AB-FUBINACA Produced Dependence Signs Without Measurable Tolerance in a Mouse Regimen
In one mouse experiment, repeated AB-FUBINACA produced antagonist-precipitated withdrawal signs without detected tolerance to the tested dose. Dependence and tolerance therefore could not be treated as the same measurement.
A short-acting synthetic agonist was tested
Investigators studied male and female mice using cannabinoid-related temperature, movement, catalepsy and antinociception assays. AB-FUBINACA is a synthetic cannabinoid-receptor agonist, not THC. Its acute effects were blocked by a CB1 antagonist, supporting receptor involvement.
Withdrawal and tolerance separated
The repeated regimen did not produce detected tolerance to AB-FUBINACA or cross-tolerance to the THC challenge. Nevertheless, rimonabant precipitated somatic withdrawal signs after repeated AB-FUBINACA. That result supports physical adaptation under the tested conditions; it does not estimate how often people experience withdrawal.
A negative cross-tolerance result had an important qualification
The THC challenge used a high dose, and the authors acknowledged that a ceiling effect could mask cross-tolerance. The absence of a detected difference at that dose is weaker evidence than a full dose-response comparison demonstrating unchanged sensitivity. Exposure spacing and route could also influence tolerance development.
Brain detection was not a human clearance rule
Parent AB-FUBINACA was undetectable in sampled brain homogenates four hours after injection, consistent with the short observed time course. That animal-tissue result does not establish zero active metabolites, a human blood-testing window or freedom from impairment. Short-lived measured effects also did not prevent dependence-related signs after the repeated regimen.
Related analysis: Similar Temperature Tolerance Did Not Make THC and JWH Cannabinoids Interchangeable.
Primary research
The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice. Drug and alcohol dependence (2020). DOI: 10.1016/j.drugalcdep.2020.108179.
