A new compound similar to the active component of marijuana (cannabis) might provide effective pain relief without the mental and physical side effects of cannabis, according to a study in the July issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The synthetic cannabinoid (cannabis-related) compound, called MDA19, seems to avoid side effects by acting mainly on one specific subtype of the cannabinoid receptor. “MDA19 has the potential for alleviating neuropathic pain without producing adverse effects in the central nervous system,” according to the study by Dr Mohamed Naguib of The University of Texas M.D. Anderson Cancer Center.

MDA19 Works on a Single Cannabinoid Receptor
The researchers performed a series of experiments to analyze the pharmacology and effects of the synthetic cannabinoid MDA19. There are two subtypes of the cannabinoid chemical receptor: CB1, found mainly in the brain; and CB2, found mainly in the peripheral immune system.

Dr. Naguib’s group has been doing research to see if the cannabinoid receptors—particularly CB2—can be a useful target for new drugs to treat neuropathic pain. Neuropathic pain is a difficult-to-treat type of pain caused by nerve damage, common in patients with trauma, diabetes, and other conditions.

MDA19 was designed to have a much stronger effect on the CB2 receptor than on the CB1 receptor. In humans, MDA19 showed four times greater activity on the CB2 receptor than on the CB1 receptor. In rats, the difference was even greater. The experiments also showed that MDA19 had “protean” effects, so-called after the shape-shifting Greek sea god Proteus—under different conditions, it could either block or activate the cannabinoid receptors.

In rats, treatment with MDA19 effectively reduced specific types of neuropathic pain, with greater effects at higher doses. At the same time, it did not seem to cause any of the behavioral effects associated with marijuana.

Potential to Develop Effective Pain Drugs that Avoid Side Effects
The “functional selectivity” of MDA19—the fact that it acts mainly on the CB2 receptor and has a range of effects under differing conditions—could have important implications for drug development. “[W]ith functionally selective drugs, it would be possible to separate the desired from the undesired effects of a single molecule through a single receptor,” Dr. Naguib and colleagues write.
This means that MDA19 could be a promising step toward developing medications that have the pain-reducing effect of cannabinoids while avoiding the mental and physical side effects of marijuana itself. However, more research will be needed before MDA19 or other agents that act on the CB2 receptor are ready for testing in humans.

“These elegant studies by Professor Naguib demonstrate remarkable analgesic properties for this synthetic cannabinoid,” comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia &Analgesia. “The studies suggest a novel mechanism for this protean agonist. Although preliminary, these studies suggest that synthetic cannabinoids may be significant step forward for patients suffering from neuropathic pain.”

SOURCE : www.news-medical.net 2nd July 2010

Researchers have found that a specific and remarkably small fragment of RNA appears to protect rats against cocaine addiction – and may also protect humans.
The discovery could lead to better ways of predicting drug abuse risk and treating addictions

In the study, researchers at The Scripps Research Institute in Jupiter, Florida found that cocaine consumption increased levels of a specific microRNA sequence in the brains of rats, named microRNA-212.

As its levels increased, the rats exhibited a growing dislike for cocaine, ultimately controlling how much they consumed.
On the other hand, as levels of microRNA-212 decreased, the rats consumed more cocaine and became the rat equivalent of compulsive users.

The study’s findings suggest that microRNA-212 plays a pivotal role in regulating cocaine intake in rats and perhaps in vulnerability to addiction.
Interestingly, the same microRNA-212 identified in this study, is also expressed in the human’s dorsal striatum, a brain region that has been linked to drug abuse and habit formation.

“This study enhances our understanding of how brain mechanisms, at their most fundamental levels, may contribute to cocaine addiction vulnerability or resistance to it,” Nature quoted National Institute on Drug Abuse (NIDA) Director Dr. Nora D. Volkow, as saying.

“This research provides a wonderful example of how basic science discoveries are critical to the development of new medical treatments and targeted prevention,” he added.

Rats with a history of extended cocaine access can demonstrate behavior similar to that observed in humans who are dependent on the drug.
Current data show that about 15 percent of people who use cocaine become addicted to it.
The findings suggest that microRNAs may be important factors
contributing to this vulnerability.

“The results of this study offer promise for the development of a totally new class of anti-addiction medications. Because we are beginning to map out how this specific microRNA works, we may be able to develop new compounds to manipulate the levels of microRNA-212 therapeutically with exquisite specificity, opening the possibility of new treatments for drug addiction,” said Paul J. Kenny, senior author on the study.
The study is published in the journal Nature. (ANI)

Source:www.sify.com/news 9th July 2010-07-10

Few studies can manage the painstaking analyses needed to identify what makes for successful counselling. This Swiss study broke new ground in dissecting why some brief interventionists had far better results than others with risky drinking A&E patients.
Abstract The featured report is one of several from a study of brief advice to heavy drinkers among injured adult patients attending a Swiss emergency department. Among 8439 patients, 1472 heavy drinkers were identified by a health screening survey, of whom 987 joined the study. They were randomly allocated to carry on as usual, to also be assessed by a researcher for about half an hour, or in addition to receive about 15 minutes of advice on drinking immediately after assessment. Adopting the style of motivational interviewing, this compared the patient’s drinking with national norms and led the patient to consider the pros and cons of their drinking and their readiness to change, culminating if appropriate in a setting a goal for change. Over the following year, this typical brief intervention format did not lead to greater reductions in drinking. About two-thirds of the patients continued to drink heavily regardless of advice and/or assessment.
During a period of the study and when patients allowed, intervention sessions were audio-taped. 97 sessions could be rated for the degree to which the counsellor adhered to a motivational style, and for comments from the patient indicative of their ability and willingness to change their drinking. Of these ratings, an initial analysis found that only the patient’s expressed degree of ability to change was related to later drinking; none of the counsellor’s behaviours was significantly linked. However, this analysis tried to separately link each behaviour (in)consistent with motivational interviewing’s principles with drinking. The possibility remained that combining these behaviours to characterise the counsellor’s overall style would yield significant results.
This was the approach taken in two further reports, one of which was the featured report. An earlier analysis established that counsellor comments consistent with the style of motivational interviewing were most likely to elicit positive statements about changing their drinking from the patient. The featured report related the same (and other) measures of counselling style to later drinking, limiting itself to interventions conducted by five counsellors with similar qualifications and experience and uniform preparatory training. Despite this they differed significantly in the their patients’ weekly drinking at the 12-month follow-up, and in the degree to which this represented an improvement on the amount they were drinking on entry to the study. At the extremes were one counsellor whose patients ended up drinking on average 18 UK units more per week, while another registered an average nine unit reduction.
These differences were at least partly accounted for by how far the counsellor was able to actually deliver the intervention in a motivational style. Drinking reductions were greater the more the counsellor demonstrated acceptance of the patient, conducted the intervention in the intended spirit, made more comments consistent versus inconsistent with a motivational approach, avoided inconsistent comments, elaborated on the patient’s comments rather than simply reflecting them back, and reflected back the patient’s comments with or without elaboration rather than asking questions. Empathy levels narrowly missed featuring among these strong and statistically significant links. These same attributes tended to even out the relationship between the patient’s expressed feelings of (in)ability to change and how much they did change their drinking over the 12 months. Highly skilled counsellors had good outcomes almost regardless of the patient’s doubts. The less skilled were effective mainly with patients who already expressed high levels of ability to change.
While accepting the need for replication in a larger study, for the authors their results suggested that an optimal combination of motivational interviewing skills results in better drinking outcomes, regardless of whether the patient is confident (or expresses confidence) in their ability to cut back. The pattern of results across all the reports from the study implies that training should focus on developing an overall approach consistent with motivational interviewing (with a particular focus on avoiding inconsistent behaviour) rather than on the frequent use of particular ‘micro’ techniques. Since training was equalised in the study, it also seems important to select staff with a ‘natural’ ability to adhere to the spirit of motivational interviewing when counselling patients.
These comments are more fully explained and referenced in the associated background notes. This study is one of the few in substance misuse to deeply address how therapists relate to clients in ways which promote positive change. It seems the first to depth-analyse interactions during a brief intervention which (from the patient’s point of view) unexpectedly addresses their drinking while they are seeking help for something else entirely. The implication is that in this situation, the impact of motivational interviewing with heavy drinkers depends on the ability of the counsellor to embody the spirit of the approach, not in minute or tick-box detail, but in broad-brush and consistent application. Given this spirit, as intended, patients in general respond not by defensively deflecting this uncalled-for advance, but by re-evaluating their drinking in ways which lead to a lasting reduction.
As intended by its creators, the findings show that true-to-type motivational interviewing can counter low motivation and doubts, elevating outcomes to near those of the most promising patients. While training doubtless played its part in developing this ability, still it left big differences between counsellors, who presumably varied in the degree to which they could implement what they learned. The more ‘trainable’ dimensions of the frequency of recommended types of comments were relatively uninfluential, the more nebulous ‘spirit’ dimensions more important. Despite expert training and supervision, the result was some therapists whose patients drank more than they did before, others whose patients drank less, a finding which turns the spotlight on staff recruitment. The implication is that without appropriate recruitment, much of the effort put in to training and supervision will be wasted.
The same message emerged from a study of motivational interviewing training which found that initial gains in skills had waned two months later. However, this was not the case for the addiction and mental health clinicians who, even before training, had been more proficient than the other trainees would be after training. Not only did these ‘natural experts’ start from a higher level, they went on to absorb and retain more of what they had learned.
How easy it is to find such people must be a concern. In the featured study all the counsellors were clinical psychologists educated to master degree level, trained by an experienced therapist and supervised throughout using actual client session recordings or observations. This exceptional combination of qualifications, training and ongoing support still resulted in just one of the therapists having a marked positive effect on drinking.
While these are important findings with echoes in other studies, inevitably they stand on a narrow and inadequate evidence base. Studies which probe deeply enough to make sense of what is going on in therapy require labour-intensive analyses, so tend to be limited to perhaps one site and a few therapists, by-products of studies designed to address the effectiveness not of therapists, but of therapies.
Particular caution is needed before assuming that the implications extend to substance misuse treatment. The dynamics in the emergency department are likely to be very different from those in substance misuse treatment clinics, whose patients have already acknowledged their problems and decided at least to give treatment a try. In this situation, the overwhelming influence is the strength of the patient’s resolution. Therapists can still make a noticeable and sometimes substantial difference, but generally more in terms of whether clients want to extend the relationship by staying in treatment, than in whether they change their substance use.
Among several less serious concerns, the featured study’s main weakness is the non-random allocation of patients to therapists, meaning varying caseloads might have influenced the therapists’ performances. However, this does not seem to account for the findings. Confidence in these and in their generalisability is increased by findings from different contexts with similar implications.
Across a range of caseloads, one review of how motivational interviewing works has highlighted (as the featured study did) the importance of therapists avoiding behaviours inconsistent with a motivational approach. Most relevant however are other brief intervention studies of patients not seeking treatment. These confirm that in such circumstances, some therapists are much more able than others to realise the potential of a motivational approach. Avoiding directive and confrontational behaviour seems particularly important with people who when they attended their GP, emergency department, or college, were not expecting their substance use to be addressed at all, let alone in such terms. Even patients who, while not seeking treatment, have volunteered for a check-up of their drinking habits, have reacted badly to such approaches. As in the featured study, other studies have also found that embodying the overall spirit of the approach is related to good outcomes, while the sheer quantity of ‘correct’ micro-behaviours is not. In one study the least effective of three therapists conducting motivational interventions for heavy drinking was also the one who most often used specific recommended techniques.
The dynamics of the therapist-patient encounter seem to differ in a treatment context. Like brief intervention studies, studies of patients actually seeking treatment for substance use problems have confirmed the importance of the overall spirit of the approach rather than micro measures of the frequency of correct therapist behaviours. However, they have been less clear about the damaging impact of behaviours inconsistent with a motivational approach. Within an overall supportive and accepting context, patients react well, or at least, not badly, to a degree of confrontation and caring concern, even if the patient’s permission has not been sought. With clients seeking help for a serious substance use disorder, there is more reason to show concern, be directive, and to warn about possible consequences. Patients who themselves are concerned and seeking direction might see the total absence of such comments from their therapists as withholding their true feelings, perhaps even as uncaring. For these patients the absence of a directive approach can be positively damaging, while those who like to see themselves as in control react badly to directive therapists.
Thanks for their comments on this entry in draft to Jacques Gaume, of the Alcohol Treatment Centre at Lausanne University Hospital. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Source: Findings Sept. 2009 Journal of Substance Abuse Treatment: 2009, 37, p. 151–159.

