By Zoe Taylor

Researchers from the National Drug Research Institute (NDRI) are trialling the efficacy of a promising medication to treat dependence on crystalline methamphetamine, also known as ‘crystal meth’ or ‘ice’.

Australia has one of the highest levels of ice use and dependence in the world. According to the Medical Journal of Australia, since 2010 the number of dependent users in Australia has risen from 72,000 to 160,000, and the number of amphetamine-related hospital admissions and arrests has more than tripled.

In light of this, the multi-institutional research team, led from Curtin by NDRI’s Associate Professor Rebecca McKetin, received a $1.55 million National Health and Medical Research Council grant to conduct a world-first out-patient trial of the medication N-acetyl-cysteine (NAC) to treat addiction to ice.

NAC is an inexpensive medication that has previously been trialled to treat addiction to substances such as cannabis and cocaine, as well as mitigate a range of compulsive behaviours, such as gambling.

“N-acetyl-cysteine has a long use in medicine for other purposes, such as paracetamol overdose and treatment of neuropsychiatric conditions,” McKetin says.

“If found to be effective, this medication has the potential to be a cost-effective treatment option for ice dependence.”

Ice is an addictive and highly pure stimulant drug. It causes a surge in the neurotransmitter dopamine, the brain’s natural pleasure chemical, giving the user intense feelings of euphoria, confidence and energy. Physical effects can include an increase in heart and breathing rates, dilated pupils, a reduced appetite and an increased sex drive.

When ice is smoked or injected, its effects can occur within minutes and usually last between four to 12 hours.

“When they come down from the drug, users feel depressed, paranoid and irritable,” McKetin says.

“This is because the brain’s dopamine levels have been exhausted, creating a short-term deficit while the brain manufactures more. Dependence can occur when users take ice repeatedly to try and regain feelings of normalcy.”

With long-term use, ice can cause changes in the functioning of dopamine and other neurotransmitters, including noradrenaline, which can trigger hallucinations and paranoia. Heavy use can also lead to neurotoxicity of the brain, where nerve terminals start to degenerate due to over-activity.

“The toxicity of the drug in high doses can affect the heart and increase the risk of stroke. It also has a terrible effect on mental health, because those chemicals in the brain that it is acting on constantly, are involved in mood regulation.”

Currently, there is no effective medication to treat addiction to ice, and this is a significant barrier for users seeking treatment. The main form of non-pharmacotherapy treatment is counselling interventions and residential rehabilitation.

For this reason, trialling NAC introduces a novel approach to treating drug addiction: it targets the parts of the brain that reduce cravings, and also protects the brain against neurotoxicity.

NAC helps to reduce cravings by restoring the homeostasis of neurotransmitters in the brain, effectively managing the levels of specific chemicals that regulate the release of dopamine, making it easier for users to manage their desire for the drug. By restoring homeostasis, NAC also protects the brain from over-activity and neural degeneration.

Another key point is that NAC is also relatively inexpensive and can be delivered as a prescribed over-the-counter medication, thereby easing demand on drug treatment services.

“The beauty of NAC is that it works with a whole range of drugs,” McKetin says. “It’s targeting the change in the brain that happens with addiction, rather than the particular substance, so therefore the effects can be carried across different drugs. There are signs of efficacy for tobacco, cannabis, cocaine and meth.”

The N-ICE trial will start in April this year and continue until 2019. It will enable McKetin and her research team to potentially detect a reduction in methamphetamine use and changes in a range of clinical outcomes, such as the agitation and paranoia that people experience when they use the drug heavily.

McKetin says the next steps will be to work out how to use NAC in conjunction with other treatments.

“Once we work out whether NAC can help people to reduce their ice use, the next step will be to work out how to use it in clinical practice.

“What we know from epidemiological data is that even if people don’t stop using altogether, if they reduce their use significantly, we actually see a really big reduction in harms. They are much less likely to have psychotic symptoms, much less likely to get aggressive. So, for us, even a moderate reduction in use would be really good.”

The N-ICE trial will be conducted in collaboration with Deakin University, Monash University, the University of Wollongong, the University of Newcastle, La Trobe University and the Burnet Institute.

More information about the N-ICE trial can be found here.

Health at Curtin

This article features in the 2018 Health at Curtin magazine, an annual showcase of some of the University’s most recent, innovative health research.