{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:14:42Z","timestamp":1780575282988,"version":"3.54.1"},"reference-count":195,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2024.00478.BD"],"award-info":[{"award-number":["2024.00478.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2023.03289.BD"],"award-info":[{"award-number":["2023.03289.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Cannabinoids are increasingly recognised for their therapeutic potential beyond well-established indications such as chronic pain, multiple sclerosis, and specific epileptic syndromes. Recent advances have highlighted their possible role in less-common or orphan diseases, opening new avenues for pharmaceutical research and clinical application. Methods: This review provides a critical synthesis of the most recent evidence (2020\u20132025), available in PubMed and Scopus, regarding the use of cannabinoids in conditions including refractory epilepsies beyond Dravet and Lennox\u2013Gastaut syndromes, movement disorders such as dystonia and Tourette syndrome, rare dermatological diseases like epidermolysis bullosa, and emerging data in Crohn\u2019s disease. Results: Negative outcomes, such as those reported in Fragile X syndrome trials, are also discussed as instructive examples of methodological and pharmacological challenges. Particular attention is given to the optimisation of pharmaceutical formulations and advanced separation technologies, including oromucosal sprays, transdermal gels, and novel nanocarrier systems, which aim to overcome issues of bioavailability and variability in patient response. Finally, safety concerns, regulatory aspects, and the need for robust clinical trials are addressed. Conclusions: Overall, cannabinoids represent a promising yet underexplored therapeutic option in rare and complex disorders, warranting further investigation supported by innovative pharmaceutical approaches.<\/jats:p>","DOI":"10.3390\/diseases14020083","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:05:11Z","timestamp":1771855511000},"page":"83","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabinoid Therapies in Less-Common Disorders: Clinical Evidence and Formulation Strategies"],"prefix":"10.3390","volume":"14","author":[{"given":"Silvia","family":"Afonso","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-415X","authenticated-orcid":false,"given":"Joana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agroenvironmental and Biological Sciences, CITAB, Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7172-348X","authenticated-orcid":false,"given":"Ana T.","family":"Brinca","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Pharmacotoxicology, UBIMedical, University of Beira Interior, EM506, 6200-000 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-8540","authenticated-orcid":false,"given":"Luana M.","family":"Rosendo","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Pharmacotoxicology, UBIMedical, University of Beira Interior, EM506, 6200-000 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0469-2895","authenticated-orcid":false,"given":"Tiago","family":"Rosado","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Pharmacotoxicology, UBIMedical, University of Beira Interior, EM506, 6200-000 Covilh\u00e3, Portugal"},{"name":"Beiras Academic Clinical Center (CACB)\u2014Group of \u201cProblemas Relacionados com Toxicofilias\u201d, UBIMedical, EM506, 6200-000 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-5977","authenticated-orcid":false,"given":"Ana Paula","family":"Duarte","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Pharmacotoxicology, UBIMedical, University of Beira Interior, EM506, 6200-000 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-8998","authenticated-orcid":false,"given":"Eugenia","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, Department of Medical Sciences, University of Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Laboratory of Pharmacotoxicology, UBIMedical, University of Beira Interior, EM506, 6200-000 Covilh\u00e3, Portugal"},{"name":"Beiras Academic Clinical Center (CACB)\u2014Group of \u201cProblemas Relacionados com Toxicofilias\u201d, UBIMedical, EM506, 6200-000 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","first-page":"17117","article-title":"Therapeutic Use of Cannabis and Cannabinoids: Benefits and Risks","volume":"135","author":"Zhai","year":"2025","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_2","unstructured":"Renard, J., Gabrys, R., and Sanger, N. (2024). Clearing the Smoke on Cannabis and Cannabinoids: Medical Use of Cannabis and Cannabinoids, Canadian Centre on Substance Use and Addiction."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1038\/sj.ijo.0803272","article-title":"The Pharmacology of Cannabinoid Receptors and Their Ligands: An Overview","volume":"30","author":"Pertwee","year":"2006","journal-title":"Int. J. Obes."},{"key":"ref_4","first-page":"1","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_5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00406-024-01880-2","article-title":"Cannabis, Cannabinoids and Health: A Review of Evidence on Risks and Medical Benefits","volume":"275","author":"Hoch","year":"2025","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_6","unstructured":"(2025, December 22). INFARMED Delibera\u00e7\u00e3o n.o 11\/CD\/2019. Available online: https:\/\/www.infarmed.pt\/web\/infarmed\/institucional\/documentacao_e_informacao\/campanhas?p_p_id=101&p_p_lifecycle=0&p_p_state=maximized&p_p_mode=view&_101_struts_action=%2Fasset_publisher%2Fview_content&_101_returnToFullPageURL=https%3A%2F%2Fwww.infarmed.pt%2Fweb%2Finfarmed%2Finstitucional%2Fdocumentacao_e_informacao%2Fcampanhas%3Fp_auth%3DxIDXTisp%26p_p_id%3D3%26p_p_lifecycle%3D1%26p_p_state%3Dnormal%26p_p_state_rcv%3D1&_101_assetEntryId=2965223&_101_type=document&inheritRedirect=false."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chou, R., Ahmed, A.Y., Morasco, B.J., Bougatsos, C., Dana, T., Fu, R., and Gilbreath, T. (2023). Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2023 Update.","DOI":"10.23970\/AHRQEPCCER250UPDATE2023"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s40122-024-00643-0","article-title":"Clinical Benefits and Safety of Medical Cannabis Products: A Narrative Review on Natural Extracts","volume":"13","author":"Mick","year":"2024","journal-title":"Pain Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s42238-024-00250-y","article-title":"Review of the Current Ongoing Clinical Trials Exploring the Possible Anti-Anxiety Effects of Cannabidiol","volume":"6","author":"Bhuller","year":"2024","journal-title":"J. Cannabis Res."},{"key":"ref_10","first-page":"123","article-title":"Cannabis for Medicinal Use in Patients with Rare Diseases","volume":"6","author":"Parovincaka","year":"2023","journal-title":"Transl. Sci. Rare Dis."