriate formulation to dilute pharmaceutical cannabis-based products that could be critical to avoid neurotoxicity at very high doses.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e907-e916"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9424654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Mitigates Lipopolysaccharide-Induced Pancreatic Pathology: A Promising Therapeutic Strategy.","authors":"Senay Topsakal, Ozlem Ozmen, Nasif Fatih Karakuyu, Mehmet Bedir, Okan Sancer","doi":"10.1089/can.2023.0153","DOIUrl":"10.1089/can.2023.0153","url":null,"abstract":"<p><p><b>Background:</b> Lipopolysaccharides (LPSs) are a component of certain types of bacteria and can induce an inflammatory response in the body, including in the pancreas. Cannabidiol (CBD), a nonpsychoactive compound found in cannabis, has been shown to have anti-inflammatory effects and may offer potential therapeutic benefits for conditions involving inflammation and damage. The aim of this study was to investigate any potential preventative effects of CBD on experimental LPS-induced pancreatic pathology in rats. <b>Materials and Methods:</b> Thirty-two rats were randomly divided into four groups as control, LPS (5 mg/kg, intraperitoneally [i.p.]), LPS+CBD, and CBD (5 mg/kg, i.p.) groups. Six hours after administering LPS, the rats were euthanized, and blood and pancreatic tissue samples were taken for biochemical, polymerase chain reaction (PCR), histopathological, and immunohistochemical examinations. <b>Results:</b> The results indicated that LPS decreased serum glucose levels and increased lipase levels. It also caused severe hyperemia, increased vacuolization in endocrine cells, edema, and slight inflammatory cell infiltrations at the histopathological examination. Insulin and amylin expressions decreased during immunohistochemical analyses. At the PCR analysis, Silent Information Regulator 2 homolog 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha expressions decreased and tumor protein p53 expressions increased in the LPS group. CBD improved the biochemical, PCR, histopathological, and immunohistochemical results. <b>Conclusions:</b> The findings of the current investigation demonstrated that LPS damages both the endocrine and exocrine pancreas. However, CBD demonstrated marked ameliorative effects in the pancreas in LPS induced rat model pancreatitis.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"809-818"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Exposure During Gestation Leads to Adverse Cardiac Outcomes Early in Postnatal Life in Male Rat Offspring.","authors":"Kendrick Lee, Sebastian Vanin, Mina Nashed, Mohammed Halit Sarikahya, Steven R Laviolette, David R C Natale, Daniel B Hardy","doi":"10.1089/can.2023.0213","DOIUrl":"10.1089/can.2023.0213","url":null,"abstract":"<p><p><b>Introduction:</b> Studies indicate that ∼7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to Δ⁹-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. <b>Methods:</b> Pregnant Wistar rats were exposed to either 3 or 30 mg/kg CBD or vehicle control i.p. daily from gestational day 6 to term. Echocardiography was used to assess cardiac function in male and female offspring at postnatal day (PND) 21. Furthermore, quantitative polymerase chain reaction (qPCR), immunoblotting, and bulk RNA-sequencing (RNA-seq) were performed on PND21 offspring hearts. <b>Results:</b> Despite no differences in the heart-to-body weight ratio, both doses of CBD led to reduced cardiac function exclusively in male offspring at 3 weeks of age. Underlying this, significant alterations in the expression of the endocannabinoid system (ECS; e.g., decreased cannabinoid receptor 2) were observed. In addition, bulk RNA-seq data demonstrated transcriptional pathways significantly enriched in mitochondrial function/metabolism as well as development. <b>Conclusion:</b> Collectively, we demonstrated for the first time that gestational exposure to CBD, a constituent perceived as safe, leads to early sex-specific postnatal cardiac deficits and alterations in the cardiac ECS in offspring.