26 November 2007

Is methadone cardio-protective or cardio-toxic? Probably neither.

Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B. Physician Awareness of the Cardiac Effects of Methadone: Results of a National Survey. Journal of Addictive Diseases 2007 26;4:79-85



Dear Colleagues,
Krantz and colleagues� latest foray into the purported cardiac consequences of methadone treatment has mixed messages. Their survey of methadone clinics finds a majority of clinicians have not heard of what might be termed �Krantz syndrome�. The paper states that �only 41% (95% CI, 37- 45) were aware of methadone�s QT-prolonging properties.� Yet further: �emerging evidence suggests [methadone] may � prolong the QT interval.� But then again more forcefully: �methadone is now categorized as a medication definitively linked with torsade de pointes ��. Are they having a bet both ways on causality? The evidence on this is conflicting as Martell apparently found a significant association between dose and QT interval where Peles, Kreek et al found no such correlation, including blood levels, in a large study from Israel. Krantz and colleagues fail to cite the Peles study although it was available on the net in early December 2006.
Most reports of QT prolongation in methadone patients, eg. Pearson; Walker; Krantz; Ehret, involve (1) �mega-doses� (>300mg daily), (2) other cardio-toxic drugs, (3) abnormal metabolic states (such as hypokaloaemia) and/or (4) heart disease. Only a small minority of reported cases could be termed �regular� methadone clinic patients from my reading. And yet it is these very patients for whom Krantz gives advice to avoid methadone if possible and when it is used to avoid �high� doses.
To most dependency researchers, �high dose� means more than 100mg daily. For discussion of QT problems �high dose� would appear to mean more than 300mg daily, with the highest reports nearly 2000mg daily! The mean daily dose in Krantz� original study was 397mg; Pearson 410mg; Walker >600mg. These are not the sort of doses dependency clinics are usually familiar with.
Since so many of the cases quoted by Krantz refer to pain management, it is surprising that this survey only involved addiction centres.
This whole exercise seems to ignore the consequences of NOT giving methadone - which about 1 million people world-wide receive today. For most there is no alternative, at least none that would be affordable. Even if methadone were a cause of cardiac complications, Krantz gives us no clear strategy to prevent them, short of forgoing treatment with methadone altogether or giving lower (and therefore sometimes inadequate) doses. Hence, apart from raising anxiety levels, it is hard to see how Krantz�s long campaign on this subject has contributed to the field. It is likely that his perspective would be broadened if he had collaborated more closely with dependency specialists. The advice he is giving to the field is contrary to almost all established guidelines which stress adequate doses of methadone to reduce harmful injecting behaviour as a high priority public health strategy.
In Lancet Krantz quotes a study of methadone related deaths to justify focusing on this issue. Yet this study finds that only 4% of the deaths occurred in patients in addiction treatment programs (Ballesteros 2003), and there was absolutely nothing to suggest that cardiac effects played any role in those deaths.
It is still likely in my view that the reduced level of cocaine and heroin use with higher methadone doses shown by Dr Lisa Borg some years ago should actually protect against cardiac arrhythmias - to say nothing of the many other life-threatening concomitants of illicit heroin use, most notably overdose. Others have written about the cardio-protective effect of methadone and the opioid system in ischaemic heart disease (Marmor; Dickson).
Adding to the confusion, while stating that doctors should take account of this syndrome when prescribing methadone, Krantz still does not recommend routine ECG before starting methadone treatment. Ellen Pearson agrees with this assessment in her paper with Woosley, stating further that limiting the dose of methadone is unlikely to completely avoid cardiac complications. As far as I am aware nobody has yet reported a series of cases of cardiac arrhythmia in �normal� methadone patients, so how can this be a public health issue?
Although Pearson�s 59 FDA reports did not specify whether methadone was prescribed as part of an addiction program or otherwise, one may deduce that no more than 14 of the cases would likely have been �normal� clinic patients and only one death occurred in this group in a patient reportedly taking 29mg daily. I understand that few clinics would be able to measure out a dose of 29mg, raising the possibility that this is a mistake or a typo on the FDA report. Even as Krantz states that the FDA reports are an underestimate of the prevalence of this complication, there are still only the most sparse number of cases considering well over a million Americans have been on the treatment over the years (~240,000 currently). I also note that of 5 deaths in Pearson�s excellent report, only one of them had torsades, the fatal arrhythmia associated with QT changes, raising the possibility that there was only one cardiac death out of 59 cases over a period of years.
In my view the majority of prescribers in this survey who had not heard of QT changes were more likely to give better treatment to their patients than the �enlightened� minority who may have tried to take heed of Krantz�s sentiments.

