An important consideration for the development of new drugs is whether they can be abused - the FDA released a guidance document in January 2017 - detailing considerations in the assessment of abuse potential for drugs.
The document defines drugs that have CNS activity and produce euphoria (or other changes in mood), hallucinations, and effects consistent with CNS depressants or stimulants as having abuse potential. Prior to in-human studies the document advises using chemistry studies, receptor binding studies and second messenger system studies to determine if a drug has CNS activity. Additionally, studies using rats can test addictiveness and other properties further.
It is recommended that abuse potential in humans is only evaluated after the phase 1 and 2 trials have completed: these trials can confirm that the drug is safe and what the optimal dose is. However, CNS related adverse events must be tracked in phase 1 and 2 trials, these can also provide indications on abuse potential.
When running in-human studies it’s recommended that objective physiological measures, like heart rate and blood draws are done in parallel to more subjective visual analogue scales (VAS). Blood plasma levels of the drug can be correlated with subjective feelings/experience of being on the drug. I find this point interesting as the FDA has recently stated: “FDA generally does not recommend the use of a visual analog scale (VAS)”. The more recent sentiment against VAS was outlined in a guidance document released in October 2025 on patient focused clinical outcome assessments.
The VAS that this older guidance document recommends are for “Drug Liking”, “High”, “Stoned”, “Hallucinations”, “Sedation”, “Stimulated”, “Take Drug Again”. If this guidance was revised, I wonder if they’d propose Likert scales instead of VAS.
Additionally, they indicate that cognitive assessments can be used to provide additional safety data and indicators for abuse potential. Specifically, they indicate that they can be used to assess the effects of a test drug on memory, perception, attention, language ability or consciousness.
Finally, a drug should be evaluated for physical dependence, both to potentially update the drugs label, but also to help with scheduling (e.g. schedule II to V).