Combining a randomised trial with a ‘real-world’ test, studies of the Dutch Drinking Less programme have gone further than any others to establish the beneficial impacts of web-based alcohol self-help interventions.

Abstract

The study was a ‘real-world’ test of a promising Dutch internet-based self-help intervention for problem drinking. A previous randomised trial employing the methodological safeguards possible in tightly controlled research (particularly the recruitment of a comparison group not given access to the intervention) had established that the intervention reduced drinking. At issue in the featured study was whether similar drinking reductions would be seen when the intervention was made freely available to the general public. If they were, then the assumption could be made that these too were caused by having access to the intervention.

Drinking Less is an on-line, interactive programme with no personal therapist input. Aimed at risky drinkers among the general adult population, the intervention is based on principles derived from motivational interviewing, cognitive-behavioural therapies and self-control training. Its home page offers links to alcohol-related information, treatment services, a discussion forum, and the Drinking Less self-help programme, the core of the intervention. Over a recommended six weeks (though this is entirely up to the user) the programme guides visitors in preparing to change their drinking, setting goals , implementing change, and finally sustaining it, preferably by drinking within recommended limits.
The earlier trial had found that six months later, at least 17% of adult problem drinkers randomly allocated to this intervention had reduced their drinking to within Dutch guidelines, compared to just 5% allocated to an on-line alcohol education brochure. Before the study, both groups had averaged about 55 UK units a week. At follow-up, the Drinking Less group had cut consumption to about 36 UK units a week, but the brochure group had barely changed.
The featured study monitored what happened when over 10 months spanning 2007 and 2008 the web site was advertised to the Dutch public. During this time round 27,500 people visited the site, of whom 1625 signed up for the self-help programme, accessing it on average 23 times. Typically they were well educated, employed, middle-aged men. On average they drank about 50 UK units a week, and nearly all who completed the on-line AUDIT screening questionnaire scored in a range indicative of alcohol abuse or dependence.
During the first seven of the 10 months, 378 of site visitors who signed up to the Drinking Less programme also agreed to participate in research to assess its impact. On average they drank roughly the same amount (95% exceeded Dutch guidelines) as all 1625 who signed up and were also similar in age, sex, employment, and motivation to change. Despite some statistically significant differences, they were also broadly similar to participants in the earlier randomised trial. Over 8 in 10 had never received professional help for their drinking. A few weeks later a survey suggested that after signing up, nearly 9 in 10 went on to use the programme, though generally only a few times.
Of the 378 in the baseline sample, 153 responded to an on-line follow-up survey six months later. Before signing up to the programme, just 4% had confined their drinking within Dutch guidelines; six month later, 39% did so. They had also nearly halved their average consumption from 50 UK units to 27. On the ‘fail-safe’ assumption that the intervention had no impact on people who were not followed up, still the drinking reductions were statistically significant; from 5%, the proportion drinking within guidelines rose to 19%, and consumption fell from 51 UK units to 42.
Next the analysts compared these results with those from the six-month follow-up in the randomised trial. Based only on respondents to the follow-up surveys, and adjusting for differences between the samples, in the ‘real-world’ test over twice as many (unadjusted figures 36% v. 19%) people moved to drinking within Dutch guidelines. When the assumption was made that in both trials the intervention had no impact on people not followed up, the figures still favoured the ‘real-world’ test (15% v. 10%), but the difference was no longer statistically significant.
The researchers concluded that the featured study had shown that the benefits established by the randomised controlled trial would be sustained when the intervention was made routinely and generally available to the public. The expected throughput of 3000 Drinking Less programme users a year would amount to nearly 3% of the country’s problem drinkers who would otherwise not have received professional help. Probably because they require the drinker to take the initiative and visit the site, such interventions reach people who, compared to the totality of problem drinkers, are more likely to be women, employed, highly educated, and motivated to change their drinking. Given its low cost per user, this type of intervention seems to have a worthwhile place in a public health approach to reducing alcohol-related problems.
Though only a minority of site visitors may sign up for web-based alcohol programmes, nevertheless the numbers engaged can be very large, and the risk-reductions seem of the order typical in studies of brief advice to drinkers identified in health care settings. In these settings screening programmes typically identify people who are not actually seeking help for drinking problems – ‘pushing’ them towards intervention and change – while web sites ‘pull’ in people already curious or concerned about their drinking. As such these two gateways can play complementary roles in improving public health and offering change opportunities to people who would not present to alcohol treatment services. However, in Britain and elsewhere, both tactics reach only small fractions of the population who drinking excessively, leaving the bulk of the public health work to be done by interventions which drinkers generally cannot avoid and do not have seek out, such as price increases and availability restrictions.
With its combination of a randomised trial and a ‘real-world’ test, the featured research programme has gone further than any other in establishing the beneficial impacts of web-based alcohol interventions. However, largely because many site users do not complete research surveys, it remains impossible to be sure that the results seen in such studies will be replicated across the entire usership of the sites. Details below.

Strengths and limitations of the featured study

The featured study’s combination of a randomised trial with all its methodological safeguards, and a ‘real-world’ trial approximating normal conditions, affords what seems to be the best indication to date of the contribution web-based self-help interventions could make to reducing heavy drinking and associated health risks. However, its twin pillars are weakened by the fact that many people either did not join the studies or did not supply follow-up data; those who did may not have been typical of all the people who might access such sites. In the randomised trial, 40% of the baseline sample did not complete the six-month follow-up survey, and in the featured study, nearly 60%. Though on the measures taken by the study the respondents generally seemed typical of the baseline sample, clearly something was sufficiently different to cause them to respond while the others did not. In both studies this problem was catered for by assuming that non-responders were also non-changers. Though this almost certainly underestimated the impact of the intervention, still in both there remained significant and worthwhile improvements.
What could not be catered for in either study was the degree to which people who join such studies differ from the much greater number who would use the web sites, but decline participation in research. This problem was especially apparent in the featured study, in which it seems that around 6% of site visitors signed up for the self-help programme. Of these, perhaps a third or slightly more of the people who signed up for the programme during the relevant period also agreed to participate in the research. In some important ways (including amount drunk and motivation to change) they seemed similar to the bulk of programme sign-ups, though the researchers suspect they were more likely to have engaged with the programme.

Opening more doors to change for more people

A review of computer-based alcohol services for the general public has rehearsed the advantages: immediate, convenient access for people (the majority in developed nations) connected to the internet; consequently able to capitalise on what may be fleeting resolve; anonymous services sidestep the embarrassment or stigma which might deter help-seeking; such services are available to people unwilling or less able to talk about their problems to a stranger; generally they are free and entail no travel costs or lost income due to time off work; very low operating cost per user if widely accessed; easily updated. In consumption terms, the drinking problems of web site users are comparable to those of drinkers who seek treatment, yet few have received professional help, perhaps partly because their higher socioeconomic status and greater resources have enabled them to restrict the consequential damage. People who actually engage with web-based assessments of their drinking problems have more severe problems than those who just visit and leave. Including the randomised trial which paved the way for the featured study, the review found eight studies which evaluated the effectiveness of computer-based interventions for the general public. In all but one the users significantly improved on at least one of the alcohol-related measures recorded by the studies.
A particular role for alcohol self-help sites may be to offer an easy, quick and accessible way to for drinkers to actualise their desire to tackle their problems, especially when that desire is allied with the resources to implement and sustain improvements without face-to-face or comprehensive assistance. After conducting the Project MATCH trial, some of the world’s leading alcohol treatment researchers argued that “access to treatment may be as important as the type of treatment available”. The implication is that in cultures which accept ‘treatment’ as a route to resolving unhealthy and/or undesirable drinking, having convincing-looking and accessible ‘treatment doors’ to go through may be more important than what lies behind those doors, as long as this fulfils the expectations of the client or patient. This is likely to be especially the case for people who retain a stake in conventional society in the form of marriages, jobs, families, and a reputation to lose. These populations – the kind the featured study suggests are attracted to self-help alcohol therapy web sites – have more of the ‘recovery capital’ resources needed to themselves do most of the work in curbing their drinking.

The British Down Your Drink site

The best known British alcohol self-help web site is the Down Your Drink site run by a team based at University College London, an initiative originally funded by the Alcohol Education and Research Council and now by the Medical Research Council’s National Prevention Research Initiative. In 2007 this was revised to offer set programmes from a one-hour brief intervention to several weeks, but also to generally give the user greater control over the use they made of the site. The approach remained based on principles and techniques derived from motivational interviewing and cognitive-behavioural therapies.
The previous version had been structured as six consecutive modules to be accessed weekly. An analysis of data provided by the first 10,000 people who registered at the site after piloting ended in September 2003 revealed that most were in their 30s and 40s, half were women, nearly two-thirds were married or living with a partner, just 4% were unemployed, and most reported occupations from higher socioeconomic strata. As an earlier study commented, site users were predominantly middle class, middle aged, white and European. Six in 10 either did not start the programme, or completed just the first week. About 17% completed the six weeks. Of these, 57% returned an outcome questionnaire. Compared to their pre-programme status, on average they were now at substantially lower risk, and functioning better and living much improved lives. The sample had been recruited over about 27 months, a registration rate of about 4500 a year. By way of comparison, in England during 2008/09, around 100,000 adults were treated for their alcohol problems at conventional services. User profile and site usage had been similar during the earlier pilot phase. Results from surveys sent to pilot programme completers indicated that three quarters had never previously sought help for their drinking.

Source: Published in Findings 19 May 2010 Alcoholism: Clinical and Experimental Research: 2009, 33(8), p. 1401–1408

Combining a randomised trial with a ‘real-world’ test, studies of the Dutch Drinking Less programme have gone further than any others to establish the beneficial impacts of web-based alcohol self-help interventions.
Abstract The study was a ‘real-world’ test of a promising Dutch internet-based self-help intervention for problem drinking. A previous randomised trial employing the methodological safeguards possible in tightly controlled research (particularly the recruitment of a comparison group not given access to the intervention) had established that the intervention reduced drinking. At issue in the featured study was whether similar drinking reductions would be seen when the intervention was made freely available to the general public. If they were, then the assumption could be made that these too were caused by having access to the intervention.

