Evidence mapPaperPMID 42162267Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026

An opioid-withholding human laboratory paradigm during opioid agonist treatment for opioid use disorder and chronic pain: Phase- and dose-dependent effects of cannabidiol.

Gabriel P A Costa, Mehmet Sofuoglu, Peggy Compton, Mohini Ranganathan, Brian Pittman, Joao P De Aquino

Abstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Gabriel P A CostaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0009-0007-8702-5436
Mehmet SofuogluDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Peggy ComptonDepartment of Family and Community Health, University of Pennsylvania School of Nursing, Philadelphia, PA, USA.
Mohini RanganathanDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8412-2923
Brian PittmanDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Joao P De AquinoDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. joao.deaquino@yale.edu.ORCID http://orcid.org/0000-0001-7357-8215

Funding

Combination of THC and CBD as a Novel Treatment for Co-Occurring Opioid Addiction and Chronic PainR01DA060066 · YALE UNIVERSITY · 2025 to 2025
$455k
Cannabidiol Pharmacotherapy for Comorbid Opioid Addiction and Chronic PainK23DA052682 · YALE UNIVERSITY · 2025 to 2025
$192k
NIDA NIH HHS K23 DA052682NIDA NIH HHS R01 DA060066U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) K23DA052682U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) R01DA060066
6 · The paper itself

Abstract

Even during opioid agonist treatment (OAT) for opioid use disorder (OUD), chronic pain remains common and unrelieved, as opioids impair endogenous pain modulation. Cannabidiol (CBD) may represent a non-opioid adjunct, but its effects among persons with co-occurring OUD and chronic pain receiving OAT are unknown. We conducted a randomized, double-blind, placebo-controlled crossover study evaluating acute oral CBD (400, 800, 1200 mg) effects on pain modulation, craving, and cognition among 23 participants (11 female) with co-occurring OUD and chronic pain receiving methadone (mean dose 85.7; SD: 29.7 mg/day). An opioid withholding model assessed CBD effects during two phases: Pre-OAT (delayed methadone dosing) and Post-OAT (following methadone administration). Primary outcomes included conditioned pain modulation (CPM; descending inhibition) and temporal summation of pain (TSP; ascending facilitation) assessed via quantitative sensory testing. Secondary outcomes included heat pain threshold and tolerance, and exploratory outcomes included cue-induced craving and cognitive performance. Pre-OAT, CBD was associated with a significant linear dose-response for enhanced descending pain inhibition (p = 0.034; d'=0.34 at 800 mg, d'=0.59 at 1200 mg). Post-OAT, CBD 1200 mg was associated with significant reduction of heat pain threshold relative to placebo (d'=-0.63, p = 0.017). CBD showed no significant effects on opioid craving. Cognitive performance was preserved across doses and CBD demonstrated a favorable safety profile. Among persons with co-occurring OUD and chronic pain receiving OAT, CBD demonstrated phase-dependent effects on pain modulation-dose-dependent enhanced descending inhibition Pre-OAT but worsened pain sensitivity Post-OAT at higher doses. These findings highlight OAT timing as a critical consideration for CBD-based pain interventions.

Identifiers

PMID42162267
PMCPMC13213852

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.