Cannabis and Cannabinoid Research最新文献

{"title":"Perception of Risk of Harm from Cannabis Use Among Women of Reproductive Age with Disabilities.","authors":"Panagiota Kitsantas, Salman M Aljoudi, Lea Sacca","doi":"10.1089/can.2023.0199","DOIUrl":"10.1089/can.2023.0199","url":null,"abstract":"<p><p><b>Objectives:</b> To examine perceived risk of harm from weekly cannabis use among reproductive-aged women with disabilities. <b>Methods:</b> Using data from the 2021 National Survey on Drug Use and Health, we assessed perceived risk of harm associated with weekly cannabis use among women of reproductive age by disability status. Disabilities included sensory, cognitive, and those related to daily activities. Logistic regression was employed to examine correlates of risk perception associated with weekly cannabis in this subpopulation of women. <b>Results:</b> A significantly higher percentage of women with any disability perceived no risk associated with weekly cannabis use (37.9%) compared to those with no disabilities (26.1%). Approximately, 60.0% of women with disabilities who used cannabis in the past 12 months perceived no risk of harm from weekly cannabis use. Overall, women with disabilities and cannabis use in the past 12 months had higher adjusted odds (AOR=2.90, 95% CI=2.10-4.10) of perceiving no risk associated with weekly use of cannabis compared to women without any disability and no cannabis use. Other significant factors associated with an increased likelihood of perceiving no risk of harm from weekly use of cannabis included younger women, having higher income, being in good health, and using alcohol or tobacco. <b>Conclusions:</b> Perceived risk of harm associated with weekly cannabis use is particularly low among women with disabilities who use cannabis. Given current attitudes toward cannabis as a harmless drug, and the potential adverse health outcomes, it is imperative to monitor and understand women's perceptions of risk of harm from cannabis use for clinical guidance, provider and patient education, and public health programs to support evidence-based approaches in addressing its use among vulnerable populations such as those of reproductive age with disabilities.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1615-e1622"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038731","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 Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.","authors":"Valentina Lorenzetti, Alexandra Gaillard, Eugene McTavish, Sally Grace, Maria Gloria Rossetti, Albert Batalla, Marcella Bellani, Paolo Brambilla, Yann Chye, Patricia Conrod, Janna Cousijn, Izelle Labuschagne, Adam Clemente, Scott Mackey, Peter Rendell, Nadia Solowij, Chao Suo, Chiang-Shan R Li, Gill Terrett, Paul M Thompson, Murat Yücel, Hugh Garavan, Carl A Roberts","doi":"10.1089/can.2023.0204","DOIUrl":"10.1089/can.2023.0204","url":null,"abstract":"<p><p><b>Background:</b> Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. <b>Methods:</b> We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). <b>Results:</b> We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (<i>p</i><0.001, <i>d</i>=0.32) and with controls (<i>p</i>=0.022, <i>d</i>=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (<i>p</i>=0.002, <i>d</i>=0.37, and <i>p</i>=0.002, <i>d</i>=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. <b>Conclusions:</b> Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1565-e1578"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142779","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":"Comparison Between Smoked Tobacco and Medical Cannabis Cigarettes Concerning Particulate Matter.","authors":"Fenna Janssen, Markus Braun, Janis Dröge, Dörthe Brüggmann, David A Groneberg","doi":"10.1089/can.2023.0201","DOIUrl":"10.1089/can.2023.0201","url":null,"abstract":"<p><p><b>Introduction:</b> Cannabis is a widely used drug like tobacco and alcohol. In the meantime, it is also prescribed for medical treatment in some countries. Tobacco smoke contains chemical carcinogens and particulate matter (PM) that are both harmful to health. <b>Method:</b> In this study, we investigated PM levels in second-hand smoke (SHS) of hand-tamped cannabis cigarettes compared to cigarettes with tubing tobacco and the 3R4F reference cigarette. <b>Results:</b> It could be demonstrated that the largest proportion of the particle mass is attributable to particles with a diameter of less than 1μm and that every tested cigarette emitted more PM than the 3R4F reference cigarette. In addition, our data clearly revealed that cannabis smoke contains higher PM levels in SHS than tobacco cigarettes. Compared to the reference cigarette, the PM₁ emissions of cannabis were 105% higher. Also, the cannabis mixed cigarettes had higher PM levels than the 3R4F cigarettes. For instance, the PM₁₀ emissions were 93% higher. Also, the Gauloises Mélange tubing tobacco also reached higher PM concentrations than the 3R4F cigarette. <b>Discussion:</b> Regardless of negative health effects, cannabis is seen as a harmless drug in the public eye. We found strong indications for potential health risks by PM from cannabis products and, therefore, the public should be educated about a potential harm.