Drinking Less is an on-line, interactive programme with no personal therapist input. Aimed at risky drinkers among the general adult population, the intervention is based on principles derived from motivational interviewing, cognitive-behavioural therapies and self-control training. Its home page offers links to alcohol-related information, treatment services, a discussion forum, and the Drinking Less self-help programme, the core of the intervention. Over a recommended six weeks (though this is entirely up to the user) the programme guides visitors in preparing to change their drinking, setting goals , implementing change, and finally sustaining it, preferably by drinking within recommended limits.
The earlier trial had found that six months later, at least 17% of adult problem drinkers randomly allocated to this intervention had reduced their drinking to within Dutch guidelines, compared to just 5% allocated to an on-line alcohol education brochure. Before the study, both groups had averaged about 55 UK units a week. At follow-up, the Drinking Less group had cut consumption to about 36 UK units a week, but the brochure group had barely changed.
The featured study monitored what happened when over 10 months spanning 2007 and 2008 the web site was advertised to the Dutch public. During this time round 27,500 people visited the site, of whom 1625 signed up for the self-help programme, accessing it on average 23 times. Typically they were well educated, employed, middle-aged men. On average they drank about 50 UK units a week, and nearly all who completed the on-line AUDIT screening questionnaire scored in a range indicative of alcohol abuse or dependence.
During the first seven of the 10 months, 378 of site visitors who signed up to the Drinking Less programme also agreed to participate in research to assess its impact. On average they drank roughly the same amount (95% exceeded Dutch guidelines) as all 1625 who signed up and were also similar in age, sex, employment, and motivation to change. Despite some statistically significant differences, they were also broadly similar to participants in the earlier randomised trial. Over 8 in 10 had never received professional help for their drinking. A few weeks later a survey suggested that after signing up, nearly 9 in 10 went on to use the programme, though generally only a few times.
Of the 378 in the baseline sample, 153 responded to an on-line follow-up survey six months later. Before signing up to the programme, just 4% had confined their drinking within Dutch guidelines; six month later, 39% did so. They had also nearly halved their average consumption from 50 UK units to 27. On the ‘fail-safe’ assumption that the intervention had no impact on people who were not followed up, still the drinking reductions were statistically significant; from 5%, the proportion drinking within guidelines rose to 19%, and consumption fell from 51 UK units to 42.
Next the analysts compared these results with those from the six-month follow-up in the randomised trial. Based only on respondents to the follow-up surveys, and adjusting for differences between the samples, in the ‘real-world’ test over twice as many (unadjusted figures 36% v. 19%) people moved to drinking within Dutch guidelines. When the assumption was made that in both trials the intervention had no impact on people not followed up, the figures still favoured the ‘real-world’ test (15% v. 10%), but the difference was no longer statistically significant.
The researchers concluded that the featured study had shown that the benefits established by the randomised controlled trial would be sustained when the intervention was made routinely and generally available to the public. The expected throughput of 3000 Drinking Less programme users a year would amount to nearly 3% of the country’s problem drinkers who would otherwise not have received professional help. Probably because they require the drinker to take the initiative and visit the site, such interventions reach people who, compared to the totality of problem drinkers, are more likely to be women, employed, highly educated, and motivated to change their drinking. Given its low cost per user, this type of intervention seems to have a worthwhile place in a public health approach to reducing alcohol-related problems.
Though only a minority of site visitors may sign up for web-based alcohol programmes, nevertheless the numbers engaged can be very large, and the risk-reductions seem of the order typical in studies of brief advice to drinkers identified in health care settings. In these settings screening programmes typically identify people who are not actually seeking help for drinking problems – ‘pushing’ them towards intervention and change – while web sites ‘pull’ in people already curious or concerned about their drinking. As such these two gateways can play complementary roles in improving public health and offering change opportunities to people who would not present to alcohol treatment services. However, in Britain and elsewhere, both tactics reach only small fractions of the population who drinking excessively, leaving the bulk of the public health work to be done by interventions which drinkers generally cannot avoid and do not have seek out, such as price increases and availability restrictions.
With its combination of a randomised trial and a ‘real-world’ test, the featured research programme has gone further than any other in establishing the beneficial impacts of web-based alcohol interventions. However, largely because many site users do not complete research surveys, it remains impossible to be sure that the results seen in such studies will be replicated across the entire usership of the sites. Details below.
Strengths and limitations of the featured study
The featured study’s combination of a randomised trial with all its methodological safeguards, and a ‘real-world’ trial approximating normal conditions, affords what seems to be the best indication to date of the contribution web-based self-help interventions could make to reducing heavy drinking and associated health risks. However, its twin pillars are weakened by the fact that many people either did not join the studies or did not supply follow-up data; those who did may not have been typical of all the people who might access such sites. In the randomised trial, 40% of the baseline sample did not complete the six-month follow-up survey, and in the featured study, nearly 60%. Though on the measures taken by the study the respondents generally seemed typical of the baseline sample, clearly something was sufficiently different to cause them to respond while the others did not. In both studies this problem was catered for by assuming that non-responders were also non-changers. Though this almost certainly underestimated the impact of the intervention, still in both there remained significant and worthwhile improvements.
What could not be catered for in either study was the degree to which people who join such studies differ from the much greater number who would use the web sites, but decline participation in research. This problem was especially apparent in the featured study, in which it seems that around 6% of site visitors signed up for the self-help programme. Of these, perhaps a third or slightly more of the people who signed up for the programme during the relevant period also agreed to participate in the research. In some important ways (including amount drunk and motivation to change) they seemed similar to the bulk of programme sign-ups, though the researchers suspect they were more likely to have engaged with the programme.
Opening more doors to change for more people
A review of computer-based alcohol services for the general public has rehearsed the advantages: immediate, convenient access for people (the majority in developed nations) connected to the internet; consequently able to capitalise on what may be fleeting resolve; anonymous services sidestep the embarrassment or stigma which might deter help-seeking; such services are available to people unwilling or less able to talk about their problems to a stranger; generally they are free and entail no travel costs or lost income due to time off work; very low operating cost per user if widely accessed; easily updated. In consumption terms, the drinking problems of web site users are comparable to those of drinkers who seek treatment, yet few have received professional help, perhaps partly because their higher socioeconomic status and greater resources have enabled them to restrict the consequential damage. People who actually engage with web-based assessments of their drinking problems have more severe problems than those who just visit and leave. Including the randomised trial which paved the way for the featured study, the review found eight studies which evaluated the effectiveness of computer-based interventions for the general public. In all but one the users significantly improved on at least one of the alcohol-related measures recorded by the studies.
A particular role for alcohol self-help sites may be to offer an easy, quick and accessible way to for drinkers to actualise their desire to tackle their problems, especially when that desire is allied with the resources to implement and sustain improvements without face-to-face or comprehensive assistance. After conducting the Project MATCH trial, some of the world’s leading alcohol treatment researchers argued that “access to treatment may be as important as the type of treatment available”. The implication is that in cultures which accept ‘treatment’ as a route to resolving unhealthy and/or undesirable drinking, having convincing-looking and accessible ‘treatment doors’ to go through may be more important than what lies behind those doors, as long as this fulfils the expectations of the client or patient. This is likely to be especially the case for people who retain a stake in conventional society in the form of marriages, jobs, families, and a reputation to lose. These populations – the kind the featured study suggests are attracted to self-help alcohol therapy web sites – have more of the ‘recovery capital’ resources needed to themselves do most of the work in curbing their drinking.
The British Down Your Drink site
The best known British alcohol self-help web site is the Down Your Drink site run by a team based at University College London, an initiative originally funded by the Alcohol Education and Research Council and now by the Medical Research Council’s National Prevention Research Initiative. In 2007 this was revised to offer set programmes from a one-hour brief intervention to several weeks, but also to generally give the user greater control over the use they made of the site. The approach remained based on principles and techniques derived from motivational interviewing and cognitive-behavioural therapies.
The previous version had been structured as six consecutive modules to be accessed weekly. An analysis of data provided by the first 10,000 people who registered at the site after piloting ended in September 2003 revealed that most were in their 30s and 40s, half were women, nearly two-thirds were married or living with a partner, just 4% were unemployed, and most reported occupations from higher socioeconomic strata. As an earlier study commented, site users were predominantly middle class, middle aged, white and European. Six in 10 either did not start the programme, or completed just the first week. About 17% completed the six weeks. Of these, 57% returned an outcome questionnaire. Compared to their pre-programme status, on average they were now at substantially lower risk, and functioning better and living much improved lives. The sample had been recruited over about 27 months, a registration rate of about 4500 a year. By way of comparison, in England during 2008/09, around 100,000 adults were treated for their alcohol problems at conventional services. User profile and site usage had been similar during the earlier pilot phase. Results from surveys sent to pilot programme completers indicated that three quarters had never previously sought help for their drinking.
Source: Published in Findings 19 May 2010 Alcoholism: Clinical and Experimental Research: 2009, 33(8), p. 1401–1408

MULTIPLE DRUG USE NOW THE NORM, HEROIN SHUNNED BY YOUNG
Government drug policy is too centred on heroin abuse, fails to take account of the realities of current usage trends and needs to focus on individual user behaviour if it is to reflect the true picture and formulate meaningful responses, a leading academic at National University of Ireland Maynooth urged.
‘A Dizzying Array of Substances; An Ethnographic Study of Drug Use in the Canal Communities’ is the result of a long-term study which closely examined the realities of drug use in local life of Rialto, Bluebell and Inchicore, three communities served by the Canal Communities Local Drugs Task Force. It was led by principal investigator Dr A Jamie Saris and primary field researcher Fiona O’Reilly at the Department of Anthropology, NUI Maynooth.
The ethnographic research, carried out mostly in 2008 and early 2009, gives the most compelling evidence to date that multiple drug use is the norm amongst drug users in the Canal Communities and, the researchers concluded, most probably in other areas.
“The big problem is that as far as government is concerned, ‘drugs’, from a treatment perspective, has traditionally meant heroin. Thus, the apparent leveling off of the need for a very opiate-centric treatment service in the Canal Communities in recent years is deceptive” said Dr Saris.
Besides the ethnographic work, the study surveyed, on a long term basis, 92 people using either heroin or methadone in the study area. Unsurprisingly most of those surveyed were on methadone (98%). Of those surveyed:
•63% claimed to have used heroin in the previous three months
•30% had used crack cocaine
•22% had used powder cocaine
•46% had also taken street tranquilisers
•50% were on prescribed tranquillisers, and
•60% had also smoked cannabis within the past three months.
“The majority of those registered on the methadone treatment programme are also using a cocktail of other substances, very often including heroin. Multiple drug use is the reality for nearly all users, and official policy needs to have this understanding at its centre”, Saris said.
In the course of their study, the research team also noted a strong stigma against heroin use amongst the 16-25 age group who still regularly used a lot of other substances, including cocaine and off-label prescription medication. “The reality is that these people are difficult for a treatment infrastructure built around opiates to service. If they have issues, they are more difficult to address,” said Saris.
” The stress that policy-makers and community activists place on ‘crack’ or ‘heroin’ or any other single drug as clear and present social dangers obscures the ubiquity of polydrug use. It makes it appear that these users are very different from other drug-users in the rest of society including cannabis and recreational cocaine users, and it also obscures how commonly legal pharmaceuticals, such as benzodiazepines, even methadone itself, are regularly consumed ‘illegally’.”
He said that a focus on drug use alone is the mistake. “The lives we examined, however damaged by an attraction to certain pharmaceuticals, are rarely defined solely by such behaviour. These people are also sons and daughters, fathers and mothers, partners and lovers, as well as employees and community members. This sensibility does in fact inform a lot of local community activities aimed at assisting users, but such work is often difficult to justify to official funders under the rubric of ‘treatment’, as currently understood. Unless we can understand who users are, what they are taking and why, we will not be able to assign the appropriate resources, treatments or management systems.”
Tony MacCarthaigh, chairperson of the Canal Communities Local Drugs Task Force commented that “individuals and not chemicals need to become the focal point of treatment, and treatment needs to assist individuals in developing another orientation not just to drugs, but to life”.
Source: www.addictiontoday.org 9th July 2010

An 18-year-old male presents complaining of crampy abdominal pain, nausea, and intractable vomiting for the past year. The symptoms are episodic, lasting several weeks and remitting for weeks to months.

The patient states that his abdominal pain is 10 out of 10 in severity, and that he has been vomiting up to 20 times each day. He has been evaluated at multiple hospitals, and he has had numerous upper endoscopies, colonoscopies, swallowing studies, and CT and MRI imaging studies, all of which were unrevealing.

He underwent a cholecystectomy, but had no improvement in his symptoms after the surgery. His pain and nausea are unresponsive to antacids and antiemetics.

The patient’s only relief is with hot water bathing: he spends hours each day in the shower with the temperature set as hot as he can bear. The patient’s history is otherwise unremarkable, except that he admits to daily marijuana use beginning at the age of 14.

This patient’s story is typical of cannabinoid hyperemesis, a clinical syndrome characterized by intractable vomiting and abdominal pain associated with the unusual learned behavior of compulsive hot water bathing, occurring in the setting of long-term heavy marijuana use.
Treatment consists of medication for immediate symptomatic relief and marijuana cessation for long-term relief. Symptoms usually remit within weeks of becoming abstinent.

If this disorder is so easily diagnosed and treated, why were the patient’s past doctors confused to the point of performing what might have been an unnecessary surgery? Cannabinoid hyperemesis is a new diagnosis, first described in 2004, and currently sixteen papers on the subject have been published.

Therefore, it is likely that the patient’s prior doctors had never considered this disorder. Second, the pathogenesis of cannabinoid hyperemesis is poorly understood.
How can marijuana, which is used in cancer clinics as an anti-emetic, cause intractable vomiting? And why would symptoms abate in response to high temperature?

