20 October 2020
‘Vaccine’ against Abu Hilalain
Published online 22 August 2017
A vaccination-based approach enables researchers to understand how the harmful stimulant works.
Researchers have developed a new pharmacological approach to understand the effect of fenethylline, an addictive amphetamine-type drug, once marketed as Captagon, but now banned in most countries.
Widely used in some Arab countries, the fenethylline molecule is a combination of two other drugs, amphetamine and theophylline, but whether fenethylline is psychoactive itself, or simply breaks down into the two constituent drugs, has remained unclear until now.
The findings of a team at the Scripps Research Institute in California, led by Kim Janda, may help improve the management of the drug’s misuse.
Their approach could also be used to investigate the activity of other complex chemicals, such as natural extracts.
While amphetamine and methamphetamine are commonly abused substances in the United States, fenethylline is more common in the Arab world.
Known as Abu Hilalain, fenethylline is the predominant drug in Gulf countries, with roughly 40% of Saudi drug users aged 12 to 22 addicted to it. Fenethylline is reportedly used to motivate fighters in some of the region’s conflicts, and sales of the drug are believed to provide funding for militants.
To investigate this, Janda’s team used ‘drug vaccination’, in which the body is provoked to produce antibodies against a target drug. By binding to the drug, the antibodies block it from reaching the central nervous system and blunt the development of addiction.
The researchers administered multiple drug vaccinations to mice in a ‘dissection through vaccination’ approach to tease apart fenethylline’s key activities.
They found that fenethylline breaks down into its constituents, and the resulting combination is more effective than amphetamine alone. “Once it's metabolized in the body, the two drugs act synergistically and individually to hit their targets at the same time and boost the overall stimulant effect,” explains Janda.
The team hopes that the dissection-through-vaccination approach will be used to investigate pharmacological interactions in other complex chemicals, from natural extracts to antidepressants and antipsychotics.
“When the body processes these chemicals, they typically have a constellation of targets,” says Janda. “Figuring out how they interact with these targets is challenging, and this approach can be used to figure that out and determine which effects are useful and which may be toxic or linked with abuse.”
The vaccine could be adapted to humans to help combat fenethylline abuse.
“It’s too early to say if such a vaccine could work in humans, but this research is a significant scientific advance” says Chara Spiliopoulou, a professor of forensic medicine and toxicology at the University of Athens, who wasn’t involved in the study. She adds that drug vaccines are relatively new biochemical tools which hold a great deal of promise, citing a heroin vaccine that is already being tested in animals.
“Fenethylline is a much more dangerous drug than we previously thought in terms of its psychoactive properties,” says Janda.
According to him, it would take less than a year to modify the vaccine and start tests in rodent models. “If there’s interest, we could use this in humans. We would just tweak some of the components to get an even stronger immune response against the drug and its components.”
- Wenthur, C. J. et al. Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity. Nature http://dx.doi.org/10.1038/nature23464 (2017).