Comments by Andrew Byrne ..



I note that of 7 web citations in this paper, 6 did not link to the correct (or indeed any) site. This may be a common problem with changes to web addresses yet it must also be a weakness of a scientific paper when peer-reviewed published citations are always to be preferred where possible in my view.

Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B. Physician Awareness of the Cardiac Effects of Methadone: Results of a National Survey. Journal of Addictive Diseases 2007 26;4:79-85

Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753

Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915-8

Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients - a cross-sectional study. Addiction 2007 102;2:289-300

Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Increase in Deaths Due to Methadone in North Carolina. JAMA 2003 290:40

Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368:556-557

Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366

Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504

Walker PW, Klein D, Kasze L. High dose methadone and ventricular arrhythimias: a report of three cases. Pain 2003 103:321-4

Ehret GB, Voide C, Gex-Fabry M, Chabert J et al. Drug-Induced Long QT Syndrome in Injection Drug Users Receiving Methadone High Frequency in Hospitalized Patients and Risk Factors. Arch Intern Med 2006 166:1280-1287

Marmor M, Penn A, Widmer K, Levin R, Maslansky R. Coronary artery disease and opioid use. Am J Cardiol. 2004;93:1295-1297

Dickson E et al. �Runners high� may protect against myocardial infarction. Am J Physiol Heart Circ Physiol 2007; Advance online publication

20 November 2007

Management of the Narcotic Addict (Halliday R. 1963)

Below is the text for the VERY FIRST description of methadone in the treatment of addiction, two years before Dole’s publication. Note that Dr Halliday recommends 40mg in divided doses for the first three days then 30, 20 and 10mg over 12 days for detoxification with some patients needing treatment over a longer period of weeks or months under supervision and with appropriate safeguards and psychosocial support. He does not state why he recommends methadone, only that he does and in the absence of any other opioid. I have included a citation and abstract for a subsequent paper co-authored by Halliday describing their experience with methadone in Vancouver from 1959 to 1964 for both short and longer term prescribed patients. This is all insightful and way ahead of their time in my view. Yet it in no way detracts from the work of Dole and Nyswander who I understand were unaware of this work in 1963 when they were doing similar things in New York City - but without the stated aim of abstinence. AB ..


Halliday R. Management of the Narcotic Addict. 1963 British Columbia Medical Journal 5(10):412-414


In recent years there has been a change of opinion as to the nature of problems of the addict, and it is now generally accepted that the addict is a sick person physically, psychologically and socially, and as such requires medical and other treatments. The practising physician should be, as in other areas of medicine, a member of the treatment team, and it is assumed that there will be an increasing demand on his time and skill in this held of treatment.

According to Press and Parliamentary reports, the Minister of National Health and Welfare, Miss Judy La Marsh, has stated there is not any legal barrier against the prescribing of narcotics by a physician for an addicted person, provided that such treatment is directed toward withdrawal from narcotics and eventual abstinence. In other words, treatment is not to be considered as continued maintenance therapy on narcotics unless all other measures have been attempted and have failed. References are frequently made to the so-called “British System’ and it is believed that the small number of drug addicts in the United Kingdom is due to this system — the system being that of drug maintenance. This belief is erroneous and it might be pertinent at this time to state the facts since this might help to clear the confusion that exists in many people’s minds about this situation,

In 1955 Mr. J. H. Walker, who was then the United Kingdom delegate to the United Nations Narcotic Commission referred to his government’s attitude to drug addicts and their treatment in his submission to the Canadian Senate Committee enquiring into the use of narcotic drugs in Canada. He made a number of points quite clear; namely:

1. The policy of the Government was based on the recommendations of the Committee appointed in 1924, and headed by Sir Humphrey Rolleston, to advise the Ministry of Health on the implementation of the Dangerous Drugs Act. (This committee maintained, with few exceptions, addiction to morphine and heroin should be regarded as a manifestation of a morbid state, and not as a mere form of vicious indulgence), That the policy did not include the mistaken notion, held by many people, that addicts should be regularly supplied with drugs on a maintenance basis. A memorandum to physicians from the Ministry of Health included this statement: “the continued supply of drugs to a patient, either direct or by prescription, solely for the gratification of addiction is not regarded as a medical need.”

