{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:33:40Z","timestamp":1789439620975,"version":"build-2803163510"},"reference-count":331,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T00:00:00Z","timestamp":1667088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation","award":["SFH180531338233"],"award-info":[{"award-number":["SFH180531338233"]}]},{"name":"Rhodes Research Committee","award":["SFH180531338233"],"award-info":[{"award-number":["SFH180531338233"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Opportunities for developing innovative and intelligent drug delivery technologies by targeting the endocannabinoid system are becoming more apparent. This review provides an overview of strategies to develop targeted drug delivery using the endocannabinoid system (ECS). Recent advances in endocannabinoid system targeting showcase enhanced pharmaceutical therapy specificity while minimizing undesirable side effects and overcoming formulation challenges associated with cannabinoids. This review identifies advances in targeted drug delivery technologies that may permit access to the full pharmacotherapeutic potential of the ECS. The design of optimized nanocarriers that target specific tissues can be improved by understanding the nature of the signaling pathways, distribution in the mammalian body, receptor structure, and enzymatic degradation of the ECS. A closer look at ligand-receptor complexes, endocannabinoid tone, tissue distribution, and G-protein activity leads to a better understanding of the potential of the ECS toolkit for therapeutics. The signal transduction pathways examine the modulation of downstream effector proteins, desensitization, signaling cascades, and biased signaling. An in-depth and overall view of the targeted system is achieved through homology modeling where mutagenesis and ligand binding examine the binding site and allow sequence analysis and the formation of libraries for molecular docking and molecular dynamic simulations. Internalization routes exploring receptor-mediated endocytosis and lipid rafts are also considered for explicit signaling. Furthermore, the review highlights nanotechnology and surface modification aspects as a possible future approach for specific targeting.<\/jats:p>","DOI":"10.3390\/ijms232113223","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"13223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Recent Advances in Endocannabinoid System Targeting for Improved Specificity: Strategic Approaches to Targeted Drug Delivery"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-4161","authenticated-orcid":false,"given":"Mendhi Henna","family":"Dasram","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-4154","authenticated-orcid":false,"given":"Roderick B.","family":"Walker","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandile M.","family":"Khamanga","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6139, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"\u015aledzi\u0144ski, P., Nowak-Terpi\u0142owska, A., and Zeyland, J. (2020). Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010263"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"An, D., Peigneur, S., Hendrickx, L.A., and Tytgat, J. (2020). Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145064"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.31887\/DCNS.2020.22.3\/mcrocq","article-title":"History of Cannabis and the Endocannabinoid System","volume":"22","author":"Crocq","year":"2020","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_4","first-page":"607","article-title":"Review of the Endocannabinoid System","volume":"6","author":"Lu","year":"2021","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lowe, H., Toyang, N., Steele, B., Bryant, J., and Ngwa, W. (2021). The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179472"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1097\/j.pain.0000000000002268","article-title":"Cannabinoids, the Endocannabinoid System, and Pain: A Review of Preclinical Studies","volume":"162","author":"Finn","year":"2021","journal-title":"Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1097\/j.pain.0000000000002269","article-title":"Systematic Review and Meta-Analysis of Cannabinoids, Cannabis-Based Medicines, and Endocannabinoid System Modulators Tested for Antinociceptive Effects in Animal Models of Injury-Related or Pathological Persistent Pain","volume":"162","author":"Soliman","year":"2021","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zou, S., and Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030833"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pagano, C., Navarra, G., Coppola, L., Avilia, G., Bifulco, M., and Laezza, C. (2022). Cannabinoids: Therapeutic Use in Clinical Practice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063344"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Haspula, D., and Clark, M.A. (2020). Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207693"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6294","DOI":"10.1039\/b902711b","article-title":"Nanomedicine for Targeted Drug Delivery","volume":"19","author":"Kim","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/1061186X.2017.1377207","article-title":"Promising Effects of Nanomedicine in Cancer Drug Delivery","volume":"26","author":"Wakaskar","year":"2018","journal-title":"J. Drug Target"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1039\/C4NR07677J","article-title":"Programmable Nanomedicine Synergistic and Sequential Drug Delivery Systems","volume":"7","author":"Pacardo","year":"2015","journal-title":"Nanoscale"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3702518","DOI":"10.1155\/2019\/3702518","article-title":"Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine","volume":"2019","author":"Lombardo","year":"2019","journal-title":"J. Nanomater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s13167-020-00203-4","article-title":"Targeting the Endocannabinoid System: A Predictive, Preventive, and Personalized Medicine-Directed Approach to the Management of Brain Pathologies","volume":"11","author":"Reddy","year":"2020","journal-title":"EPMA J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Millar, S.A., Maguire, R.F., Yates, A.S., and O\u2019sullivan, S.E. (2020). Towards Better Delivery of Cannabidiol (Cbd). Pharmaceuticals, 13.","DOI":"10.3390\/ph13090219"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.2174\/1568026619666190708164841","article-title":"Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development","volume":"19","author":"Nguyen","year":"2019","journal-title":"Curr. Top Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.beem.2008.09.003","article-title":"Central Side-Effects of Therapies Based on CB1 Cannabinoid Receptor Agonists and Antagonists: Focus on Anxiety and Depression","volume":"23","author":"Moreira","year":"2009","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Moreno, E., Cavic, M., Krivokuca, A., and Canela, E.I. (2020). The Interplay between Cancer Biology and the Endocannabinoid System\u2014Significance for Cancer Risk, Prognosis and Response to Treatment. Cancers, 12.","DOI":"10.3390\/cancers12113275"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/aps.2016.149","article-title":"Brain Cannabinoid Receptor 2: Expression, Function and Modulation","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Almogi-Hazan, O., and Or, R. (2020). Cannabis, the Endocannabinoid System and Immunity\u2014The Journey from the Bedside to the Bench and Back. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124448"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/febs.12260","article-title":"Modulating the Endocannabinoid System in Human Health and Disease\u2014Successes and Failures","volume":"280","author":"Pacher","year":"2013","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stasiulewicz, A., Znajdek, K., Grudzie\u0144, M., Pawi\u0144ski, T., and Sulkowska, J.I. (2020). A Guide to Targeting the Endocannabinoid System in Drug Design. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082778"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Behl, T., Makkar, R., Sehgal, A., Singh, S., Makeen, H.A., Albratty, M., Alhazmi, H.A., Meraya, A.M., and Bungau, S. (2022). Exploration of Multiverse Activities of Endocannabinoids in Biological Systems. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105734"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Della Pietra, A., Savinainen, J., and Giniatullin, R. (2022). Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084407"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.cell.2020.01.008","article-title":"Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures","volume":"180","author":"Hua","year":"2020","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bassani, D., Pavan, M., Federico, S., Spalluto, G., Sturlese, M., and Moro, S. (2022). The Multifaceted Role of GPCRs in Amyotrophic Lateral Sclerosis: A New Therapeutic Perspective?