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
{"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}
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
{"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 (CB<sub>1</sub>R and CB<sub>2</sub>R) 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 CB<sub>1</sub>R and CB<sub>2</sub>R antagonists showed that ABX1431 exhibited its effects partially through CB<sub>1</sub>R. <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 CB<sub>1</sub>R expression levels; however, CB<sub>2</sub>R 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 CB<sub>1</sub>R. 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}
Rachel S Bergmans, Christine Yu, Bhaavna Yalavarthi, Lillian Z Xiao, Riley Wegryn-Jones, Johari Summerville, Sia Rajgarhia, Vivian Kurtz, Samantha Dell'Imperio, Amy S B Bohnert, Kevin F Boehnke
{"title":"How Veterans with Chronic Pain Approach Using Cannabis for Symptom Management: Results from a Qualitative Interpretive Description Study.","authors":"Rachel S Bergmans, Christine Yu, Bhaavna Yalavarthi, Lillian Z Xiao, Riley Wegryn-Jones, Johari Summerville, Sia Rajgarhia, Vivian Kurtz, Samantha Dell'Imperio, Amy S B Bohnert, Kevin F Boehnke","doi":"10.1089/can.2024.0135","DOIUrl":"https://doi.org/10.1089/can.2024.0135","url":null,"abstract":"<p><p><b>Introduction:</b> Veterans use cannabis as a chronic pain treatment due to a combination of the easing of restrictions and dissatisfaction with care standards. The segregation of medical cannabis from conventional health systems may translate to opportunities and disadvantages that are not well defined. Our study aimed to characterize how Veterans with chronic pain approach using cannabis for symptom management, including product access, developing a treatment plan, and its integration into daily life. <b>Materials and Methods:</b> We used an interpretive description design and conducted semi-structured interviews with U.S. Veterans in Michigan who had chronic pain; were aged 21 years or older; and (a) used cannabis, (b) were planning to use cannabis, or (c) interested in learning about how cannabis could help with pain. We analyzed deidentified interview transcripts to develop themes that focused on how Veterans approached new and continued use of cannabis for chronic pain management. <b>Results:</b> Participants were Veterans with chronic pain, median age = 50 years (<i>n</i> = 32). Participants described how factors at the individual, relationship, community, and societal levels influenced their interest in and use of cannabis for chronic pain. We identified five main themes: (1) cannabis supports holistic wellness, but there are also undesired effects; (2) medical cannabis requires a personalized treatment approach; (3) Veterans seek expanded access to medical cannabis and more assurance regarding product safety and efficacy; (4) sociopolitical attitudes and advocacy shape medical cannabis acceptability; and (5) the interest in research to inform treatment approaches and facilitate access. <b>Discussion:</b> This article illustrates how Veterans approached using cannabis for chronic pain management. Findings illuminate the potential value of cannabis for Veterans with chronic pain while also highlighting numerous obstacles and limitations related to its use. There are opportunities for health care providers to support Veterans who are interested in cannabis while research regarding efficacy and safety continues. Future efforts should engage Veterans to collectively work toward a better understanding of cannabis as a pain treatment option.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709119","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":"Drug Interactions in People on Cannabidiol: Is There Cause for Concern?","authors":"Georgia Downs, Ristan Greer, Geraldine Moses, Taylan Gurgenci, Phillip Good, Janet Hardy","doi":"10.1089/can.2024.0041","DOIUrl":"https://doi.org/10.1089/can.2024.0041","url":null,"abstract":"<p><p><b>Introduction:</b> Cannabidiol (CBD) exhibits multiple therapeutic properties, but its use in advanced cancer patients raises concerns about potential drug-drug interactions (DDIs) due to polypharmacy. This study aims to look for evidence of DDIs between concomitant medications and CBD oil in a randomized placebo-controlled trial of CBD oil for symptom control (MedCan-1 parent study). <b>Materials and Methods:</b> Surrogate measures were used to identify possible drug interactions: (1) the maximum mL of oil self-selected by patients in CBD or placebo groups in relation to opioids, specific drug groups, or individual agents; (2) the occurrence of any new or worse adverse effect in relation to the study arm and the concomitant medication classes/medications of interest. <b>Results:</b> The dose of CBD self-selected by participants was not related to opioid use or medications, including benzodiazepines and antipsychotics. The likelihood of developing an adverse effect while on study or when taking specific medications was not increased by CBD. Participants on paracetamol tolerated a higher dose of CBD. <b>Discussion:</b> Concerns regarding the development of clinically significant drug interactions when taking CBD in the context of anti-cancer and other concomitant medications at least in the short term may be unfounded.