{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:19Z","timestamp":1785411499496,"version":"3.56.0"},"reference-count":79,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danish Regions","award":["2627"],"award-info":[{"award-number":["2627"]}]},{"name":"A.P. M\u00f8ller Fund for the Advancement of Medical Science","award":["19-L-0217"],"award-info":[{"award-number":["19-L-0217"]}]},{"DOI":"10.13039\/501100009898","name":"Beckett-Fonden","doi-asserted-by":"publisher","award":["24-2-13188"],"award-info":[{"award-number":["24-2-13188"]}],"id":[{"id":"10.13039\/501100009898","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-2-13188"],"award-info":[{"award-number":["24-2-13188"]}],"id":[{"id":"https:\/\/ror.org\/03y4t9m88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Poor appetite, a major contributor to malnutrition, is highly prevalent among older adults and associated with adverse clinical outcomes. Nevertheless, there are currently no widely accepted or consistently effective pharmacological treatments targeting appetite that are routinely recommended alongside nutritional interventions. Medical cannabis has been proposed as a potential appetite stimulant in older adults with poor appetite through modulation of appetite-regulating hormones such as glucagon-like peptide-1 (GLP-1) and total ghrelin, but the evidence remains limited. Aims: To investigate the effects of Sativex\u00ae versus placebo on postprandial GLP-1 and total ghrelin concentrations following a single dose (8.1 mg \u03949-tetrahydrocannabinol (THC) and 7.5 mg cannabidiol (CBD)), and on subjective appetite following two separated doses, in older adults with poor appetite, and to investigate the associations between plasma concentrations of THC and its metabolites on these outcomes. Methods: This protocolized secondary analysis included 17 participants (\u226565 years) with poor appetite from a double-blind, randomized, placebo-controlled crossover trial. Participants received Sativex\u00ae or placebo on two separate study days. GLP-1 and total ghrelin were measured following one dose of Sativex\u00ae\/placebo and a standardized breakfast, and subjective appetite was assessed repeatedly using visual analog scales throughout the administration of two separate doses of Sativex\u00ae\/placebo, the consumption of a standardized breakfast, and an ad libitum lunch meal. Effects\/associations were analyzed using linear mixed-effects models. Results: Compared with placebo, Sativex\u00ae produced an estimated 2.38 pmol\/L (95% confidence intervals (CI): \u22120.71 to 5.46; Bonferroni-corrected p = 0.274) reduction in mean GLP-1 and time-dependent changes in mean total ghrelin (Bonferroni-corrected p = 0.054). Compared with placebo, Sativex\u00ae produced minimal changes in separate subjective appetite sensations (all Bonferroni-corrected p = 1.00) and a slightly lower combined appetite score (\u22125.2 mm; 95% CI: \u221224.4 to 4.0; Bonferroni-corrected p = 1.00). Increased plasma concentrations of THC and metabolites were associated with reduced estimates of mean GLP-1 concentrations and subjective appetite, as well as increased mean total ghrelin concentrations. However, no statistically significant differences were detected for any analyses, and estimates had wide CIs, warranting cautious interpretation. Conclusions: In conclusion, no statistically significant differences were detected between Sativex\u00ae and placebo in postprandial GLP-1, total ghrelin, or subjective appetite over time in older adults with poor appetite. Similarly, no statistically significant associations were observed between plasma concentrations of THC and its metabolites and GLP-1, total ghrelin, or subjective appetite. Trial registration: ClinicalTrials.gov ID: NCT05503147; EudraCT nr.: 2021-002318-15.<\/jats:p>","DOI":"10.3390\/nu18142274","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:05:31Z","timestamp":1783929931000},"page":"2274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Sativex\u00ae Versus Placebo on Glucagon-like Peptide-1, Total Ghrelin, and Subjective Appetite in Older Adults with Poor Appetite: A Protocolized Secondary Analysis of a Double-Blind, Randomized, Placebo-Controlled Crossover Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-8153","authenticated-orcid":false,"given":"Olivia","family":"Born\u00e6s","sequence":"first","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-7349","authenticated-orcid":false,"given":"Rikke