{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:37:46Z","timestamp":1768880266840,"version":"3.49.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cannabidiol (CBD) has anti-nociceptive and anti-inflammatory characteristics, and was reported to provide analgesia in dogs with osteoarthritis. However, oral CBD has poor bioavailability due to significant first-pass hepatic metabolism. Encapsulation of CBD into liposomes was reported by our group to facilitate CBD slow-release, and provide high bioavailability and analgesia in a pilot study in dogs with osteoarthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the pharmacokinetics and effects of liposomal-synthetic-cannabidiol (L-sCBD) injection compared with placebo in dogs with radiographically confirmed naturally-occurring osteoarthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Eight client-owned dogs (4 males, 4 females; 8.5 [4.5\u201312.5] years-old; 34.9 [22.7\u201342.7] kg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Dogs were injected subcutaneously twice with a 4-week interval; once with 7\u202fmg\/kg\u202fL-sCBD (50\u202fmg\/mL) and once with empty liposomes of identical lipid composition (placebo; equivalent volume) in a randomized, blinded, crossover design. Each dog routine analgesics (e.g., non-steroidal anti-inflammatories) were continued. Blood was sampled for CBD and metabolites concentrations, complete blood count and serum chemistry up to 4-weeks post-injections. Efficacy was assessed\n                      <jats:italic>via<\/jats:italic>\n                      activity monitoring collar and scorings by owners and two veterinary specialists. Vital signs and local response were monitored. Data analysis used aligned rank transform ANOVA, permutation test and Wilcoxon signed-rank test (\n                      <jats:italic>p<\/jats:italic>\n                      -value &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CBD plasma concentrations were detected up to 4-weeks; median peak plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) was 58.2 [range 35.1\u2013141.0] ng\/mL, median time to C\n                      <jats:sub>max<\/jats:sub>\n                      was 3 [3\u20137] days and median half-life 6.1 [4.6\u20139.5] days. The metabolites 6\/7-hydroxy-CBD, and\n                      <jats:italic>7-<\/jats:italic>\n                      carboxy-CBD were detected at low concentrations. Pain and lameness scores and behavior were significantly improved after L-sCBD treatment\n                      <jats:italic>versus<\/jats:italic>\n                      placebo. At 3-days after L-sCBD treatment, neutrophils and alkaline-phosphatase increased significantly, while hematocrit and albumin decreased (all within reference range, except neutrophils in 2\/8 dogs). Adverse effects included 2-days fever and a minor-moderate local swelling, which resolved spontaneously.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical relevance<\/jats:title>\n                    <jats:p>Subcutaneous L-sCBD provided long-term CBD plasma concentrations, improved analgesia and was tolerated by all dogs. A larger clinical cohort is required to further assess L-sCBD benefits and safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2025.1746266","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T15:05:01Z","timestamp":1768835101000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy, pharmacokinetics and safety of liposomal synthetic cannabidiol injected subcutaneously in dogs: a randomized, blinded, placebo-controlled, crossover clinical trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Yael","family":"Shilo-Benjamini","sequence":"first","affiliation":[{"name":"Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hadassah Medical School, The Hebrew University of Jerusalem","place":["Jerusalem, Israel"]},{"name":"Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem","place":["Rehovot, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Milgram","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem","place":["Rehovot, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Lavy","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem","place":["Rehovot, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Quint","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem","place":["Rehovot, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinorah","family":"Barasch","sequence":"additional","affiliation":[{"name":"The Mass Spectrometry Unit, School of Pharmacy, The Hebrew University of Jerusalem","place":["Jerusalem, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahuva","family":"Cern","sequence":"additional","affiliation":[{"name":"Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hadassah Medical School, The Hebrew University of Jerusalem","place":["Jerusalem, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yechezkel","family":"Barenholz","sequence":"additional","affiliation":[{"name":"Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hadassah Medical School, The Hebrew University of Jerusalem","place":["Jerusalem, 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