13 September 2007

Tobacco associated with new mental illness in prospective study.

Smoking is associated with first-ever incidence of mental disorders: a prospective population-based study. Cuijpers P, Smit F, ten Have M, de Graaf R.

Addiction 2007 102:1303-9

Dear Colleagues,

This month�s Addiction journal contains a most important study, almost hidden at the back of an issue packed with other meaty items. For the first time, I believe, the intrepid Dutch group (NEMESIS or Netherlands Mental Health Survey and Incidence Study) has found a significant association between tobacco smoking and mental illness. With up to 80% response rates in over 5000 Dutch adults this study looked at who was smoking and/or had a mental illness at the start, one and three years (along with many other variables).

A significant association found was between smoking and the development of anxiety, dysthymia and new alcohol abuse. Unlike cannabis, no association was found with psychosis. Considering the prevalence of smoking the findings are still highly significant. The prospective nature and accounting for confounders in these findings supports a causal association from the tobacco, yet no dose relation was found. Hence further research will need to look at these areas, according to the authors. Also, a rational pathogenic pathway from smoking to mental disease needs to be confirmed. It may not be a coincidence that some mental illness is increasing in extent and severity in certain countries.

Two other recent studies have apparently shown links between smoking and dementia (Holland; ANU). The Erasmus Medical Centre in Holland found a 50% increase in dementia in age matched smokers. The links with lung cancer and arterial disease are well known. An Adelaide hospital has apparently restricted elective surgery for those who continue to smoke. This month�s Addiction journal reports the same thing from the NHS in Leicester, England (p1331). Yet another report in this issue points to equal outcomes for those who quit abruptly and those who cut down gradually (Hughes p1326).

So the ground-swell against tobacco continues, based on its being the largest single reversible cause of death and morbidity in our society. Over 19,000 Australians die each year from tobacco related illnesses. While we know how to treat established nicotine addiction, we still do not know why people smoke and whether there are safer pharmaceutical alternatives and when these may be appropriate. One innovation which should be considered in Australia is the oral tobacco wad (�chewing tobacco� or Swedish �snus�) which may offer more advantages than harms, although it probably just as addictive as the smoked variety.

Comments by Andrew Byrne ..

Van Laar M, van Dorsselaer S, Monshouwer K, de Graaf R. Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? Addiction 2007 102:1251-1260

11 September 2007

Methadone works if used properly


BMJ 2007;335:464 (8 September), doi:10.1136/bmj.39317.563600.80


Drug misusers and incentives

Methadone works if used properly

Stevenson, a senior British forensic doctor, observes that methadone treatment does not work, contrary to 40 years of high quality research showing that it does.1

The reason can be found in the lack of adherence to evidence based clinical guidelines in much of the United Kingdom.2 With some notable exceptions, UK addicts are routinely given dose schedules that are contrary to guidelines (such as mean doses of less than 40 mg daily in place of double that found in well run clinics). These advise strict dose supervision for new and unstable patients with an effective dose range from 60 mg to 120 mg daily after careful induction starting with no more than 40 mg daily.3

Hong Kong, Australia, and New Zealand may be the only places where methadone has been available for over 30 years under reasonably open access and with a largely evidence based approach. Uniquely, all three have very little HIV in their large injecting populations. Few would believe this is coincidental (although hepatitis C has been a different and as yet unanswered story).

The question of whether addicts should receive incentives in treatment should be decided by practical research, not moralist opinions.4 5 Methadone treatment is already one of the most cost effective things we do in medicine and probably compares with washing hands. It would seem logical to raise the abysmal standards of practice in the UK and then examine incentives to improve results still further if needed.

Andrew Byrne, private addictions physician

75 Redfern Street, Redfern, NSW 2016, Australia



Competing interests: AB charges a fee for administration of drugs in the treatment of addiction.


1. Stevenson RJ. Drug misusers are likely to abuse the system. BMJ 2007;335:317. (18 August.)

2. Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Br J Gen Pract 2005;515: 444-51.

3. Strang J. Drug misuse and dependence-guidelines on clinical management. London: Department of Health, 1999. www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digit alasset/dh_4078198.pdf

4. Burns T. Is it acceptable for people to be paid to adhere to medication? Yes. BMJ 2007;335:232. (4 August.)

5. Shaw J. Is it acceptable for people to be paid to adhere to medication? No. BMJ 2007;335:233. (4 August.)

Rapid Responses:

A Toast to the Family, By STANTON PEELE

The following piece was sent to me by the author. It was originally published in the Wall Street Journal and brings out some basic common sense from the myth and hype which is often found in the addictions area.

A Toast to the Family


August 31, 2007; Page A9

Florida, Michigan and New Hampshire are some of a growing number of states to enact laws holding parents accountable for underage drinking at their homes. These laws typically involve hosting parties where alcohol is served to minors.

The target is parents who blithely allow keg parties in their basements and then let the teenagers who attend them drive home drunk. One such couple in Deerfield, Ill., was recently convicted when two 18-year-olds died in a car accident after such a party. Earlier this month, Karen Dittmer was arrested for allowing her 18-year-old son and his friends to drink beer at her birthday barbecue in New York's Suffolk County.

What kind of parents would ever allow their children to drink at home? Doesn't this put youngsters at risk?

The answer to the first question is simple. Most of the state laws include a specific exemption for children drinking at home during family and religious ceremonies. Observant Jews, for example, traditionally serve children small glasses of wine during Friday night Sabbath ceremonies. Other cultures also begin socializing children into drinking at an early age -- including Mediterranean societies such as Italy, Greece and Turkey (and non-Mediterranean societies such as China).