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615309","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":"Federal Courts Will No Longer Need to Follow the DEA's Interpretation of Cannabis-Related Law.","authors":"Bob Solomon","doi":"10.1089/can.2024.0176","DOIUrl":"10.1089/can.2024.0176","url":null,"abstract":"","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589413","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}
Daniela Schwotzer, Justyna Kulpa, Andrew Gigliotti, Wendy Dye, Kristen Trexler, Hammad Irshad, Tim Lefever, Mark Ware, Marcel Bonn-Miller, Jacob McDonald
{"title":"Biological Response after 14-Day Cannabidiol and Propylene Glycol Inhalation in Sprague-Dawley Rats.","authors":"Daniela Schwotzer, Justyna Kulpa, Andrew Gigliotti, Wendy Dye, Kristen Trexler, Hammad Irshad, Tim Lefever, Mark Ware, Marcel Bonn-Miller, Jacob McDonald","doi":"10.1089/can.2023.0132","DOIUrl":"https://doi.org/10.1089/can.2023.0132","url":null,"abstract":"<p><p><b>Objective:</b> Cannabidiol (CBD), a phytocannabinoid of increasing interest for its purported therapeutic effects, is primarily consumed <i>via</i> ingestion and inhalation. While the toxicology of orally administered CBD has been reported, little is known about the effects of CBD inhalation. Doses selected for the present analysis allowed for evaluation of dose-response at concentrations >100-fold higher than typical human consumption levels. <b>Materials and Methods:</b> CBD (98.89% pure) was formulated in propylene glycol (PG) and aerosolized by nebulization to evaluate biological response after nose-only inhalation. Sprague Dawley rats (<i>n</i> = 35 males, 30 females) were exposed to 1.0 and 1.3 mg/L nominal concentrations of CBD and PG, respectively, for 12-180 min. Resulting average daily presented dose ranges were 8.9-138.5 mg/kg CBD and 11.3-176.0 mg/kg PG. Aerosols of 1.4 µm median diameter were achieved. Biological response indicators included clinical signs, clinical chemistry, hematology, body/organ weights, and pulmonary/systemic histopathology. <b>Results:</b> Inflammatory and necrotic responses were observed in the nose at the highest doses of CBD. Limited findings in the larynx and lung were mainly observed at higher doses. There were no histological findings in extrapulmonary organs. Dosimetry modeling differentiated the no observable adverse effect level between the nasal region and lungs to be 2.8 and 10.6 mg/kg CBD, respectively. <b>Conclusions:</b> Dose-depending findings of histological changes in the respiratory tract are observed at high doses. At lower doses consistent with typical over-the-counter vape products there appears to be substantial safety margin in the present study (93- and 353-fold lower for nose and lung, respectively).</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495625","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}
Alan P Baltz, Cheng Peng, Laura Gressler, Sajjad Bhatti, Kanna Lewis
{"title":"Association Between Medical Marijuana Cardholder Status and Antiemetic Overuse.","authors":"Alan P Baltz, Cheng Peng, Laura Gressler, Sajjad Bhatti, Kanna Lewis","doi":"10.1089/can.2024.0083","DOIUrl":"https://doi.org/10.1089/can.2024.0083","url":null,"abstract":"<p><p><b>Introduction:</b> The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) \"Choosing Wisely\" recommendations. The pharmacologic properties of medical marijuana (MMJ) may allow for decreased incidence of CINV; however, little is known about the effects of MMJ on the use of antiemetics. This study aimed to determine if MMJ cardholder status, which enables access to MMJ, is associated with antiemetic overuse among patients with cancer. <b>Materials and Methods:</b> This population-based secondary data analysis examined a retrospective cohort derived from the linked Arkansas All Payers Claims Database (2013-2020) and MMJ cardholder registry (2013-2019). The cohort consisted of 20,558 patients with cancer aged 18 and older with a chemotherapy claim in an outpatient setting within 12 months of a cancer diagnosis. Exposure was a registration to receive an MMJ card that permitted access to MMJ. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use associated with chemotherapy was identified through filled prescriptions and medical claims. Multivariable logistic regression, adjusted for baseline demographic and prescription characteristics, was used to calculate the adjusted odds ratios (aOR) of antiemetic overuse among MMJ cardholders compared with non-MMJ cardholders. <b>Results:</b> Among 20,558 eligible patients, 436 (2.1%) had an MMJ card at some point in the study period. Antiemetic overuse was identified in 7.5% of chemotherapy cycles. Compared with non-MMJ cardholders, MMJ cardholders were less likely to experience antiemetics overuse (aOR: 0.76, <i>p</i> < 0.001). Patients with fewer chemotherapy cycles and younger in age had higher odds of antiemetic overuse compared with those with more chemotherapy cycles. The risk of antiemetic overuse did not differ based on gender and rurality of residency. Route of chemotherapy administration, CINV risk category, and type of cancer also impacted the odds of antiemetic overuse. <b>Discussion:</b> The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than non-MMJ cardholders. Further investigation into the use, effectiveness, and safety of cannabis for CINV mitigation is needed to inform patient and provider decision-making.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458562","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}
Avery G Boals, Daniel M Collier, Julian R Romero, Cecilia J Hillard, Frank Park
{"title":"Lack of Cannabinoid Type 2 Promoter Activity in Normal or Injured Kidneys Using a Cnr2-GFP Reporter Mouse.","authors":"Avery G Boals, Daniel M Collier, Julian R Romero, Cecilia J Hillard, Frank Park","doi":"10.1089/can.2024.0142","DOIUrl":"https://doi.org/10.1089/can.2024.0142","url":null,"abstract":"<p><p><b>Introduction:</b> Although cannabinoid type 2 (CB2) receptor activity is known to promote diverse biological functions in the kidney, published data regarding CB2 receptor protein levels and cellular distribution within the kidney is inconsistent. The goal of the present study was to investigate the changes of CB2 in the kidney obtained from mice exposed to various forms of kidney injury using a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous cannabinoid receptor 2 (Cnr2) promoter. <b>Materials and Methods:</b> Kidney injury was established in a genetic mouse model expressing green fluorescent protein (GFP) driven by the endogenous Cnr2 promoter. Kidney injury was initiated by either treatment with different chemicals [cisplatin or lipopolysaccharide (LPS)] or by unilateral ureteral obstruction (UUO). Changes in the detection of GFP were used as a proxy for CB2 levels and localization. Histological changes due to the injury stimuli were observed by time-related, morphological changes in kidney cytoarchitecture and blood parameters, such as serum creatinine levels. Cnr2 mRNA levels were detected by reverse transcription coupled to polymerase chain reaction (RT-PCR) while protein changes in the tissue lysates were measured by Western blot analysis. Cellular localization of GFP was detected by fluorescent microscopy. <b>Results:</b> Our data demonstrated that there was no band or a minimally detectable band for GFP using kidney lysates from vehicle- or cisplatin-treated mice. A similar lack of GFP was detected in the UUO kidney versus the contralateral control kidney. This is consistent with the low, albeit detectable levels of Cnr2 mRNA in the kidney samples from control or cisplatin treatment. In frozen kidney sections from vehicle and cisplatin-treated mice, GFP fluorescence was not detectable in tubular epithelia, glomeruli or blood vessels in the cortex. Instead, GFP was detected in rare cells within the interstitial space. A second chemical injury model using LPS found a similar lack of GFP protein levels and an absence of legitimate GFP fluorescence in the main cell types within the kidney. <b>Conclusion:</b> These findings suggest that Cnr2 promoter activity is minimally active in normal or injured kidneys, and that pharmacological manipulation of CB2 receptors may be associated with receptors being expressed in cells recruited to the kidney.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388262","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}
Xiaoxi Zheng, Beth Ehrlich, David Finlay, Michelle Glass