The connection between marijuana, vomiting, and heat is non-intuitive, and a medical team unfamiliar with this syndrome would be hard-pressed to reach the diagnosis.
The largest study of cannabinoid hyperemesis to date was the landmark report by Allen et al in 2004 in an area of Southern Australia where marijuana use is largely decriminalized.

The report tracked 10 patients who presented with cyclic vomiting after 3 to 27 years of cannabis abuse and no other history of drug abuse. All but one displayed compulsive hot water bathing; the remaining patient had only experienced his symptoms for 6 months, and the authors theorize that he had not yet learned to associate hot water with symptom palliation.

The 9 compulsive bathers reported that this bizarre behavior occupied hours of their days and said that their symptoms were ameliorated within minutes of bathing and returned when the water cooled. All 10 patients were counseled to cease cannabis use, and 7 did so. Within weeks of cessation, the symptoms resolved for these 7 patients; the remaining 3 patients did not cease cannabis use and continued to have cyclic vomiting and abdominal pain.

After several years of abstinence, 3 patients resumed cannabis use and were hospitalized again with cyclic vomiting and abdominal pain. Once again, 2 of these patients successfully stopped using cannabis, and their symptoms resolved. The remaining patient continued to use cannabis and continued to experience symptoms at the time of publication.
Following the first case report, further cases have been described on three continents.

All patients presented with the classic triad of symptoms described by Allen et al: cyclic vomiting and abdominal pain, an extensive history of cannabis abuse, and palliation with hot water bathing. The fact that this unique triad is preserved in diverse patient populations suggests that there is a pathogenic mechanism that underlies this syndrome.

Several authors have speculated about the pathophysiology of cannabinoid hyperemesis, and though the specifics remain unclear, there is consensus over some of the basic principals: It appears that the high lipophilicity of delta-9-tetrahydrocannabinol (Δ9-THC, the active compound in marijuana) causes cumulative increases in concentration with chronic use, which may lead to toxicity in susceptible patients.

The abdominal pain and vomiting are explained by the effect of cannabinoids on CB-1 receptors in the intestinal nerve plexus, causing relaxation of the lower esophageal sphincter and inhibition of gastrointestinal motility. This finding is supported by gastric emptying studies performed on one of the patients presented by Allen et al, which revealed severely delayed emptying. While cannabis appears to have anti-emetic effects that are centrally mediated, it is possible that these effects predominate at low doses whereas the gastrointestinal effects predominate at the high concentrations that occur with long-term use.

The proposed explanation for compulsive hot water bathing is based on the fact that cannabis disrupts autonomic and thermoregulatory functions of the hippocampal-hypothalamic-pituitary system. There is a high concentration of CB1 receptors within the limbic system, and the hypothalamus in particular is known to be responsible for integrating central and peripheral thermosensory input. Furthermore, Δ9-

THC induces hypothermia in mice in a dose-dependent manner. While this evidence links cannabis to the hypothalamus and to thermoregulation, it does not provide a causal relationship. Two mechanisms proposed by Chang et al are that (1) cannabinoid-induced hypothermia causes the desire for hot water bathing, or (2) hot water bathing is the direct result of CB1 activation in the hypothalamus.

The true mechanism underlying hot water bathing remains enigmatic, and further studies are needed to elucidate the relationship between this bizarre learned behavior and the other features of cannabinoid hyperemesis.

A timely diagnosis of cannabinoid hyperemesis is essential not only to effect proper treatment but also to prevent iatrogenic morbidity and mortality from unnecessary diagnostic procedures and surgical interventions. There are, however, several obstacles to effective diagnosis:

First, the legal status of marijuana makes eliciting an accurate drug history challenging. Second, the bizarre hot water bathing is likely often attributed to psychological conditions such as obsessive-compulsive behavior. Third, the knowledge of the anti-emetic effects of cannabis likely disguises cases of cannabinoid hyperemesis, leading to the erroneous belief that cannabis is treating cyclic vomiting rather than causing it.

Finally, the fact that this syndrome is so recently described and relatively unknown outside an esoteric subset of the GI literature means that most clinicians are unaware of its existence. The following diagnostic criteria adapted from Sontineni et al can be used to facilitate a diagnosis of cannabinoid hyperemesis syndrome:

ESSENTIAL FEATURES
History of chronic cannabis use
Nausea and cyclic vomiting over months
Relief with cessation of cannabis use
SUPPORTING FEATURES
Compulsive hot water bathing with transient relief of symptoms
Colicky abdominal pain
Exclusion of other etiologies (especially gall-bladder and pancreas)
In the case of the 18-year-old patient presented above, asking the open-ended question, “What makes you feel better?” followed by more focused questions regarding the temperature of the water and the history of marijuana use were sufficient to suggest the diagnosis of cannabinoid hyperemesis.
We propose that these questions be used as a screening tool for all patients presenting with cyclic vomiting. Based on our experience and a review of the literature, we believe that these questions may be both sensitive and specific for detecting this unusual syndrome.
The patient presented in this case was counseled on his likely diagnosis.

Though he was initially skeptical, giving him printouts of case reports on cannabinoid hyperemesis syndrome and discussing the etiology of the disease were sufficient to convince him of the diagnosis. He was treated symptomatically in the hospital. Two weeks after discharge, he remains abstinent from marijuana and reports that his symptoms are improving.
Sarah A. Buckley and Nicholas M. Mark both are 4th year medical students at NYU School of Medicine
Faculty reviewed by Robert Hoffman, MD, Director NYU Poison Control Center, Associate Professor Departments of Medicine and Emergency Medicine, NYU Langone Medical Center

Source http://www.clinicalcorrelations.org/?p=2877 July 15th 2010

A TENFOLD increase in hospital treatment for cannabis poisoning or dependence among people in their 30s and 40s suggests the habit has run out of control for a hard core of long-term users.
Australian research shows that while cannabis consumption overall decreased during the past decade, the rate of hospital treatment rose. Treatment rates are highest among people in their 20s, but the steepest increase has been among older people, with those in their 30s only slightly less likely to seek help than younger people by 2007, the study shows.
Seven years earlier, people in their 30s were being treated at only half the rate of their younger counterparts, according to the findings of the National Drug and Alcohol Research Centre at the University of NSW. Their faster rise in cannabis-related health problems coincided with greater frequency of daily use.
“These people started their use early and have [in some cases] then gone on to develop problems,” the study leader, Amanda Roxburgh, said. “They might not necessarily think that they have a problem with their use until it kicks into crisis mode.” People in their 20s were about 50 per cent more likely to have used cannabis during a one-year period compared with those in their 30s. But of those who did so, nearly 20 per cent of the older age group had developed a daily habit, against about 15 per cent of the younger adults.
Ms Roxburgh, whose results are published in the journal Addiction, said the rise in problematic use might reflect increased cannabis potency, though there was no formal evidence the drug had become stronger. Its falling price suggested it was being produced more efficiently – perhaps through indoor hydroponic cultivation – and this might have made it more accessible.
Jan Copeland, who heads the National Cannabis Prevention and Information Centre, said older people were more likely to consider cannabis safe. “These people come from age groups where cannabis is a benign herb and natural,” she said. “But when you are doing something every day you don’t realise the difficulties when you try to stop”.
Cannabis use among people aged 14 to 19 more than halved between 1996 and 2005, but the study also found pockets of harmful use in that group. Nearly two-thirds of young daily cannabis users reported difficulties controlling their use.
Members of this group were also more likely to report smoking 10 or more cones or joints a day, and if they were treated in hospital for their cannabis use were more likely to be treated for psychosis than older users.
Professor Copeland said young people now understood cannabis could be dangerous, and fewer were experimenting, but dedicated treatment programs were still needed for young people with a serious habit.
Will Temple, chief executive officer of the Watershed drug and alcohol recovery and education centre in Wollongong, said his centre had gone from treating almost no cannabis users to in the past six months treating 30 per cent of clients for cannabis use.
Source: The Sydney Morning Herald 29th March 2010

Scientists at Melbourne’s Howard Florey Institute have discovered a system in the brain that stops an alcoholic’s craving for alcohol, as well as prevent relapse once they have recovered from alcohol addiction.
________________________________________
The ‘Orexin’ system is a group of cells in a part of the brain called the hypothalamus. These cells produce Orexin, which was originally implicated in the regulation of feeding, but it soon became apparent that Orexin was also involved in the ‘high’ felt after drinking alcohol or taking illicit drugs.

In studies conducted with rats, Dr Andrew Lawrence and his Florey colleagues used a drug that blocked Orexin’s euphoric effects in the brain and the results were remarkable.
“In one experiment, rats that had alcohol freely available to them stopped drinking it after receiving the Orexin blocker.” Dr Lawrence said. “In another experiment, rats that had gone through a detox program and were then given the Orexin blocking drug, did not relapse into alcohol addiction when they were reintroduced to an environment in which they had been conditioned to associate with alcohol use.

“Orexin reinforces the euphoria felt when drinking alcohol, so if a drug can be developed to block the Orexin system in humans, we should be able to stop an alcoholic’s craving for alcohol, as well as preventing relapse once the alcoholic has recovered,” he said.
Dr Lawrence said that this research could also lead to treatments for eating disorders, such chronic over-eating, which leads to obesity. “Our research shows that alcohol addiction and eating disorders set off common triggers in the brain, so further investigations may uncover drug targets in the Orexin system to treat both conditions,” Dr Lawrence said.

The Florey scientists are now conducting multiple experiments to discover the precise circumstances that activate the Orexin system. “To explore this discovery further we are now investigating how different experimental paradigms and environmental situations impact on the Orexin system, which will hopefully pinpoint therapeutic drug targets,” Dr Lawrence said.
“Before a therapeutic Orexin-blocking drug can be developed, we need to ensure that it will be safe to use in the long-term and that issues surrounding a person’s compliance in taking the drug are considered,” he said.

According to the World Health Organisation, alcohol is one of the most widely used and abused substances in the world and causes as much, if not more death and disability as measles, malaria, tobacco, or illegal drugs.
Dr Lawrence and his colleagues were the first in the world to demonstrate the Orexin system’s involvement in alcohol addiction and their research paper was recently published in the prestigious British Journal of Pharmacology. Dr Lawrence’s paper was downloaded 658 times by researchers from around the world in the first three months of its publication, making it the most downloaded research paper in that issue and supporting the research’s importance.
The Howard Florey Institute is Australia’s leading brain research centre. Its scientists undertake clinical and applied research that can be developed into treatments to combat brain disorders, and new medical practices. Their discoveries will improve the lives of those directly, and indirectly, affected by brain and mind disorders in Australia, and around the world. The Florey’s research areas cover a variety of brain and mind disorders including Parkinson’s disease, stroke, motor neuron disease, addiction, epilepsy, multiple sclerosis, autism and dementia.

Source: ScienceDaily. Retrieved March 28, 2010 Howard Florey Institute (2006, December 13).
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Abstract

Aims
The present study represents the first large-scale test of the capacity to predict illicit drug treatment outcomes of an instrument [Stages of Change and Treatment Eagerness Scale (SOCRATES)] purporting to measure processes underlying stages of change. The main hypothesis was that ‘taking steps’ should be predictive of less frequent use of illicit opiates (heroin and non-prescribed methadone) at follow-up.

Design
The sample comprised 1075 people seeking treatment for drug abuse problems in 54 treatment agencies in England. The study uses a longitudinal, prospective cohort design. Structured interviews were conducted at treatment intake and at 1-year follow-up. Data were collected about illicit drug use (frequency of use of heroin, non-prescribed methadone, cocaine and amphetamines, and non-prescribed benzodiazepines) and other problems.

Findings
Results failed to support the hypothesis that taking steps should be associated with less frequent use of illicit opiates at follow-up. No statistically significant associations of any kind were found between readiness for change measures and use of opiates or stimulants at follow-up. A negative association was found between taking steps and benzodiazepine misuse. Readiness for change measures were correlated with heroin use and psychiatric symptom scores at treatment intake.
Conclusions
Readiness for change measures were not associated with illicit drug use outcomes. Of the 12 hypothesized relationships between readiness for change measures and outcomes, our results show only one ‘hit’ and 11 ‘misses’.