As for the second, two international surveys -- one conducted by the World Health Organization -- revealed that these Mediterranean countries and Israel had the lowest binge drinking rates among European adolescents.

In societies where children drink with their parents, this typically means giving a kid a small amount of wine or other alcohol, often watered down on special occasions or a family dinner. Many European countries also lower the drinking age for children when they are accompanied by parents. In the United Kingdom, for example, the legal age is 18, but for a family at a restaurant it is 16. In France and Italy, where the legal age is 16, there is no age limit for children drinking with parents.

But what might all of this mean for teen drinking problems in America?

Several studies have shown that the younger kids are when they start to drink, the more likely they are to develop severe drinking problems. But the kind of drinking these studies mean -- drinking in the woods to get bombed or at unattended homes -- is particularly high risk.

Research published in the Journal of Adolescent Health in 2004 found that adolescents whose parents permitted them to attend unchaperoned parties where drinking occurred had twice the average binge-drinking rate. But the study also had another, more arresting conclusion: Children whose parents introduced drinking to the children at home were one-third as likely to binge.

"It appears that parents who model responsible drinking behaviors have the potential to teach their children the same," noted Kristie Foley, the principal author of the study. While the phrasing was cautious, the implication of the study's finding needs to be highlighted: Parents who do not introduce children to alcohol in a home setting might be setting them up to become binge drinkers later on. You will not likely hear this at your school's parent drug- and alcohol-awareness nights.

Obviously, if a parent isn't comfortable consuming alcohol -- for whatever reason -- he or she is going to find it difficult to teach a child moderate social drinking. Fair enough. But neither should parents feel guilty or intimidated about responsibly introducing their children to alcohol in a home setting. The research suggests that this is more likely, not less, to protect the kids against the excessive drinking that permeates American high schools and colleges.

The youngest of my three children attends New York University, in a metropolis that is no stranger to alcohol. But alcohol is not forbidden fruit, since Anna drank wine at home. She says binge drinking holds no allure. I believe her.

Mr. Peele, a psychologist, therapist and attorney, is the author of several books on addiction, including the just-published "Addiction-Proof Your Child" (Three Rivers Press).

4 September 2007

Rats alive! Alcohol reductions possible with adequate buprenorphine doses.

Biological Psychiatry 2007 61:4-12

Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System. Ciccocioppo R, Economidou D, Rimondini R, Sommer W, Massi M, Heilig M.

Dear Colleagues,

In spite of the title, this rat experiment showed both significant increases (at low doses) and decreases (at high doses) in alcohol consumption with the use of buprenorphine injected intraperitoneally 1� hours before access to alcohol. Four dose levels ranged over 3+ orders of magnitude from 0.03 to 6mg/kg. Additional experimental conditions included the use of pre-treatment naltrexone which predictably blocked some of the increased alcohol consumption while using �the selective NOP receptor antagonist UFP-101� in two similar dose ranges abolished the suppression of drinking at the higher range dose level of buprenorphine administration.

While there may be relevant receptor issues here, clinicians will be more interested in the behavioural findings and their relevance to humans. Hence these detailed rodent experiments show two quite separate outcomes: (1) the consumption of alcohol, food and liquids and (2) deductions as to the reasons behind these observations based on changes when certain blockers are used. Cicciocioppo, Heilig and colleagues� conclusions about why these rats drank more or less alcohol are well beyond my field. Further, they are of limited interest clinically at the present time.

Sinclair reported the addition of morphine reducing alcohol consumption in rats many years ago (Nature 1973) and 14 years later wrote an editorial in BMJ about the feasibility of using drugs for alcoholism. We now use effective anti-craving drugs which are not psychoactive themselves (acamprosate and naltrexone for example). Tennant reported a possible link between increasing methadone levels and reducing alcohol use in a small study (n=18). Unfortunately, this has not yet been replicated, despite its simplicity and apparent significance.

By my raw calculations the experimental dose levels used in these rat studies translated to a 70kg person would equate to 2mg, 20mg, 200mg and 400mg as single doses. These are all well above the normal therapeutic range for analgesic use (0.2-0.8mg) although the lower two doses are well within the range used in dependency treatments (doses vary from about 1mg to 32mg daily). The high doses (200 and 400mg) are supratherapeutic and could be fatal, especially in combination with alcohol as given here. Such doses are not realistic in humans, being cumbersome to administer while the cost may be over $100 daily. Evidently no rat died in this study and the lead author believes that this may be due to the hyposensitivity of Sardinian rats to opioids and other depressants.

The study of drug �replacement� is still in its infancy but already it is clear that some opioid users become stimulant users and vice versa (see Darke 1999). Equally, some alcoholics largely cease alcohol use once they �discover� opioids. Others, probably a certain minority, continue to consume both drugs.

At the same time, this study reminds us that inadequate doses of buprenorphine will limit its usefulness. This is the same as penicillin, cortisone, insulin or any other medication. And the consequences from excessive dosing in a supervised treatment setting are usually limited to minor sedation, causing the patient to seek a dose decrease or simply to miss days.

Comments by Andrew Byrne ..


Sinclair JD, Adkins J, Walker S. Morphine-induced suppression of voluntary alcohol drinking in rats. Nature (1973) 246: 425-427

Sinclair JD. The feasibility of effective psychopharmacological treatments for alcoholism. British Journal of Addiction (1987) 82: 1213-1223

Tennant FS. Inadequate Plasma Concentrations in Some High-Dose Methadone Maintenance Patients. Am J Psychiatry 1987; 144: 1349-1350.

Darke S, Kaye S, Ross J. Transitions between the injection of heroin and amphetamines. Addiction 1999 94:1795-1803