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"118673","DOI":"10.1016\/j.biopha.2025.118673","article-title":"Perspectives of Cannabis-Based Medicines in a View of Pharmacokinetic Studies of \u03949-THC and CBD in Humans","volume":"192","author":"Kaszewska","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.2174\/1389200217666151210142051","article-title":"Cannabinoids and Cytochrome P450 Interactions","volume":"17","author":"Zendulka","year":"2016","journal-title":"Curr. Drug Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jep.2018.09.004","article-title":"Cannabis sativa: A Comprehensive Ethnopharmacological Review of a Medicinal Plant with a Long History","volume":"227","author":"Bonini","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1021\/acsmedchemlett.8b00571","article-title":"Cannabinoids from Cannabis sativa L.: A New Tool Based on HPLC\u2013DAD\u2013MS\/MS for a Rational Use in Medicinal Chemistry","volume":"10","author":"Protti","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, J., Rosado, T., Soares, S., Sim\u00e3o, A.Y., Caramelo, D., Lu\u00eds, \u00c2., Fern\u00e1ndez, N., Barroso, M., Gallardo, E., and Duarte, A.P. (2019). Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination. Medicines, 6.","DOI":"10.3390\/medicines6010031"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.2174\/092986711794940888","article-title":"Cannabinoids: Occurrence and Medicinal Chemistry","volume":"18","author":"Appendino","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.lfs.2005.09.011","article-title":"Chemical Constituents of Marijuana: The Complex Mixture of Natural Cannabinoids","volume":"78","author":"ElSohly","year":"2005","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1016\/j.jchromb.2009.11.004","article-title":"Innovative Development and Validation of an HPLC\/DAD Method for the Qualitative and Quantitative Determination of Major Cannabinoids in Cannabis Plant Material","volume":"877","author":"Debrus","year":"2009","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1039\/C6NP00074F","article-title":"Phytocannabinoids: A Unified Critical Inventory","volume":"33","author":"Meyer","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.tips.2009.07.006","article-title":"Non-Psychotropic Plant Cannabinoids: New Therapeutic Opportunities from an Ancient Herb","volume":"30","author":"Izzo","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/sj.bjp.0707442","article-title":"The Diverse CB1 and CB2 Receptor Pharmacology of Three Plant Cannabinoids: Delta9-Tetrahydrocannabinol, Cannabidiol and Delta9-Tetrahydrocannabivarin","volume":"153","author":"Pertwee","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","article-title":"Pharmacokinetics and Pharmacodynamics of Cannabinoids","volume":"42","author":"Grotenhermen","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pharmthera.2017.08.014","article-title":"Cannabis Use during Pregnancy: Pharmacokinetics and Effects on Child Development","volume":"182","author":"Grant","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2174\/1389557516666161004162133","article-title":"Cannabis: A Treasure Trove or Pandora\u2019s Box?","volume":"17","author":"Solymosi","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-030-57369-0_3","article-title":"Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review","volume":"1264","author":"Hallak","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/MJT.0b013e3180a5e581","article-title":"The Future of Cannabinoids as Analgesic Agents: A Pharmacologic, Pharmacokinetic, and Pharmacodynamic Overview","volume":"14","author":"McCarberg","year":"2007","journal-title":"Am. J. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4790","DOI":"10.1111\/bph.13250","article-title":"Cannabidiol Is a Negative Allosteric Modulator of the Cannabinoid CB1 Receptor","volume":"172","author":"Laprairie","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1691428","DOI":"10.1155\/2018\/1691428","article-title":"Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer","volume":"2018","author":"Pellati","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107176","DOI":"10.1016\/j.phrs.2024.107176","article-title":"Cannabidiol and Positive Effects on Object Recognition Memory in an in Vivo Model of Fragile X Syndrome: Obligatory Role of Hippocampal GPR55 Receptors","volume":"203","author":"Manduca","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108279","DOI":"10.1016\/j.pharmthera.2022.108279","article-title":"Are the Epigenetic Changes Predictive of Therapeutic Efficacy for Psychiatric Disorders? A Translational Approach towards Novel Drug Targets","volume":"241","author":"Micale","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/sj.bjp.0707133","article-title":"Cannabidiol Displays Unexpectedly High Potency as an Antagonist of CB1 and CB2 Receptor Agonists in Vitro","volume":"150","author":"Thomas","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.bjp.0704327","article-title":"Molecular Targets for Cannabidiol and Its Synthetic Analogues: Effect on Vanilloid VR1 Receptors and on the Cellular Uptake and Enzymatic Hydrolysis of Anandamide","volume":"134","author":"Bisogno","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.2174\/092986710790980078","article-title":"Endocannabinoids as Regulators of Transient Receptor Potential (TRP) Channels: A Further Opportunity to Develop New Endocannabinoid-Based Therapeutic Drugs","volume":"17","author":"Marzo","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/22761","article-title":"Vanilloid Receptors on Sensory Nerves Mediate the Vasodilator Action of Anandamide","volume":"400","author":"Zygmunt","year":"1999","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1590\/S1516-44462008000300015","article-title":"Cannabidiol: From an Inactive Cannabinoid to a Drug with Wide Spectrum of Action","volume":"30","author":"Zuardi","year":"2008","journal-title":"Braz. J. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s11064-005-6978-1","article-title":"Agonistic Properties of Cannabidiol at 5-HT1a Receptors","volume":"30","author":"Russo","year":"2005","journal-title":"Neurochem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00213-008-1168-x","article-title":"Involvement of 5HT1A Receptors in the Anxiolytic-like Effects of Cannabidiol Injected into the Dorsolateral Periaqueductal Gray of Rats","volume":"199","author":"Campos","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1124\/jpet.106.105247","article-title":"Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma","volume":"318","author":"Ligresti","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s00018-006-6156-x","article-title":"The Non-Psychoactive Cannabidiol Triggers Caspase Activation and Oxidative Stress in Human Glioma Cells","volume":"63","author":"Massi","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1124\/jpet.107.120865","article-title":"A Cannabinoid Anticancer Quinone, HU-331, Is More Potent and Less Cardiotoxic than Doxorubicin: A Comparative in Vivo Study","volume":"322","author":"Kogan","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1111\/bph.13497","article-title":"An Update on PPAR Activation by Cannabinoids","volume":"173","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1124\/jpet.107.134809","article-title":"Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8","volume":"325","author":"Vellani","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/bph.12944","article-title":"Are Cannabidiol and \u0394(9) -Tetrahydrocannabivarin Negative Modulators of the Endocannabinoid System? A Systematic Review","volume":"172","author":"McPartland","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/j.1476-5381.2008.00107.x","article-title":"Synthetic and Plant-Derived Cannabinoid Receptor Antagonists Show Hypophagic Properties in Fasted and Non-Fasted Mice","volume":"156","author":"Riedel","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1111\/j.1528-1167.2010.02523.x","article-title":"\u03949-Tetrahydrocannabivarin Suppresses in Vitro Epileptiform and in Vivo Seizure Activity in Adult Rats","volume":"51","author":"Hill","year":"2010","journal-title":"Epilepsia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The Pharmacokinetics and the Pharmacodynamics of Cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/3-540-26573-2_23","article-title":"Pharmacokinetics and Metabolism of the Plant Cannabinoids, Delta9-Tetrahydrocannabinol, Cannabidiol and Cannabinol","volume":"168","author":"Huestis","year":"2005","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/jat\/16.5.276","article-title":"Blood Cannabinoids. I. Absorption of THC and Formation of 11-OH-THC and THCCOOH during and after Smoking Marijuana","volume":"16","author":"Huestis","year":"1992","journal-title":"J. Anal. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/bms.1200130206","article-title":"Single-Dose Kinetics of Deuterium-Labelled Cannabidiol in Man after Smoking and Intravenous Administration","volume":"13","author":"Ohlsson","year":"1986","journal-title":"Biomed. Environ. Mass Spectrom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/jat\/32.7.470","article-title":"Comparison of Cannabinoid Pharmacokinetic Properties in Occasional and Heavy Users Smoking a Marijuana or Placebo Joint","volume":"32","author":"Toennes","year":"2008","journal-title":"J. Anal. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Solowij, N., Broyd, S.J., van Hell, H.H., and Hazekamp, A. (2014). A Protocol for the Delivery of Cannabidiol (CBD) and Combined CBD and \u22069-Tetrahydrocannabinol (THC) by Vaporisation. BMC Pharmacol. Toxicol., 15.","DOI":"10.1186\/2050-6511-15-58"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s40262-017-0599-0","article-title":"Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction?","volume":"57","author":"Martin","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.pharma.2008.07.006","article-title":"Pharmacocin\u00e9tique Du Delta-9-T\u00e9trahydrocannabinol (THC)","volume":"66","author":"Saussereau","year":"2008","journal-title":"Ann. Pharm. Fr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/BF02085029","article-title":"Interactions of Delta 1-Tetrahydrocannabinol with Cannabinol and Cannabidiol Following Oral Administration in Man. Assay of Cannabinol and Cannabidiol by Mass Fragmentography","volume":"37","author":"Agurell","year":"1981","journal-title":"Experientia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1055\/s-0031-1298334","article-title":"Heat Exposure of Cannabis sativa Extracts Affects the Pharmacokinetic and Metabolic Profile in Healthy Male Subjects","volume":"78","author":"Eichler","year":"2012","journal-title":"Planta Med."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1007\/s00213-015-3889-y","article-title":"Safety, Pharmacodynamics, and Pharmacokinetics of Multiple Oral Doses of Delta-9-Tetrahydrocannabinol in Older Persons with Dementia","volume":"232","author":"Ahmed","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1373\/clinchem.2008.122119","article-title":"Delta9-Tetrahydrocannabinol (THC), 11-Hydroxy-THC, and 11-nor-9-Carboxy-THC Plasma Pharmacokinetics during and after Continuous High-Dose Oral THC","volume":"55","author":"Schwilke","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/jps.2600630705","article-title":"Physicochemical Properties, Solubility, and Protein Binding of \u03949-tetrahydrocannabinol","volume":"63","author":"Garrett","year":"1974","journal-title":"J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0378-5173(02)00262-4","article-title":"In Vitro Experiment Optimization for Measuring Tetrahydrocannabinol Skin Permeation","volume":"241","author":"Challapalli","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1211\/0022357022791","article-title":"Human Skin Permeation of Delta8-Tetrahydrocannabinol, Cannabidiol and Cannabinol","volume":"56","author":"Stinchcomb","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jconrel.2003.09.001","article-title":"Cannabidiol\u2014Transdermal Delivery and Anti-Inflammatory Effect in a Murine Model","volume":"93","author":"Lodzki","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/jps.20036","article-title":"In Vitro\/in Vivo Correlation Studies for Transdermal \u0394 8-THC Development","volume":"93","author":"Valiveti","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.clinthera.2017.12.008","article-title":"Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer","volume":"40","author":"Lucas","year":"2018","journal-title":"Clin. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1002\/cbdv.200790152","article-title":"Human Cannabinoid Pharmacokinetics","volume":"4","author":"Huestis","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.yebeh.2016.11.016","article-title":"Pharmacology of Cannabinoids in the Treatment of Epilepsy","volume":"70","author":"Gaston","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3109\/03602532.2015.1137307","article-title":"Metabolomics of \u03949-Tetrahydrocannabinol: Implications in Toxicity","volume":"48","year":"2016","journal-title":"Drug Metab. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.pain.2009.04.012","article-title":"Transdermal Fentanyl in Cachectic Cancer Patients","volume":"144","author":"Heiskanen","year":"2009","journal-title":"Pain"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/0091-3057(91)90386-G","article-title":"Controlled Clinical Trial of Cannabidiol in Huntington\u2019s Disease","volume":"40","author":"Consroe","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Brown, J.D., Winterstein, A.G., Brown, J.D., and Winterstein, A.G. (2019). Potential Adverse Drug Events and Drug\u2013Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J. Clin. Med., 8.","DOI":"10.3390\/jcm8070989"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S1474-4422(16)00120-4","article-title":"Cannabidiol in Patients with Treatment-Resistant Epilepsy\u2014Authors\u2019 Reply","volume":"15","author":"Devinsky","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/cpdd.408","article-title":"Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology","volume":"7","author":"Atsmon","year":"2018","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1476-5381.1972.tb07261.x","article-title":"Effect of Cannabis and Certain of Its Constituents on Pentobarbitone Sleeping Time and Phenazone Metabolism","volume":"44","author":"Paton","year":"1972","journal-title":"Br. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/0006-2952(79)90472-6","article-title":"Cannabidiol and \u03949-Tetrahydrocannabinol Metabolism: In Vitro Comparison of Mouse and Rat Liver Crude Microsome Preparations","volume":"28","author":"Borys","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/01.ftd.0000177223.19294.5c","article-title":"Randomized, Double-Blind, Placebo-Controlled Study about the Effects of Cannabidiol (CBD) on the Pharmacokinetics of Delta9-Tetrahydrocannabinol (THC) after Oral Application of THC Verses Standardized Cannabis Extract","volume":"27","author":"Nadulski","year":"2005","journal-title":"Ther. Drug Monit."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/01.ftd.0000211812.27558.6e","article-title":"Toxicokinetics of Drugs of Abuse: Current Knowledge of the Isoenzymes Involved in the Human Metabolism of Tetrahydrocannabinol, Cocaine, Heroin, Morphine, and Codeine","volume":"28","author":"Maurer","year":"2006","journal-title":"Ther. Drug Monit."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejphar.2006.11.006","article-title":"The Non-Psychoactive Cannabis Constituent Cannabidiol Is an Orally Effective Therapeutic Agent in Rat Chronic Inflammatory and Neuropathic Pain","volume":"556","author":"Costa","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_80","unstructured":"United Nations (2025, December 17). The Single Convention on Narcotic Drugs. Available online: https:\/\/www.euda.europa.eu\/drugs-library\/single-convention-narcotic-drugs-1961_en."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ejim.2018.01.001","article-title":"Medical Use of Cannabis and Cannabinoids Containing Products\u2014Regulations in Europe and North America","volume":"49","author":"Abuhasira","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_82","unstructured":"Food and Drug Administration (2025, December 17). FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)|FDA, Available online: https:\/\/www.fda.gov\/news-events\/public-health-focus\/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd."},{"key":"ref_83","unstructured":"Food and Drug Administration (2025, December 17). FDA and Cannabis: Research and Drug Approval Process|FDA, Available online: https:\/\/www.fda.gov\/news-events\/public-health-focus\/fda-and-cannabis-research-and-drug-approval-process."},{"key":"ref_84","unstructured":"European Union Drugs Agency (2025, December 15). New Report Describes Growing Complexity and Change in Cannabis Laws in Europe|www.euda.europa.eu. Available online: https:\/\/www.euda.europa.eu\/news\/2023\/cannabis-laws-europe-questions-and-answers-policymaking_en."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/cpt.115","article-title":"Medicinal Chemistry of Cannabinoids","volume":"97","author":"Makriyannis","year":"2015","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Voicu, V., Brehar, F.M., Toader, C., Covache-Busuioc, R.A., Corlatescu, A.D., Bordeianu, A., Costin, H.P., Bratu, B.G., Glavan, L.A., and Ciurea, A.V. (2023). Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy. Biomolecules, 13.","DOI":"10.3390\/biom13091388"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/npp.2017.198","article-title":"US Epidemiology of Cannabis Use and Associated Problems","volume":"43","author":"Hasin","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_88","unstructured":"New York State Office of Cannabis Management|Office of Cannabis Management (2025, December 17). Available online: https:\/\/cannabis.ny.gov\/."},{"key":"ref_89","unstructured":"(2025, December 17). FDA CESAMETTM (Nabilone) Capsules, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2006\/018677s011lbl.pdf."},{"key":"ref_90","unstructured":"(2025, December 17). FDA SYNDROS (Dronabinol) Oral Solution, CX, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/205525s000lbl.pdf."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1111\/add.13910","article-title":"Mapping Medical Marijuana: State Laws Regulating Patients, Product Safety, Supply Chains and Dispensaries, 2017","volume":"112","author":"Klieger","year":"2017","journal-title":"Addiction"},{"key":"ref_92","unstructured":"(2025, December 17). Florida Department of State Constitutional Initiatives, Available online: https:\/\/constitutionalinitiatives.dos.fl.gov\/."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00482-015-0083-4","article-title":"Medical Use of Cannabis Products","volume":"30","author":"Ablin","year":"2016","journal-title":"Schmerz"},{"key":"ref_94","unstructured":"(2025, December 17). Canada Ministry of Justice Access to Cannabis for Medical Purposes Regulations. Available online: https:\/\/laws-lois.justice.gc.ca\/eng\/regulations\/sor-2018-144\/20180627\/P1TT3xt3.html."},{"key":"ref_95","unstructured":"(2025, December 17). Government of Canada Understanding the Access to Cannabis for Medical Purposes Regulations\u2014Canada. Available online: https:\/\/www.canada.ca\/en\/health-canada\/services\/publications\/drugs-health-products\/understanding-new-access-to-cannabis-for-medical-purposes-regulations.html?_ga=2.160051705.575108858.1511160845-1024719169.1511160845."},{"key":"ref_96","unstructured":"(2025, December 17). Government of Canada Information for Health Care Professionals: Cannabis (Marihuana, Marijuana) and the Cannabinoids. Available online: https:\/\/www.canada.ca\/en\/health-canada\/services\/drugs-medication\/cannabis\/information-medical-practitioners\/information-health-care-professionals-cannabis-cannabinoids.html."