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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

N-ICE Trial
Date Commenced:
Expected Date of Completion:
Project Supporters:

The N-ICE trial is funded by the National Health and Medical Research Council (Project Grant No. 1128147). This is an independent body that awards research grants on a competitive basis.

Drug Type:
Project Members: 
image - Rebecca McKetin   Lo Rez Uncropped Linkedin
Associate Professor
Ph 02 93850331 (Ext x 50294)
Project Main Description: 

For information on services available in your area please contact the
National Alcohol and Other Drug Hotline on 1800 250 015

In a world first, the N-ICE Trial will study a much needed new approach to treating crystal methamphetamine - or “ice” - dependence.

The N-ICE Trial will establish if N-Acetyl Cysteine (NAC) can reduce craving for ice and help people stop using ice.

Why NAC for ice addiction?

When someone first takes ice, they experience the seemingly desirable effects from being intoxicated with the drug. Then, as they become addicted, there are changes in the brain that cause cravings and make it hard to stop using it.

NAC targets these brain changes that underpin craving and addiction. It helps restore balance to those brain systems, and in doing this, it helps reduce the craving for ice.

Previous studies have shown that NAC can reduce cravings for various drugs, including ice, cocaine, cannabis and tobacco. This trial will find out whether NAC can help people reduce their use of ice or stop using ice altogether.

We also hope that NAC will help reduce the paranoia and mood changes people experience when they become addicted to ice. Some of these symptoms are related to the toxic effects of ice on the brain, and NAC has been found to protect the brain from this toxicity.

Most importantly, we want to make sure that NAC is safe. NAC has been used safely in various other trials, and is an approved medicine for other purposes. We will be assessing whether it is safe take-home medication for people who use ice.

Where is the N-ICE Trial being conducted?

The N-ICE trial is being conducted in Wollongong, Geelong and Melbourne. See below for further details on our study sites and team, or visit us on Facebook

How long will the trial run for?

The N-ICE trial started in mid-2018 and we expect recruitment of participants will continue until the end of 2019. This may vary depending on the trial site. Please refer to your local trial site for more specific details.

How do I enrol in the trial?

Recruitment has now closed. For information on treatment options in your area please contact the  National Alcohol and Other Drug Hotline on 1800 250 015

What does the trial involve?

The trial will involve taking two capsules of NAC morning and night for 12 weeks. During the trial there will be weekly assessments to monitor drug use and mood. All participants must undergo a comprehensive screening interview and medical assessment prior to receiving NAC. Participants must also agree to attend medical assessments during the trial as requested, and a final medical assessment within one month of completing the trial.

Does it cost anything to participate?

Participation in the trial is free.

What happens at the end of the trial?

At the end of the trial, you must have a final medical assessment. We are unable to provide NAC after the end of the trial. However, we will offer you a referral to other services that are available.

Can I get other treatment while I’m on the trial?

Once you are enrolled in the trial, you are free to access other services and treatments provided that this does not prevent you from taking the trial medication, participating in the trial assessments, or put your health at risk. Your trial doctor will make this decision and stop the medication if he or she sees fit.

What if I have a loved one addicted to ice?

Participation in the trial is completely voluntary and each participant must contact us directly to enrol. We cannot take referrals from family, friends, or other health services.

Where else can I get help for ice use?

A number of free and confidential support services are available for people experiencing problems with ice, as well as their family and friends. Call the National Alcohol and Other Drug Hotline on 1800 250 015 to be automatically directed to the Alcohol and Drug Information Service in your state or territory.

For emergency support, call Lifeline on 131 114 or dial '000' for an ambulance or police.

The N-ICE team and trial sites

Our team are an internationally recognised team of researchers who have experience trialling treatments for ice and other drugs, and we have conducted several of the largest trials of NAC in the world. Further details about the trial investigators and their institutions are below.

Associate Professor McKetin, National Drug and Alcohol Research Centre, University of New South Wales.

Dr Olivia DeanDr Alyna Turner and Professor Michael Berk , IMPACT Strategic Research Centre, Deakin University and Barwon Health

Professor Dan Lubman and Dr Victoria ManningMonash University Eastern Health Clinical School and Turning Point

Associate Professor Peter Kelly and Ms Dayle Raftery , Illawarra Health and Medical Research Institute, University of Wollongong and the Illawarra Drug and Alcohol Service (iDAS)

Professor Paul Dietze and Dr Brendan Quinn, Burnet Institute

Dr Peter Higgs, La Trobe University

Professor Gregory Carter and Professor Amanda BakerSchool of Medicine and Public Health, University of Newcastle

Project Collaborators: External: 

Olivia Dean, Alyna Turner and Michael Berk
Deakin University

Dan Lubman, Shalini Arunogiri and Victoria Manning
Monash University

Peter Kelly
University of Wollongong

Barbara Sinclair and David Reid
Illawarra Drug and Alcohol Service

Greg Carter and Amanda Baker
University of Newcastle

Brendan Quinn and Paul Dietze
Burnet Institute

Peter Higgs
La Trobe University


Design and Method: 

This is a two-arm, parallel, double-blind, placebo-controlled, three-site, randomised (ratio 1:1) trial using permuted block randomisation, with variable block sizes, stratified by site, sex and injecting (vs. non-injecting) methamphetamine use. Participants (N = 180; 60 per site) need to be dependent on methamphetamine, interested in reducing their methamphetamine use, and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2,400 mg oral NAC or matched placebo, delivered as a take-home medication for 12 weeks (2 x 600 mg capsules, self-administered morning and evening). Adherence is being monitored using eCAP™ medication bottle lids which record the date and time of bottle opening. The primary outcome measure is methamphetamine use during the 12-week trial medication period measured as (a) days of use, assessed using the Timeline Followback, and (b) methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of methamphetamine craving, severity of methamphetamine dependence, methamphetamine withdrawal symptoms, and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication.


Data collection complete. Analysis underway. People who participated in the trial can expect to receive their individual results soon. If you have questions about your results, please contact your local trial site or email r.mcketin@unsw.edu.au.


Results of the trial were presented at the NDARC Symposium on Thursday November 26th 2020: 


Final results will also be reported on the Australian and New Zealand Clinical Trials Registry for details (ACTRN12618000366257).


Opportunities (Scholarships, Grants and Research Positions): 

Data can be made available from the project to support PhD and post-doctoral research projects.




The N-ICE trial is the first clinical trial to assess whether NAC can reduce methamphetamine use. This trial will provide a platform for understanding the potential utility of NAC in managing methamphetamine dependence and clinically related outcomes. If found to be effective, take-home NAC could provide a potentially scalable and affordable pharmacotherapy option for methamphetamine dependence.


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