Abuse liability assessments: Physical dependence

Record Type: Evaluation

Validation: GLP

Models: Rat

Physical dependance test evaluates whether chronic administration of a drug at therapeutic plasma levels produces a withdrawal syndrome (i.e., negative ‘feelings’) upon drug discontinuation. In general, withdrawal effects are the opposite to those seen during dosing, with symptoms typically more severe for drugs with short half-lives. 

Different pharmacological classes of drugs tend to produce different withdrawal syndromes, although there can be overlapping responses. These withdrawal signs are often opposite to the signs observed during drug administration.

The test forms a part of the regulatory required abuse liability assessment for CNS active drugs. Physical dependence should be assessed during the safety evaluation of a drug, and it is also considered to be part of the abuse potential assessment.