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094504"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.tips.2019.04.001","article-title":"GPCRomics: An Approach to Discover GPCR Drug Targets","volume":"40","author":"Insel","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/ph4020244","article-title":"GPCRs Revisited: New Insights Lead to Novel Drugs","volume":"4","author":"Eglen","year":"2011","journal-title":"Pharmaceuticals"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3390\/ph4010007","article-title":"GPCR Conformations: Implications for Rational Drug Design","volume":"4","author":"Parrill","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41592-018-0302-x","article-title":"Flock an Online Resource for GPCR Structure Determination and Analysis","volume":"16","author":"Munk","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cell.2018.12.011","article-title":"Crystal Structure of the Human Cannabinoid Receptor CB2","volume":"176","author":"Li","year":"2019","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6941","DOI":"10.1074\/jbc.271.12.6941","article-title":"Structural Features of the Central Cannabinoid CB1 Receptor Involved in the Binding of the Specific CB1 Antagonist SR 141716A (\u2217)","volume":"271","author":"David","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1874467212666190215112036","article-title":"New Insights in Cannabinoid Receptor Structure and Signaling","volume":"12","author":"Ye","year":"2019","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kibret, B.G., Ishiguro, H., Horiuchi, Y., and Onaivi, E.S. (2022). New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020975"},{"key":"ref_36","first-page":"2643","article-title":"Expression of the Endocannabinoid Receptors in Human Fascial Tissue","volume":"2","author":"Fede","year":"2016","journal-title":"Eur. J. Histochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1365-2826.2008.01671.x","article-title":"Cannabinoid Receptors: Where They Are and What They Do","volume":"20","author":"Mackie","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1073\/pnas.0504187103","article-title":"Peripheral Cannabinoid Receptor, CB2, Regulates Bone Mass","volume":"103","author":"Ofek","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1432-1033.1995.tb20780.x","article-title":"Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations","volume":"232","author":"Mary","year":"1995","journal-title":"Eur. J. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.2174\/092986708784567716","article-title":"Cannabinoid CB1 and CB2 Receptor Ligand Specificity and the Development of CB2-Selective Agonists","volume":"15","author":"Ashton","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1089\/can.2016.0037","article-title":"Cannabinoid CB1 and CB2 Receptor Signaling and Bias","volume":"2","author":"Ibsen","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrd2553","article-title":"Targeting the Endocannabinoid System: To Enhance or Reduce?","volume":"7","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.lfs.2018.04.054","article-title":"Enhanced Endocannabinoid Tone as a Potential Target of Pharmacotherapy","volume":"204","author":"Toczek","year":"2018","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.addr.2020.07.026","article-title":"Application of Advances in Endocytosis and Membrane Trafficking to Drug Delivery","volume":"157","author":"Ju","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1152\/physrev.00015.2016","article-title":"Leveraging Physiology for Precision Drug Delivery","volume":"97","author":"Sun","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.addr.2019.05.010","article-title":"Ligand Density on Nanoparticles: A Parameter with Critical Impact on Nanomedicine","volume":"143","author":"Alkilany","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.2174\/13816128113199990375","article-title":"The Smart Targeting of Nanoparticles","volume":"19","author":"Friedman","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/09595230310001613976","article-title":"Being Stoned: A Review of Self-Reported Cannabis Effects","volume":"22","author":"Green","year":"2003","journal-title":"Drug Alcohol. Rev."},{"key":"ref_49","unstructured":"Baudelaire, C., and De Quincey, T. (1860). Les Paradis Artificiels, Opium et Haschisch, Poulet-Malassis Et De Broise."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3906\/bot-1907-15","article-title":"The Application of Hemp Cannabis Sativa L. for a Green Economy: A Review","volume":"43","author":"Karche","year":"2019","journal-title":"Turk J. Botany"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1590\/S1516-44462006000200015","article-title":"History of Cannabis as a Medicine: A Review","volume":"28","author":"Zuardi","year":"2006","journal-title":"Revista Brasileira de Psiquiatria"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1007\/s00381-011-1423-z","article-title":"China\u2019s First Surgeon: Hua Tuo (c. 108\u2013208 AD)","volume":"27","author":"Tubbs","year":"2011","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/15377880802393239","article-title":"Early Iconography of Cannabis Sativa and Cannabis Indica","volume":"13","author":"McPartland","year":"2008","journal-title":"J. Ind. Hemp"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF02862859","article-title":"An Archaeological and Historical Account of Cannabis in China","volume":"28","author":"Li","year":"1973","journal-title":"Econ. Bot."},{"key":"ref_55","unstructured":"Dictionary, S.M. (2022, June 27). Pen Ts\u2019ao. (n.d.). Available online: https:\/\/medical-dictionary.thefreedictionary.com\/Pen+Ts%27ao."},{"key":"ref_56","first-page":"117","article-title":"The Development of Chinese Herbal Medicine and the Pen-Ts\u2019ao","volume":"5","author":"Hou","year":"1977","journal-title":"Comp. Med. East West"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wedman-St. Louis, B. (2019). Cannabis Use in Chinese Medicine, Ayurvedic Medicine, & Different Religions. Cannabis as Medicine, CRC Press.","DOI":"10.1201\/9780429054723"},{"key":"ref_58","first-page":"407","article-title":"The Cannabis Spread throughout the Continents and Its Therapeutic Use in History","volume":"21","author":"Charitos","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2307\/1220524","article-title":"Cronquist A Practical and Natural Taxonomy for Cannabis","volume":"25","author":"Small","year":"1976","journal-title":"Taxon"},{"key":"ref_60","unstructured":"R\u00e4tsch, C. (2001). Marijuana Medicine: A World Tour of the Healing and Visionary Powers of Cannabis, Inner Traditions\/Bear & Co."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/cbdv.200790144","article-title":"History of Cannabis and Its Preparations in Saga Science and Sobriquet, C","volume":"4","author":"Russo","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_62","first-page":"22","article-title":"An Indian Perspective on Cannabis for Treatment of Pain","volume":"7","author":"Hazekamp","year":"2017","journal-title":"Int. J. Ayurveda Pharm. Chem."},{"key":"ref_63","unstructured":"Mackworth, Y.W., and Kaplan, J. (1969). Marijuana: Report of the Indian Hemp Drugs Commission, 1893-1894, Thomas Jefferson Publishing Company."},{"key":"ref_64","unstructured":"Russo, E.B. (2002). History of Cannabis in Western Medicine. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential, The Haworth Integrative Healing Press."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s12210-020-00956-0","article-title":"The Early History of Cannabinoid Research","volume":"31","author":"Appendino","year":"2020","journal-title":"Rendiconti Lincei"},{"key":"ref_66","unstructured":"United Nations Commission on Narcotic Drugs (2020). CND Votes on Recommendations for Cannabis and Cannabis-Related Substances, United Nations Commission on Narcotic Drugs."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Simiyu, D., Jang, J., and Lee, O.R. (2022). Understanding Cannabis Sativa, L.: Current Status of Propagation, Use, Legalization, and Haploid-Inducer-Mediated Genetic Engineering. Plants, 11.","DOI":"10.3390\/plants11091236"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.biopsych.2016.01.004","article-title":"Changes in Cannabis Potency Over the Last 2 Decades (1995\u20132014): Analysis of Current Data in the United States","volume":"79","author":"ElSohly","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0301-0082(02)00007-2","article-title":"Endocannabinoids and Cannabinoid Receptor Genetics","volume":"66","author":"Onaivi","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.biopsych.2015.07.028","article-title":"An Introduction to the Endogenous Cannabinoid System","volume":"79","author":"Lu","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.1470919","article-title":"Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor","volume":"258","author":"Devane","year":"1992","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0009-3084(00)00196-1","article-title":"Endocannabinoids and Fatty Acid Amides in Cancer, Inflammation and Related Disorders","volume":"108","author":"Melck","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1021\/ja01577a066","article-title":"The Identification of N-(2-Hydroxyethyl)-Palmitamide as a Naturally Occurring Anti-Inflammatory Agent","volume":"79","author":"Kuehl","year":"1957","journal-title":"J. Am. Chem. Soc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0006-291X(90)92338-Z","article-title":"Isolation of Fatty Acid Amide as an Angiogenic Principle from Bovine Mesentery","volume":"168","author":"Wakamatsu","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1021\/ja00317a064","article-title":"Rationally Designed, Potent Competitive Inhibitors of Leukotriene Biosynthesis","volume":"106","author":"Corey","year":"1984","journal-title":"J. Am. Chem. Soc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.beem.2008.10.013","article-title":"An Introduction to the Endocannabinoid System: From the Early to the Latest Concepts","volume":"23","year":"2009","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuron.2012.09.020","article-title":"Endocannabinoid Signaling and Synaptic Function","volume":"76","author":"Castillo","year":"2012","journal-title":"Neuron"},{"key":"ref_78","first-page":"429","article-title":"Cannabinoid Inhibition of Adenylate Cyclase. Biochemistry of the Response in Neuroblastoma Cell Membranes","volume":"27","author":"Howlett","year":"1985","journal-title":"Mol. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.addr.2012.09.041","article-title":"Targeting Receptor-Mediated Endocytotic Pathways with Nanoparticles: Rationale and Advances","volume":"65","author":"Xu","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7920","DOI":"10.1073\/pnas.84.22.7920","article-title":"Cloning of the CDNA for the Human \u03921-Adrenergic Receptor","volume":"84","author":"Frielle","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0165-6147(00)01636-9","article-title":"Orphan G-Protein-Coupled Receptors and Natural Ligand Discovery","volume":"22","author":"Howard","year":"2001","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/1439-7633(20021004)3:10<928::AID-CBIC928>3.0.CO;2-5","article-title":"Drug Design Strategies for Targeting G-Protein-Coupled Receptors","volume":"3","author":"Klabunde","year":"2002","journal-title":"ChemBioChem"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1615\/CritRevNeurobiol.v11.i2-3.30","article-title":"Molecular Aspects of Cannabinoid Receptors","volume":"11","author":"Matsuda","year":"1997","journal-title":"Crit. Rev. Neurobiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.pbb.2008.05.010","article-title":"Cannabinoid Receptors 1 and 2 (CB1 and CB2), Their Distribution, Ligands and Functional Involvement in Nervous System Structures\u2014A Short Review","volume":"90","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2016.10.004","article-title":"Crystal Structure of the Human Cannabinoid Receptor CB1","volume":"167","author":"Hua","year":"2016","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/0024-3205(95)00178-9","article-title":"Construction of a 3D Model of the Cannabinoid Cb1 Receptor: Determination of Helix Ends and Helix Orientation","volume":"56","author":"Bramblett","year":"1995","journal-title":"Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2174\/1389557054368808","article-title":"Signal Transduction Activated by Cannabinoid Receptors","volume":"5","year":"2005","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1021\/acs.biochem.7b00747","article-title":"Structural Basis for G Protein-Coupled Receptor Activation","volume":"56","author":"Manglik","year":"2017","journal-title":"Biochemistry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1021\/acs.chemrev.6b00177","article-title":"GPCR Dynamics: Structures in Motion","volume":"117","author":"Latorraca","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/nature23272","article-title":"Crystal Structures of Agonist-Bound Human Cannabinoid Receptor CB 1","volume":"547","author":"Hua","year":"2017","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.cell.2020.01.007","article-title":"Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex","volume":"180","author":"Xing","year":"2020","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1021\/acschemneuro.9b00696","article-title":"Prediction of the Binding Affinities and Selectivity for CB1 and CB2 Ligands Using Homology Modeling, Molecular Docking, Molecular Dynamics Simulations, and MM-PBSA Binding Free Energy Calculations","volume":"11","author":"Ji","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1111\/j.1476-5381.2010.01006.x","article-title":"Structural Determinants in the Second Intracellular Loop of the Human Cannabinoid CB 1 Receptor Mediate Selective Coupling to G s and G i","volume":"161","author":"Chen","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zheng, C., Chen, L., Chen, X., He, X., Yang, J., Shi, Y., and Zhou, N. (2013). The Second Intracellular Loop of the Human Cannabinoid CB2 Receptor Governs G Protein Coupling in Coordination with the Carboxyl Terminal Domain. PLoS ONE, 8.","DOI":"10.1371\/annotation\/11146424-f236-4fc6-85b2-cd393cfb6a94"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101301","DOI":"10.1016\/j.isci.2020.101301","article-title":"Cannabinoids and Cannabinoid Receptors: The Story so Far","volume":"23","author":"Shahbazi","year":"2020","journal-title":"iScience"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/0306-4522(94)90511-8","article-title":"Cannabinoid Receptor Binding and Messenger RNA Expression in Human Brain: An in Vitro Receptor Autoradiography and in Situ Hybridization Histochemistry Study of Normal Aged and Alzheimer\u2019s Brains","volume":"63","author":"Westlake","year":"1994","journal-title":"Neuroscience"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1073\/pnas.87.5.1932","article-title":"Cannabinoid Receptor Localization in Brain","volume":"87","author":"Herkenham","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0091-3057(91)90380-K","article-title":"Neurotoxicology of Cannabis and THC: A Review of Chronic Exposure Studies in Animals","volume":"40","author":"Scallet","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0304-3940(98)00368-1","article-title":"Cannabinoid Effects in Basal Ganglia in a Rat Model of Parkinson\u2019s Disease","volume":"248","author":"Patrick","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/0306-4522(93)90352-G","article-title":"Loss of Cannabinoid Receptors in the Substantia Nigra in Huntington\u2019s Disease","volume":"56","author":"Glass","year":"1993","journal-title":"Neuroscience"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1172\/JCI17725","article-title":"The Endogenous Cennabinoid System Affects Energy Balance via Central Orexigenic Drive and Peripheral Lipogenesis","volume":"112","author":"Cota","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1369-1600.2008.00107.x","article-title":"Advances in the Field of Cannabinoid-Opioid Cross-Talk","volume":"13","author":"Robledo","year":"2008","journal-title":"Addict. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0006-8993(98)01031-2","article-title":"Evidence for a Role of Endogenous Cannabinoids in the Modulation of Acute and Tonic Pain Sensitivity","volume":"813","author":"Strangman","year":"1998","journal-title":"Brain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/3-540-26573-2_10","article-title":"Distribution of Cannabinoid Receptors in the Central and Peripheral Nervous System","volume":"168","author":"Mackie","year":"2005","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0014-2999(01)01112-8","article-title":"Hemodynamic Effects of Cannabinoids: Coronary and Cerebral Vasodilation Mediated by Cannabinoid CB1 Receptors","volume":"423","author":"Wagner","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0163-7258(97)82001-3","article-title":"Pharmacology of Cannabinoid CB1 and CB2 Receptors","volume":"74","author":"Pertwee","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1006\/nbdi.1998.0217","article-title":"Role of the Endogenous Cannabinoid System in the Regulation of Motor Activity","volume":"5","author":"Gorriti","year":"1998","journal-title":"Neurobiol. Dis."},{"key":"ref_109","first-page":"880","article-title":"Genetic and Physical Mapping of the Human Cannabinoid Receptor Gene to Chromosome 6q14-Q15","volume":"3","author":"Hoehe","year":"1991","journal-title":"New Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/npp.2012.92","article-title":"Associations between Cannabinoid Receptor-1 (CNR1) Variation and Hippocampus and Amygdala Volumes in Heavy Cannabis Users","volume":"37","author":"Schacht","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.drugalcdep.2009.01.022","article-title":"The Association between Cannabinoid Receptor 1 Gene (CNR1) and Cannabis Dependence Symptoms in Adolescents and Young Adults","volume":"104","author":"Hartman","year":"2009","journal-title":"Drug Alcohol Depend."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/j.1360-0443.2009.02504.x","article-title":"Candidate Genes for Cannabis Use Disorders: Findings, Challenges and Directions","volume":"104","author":"Agrawal","year":"2009","journal-title":"Addiction"},{"key":"ref_113","first-page":"476","article-title":"Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration","volume":"7","author":"Melser","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1006\/mcne.2000.0844","article-title":"Cannabinoid CB1 Receptor Expression in Rat Spinal Cord","volume":"15","author":"Bradbury","year":"2000","journal-title":"Mol. Cell Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/syn.20569","article-title":"Postsynaptic Localization of CB2 Cannabinoid Receptors in the Rat Hippocampus","volume":"62","author":"Brusco","year":"2008","journal-title":"Synapse"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1196\/annals.1432.037","article-title":"Ultrastructural Localization of Neuronal Brain CB2 Cannabinoid Receptors","volume":"1139","author":"Brusco","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1523\/JNEUROSCI.11-02-00563.1991","article-title":"Characterization and Localization of Cannabinoid Receptors in Rat Brain: A Quantitative in Vitro Autoradiographic Study","volume":"11","author":"Herkenham","year":"1991","journal-title":"J. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Freundt-Revilla, J., Kegler, K., Baumg\u00e4rtner, W., and Tipold, A. (2017). Spatial Distribution of Cannabinoid Receptor Type 1 (CB1) in Normal Canine Central and Peripheral Nervous System. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181064"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.2174\/0929867053764617","article-title":"Targeting the Cannabinoid CB2 Receptor: Mutations, Modeling and Development of CB2 Selective Ligands","volume":"12","author":"Raitio","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1196\/annals.1369.052","article-title":"Discovery of the Presence and Functional Expression of Cannabinoid CB2 Receptors in Brain","volume":"1074","author":"Onaivi","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/sj.bjp.0707593","article-title":"Cannabinoid Receptors and the Regulation of Bone Mass","volume":"153","author":"Bab","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/sj.bjp.0707444","article-title":"CB 2 Receptors in Reproduction","volume":"153","author":"Maccarrone","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0301-0082(00)00031-9","article-title":"Cannabinoid Receptors and Pain","volume":"63","author":"Pertwee","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0301-0082(98)00087-2","article-title":"The Effects of Cannabinoids on the Brain","volume":"58","author":"Ameri","year":"1999","journal-title":"Prog. Neurobiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainres.2005.11.035","article-title":"Cannabinoid CB2 Receptors: Immunohistochemical Localization in Rat Brain","volume":"1071","author":"Gong","year":"2006","journal-title":"Brain. Res"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2021.02.001","article-title":"Modulating the Neuromodulators: Dopamine, Serotonin, and the Endocannabinoid System","volume":"44","author":"Peters","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"118109","DOI":"10.1016\/j.lfs.2020.118109","article-title":"The Endocannabinoid Signaling Pathway as an Emerging Target in Pharmacotherapy, Earmarking Mitigation of Destructive Events in Rheumatoid Arthritis","volume":"257","author":"Kaur","year":"2020","journal-title":"Life Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1152\/physrev.00019.2008","article-title":"Endocannabinoid-Mediated Control of Synaptic Transmission","volume":"89","author":"Kano","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1113\/jphysiol.2011.220855","article-title":"Endocannabinoids at the Synapse a Decade after the Dies Mirabilis (29 March 2001): What We Still Do Not Know","volume":"590","author":"Alger","year":"2012","journal-title":"J. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0009-3084(00)00187-0","article-title":"Cellular Signal Transduction by Anandamide and 2-Arachidonoylglycerol","volume":"108","author":"Howlett","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"13175","DOI":"10.1074\/jbc.271.22.13175","article-title":"Cannabinoid Inhibition of Adenylate Cyclase-Mediated Signal Transduction and Interleukin 2 (IL-2) Expression in the Murine T-Cell Line, EL4.IL-2","volume":"271","author":"Condie","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_132","unstructured":"Brunton, L., Parker, K., Blumenthal, D., and Buxton, I. (2008). Goodman & Gilman\u2019s: Manual of Pharmacology and Therapeutics, McGraw-Hill Companies."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/346561a0","article-title":"Structure of a Cannabinoid Receptor and Functional Expression of the Cloned CDNA","volume":"346","author":"Matsuda","year":"1990","journal-title":"Nature"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Walsh, K.B., and Andersen, H.K. (2020). Molecular Pharmacology of Synthetic Cannabinoids: Delineating Cb1 Receptor-Mediated Cell Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176115"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1124\/pr.110.003004","article-title":"International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2","volume":"62","author":"Pertwee","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-20825-1_1","article-title":"Endocannabinoids and Their Pharmacological Actions","volume":"Volume 231","author":"Pertwee","year":"2015","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.prostaglandins.2008.12.002","article-title":"Biology of Endocannabinoid Synthesis System","volume":"89","author":"Wang","year":"2009","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/s41401-020-0385-7","article-title":"hong Potential Application of Endocannabinoid System Agents in Neuropsychiatric and Neurodegenerative Diseases\u2014Focusing on FAAH\/MAGL Inhibitors","volume":"41","author":"Ren","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zhu, D., Gao, F., and Chen, C. (2021). Endocannabinoid Metabolism and Traumatic Brain Injury. Cells, 10.","DOI":"10.3390\/cells10112979"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.prostaglandins.2014.11.002","article-title":"Endocannabinoid Metabolism by Cytochrome P450 Monooxygenases","volume":"116\u2013117","author":"Zelasko","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Di Marzo, V. (2006). Endocannabinoids: Synthesis and Degradation. Reviews of Physiology, Biochemistry and Pharmacology, Springer.","DOI":"10.1007\/112_0505"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.lfs.2015.12.053","article-title":"Ligands for Cannabinoid Receptors, Promising Anticancer Agents","volume":"146","author":"Nikan","year":"2016","journal-title":"Life Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/head.13345","article-title":"Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science","volume":"58","author":"Baron","year":"2018","journal-title":"Headache"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ja01062a046","article-title":"Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish","volume":"86","author":"Gaoni","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1021\/ja01858a058","article-title":"Structure of Cannabidiol, a Product Isolated from the Marihuana Extract of Minnesota Wild Hemp. I","volume":"62","author":"Adams","year":"1940","journal-title":"J. Am. Chem. Soc."},{"key":"ref_146","first-page":"2","article-title":"New Insights into Peptide Cannabinoids: Structure, Biosynthesis and Signaling","volume":"11","author":"Miyakoshi","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Kinghorn, A., Gibbons, S., and Kobayashi, J.I. (2017). Phytocannabinoids, Springer International.","DOI":"10.1007\/978-3-319-45541-9"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Vago, R., Fiorio, F., Trevisani, F., Salonia, A., Montorsi, F., and Bettiga, A. (2022). The Mediterranean Diet as a Source of Bioactive Molecules with Cannabinomimetic Activity in Prevention and Therapy Strategy. Nutrients, 14.","DOI":"10.3390\/nu14030468"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Maffei, M.E. (2020). Plant Natural Sources of the Endocannabinoid (E)-\u03b2-Caryophyllene: A Systematic Quantitative Analysis of Published Literature. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186540"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1124\/pr.58.3.2","article-title":"The Endocannabinoid System as an Emerging Target of Pharmacotherapy","volume":"58","author":"Pacher","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0009-3084(02)00143-3","article-title":"Cannabinergic Ligands","volume":"121","author":"Palmer","year":"2002","journal-title":"Chem. Phys. Lipids"},{"key":"ref_152","unstructured":"Makriyannis, A., and Hongfeng, D. (2001). Cannabimimetic Indole Derivatives. (WO2001028557B1), US Patent, 1999\u20132001."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/sj.bjp.0707273","article-title":"The Synthetic Cannabinoid HU210 Induces Spatial Memory Deficits and Suppresses Hippocampal Firing Rate in Rats","volume":"151","author":"Robinson","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0968-0896(02)00451-0","article-title":"3-Indolyl-1-Naphthylmethanes: New Cannabimimetic Indoles Provide Evidence for Aromatic Stacking Interactions with the CB1 Cannabinoid Receptor","volume":"11","author":"Huffman","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1016\/j.bmcl.2005.06.008","article-title":"1-Pentyl-3-Phenylacetylindoles, a New Class of Cannabimimetic Indoles","volume":"15","author":"Huffman","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.tips.2020.06.010","article-title":"Structural and Functional Insights into Cannabinoid Receptors","volume":"41","author":"Li","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/j.lfs.2005.05.020","article-title":"Recent Developments in Cannabinoid Ligands","volume":"77","author":"Padgett","year":"2005","journal-title":"Life Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1080\/03602532.2018.1428341","article-title":"The Future of Type 1 Cannabinoid Receptor Allosteric Ligands","volume":"50","author":"Alaverdashvili","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/03602532.2018.1428342","article-title":"Allosteric Modulators of Cannabinoid Receptor 1: Developing Compounds for Improved Specificity","volume":"50","author":"Dopart","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Hryhorowicz, S., Kaczmarek-Ry\u015b, M., Andrzejewska, A., Staszak, K., Hryhorowicz, M., Korcz, A., and S\u0142omski, R. (2019). Allosteric Modulation of Cannabinoid Receptor 1\u2014Current Challenges and Future Opportunities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235874"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1089\/can.2015.0005","article-title":"Allosteric Modulators of the CB1 Cannabinoid Receptor: A Structural Update Review","volume":"1","author":"Morales","year":"2016","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1021\/acs.jmedchem.6b01448","article-title":"Pyrimidinyl Biphenylureas: Identification of New Lead Compounds as Allosteric Modulators of the Cannabinoid Receptor CB1","volume":"60","author":"Khurana","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1124\/pr.55.4.4","article-title":"International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology","volume":"55","author":"Neubig","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e223","DOI":"10.1016\/j.ddtec.2012.07.007","article-title":"The Concept of Allosteric Modulation: An Overview","volume":"10","author":"Changeux","year":"2013","journal-title":"Drug Discov. Today Technol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tips.2012.10.003","article-title":"Bridging the Gap: Bitopic Ligands of G-Protein-Coupled Receptors","volume":"34","author":"Lane","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.pharmtox.47.120505.105159","article-title":"Allosteric Modulation of G Protein-Coupled Receptors","volume":"47","author":"May","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"21134","DOI":"10.1073\/pnas.1202906109","article-title":"Anti-Inflammatory Lipoxin A4 Is an Endogenous Allosteric Enhancer of CB1 Cannabinoid Receptor","volume":"109","author":"Pamplona","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Polini, B., Cervetto, C., Carpi, S., Pelassa, S., Gado, F., Ferrisi, R., Bertini, S., Nieri, P., Marcoli, M., and Manera, C. (2020). Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R\/CB2R Orthosteric Agonist. Life, 10.","DOI":"10.3390\/life10120333"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1021\/acschemneuro.6b00310","article-title":"Enantiospecific Allosteric Modulation of Cannabinoid 1 Receptor","volume":"8","author":"Laprairie","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1021\/acs.jmedchem.8b00368","article-title":"Identification of the First Synthetic Allosteric Modulator of the CB2 Receptors and Evidence of Its Efficacy for Neuropathic Pain Relief","volume":"62","author":"Gado","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41589-019-0387-2","article-title":"Structure of an Allosteric Modulator Bound to the CB1 Cannabinoid Receptor","volume":"15","author":"Shao","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/joim.13229","article-title":"The Endocannabinoid System\u2014Current Implications for Drug Development","volume":"290","author":"Fowler","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.phrs.2017.08.008","article-title":"Characterization of Structurally Novel G Protein Biased CB1 Agonists: Implications for Drug Development","volume":"125","author":"Ford","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1471-4159.2008.05336.x","article-title":"Regulation of CB1 Cannabinoid Receptor Internalization by a Promiscuous Phosphorylation-Dependent Mechanism","volume":"106","author":"Daigle","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/mol.117.109355","article-title":"Slowly Signaling G Protein-Biased CB2 Cannabinoid Receptor Agonist LY2828360 Suppresses Neuropathic Pain with Sustained Efficacy and Attenuates Morphine Tolerance and Dependence","volume":"93","author":"Lin","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sjpain.2012.08.004","article-title":"Evaluation of the Analgesic Efficacy of AZD1940, a Novel Cannabinoid Agonist, on Post-Operative Pain after Lower Third Molar Surgical Removal","volume":"4","author":"Segerdahl","year":"2013","journal-title":"Scand. J. Pain"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/1440-1681.12051","article-title":"Evaluation of the Analgesic Efficacy and Psychoactive Effects of AZD1940, a Novel Peripherally Acting Cannabinoid Agonist, in Human Capsaicin-Induced Pain and Hyperalgesia","volume":"40","author":"Annas","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.pain.2010.07.019","article-title":"A Peripherally Restricted Cannabinoid Receptor Agonist Produces Robust Anti-Nociceptive Effects in Rodent Models of Inflammatory and Neuropathic Pain","volume":"151","author":"Yu","year":"2010","journal-title":"Pain"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrd1495","article-title":"The Endocannabinoid System and Its Therapeutic Exploitation","volume":"3","author":"Bifulco","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_180","unstructured":"(2022, February 22). Servier Medical Art Anatomy and The Human Body. Available online: https:\/\/smart.servier.com\/smart_image\/osteoporosis-7\/."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.drudis.2016.08.005","article-title":"Targeting the Endocannabinoid System: Future Therapeutic Strategies","volume":"22","author":"Elezgarai","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.phrs.2009.02.010","article-title":"The Endocannabinoid System: Its General Strategy of Action, Tools for Its Pharmacological Manipulation and Potential Therapeutic Exploitation","volume":"60","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Pertwee, R.G. (2008). The Therapeutic Potential of Drugs That Target Cannabinoid Receptors or Modulate the Tissue Levels or Actions of Endocannabinoids. Drug Addiction: From Basic Research to Therapy, Springer.","DOI":"10.1007\/978-0-387-76678-2_38"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Iannotti, F.A., and Vitale, R.M. (2021). The Endocannabinoid System and PPARs: Focus on Their Signalling Crosstalk Action and Transcriptional Regulation. Cells, 10.","DOI":"10.3390\/cells10030586"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Rusconi, F., Rubino, T., and Battaglioli, E. (2020). Endocannabinoid-Epigenetic Cross-Talk: A Bridge toward Stress Coping. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176252"},{"key":"ref_186","first-page":"153","article-title":"Endocannabinoid System: An Overview of Its Potential in Current Medical Practice","volume":"30","author":"Mouslech","year":"2009","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1017\/S0029665113003649","article-title":"Elevating Endocannabinoid Levels: Pharmacological Strategies and Potential Therapeutic Applications","volume":"73","author":"Pertwee","year":"2014","journal-title":"Proc. Nutr. Soc."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/jnci\/55.3.597","article-title":"Antineoplastic Activity of Cannabinoids","volume":"55","author":"Munson","year":"1975","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nrc3247","article-title":"Towards the Use of Cannabinoids as Antitumour Agents","volume":"12","author":"Velasco","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s001090000177","article-title":"Control of the Cell Survival\/Death Decision by Cannabinoids","volume":"78","year":"2001","journal-title":"J. Mol. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tips.2006.11.001","article-title":"Cannabinoid CB2 Receptor: A New Target for Controlling Neural Cell Survival?","volume":"28","author":"Romero","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/ptr.3375","article-title":"Cannabis Sativa and the Endogenous Cannabinoid System: Therapeutic Potential for Appetite Regulation","volume":"25","author":"Farrimond","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Kola, B., Farkas, I., Christ-Crain, M., Wittmann, G., Lolli, F., Amin, F., Harvey-White, J., Liposits, Z., Kunos, G., and Grossman, A.B. (2008). The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001797"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Cecconi, S., Rossi, G., Oddi, S., Di Nisio, V., and Maccarrone, M. (2019). Role of Major Endocannabinoid-Binding Receptors during Mouse Oocyte Maturation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122866"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13048-018-0478-9","article-title":"The Role of the Endocannabinoid System in Female Reproductive Tissues","volume":"12","author":"Walker","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_196","first-page":"1","article-title":"Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis","volume":"7","author":"Hillard","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3389\/fendo.2014.00054","article-title":"Endocannabinoids Are Involved in Male Vertebrate Reproduction: Regulatory Mechanisms at Central and Gonadal Level","volume":"5","author":"Bovolin","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"412354","DOI":"10.1155\/2014\/412354","article-title":"Updates in Reproduction Coming from the Endocannabinoid System","volume":"2014","author":"Meccariello","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Raux, P., and Vall\u00e9e, M. (2022). Cross-talk between Neurosteroid and Endocannabinoid Systems in Cannabis Addiction. J. Neuroendocrinol., e13191.","DOI":"10.1111\/jne.13191"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1152\/physrev.00002.2016","article-title":"From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles through Complex Pharmacology","volume":"96","author":"Ligresti","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.prostaglandins.2013.02.002","article-title":"Endogenous Cannabinoids Revisited: A Biochemistry Perspective","volume":"102\u2013103","author":"Fonseca","year":"2013","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2174\/0929867306666220401153732","article-title":"The Palmitoylethanolamide and Oleamide Enigmas: Are These Two Fatty Acid Amides Cannabimimetic?","volume":"6","author":"Lambert","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0014-2999(98)00392-6","article-title":"An Entourage Effect: Inactive Endogenous Fatty Acid Glycerol Esters Enhance 2-Arachidonoyl-Glycerol Cannabinoid Activity","volume":"353","author":"Fride","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1021\/cn300015x","article-title":"\u201cRedundancy\u201d of Endocannabinoid Inactivation: New Challenges and Opportunities for Pain Control","volume":"3","author":"Piscitelli","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"111953","DOI":"10.1016\/j.ejmech.2019.111953","article-title":"A Perspective Review on Fatty Acid Amide Hydrolase (FAAH) Inhibitors as Potential Therapeutic Agents","volume":"188","author":"Tripathi","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1080\/13543776.2018.1389899","article-title":"A Patent Review of Monoacylglycerol Lipase (MAGL) Inhibitors (2013\u20132017)","volume":"27","author":"Granchi","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.1111\/bph.15469","article-title":"Mechanisms of Endocannabinoid Transport in the Brain","volume":"179","author":"Kaczocha","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1074\/jbc.M111.304907","article-title":"Fatty Acid-Binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors","volume":"287","author":"Kaczocha","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nn.3011","article-title":"Moving Bliss: A New Anandamide Transporter","volume":"15","author":"Marsicano","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/bs.vh.2014.12.011","article-title":"Endocannabinoid Transport Revisited","volume":"98","author":"Nicolussi","year":"2015","journal-title":"Vitam. Horm."