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"781-796"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Licensed Medical Cannabis Use in Gilles de la Tourette Syndrome: A Retrospective Long-term Follow-Up.","authors":"Saar Anis, Corinne Zalomek, Amos D Korczyn, Simon Lassman, Alina Rosenberg, Tanya Gurevich","doi":"10.1089/can.2022.0281","DOIUrl":"10.1089/can.2022.0281","url":null,"abstract":"<p><p><b>Background:</b> Medical cannabis (MC) is widely used in clinical practice to treat Gilles de la Tourette syndrome (GTS). However, legislation, multiple modes of administration, and inconsistent plant preparations have limited trials to assess its benefits and long-term safety. For the past decade, licensed MC has been authorized in Israel for use in resistant GTS. We aimed to describe subjects' satisfaction, consumption habits, and THC dose increment during long-term usage. <b>Materials and Methods:</b> A retrospective longitudinal data collection (up to 9 years) on cannabis use habits and structured questionnaires evaluating disease characteristics and MC influence from GTS subjects being treated in the Movement Disorders Unit of the Tel-Aviv Medical Center, Israel. <b>Results:</b> Twenty-five patients (84% male) participated in the study. The mean duration of MC use was 4.0±2.3 years (range 0.5-10). The majority of patients (96%) consumed MC primarily, but not exclusively, through inhalation methods such as smoking or vaporizing dried inflorescence. A linear increase was observed in mean monthly THC dose (<i>p</i><0.0001) with an average increase of 0.6-0.7 g/year. MC led to a subjectively reported reduction in tics (75% average reduction) and symptoms associated with common comorbidities of GTS. MC was generally well tolerated, although most participants (88%) reported experiencing side effects. <b>Conclusions:</b> A subset of GTS subjects who use MC long term under clinical observation may subjectively improve control of symptoms. Subject-led dose increase can indicate emerging tolerance. Large randomized controlled and observational long-term trials are required to confirm these observations.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e878-e885"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth.","authors":"Sofia Allen, Bryony V Natale, Alexis O Ejeckam, Kendrick Lee, Daniel B Hardy, David R C Natale","doi":"10.1089/can.2023.0166","DOIUrl":"10.1089/can.2023.0166","url":null,"abstract":"<p><p><b>Introduction:</b> Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as \"natural\" and \"safe\" as it is non-intoxicating. <i>In utero</i>, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of Δ⁹-THC, there has been limited investigation into the impacts of <i>in utero</i> gestational CBD exposure on the placenta. <b>Methods:</b> This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat placentas from vehicle and CBD (3 mg/kg intraperitoneal injection) exposed pregnancies (E6.5-18.5). <b>Results:</b> The study revealed that pups from CBD-exposed pregnancies were 10% smaller, with the placentae displaying a decreased fetal blood space perimeter-to-area ratio. The transcriptomic analysis supported compromised angiogenesis and blood vessel formation with downregulated biological processes, including tube morphogenesis, angiogenesis, blood vessel morphogenesis, blood vessel development and vasculature development. Further, the CBD-exposed placentas displayed changed expression of glucose transporters (decreased GLUT1 and GR expression and increased GLUT3 expression). Transcriptomic analysis further revealed upregulated biological processes associated with metabolism. Finally, histological and transcriptomic analysis revealed altered cell populations within the placenta, specifically to syncytiotrophoblast layer II and endothelial cells. <b>Conclusion:</b> Together these results suggest that the structural changes in CDB-exposed placentae, including the altered expression of nutrient transporters and the changes to the placental fetal vasculature, may underlie the reduced fetal growth.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"766-780"},"PeriodicalIF":3.