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1111\/epi.17247","article-title":"Efficacy and Safety of Cannabidivarin Treatment of Epilepsy in Girls with Rett Syndrome: A Phase 1 Clinical Trial","volume":"63","author":"Hurley","year":"2022","journal-title":"Epilepsia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110032","DOI":"10.1016\/j.yebeh.2024.110032","article-title":"Psychiatric Comorbidities before and after Cannabidiol Treatment in Adult Patients with Drug Resistant Focal Epilepsy","volume":"160","author":"Lamonarca","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"E2220189","DOI":"10.1001\/jamanetworkopen.2022.20189","article-title":"Adjunctive Transdermal Cannabidiol for Adults with Focal Epilepsy: A Randomized Clinical Trial","volume":"5","author":"Berkovic","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/epi.17199","article-title":"Time to Onset of Cannabidiol Treatment Effect and Resolution of Adverse Events in Tuberous Sclerosis Complex: Post Hoc Analysis of Randomized Controlled Phase 3 Trial GWPCARE6","volume":"63","author":"Wu","year":"2022","journal-title":"Epilepsia"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"173971","DOI":"10.1016\/j.pbb.2025.173971","article-title":"Purified Cannabidiol Leads to Improvement of Severe Treatment-Resistant Behavioral Symptoms in Children with Autism Spectrum Disorder","volume":"249","author":"Fortini","year":"2025","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13229-021-00420-2","article-title":"Cannabinoid Treatment for Autism: A Proof-of-Concept Randomized Trial","volume":"12","author":"Aran","year":"2021","journal-title":"Mol. Autism"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.pediatrneurol.2022.10.014","article-title":"Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome","volume":"139","author":"Smegal","year":"2023","journal-title":"Pediatr. Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pediatrneurol.2017.02.009","article-title":"Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome","volume":"71","author":"Kaplan","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejpn.2024.11.007","article-title":"Plant-Derived Cannabinoids for Treatment of Spasticity in Children and Adolescents with Severe Cerebral Palsy: Double-Blind, Placebo-Controlled Trial","volume":"54","author":"Osredkar","year":"2025","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1177\/13872877251389608","article-title":"A Randomized Clinical Trial of Low-Dose Cannabis Extract in Alzheimer\u2019s Disease","volume":"108","author":"Cury","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"zsab149","DOI":"10.1093\/sleep\/zsab149","article-title":"Treating Insomnia Symptoms with Medicinal Cannabis: A Randomized, Crossover Trial of the Efficacy of a Cannabinoid Medicine Compared with Placebo","volume":"44","author":"Walsh","year":"2021","journal-title":"Sleep"},{"key":"ref_108","first-page":"1","article-title":"The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial","volume":"43","author":"Saleska","year":"2024","journal-title":"J. Am. Nutr. Assoc."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"753","DOI":"10.5664\/jcsm.10998","article-title":"Cannabidiol for Moderate-Severe Insomnia: A Randomized Controlled Pilot Trial of 150 Mg of Nightly Dosing","volume":"20","author":"Narayan","year":"2024","journal-title":"J. Clin. Sleep Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/mds.28577","article-title":"Cannabidiol for Rapid Eye Movement Sleep Behavior Disorder","volume":"36","author":"Brito","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00213-024-06674-x","article-title":"The Effect of Nightly Use of 150 Mg Cannabidiol on Daytime Neurocognitive Performance in Primary Insomnia: A Randomized Controlled Pilot Trial","volume":"242","author":"Narayan","year":"2025","journal-title":"Psychopharmacology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1089\/can.2021.0224","article-title":"The Potential of Salivary Lipid-Based Cannabis-Responsive Biomarkers to Evaluate Medical Cannabis Treatment in Children with Autism Spectrum Disorder","volume":"8","author":"McKee","year":"2023","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1007\/s00415-024-12421-1","article-title":"CDKL5 Deficiency-Related Neurodevelopmental Disorders: A Multi-Center Cohort Study in Italy","volume":"271","author":"Antonella","year":"2024","journal-title":"J. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13229-021-00454-6","article-title":"Modulation of Striatal Functional Connectivity Differences in Adults with and without Autism Spectrum Disorder in a Single-Dose Randomized Trial of Cannabidivarin","volume":"12","author":"Pretzsch","year":"2021","journal-title":"Mol. Autism"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"afaf149","DOI":"10.1093\/ageing\/afaf149","article-title":"Sativex (Nabiximols) for the Treatment of Agitation & Aggression in Alzheimer\u2019s Dementia in UK Nursing Homes: A Randomised, Double-Blind, Placebo-Controlled Feasibility Trial","volume":"54","author":"Albertyn","year":"2025","journal-title":"Age Ageing"},{"key":"ref_116","first-page":"53","article-title":"Oral Thc: Cbd Cannabis Extract in Main Symptoms of Alzheimer Disease: Agitation and Weight Loss","volume":"174","author":"Palmieri","year":"2023","journal-title":"Clin. Ter."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jpsychires.2023.05.019","article-title":"The Impact of Cannabidiol Treatment on Resting State Functional Connectivity, Prefrontal Metabolite Levels and Reward Processing in Recent-Onset Patients with a Psychotic Disorder","volume":"163","author":"Gangadin","year":"2023","journal-title":"J. Psychiatr. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1590\/1516-4446-2021-2317","article-title":"The Anxiolytic Effect of Cannabidiol Depends on the Nature of the Trauma When Patients with Post-Traumatic Stress Disorder Recall Their Trigger Event","volume":"44","author":"Bolsoni","year":"2022","journal-title":"Braz. J. Psychiatry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00213-021-06043-y","article-title":"Effects of Cannabidiol on Symptoms Induced by the Recall of Traumatic Events in Patients with Posttraumatic Stress Disorder","volume":"239","author":"Bolsoni","year":"2022","journal-title":"Psychopharmacology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"107758","DOI":"10.1016\/j.nlm.2023.107758","article-title":"Cannabinoid Modulation of Corticolimbic Activation during Extinction Learning and Fear Renewal in Adults with Posttraumatic Stress Disorder","volume":"201","author":"Zabik","year":"2023","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"104073","DOI":"10.1016\/j.ajp.2024.104073","article-title":"Evaluation of the Efficacy, Safety, and Pharmacokinetics of Nanodispersible Cannabidiol Oral Solution (150 mg\/ML) versus Placebo in Mild to Moderate Anxiety Subjects: A Double Blind Multicenter Randomized Clinical Trial","volume":"97","author":"Gundugurti","year":"2024","journal-title":"Asian J. Psychiatr."