The N-ICE trial: A randomised controlled trial of the safety and efficacy of N-acetyl cysteine (NAC) as a pharmacotherapy for methamphetamine ('ice') dependence

Crystal methamphetamine (‘ice’) is a significant and growing public health concern in Australia. An estimated 160,000 Australians are now dependent on methamphetamine. Currently, there are no approved medications to treat methamphetamine dependence.

N-acetyl-cysteine (NAC) is a promising pharmacotherapy for methamphetamine dependence. NAC is a glutamatergic agent that helps restore homeostasis to brain systems compromised in addiction. It has shown signs of efficacy in multiple addictions (cocaine, cannabis and tobacco) and has particular potential for methamphetamine dependence because of its multiple actions, which aid in the management of comorbid psychiatric symptoms, and which protect against methamphetamine neurotoxicity.

A recent Phase I trial (N = 23) of NAC for methamphetamine dependence in humans found a large reduction in craving, good adherence to non-supervised dosing, no serious adverse events, and that NAC was well-tolerated, indicating the need for a Phase II trial.

NDRI, in collaboration with Deakin University, Monash University, the University of Wollongong, the University of Newcastle, La Trobe University, the Burnet Institute and Turning Point, will conduct a world-first, Phase IIb, double-blind randomised placebo-controlled trial (N = 180) to assess the safety and efficacy of NAC as a medication for methamphetamine dependence. This multi-site, 12-week trial will be powered to confirm whether NAC has a clinically relevant benefit on methamphetamine use and a range of related clinical outcomes. The trial will use a pragmatic and inclusive design with feasible implementation procedures that will establish realistic treatment effects and facilitate translation into practice.

Oral NAC is cheap, available as an over-the-counter medication in the USA and the European Union, and can be provided as a PBS schedule 4 medication in Australia, allowing it to be delivered as a prescribed medication with minimal clinical supervision in an out-patient setting. If found to be effective, translation of this medication into practice will have far reaching clinical and public health implications, potentially leading to a cost-effective treatment option for methamphetamine dependence.

Name & Contact Details Role Research Program Location
  • Chief Investigator: Olivia Dean, Deakin University
  • Chief Investigator: Dan Lubman, Monash University
  • Chief Investigator: Paul Dietze, Burnet Institute
  • Chief Investigator: Peter Kelly, University of Wollongong
  • Chief Investigator: Alyna Turner, University of Newcastle
  • Chief Investigator: Brendan Quinn, Burnet Institute
  • Chief Investigator: Gregory Carter, Calvary Mater Newcastle Hospital
  • Co-investigator: Amanda Baker, University of Newcastle
  • Co-investigator: Michael Berk, Deakin University
  • Co-investigator: Barbara Sinclair, Wollongong Hospital
  • Co-investigator: David Reid, Drug and Alcohol Services, Wollongong
  • Co-investigator: Ruth Collins, Drug and Alcohol Clinical Services, Barwon Health

McKetin, R., Dean, O., Turner, A., Kelly, P., Quinn, B., Lubman, D., Dietze, P., Carter, G., Higgs, P., Baker, A., Sinclair, B., Reid, D., Manning, V., te Pas, N., Liang, W., Thomas, T., Bathish, R., Kent, M., Raftery, D., Arunogiri, S. and Berk, M. (2019). A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (ice) dependence. Trials, 20, (1). DOI: 10.1186/s13063-019-3450-0 [RJ1485] View web page

McKetin, R., Dean, O., Baker, A., Carter, G., Turner, A., Kelly, P. and Berk, M. (2017). A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug and Alcohol Review, 36, (2), pp. 153–159. DOI: 10.1111/dar.12414 [RJ1236] View web page