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1492-1499"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641641","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":"Endocannabinoid Receptor 2 Function is Associated with Tumor-Associated Macrophage Accumulation and Increases in T Cell Number to Initiate a Potent Antitumor Response in a Syngeneic Murine Model of Glioblastoma.","authors":"Jin Duan, Jieling Chen, Yilin Lin, Stanley L Lin, Jie Wu","doi":"10.1089/can.2024.0063","DOIUrl":"10.1089/can.2024.0063","url":null,"abstract":"<p><p><b>Introduction:</b> Glioblastoma patients have a highly immunosuppressive tumor microenvironment and systemic immunosuppression that comprise a major barrier to immune checkpoint therapy. Based on the production of endocannabinoids by glioblastomas, we explored involvement of endocannabinoid receptor 2 (CB2R), encoded by the CNR2 gene, which is predominantly expressed by immune cells, in glioblastoma-related immunosuppression. <b>Materials & Methods:</b> Bioinformatics of human glioblastoma databases was used to correlate enzymes involved in the synthesis and degradation of endocannabinoids, as well as CB2Rs, with patient overall survival. Intrastriatal administration of luciferase-expressing, murine GL261 glioblastoma cells was used to establish in in vivo glioblastoma model for characterization of tumor growth and intratumoral immune cell infiltration, as well as provide immune cells for in vitro co-culture experiments. Involvement of CB2Rs was determined by treatment with CB2R agonist (GW405833) or CB2R antagonist (AM630). ELISA, FACS, and immunocytochemistry were used to determine perforin, granzyme B, and surface marker levels. <b>Results:</b> Bioinformatics of human glioblastoma databases showed high expression of CB2R and elevated endocannabinoid production correlated with poorer prognosis, and involved immune-associated pathways. AM630treatment of GL261 glioblastoma-bearing mice induced a potent antitumor response, with survival plateauing at 50% on Day 40, when all control mice (median survival 28 days) and mice treated with GW405833 (median survival 21 days) had died. Luciferase tumor imaging revealed accelerated tumor growth by GW405833 treatment, but stable or regressing tumors in AM630-treated mice. Notably, in spleens, AM630 treatment caused an 83% decrease in monocytes/macrophages, and 1.8- and 1.6-fold increases in CD8+ and CD4+ cells, respectively. Within tumors, there was a corresponding decrease in tumor-associated macrophages (TAMs) and increase in CD8+ T cells. In vitro, lymphocytes from AM630-treated mice showed greater cytotoxic function (increased percentage of perforin- and granzyme B-positive CD8+ T cells). <b>Discussion:</b> These results suggest that inhibition of CB2R enhances both immunosuppressive TAM infiltration and systemic T-cell suppression through CB2R activation, and that inhibition of CB2Rs can potently counter both the immunosuppressive tumor microenvironment, as well as systemic immunosuppression in glioblastoma.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1524-1536"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417898","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":"Cannabinoid Receptor 2 Gene Polymorphism and the Risk of Developing Rheumatoid Arthritis in Lebanese Patients.","authors":"Morouj Ismail, Ghada Khawaja","doi":"10.1089/can.2023.0220","DOIUrl":"10.1089/can.2023.0220","url":null,"abstract":"<p><p><b>Objective:</b> Evidence supports a role of cannabinoid receptor 2 (CB2) in regulating the immune response. Some variations in the CB2 receptor gene (CB2) were linked to the susceptibility of developing rheumatoid arthritis (RA). The aim of this study is to assess the relationship between <i>CNR2</i> rs2501431 and the risk of developing RA in Lebanese patients. <b>Methods:</b> A total of one hundred five Lebanese RA patients and one hundred five controls participated in the study. <i>CNR2</i> was genotyped and analyzed. <b>Results:</b> Using <i>χ</i>² test, our results show that the CC genotype was the most common (47.6%, <i>p</i><0.00001) and that the C allele highly predominated (64%, <i>p</i><0.00001) in the RA group compared to the control group. The relative odds ratio show that carriers of the CC genotype have more than 13-fold risk of developing RA as compared to TT. <b>Conclusion:</b> Our results suggest that the rs2501431 variant of <i>CNR2</i> gene can be considered as a risk factor for RA development, and thus implicate the potential targeting of CB2 receptor for the treatment of RA.