Abuse liability assessment refers to the testing of a neuroactive substance for its potential to become a drug of abuse.
Any prescription medicine has the potential to be abused. However, drug products capable of producing rewarding psychoactive effects such as sedation, euphoria, hallucinations or mood changes, are considered to be at greater risk of being used recreationally.
As a result, new drug applications (NDA) for medications that could affect the central nervous system (CNS) must include an assessment of their potential for abuse.
Assessment of abuse liability not only involves a consideration of a drug’s potential for addiction, but a broad range of other factors associated with its potential for misuse, abuse and diversion. These can include the drug’s therapeutic indication, availability and ease of synthesis, as well as the potential for negative outcomes resulting from abuse, such as overdose or toxicity.
A comprehensive package of information is essential in guiding the decisions of pharmaceutical companies, government agencies, healthcare professionals, and ultimately, the patients who use the product.
Increasingly, abuse liability is incorporated early in development to allow for proper risk mitigation. Thus, planning for potential abuse liability should begin at the candidate selection stage to avoid unexpected surprises during early clinical trials.
Evotec uses a two-tiered, integrated approach for its abuse liability assessment programmes.
First, the compound undergoes pharmacological and pharmacokinetic characterisation.
Second, Evotec can then determine and perform the most suitable behavioural studies to unveil a compound’s abuse potential from different perspectives, including:
- Drug discrimination to determine the compound’s similarity with known abused drugs
- Self-administration to understand the compound’s reinforcing properties
- Conditioned place preference as an additional approach to assess a drug’s rewarding or aversive effects
- Physical dependence to analyse the compound’s potential to cause withdrawal symptoms
The scheme below can effectively illustrate this approach:
