Evidence map›Paper›PMID 41656401›Full record

ArticlePharmacological reports : PR2026

The Sigma

Elmira Zolali, Mallory Burns, Sebastiano Intagliata, Avi Patel, Nicholas P Ho, Luis F Restrepo, Lea R Gamez-Jimenez, Manuel A Alvarez, Lisa L Wilson, Stephen J Cutler and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmacological reports : PR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Elmira Zolali *Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA.
Mallory Burns *Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1225 Center Drive, PO Box 100484, Gainesville, FL, 32610, USA.
Sebastiano IntagliataDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, 1225 Center Drive, PO Box 100484, Gainesville, FL, 32610, USA.
Avi PatelDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Nicholas P HoDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Luis F RestrepoDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Lea R Gamez-JimenezDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Manuel A AlvarezDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Lisa L WilsonDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Stephen J CutlerCollege of Pharmacy, University of South Carolina, Columbia, SC, 29208, USA.
Lance R McMahonDepartment of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA.
Takato HiranitaDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, Catania, 95125, Italy.
Samuel ObengDepartment of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA.
Christopher R McCurdyDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, 1225 Center Drive, PO Box 100484, Gainesville, FL, 32610, USA. CMccurdy@cop.ufl.edu.

Funding

NIDA NIH HHS DA48353U.S. Public Health Service R01DA058018
6 · The paper itself

Abstract

backgroundMu opioid receptor (MOR) agonists are the primary medication class used to treat moderate to severe pain; however, the ongoing opioid overdose crisis underscores the need for alternatives to MOR agonists for pain treatment. Delta9-tetrahydrocannabinol (THC), a cannabinoid CB1 receptor (CB1R) agonist, and sigma1 receptor (σ1R) antagonists elicit antinociceptive effects albeit less effectively than MOR agonists. Co-administration of σ1R antagonists with THC may offer a safer alternative for pain management.

methodsAntinociception (warm water tail withdrawal in mice and hot plate assays in rats), hypothermia (mice and rats), locomotion (mice), and drug discrimination (rats) assays were employed to evaluate the effects of the σ1R antagonist CM304 alone and in combination with THC.

resultsIn naïve mice, CM304 (ip) shifted the antinociceptive time-effect function of 32 mg/kg (ip) THC upward. Similarly, greater hypothermia was observed with combinations of THC and CM304 than each compound alone. Only the high dose of CM304 (56 mg/kg) induced hypolocomotion. In naïve rats, CM304 (1.0 and 3.2 mg/kg, iv) dose-dependently shifted the antinociceptive dose-effect function of THC to the left. In rats trained to discriminate THC (3.2 mg/kg, ip), CM304 (10 and 17.8 mg/kg) did not elicit THC-like discriminative stimulus effects. In contrast to the antinociceptive experiments, CM304 (10 mg/kg) did not significantly shift the discrimination dose-effect function of THC. These results suggest that σ1R antagonists like CM304 can potentiate the antinociceptive effects of THC without potentiating its adverse effects, supporting their potential as adjuncts to CB1R agonists for acute pain treatment.

Indexed as

AnalgesicsCannabinoid Receptor AgonistsDronabinolReceptors, sigmaAnimalsDose-Response Relationship, DrugDrug SynergismHypothermiaMaleMicePainPain MeasurementRatsRats, Sprague-DawleyReceptor, Cannabinoid, CB1Sigma-1 ReceptorAnalgesicsCannabinoid Receptor AgonistsDronabinolReceptor, Cannabinoid, CB1Receptors, sigmaSigma-1 ReceptorAntinociceptionCannabinoidCM304Drug discriminationSigma1 receptor

Identifiers

PMID41656401

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.