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1597-e1603"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142778","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":"Temporal Trends in Semen Quality, Hormone Levels, and Substance Use Among Infertile Men in Pre- and Post-Cannabis Legalization Eras in Canada.","authors":"Gilad Karavani, Adam Bobrowski, Katherine Lajkosz, Susan Lau, Kirk C Lo, Ethan D Grober, Yonah Krakowsky, Keith Jarvi","doi":"10.1089/can.2023.0164","DOIUrl":"10.1089/can.2023.0164","url":null,"abstract":"<p><p><b>Background:</b> The Cannabis Act (Bill C-45) was enacted in 2018, to legalize and regulate the use, production, and sale of nonmedical cannabis in Canada. While public health and safety implications of cannabis legalization have yet to be elucidated, the wide availability of cannabis necessitates health care providers to be knowledgeable about therapeutic potential and side effects of use. This study aimed to examine the temporal trends over two decades and the impact of the Cannabis Act in Canada, implemented in October 2018, on substance use, semen parameters, and testosterone levels of infertile men. <b>Methods:</b> We conducted a retrospective cohort study from a prospectively maintained database of a single infertility clinic. Demographic, fertility, and substance use history were correlated with semen and hormone assessments. Temporal trends in cannabis use and semen quality between 2001 and 2021 were investigated and compared between pre-cannabis legalization eras (PRCL) and post-cannabis legalization eras (POCL). <b>Results:</b> Our cohort included 11,630 patients (9411 PRCL and 2230 POCL). Cannabis use increased by 8.4% per year (<i>p</i><0.001), while alcohol and tobacco consumption declined (0.8% and 1.5% per year, <i>p</i><0.05 and <i>p</i>=0.004, respectively). Similar trends were noticed in the POCL, with higher rates of cannabis use (22.4% vs. 12.9%, <i>p</i><0.001) and decreased tobacco and alcohol intake (15.2% vs. 17.7%, <i>p</i>=0.005 and 50.5% vs. 55.2%, <i>p</i><0.001, respectively) compared to the PRCL group. Semen concentration was lower in the POCL group (24.8±44.8 vs. 28.7±48.3 million/mL, <i>p</i>=0.03). Testosterone did not differ between the cohorts. Comparison between cannabis users (<i>n</i>=1715) and nonusers (<i>n</i>=9924) demonstrated a slight increase in sperm motility (25.9%±15.3% vs. 23.9%±15.0%, <i>p</i>=0.002) and decreased sperm concentration among users (27.6±53.5 vs. 23.9±15.0 million/mL, <i>p</i>=0.03). <b>Conclusion:</b> A nearly 10% rise in cannabis use in the POCL era was observed among men being investigated for infertility. Our data suggest cannabis use may be associated with an increase in testosterone, slightly improved sperm motility, and decreased sperm concentration.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1588-e1596"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402004","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":"Topical Cannabidiol for Established Chemotherapy-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Trial.","authors":"Stacy D'Andre, Paul Novotny, Camille Walters, Susie Lewis-Peters, Stephan Thomé, Cindy S Tofthagen, Karthik V Giridhar, Charles Loprinzi","doi":"10.1089/can.2023.0253","DOIUrl":"10.1089/can.2023.0253","url":null,"abstract":"<p><p><b>Background:</b> Patients have been known to use cannabinoids for treating established chemotherapy-induced peripheral neuropathy (CIPN) based on anecdotal information and retrospective reports suggesting that such might be beneficial. In response, a double-blinded, placebo-controlled, randomized, pilot clinical trial was developed to evaluate whether resultant data would support a phase III trial for testing whether a cannabidiol (CBD) cream might improve CIPN. <b>Methods:</b> Forty patients with established CIPN were randomized, in a double-blinded manner, to topical CBD or a placebo cream. The study product was applied for 2 weeks, followed by a crossover for 2 weeks. Neuropathy was evaluated using the European Organization of Research and Treatment of Cancer (EORTC)-CIPN20, the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, and the Global Impression of Change instruments. Side effects were recorded by symptom diaries. <b>Results:</b> The EORTC-CIPN20 scores were similar in the patients receiving CBD versus the placebo. Likewise, the toxicity scores were similar in patients who received the CBD versus the placebo. <b>Conclusions:</b> This pilot trial did not support that the studied CBD isolate cream improved painful established CIPN. It was well tolerated overall. <b>Clinical Trial Registration Number:</b> NCT05388058.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"e1556-e1564"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626085","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":"Challenges of Extracting and Determining Cannabinoids in Different Matrices.","authors":"Janis Vella Szijj","doi":"10.1089/can.2024.0087","DOIUrl":"10.1089/can.2024.0087","url":null,"abstract":"<p><p><b>Introduction:</b> Accurate and precise analysis of cannabinoids is important for elucidating their therapeutic potential and developing therapies, which are targeted toward different medical conditions. A wide range of cannabis products are present on the market and are available in different dosage forms, including dried flowers, extracts, and consumables. The aim of this article is to provide an updated narrative review of literature on challenges of analyzing cannabinoids in plant material, oils, and edibles. <b>Method:</b> Literature search was conducted to identify sample preparation and analytical techniques for determination of cannabinoids in plant material, oils, and edibles and associated challenges. <b>Results:</b> Challenges related to determination of cannabinoids in plant material include matrix complexity, co-extraction of unwanted compounds during sample preparation, and differences in matrix composition between calibration standards and sample