Abuse Liability Assessment

Abuse liability assessment refers to the testing of a neuroactive substance for its potential to become a drug of abuse. At Evotec we have significant expertise and experience to design an abuse liability strategy and deliver all the required studies.

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 preclinical abuse liability should begin at the candidate selection stage to avoid unexpected surprises during early clinical trials.

First, the compound undergoes pharmacological and pharmacokinetic characterization.

Second, Evotec can then determine and perform the most suitable preclinical behavioral 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 analyze the compound’s potential to cause withdrawal symptoms
  

The scheme below can effectively illustrate this approach.

• GLP safety and behavioral assessment (including abuse liability assessment) 
• Consulting on abuse liability strategy including 8-factor analysis
• Evaluation of chemical similarity to drugs of abuse
• Broad range of behavioral studies including: drug discrimination; self-administration; withdrawal; locomotor activity
• Integration of behavioral assessment with DMPK assessment to establish PK/PD relationship

Evotec can deliver all the required studies as integrated development programs addressing benefits such as: 

• Anticipate and address potential issues timely 
• Minimize development time
• Maximize likelihood of success
• Ensure effective team interaction and communication
• Drive program by the right experts through all its phases