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/bs.mie.2017.06.017","article-title":"Endocannabinoid Transport Proteins: Discovery of Tools to Study Sterol Carrier Protein-2","volume":"593","author":"Hillard","year":"2017","journal-title":"Methods Enzymol."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Meccariello, R., Santoro, A., D\u2019Angelo, S., Morrone, R., Fasano, S., Viggiano, A., and Pierantoni, R. (2020). The Epigenetics of the Endocannabinoid System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031113"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/eat.22989","article-title":"Transcriptional Regulation of the Endocannabinoid System in a Rat Model of Binge-Eating Behavior Reveals a Selective Modulation of the Hypothalamic Fatty Acid Amide Hydrolase Gene","volume":"52","author":"Pucci","year":"2019","journal-title":"Int. J. Eat. Disord."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"pyu028","DOI":"10.1093\/ijnp\/pyu028","article-title":"Ethanol Exposure Induces Neonatal Neurodegeneration by Enhancing CB1R Exon1 Histone H4K8 Acetylation and Up-Regulating CB1R Function Causing Neurobehavioral Abnormalities in Adult Mice","volume":"18","author":"Subbanna","year":"2015","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jcp.22727","article-title":"Interaction of Endocannabinoid System and Steroid Hormones in the Control of Colon Cancer Cell Growth","volume":"227","author":"Proto","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"D\u2019Addario, C., Di Francesco, A., Arosio, B., Gussago, C., Dell\u2019Osso, B., Bari, M., Galimberti, D., Scarpini, E., Altamura, A.C., and Mari, D. (2012). Epigenetic Regulation of Fatty Acid Amide Hydrolase in Alzheimer Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039186"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Etcheverry, A., Aubry, M., de Tayrac, M., Vauleon, E., Boniface, R., Guenot, F., Saikali, S., Hamlat, A., Riffaud, L., and Menei, P. (2010). DNA Methylation in Glioblastoma: Impact on Gene Expression and Clinical Outcome. BMC Genomics, 11.","DOI":"10.1186\/1471-2164-11-701"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ijc.31030","article-title":"G Protein-Coupled Receptor GPR55 Promotes Colorectal Cancer and Has Opposing Effects to Cannabinoid Receptor 1","volume":"142","author":"Hasenoehrl","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/schbul\/sbt080","article-title":"Methylation Patterns in Whole Blood Correlate with Symptoms in Schizophrenia Patients","volume":"40","author":"Liu","year":"2014","journal-title":"Schizophr. Bull."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/15592294.2019.1656158","article-title":"Cannabis Use Is Associated with Potentially Heritable Widespread Changes in Autism Candidate Gene DLGAP2 DNA Methylation in Sperm","volume":"15","author":"Schrott","year":"2020","journal-title":"Epigenetics"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1074\/jbc.M608900200","article-title":"Cannabinoids Induce Glioma Stem-like Cell Differentiation and Inhibit Gliomagenesis","volume":"282","author":"Aguado","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/jcp.25914","article-title":"HDAC1 and HDAC3 Underlie Dynamic H3K9 Acetylation during Embryonic Neurogenesis and in Schizophrenia-like Animals","volume":"233","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2004.09.058","article-title":"Species Comparison and Pharmacological Characterization of Rat and Human CB 2 Cannabinoid Receptors","volume":"505","author":"Mukherjee","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1111\/j.1476-5381.2011.01744.x","article-title":"Differential Signalling in Human Cannabinoid CB 1 Receptors and Their Splice Variants in Autaptic Hippocampal Neurones","volume":"165","author":"Straiker","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/sj.bjp.0707303","article-title":"Species-Specific in Vitro Pharmacological Effects of the Cannabinoid Receptor 2 (CB2) Selective Ligand AM1241 and Its Resolved Enantiomers","volume":"151","author":"Bingham","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"498","DOI":"10.5414\/CP202687","article-title":"FAAH Inhibitors in the Limelight, but Regrettably","volume":"54","author":"Mallet","year":"2016","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4103\/0976-500X.189661","article-title":"What Failed BIA 10-2474 Phase I Clinical Trial? Global Speculations and Recommendations for Future Phase I Trials","volume":"7","author":"Kaur","year":"2016","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1073\/pnas.0901515106","article-title":"Identification of Intracellular Carriers for the Endocannabinoid Anandamide","volume":"106","author":"Kaczocha","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/biot.201200335","article-title":"Bioportides: Bioactive Cell-Penetrating Peptides That Modulate Cellular Dynamics","volume":"8","author":"Lukanowska","year":"2013","journal-title":"Biotechnol. J."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.coph.2016.10.005","article-title":"Cannabinoid Receptor Ligand Bias: Implications in the Central Nervous System","volume":"32","author":"Laprairie","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1124\/mol.104.003558","article-title":"Chemically Distinct Ligands Promote Differential CB1 Cannabinoid Receptor-Gi Protein Interactions","volume":"67","author":"Mukhopadhyay","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_232","first-page":"884","article-title":"Dual Activation and Inhibition of Adenylyl Cyclase by Cannabinoid Receptor Agonists: Evidence for Agonist-Specific Trafficking of Intracellular Responses","volume":"287","author":"Bonhaus","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Polit, A., Mystek, P., and B\u0142asiak, E. (2021). Every Detail Matters. That Is, How the Interaction between G\u03b1 Proteins and Membrane Affects Their Function. Membranes, 11.","DOI":"10.3390\/membranes11030222"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"ra51","DOI":"10.1126\/scisignal.2001707","article-title":"Distinct Phosphorylation Sites on the \u03b2 2-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of \u03b2-Arrestin","volume":"4","author":"Nobles","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1126\/scisignal.2002331","article-title":"Phosphorylation Barcoding as a Mechanism of Directing GPCR Signaling","volume":"4","author":"Liggett","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1124\/mol.116.104539","article-title":"The Multiple Waves of Cannabinoid 1 Receptor Signaling","volume":"90","author":"Yudowski","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mce.2015.11.011","article-title":"Anandamide Acts via Kisspeptin in the Regulation of Testicular Activity of the Frog, Pelophylax Esculentus","volume":"420","author":"Ciaramella","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"165973","DOI":"10.1016\/j.bbadis.2020.165973","article-title":"Biased Signaling in Naturally Occurring Mutations of G Protein-Coupled Receptors Associated with Diverse Human Diseases","volume":"1867","author":"Yang","year":"2021","journal-title":"Biochim. Et Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1210\/en.2014-1304","article-title":"KISS1R Signals Independently of G\u03b1q\/11 and Triggers LH Secretion via the \u03b2-Arrestin Pathway in the Male Mouse","volume":"155","author":"Ahow","year":"2014","journal-title":"Endocrinology"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"113618","DOI":"10.1016\/j.ygcen.2020.113618","article-title":"Kisspeptins, New Local Modulators of Male Reproduction: A Comparative Overview","volume":"299","author":"Meccariello","year":"2020","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Meccariello, R., Chianese, R., Fasano, S., and Pierantoni, R. (2013). Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity. Gonadotropin, IntechOpen.","DOI":"10.5772\/48443"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.2174\/0929867323666160902155434","article-title":"Kisspeptins, Estrogens and Male Fertility","volume":"23","author":"Chianese","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Santoro, A., Mele, E., Marino, M., Viggiano, A., Nori, S.L., and Meccariello, R. (2021). The Complex Interplay between Endocannabinoid System and the Estrogen System in Central Nervous System and Periphery. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020972"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1007\/s00429-021-02339-z","article-title":"Expression of Type One Cannabinoid Receptor in Different Subpopulation of Kisspeptin Neurons and Kisspeptin Afferents to GnRH Neurons in Female Mice","volume":"226","author":"Wilheim","year":"2021","journal-title":"Brain Struct. Funct."