{"title":"No Evidence for Endocannabinoid-Induced G Protein Subtype Selectivity at Human and Rodent Cannabinoid CB<sub>1</sub> Receptors.","authors":"Xiaoxi Zheng, Beth Ehrlich, David Finlay, Michelle Glass","doi":"10.1089/can.2024.0133","DOIUrl":"https://doi.org/10.1089/can.2024.0133","url":null,"abstract":"<p><p><b>Introduction:</b> The endocannabinoid system (ECS) is a widespread neurotransmitter system. A key characteristic of the ECS is that there are multiple endogenous ligands (endocannabinoids). Of these, the most extensively studied are arachidonoyl ethanolamide (AEA) and 2-arachidonoyl-glycerol (2-AG), both act as agonists at the cannabinoid CB<sub>1</sub> receptor. In humans, three CB<sub>1</sub> variants have been identified: hCB<sub>1</sub>, considered the most abundant G protein-coupled receptor in the brain, alongside the less abundant and studied variants, hCB<sub>1a</sub> and hCB<sub>1b</sub>. CB<sub>1</sub> exhibits a preference for coupling with inhibitory G<sub>i/o</sub> proteins, although its interactions with specific members of the G<sub>i/o</sub> family remain poorly characterized. This study aimed to compare the AEA and 2-AG-induced activation of various G protein subtypes at CB<sub>1</sub>. Furthermore, we compared the response of human CB<sub>1</sub> (hCB<sub>1</sub>, hCB<sub>1a</sub>, hCB<sub>1b</sub>) and explored species differences by examining rodent receptors (mCB<sub>1</sub>, rCB<sub>1</sub>). <b>Materials and Methods:</b> Activation of individual G protein subtypes in HEK293 cells transiently expressing CB<sub>1</sub> was measured with G protein dissociation assay utilizing TRUPATH biosensors. The performance of the TRUPATH biosensors was evaluated using Z-factor analysis. Pathway potencies and efficacies were analyzed using the operational analysis of bias to determine G protein subtype selectivity for AEA and 2-AG. <b>Results:</b> Initial screening of TRUPATH biosensors performance revealed variable sensitivities within our system. Based on the biosensor performance, the G protein subtypes pursued for further characterization were G<sub>i1</sub>, G<sub>i3</sub>, G<sub>oA</sub>, G<sub>oB</sub>, G<sub>Z</sub>, G<sub>12</sub>, and G<sub>13</sub>. Across all pathways, AEA demonstrated partial agonism, whereas 2-AG exhibited full or high-efficacy agonism. Notably, we provide direct evidence that the hCB<sub>1</sub> receptor couples to G<sub>12</sub> and G<sub>13</sub> proteins. Our findings do not indicate any evidence of G protein subtype selectivity. Similar observations were made across the human receptor variants (hCB<sub>1</sub>, hCB<sub>1a</sub>, hCB<sub>1b</sub>), as well as at mCB<sub>1</sub> and rCB<sub>1</sub>. <b>Discussion:</b> There was no evidence suggesting G protein subtype selectivity for AEA and 2-AG at CB<sub>1</sub>, and this finding remained consistent across human receptor variants and different species.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380084","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}
María Andrea Arnanz, Samuel Ruiz de Martín Esteban, Ana María Martínez Relimpio, Neta Rimmerman, Nurit Tweezer Zaks, María Teresa Grande, Julián Romero
{"title":"Effects of Chronic, Low-Dose Cannabinoids, Cannabidiol, Delta-9-Tetrahydrocannabinol and a Combination of Both, on Amyloid Pathology in the 5xFAD Mouse Model of Alzheimer's Disease.","authors":"María Andrea Arnanz, Samuel Ruiz de Martín Esteban, Ana María Martínez Relimpio, Neta Rimmerman, Nurit Tweezer Zaks, María Teresa Grande, Julián Romero","doi":"10.1089/can.2023.0101","DOIUrl":"10.1089/can.2023.0101","url":null,"abstract":"<p><p><b>Background:</b> There is an urgent need for novel therapies to treat Alzheimer's disease. Among others, the use of cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been proposed as a putative approach based on their anti-inflammatory effects. <b>Methods:</b> The present work was designed to explore the effects of chronic (28 days) treatment with low doses of cannabinoids: CBD (0.273 mg/kg), THC (0.205 mg/kg) or a combination of both (CBD:THC; 0.273 mg/kg:0.205 mg/kg) in the 5xFAD mouse model of AD. <b>Results:</b> Our data revealed that THC-treated 5xFAD mice (but not other treatment groups) exhibited anxiogenic and depressant-like behavior. A significant improvement in spatial memory was observed only in the CBD:THC-treated group. Interestingly, all cannabinoid-treated groups showed significantly increased cortical levels of the insoluble form of beta amyloid 1-42. These effects were not accompanied by changes in molecular parameters of inflammation at the mRNA or protein level. <b>Conclusions:</b> These data reveal differential effects of chronic, low-dose cannabinoids and point to a role of these cannabinoids in the processing of amyloid peptides in the brains of 5xFAD mice.</p>","PeriodicalId":9386,"journal":{"name":"Cannabis and Cannabinoid Research","volume":" ","pages":"1312-1325"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674611","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}