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Schr\u00e4der, N.H.B., Duipmans, J.C., Renken, R.J., S\u00f6r\u00f6s, P., Vermeulen, K.M., Bolling, M.C., and Wolff, A.P. (2022). The C4EB Study\u2014Transvamix (10% THC\/5% CBD) to Treat Chronic Pain in Epidermolysis Bullosa: A Protocol for an Explorative Randomized, Placebo Controlled, and Double Blind Intervention Crossover Study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0277512"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"adv43026","DOI":"10.2340\/actadv.v105.43026","article-title":"Long-Term Progressive Improvement of Atopic Dermatitis by an Herbal Emollient Plus Combination in a 12-Week Clinical Trial","volume":"105","author":"Herrmann","year":"2025","journal-title":"Acta Derm. Venereol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/jre.13234","article-title":"Phytocannabinoids and Gingival Inflammation: Preclinical Findings and a Placebo-Controlled Double-Blind Randomized Clinical Trial with Cannabidiol","volume":"59","author":"Jirasek","year":"2024","journal-title":"J. Periodontal Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/ecco-jcc\/jjab069","article-title":"Oral CBD-Rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn\u2019s Disease, a Randomised Controlled Trial","volume":"15","author":"Naftali","year":"2021","journal-title":"J. Crohns Colitis"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1016\/j.cgh.2023.07.008","article-title":"A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis","volume":"21","author":"Zheng","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s11689-022-09466-6","article-title":"A Randomized, Controlled Trial of ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents with Fragile X Syndrome (CONNECT-FX)","volume":"14","author":"Hagerman","year":"2022","journal-title":"J. Neurodev. Disord."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s11689-025-09657-x","article-title":"Long-Term Safety and Tolerability of Transdermal Cannabidiol Gel in Children and Adolescents with Fragile X Syndrome (ZYN2-CL-017): An Interim Analysis of an Ongoing Open-Label Extension Study","volume":"17","author":"Hagerman","year":"2025","journal-title":"J. Neurodev. Disord."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.parkreldis.2021.01.001","article-title":"A Single Oral Dose of Cannabidiol Did Not Reduce Upper Limb Tremor in Patients with Essential Tremor","volume":"83","author":"Crippa","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s00213-024-06595-9","article-title":"Evaluating Possible \u2018next Day\u2019 Impairment in Insomnia Patients Administered an Oral Medicinal Cannabis Product by Night: A Pilot Randomized Controlled Trial","volume":"241","author":"Suraev","year":"2024","journal-title":"Psychopharmacology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e071148","DOI":"10.1136\/bmjopen-2022-071148","article-title":"Cannabinol (CBN; 30 and 300 Mg) Effects on Sleep and next-Day Function in Insomnia Disorder (\u201cCUPID\u201d Study): Protocol for a Randomised, Double-Blind, Placebo-Controlled, Cross-over, Three-Arm, Proof-of-Concept Trial","volume":"13","author":"Lavender","year":"2023","journal-title":"BMJ Open"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.euroneuro.2022.04.003","article-title":"Cannabidiol Enhancement of Exposure Therapy in Treatment Refractory Patients with Social Anxiety Disorder and Panic Disorder with Agoraphobia: A Randomised Controlled Trial","volume":"59","author":"Kwee","year":"2022","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"119829","DOI":"10.1016\/j.jad.2025.119829","article-title":"Acute and Chronic Effects of Medicinal Cannabis Use on Anxiety and Depression in a Prospective Cohort of Patients New to Cannabis","volume":"390","author":"Wolinsky","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1177\/07067437231209650","article-title":"Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le Cannabidiol Comme Traitement d\u2019appoint de La D\u00e9pression Bipolaire Aigu\u00eb: Une \u00c9tude Pilote","volume":"69","author":"Pinto","year":"2024","journal-title":"Can. J. Psychiatry"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"107841","DOI":"10.1016\/j.parkreldis.2025.107841","article-title":"Cannabidiol and Cognitive Functions\/Inflammatory Markers in Parkinson\u2019s Disease: A Double-Blind Randomized Controlled Trial at Buriram Hospital (CBD-PD-BRH Trial)","volume":"135","author":"Mitarnun","year":"2025","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1002\/mds.29447","article-title":"Cognitive Safety Data from a Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase IIb Study of the Effects of a Cannabidiol and \u03949-Tetrahydrocannabinol Drug on Parkinson\u2019s Disease-Related Motor Symptoms","volume":"38","author":"Domen","year":"2023","journal-title":"Mov. Disord."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/mds.29768","article-title":"Short-Term Cannabidiol with \u0394-9-Tetrahydrocannabinol in Parkinson\u2019s Disease: A Randomized Trial","volume":"39","author":"Liu","year":"2024","journal-title":"Mov. Disord."},{"key":"ref_138","first-page":"374","article-title":"The Effect of Cannabidiol for Restless Legs Syndrome\/Willis-Ekbom Disease in Parkinson\u2019s Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2\/3 Clinical Trial","volume":"8","author":"Brito","year":"2023","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/s41386-025-02175-3","article-title":"Does Cannabidiol Reduce the Adverse Effects of Cannabis in Schizophrenia? A Randomised, Double-Blind, Cross-over Trial","volume":"50","author":"Chesney","year":"2025","journal-title":"Neuropsychopharmacology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"8875138","DOI":"10.1155\/crps\/8875138","article-title":"An Adolescent Female with Disordered Eating and Cannabis Use Found to Have Acute Intermittent Porphyria","volume":"2025","author":"Gertz","year":"2025","journal-title":"Case Rep. Psychiatry"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000535726","article-title":"Pharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects","volume":"7","author":"Zhang","year":"2024","journal-title":"Med. Cannabis Cannabinoids"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1200\/JCO.23.02596","article-title":"Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline","volume":"42","author":"Braun","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Naya, N.M., Kelly, J., Corna, G., Golino, M., Polizio, A.H., Abbate, A., Toldo, S., Mezzaroma, E., Naya, N.M., and Kelly, J. (2024). An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects. Molecules, 29.","DOI":"10.3390\/molecules29020473"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Lee, J., Beers, J.L., Geffert, R.M., and Jackson, K.D. (2024). A Review of CYP-Mediated Drug Interactions: Mechanisms and In Vitro Drug-Drug Interaction Assessment. Biomolecules, 14.","DOI":"10.3390\/biom14010099"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s42238-024-00256-6","article-title":"Hypothesized Pharmacogenomic and Medication Influences on Tetrahydrocannabinol and Cannabidiol Metabolism in a Cohort of Unselected Oral Cannabis Users","volume":"7","author":"Wright","year":"2025","journal-title":"J. Cannabis Res."