A not-for-profit charity founded by the Australian Medical Procedures Research Foundation Ltd.

Research Links

For background on the research areas which are being investigated by the Fresh Start Research Team, see below:

Naltrexone Implants

‘Improving clinical outcomes in treating heroin dependence: Randomised, controlled trial of oral or implant naltrexone’
Gary K Hulse, Noella Morris, Diane Arnold-Reed, Robert J Tait
Archives of General Psychiatry 2009:66(10); 1108-1115
70 subjects were randomized into two treatment groups. Subjects in the first group received a naltrexone implant (and placebo tablets), while subjects in the second group received naltrexone tablets (and a placebo implant). At 6 months, 83% of the subjects with a naltrexone implant had not returned to regular heroin use. In contrast, only 38% of subjects with naltrexone tablets had not returned to regular heroin use. 
Available here.

‘Comparative treatment and mortality correlates and adverse event profile of implants and sublingual buprenorphine’
Albert Stuart Reece
Journal of Substance Abuse Treatment 2009 37: 256-265
255 naltrexone implant patients and 2518 buprenorphine patients were followed up following treatment. The study showed that although implant insertion is an intensive procedure, it resulted in significantly fewer treatment episodes and substantially longer treatment retention as compared to buprenorphine. Serious local tissue reaction or infection each occurred in 1% of the naltrexone implant patients.
Available here.

‘Histological changes over time around the site of sustained release naltrexone-poly (DL-lactide) implants in humans’
G K Hulse, V Stalenberg, D McCallum, W Smit, G O’Neil, N Morris and R J Tait
Journal of Controlled Release 2005; 108: 43-55
This study looks at the implant site for up to 25 months after the patient has been implanted with naltrexone. It aims to understand how well the implant dissolves, and to detect any problems that may occur in the skin over and around the implant. The study found that the implant does not cause necrosis (breakdown of the tissues around the implant), or acute inflammation, nor does it appear to be rejected as a foreign body, thus making it a safe administration route for naltrexone.
Available here.

‘Naltrexone implant after in-patient treatment for opioid dependence: randomised controlled trial’
N Kunøe, P Lobmaier, J K Vederhus, B Hjerkinn, S Hegstad, M Gossop, Ø Kristensen and H Waal
The British Journal of Psychiatry 2009; 194(6): 541-546
This journal article describes a large trial that looked at how safe naltrexone implants are when used in patients who are opiate dependent. The study found that patients who received the naltrexone implant spent both 45 days free from heroin use, and 60 days free from opioid use, when compared to the controls (patients without a naltrexone implant) over 180 days. The study concluded that having a naltrexone implant not only reduced opioid use in patients, but does so safely.
Available here.

‘Reducing hospital presentation for opiate overdose in patients treated with sustained release naltrexone implants’
Gary K Hulse, Robert J Tait, Sandra D Comer, Maria A Sullivan, Ian G Jacobs and Diane Arnold-Reed
Drug and Alcohol Dependence 2005; 79(3): 351-357
The study aimed to look at the number of overdoses in a group of patients for the six months prior to being implanted with naltrexone, and compared it with the number of overdoses in the same group of people, six months after they received a naltrexone implant. The study found that there were 20 people who had an overdose requiring hospital treatment in the six months prior to receiving an implant, whilst there were no overdoses in the six months after receiving an implant. Thus, the study concluded that naltrexone implants successfully reduce the incidence of overdoses in opiate users.
Available here.

‘Blood naltrexone and 6-beta-naltrexone levels following naltrexone implant: comparing two naltrexone implants’
G K Hulse, D E Arnold-Reed, G O'Neil, C T Chan, R Hansson and P O'Neil
Addiction Biology 2004; 9(1): 59-65
Blood naltrexone levels were compared from patients who received two different sustained release rate naltrexone implants prepared by Go Medical Industries.  Patients who received the higher level implant indicated blood levels and 6-beta-naltrexone levels that were higher compared to the other group, and provided a longer duration of heroin free use.
Available here.