The Rolleston Committee concluded that morphine or heroin might properly be administered to addicts in the following circumstances:
(a) where patients are under treatment by the gradual withdrawal method with a view to cure;
(b) where it has been demonstrated that after a prolonged attempt at cure that the use of the drug cannot be safely discontinued entirely on account of the severity of the withdrawal symptoms produced;
(c) where it has been clearly demonstrated that the patient, while capable of leading a useful and relatively normal life when a certain minimum dose is regularly administered, becomes incapable of this when the drug is entirely discontinued.

The physician is the only person who interprets these recommendations, particularly the last one, in regard to the treatment of his patient, and it is because of misunderstanding about this that the concept of a “British System” in terms of maintenance therapy for all addicts has become a widely accepted, however erroneous, belief. This belief is another one of the legends that confuse ideas about the problem of narcotic addiction. Other legends include beliefs that British addicts are registered for treatment and that there are ‘drug clinics set up by the Government to which addicts report regularly for their drugs, either by drug supply or by prescription. Reliable investigators like Schur (2) and Brill and Larimore (3) have demonstrated that there is no such thing as a “British System” for these addicts and one agreed that the narcotic problem in the United Kingdom is a relatively minor one, largely owing to social and cultural factors rather than to superior legislative controls. The most significant and different attitude however is that of accepting the addicts as a sick person rather than a criminal.

In this country, as in the United States, the absence of community treatment facilities must he directly related to the social concept of the addict as a criminal first, and a sick person second. All available statistics from the treatment centres located in correctional institutions indicate that not more than 5% - 10% of addicts have been helped to abstain following such treatment alter a suitable follow-up period - say, 5 years. (4) One of the major drawbacks in such treatment programs, which within the institutional setting have been well developed in many instances, has been the lack of adequate follow-up and rehabilitation in the community as well as the lack of community facilities at which the addict might seek treatment in the first instance. The medical practitioner (and this is particularly true in the United States) has been threatened, and in many cases prosecuted, if he prescribed narcotics for addict patients when such patients were not in a hospital or clinic. It is true that it is extremely difficult to treat many addicts unless they are in a dosed setting such as a hospital or clinic and that ambulant treatment, as this has been practised in the past, is unsatisfactory. However it is not illegal to treat the patient on an ambulant basis. This being so, the physician may properly prescribe narcotics or other drugs for the treatment of the addict provided that such treatment is part of a more comprehensive program designed to help the addict eventually abstain from the use of narcotic drugs.

As it is not possible in most areas to admit the addict into a general or psychiatric hospital for the treatment of his addiction as such, it is suggested that the physician should do whatever he can to establish and maintain contact with the addict patients in his practice. The physician may need help from other colleagues, agencies and so on to ensure that a comprehensive treatment program is established for his patient. He can initiate a gradual withdrawal program by the administering of suitable drugs, either directly or by prescription. Such drugs may require to be dispensed on a daily basis or be given to a “sponsor” or “chaperone” where the patient is incapable of proper self administration, and this has been the practice at the Narcotic Addiction Foundation of B.C. A typical drug withdrawal program is as follows:
1.
Tabs. Methadone 10 mgms. q.i.d. x 3 days, then
10 mgms. tid. x 3 days
10 mgms. bid. x 3 days
5 mgms. bid. x 3 days
2.
Tabs. Perphenazine 4 mgms. t.i.d. 6 hourly
4 mgms. x 12 days
3.
Chloral Hydrate Grs 7½ @ H.S. x 12 days

In selected patients a more gradual withdrawal program is set up, during which the patient may have narcotics (methadone) prescribed on a continuing basis over a period of weeks or months. Such a program demands careful selection of patients who are considered to have good motivation and prospects for rehabilitation, and also requires close and continuing supervision of the therapist or therapists concerned. It follows that narcotics are not then being prescribed in such instances ‘solely for the gratification of addiction’, but are being used because they are considered to be necessary in the overall treatment of the patient. A comparable situation might be the continuing and controlled prescription of tranquillisers to severely mentally ill patients, who are thereby able to live and function in the community, rather than to be hospitalized. In the last analysis the responsible physician determines his treatment program in the light of what is considered to be sound and ethical medical practice. Some clarification on this is required from the national and provincial Colleges of Physicians and Surgeons.