Lundsgaard","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8954-2675","authenticated-orcid":false,"given":"Louise Westberg Strejby","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida Klitzing","family":"Storgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7356-6481","authenticated-orcid":false,"given":"Thomas","family":"Kallemose","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-9201","authenticated-orcid":false,"given":"Helle Gybel","family":"Juul-Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-9974","authenticated-orcid":false,"given":"Juliette","family":"Tavenier","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6915-744X","authenticated-orcid":false,"given":"Baker","family":"Jawad","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ove","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"The Emergency Department, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-3805","authenticated-orcid":false,"given":"Jens Juul","family":"Holst","sequence":"additional","affiliation":[{"name":"The Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-2036","authenticated-orcid":false,"given":"Bolette","family":"Hartmann","sequence":"additional","affiliation":[{"name":"The Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1449-1931","authenticated-orcid":false,"given":"Aino Leegaard","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-017X","authenticated-orcid":false,"given":"Ingrid","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Peick","family":"Sonne","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg Hospital, 2400 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-3012","authenticated-orcid":false,"given":"Morten Baltzer","family":"Houlind","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark"},{"name":"Department of Nephrology and Endocrinology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-2531","authenticated-orcid":false,"given":"Mette Merete","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, 2650 Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1002\/puh2.213","article-title":"Public Health Challenges and Responses to the Growing Ageing Populations","volume":"3","author":"Khan","year":"2024","journal-title":"Public Health Chall."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.clnu.2013.05.007","article-title":"Prevalence and Determinants for Malnutrition in Geriatric Outpatients","volume":"32","author":"Danner","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.clnesp.2021.02.020","article-title":"The Nutritional Status and Dietary Intake of Free-Living Seniors: A Cross-Sectional Study","volume":"43","author":"Coppinger","year":"2021","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.clnu.2009.12.013","article-title":"Malnutrition and Associated Factors in Elderly Hospital Patients: A Belgian Cross-Sectional, Multi-Centre Study","volume":"29","author":"Vanderwee","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sieske, L., Janssen, G., Babel, N., Westhoff, T.H., Wirth, R., and Pourhassan, M. (2019). Inflammation, Appetite and Food Intake in Older Hospitalized Patients. Nutrients, 11.","DOI":"10.3390\/nu11091986"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Andersen, A.L., Nielsen, R.L., Houlind, M.B., Tavenier, J., Rasmussen, L.J.H., J\u00f8rgensen, L.M., Treldal, C., Beck, A.M., Pedersen, M.M., and Andersen, O. (2021). Risk of Malnutrition upon Admission and after Discharge in Acutely Admitted Older Medical Patients: A Prospective Observational Study. Nutrients, 13.","DOI":"10.3390\/nu13082757"},{"key":"ref_7","first-page":"84","article-title":"Nutritional Risk in Acutely Admitted Older Medical Patients","volume":"3","author":"Petersen","year":"2025","journal-title":"Am. J. Food Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nut.2019.04.005","article-title":"Undernutrition Measured by the Mini Nutritional Assessment (MNA) Test and Related Risk Factors in Older Adults under Hospital Emergency Care","volume":"66","year":"2019","journal-title":"Nutrition"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.clnesp.2023.06.012","article-title":"\u201cMore2Eat\u201d in Patients at Nutritional Risk during Hospital Stay Lowers the Risk of Three-Month Mortality","volume":"57","author":"Mikkelsen","year":"2023","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0261-5614(02)00215-7","article-title":"The Impact of Malnutrition on Morbidity, Mortality, Length of Hospital Stay and Costs Evaluated through a Multivariate Model