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-21737-2_1","article-title":"Endocannabinoid System Components: Overview and Tissue Distribution","volume":"Volume 1162","author":"Joshi","year":"2019","journal-title":"Recent Advances in Cannabinoid Physiology and Pathology"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev-pharmtox-010716-104710","article-title":"Nanobodies to Study G Protein-Coupled Receptor Structure and Function","volume":"57","author":"Manglik","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.2174\/138161209789824803","article-title":"Unraveling the Structure and Function of G Protein-Coupled Receptors Through NMR Spectroscopy","volume":"15","author":"Tikhonova","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cell.2017.07.009","article-title":"How Ligands Illuminate GPCR Molecular Pharmacology","volume":"170","author":"Wacker","year":"2017","journal-title":"Cell"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1021\/cr040426m","article-title":"Molecular Dynamics: Survey of Methods for Simulating the Activity of Proteins","volume":"106","author":"Adcock","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jconrel.2019.11.037","article-title":"Dual and Multi-Targeted Nanoparticles for Site-Specific Brain Drug Delivery","volume":"317","author":"Luo","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.addr.2019.07.010","article-title":"Nanocarrier-Based Systems for Targeted and Site Specific Therapeutic Delivery","volume":"144","author":"Majumder","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Mishra, B., and Patel, R.R. (2018). Nanotheranostics: Implications of Nanotechnology in Simultaneous Diagnosis and Therapy. Nanobiotechnology, CRC Press.","DOI":"10.1201\/9781351031585-2"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.2217\/nnm.14.127","article-title":"Cancer Nanoimmunotherapy Using Advanced Pharmaceutical Nanotechnology","volume":"9","author":"Li","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nnano.2007.387","article-title":"Nanocarriers as an Emerging Platform for Cancer Therapy","volume":"2","author":"Peer","year":"2007","journal-title":"Nat Nanotechnol"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/1573413714666180426112851","article-title":"Nanotechnology Derived Nanotools in Biomedical Perspectives: An Update","volume":"15","author":"Patil","year":"2018","journal-title":"Curr. Nanosci."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.1021\/acsabm.0c01272","article-title":"Designing and Engineering of Nanocarriers for Bioapplication in Cancer Immunotherapy","volume":"3","author":"Li","year":"2020","journal-title":"ACS Appl. Bio. Mater."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1210\/en.2009-1082","article-title":"Minireview: Nanoparticles and the Immune System","volume":"151","author":"Zolnik","year":"2010","journal-title":"Endocrinology"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/cbin.10459","article-title":"Effect of the Surface Modification, Size, and Shape on Cellular Uptake of Nanoparticles","volume":"39","author":"Salatin","year":"2015","journal-title":"Cell Biol. Int."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.biopha.2004.01.007","article-title":"Nanomedicines for Overcoming Biological Barriers","volume":"58","author":"Alonso","year":"2004","journal-title":"Biomed. Pharmacother."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.2174\/0929867311320220003","article-title":"The Fate of Nanocarriers as Nanomedicines In Vivo: Important Considerations and Biological Barriers to Overcome","volume":"20","author":"Moros","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.actbio.2021.01.005","article-title":"Advances in Regulating Physicochemical Properties of Mesoporous Silica Nanocarriers to Overcome Biological Barriers","volume":"123","author":"Wang","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1166\/jnn.2013.7525","article-title":"Influence of Nanoparticle Shape, Size, and Surface Functionalization on Cellular Uptake","volume":"13","author":"Ma","year":"2013","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.2174\/092986712800784702","article-title":"Drug-Loaded Nanocarriers: Passive Targeting and Crossing of Biological Barriers","volume":"19","author":"Rabanel","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1146\/annurev.bi.47.070178.004441","article-title":"Cellular Transport Mechanisms","volume":"47","author":"Wilson","year":"1978","journal-title":"Annu. Rev. Biochem."},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Devarajan, P.V., Dandekar, P., and D\u2019souza, A.A. (2019). Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis, Springer.","DOI":"10.1007\/978-3-030-29168-6"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v18.i1.10","article-title":"Ligand-Receptor-Mediated Drug Delivery: An Emerging Paradigm in Cellular Drug Targeting","volume":"18","author":"Vyas","year":"2001","journal-title":"Crit. Rev. Ther. Drug Carrier. Syst."},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Wang, S., Meng, Y., Li, C., Qian, M., and Huang, R. (2015). Receptor-Mediated Drug Delivery Systems Targeting to Glioma. Nanomaterials, 6.","DOI":"10.3390\/nano6010003"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.apsb.2019.08.003","article-title":"Recent Progress in Drug Delivery","volume":"9","author":"Li","year":"2019","journal-title":"Acta. Pharm. Sin. B"},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.nantod.2014.04.008","article-title":"Challenges Associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects","volume":"9","author":"Barua","year":"2014","journal-title":"Nano Today"},{"key":"ref_270","first-page":"451","article-title":"Receptor-Mediated Drug Delivery","volume":"Volume 451","year":"2016","journal-title":"Drug Delivery: Principles and Applications"},{"key":"ref_271","doi-asserted-by":"crossref","unstructured":"Balogh, L.P. (2020). Nano-Enabled Medical Applications, Jenny Stanford Publishing.","DOI":"10.1201\/9780429399039"},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"Shen, Z., Nieh, M.P., and Li, Y. (2016). Decorating Nanoparticle Surface for Targeted Drug Delivery: Opportunities and Challenges. Polymers, 8.","DOI":"10.3390\/polym8030083"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.1002\/adma.201200224","article-title":"Biomimetic Delivery with Micro- and Nanoparticles","volume":"24","author":"Balmert","year":"2012","journal-title":"Adv. Mater."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1021\/acsnano.5b03184","article-title":"Physical Principles of Nanoparticle Cellular Endocytosis","volume":"9","author":"Zhang","year":"2015","journal-title":"ACS Nano."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1517\/17425247.2014.877442","article-title":"The Interaction of Nanoparticles with Plasma Proteins and the Consequent Influence on Nanoparticles Behavior","volume":"11","author":"Gao","year":"2014","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nmat2442","article-title":"Understanding Biophysicochemical Interactions at the Nano-Bio Interface","volume":"8","author":"Nel","year":"2009","journal-title":"Nat. Mater."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2217\/nnm.15.188","article-title":"The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery","volume":"11","author":"Corbo","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0168-3659(03)00328-6","article-title":"Polymer Degradation and in Vitro Release of a Model Protein from Poly(D,L-Lactide-Co-Glycolide) Nano- and Microparticles","volume":"92","author":"Panyam","year":"2003","journal-title":"J. Control Release"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1002\/smll.200900923","article-title":"Intracellular Localization and Cytotoxicity of Spherical Mesoporous Silica Nano-and Microparticles","volume":"5","author":"He","year":"2009","journal-title":"Small"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/jat.1382","article-title":"Comparison of Cytotoxic and Inflammatory Responses of Photoluminescent Silicon Nanoparticles with Silicon Micron-Sized Particles in RAW 264.7 Macrophages","volume":"29","author":"Choi","year":"2009","journal-title":"J. Appl. Toxicol."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1016\/j.biomaterials.2010.01.065","article-title":"Effects of Particle Size and Surface Charge on Cellular Uptake and Biodistribution of Polymeric Nanoparticles","volume":"31","author":"He","year":"2010","journal-title":"Biomaterials"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/smll.200901622","article-title":"The Effects of Size, Shape, and Surface Functional Group of Gold Nanostructures on Their Adsorption and Internalization by Cells","volume":"6","author":"Cho","year":"2010","journal-title":"Small"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ejpb.2010.11.010","article-title":"Geometry and Surface Characteristics of Gold Nanoparticles Influence Their Biodistribution and Uptake by Macrophages","volume":"77","author":"Arnida","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/smll.200801480","article-title":"Colloidal Gold and Silver Triangular Nanoprisms","volume":"5","author":"Millstone","year":"2009","journal-title":"Small"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"10836","DOI":"10.1021\/jp509953f","article-title":"Plasmon Modes and Hot Spots in Gold Nanostar-Satellite Clusters","volume":"119","author":"Shiohara","year":"2015","journal-title":"J. Phys. Chem. C"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"8648","DOI":"10.1021\/ja047846d","article-title":"Room Temperature, High-Yield Synthesis of Multiple Shapes of Gold Nanoparticles in Aqueous Solution","volume":"126","author":"Sau","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.cplett.2008.12.028","article-title":"Size-Controlled Synthesis of Monodisperse Gold Nanooctahedrons and Their Surface-Enhanced Raman Scattering Properties","volume":"468","author":"Kim","year":"2009","journal-title":"Chem. Phys. Lett."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1021\/ja043245a","article-title":"Observation of a Quadrupole Plasmon Mode for a Colloidal Solution of Gold Nanoprisms","volume":"127","author":"Millstone","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"17247","DOI":"10.1073\/pnas.1305000110","article-title":"Mammalian Cells Preferentially Internalize Hydrogel Nanodiscs over Nanorods and Use Shape-Specific Uptake Mechanisms","volume":"110","author":"Agarwal","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1021\/nl403949h","article-title":"Shape and Orientation Matter for the Cellular Uptake of Nonspherical Particles","volume":"14","author":"Dasgupta","year":"2014","journal-title":"Nano Lett."