During the program of withdrawal medication, whether rapid or prolonged, the medication is constantly under review, and if necessary altered to suit the patient’s needs - e.g. depression may become a prominent and severe symptom, and anti-depressants may require to be introduced to alleviate this condition.

Other needs of the patient are explored by the psychiatric and social work staff of the Narcotic Addiction Foundation, and attempts are made to understand these and to develop a suitable treatment program around meeting these or giving the patient adequate support until his problems can be dealt with in a more satisfactory manner. Where in-patient treatment is desirable, the patient is admitted to the nine bedded unit available for this purpose. With such a small number of beds delays in admission for such treatment are unavoidable.

It is intended to make further communications on this complex problem of drug addiction but it is hoped that this introductory statement may be of some help to those physicians who are interested and are anxious to participate in the treatment of this problem which has made such extensive inroads into our own community.

If further information is desired please address enquiries to:
The Narcotic Addiction Foundation of B-C.
640 West Broadway, Vancouver 9, B.C.
or Telephone TRinity 9-4585

REFERENCES

1. Proceedings of the special committee on the Traffic in Narcotic Drugs in Canada.
Queen’s Printer, Ottawa, 1955, pp. 362-363.

2. Schur, E. M. Narcotic Drug Addiction in Britain and America. Indiana University Press, 1962, p. 316.

3. Larimore, G. W. and Brill, H.
On the Site Study of the British Narcotic System Report to Governor Nelson Rockefeller, New York, 1959, pp. 23-26.

4. Pescor, M. J. Follow-up Study of Treated Narcotic Drug Addicts. U.S. Public Health Report Supplement 170, 1943, pp. 1-18.

5. Hunt, O. H. and Odoroff, M. Follow-up Study of Narcotic Drug Addicts After Hospitalization. U.S. Public Health Services Report, Volume 77, No. 1, Jan., 1962, pp. 41-54.



Paulus I, Halliday R. Rehabilitation and the Narcotic Addict: Results of a Comparative Methadone Withdrawal Program. CMAJ 1967 96:655-659

The purpose of this retrospective study was to compare (1) regular methadone withdrawal treatment and (2) prolonged methadone withdrawal treatment in 105 and 71 voluntary patients respectively, who attended the Narcotic Addiction Foundation (N.A.F.) between 1959 and mid-1964. Treatment consisted of individual counselling and medical care for all, and only residential care and psychiatric assessment for selected cases. The number of treatment sessions and the details of drug therapy are described.

One hundred and fifty-three of 176 patients (87%) were interviewed approximately one to five years after the first clinic contact. Forty-three per cent showed some overall improvement in their behaviour. Rehabilitation was defined as change in a specific area, drug use, work, criminal behaviour, community associations, friendship patterns and family relationships rather than in terms of abstention from drugs only. Age affected comparative results.

10 November 2007

Lancet items relating to cannabis regulation versus cannabis harms

Dear Colleagues,

Degenhardt, Hall and colleagues� Lancet letter is the only one this week to be classified �premium content� and thus is not available to casual �browsers� like myself. Yet once read, it seems to be almost the last word on the subject of cannabis harms. This debate has been raging in England since 1995 when Lancet famously wrote: �The smoking of cannabis, even long term, is not harmful to health.� This was both incorrect and unhelpful in a difficult area needing clarity, not bland over-simplifications. In the past, Hall has written similar sentiments � but in a more guarded and scientific manner along the lines of �For a majority of users, cannabis causes few if any adverse health consequences.� But this is a long way from saying it is harmless.

And from the current state of knowledge, summarised in this week�s insightful letters, we can now say confidently that the legal status of cannabis is not related to the rate of its use, harmful or otherwise. To quote: �Cannabis use changed at similar rates across States irrespective of these [differing] penalties. This finding strongly suggests that other factors - such as social attitudes and perceived harms - are more important drivers of consumption than penalties for use.� Regarding Australian jurisdictions, �about half have criminal penalties for possession or use, and the remainder have fines�.

