In part fueled by the Opioid crisis, the assessment of abuse liability is an area of increased scrutiny. An FDA guidance outlines some recommendations on how to assess abuse potential1.  Several recent publications have illustrated how in silico approaches could be applied to this problem.2,3 Such an assessment could be used as part of early screening to prioritize chemicals, as part of the weight of evidence in assessing a testing strategy and to support regulatory questions.

In collaboration with the FDA, we have also been looking into assessing abuse liability through the development of an abuse liability reference database – an important first step. This database includes chemicals with known abuse liability that are identified as part of national or international registries, such as the United States Drug Enforcement Administration (DEA) scheduled drugs list4 or other publications. Marketed pharmaceuticals that are not on any such list, with no other evidence of abuse potential, are used to classify chemicals as having no evidence of abuse liability.

This database containing positive and negative examples is being used to support both a read-across assessment and to generate structural alerts to profile untested chemicals. By integrating other sources of information, it may be possible to perform a more mechanistic assessment of abuse potential.

Please feel free to contact me (Glenn Myatt; if you are interested in collaborating on this interesting and emerging topic.


  1. FDA Assessment of Abuse Potential of Drugs – Guidance for industry
  2. Christopher R. Ellis , Rebecca Racz , Naomi L. Kruhlak , Marlene T. Kim , Edward G. Hawkins , David G. Strauss and Lidiya Stavitskaya, Assessing the Structural and Pharmacological Similarity of Newly Identified Drugs of Abuse to Controlled Substances Using Public Health Assessment via Structural Evaluation CLINICAL PHARMACOLOGY & THERAPEUTICS | VOLUME 106 NUMBER 1 | JULY 2019 doi:10.1002/cpt.1418
  3. James W. Firman, Samuel J. Belfield, George Chen, Megan Jackson, Fai Hou Lam, Callum Richmond,  James Smith, Fabian P. Steinmetz, and Mark T. D. Cronin Chemoinformatic Consideration of Novel Psychoactive Substances: Compilation and Preliminary Analysis of a Categorised Dataset. Mol. Inf. 2019, 38, 1800142. DOI: 10.1002/minf.201800142

Published by Glenn Myatt

Glenn J. Myatt is the co-founder of Leadscope and currently Senior Vice President, In Silico & Translational Science Solutions at Instem with over 30 years’ experience in computational chemistry/toxicology. He holds a Bachelor of Science degree in Computing, a Master of Science degree in Artificial Intelligence and a Ph.D. in Chemoinformatics. He has published 37 papers, 11 book chapters and three books.

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