Source: Addiction Volume 102 Issue 2 Page null – February 2007 Addiction 102 (2)

Research Summary

Researchers from Stanford University found that a *12-step oriented treatment program that included attending Alcoholics Anonymous meetings boosted two-year sobriety rates by 30 percent compared to cognitive-behavioral (CB) programs, the BBC reported Jan. 29.
Twelve-step oriented programs also cost 30 percent less than CB-based treatment for addiction, the researchers said.
Lead study author Keith Humphreys said the spiritual dimension of AA may explain why recovering alcoholics in such programs are better able to resist the temptation to return to drinking.
The study appears in the journal Alcoholism: Clinical and Experimental Research.
*Editor’s Note, Jan. 31, 2007:
As originally published on January 30, the title of the summary read: “AA Boosts Sobriety by 30 Percent, Study Says.” We have changed the title and summary to clarify that the researchers studied 12-step oriented treatment programs — not only AA meetings.

Source: Humphreys, K., Moos, R.H. (2007) Encouraging Posttreatment Self-Help Group Involvement to Reduce Demand for Continuing Care Services: Two-Year Clinical and Utilization Outcomes. Alcoholism: Clinical and Experimental Research, 31(1): 64–68; doi: 10.1111/j.1530-0277.2006.00273.x.

Brief skills training is effective to curb college drinking
A study in Swedish colleges, where over-use of alcohol is widespread, showed that a Brief Skills Training Program was effective in reducing alcohol consumption over a two-year period.

Students were randomly assigned to a brief skills training program (BSTP) with interactive lectures and discussions, a twelve-step–influenced (TSI) program with didactic lectures by therapists trained in the 12-step approach, and a control group. More than three quarters of the students were rated “high risk” on an alcohol consumption score.

At follow-up two years later, the high-risk students who had received the BSTP program showed significantly better outcomes than high-risk students who had undergone TSI. The TSI students did no better than the control group.

Source:The study results are in the March issue of Alcoholism: Clinical and Experimental

Research Summary

Smoking among young adults has plummeted since California implemented a groundbreaking tobacco-control plan 12 years ago, according to new research from the University of California at San Diego.

The California Tobacco Control Program, established in 1989, has been credited with reducing smoking among all adult smokers, but the decline among young adults has been especially striking, researchers said. Notably, cessation rates among young Californians were higher than among young adults in New York and New Jersey, which have similarly high tobacco prices but lack comprehensive stop-smoking campaigns, as well as compared to young adults in tobacco-growing states (TGS).

“We were surprised to find that, since the advent of the California campaign, young people have increased their rate of quitting by 50 percent, far more than their older counterparts,” said study author Karen Messer, Ph.D. “It used to be that smokers over age 50 were the ones quitting because they understood the health consequences of smoking …
“These young adults have grown up in a tobacco-controlled climate, where smoking isn’t the norm and isn’t socially supported. We may be seeing the first generation who believe it’s not cool to smoke, which could pay huge dividends in their future health.”

Another UCLA study focused on tobacco consumption trends. “We found that there is a national trend of declining cigarette consumption for all age groups, but the most significant by far was observed in California smokers over age 35,” noted researcher Wael K. Al-Delaimy, M.D., Ph.D.
“The data suggest that — compared with states with no tobacco control initiatives (TGS) or states with an increased cigarette price as the principal tobacco control measure (NY/NJ) – California’s comprehensive tobacco control program is more effective in decreasing cigarette consumption for those over age 35.”

Source: journal Tobacco Control April 2007

A Temple University psychologist argues that society would be better off using strict laws to prevent risky behaviors by adolescents rather than education programs, saying that teens’ brains are too immature to avoid risk-taking, USA Today reported April 5.
“We need to rethink our whole approach to preventing teen risk,” said researcher Laurence Steinberg, who drew his conclusions after reviewing a decade’s worth of research on the adolescent brain. “Adolescents are at an age where they do not have full capacity to control themselves. As adults, we need to do some of the controlling.”
Steinberg said society would be best served by raising the driving age, increasing cigarette prices, and enforcing underage-drinking laws than investing in prevention programs. “I don’t believe the problem behind teen risky behavior is a lack of knowledge,” he said. “The programs do a good job in teaching kids the facts. Education alone doesn’t work. It doesn’t seem to affect their behavior.”
“Kids will sign drug pledges. They really mean that, but when they get in a park on a Friday night with their friends, that pledge is nowhere to be found in their brain structure,” agreed psychologist Michael Bradley. “They’re missing the neurologic brakes that adults have.”
Isabel Sawhill, co-director of the Center on Children and Families at the Washington-based Brookings Institution, said the findings are “good research for policymakers to consider, but we shouldn’t infer from this research that all our past efforts have been ineffective. I’m not in favor of just doing education, but I’m also not in favor of not doing it, either. We need to do some of both.”

Source: Current Directions in Psychological Science. April 2007

A drug which reduces the desire for marijuana and blocks its effect on the brain has been successfully tested in rats. Scientists say the findings may translate into better therapies for cannabis addiction in humans.
Rodents given a compound derived from a plant in the buttercup family lose their hankering for a synthetic version of tetrahydrocannabinol (THC) – the active compound in marijuana. The treatment also blocked a reward response in the animals’ brains when they did receive synthetic THC.
In the first part of the experiment, Steven Goldberg at the National Institute on Drug Abuse in Maryland, US, and his colleagues placed rats in a cage with a lever the animals could push. Each time the rats leaned on the lever, they received a dose of the synthetic THC through a small tube running into their body.
Over a period of three weeks the rats learned to enjoy the effects of synthetic THC and frequently self-administered the drug. By comparison, rats that received saline solution did not press the lever often.
Goldberg’s team then injected the rats with a compound derived from the seeds of the Delphinium brownii plant, which is in the buttercup family. The compound, known as methyllycaconitine (MLA), had a dramatic effect on the animals’ behaviour.

Blocking dopamine
On the day that they received MLA they pushed the lever for synthetic THC 70% less than before. The drug did not seem to otherwise change the rats’ movement and coordination, and had no other apparent side effects.
The scientists also took a close look at the effects of MLA on the rats’ brains. They used a technique called microdialysis to take tiny fluid samples from a reward-signalling area of the brain known as the nucleus accumbens, which sits near the base of the head.
When rats receive synthetic THC, levels of the reward chemical dopamine normally shoot up in the nucleus accumbens – but MLA blocked the release of dopamine in this brain region.
“The increases in dopamine are virtually non-existent because of MLA,” says Goldberg. He adds that MLA did not lower dopamine levels below normal amounts. This is important, says Goldberg, because it suggests that a similar therapy for humans would not interfere with normal reward signalling in the brain.
He notes that the drug Rimonobant, which makes monkeys less likely to self-administer THC, has been linked to depression in humans.
The exact mechanism by which MLA works remains a mystery. Scientists know that MLA binds to specific cell receptors in the brain called alpha-7 nicotinic receptors. They speculate that cannabis indirectly triggers these receptors, but cannot do so when the receptors are blocked by MLA.

Human potential
There is a genuine need for medications to help cannabis addicts overcome their drug problem, according to Goldberg: “About 10% of the people who experiment with it go on to heavy use and have trouble voluntarily giving it up. I think there is a proportion of the population who need ways to make them stop.”
Drug-makers have recently made medications such as Chantix available to help people quit tobacco smoking. But researchers say that these drugs affect different nicotinic receptors than those triggered by THC.
And while some people have pushed Rimonobant as a possible remedy for addiction, Goldberg says that more options – such as one based on MLA – must be explored: “Each patient is different and what works in one might not work in another.”

Source: Journal of Neuroscience (DOI: 10.1523/JNEUROSCI.0027-07.2007)

May 23, 2007
Research Summary

A compound known as methyllycaconitine (MLA) appears to block craving for and the effects of a synthetic version of THC, the main active ingredient in marijuana, New Scientist reported May 22.
Animal tests revealed that MLA, derived from Delphinium brownii, a plant in the buttercup family, cut craving for THC and blocked the brain’s reward response for the drug. Rats that received injections of MTA pushed a lever for doses of THC 70 percent fewer times than on days where they did not receive MLA.
Studies of the rats’ brains also showed that THC did not increase dopamine levels when MLA was present. “The increases in dopamine are virtually nonexistent because of MLA,” said lead researcher Steven Goldberg of the National Institute on Drug Abuse, who said the findings could have implications for addiction treatment for humans.

Source: The study was published in the Journal of Neuroscience.

A prescription-only pill with a high success rate in helping people to quit smoking is to become available on the NHS after a decision yesterday by the government’s drugs watchdog.
The National Institute for Clinical Excellence gave draft approval for the health service to provide varenicline, which is manufactured by Pfizer under the brand name Champix. Trials showed the twice-daily pill provided relief from cravings and withdrawal symptoms experienced by smokers in the weeks after quitting.

The manufacturers said it also reduced the satisfaction smokers would get from cigarettes in the event of a relapse.
During the trials, 44% of smokers had quit by the end of a 12-week course. This compared with a 30% success rate for the anti-smoking drug Zyban and 18% for smokers who were given a placebo.
The recommended 12-week course of treatment costs about £163.80.
Giving draft approval allows NHS trusts or professional bodies to register objections before a decision in July. NHS trusts would then have three months to make funding available. A spokeswoman for Nice said: “Having looked at all the evidence, our independent committee has concluded that varenicline appears to be a good way to help people who want to quit smoking.”
Robert West, professor of health psychology at University College London, said: “This guidance gives smokers who are serious about stopping another choice from a good range of clinically proven treatments. Smokers who combine treatments with the right support…could significantly increase their odds of successfully quitting for life.”

Source Thursday May 31, 2007 The Guardian

Research Summary

Vitamin K helps prevent brain injury in newborns. If alcohol dependence is associated with brain development in infancy, giving babies vitamin K might reduce their future risk of dependence. To explore this possibility, researchers studied a 30-year prospective cohort of male infants in Denmark.
Of 238 men, 18% had received 1 mg of vitamin K intramuscularly at birth, 16% had alcohol dependence (assessed at age 30), and 68% had fathers with alcohol dependence. Receipt of vitamin K was not significantly associated with gestational age, birth weight, birth complications, or signs of neurological impairment at birth.
• Only 5% of men who had received vitamin K at birth had alcohol dependence compared with 18% of men who had not received the vitamin.
• In an analysis adjusted for birth weight and having a father with alcohol dependence, men who had received vitamin K had significantly fewer symptoms of alcohol dependence.
Comments by Richard Saitz, MD, MPH:
The results of this analysis suggest that perinatal brain injury (e.g., hemorrhage, which is now much less common due to universal administration of vitamin K to neonates) increases the risk of alcohol dependence. These results also imply that preventive interventions that reduce neurological trauma early in life may lower vulnerability to dependence later.
Reprinted with permission from Alcohol and Health: Current Evidence.

Source: JoinTogether Online. Jan.2006

A longer-acting alternative to methadone that never quite caught on following its FDA approval in 1993 may now greatly increase the number of addicts who stick with treatment, thanks to a new Johns Hopkins study.