As Degenhardt and colleagues rightly state, more serious than the small risk of psychosis is the 16% risk of dependence in young people using cannabis. Further, as Macleod points out in his letter, respiratory symptoms both from tobacco mixed with cannabis and even cannabis alone, also loom large as good reasons to advise young people to avoid cannabis.

Comments by Andrew Byrne ..



Degenhardt L, Hall WD, Roxburgh A, Mattick RP. UK classification of cannabis: is a change needed and why? Lancet 2007 370:1541

Zullino DF, Rathelot T, Khazaal Y. Cannabis and psychosis. Lancet 2007; 370:1540

Macleod J, Oakes R, Copello A, et al. The psychosocial sequelae of use of cannabis and other illicit drugs by young people: systematic review of longitudinal, general population studies. Lancet 2004; 363: 1579-1588

Moore THN, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319-328 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611623/abstract

Editorial. Rehashing the evidence on psychosis and cannabis. Lancet 2007; 370:292 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611337/fulltext

http://www.thelancet.com/journals/lancet/article/PIIS0140673607611350/fulltext

8 November 2007

Drug and Alcohol Dependence, December 2007. Some interesting titles.

Alcoholic monkeys, clinic accreditation, ‘antagonists’ fail opiate and cocaine users (again), methadone success in US prisoners, buprenorphine/benzo interactions and hep C.


Dear Readers,

Some of you have written to enquire after my health. In fact my internet silence in recent weeks is due to the wasteful, costly and time consuming exercise of practice accreditation. Most health care providers are now subject to this exaction, yet few such interventions could be less productive than for addiction treatment providers in New South Wales. We are routinely assessed by well meaning people who have never written a prescription. Imagine a pharmacy or fire brigade being accredited by non-pharmacists or non-fire officers?! And there is no determination as to whether the right patients are getting the right dose of the right drug! That is a state Health Department responsibility, we are told, yet there is only one single inspector for the entire state! Sadly many addiction patients in NSW receive relatively poor care. Some receive inadequate doses and no access to take-away doses, contrary to the Federal treatment guidelines’ advice that such dosing improves outcomes significantly where used appropriately.

So getting back to a list of meaty scientific titles has been a great pleasure, this time the December edition of Drug and Alcohol Dependence, the largest circulation American addiction publication.

It is nice to see familiar names coming up in the research literature. Some one has never met, others one may have met at conferences, others still have become real friends over the years. In this edition alone we find Cicero, Grabowski, Mitchell TB, Lintzeris, Ciraulo, Strang, Schwartz RP, Dolan, Dore, Westcott, Wodak, Vlahov, Inciardi, Degenhardt, Grulich, Kaldor, Kippax, McCance-Katz, Comer and Nunes. This is a breathtaking array of scientific talent and it is quite something that they would all be represented in a single edition of a medical journal.

Several titles immediately caught my eye so I glanced at their abstracts. Hence I would advise those interested to obtain the full article where appropriate. As ever, there are repetitive themes popular with funding authorities despite usually come up with the same outcomes. Many do not learn from history and keep trying the same thing, hoping for different results. Albert Einstein said this was a form of madness.

Various medications have been tried in cocaine users but researchers seem to ignore the fact that most cocaine users are in for a good time. As such, they are unlikely to continue with a drug which gives them a ‘bad time’ (reserpine makes many normal people feel ill, so why give it to cocaine users?). Likewise the same group from the University of Cincinnati, tried tiagabine in yet another costly RCT with no significant difference (placebo does not give much of a predictable ‘good time’ either!).

Next we learn of yet another study showing that oral naltrexone does not work for relapse prevention in heroin users. Yet this new observational study, with some ethical issues to my mind, shows one marginally interesting finding. The failure rate of 70% in those who ‘tested the block’ (relapsed while still taking the naltrexone) was even worse in those who had waited for the block to wear off where a 90% drop-out rate was found. Is this a joke? Or are 70-90% failure rates encouraging enough to warrant more research?