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2217\/nnm.13.191","article-title":"Shaping Cancer Nanomedicine: The Effect of Particle Shape on the in Vivo Journey of Nanoparticles","volume":"9","author":"Toy","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1038\/s41598-017-04229-z","article-title":"The Effect of Shape on Cellular Uptake of Gold Nanoparticles in the Forms of Stars, Rods, and Triangles","volume":"7","author":"Xie","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1038\/srep04871","article-title":"Margination of Micro- and Nano-Particles in Blood Flow and Its Effect on Drug Delivery","volume":"4","author":"Fedosov","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"31002","DOI":"10.1115\/1.4025609","article-title":"Size-Dependent Nanoparticle Margination and Adhesion Propensity in a Microchannel","volume":"4","author":"Jurney","year":"2013","journal-title":"J. Nanotechnol. Eng. Med."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1039\/C6NR07179A","article-title":"Kinetics of Receptor-Mediated Endocytosis of Elastic Nanoparticles","volume":"9","author":"Yi","year":"2017","journal-title":"Nanoscale"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.1114397","article-title":"Toxic Potential of Materials at the Nanolevel","volume":"311","author":"Nel","year":"2006","journal-title":"Science"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1126\/science.1125527","article-title":"Dynamic Forces between Two Deformable Oil Droplets in Water","volume":"313","author":"Dagastine","year":"2006","journal-title":"Science"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1021\/acsnano.5b00147","article-title":"Elasticity of Nanoparticles Influences Their Blood Circulation, Phagocytosis, Endocytosis, and Targeting","volume":"9","author":"Anselmo","year":"2015","journal-title":"ACS Nano."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1002\/adma.201404788","article-title":"Tunable Rigidity of (Polymeric Core)-(Lipid Shell) Nanoparticles for Regulated Cellular Uptake","volume":"27","author":"Sun","year":"2015","journal-title":"Adv. Mater."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41467-017-02588-9","article-title":"Nanoparticle Elasticity Directs Tumor Uptake","volume":"9","author":"Guo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_301","first-page":"249","article-title":"Biomimetic Nanoparticles: Preparation, Characterization and Biomedical Applications","volume":"5","year":"2010","journal-title":"Int. J. Nanomed."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s40265-021-01579-x","article-title":"Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain","volume":"81","author":"Stella","year":"2021","journal-title":"Drugs"},{"key":"ref_303","doi-asserted-by":"crossref","unstructured":"Bruni, N., Della Pepa, C., Oliaro-Bosso, S., Pessione, E., Gastaldi, D., and Dosio, F. (2018). Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules, 23.","DOI":"10.3390\/molecules23102478"},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-3-319-20825-1_2","article-title":"Biosynthesis and Fate of Endocannabinoids","volume":"231","author":"Cascio","year":"2015","journal-title":"Handb Exp. Pharmacol."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/sj.bjp.0706831","article-title":"Is There a Temperature-Dependent Uptake of Anandamide into Cells?","volume":"149","author":"Thors","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"7055","DOI":"10.1039\/c3cs90057f","article-title":"Stimuli Responsive Materials","volume":"42","author":"Theato","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bbalip.2011.06.009","article-title":"Lipid Classification, Structures and Tools","volume":"1811","author":"Fahy","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jconrel.2014.04.047","article-title":"Designer Lipids for Drug Delivery: From Heads to Tails","volume":"190","author":"Kohli","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/jps.23393","article-title":"In Vivo Efficacy of Enabling Formulations Based on Hydroxypropyl-\u03b2-Cyclodextrins, Micellar Preparation, and Liposomes for the Lipophilic Cannabinoid CB2 Agonist, MDA7","volume":"102","author":"Mcdaniel","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ijpharm.2019.05.042","article-title":"Strategizing Biodegradable Polymeric Nanoparticles to Cross the Biological Barriers for Cancer Targeting","volume":"565","author":"Choudhury","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Dmour, I., and Taha, M.O. (2018). Natural and Semisynthetic Polymers in Pharmaceutical Nanotechnology. Organic Materials as Smart Nanocarriers for Drug Delivery, William Andrew.","DOI":"10.1016\/B978-0-12-813663-8.00002-6"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijpharm.2017.09.005","article-title":"Polymeric Micelles: Basic Research to Clinical Practice","volume":"532","author":"Deshmukh","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_313","first-page":"4707","article-title":"The Use of Styrene Maleic Acid Nanomicelles Encapsulating the Synthetic Cannabinoid Analog WIN55,212-2 for the Treatment of Cancer","volume":"35","author":"Xian","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.colsurfb.2014.09.002","article-title":"Engineering of \u03949-Tetrahydrocannabinol Delivery Systems Based on Surface Modified-PLGA Nanoplatforms","volume":"123","author":"Arias","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jconrel.2012.05.003","article-title":"Poly-\u03b5-Caprolactone Microspheres as a Drug Delivery System for Cannabinoid Administration: Development, Characterization and in Vitro Evaluation of Their Antitumoral Efficacy","volume":"161","author":"Ligresti","year":"2012","journal-title":"J. Control Release"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11051-015-2875-y","article-title":"Comparative Study of Chitosan- and PEG-Coated Lipid and PLGA Nanoparticles as Oral Delivery Systems for Cannabinoids","volume":"17","author":"Almeida","year":"2015","journal-title":"J. Nanoparticle Res."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.lfs.2005.05.040","article-title":"Lipids, Lipid Rafts and Caveolae: Their Importance for GPCR Signaling and Their Centrality to the Endocannabinoid System","volume":"77","author":"Lynch","year":"2005","journal-title":"Life Sci."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/j.1582-4934.2008.00295.x","article-title":"Caveolae Structure and Function: Caveolae Review Series","volume":"12","author":"Thomas","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0006-8993(03)02970-6","article-title":"Multiple Mechanisms of CB1 Cannabinoid Receptors Regulation","volume":"980","author":"Keren","year":"2003","journal-title":"Brain Res."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1074\/jbc.274.9.5843","article-title":"The Dually Acylated NH2-Terminal Domain of G(I1\u03b1) Is Sufficient to Target a Green Fluorescent Protein Reporter to Caveolin-Enriched Plasma Membrane Domains: Palmitoylation of Caveolin-1 Is Required for the Recognition of Dually Acylated G-Protein \u03b1 Subuni","volume":"274","author":"Galbiati","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1074\/jbc.272.10.6525","article-title":"Identification of Peptide and Protein Ligands for the Caveolin- Scaffolding Domain. Implications for the Interaction of Caveolin with Caveolae-Associated Proteins","volume":"272","author":"Couet","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/sj.bjp.0704293","article-title":"Cannabinoid CB1-Receptor Mediated Regulation of Gastrointestinal Motility in Mice in a Model of Intestinal Inflammation","volume":"134","author":"Izzo","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nrm883","article-title":"Signal Transduction and Endocytosis: Close Encounters of Many Kinds","volume":"3","author":"Sorkin","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0165-6147(00)01620-5","article-title":"Role of Endocytosis in Mediating Downregulation of G-Protein-Coupled Receptors","volume":"22","author":"Tsao","year":"2001","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1039\/c2ra01168a","article-title":"Ligand Density and Clustering Effects on Endocytosis of Folate Modified Nanoparticles","volume":"2","author":"Moradi","year":"2012","journal-title":"RSC Adv."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"1800091","DOI":"10.1002\/adtp.201800091","article-title":"Advances in Receptor-Mediated, Tumor-Targeted Drug Delivery","volume":"2","author":"Large","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1038\/ncomms5589","article-title":"Ligand-Specific Endocytic Dwell Times Control Functional Selectivity of the Cannabinoid Receptor 1","volume":"5","author":"Ahn","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1073\/pnas.98.1.93","article-title":"Constitutive Arrestin-Mediated Desensitization of a Human Vasopressin Receptor Mutant Associated with Nephrogenic Diabetes Insipidus","volume":"98","author":"Barak","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.nano.2010.07.008","article-title":"Highly Stable, Ligand-Clustered \u201cPatchy\u201d Micelle Nanocarriers for Systemic Tumor Targeting","volume":"7","author":"Poon","year":"2011","journal-title":"Nanomedicine"},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"7266","DOI":"10.1002\/anie.201003445","article-title":"Ligand-Clustered \u201cPatchy\u201d Nanoparticles for Modulated Cellular Uptake and in Vivo Tumor Targeting","volume":"49","author":"Poon","year":"2010","journal-title":"Angew. Chem.-Int. 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