‘Serum naltrexone and 6-beta-naltrexone levels from naltrexone implants can block very large amounts of heroin: a report of two cases’
Colin Brewer
Addiction Biology 2002; 7(3): 321-323
Two clients, with known diamorphine doses, received naltrexone implants and were followed up with regular blood testing, to investigate the minimum levels of 6-beta-naltrexone required to block all opiate effects. Although genetic variances may alter individual responses, results suggested that implanted naltrexone provided antagonist levels similar to those of oral naltrexone, thus eliminating the problems associated with poor oral naltrexone compliance.
Available here.

‘A comparison of oral and implant naltrexone outcomes at 12 months’
R Colquhoun, D Y Tan and S Hull
Journal of Opioid Management 2005; 1(5) 249-256
To assess differences in patient compliance with naltrexone treatment, two groups of patients, treated with either oral or implant naltrexone were compared. Rates of abstinence were significantly higher in the implant treatment group. In both groups, patients who were compliant with the treatment showed much higher rates of abstinence.
Available here.

‘Biodegradability of naltrexone-poly(dl-lactide) implants in vivo assessed under ultrasound in humans’
G Hulse, V Low, V Stalenberg, N Morris, R Thompson, R Tait, C Phan and D Arnold-Reed
Addiction Biology 2008; 13(3/4): 364-374
Ultrasound by independent radiologists, clinical examination (including measurement) and patient self reports were used to assess the biodegradability of the Go Medical sustained release naltrexone implants in 71 humans.  Information gathered provided evidence that the implants changed over time indicating biodegradation and in vivo reabsorption
Available here.

Naltrexone Implants and Hepatitis C

‘Hepatitis C Virus Eradication in Intravenous Drug Users Maintained with Subcutaneous Naltrexone Implants’
G P Jeffrey, G MacQuillan, F Chua, S Galhenage, J Bull, E Young, G Hulse and G O'Neil.
Hepatology 2007; 45(1): 111-117
Intravenous drug users who received a naltrexone implant and were also Hepatitis C positive received antiviral medical treatment.  Successful viral eradication was similar to those found in hospital-based clinics treating non-intravenous drug users.
Available here.

Naltrexone Implants and Pregnancy

‘A possible role for implantable naltrexone in the management of the high-risk pregnant heroin users’
G K Hulse and G O’Neill
Australian and New Zealand Journal of Obstetrics and Gynaecology 2002; 42(1): 104-105
Poor neonatal outcomes are associated with the use of opiates during pregnancy. This paper follows a pregnant heroin dependent person who undergoes rapid opiate detoxification and then is treated with a naltrexone implant. No complications were observed during the pregnancy, her offspring was born at 37 weeks with unremarkable neonatal outcomes and she remained opiate free.
Available here.

‘Methadone maintenance vs. implantable naltrexone treatment in the pregnant heroin user’
G K Hulse, G O’Neil and D E Arnold-Reed
International Journal of Gynaecology and Obstetrics 2004; 85(2): 170-171
This article looks at pregnancy outcomes of patients on methadone maintenance programmes, compared to patients on implanted naltrexone for opioid dependence. The study looked at children born to each group of patients, and compared different characteristics of the babies. It found that children born to mothers with no opioid dependence were healthiest, followed by children born to mothers who were on implanted naltrexone, and lastly were children born to mothers who were in a methadone maintenance program throughout the pregnancy. The study concluded that the safest option for babies whose mothers have opiate addictions is for the mothers to be treated with implanted naltrexone, as opposed to a methadone maintenance programme.
Available here.

Detoxification

‘A comparison of rapid (opioid) detoxification with clonidine-assisted detoxification for heroin dependent persons’
D E Arnold-Reed and G K Hulse
Journal of Opioid Management 2005; 1(1):17-23
This article looked that the two different types of detoxification used in Western Australia: one being used at Fresh Start, known as Rapid Opiate Detoxification (ROD), the other used by other agencies known as Clonidine-assisted Detoxification (CD). Eighty patients underwent either treatment, and it was found that most patients who detoxed via ROD completed the detox successfully, compared to those who detoxed via CD, of which less than one-third completed their detox successfully. The article discusses the success of both treatments, and the reasons behind the differences between both types of detoxification.
Available here.

