Crossing the Blood-Brain Barrier? FDA Requires an Abuse Potential Assessment

Life Sciences, Clinical Trials, Pharmaceutical Regulation, Pharmaceutical, Drug Discovery & Development, Drug Safety,
  • Thursday, June 28, 2018

Developers of drugs with central nervous system (CNS) activity rightly focus on physical safety and efficacy first, particularly in the case of products intended for rare disorders or diagnoses often unresponsive to existing therapeutic options. These products may have little if any apparent CNS mediated effects, but crossing the blood-brain barrier is sufficient to trigger the FDA requirement for an abuse potential assessment.

It is widely understood that drugs under development for the treatment of CNS disorders, including pain, will require abuse potential assessment, but many substances that are not intended for treatment of CNS disorders may also require some level of assessment. Examples of categories that might trigger an abuse potential assessment include certain dietary supplements, cannabinoids, atypical antipsychotics, antidepressants, antiepileptics, novel analgesics and other drugs that primarily act peripherally, and even chemotherapies, that enter the brain and interact with receptors that are known to modulate abuse-related effects.

To avoid delays and unexpected costs late in development, drug development timelines need to take into consideration the 2017 FDA Guidance on Assessment of Abuse Potential of Drugs, which indicates that all CNS-active drugs will need some level of abuse potential assessment.  While an assessment on the level that would be expected for an analog of an opioid, stimulant, or sedative would not necessarily be required for every drug candidate, at least some level of assessment would be expected to characterize the drug’s abuse potential as part of the safety evaluation of the substance. Nonclinical safety assessments and human data from early trials can be useful to collect early on. This would also allow time to meet with regulators for an early opinion as to the range of studies needed to properly assess abuse potential rather than waiting until the middle or end of Phase III studies. These abuse potential assessments may also provide early indication of the potential need for risk management programs to monitor and/or reduce abuse.

In this session, presenters will focus on the role of an abuse potential assessment (also referred to as the Controlled Substances Act 8-factor analysis) in the development of CNS-active drugs and related interactions with FDA and DEA.

Topics will include:

  • Definitions and studies for assessment of abuse potential, from nonclinical to clinical
  • Practical application of FDA guidance on Assessment of Abuse Potential of Drugs
  • Optimal timelines for abuse potential of CNS-active drugs
  • Regulatory timelines and abuse potential assessment
  • Examples of drug and dietary supplement categories that may trigger an abuse potential assessment

This webinar is the first of a 2-part series. Click here for information about Part 2.


Jack Henningfield, Ph.D., Vice President, Research, Health Policy, and Abuse Liability, PinneyAssociates

Jack E. Henningfield is one of the world’s leading experts on addiction, and the behavioral, cognitive, and central nervous system (CNS) effects of drugs. He headed clinical pharmacology and abuse potential assessment at the National Institute on Drug Abuse (NIDA) where his responsibilities included Controlled Substances Act (CSA) abuse potential and drug scheduling recommendations. His NIDA Clinical Pharmacology laboratories conducted pioneering assessments of cannabis abuse potential and effects. He counsels clients on assessment of the abuse liability of new CNS-acting drugs and formulations, evaluation of potential application of the Controlled Substances Act to new products, assessment of the tamper resistance of novel formulations, and development of risk management approaches. Jack frequently liaises with the Food and Drug Administration on issues concerning drug scheduling and addiction, and has presented frequently to FDA Advisory Committees. He has contributed to numerous comments to FDA on topics including prescribing of opioids for chronic pain, development and regulation of abuse-deterrent opioid formulations, and abuse potential assessment.

Message Presenter

Reginald Fant, Ph.D., Director, Clinical Pharmacology and Abuse Potential Assessment, PinneyAssociates

Dr. Fant has a background that includes nonclinical and clinical research on the abuse liability of a broad range of substances of known and suspected abuse potential (including opioids, stimulants, sedatives, cannabis, nicotine, and alcohol), as well as laboratory studies of marijuana and potential tobacco and opioid use disorder treatment medications. Dr. Fant has written literature reviews, reports, and peer-reviewed articles on topics such as abuse liability of prescription and over-the-counter medications, nicotine replacement, smoking cessation medications, and new product development. He advises developers of prescription and OTC medications, as well as cannabinoids and dietary supplement clients on abuse liability and drug scheduling issues. He also participates in meetings with the Controlled Substances Staff at FDA on behalf of Sponsors and prepares FDA submissions including meeting briefing packages and abuse potential assessments often referred to as 8-Factor Analyses.

Message Presenter

Who Should Attend?

Mid and senior-level professionals responsible for clinical and regulatory affairs and the clinical development of CNS-active drug products.

Relevant areas of expertise include:

  • Regulatory affairs
  • Drug safety/pharmacovigilance
  • Risk management
  • Project management
  • Clinical research
  • Commercial
  • Medical

What You Will Learn

  • Abuse potential assessment in the context of drug products for products that cross the blood-brain barrier, but not typically considered as having abuse potential
  • The Final FDA Guidance to Industry on Assessment of Abuse Potential of Drugs
  • The role of abuse potential assessment and the 8-factor analysis in drug scheduling and control
  • Studies to assess abuse potential of CNS-active products during the development cycle
  • How to leverage assessment results to support appropriate scheduling and patient access

Xtalks Partners


PinneyAssociates helps our pharmaceutical and consumer healthcare clients to reduce their regulatory risk and enhance the commercial and public health value of their life sciences products. During the past 40 years, PinneyAssociates experts have advised and served with pharmaceutical companies, the National Institute on Drug Abuse, College on Problems of Drug Dependence, the Food and Drug Administration, and others in the development of comprehensive abuse potential assessment, tamper testing of abuse deterrent formulations, and risk management for CNS drugs.

PRA Health Sciences

PRA Health Sciences delivers innovative drug development solutions that improve patients’ lives. Our people love what they do, working tirelessly for clients across all phases and therapeutic areas. With 13,000+ employees covering 85+ countries, we provide an impressive global presence and in-depth knowledge of local regulations, standards of care and cultural customs.

With a wealth of experience across neurological, psychiatric, and analgesic drug development, including pediatric and rare indications. PRA Health Sciences is an industry-leader in providing innovative clinical research solutions. PRA has carried out the pivotal trials leading to the approval of 20 drugs for the treatment, prevention and cure of neurological, psychiatric and pain disorders under the expert guidance of the 15+ Board Certified Neurologists and Psychiatrists we have on staff. We are dedicated to gathering quality, actionable data to advance clinical research, with a strong focus on the patient journey.

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