Analysis","volume":"22","author":"Isabel","year":"2003","journal-title":"Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/BF03324863","article-title":"Mini Nutritional Assessment (Short Form) and Functional Decline in Older Patients Admitted to an Acute Medical Ward","volume":"20","author":"Salvi","year":"2008","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/jhn.12167","article-title":"The Consequences of Malnutrition Following Discharge from Rehabilitation to the Community: A Systematic Review of Current Evidence in Older Adults","volume":"27","author":"Marshall","year":"2014","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3945\/an.115.011254","article-title":"Risk Factors for Malnutrition in Older Adults: A Systematic Review of the Literature Based on Longitudinal Data","volume":"7","author":"Matthys","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/jcsm.13186","article-title":"Association of Anorexia\/Appetite Loss with Malnutrition and Mortality in Older Populations: A Systematic Literature Review","volume":"14","author":"Fielding","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hansen, T., Nielsen, R.L., Houlind, M.B., Tavenier, J., Rasmussen, L.J.H., J\u00f8rgensen, L.M., Treldal, C., Beck, A.M., Pedersen, M.M., and Andersen, O. (2021). Dysphagia Prevalence, Time Course, and Association with Probable Sarcopenia, Inactivity, Malnutrition, and Disease Status in Older Patients Admitted to an Emergency Department: A Secondary Analysis of Cohort Study Data. Geriatrics, 6.","DOI":"10.3390\/geriatrics6020046"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.clnesp.2022.03.007","article-title":"The Association between Polypharmacy and Malnutrition(Risk) in Older People: A Systematic Review","volume":"49","author":"Kok","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.clnu.2024.06.005","article-title":"Growth Differentiation Factor 15 (GDF15) Levels Are Associated with Malnutrition in Acutely Admitted Older Adults","volume":"43","author":"Nielsen","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.arr.2014.09.001","article-title":"Determinants of Protein\u2013Energy Malnutrition in Community-Dwelling Older Adults: A Systematic Review of Observational Studies","volume":"18","author":"Wijnhoven","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.clnu.2024.06.020","article-title":"Nutrition for the Older Adult\u2014Current Concepts. Report from an ESPEN Symposium","volume":"43","author":"Volkert","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100745","DOI":"10.1016\/j.jnha.2025.100745","article-title":"Potential Causes of Malnutrition in Older Adults in Primary Healthcare\u2014A Cross-Sectional Study","volume":"30","author":"Pfannkuch","year":"2025","journal-title":"J. Nutr. Health Aging"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Donini, L.M., Poggiogalle, E., Piredda, M., Pinto, A., Barbagallo, M., Cucinotta, D., and Sergi, G. (2013). Anorexia and Eating Patterns in the Elderly. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063539"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1111\/jgs.15017","article-title":"Poor Appetite and Dietary Intake in Community-Dwelling Older Adults","volume":"65","author":"Wijnhoven","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ii4","DOI":"10.1093\/ageing\/afae040","article-title":"Dietary Characteristics of Community-Dwelling Older Adults with Poor Appetite: A Cross-Sectional Analysis","volume":"53","author":"Scheufele","year":"2024","journal-title":"Age Ageing"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11357-015-9821-x","article-title":"Mechanisms of the Anorexia of Aging\u2014A Review","volume":"37","author":"Kostka","year":"2015","journal-title":"Age"},{"key":"ref_25","first-page":"44","article-title":"New Insights into the Anorexia of Ageing: From Prevention to Treatment","volume":"22","author":"Dent","year":"2019","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_26","unstructured":"Morley, J.E., and Silver, A.J. (1988, January 20\u201325). Geriatric Research, Education and Clinical Center, Sepulveda VA Medical Center, Sepulveda, CA 91343 Department of Medicine, University of California, Los Angeles, CA 90024. Proceedings of the 13th Congress of the International Diabetes Federation, Sydney, Australia."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/S0140-6736(18)32776-4","article-title":"Individualised Nutritional Support in Medical Inpatients at Nutritional Risk: A Randomised Clinical Trial","volume":"393","author":"Schuetz","year":"2019","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, M., Zhao, S., Wu, S., Yang, X., and Feng, H. (2021). Effectiveness of Oral Nutritional Supplements on Older People with Anorexia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 13.","DOI":"10.3390\/nu13030835"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.clnu.2018.07.023","article-title":"Effectiveness of Nutritional Interventions in Older Adults at Risk of Malnutrition across Different Health Care Settings: Pooled Analyses of Individual Participant Data from Nine Randomized Controlled Trials","volume":"38","author":"Reinders","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_30","first-page":"CD002008","article-title":"Dietary Advice with or without Oral Nutritional Supplements for Disease-related Malnutrition in Adults","volume":"2011","author":"Baldwin","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.clnesp.2024.02.031","article-title":"Effectiveness of a Multidisciplinary and Transitional Nutritional Intervention Compared with Standard Care on Health-Related Quality of Life among Acutely Admitted Medical Patients Aged \u226565 Years with Malnutrition or Risk of Malnutrition: A Randomized Controlled Trial","volume":"61","author":"Andersen","year":"2024","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1017\/S0007114521000799","article-title":"Prevalence of Low Protein Intake in 80+-Year-Old Community-Dwelling Adults and Association with Dietary Patterns and Modifiable Risk Factors: A Cross-Sectional Study","volume":"127","author":"Buhl","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Landi, F., Calvani, R., Tosato, M., Martone, A., Ortolani, E., Savera, G., Sisto, A., and Marzetti, E. (2016). Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments. Nutrients, 8.","DOI":"10.3390\/nu8020069"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cox, N.J., Ibrahim, K., Sayer, A.A., Robinson, S.M., and Roberts, H.C. (2019). Assessment and Treatment of the Anorexia of Aging: A Systematic Review. Nutrients, 11.","DOI":"10.3390\/nu11010144"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cox, N.J., Jones, L., and Lim, S.E.R. (2025). Focussing on Appetite Decline to Optimise Management of Undernutrition in Later Life: A Geriatric Medicine Perspective. Proc. Nutr. Soc., 1\u20136.","DOI":"10.1017\/S0029665125102115"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/ncp.10839","article-title":"A Review of the Efficacy of Appetite Stimulating Medications in Hospitalized Adults","volume":"38","author":"Steiner","year":"2022","journal-title":"Nutr. Clin. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1111\/j.1532-5415.2005.53307.x","article-title":"The Effects of Megestrol Acetate Suspension for Elderly Patients with Reduced Appetite After Hospitalization: A Phase II Randomized Clinical Trial","volume":"53","author":"Reuben","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1532-5415.2000.tb04993.x","article-title":"Improvement in Quality-of-Life Measures and Stimulation of Weight Gain After Treatment with Megestrol Acetate Oral Suspension in Geriatric Cachexia: Results of a Double-Blind, Placebo-Controlled Study","volume":"48","author":"Yeh","year":"2000","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1532-5415.2006.01010.x","article-title":"Effects of Muscle Strength Training and Megestrol Acetate on Strength, Muscle Mass, and Function in Frail Older People","volume":"55","author":"Sullivan","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1532-5415.1995.tb07065.x","article-title":"Megestrol Acetate Suspension Therapy in the Treatment of Geriatric Anorexia\/Cachexia in Nursing Home Patients","volume":"43","author":"Castle","year":"1995","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1017\/S0954422414000080","article-title":"The Endocannabinoid System and Appetite: Relevance for Food Reward","volume":"27","author":"Jager","year":"2014","journal-title":"Nutr. Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jcrt.JCRT_488_18","article-title":"Emerging Role of Cannabinoids and Synthetic Cannabinoid Receptor 1\/Cannabinoid Receptor 2 Receptor Agonists in Cancer Treatment and Chemotherapy-Associated Cancer Management","volume":"17","author":"Shah","year":"2021","journal-title":"J. Can. Res. Ther."},{"key":"ref_43","unstructured":"Aronne, L.J. (Bariatric Times, 2007). The Endocannabinoid System as a Mechanism Regulating Appetite and Energy Balance, Bariatric Times."