The study suggests better ways of taking LAAM (levomethadyl acetate hydrochloride), a drug similar to methadone in its capacity to discourage heroin use and block withdrawal symptoms. However, unlike methadone, which addicts must use daily, LAAM can be taken three times a week, making it far more convenient and potentially less expensive.
LAAM isn’t widely used, because of both uncertainties about how effective it is in the first stages of addiction treatment and doubts that it would be accepted by addicts. Earlier this year, for example, only about 3,000 U.S. patients were getting the drug.
“Use of LAAM has been less than hoped for since its approval by the Food and Drug Administration,” says Rolley E. Johnson, Pharm.D, associate professor of psychiatry, who headed the Hopkins study. Early studies didn’t test participants’ responses at various dosages, and under the cautious little-by-little approach to giving the medication, it appeared less effective than methadone at the first stage of treatment. Because of this, many assumed that LAAM lacked the necessary opiate-like effects early on. “Users said they couldn’t feel the drug working and were more likely to drop out of treatment,” Johnson noted.
The new Hopkins study, however, reported in this month’s Archives of General Psychiatry, shows that at the proper dosage on the proper schedule, LAAM is safe, effective and acceptable to addicts. “It could become a valuable addition to heroin addiction programs. Its convenience compared with methadone is a great advantage for addicts who hold jobs,” says Hendree Jones, Ph.D., one of the investigators. “They can earn a living more easily while continuing to receive treatment.”
To test LAAM, researchers gave 180 heroin-addicted volunteers either low-, medium-, or high-dose schedules, phasing in the drug over 17 days. They then looked at a combination of drug tests on subjects’ urine samples and subjects’ own reports to get a picture of how their heroin use had changed.
Heroin use dropped in all groups. The reduction was significant, though, in the high-dose group, showing a more than 80 percent plunge in self-reported heroin use. Also, more than 80 percent of the volunteers stayed with the trials, says Johnson. “That’s high for a study like this. It’s a good sign that most participants accepted LAAM.”
Though LAAM seems to work best on the high-dose course, Johnson says, that dose also had the most subjects drop out of the study. “It’s mostly because side effects begin to appear at higher doses.” So he suggests an approach that uses careful monitoring as the dose gets higher. Johnson would like to see more studies to help figure the optimal LAAM dose for individual patients: “Then we’ll be able to help even more addicts.”
LAAM works on the tiny receptors in the membranes of nerve cells in the brain. It binds to the so-called mu opioid receptors, the same ones that heroin and methadone target. Once attached, molecules of LAAM stimulate the receptors. But because LAAM remains there for a relatively long time, it blocks receptor access for other opioid drugs: addicts take heroin, for example, and it has none of its usual effects.

Source. ScienceDaily. Retrieved March 11, 2009, from http://www.sciencedaily.com¬ /releases/1998/08/980817081828.htm

According to details given by the NHS, there has been a 65 per cent increase in people receiving treatment for cocaine addiction in UK. These are teenagers which is cause of concern.
These figures correspond to the announcement by the Advisory Council on the Misuse of Drugs (ACMD) earlier. It was found by an NHS study, conducted by the National Treatment Agency for Substance Misuse, that the number these teenagers has doubled since 2005.
It was reported that users were combining cocaine with alcohol that causes more damage to the heart and makes users more violent. It was noticed that a six-month treatment treated four in 10 people and they were no longer addicted, but several left the treatment midway.
In England, about 12,354 people were treated for cocaine addiction last year. Between 2005-06 and 2008-09 a rise was seen in the number of people coming for treatment and the figures increased from 453 to 745, and the number of 18- to 24-year-olds doubled from 1,586 to 3,005.
The chairman of the ACMD, Professor Les Iversen stated, “The figures were deeply concerning.”
The Conservatives and Liberal Democrats both stated that a change was needed in the government’s approach to tackling addiction.

Source: www.topnews.net.nz 3rdMarch 2010

Research Summary
Using electrical charges to stimulate the subthalmic nucleus region of the brain may mitigate cocaine addiction without disrupting the dopamine system like current anti-addiction medications, according to French researchers.
The Los Angeles Times reported Dec. 28 that researchers reported that deep brain stimulation performed on cocaine-addicted lab rats resulted in the rats exhibiting less self-administration of the drug than an untreated control group.
Researchers also found that the treated rats seemed to break the association with an area where cocaine had been distributed, preferring to instead linger in an area where food was provided.
Source: Proceedings of the National Academy of Sciences (PDF). Dec.2009

For Immediate Release – January 5, 2010 – (Toronto) – A recent evaluation by the Centre for Addiction and Mental Health (CAMH) shows that online interventions for problem alcohol use can be effective in changing drinking behaviours and offers a significant public health benefit.
In the first evaluation of its kind, the study published in Addiction found that problem drinkers provided access to the online screener www.CheckYourDrinking.net, reduced their alcohol consumption by 30% — or six to seven drinks weekly – rates that are comparable to face-to-face interventions. This result was sustained in both the three and six month follow-up.
Source: www.camh.net 5 Jan.2010

ABSTRACT
The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit.
Eleven were maintained on methadone 50 mg PO daily as treatment for their opioid abuse; 11 were opioid abusers who were not physically dependent on opioids and who provided opioid-free urines throughout the study. Each subject received acute cocaine challenge doses of 0, 12.5, 25, and 50 mg intravenously in random order under double-blind conditions in separate test sessions.
Physiologic and subject-rated responses were measured before injection and for 2 h after. In the methadone maintenance group, cocaine challenge sessions occurred 15.5 h after the daily methadone dose. There were significant differences between the methadone-dependent and nondependent groups: 1) baseline differences related to chronic methadone administration and not associated with cocaine administration (lower respiration rates and pupil diameter; higher skin temperature) and 2) differences in response to cocaine administration; cocaine-induced increases in subject ratings of Drug Effect, Rush, Good Effects, Liking, and Desire for Cocaine and in heart rate were greater in the methadone maintenance patients compared to the non-dependent group.
These results indicate that the positive subjective effects and some physiological effects of cocaine are enhanced in methadone-maintained individuals, suggesting a pharmacological basis for the high rates of cocaine abuse among methadone maintenance patients.

Source: Psychopharmacology (Berl) 1996 Jan;123(1):15-25

Although methadone failure has been studied, the contribution of plasma binding proteins like AGP (α1-acid-glycoprotein) has not been thoroughly examined. For a drug to confer a desired therapeutic effect it must reach a minimal effective concentration (MEC) at its site of action, often accessed via the bloodstream. It is proposed that when plasma AGP concentration increases, like in the acute phase response to stress and inflammation (Elliott et al., 1997, Paterson et al., 2003) more methadone binds the protein and so there is less free (unbound) drug available to bind receptors and achieve the desired therapeutic effect. This could cause therapy failure with patients taking additional opiates to compensate; Methadone Maintenance is a corrective, not a permanent curative procedure (Sees et al., 2000).

The aim of this research is to determine, in a sample of people undergoing methadone therapy, whether there are individual differences in the concentration and glycosylation pattern of the plasma protein AGP. Also, the extent it binds methadone will be investigated to determine whether the MEC is reduced and therefore the therapeutic effect.

It is hypothesised that there will be an increased concentration of AGP present in the samples which will cause a decrease in the concentration of free methadone available to bind receptors. Therefore the normal pharmaco-logical effect is lost causing the therapy to fail (individuals would take additional opiates).

The work is being carried out at School of Life Sciences, Napier University, Edinburgh who is working in conjunction with Dr Malcolm Bruce, Consultant Psychiatrist in Addiction, Community Drug Problem Service, 22-24 Spittal Street, Edinburgh, EH3 9DU and is being funded by the Carnegie Trust.

Use of a controversial stomach implant designed to block the effects of heroin must be urgently reined in, according to drug specialists who say addicts are being harmed. A new report found that naltrexone implants commonly cause severe adverse reactions, including extreme dehydration and acute renal failure in those who are fitted with them.
Nine Sydney specialists writing in the Medical Journal of Australia have called for an urgent review of use of the product, which blocks the effects of heroin and stops cravings for about six months. It has not been registered or rigorously tested in Australia but about 1,500 addicts have obtained it through the Therapeutic Goods Administration’s Special Access Scheme for people with a life-threatening need.
Controversy has surrounded the use of the implants for several years, with advocates arguing they offer addicts the best chance of overcoming their addiction and opponents branding them dangerous and ineffective.
One study published last March linked the implant to five deaths. A new study published has found that of 12 implant patients who were admitted to two Sydney hospitals last year, eight hospitalisations were implant-related. Six were suffering severe dehydration, one had acute renal failure and another had an abscess at the implant site.
“These cases challenge the notion that a naltrexone implant is a safe procedure,” said study leader Nicholas Lintzeris, a senior addiction specialist at the Sydney South West Area Health Service. He called for the widespread and unregulated use of implants to be restricted until they have been properly tested for safety and effectiveness.
Professor Robert Ali, director of the Drug Alcohol Services Council in Adelaide, agreed the product should not be so widely available.
“The disturbing suggestions of mortality and morbidity from unregistered naltrexone implants makes a strong case for an independent review to determine whether this treatment is sufficiently safe for such widespread use,” Prof Ali said.
However, another specialist, University of Western Australia Professor of Addiction Gary Hulse, said a trial he had undertaken had found the implant to be just as safe and effective as the oral form of the drug. He defended its use and said many of the criticisms levelled at naltrexone occurred because people’s withdrawals from heroin were not being managed properly.
Source: www.theage.com April 17th 2008

Long-acting injections of the drug naltrexone, combined with psychotherapy, significantly reduced heavy drinking in patients being treated for alcohol dependence, according to a study in the Journal of the American Medical Association by a Yale School of Medicine researcher.

“The decision to take medication can wane over time,” said Stephanie O’Malley, professor of psychiatry and director of the Division of Substance Abuse Research at the Connecticut Mental Health Center at Yale. “This provides coverage for an entire month.”
Acohol dependence ranks as the fourth leading cause of disability worldwide, as reported by the World Health Organization’s Global Burden of Disease project. Nationwide, it is believed to contribute to more than 100,000 preventable deaths a year.
Naltrexone belongs to a class of drugs called opioid antagonists. Although many clinical trials have shown that oral naltrexone can be effective in treating alcohol dependence, its use in clinical practice has been limited, in part patients have to take the pill daily.
In this trial conducted at 24 sites, 627 alcohol dependent patients were randomly assigned to receive either an injection of long-acting naltrexone or a placebo injection; 624 ultimately received at least one injection. All participants received 12 counseling sessions during the six-month study in addition to the medication. Long-acting naltrexone was associated with a reduction in heavy drinking within the first month of treatment, and this response was maintained over the six month treatment period.

Source:Yale University (2005, May 17). Once-a-month Naltrexone Successfully Used To Treat Alcohol Dependence. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2005/05/050517094735.htm

While youth who had a history of abuse or mental health problems were more likely to become homeless, those same characteristics didn’t predict teens and young adults getting off the street six months later.

“It looks like the predictors of homelessness might be different than the predictors of exiting homelessness,” lead author Natasha Slesnick of Ohio State University said in a statement. “So that means prevention targets should be different from intervention targets.”

Naltrexone is one of four oral medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcoholism. A recent large multicenter research study of alcohol dependence supported by the National Institute of Alcoholism and Alcohol Abuse (NIAAA), the COMBINE Study, suggested that naltrexone produced a modest but significant benefit but another FDA-approved medication, acamprosate, was ineffective.   Perhaps consistent with its modest effects in COMBINE, naltrexone is not widely prescribed in the treatment of alcoholism. Yet, clinicians report that naltrexone may have significant benefits for individual patients. To make naltrexone a more useful medication, it would be important to begin to identify groups of patients who might be more or less likely to show a significant clinical benefit from naltrexone prescription and to understand the causes of differential naltrexone efficacy.
A new study that will appear in the September 15th issue of Biological Psychiatry suggests that alcohol dependent individuals with a family history of alcohol dependence may be more likely than alcohol dependent individuals without a family history of alcohol dependence to reduce their drinking in the laboratory when prescribed naltrexone.
Krishnan-Sarin and colleagues at the NIAAA Center for the Translational Neuroscience of Alcoholism studied alcohol consumption in the laboratory by alcohol-dependent individuals who were not seeking treatment. The participants were studied in the laboratory after 6 days of treatment with 0 mg (placebo), 50 mg, or 100 mg of naltrexone. The authors discovered that naltrexone decreased drinking in those with a family history of alcoholism and this effect was greatest with the highest naltrexone dose. However, it increased drinking in those without a family history of alcoholism and this effect was greatest at the highest naltrexone dose.
John H. Krystal, M.D., one of the authors, notes that “When studied in large groups, naltrexone appears to have a rather small effect upon the ability to reduce drinking or remain abstinent from alcohol. However, there is growing evidence that there are subgroups of patients who show substantial benefit from naltrexone, even when naltrexone fails to work in the overall trial.*
“According to Suchitra Krishnan-Sarin, Ph.D., the lead author, “The results suggest that family history of alcoholism may be an important predictor of clinical response to naltrexone and could potentially be used to guide clinical practice.” Dr. Krystal agrees, “These data suggest that family history might influence the optimal dosing of naltrexone and the nature of the clinical response.” Their hope is that these findings ultimately can contribute to a better treatment experience for some who are seeking to end their battle with alcohol.
This research article: “Family History of Alcoholism Influences Naltrexone-Induced Reduction in Alcohol Drinking” by Suchitra Krishnan-Sarin, John H. Krystal, Julia Shi, Brian Pittman and Stephanie S. O’Malley. All authors are affiliated with the Department of Psychiatry at Yale University School of Medicine in New Haven, Connecticut. Dr. Krystal is also affiliated with the VA Connecticut Healthcare System in West Haven, Connecticut and he serves as the Editor of Biological Psychiatry. This article appears in Biological Psychiatry, Volume 62, Issue 6 (September 15, 2007), published by Elsevier.