},{"key":"ref_146","first-page":"41","article-title":"Specific Features of Cannabidiol Metabolism and Excretion during Long-Term Consumption of Cannabis","volume":"11","author":"Shevchuk","year":"2025","journal-title":"Int. J. Minor Fruits Med. Aromat. Plants"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/bcp.70284","article-title":"Population Pharmacokinetic Modelling Revealed Large Variability in Oromucosal Absorption of \u03949-Tetrahydrocannabinol in Older Patients with Poor Appetite","volume":"92","author":"Storgaard","year":"2025","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/ptr.7742","article-title":"Nanoformulations as a Strategy to Overcome the Delivery Limitations of Cannabinoids","volume":"37","author":"Reddy","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"O\u2019Sullivan, S.E., Jensen, S.S., Kolli, A.R., Nikolajsen, G.N., Bruun, H.Z., and Hoeng, J. (2024). Strategies to Improve Cannabidiol Bioavailability and Drug Delivery. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020244"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s40001-024-01803-w","article-title":"Perceptions and Engagement of Patients with Chronic Conditions on the Use of Medical Cannabis: A Scoping Review","volume":"29","author":"Pomey","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/cpt.3407","article-title":"Getting the Dose Right in Drug Development for Rare Diseases: Barriers and Enablers","volume":"116","author":"Ahmed","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Debnath, A., Mazumder, R., Mazumder, A., Tyagi, P.K., and Singh, R.K. (2025). Challenges and Progress of Orphan Drug Development for Rare Diseases. Curr. Pharm. Biotechnol., 26.","DOI":"10.2174\/0113892010371761250616112614"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Bahraminejad, S., Almoazen, H., Bahraminejad, S., and Almoazen, H. (2025). Sublingual and Buccal Delivery: A Historical and Scientific Prescriptive. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17081073"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"B\u00e1cskay, I., Arany, P., Feh\u00e9r, P., J\u00f3zsa, L., Vasv\u00e1ri, G., Nemes, D., Pet\u0151, \u00c1., K\u00f3sa, D., Haimhoffer, \u00c1., and Ujhelyi, Z. (2025). Bioavailability Enhancement and Formulation Technologies of Oral Mucosal Dosage Forms: A Review. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17020148"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijpharm.2023.122789","article-title":"Buccal Delivery of Small Molecules and Biologics: Of Mucoadhesive Polymers, Films, and Nanoparticles\u2014An Update","volume":"636","author":"Nair","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/a-2560-9884","article-title":"Drug Delivery Approaches for Buccal and Sublingual Administration","volume":"75","author":"Ahmad","year":"2025","journal-title":"Drug Res."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Sacco, R., Riccitelli, G.C., Disanto, G., Bogousslavsky, J., Cavelti, A., Czell, D., Kamm, C.P., Kliesch, U., Ramseier, S.P., and Gobbi, C. (2024). Effectiveness, Safety and Patients\u2019 Satisfaction of Nabiximols (Sativex\u00ae) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13102907"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"115135","DOI":"10.1016\/j.psychres.2023.115135","article-title":"CANNA-TICS: Efficacy and Safety of Oral Treatment with Nabiximols in Adults with Chronic Tic Disorders\u2014Results of a Prospective, Multicenter, Randomized, Double-Blind, Placebo Controlled, Phase IIIb Superiority Study","volume":"323","author":"Pisarenko","year":"2023","journal-title":"Psychiatry Res."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Sivadasan, D., Madkhali, O.A., Sivadasan, D., and Madkhali, O.A. (2024). The Design Features, Quality by Design Approach, Characterization, Therapeutic Applications, and Clinical Considerations of Transdermal Drug Delivery Systems\u2014A Comprehensive Review. Pharmaceuticals, 17.","DOI":"10.20944\/preprints202401.0524.v1"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Bakhrushina, E.O., Shumkova, M.M., Avdonina, Y.V., Ananian, A.A., Babazadeh, M., Pouya, G., Grikh, V.V., Zubareva, I.M., Kosenkova, S.I., and Krasnyuk, I.I. (2025). Transdermal Drug Delivery Systems: Methods for Enhancing Skin Permeability and Their Evaluation. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17070936"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Brito, S., Baek, M., and Bin, B.H. (2024). Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16111403"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Chelu, M., Musuc, A.M., Chelu, M., and Musuc, A.M. (2023). Polymer Gels: Classification and Recent Developments in Biomedical Applications. Gels, 9.","DOI":"10.3390\/gels9020161"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.2147\/IJN.S455032","article-title":"Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in Vivo","volume":"19","author":"Chu","year":"2024","journal-title":"Int. J. Nanomedicine"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/jat\/bkae001","article-title":"Pharmacokinetics and Pharmacodynamics of Five Distinct Commercially Available Hemp-Derived Topical Cannabidiol Products","volume":"48","author":"Zamarripa","year":"2024","journal-title":"J. Anal. Toxicol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Mahmoudinoodezh, H., Telukutla, S.R., Bhangu, S.K., Bachari, A., Cavalieri, F., and Mantri, N. (2022). The Transdermal Delivery of Therapeutic Cannabinoids. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020438"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"66595","DOI":"10.12775\/JEHS.2025.85.66595","article-title":"The Role of Cannabinoids in the Treatment of Skin Diseases: A Review of Mechanisms of Action and Clinical Evidence","volume":"85","author":"Marciniak","year":"2025","journal-title":"J. Educ. Health Sport"},{"key":"ref_167","unstructured":"(2025, December 21). InMed Pharmaceuticals INM-755 Topical Cream for Epidermolysis Bullosa (EB). Available online: https:\/\/www.inmedpharma.com\/pharmaceutical\/inm-755-for-epidermolysis-bullosa\/."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3109\/03639041003657295","article-title":"Cannabidiol Bioavailability after Nasal and Transdermal Application: Effect of Permeation Enhancers","volume":"36","author":"Paudel","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"122727","DOI":"10.1016\/j.ijpharm.2023.122727","article-title":"An Update of Nano-Based Drug Delivery Systems for Cannabinoids: Biopharmaceutical Aspects & Therapeutic Applications","volume":"635","author":"Rauber","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Assadpour, E., Rezaei, A., Das, S.S., Rao, B.V.K., Singh, S.K., Kharazmi, M.S., Jha, N.K., Jha, S.K., Prieto, M.A., and Jafari, S.M. (2023). Cannabidiol-Loaded Nanocarriers and Their Therapeutic Applications. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040487"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Paczkowska-Walendowska, M., Trzaskoma, P., Dziopa, A., Moeini, A., Soczawa, M., Krasi\u0144ski, Z., Cielecka-Piontek, J., Paczkowska-Walendowska, M., Trzaskoma, P., and Dziopa, A. (2025). Innovative Strategies to Enhance the Bioavailability of Cannabidiol: Nanotechnology and Advanced Delivery Systems. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111637"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1208\/s12249-024-02836-4","article-title":"Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts","volume":"25","author":"Villate","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_173","first-page":"1429","article-title":"Stronger Weed, Higher Risk? Potent THC Linked to Psychosis and Addiction","volume":"178","author":"Rittiphairoj","year":"2025","journal-title":"ScienceDaily"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Nachnani, R., Knehans, A., Neighbors, J.D., Kocis, P.T., Lee, T., Tegeler, K., Trite, T., Raup-Konsavage, W.M., and Vrana, K.E. (2024). Systematic Review of Drug-Drug Interactions of Delta-9-Tetrahydrocannabinol, Cannabidiol, and Cannabis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1282831"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/cpt.2973","article-title":"Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants","volume":"114","author":"Bansal","year":"2023","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Geneau, H., Kovasala, M., Brown, G., Holmes, S., Hime, O., McNally, M., McFayden, M., Brewer, K., and Jones, G.K. (2025). Prevalence of Cannabidiol (CBD) Use Among Patients Taking Medications with Known Drug-Drug Interactions: A Cross-Sectional Analysis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14217776"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/epi4.12815","article-title":"Final Analysis of Potential Drug-Drug Interactions between Highly Purified Cannabidiol and Anti-Seizure Medications in an Open-Label Expanded Access Program","volume":"8","author":"Gaston","year":"2023","journal-title":"Epilepsia Open"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1038\/s41380-025-03057-2","article-title":"Cannabinoid CB1 Receptor-Sensitive Neurodevelopmental Processes and Trajectories","volume":"30","author":"Tseng","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Qian, L., Beers, J.L., Jackson, K.D., and Zhou, Z. (2024). CBD and THC in Special Populations: Pharmacokinetics and Drug-Drug Interactions. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16040484"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Koyama, S., Etkins, J., Jun, J., Miller, M., So, G.C., Gisch, D.L., and Eadon, M.T. (2025). Utilization of Cannabidiol in Post-Organ-Transplant Care. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020699"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1111\/ajt.15398","article-title":"Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus","volume":"19","author":"Leino","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Lippert, A., and Renner, B. (2022). Herb\u2013Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplements. J. Clin. Med., 11.","DOI":"10.3390\/jcm11061567"},{"key":"ref_183","unstructured":"Kreusel, K. (2025, December 20). Clinical Overview: Cannabis May Interact with Prescription Medications, Pharmacy Times, Available online: https:\/\/www.pharmacytimes.com\/view\/clinical-overview-cannabis-may-interact-with-prescription-medications."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/cpt.3504","article-title":"A Phase I Trial of the Pharmacokinetic Interaction Between Cannabidiol and Tacrolimus","volume":"117","author":"So","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Simei, J.L.Q., Souza, J.D.R., Pedrazzi, J.F., Guimar\u00e3es, F.S., Campos, A.C., Zuardi, A., Hallak, J.E.C., and Crippa, J.A.S. (2024). Research and Clinical Practice Involving the Use of Cannabis Products, with Emphasis on Cannabidiol: A Narrative Review. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121644"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"90","DOI":"10.5935\/2595-0118.20230037-en","article-title":"Current Legislation on Medical Cannabis in the European Union: Historical Background, Movements, Trends, and Counter-Trends Lessons for Brazil","volume":"6","author":"Silva","year":"2023","journal-title":"BrJP"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1055\/a-1808-9708","article-title":"Quality Requirements for Medicinal Cannabis and Respective Products in the European Union\u2014Status Quo","volume":"89","author":"Veit","year":"2023","journal-title":"Planta Med."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Jardim, C., and Delgado-Charro, M.B. (2025). The Regulatory Environment Surrounding Cannabis Medicines in the EU, the USA, and Australia. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17050635"},{"key":"ref_189","unstructured":"European Medicines Agency Epidyolex|European Medicines Agency (EMA) (2025, December 21). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/epidyolex."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13023-025-03756-7","article-title":"EMA Approved Orphan Medicines since the Implementation of the Orphan Legislation","volume":"20","author":"Hahl","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1080\/13696998.2025.2577514","article-title":"Toward an Ethical Future for Orphan Drugs: Balancing Access, Affordability, and Innovation","volume":"28","author":"Alum","year":"2025","journal-title":"J. Med. Econ."},{"key":"ref_192","unstructured":"(2025, December 21). Orphanet Orphanet: Quality Charter: Knowledge on Rare Diseases and Orphan Drugs. Available online: https:\/\/www.orpha.net\/en\/other-information\/about-orphan-drugs."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e073242","DOI":"10.1136\/bmj-2022-073242","article-title":"FDA Approval, Clinical Trial Evidence, Efficacy, Epidemiology, and Price for Non-Orphan and Ultra-Rare, Rare, and Common Orphan Cancer Drug Indications: Cross Sectional Analysis","volume":"381","author":"Michaeli","year":"2023","journal-title":"BMJ"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"104102","DOI":"10.1016\/j.drudis.2024.104102","article-title":"Clinical Trial Evidence Supporting FDA Approval of Novel Orphan Drugs between 2017 and 2023","volume":"29","author":"Chen","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/s13023-023-02915-y","article-title":"Pharmacovigilance for Rare Diseases: A Bibliometrics and Knowledge-Map Analysis Based on Web of Science","volume":"18","author":"Xu","year":"2023","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/2\/83\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:20:04Z","timestamp":1771996804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/2\/83"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,23]]},"references-count":195,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["diseases14020083"],"URL":"https:\/\/doi.org\/10.3390\/diseases14020083","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,23]]}}}