Freebasing flies point to new treatments for addiction

The administration of freebase cocaine to fruit flies has uncovered novel pathways central to the development of addiction and may eventually lead to the development of drugs to cure or prevent it.

Prof Jay Hirsh from the University of Virginia talked about his research at a public forum, 'Addiction: what if it's genetic?' held on Sunday as part of the XIX International Congress of Genetics.

Hirsh has demonstrated that flies exposed to freebase cocaine -- the most volatile form of the drug -- develop distinctive motor behaviour including reflexive grooming and circling locomotion. Significantly, the behaviour resembles the effects of cocaine in vertebrate models.

"We see similar motor behaviour in both mice and flies," he said. Using fly genetics, Hirsh and his team have uncovered a number of genes and pathways involved in the addiction process, which then can be studied in more complex animal models like mice, where other addictive behaviour such as rewarding properties can also be investigated.

Among the genes identified are the circadian genes, which control the body's internal clock. Recent work by other scientists has confirmed that circadian genes play in a role in addiction in mice as well as flies, validating Hirsh's approach.

Hirsh said that while these studies were by nature artificial, the results would prove useful for pharmaceutical development as well as providing a greater understanding of the underlying biological basis.

"We see the benefits really as being long term, not short term," he said. "The pathways and genes are being identified as targets for pharmaceutical and biotechnology companies to design inhibitors -- it's a more targeted approach."

Environmental causes

But Hirsh warned that roughly half of the underlying cause of addiction was environmental, not genetic. And the genetic component was likely to be complicated, with small variations in multiple genes leading to greater susceptibility to addictive drugs.

While Hirsh himself has focused on the basic biology of addiction, he noted that pharmaceutical and biotechnology companies were already showing interest in the work performed by his lab and by other scientists.

Prof Wayne Hall, director of the office of public policy and ethics at the University of Queensland's Institute of Molecular Bioscience, said that Hirsh's work could lead to pharmaceutical products able to help people who already had a drug problem, a suggestion welcomed by Monash psychiatry professor Jayashri Kulkarni.

Kulkarni, who is involved in a trial of a drug that blocks the cannabis receptor as a method of curing nicotine addiction, said that most of the treatments commonly used to treat drug addiction, such as methadone or naltrexone, were "total crap".

Les Twentyman, a youth worker also taking part in the public forum, also welcomed the possibility that greater understanding of addiction processes would lead to therapeutic drugs allowing social workers to concentrate on the environmental aspects of drug addiction such as abuse and unemployment.

"We can look at it in terms of a health problem instead of as a law and order problem," he said.

And Prof Loane Skene, from the University of Melbourne's Centre for Law and Genetics, said that a biological propensity to drug addiction could impact on concepts of criminal responsibility.