Naltrexone and Amphetamines

‘Naltrexone for the Treatment of Amphetamine Dependence: A Randomized, Placebo-Controlled Trial’
Nitya Jayaram-Lindström, Anders Hammarberg, Olof Beck and Johan Franck
American Journal of Psychiatry 2008; 165: 1442-1448
A 12-week double blind study was carried out comparing the use of naltrexone for amphetamine use with a placebo group. Results showed that the naltrexone group had a significantly higher level of negative urine samples, significant reduction in craving and self-reported use of amphetamines in comparison to the placebo group.
Available here.

‘An open clinical trial of naltrexone for amphetamine dependence: Compliance and tolerability’
Nitya Jayaram-Lindström, Peter Wennberg, Olof Beck and Johan Franck
Nordic Journal of Psychiatry 2005; 59(3): 167-171
Twenty amphetamine-dependent patients took part in a 12-week trial to assess the feasibility of naltrexone as a potential treatment for amphetamine dependence. Results found that the frequency and amount of amphetamine use was significantly less during the time of treatment in comparison to pretreatment. A larger, placebo-controlled trial was recommended as a consequence.
Available here.

Naltrexone and Alcohol

‘Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting’
Noeline C Latt, Stephen Jurd, Jennie Houseman and Sonia E Wutzke
Medical Journal of Australia 2002; 176(11): 530-534
A 12 week study was conducted with 107 alcohol dependent patients. Subjects were randomly allocated to naltrexone or placebo to determine the effectiveness of naltrexone as treatment. Results showed that naltrexone was effective treatment irrespective of other psychosocial interventions.
Available here.

‘A systematic review of the effectiveness of naltrexone in the maintenance treatment of opioid and alcohol dependence’
Hendrik G Roozen, Ranne de Waart, Danielle A W M van der Windt, Wim van den Brink, Cor A J de Jong and Ad J F M Kerkhof
European Neuropsychopharmacology 2006; 16(5): 311-323
A systematic review summarized the effectiveness of naltrexone in the treatment of opioid and alcohol dependence. Data collected suggested that when combined with cognitive behavioural relapse prevention therapy naltrexone was beneficial for alcohol dependent patients.
Available here.

‘Naltrexone for alcohol dependence: a randomized controlled trial’
Philip L Morris, Malcolm Hopwood, Greg Whelan, John Gardiner and Elizabeth Drummond
Addiction 2001; 96(11): 1556-1573
A 12-week randomized, placebo controlled trial was conducted with 55 male alcohol dependent subjects. Findings showed that naltrexone produced a reduction in consumption of alcohol for those who completed the trial and was considered effective in prevention of relapse.
Available here.

Flumazenil

‘The role of flumazenil in the treatment of benzodiazepine dependence: physiological and psychological profiles’
S Hood, G O’Neil and G Hulse
Journal of Psychopharmacology 2009; 23(4): 401-409
The research has examined benzodiazepine dependant patients treated over a period of 4 days with flumazenil. The research focused on the tracking of withdrawal symptoms, including psychological and cardiovascular measures of 13 patients. No clinically significant complications or major discomfort were observed during the withdrawal phase, with the use of low dose flumazenil reported as a safe and effective method for managing benzodiazepine withdrawals. 
Available here.

‘Intravenous flumazenil following prolonged exposure to lormetazepam in humans: lack of precipitated withdrawal’
G Gerra, G Giucasto, A Zaimovic, G Fertonani, B Chittolini, P Avanzini, R Caccavari and R Delsignore
International Clinical Psychopharmacology 1996 11(2): 81-88
The research examined the use of flumazenil, for benzodiazepine withdrawal, with subjects who had undergone 30 days of treatment with lormetazepam.  Measurements were taken examining balance, subject and observer-rated symptoms regarding the withdrawal. The researchers found there were no significant withdrawal symptoms noted, with a slight increase in anxiety, heart rate and perspiration. The research indicates that flumazenil could re-set the benzodiazepine receptors (GABA-A) and might be an agonist.
Available here.