{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:04:57Z","timestamp":1779368697361,"version":"3.53.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Many people use cannabis to self\u2010medicate for pain. Little is known about the impact of pain on tolerance and spontaneous withdrawal to delta\u20109\u2010tetrahydrocannabinal (\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      ), the primary psychoactive compound in cannabis. Our previous research with the opioid morphine suggests persistent pain will increase the magnitude and duration of\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female Sprague\u2013Dawley rats were individually housed in a cage with a running wheel to provide a continuous and objective measure of well\u2010being. All rats were injected with Complete Freund's Adjuvant (\n                      <jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\n                      ) into the right hindpaw to induce inflammatory pain. Beginning 1\u2009day later, rats received twice daily\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      or vehicle injections for 7\u2009days followed by assessment of tolerance and spontaneous withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Administration of\n                      <jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\n                      decreased wheel running. Twice daily injections of\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      (3\u2009mg\/kg\/injection) caused a further reduction in running in male and female rats. Tolerance to the\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      \u2010induced decrease in running was more pronounced in male compared to female rats. There was no evidence of spontaneous withdrawal to\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      despite continuous assessment for 6\u2009days. Likewise, withdrawal had no effect on body weight.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The lack of spontaneous withdrawal in rats with hindpaw inflammation is consistent with our recent study showing a lack of spontaneous withdrawal to\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      in pain free rats, but opposite to our opioid research showing enhancement of spontaneous withdrawal to morphine in rats with hindpaw inflammation. In sum, persistent inflammatory pain does not appear to alter the effects of repeated\n                      <jats:styled-content style=\"fixed-case\">THC<\/jats:styled-content>\n                      injections in male or female rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The use of THC as a treatment for pain is limited by side effects and tolerance but not by dependence associated withdrawal symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70279","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:37:38Z","timestamp":1777034258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated Tetrahydrocannabinol Injections Induce Tolerance but Do Not Disrupt Ongoing Behaviour Upon Withdrawal in Male and Female 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