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Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.

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Title: Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.
Authors: Pitts, Kayla M. (AUTHOR), Pilz, Emma M. (AUTHOR), Colloca, Luana (AUTHOR), Shaham, Yavin (AUTHOR), Chow, Jonathan J. (AUTHOR)
Source: Psychopharmacology. May2026, Vol. 243 Issue 5, p1225-1236. 12p.
Subjects: Buprenorphine, Opioids, Placebos, Animal disease models, Drug administration, Treatment of addictions, Remifentanil
Abstract: Rationale and Objective: Clinical studies have shown that exposure to placebos or combining placebos with a lower medication dose can mimic the effect of a higher effective medication dose. This "dose-extending placebo effect" has been demonstrated in treatment for pain and other medical conditions but not in addiction. Here, we tested if a "dose-extending placebo effect" occurs in a rat model of opioid (buprenorphine) maintenance. Methods: We trained 27 rats to self-administer remifentanil (5 µg/kg/infusion, 1-h per day). Next, we implanted some rats with buprenorphine minipumps (3 mg/kg/day, Exp. 1) or pretreated others with daily intravenous buprenorphine (0.3 mg/kg, Exp. 2), and introduced a discriminative cue (houselight + tone) during the self-administration sessions (the buprenorphine-maintenance cue). After discontinuing buprenorphine treatment, we retrained the rats for remifentanil self-administration without the cue. Next, we tested the effect of low and high buprenorphine doses (0.15 and 0.3 mg/kg), the buprenorphine-maintenance cue, and the combination of the low-dose with the cue on remifentanil self-administration. Results: Rats learned to self-administer remifentanil, and buprenorphine maintenance suppressed drug self-administration. The low buprenorphine dose modestly decreased self-administration, while the high dose caused a strong inhibition. Tests for the "dose-extending placebo effect" showed that discriminative buprenorphine cue alone had no effect, while the low dose plus the buprenorphine cue mimicked the inhibitory effect of the high dose. Conclusions: This proof-of-concept study suggests that a "dose-extending placebo effect" can be modeled in rats undergoing opioid maintenance. This approach could support dose-reduction strategies in humans undergoing opioid maintenance therapy. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. May2026, Vol. 243 Issue 5, p1225-1236. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Buprenorphine%22">Buprenorphine</searchLink><br /><searchLink fieldCode="DE" term="%22Opioids%22">Opioids</searchLink><br /><searchLink fieldCode="DE" term="%22Placebos%22">Placebos</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+disease+models%22">Animal disease models</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+administration%22">Drug administration</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+of+addictions%22">Treatment of addictions</searchLink><br /><searchLink fieldCode="DE" term="%22Remifentanil%22">Remifentanil</searchLink>
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  Data: Rationale and Objective: Clinical studies have shown that exposure to placebos or combining placebos with a lower medication dose can mimic the effect of a higher effective medication dose. This "dose-extending placebo effect" has been demonstrated in treatment for pain and other medical conditions but not in addiction. Here, we tested if a "dose-extending placebo effect" occurs in a rat model of opioid (buprenorphine) maintenance. Methods: We trained 27 rats to self-administer remifentanil (5 µg/kg/infusion, 1-h per day). Next, we implanted some rats with buprenorphine minipumps (3 mg/kg/day, Exp. 1) or pretreated others with daily intravenous buprenorphine (0.3 mg/kg, Exp. 2), and introduced a discriminative cue (houselight + tone) during the self-administration sessions (the buprenorphine-maintenance cue). After discontinuing buprenorphine treatment, we retrained the rats for remifentanil self-administration without the cue. Next, we tested the effect of low and high buprenorphine doses (0.15 and 0.3 mg/kg), the buprenorphine-maintenance cue, and the combination of the low-dose with the cue on remifentanil self-administration. Results: Rats learned to self-administer remifentanil, and buprenorphine maintenance suppressed drug self-administration. The low buprenorphine dose modestly decreased self-administration, while the high dose caused a strong inhibition. Tests for the "dose-extending placebo effect" showed that discriminative buprenorphine cue alone had no effect, while the low dose plus the buprenorphine cue mimicked the inhibitory effect of the high dose. Conclusions: This proof-of-concept study suggests that a "dose-extending placebo effect" can be modeled in rats undergoing opioid maintenance. This approach could support dose-reduction strategies in humans undergoing opioid maintenance therapy. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00213-025-06815-w
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        Text: English
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        Type: general
      – SubjectFull: Opioids
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      – SubjectFull: Placebos
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      – SubjectFull: Drug administration
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      – SubjectFull: Treatment of addictions
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      – SubjectFull: Remifentanil
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      – TitleFull: Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.
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              Text: May2026
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              Y: 2026
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