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabis Use Disorder Symptoms in Weekly Cannabis Users: A Network Comparison Between Daily Cigarette Users and Nondaily Cigarette Users.","authors":"René Freichel, Emese Kroon, Lauren Kuhns, Francesca Filbey, Ilya M Veer, Reinout Wiers, Janna Cousijn","doi":"10.1089/can.2022.0239","DOIUrl":"10.1089/can.2022.0239","url":null,"abstract":"<p><p><b>Background:</b> Concurrent use (co-use) of cannabis and tobacco is common and associated with worse clinical outcomes compared with cannabis use only. The mechanisms and interactions of cannabis use disorder (CUD) symptoms underlying co-use remain poorly understood. <b>Methods:</b> We examined differences in the symptom presence and symptom network configurations between weekly cannabis users who use tobacco daily (co-users, <i>n</i>=789) or non- or nondaily (nondaily co-users, <i>n</i>=428). <b>Results:</b> First, we identified a range of symptoms (<i>craving</i>, failed <i>reduce or quit attempts</i>, neglected <i>responsibilities</i>, and negative <i>social</i> effects) that are most central to the highly interconnected CUD symptom network. Risky cannabis use was mostly associated with negative social and health effects, and independent of other CUD symptoms. Craving symptoms act as a bridge between different CUD and withdrawal symptoms. Among co-users, (1) craving is more strongly associated with negative psychosocial effects, (2) feelings of depression and negative health effects are more central to the network, and (3) the negative health effects are more strongly associated with failed attempts to reduce or quit attempts compared with nondaily co-users. <b>Discussion:</b> Our results go beyond existing findings focused on the mere increase in CUD symptom presence, and speak to the potential synergistic effects of co-use on dependence and withdrawal symptoms. We outline clinical implications with respect to targeting specific CUD symptoms in co-users, and point to future research to disentangle tobacco and cannabis craving symptoms.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e847-e858"},"PeriodicalIF":3.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9440718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Cannabidiol on the Functions of Chimeric Antigen Receptor T Cells in Hematologic Malignancies.","authors":"Natthida Chantarat, Kristine Cate S Pe, Koramit Suppipat, Sornkanok Vimolmangkang, Supannikar Tawinwung","doi":"10.1089/can.2023.0108","DOIUrl":"10.1089/can.2023.0108","url":null,"abstract":"<p><p><b>Introduction:</b> CD19-chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy for cancer treatment that has shown remarkable clinical responses, leading to approval by the FDA for relapsed and refractory B cell hematological malignancy treatment. Cannabidiol (CBD) is a nonpsychoactive cannabinoid compound that has been utilized as a palliative treatment in cancer patients due to its immunosuppressive properties. Currently, studies on using CBD during immunotherapy have gained increasing attention. However, the possible interaction between CBD and CAR T cell therapy has not been studied. Therefore, in this study, we aimed to examine the direct effects of CBD on CD19-CAR T cell function against hematologic malignancies. <b>Materials and Methods:</b> The cytotoxic effect of CBD was determined by a cell proliferation reagent water-soluble tatrazolium salt (WST-1) assay. CAR T cells were generated by retroviral transduction and treated with CBD at a nontoxic dose. The effect of CBD on immune characteristics, including transgene expression, T cell subset, and memory phenotype, was analyzed by flow cytometry. Proliferation, apoptosis, and cell cycle distribution were analyzed with standard methods. The effect on cytotoxic function was evaluated using degranulation assays, and antitumor activity was evaluated using flow cytometry. <b>Results:</b> The half-maximum inhibitory concentration (IC₅₀) of CBD on NALM6, Raji, and T cells ranged from 16 to 22 μM. The maximum nontoxic dose of CBD that maintained cell viability at ∼100% was 8 μM. For the generation of CD19-CAR T cells, primary T cells were activated and transduced with a retroviral vector encoding CD19-CAR. CBD did not alter the surface expression or immune characteristics, including the T cell subset and memory phenotype, of CD19-CAR T cells. However, CBD suppressed CD19-CAR T cell proliferation by inducing apoptosis, as evidenced by an increase in the proportion of cells in the Sub-G1 phase in cell cycle arrest. However, the antitumor activity and cytokine secretion of CD19-CAR T cells were not altered by exposure to CBD in this study. <b>Conclusions:</b> In this study, a nontoxic dose of CBD affected CD19-CAR T cell proliferation but not its immune characteristics or cytotoxic function.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"819-829"},"PeriodicalIF":3.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50157109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}