Source: Elsevier (2007, September 24). Family History Of Alcoholism Affects Response To Drug Used To Treat Heavy Drinking. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2007/09/070919101735.htm

Long-acting injections of the drug naltrexone, combined with psychotherapy, significantly reduced heavy drinking in patients being treated for alcohol dependence, according to a study in the Journal of the American Medical Association by a Yale School of Medicine researcher.
“The decision to take medication can wane over time,” said Stephanie O’Malley, professor of psychiatry and director of the Division of Substance Abuse Research at the Connecticut Mental Health Center at Yale. “This provides coverage for an entire month.”
Acohol dependence ranks as the fourth leading cause of disability worldwide, as reported by the World Health Organization’s Global Burden of Disease project. Nationwide, it is believed to contribute to more than 100,000 preventable deaths a year.
Naltrexone belongs to a class of drugs called opioid antagonists. Although many clinical trials have shown that oral naltrexone can be effective in treating alcohol dependence, its use in clinical practice has been limited, in part patients have to take the pill daily.
In this trial conducted at 24 sites, 627 alcohol dependent patients were randomly assigned to receive either an injection of long-acting naltrexone or a placebo injection; 624 ultimately received at least one injection. All participants received 12 counseling sessions during the six-month study in addition to the medication. Long-acting naltrexone was associated with a reduction in heavy drinking within the first month of treatment, and this response was maintained over the six month treatment period.Source: Yale University (2005, May 17). Once-a-month Naltrexone Successfully Used To Treat Alcohol Dependence. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2005/05/050517094735.htm

Patients with a certain gene variant drank less and experienced better overall clinical outcomes than patients without the variant while taking the medication naltrexone, according to an analysis of participants in the National Institutes of Health’s 2001-2004 COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) Study. About 87 percent of patients with the variant who received naltrexone experienced good outcomes, compared with about 49 percent of those who received a placebo. About 55 percent of patients without the variant experienced a good outcome regardless of whether they received naltrexone or placebo. Good outcome was defined as abstinence or moderate drinking without related problems, according to an article in the Feb. 4 issue of the Archives of General Psychiatry.Drinking alcohol increases the release of endogenous opioids, compounds that originate in the body and promote a sense of pleasure or well-being. An opioid antagonist, naltrexone blocks brain receptors for endogenous opioids, making it easier for patients to remain abstinent or stop quickly in the event of a slip. In clinical studies, naltrexone has been shown to reduce relapse and craving for alcohol in some but not all treated patients. Earlier studies had suggested that a specific DNA variant of the opioid receptor gene (OPRM1) might have role in patients’ response to naltrexone.
“Analysis of the large COMBINE patient population increases confidence that the OPRM1 variant is in part responsible for positive responses to naltrexone. This study points to the promise of research on gene-medication interactions to refine treatment selection, improve clinical results, and inform ongoing medications development,” said National Institute on Alcohol Abuse and Alcoholism (NIAAA) director Ting-Kai Li, M.D.
Of the original 1383 COMBINE Study participants, 1013 were available to be genotyped for the current study, conducted by Raymond F. Anton, M.D., Medical University of South Carolina, and other COMBINE Study principal investigators in collaboration with David Goldman, M.D., and his colleagues in NIAAA’s Laboratory of Neurogenetics. The researchers successfully genotyped 911 of the available patients and conducted their initial analysis in 604 who are white, 135 of whom were found to carry the genetic variant. Approximately 15 to 25 percent of humans carry the variant, with considerable variation among ethnicities.
As in the COMBINE clinical trial, drinking variables evaluated in the pharmacogenetic study included the percentage of days abstinent from alcohol, the percentage of heavy drinking days, and clinical outcome during 16 weeks of active treatment. In addition to naltrexone or placebo, all patients received medical management (nine brief, structured outpatient sessions delivered by a health professional) and some also received a combined behavioral intervention (integrated cognitive-behavioral and motivational enhancement therapies, together with techniques to enhance mutual-help participation).
The researchers found that, compared with patients who do not carry the variant, white variant carriers who received naltrexone fared substantially better than other groups on all measures, including almost a 6 times greater likelihood of good clinical outcome. Extending the clinical outcome measure to variant carriers of all ethnicities reduced the benefit to just over a 3 times greater likelihood of good outcome. The researchers found no gene-medication interaction in patients who received specialized alcohol counseling, leading to them to conclude that genotyping for the variant may be most useful when naltrexone is used without intensive counseling.
Approved by the U.S. Food and Drug Administration in 1994, naltrexone is one of three indicated medications* shown to help patients reduce drinking, avoid relapse to heavy drinking, achieve and maintain abstinence, or gain a combination of these effects. The COMBINE trial showed either specialized counseling or naltrexone–each delivered with medications management–to be effective options for treating alcohol dependence. “Given that alternative treatments such as combined behavioral interventions, acamprosate, and topiramate can be offered, one could make the case that naltrexone should be used first or used primarily in carriers of the OPRM1 [variant],” state the authors.
“Research studies designed to ensure appropriate medication targeting are critical, especially as treatment for alcohol use disorders increasingly involves primary care physicians as well as specialists,” notes Mark L. Willenbring, M.D., director of NIAAA’s Division of Treatment and Recovery Research. “Without the ability to predict response for a specific patient, we must use trial-and-error to determine the correct medication–a process that may prolong illness and lead to more side effects. This study highlights the promise of truly personalized medicine and could help to move treatment of alcohol dependence into the medical mainstream.”

Source: NIH/National Institute on Alcohol Abuse and Alcoholism (2008, February 12). Gene Variant Predicts Medication Response In Patients With Alcohol Dependence. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2008/02/080207172332.htm

Source:Reported in Join Together April 2006

Scientists at Stanford University School of Medicine have discovered that a commonly available non-addictive drug can prevent symptoms of withdrawal from opioids with little likelihood of serious side effects.
The drug, ondansetron, which is already approved to treat nausea and vomiting, appears to avoid some of the problems that accompany existing treatments for addiction to these powerful painkillers, the scientists said.
Opioids encompass a diverse array of prescription and illegal drugs, including codeine, morphine and heroin. In 2007, about 12.5 million Americans aged 12 and older used prescription pain medications for non-medical purposes, according to the National Survey on Drug Use and Health, administered by the federal government’s Substance Abuse and Mental Health Services Administration.
“Opioid abuse is rising at a faster rate than any other type of illicit drug use, yet only about a quarter of those dependent on opioids seek treatment,” said Larry F. Chu, MD, assistant professor of anesthesia at the School of Medicine and lead author of the study that will be published online Feb. 17 in the Journal of Pharmacogenetics and Genomics. “One barrier to treatment is that when you abruptly stop taking the drugs, there is a constellation of symptoms associated with withdrawal.” Chu described opioid withdrawal as a “bad flu,” characterized by agitation, insomnia, diarrhea, nausea and vomiting.
Current methods of treatment are not completely effective, according to Chu. One drug used for withdrawal, clonidine, requires close medical supervision as it can cause severe side effects, while two others, methadone and buprenorphine, don’t provide a satisfactory solution because they act through the same mechanism as the abused drugs. “It’s like replacing one drug with another,” said co-investigator Gary Peltz, MD, PhD, professor of anesthesia.  “What we need is a magic bullet,” said Chu. “Something that treats the symptoms of withdrawal, does not lead to addiction and can be taken at home.”
The researchers’ investigation led them to the drug ondansetron, after they determined that it would block certain receptors involved in withdrawal symptoms.
The scientists were able to make this connection thanks to their having a good animal model for opioid dependence. Mice given morphine for several days develop the mouse equivalent of addiction. Researchers then stop providing morphine to trigger withdrawal symptoms. Strikingly, these mice, when placed into a plastic cylinder, will start to jump into the air. One can measure how dependent these mice are by counting how many times they jump. Like humans, dependent mice also become very sensitive to pain when they stop receiving morphine.
But the responses vary among the laboratory animals. There are “different flavors of mice,” explained Peltz. “Some strains of mice are more likely to become dependent on opioids.” By comparing the withdrawal symptoms and genomes of these different strains, it’s possible to figure out which genes play a major role in addiction.
To accomplish this feat, Peltz and his colleagues used a powerful computational “haplotype-based” genetic mapping method that he had recently developed, which can sample a large portion of the genome within just a few hours. This method pinpoints genes responsible for the variation in withdrawal symptoms across these strains of mice.
The analysis revealed an unambiguous result: One particular gene determined the severity of withdrawal. That gene codes for the 5-HT3 receptor, a protein that responds to the brain-signaling chemical serotonin.   To confirm these results, the researchers injected the dependent mice with ondansetron, a drug that specifically blocks 5-HT3 receptors. The drug significantly reduced the jumping behavior of mice as well as pain sensitivity – two signs of addiction.
The scientists were able to jump from “from mouse to man” by sheer luck: It turns out that ondansetron is already on the market for the treatment of pain and nausea. As a result, they were able to immediately use this drug, approved by the Food and Drug Administration, in eight healthy, non-opioid-dependent humans. In one session, they received only a single large dose of morphine, and in another session that was separated by at least week, they took ondansetron in combination with morphine. They were then given questionnaires to assess their withdrawal symptoms.
Similar to mice, humans treated with ondansetron before or while receiving morphine showed a significant reduction in withdrawal signs compared with when they received morphine but not ondansetron. “A major accomplishment of this study was to take lab findings and translate them to humans,” said principal investigator J. David Clark, MD, PhD, professor of anesthesia at Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System.
Chu plans on conducting a clinical study to confirm the effectiveness of another ondansetron-like drug in treating opioid withdrawal symptoms in a larger group of healthy humans. And the research team will continue to test the effectiveness of ondansetron in treating opioid addiction.
The scientists warned that ondansetron will not by itself resolve the problems that arise with continued use of these painkillers. Addiction is a long-term, complex process, involving both physical and psychological factors that lead to compulsive drug use. “This is not a cure for addiction,” said Clark. “It’s (wrong) to think that any one receptor is a panacea for treatment. Treating the withdrawal component is only one way of alleviating the suffering. With luck and determination, we can identify additional targets and put together a comprehensive treatment program.”
Collaborators on this study included De-Yong Liang, PhD, the study’s co-lead author, previously a research associate in the Department of Anesthesia and currently a research associate at the Palo Alto Institute for Research and Education; Xiangqi Li, MD, a life science research assistant in the department; Nicole D’Arcy, a medical student: Peyman Sahbaie, MD, a research associate at the institute; and Guochun Liao, PhD, of the pharmaceutical company Hoffman-La Roche. This work was supported by grants to Clark from the National Institutes of Health and the National Institute on Drug Abuse, and grants to Chu from the NIH and the National Institute of General Medical Sciences.
The researchers are working with the Stanford University Office of Technology Licensing to seek a patent for the use of ondansetron and related medicines in the treatment of drug addiction.
Source:  http://med-www.stanford.edu/   18-Feb-2009

ScienceDaily (Feb. 20, 2009) — An ingredient in licorice shows promise as an antidote for the toxic effects of cocaine abuse, including deadly overdoses of the highly addictive drug, researchers in Korea and Pennsylvania are reporting.
In the new study, Meeyul Hwang, Chae Ha Yang, and colleagues note that there is currently no effective medicine for treating cocaine abuse or addiction. Recent animal studies conducted by the researchers show that a licorice ingredient called isoliquiritigenin (ISL) can block the nervous system’s production of dopamine. That neurotransmitter is involved in emotion, movement, and other brain activities.
Cocaine and other addictive drugs stimulate dopamine and help produce the pleasurable and addictive effects. Drugs that block dopamine block this response. The scientists used rats as model animals to show that rats injected with ISL just prior to cocaine-administration showed 50 percent less of the behavioral effects associated with the illicit drug.
They also showed that ISL injections protected nerve cells in the brain from cocaine-associated damage.

