A vaccine that can mitigate the addictive effects of the synthetic psychoactive stimulant fenethylline, as well as identify its active chemical components, is demonstrated in a mouse study published in Nature this week. Fenethylline’s unique chemical complexity has prevented previous efforts to identify the specific components responsible for the rapid onset of its distinct psychoactive properties.

Fenethylline, known by the trade name Captagon, is linked to substance abuse and ‘pharmacoterrorism’ in the Middle East. In Saudi Arabia, it has been estimated that 40% of drug users aged 12-22 are addicted to fenethylline.

Kim Janda and colleagues developed a ‘dissection through vaccination’ approach, called DISSECTIV, which vaccinates against the various components found in fenethylline to determine those responsible for the behavioural effects of the drug. This approach identified a functional synergy between theophylline, a drug traditionally used to treat respiratory diseases, and amphetamine, a stimulant, as the chemicals responsible for fenethylline’s distinct effects. Incremental vaccination of mice against components of fenethylline using this approach on days 0, 14 and 28 of the study attenuated its pharmacodynamic effects. The authors’ results demonstrate that incremental vaccination against single chemical species within a multi-component mixture can be used to uncover properties of drugs that act on multiple target or disease pathways. They suggest that DISSECTIV can be used to expose unidentified active chemical species in pharmaceuticals and illuminate how different complex drugs interact with each other.