What topics does this cannabis study cover?

This study covers research on: THC, Addiction.

Where was this research published?

Published in Drug and alcohol dependence on September 6, 2026.

THC Addiction

Repeated CBN exposure caused tolerance and dependence in mice

Q: What did this research study find?

Repeated *CBN* administration produced **tolerance** to catalepsy, antinociception, and hypothermia in mice.

Tolerance, physical dependence, and Δ9-THC-like interoceptive effects of cannabinol in mice.

Drug and alcohol dependence • September 6, 2026 • Highly Relevant

🤖

AI Summary

This animal study examined whether repeated exposure to cannabinol (CBN) produces tolerance or physical dependence, and whether CBN has Δ9-tetrahydrocannabinol (THC)-like effects. Adult C57BL/6 mice received CBN twice daily for five days and were assessed using behavioral tests of catalepsy, pain sensitivity, body temperature, withdrawal, and drug discrimination. A separate group of mice was trained to distinguish THC from vehicle.

Repeated CBN exposure produced tolerance to several cannabinoid-like effects and cross-tolerance to the synthetic cannabinoid agonist WIN 55,212-2. Blocking cannabinoid receptors with rimonabant produced withdrawal-related signs in CBN-treated mice, supporting physical dependence in this mouse model. CBN also fully substituted for THC in the discrimination test, while CBN combined with THC reduced THC's psychoactive effects. Because this was a laboratory study in mice, the abstract cannot establish whether the same effects occur in humans or what they would mean clinically; this is an abstract-based summary, not a full-text review.

💡 Key Findings

Repeated CBN administration produced tolerance to catalepsy, antinociception, and hypothermia in mice.

Limited

35%

Mice repeatedly exposed to CBN showed cross-tolerance to the synthetic CB1/CB2 agonist WIN 55,212-2.

Limited

35%

Rimonabant triggered withdrawal-related somatic signs and increased struggling in CBN-treated mice, indicating physical dependence in this model.

Limited

35%

CBN fully substituted for THC in a drug-discrimination test, showing THC-like interoceptive effects in mice.

Limited

35%

Combining CBN with THC attenuated THC's psychoactive effects, while the tested rimonabant dose was less effective at reducing CBN's effects than THC's effects.

Limited

35%

📄 Original Abstract

BACKGROUND AND PURPOSE: Cannabinoids, including Δ9-tetrahydrocannabinol (THC) and synthetic CB1 agonists elicit acute psychotropic effects that undergo tolerance with repeated exposure. In contrast, the effects of prolonged cannabinol (CBN) use are unknown. This study examined (1) the effects of repeated CBN administration on classic cannabimimetic outcomes, (2) whether these effects undergo tolerance or induce physical dependence, and (3) the THC-like discriminative stimulus effects of CBN, including whether CBN alters THC's discriminative stimulus. EXPERIMENTAL APPROACH: Adult C57BL/6 mice were administered CBN twice daily for five days and tested in the tetrad battery to measure tolerance. On the sixth day, rimonabant was administered and somatic signs of withdrawal (i.e., head twitches and paw tremors) and struggling in the tail suspension test were assessed. Cross-tolerance to the CB1/CB2 agonist WIN 55,212-2 was also assessed in mice repeatedly administered CBN. A separate cohort of mice was trained to discriminate THC from vehicle. KEY RESULTS: Mice displayed tolerance to CBN-induced catalepsy, antinociception, and hypothermia. Cannabimimetic effects of WIN 55,212-2 were attenuated in CBN-treated mice, indicating cross-tolerance. Similarly, rimonabant induced somatic withdrawal signs and increased struggling in CBN-treated mice. Finally, CBN fully substituted for THC. Although rimonabant substantially lowered the psychoactive effects of THC, the specific dose tested was less effective in lowering CBN's psychoactive effects. Administration of CBN plus THC also attenuated THC's psychoactive effects. CONCLUSION AND IMPLICATIONS: These data indicate that repeated CBN administration induces tolerance and physical dependence and that CBN reduces THC's psychoactive effects.

Paper Type

📄 Research

Publication

Journal: Drug and alcohol dependence
Published: September 6, 2026
PMID: 42748645
DOI: 10.1016/j.drugalcdep.2026.113341

Authors (5)

S O Vanegas Elisabeth DeLuca School of Nursing, University of Connecticut, Storrs, CT, USA; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
J A Marusich RTI International, Durham, NC, USA.
J Maturano Department of Chemistry, Rice University, Houston, TX, USA.
D Sarlah Department of Chemistry, Rice University, Houston, TX, USA.
S G Kinsey Elisabeth DeLuca School of Nursing, University of Connecticut, Storrs, CT, USA; Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA. Electronic address: kinsey@uconn.edu.