Next we have a report of what should be the very last RCT of methadone treatment, this time in pre-release prisoners in Baltimore. Jail inmates have never been considered quite the same as others regarding medical and psychiatric needs in many parts of the world, including China, Russia, Cuba and America. So now we know that methadone also ‘works’ in pre-release prisoners. And even American prisoners … surprise, surprise! This was introduced into NSW prisons over 20 years ago, initially as a pre-release measure like in this trial. It has consistently produced enormous benefits for the entire community at very modest cost. Along with some other quite backward things in our state, this is one innovation we can be proud of and which is now being slowly copied around the world.

Next we have a fascinating item in which mature monkeys were found to enjoy alcohol with flavouring and to cut down their voluntary intake significantly when accompaniments were altered. Shades of ice-pops and mixers. Hence there seem to be some parallels between us and our close animal cousins. Again, no real surprise here, but gratifying confirmation that humans are not completely unique freaks in the animal kingdom in our desire to be ‘high’.

A group from Australia has done a careful study of the chronological march of the hepatitis C epidemic with very little good news to date. Despite harm reduction measures, treatment availability, education, etc, Australia still has a major public health problem with up to 9,000 new cases each year. More effective interventions might reduce this, as with HIV to hundreds or even dozens.

Another item looks at over 1000 gay men and finds that each year, about 5% started at least once weekly amphetamine use with the same proportion taking up at least once weekly MDMA (ecstasy) use. The proportions would have been very different 10 years ago when ecstasy use would probably have been much more popular. But we now live in the ‘ice age’ as Walter Ling calls it, where Pam Lichty calls it the ‘drug for today’ (which it is!). Yet few researchers have really addressed stimulant use in a logical manner, looking unemotionally at the harms and benefits as perceived by the users and to society generally. This is extraordinary when these drugs have been used across the world for generations now. Anabolic steroids probably fit into the same category and because of their often illicit or unprescribed nature, research is extremely limited and thus advice to the many users of these drugs is necessarily perfunctory: ‘say no to drugs’, keep fit, don’t share needles, don’t use too much, use with a friend, use an injecting room, etc.

Lastly there are two items on drug interactions. We have what might be the first serious report of a significant buprenorphine interaction. Some buprenorphine patients developed sedation on anti-retroviral drugs and needed dose reductions. This is just normal therapeutics, but nice to see it formally reported by a clinical experiment rather than happenstance. Lintzeris reports on giving 20mg diazepam or placebo to methadone or buprenorphine patients in a small RCT with variations in the opioid as well. He concludes: ‘High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine’. No great surprise here, either.

Comments by Andrew Byrne ..

http://www.redfernclinic.com/

http://www.sciencedirect.com/science/journal/03768716

Winhusen T, Somoza E, Ciraulo DA, Harrer JM, Goldsmith RJ, Grabowski J, et al. A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence. Drug and Alcohol Dependence 2007 91;2-3:141-148

Winhusen T, Somoza E, Sarid-Segald O, Goldsmith JR,,,. A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence. Drug and Alcohol Dependence 2007 91;2-3:205-212

Sullivan MA, Garawi F, Bisaga A, Comer SD,,,Nunes EV. Management of relapse in naltrexone maintenance for heroin dependence. Drug and Alcohol Dependence 2007 91;2-3:289-292

Kinlock TW, Gordon MS, Schwartz RP, O’Grady K, Fitzgerald TT, Wilson M. A randomized clinical trial of methadone maintenance for prisoners: Results at 1-month post-release. Drug and Alcohol Dependence 2007 91;2-3:220-227

Katner SN, Von Huben SN, Davis SA, et al. Robust and stable drinking behavior following long-term oral alcohol intake in rhesus macaques. Drug and Alcohol Dependence 2007 91;2-3:236-243

Razali K, Thein HH, Bell J, Cooper-Stanbury M, Dolan K, Dore G et al. Modelling the hepatitis C virus epidemic in Australia. Drug and Alcohol Dependence 2007 91;2-3:228-235

Prestage G, Degenhardt L, Jin F, Grulich A, Imrie J, Kaldor J, Kippax S. Predictors of frequent use of amphetamine type stimulants among HIV-negative gay men in Sydney, Australia. Drug and Alcohol Dependence 2007 91;2-3:260-268

McCance-Katz EF, Moody DE ,,,. Interaction between buprenorphine and atazanavir or atazanavir/ritonavir. Drug and Alcohol Dependence 2007 91 2-3:269-278

Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J. Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients. Drug and Alcohol Dependence 2007 91;2-3:187-194