extracts. During analysis of cannabinoids in oil, the unique properties of carrier oils need to be taken into consideration. Analysis of cannabinoids in edibles can be considered to be challenging due to the wide range of matrix types that are available on the market, rendering analysis resource-intensive, time-consuming, and impractical. <b>Discussion:</b> Analysis of cannabinoids in plant material, oils, and edibles requires a multifaceted approach that includes regulatory guidance, method development, and technological innovation. In the face of an evolving analytical landscape where novel cannabinoids are being identified and require determination, there is a need for the development and validation of standardized accurate and precise analytical methods, which are specifically tailored for each matrix.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1470-1477"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970672","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":"California Cannabis Research Briefing, April 2023: Meeting Summary.","authors":"Margarete C Kulik, Youn Ok Lee, Van Butsic, Timmen L Cermak, Ziva D Cooper, Dominic Corva, Thomas D Marcotte, Dilara K Üsküp, Tracy Richmond McKnight, Agnes Balla","doi":"10.1089/can.2024.0074","DOIUrl":"10.1089/can.2024.0074","url":null,"abstract":"<p><p>On April 28, 2023, the University of California Office of the President, in partnership with the California Department of Cannabis Control (DCC), hosted the California Cannabis Research Briefing. The California Cannabis Research Briefing brought together researchers and state agencies/policymakers to discuss pertinent policy issues on cannabis within the state. Researchers across six different topic areas (environment, cannabis markets, social equity matters, public health, medicinal cannabis use, and public safety) provided brief explanations of their research and its policy implications. A moderated discussion with stakeholders followed these presentations. The goals of this event were to highlight research that can inform policy issues relevant to the state, and to discuss how research can be incorporated into the cannabis policy landscape.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1463-1469"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890916","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":"Acute Effects of Monoacylglycerol Lipase Inhibitor ABX1431 on Neuronal Hyperexcitability, Nociception, Locomotion, and the Endocannabinoid System in HIV-1 Tat Male Mice.","authors":"Barkha J Yadav-Samudrala, Havilah P Ravula, Karenna M Barmada, Hailey Dodson, Justin L Poklis, Bogna M Ignatowska-Jankowska, Aron H Lichtman, Kathryn J Reissner, Sylvia Fitting","doi":"10.1089/can.2023.0247","DOIUrl":"10.1089/can.2023.0247","url":null,"abstract":"<p><p><b>Background:</b> Evidence suggests that monoacylglycerol lipase (MAGL) inhibitors can potentially treat HIV symptoms by increasing the concentration of 2-arachidonoylglycerol (2-AG). We examined a selective MAGL inhibitor ABX1431 in the context of neuroHIV. <b>Methods:</b> To assess the effects of ABX1431, we conducted <i>in vitro</i> and <i>in vivo</i> studies. <i>In vitro</i> calcium imaging on frontal cortex neuronal cultures was performed to evaluate the role of ABX1431 (10, 30, 100 nM) on transactivator of transcription (Tat)-induced neuronal hyperexcitability. Following <i>in vitro</i> experiments, <i>in vivo</i> experiments were performed using Tat transgenic male mice. Mice were treated with 4 mg/kg ABX1431 and assessed for antinociception using tail-flick and hot plate assays followed by locomotor activity. After the behavioral experiments, their brains were harvested to quantify endocannabinoids (eCB) and related lipids through mass spectrometry, and cannabinoid type-1 and -2 receptors (CB₁R and CB₂R) were quantified through western blot. <b>Results:</b> <i>In vitro</i> studies revealed that adding Tat directly to the neuronal cultures significantly increased intracellular calcium concentration, which ABX1431 completely reversed at all concentrations. Preincubating the cultures with CB₁R and CB₂R antagonists showed that ABX1431 exhibited its effects partially through CB₁R. <i>In vivo</i> studies demonstrated that acute ABX1431 increased overall total distance traveled and speed of mice regardless of their genotype. Mass spectrometry and western blot analyses revealed differential effects on the eCB system based on Tat expression. The 2-AG levels were significantly upregulated following ABX1431 treatment in the striatum and spinal cord. Arachidonic acid (AA) was also upregulated in the striatum of vehicle-treated Tat(+) mice. No changes were noted in CB₁R expression levels; however, CB₂R levels were increased in ABX1431-treated Tat(-) mice only. <b>Conclusion:</b> Findings indicate that ABX1431 has potential neuroprotective effects <i>in vitro</i> partially mediated through CB₁R. Acute treatment of ABX1431 <i>in vivo</i> shows antinociceptive effects, and seems to alter locomotor activity, with upregulating 2-AG levels in the striatum and spinal cord.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1500-1513"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939735","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}