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1111\/bcp.13695","article-title":"Cannabis Contaminants: Sources, Distribution, Human Toxicity and Pharmacologic Effects","volume":"84","author":"Dryburgh","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1210\/jc.2002-021656","article-title":"Appetite, Food Intake, and Plasma Concentrations of Cholecystokinin, Ghrelin, and Other Gastrointestinal Hormones in Undernourished Older Women and Well-Nourished Young and Older Women","volume":"88","author":"Sturm","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.appet.2010.08.010","article-title":"Effects of Nutritional Supplementation on the Appetite and Energy Intake Responses to IV Cholecystokinin in Older Adults","volume":"55","author":"Tai","year":"2010","journal-title":"Appetite"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s40520-019-01292-6","article-title":"Differences in Circulating Appetite-Related Hormone Concentrations between Younger and Older Adults: A Systematic Review and Meta-Analysis","volume":"32","author":"Johnson","year":"2020","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.brainres.2011.11.001","article-title":"A Pilot Study of the Effects of Cannabis on Appetite Hormones in HIV-Infected Adult Men","volume":"1431","author":"Riggs","year":"2012","journal-title":"Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41398-020-0756-3","article-title":"Effects of Oral, Smoked, and Vaporized Cannabis on Endocrine Pathways Related to Appetite and Metabolism: A Randomized, Double-Blind, Placebo-Controlled, Human Laboratory Study","volume":"10","author":"Farokhnia","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/bcpt.13914","article-title":"Appetite Stimulation with Cannabis-Based Medicine and Methods for Assessment of Glomerular Filtration in Older Patients with Medical Illness: A Study Protocol","volume":"133","author":"Nielsen","year":"2023","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_51","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":"2026","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.clnu.2025.02.024","article-title":"The Appetite Stimulating Effect and Safety of Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Older Patients with Poor Appetite: A Triple-Blinded, Randomized, Placebo-Controlled, Cross-over Trial","volume":"47","author":"Nielsen","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/ajcn\/82.5.1074","article-title":"Appetite Assessment: Simple Appetite Questionnaire Predicts Weight Loss in Community-Dwelling Adults and Nursing Home Residents","volume":"82","author":"Wilson","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_54","unstructured":"(2026, March 10). Sativex Oromucosal Spray\u2014Summary of Product Characteristics (SmPC)\u2014(Emc)|602. Available online: https:\/\/www.medicines.org.uk\/emc\/product\/602\/smpc."},{"key":"ref_55","unstructured":"Danish Medicines Agency (2026, March 10). Produkt Resume for Sativex, Oromucosal Spray, (In Danish)."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2337\/diab.43.4.535","article-title":"Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans","volume":"43","author":"Wettergren","year":"1994","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.appet.2010.01.016","article-title":"Comparison of 150-Mm versus 100-Mm Visual Analogue Scales in Free Living Adult Subjects","volume":"54","author":"Chaput","year":"2010","journal-title":"Appetite"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.numecd.2008.09.006","article-title":"Viscosity of Fiber Preloads Affects Food Intake in Adolescents","volume":"19","author":"Vuksan","year":"2009","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E1062","DOI":"10.1152\/ajpendo.00450.2006","article-title":"Effects of PYY 1\u201336 and PYY 3\u201336 on Appetite, Energy Intake, Energy Expenditure, Glucose and Fat Metabolism in Obese and Lean Subjects","volume":"292","author":"Sloth","year":"2007","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/oby.23204","article-title":"Association of Gastric Emptying with Postprandial Appetite and Satiety Sensations in Obesity","volume":"29","author":"Campos","year":"2021","journal-title":"Obesity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1467-789X.2010.00714.x","article-title":"Appetite control: Methodological aspects of the evaluation of foods","volume":"11","author":"Blundell","year":"2010","journal-title":"Obes. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0261-5614(02)00214-5","article-title":"Nutritional Risk Screening (NRS 2002): A New Method Based on an Analysis of Controlled Clinical Trials","volume":"22","author":"Kondrup","year":"2003","journal-title":"Clin. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ejcn.2014.76","article-title":"Nutrition Impact Symptoms and Body Composition in Patients with COPD","volume":"69","author":"Bosaeus","year":"2015","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_64","unstructured":"InBody USA (2026). Body Composition Analysis: Muscle, Fat & Water, InBody USA."},{"key":"ref_65","unstructured":"Team, R.C. (2021). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_66","unstructured":"Pinheiro, J., and Bates, D. (2023). Nlme: Linear and Nonlinear Mixed Effects Models, R Core Team."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Schulz, K.F., Altman, D.G., and Moher, D. (2010). for the CONSORT Group. CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials. PLoS Med., 7.","DOI":"10.2427\/5718"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","article-title":"The Physiology of Glucagon-like Peptide 1","volume":"87","author":"Holst","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cell.2007.04.001","article-title":"The Hormonal Control of Food Intake","volume":"129","author":"Coll","year":"2007","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s00228-012-1393-4","article-title":"A Phase I Study to Assess the Effect of Food on the Single Dose Bioavailability of the THC\/CBD Oromucosal Spray","volume":"69","author":"Stott","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1373\/clinchem.2010.152439","article-title":"Plasma Cannabinoid Pharmacokinetics Following Controlled Oral \u03949-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration","volume":"57","author":"Karschner","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1089\/can.2023.0229","article-title":"Comparative Pharmacokinetic Assessment of Innovative Sublingual, Rectal and Vaporizer Cannabis Products Versus Approved Cannabis Products in Healthy Volunteers","volume":"10","author":"Tarlovski","year":"2025","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1080\/17425247.2019.1653852","article-title":"A Meta-Opinion: Cannabinoids Delivered to Oral Mucosa by a Spray for Systemic Absorption Are Rather Ingested into Gastro-Intestinal Tract: The Influences of Fed\/Fasting States","volume":"16","author":"Itin","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_74","unstructured":"Strougo, A., Zuurman, L., Roy, C., Pinquier, J., van Gerven, J., Cohen, A., and Schoemaker, R. (2026, May 08). Modelling of the Concentration\u2014Effect Relationship of THC on Central Nervous System Parameters and Heart Rate\u2014Insight into Its Mechanisms of Action and a Tool for Clinical Research and Development of Cannabinoids. Available online: https:\/\/journals-sagepub-com.kb-ku.idm.oclc.org\/doi\/epdf\/10.1177\/0269881108089870."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","unstructured":"Sinclair, A.J., Morley, J.E., and Vellas, B. (2012). The Anorexia of Ageing. Pathy\u2019s Principles and Practice of Geriatric Medicine, Wiley.","DOI":"10.1002\/9781119952930"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s13679-024-00604-w","article-title":"Hallmarks of Appetite: A Comprehensive Review of Hunger, Appetite, Satiation, and Satiety","volume":"14","author":"Garutti","year":"2025","journal-title":"Curr. Obes. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112910","DOI":"10.1016\/j.nut.2025.112910","article-title":"Ghrelin\u2019s Role in Regulating Food Intake among Inpatients at Nutritional Risk: A Secondary Analysis of the Randomized Clinical Trial EFFORT","volume":"140","author":"Urbach","year":"2025","journal-title":"Nutrition"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/sj.ejcn.1601768","article-title":"Relation between Food Intake and Visual Analogue Scale Ratings of Appetite and Other Sensations in Healthy Older and Young Subjects","volume":"58","author":"Parker","year":"2004","journal-title":"Eur. J. Clin. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2274\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:20:45Z","timestamp":1784175645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/14\/2274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":79,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18142274"],"URL":"https:\/\/doi.org\/10.3390\/nu18142274","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]}}}