Source: ScienceDaily. http://www.sciencedaily.com¬ /releases/2009 February 22, 2009

ScienceDaily (Feb. 19, 2009) — Scientists at Stanford University School of Medicine have discovered that a commonly available non-addictive drug can prevent symptoms of withdrawal from opioids with little likelihood of serious side effects. The drug, ondansetron, which is already approved to treat nausea and vomiting, appears to avoid some of the problems that accompany existing treatments for addiction to these powerful painkillers, the scientists said.

Opioids encompass a diverse array of prescription and illegal drugs, including codeine, morphine and heroin. In 2007, about 12.5 million Americans aged 12 and older used prescription pain medications for non-medical purposes, according to the National Survey on Drug Use and Health, administered by the federal government’s Substance Abuse and Mental Health Services Administration.
“Opioid abuse is rising at a faster rate than any other type of illicit drug use, yet only about a quarter of those dependent on opioids seek treatment,” said Larry F. Chu, MD, assistant professor of anesthesia at the School of Medicine and lead author of the study that will be published online Feb. 17 in the Journal of Pharmacogenetics and Genomics. “One barrier to treatment is that when you abruptly stop taking the drugs, there is a constellation of symptoms associated with withdrawal.” Chu described opioid withdrawal as a “bad flu,” characterized by agitation, insomnia, diarrhea, nausea and vomiting.
Current methods of treatment are not completely effective, according to Chu. One drug used for withdrawal, clonidine, requires close medical supervision as it can cause severe side effects, while two others, methadone and buprenorphine, don’t provide a satisfactory solution because they act through the same mechanism as the abused drugs. “It’s like replacing one drug with another,” said co-investigator Gary Peltz, MD, PhD, professor of anesthesia.
“What we need is a magic bullet,” said Chu. “Something that treats the symptoms of withdrawal, does not lead to addiction and can be taken at home.”
The researchers’ investigation led them to the drug ondansetron, after they determined that it would block certain receptors involved in withdrawal symptoms.
The scientists were able to make this connection thanks to their having a good animal model for opioid dependence. Mice given morphine for several days develop the mouse equivalent of addiction. Researchers then stop providing morphine to trigger withdrawal symptoms. Strikingly, these mice, when placed into a plastic cylinder, will start to jump into the air. One can measure how dependent these mice are by counting how many times they jump. Like humans, dependent mice also become very sensitive to pain when they stop receiving morphine.
But the responses vary among the laboratory animals. There are “different flavors of mice,” explained Peltz. “Some strains of mice are more likely to become dependent on opioids.” By comparing the withdrawal symptoms and genomes of these different strains, it’s possible to figure out which genes play a major role in addiction.
To accomplish this feat, Peltz and his colleagues used a powerful computational “haplotype-based” genetic mapping method that he had recently developed, which can sample a large portion of the genome within just a few hours. This method pinpoints genes responsible for the variation in withdrawal symptoms across these strains of mice.
The analysis revealed an unambiguous result: One particular gene determined the severity of withdrawal. That gene codes for the 5-HT3 receptor, a protein that responds to the brain-signaling chemical serotonin.
To confirm these results, the researchers injected the dependent mice with ondansetron, a drug that specifically blocks 5-HT3 receptors. The drug significantly reduced the jumping behavior of mice as well as pain sensitivity — two signs of addiction.
The scientists were able to jump from “from mouse to man” by sheer luck: It turns out that ondansetron is already on the market for the treatment of pain and nausea. As a result, they were able to immediately use this drug, approved by the Food and Drug Administration, in eight healthy, non-opioid-dependent humans. In one session, they received only a single large dose of morphine, and in another session that was separated by at least week, they took ondansetron in combination with morphine. They were then given questionnaires to assess their withdrawal symptoms.
Similar to mice, humans treated with ondansetron before or while receiving morphine showed a significant reduction in withdrawal signs compared with when they received morphine but not ondansetron. “A major accomplishment of this study was to take lab findings and translate them to humans,” said principal investigator J. David Clark, MD, PhD, professor of anesthesia at Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System.
Chu plans on conducting a clinical study to confirm the effectiveness of another ondansetron-like drug in treating opioid withdrawal symptoms in a larger group of healthy humans. And the research team will continue to test the effectiveness of ondansetron in treating opioid addiction.
The scientists warned that ondansetron will not by itself resolve the problems that arise with continued use of these painkillers. Addiction is a long-term, complex process, involving both physical and psychological factors that lead to compulsive drug use. “This is not a cure for addiction,” said Clark. “It’s naïve to think that any one receptor is a panacea for treatment. Treating the withdrawal component is only one way of alleviating the suffering. With luck and determination, we can identify additional targets and put together a comprehensive treatment program.”
Collaborators on this study included De-Yong Liang, PhD, the study’s co-lead author, previously a research associate in the Department of Anesthesia and currently a research associate at the Palo Alto Institute for Research and Education; Xiangqi Li, MD, a life science research assistant in the department; Nicole D’Arcy, a medical student: Peyman Sahbaie, MD, a research associate at the institute; and Guochun Liao, PhD, of the pharmaceutical company Hoffman-La Roche. This work was supported by grants to Clark from the National Institutes of Health and the National Institute on Drug Abuse, and grants to Chu from the NIH and the National Institute of General Medical Sciences.
The researchers are working with the Stanford University Office of Technology Licensing to seek a patent for the use of ondansetron and related medicines in the treatment of drug addiction.

Source:  Science Daily 19th Feb 2009

ScienceDaily (Mar. 8, 2009) — New findings may significantly improve the safety of methadone, a drug widely used to treat cancer pain and addiction to heroin and other opioid drugs, according to researchers at Washington University School of Medicine in St. Louis and the University of Washington in Seattle.
The researchers discovered that the body processes methadone differently than previously believed. Those incorrect assumptions about methadone have been making it difficult for physicians to understand how and when the drug is cleared from the body and may be responsible for unintentional under- or overdosing, inadequate pain relief, side effects and even death.
For many years, methadone has been a mainstay in the treatment of opioid addiction. Taken orally, it suppresses withdrawal and reduces cravings. In recent years, doctors have prescribed methadone more frequently as an effective treatment for acute, chronic and cancer pain. Use of the drug for pain treatment rose 1,300 percent between 1997 and 2006. As more methadone was prescribed, however, adverse events increased by approximately 1,800 percent, and fatalities were up more than 400 percent (from 786 to 3,849) between the years 1999 and 2004.
“Unfortunately, increased methadone use for pain has coincided with a significant increase in adverse events and fatalities related to methadone,” says principal investigator Evan D. Kharasch, M.D., Ph.D., an anesthesiologist and clinical pharmacologist at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis. “The important message is that guidelines used by clinicians to direct methadone therapy may be incorrect.”
Kharasch, the Russell D. and Mary B. Shelden Professor and director of the Division of Clinical and Translational Research in Anesthesiology at the School of Medicine, and his colleagues report the findings in the March issue of the journal Anesthesiology and online in the journal Drug and Alcohol Dependence.
The investigators wanted to understand how protease inhibitors, drugs that keep the immune system functioning in patients with HIV, interact with methadone. For years, the enzyme P4503A was believed to be responsible for clearing methadone from the body. But when healthy volunteers were given a low dose of methadone together with protease inhibitors that caused profound decreases in the activity of P4503A, there was no reduction in the clearance of methadone.
There were two reasons to study what happened to methadone when taken together with those drugs: First, HIV-AIDS patients may receive methadone for pain and, in some cases, for accompanying substance abuse problems, along with one or more protease inhibitors. In addition, many protease inhibitors interact with the P4503A enzyme that traditionally was thought to be important to methadone clearance. In these studies, Kharasch and his team looked at interactions among methadone, the P4503A enzyme in the intestine and liver and the protease inhibitors nelfinavir, indinavir and ritonavir.
They gave study volunteers a combination of the protease inhibitors ritonavir and indinavir. Both drugs profoundly inhibited the actions of the enzyme. If that enzyme were responsible for methadone clearance, then inhibiting it should have caused methadone to build up in the body. But the researchers found that it had no effect on methadone levels.
Volunteers in the second study received the protease inhibitor nelfinavir. Again, the drug inhibited the action of the P4503A enzyme. That should have meant methadone concentrations would rise, but they actually decreased by half.
“For more than a decade, practitioners have been warned about drug interactions involving the enzyme P4503A that might alter methadone metabolism,” Kharasch says. “The package insert says inhibiting the enzyme may cause decreased clearance of methadone, but our research demonstrates that P4503A has no effect on clearing methadone from the body. So the package insert appears to be incorrect, or certainly needs to be reevaluated, as do guidelines that explain methadone dosing and potential drug interactions.”
That can be dangerous, Kharasch explains, because a clinician may prescribe too much or too little methadone for patients taking drugs that interact with P4503A, having been informed that they also would influence methadone clearance. Too little methadone will not relieve pain. Too much can contribute to the unintentional build-up of methadone in the system, which can cause slow or shallow breathing and dangerous changes in heartbeat. Physicians could be unintentionally prescribing methadone incorrectly.
“The highest risk period for inadequate pain therapy or adverse side effects is during the first two weeks a patient takes methadone,” Kharasch says. “If we can provide clinicians with better dosing guidelines, then I believe we will be able to better treat pain and limit deaths and other adverse events.”
About a dozen related liver enzymes are part of the P450 family, and Kharasch believes another enzyme from that family may be the one actually involved in methadone metabolism and clearance. His laboratory is determined to identify the correct enzyme to limit over-and under-dosing of patients taking methadone to improve addiction and pain treatment as well as patient safety. Currently, he’s testing the related enzyme P4502B. Laboratory studies and preliminary clinical results indicate that P4502B may be involved, but he says more clinical research is needed.
“The research also is important for the treatment of HIV-AIDS,” Kharasch says. “Protease inhibitors can interfere with the activity of P4503A but increase the activity of P4502B. This paradox is highly unusual, and because these two enzymes metabolize so many prescription drugs, there are many potential drug interactions that we’ll be able to understand better if we can get a better handle on how these pathways absorb drugs into the system and clear them from the body.”
This research was supported by grants from the National Institute on Drug Abuse of the National Institute of Health and by an NIH grant to the University of Washington General Clinical Research Center.
Source: ScienceDaily 8 March 2009. 11 March 2009 <http://www.sciencedaily.com¬ /releases/2009/03/090303102736.htm>.

Researchers in the Discipline of Pharmacology have discovered a genetic variation that may help determine the most effective methadone dosage levels for individual heroin addicts.
The genetic discovery reveals why some people are either less efficient or more effective in distributing drugs throughout their body to the central nervous system.
Lead researcher Dr Janet Coller says accurate dosing of methadone is essential to successfully treat drug addicts because up to 62% fail to remain in the methadone program due to the severe withdrawal symptoms.
“Individualised dosing may decrease the incidence of withdrawal symptoms in some people and therefore encourage them to continue with the methadone treatment.”
An estimated 10 million people worldwide are heroin dependent, including 74,000 Australians, incurring enormous health, social and economic costs.
“More than 40,000 people are undergoing methadone treatment in Australia and only 38% of them are staying in the program at the moment. Most drop out at the start of the treatment when the withdrawal effects are severe,” Dr Coller says.
This breakthrough will allow individuals undergoing the methadone treatment program to be tested for the genetic variation to determine optimal treatment doses.
The pharmacology study was conducted collaboratively as part of Dr Coller’s postdoctoral and Daniel Barratt’s PhD studies, supervised by Professor Andrew Somogyi, with the assistance of Karianne Dahlen and Morten Loennechen, Masters of Science students from Denmark. The results have been published in the December issue of the journal Clinical Pharmacology and Therapeutics.
Source: University Of Adelaide (2007, January 29). Breakthrough For Heroin Addiction Treatment. ScienceDaily. Retrieved March 11, 2009, from http://www.sciencedaily.com¬ /releases/2007/01/070128135642.htm

 COST OF SUBSTANCE  The breakdown on federal and state money for substance abuse and addiction (numbers don’t add up to 100% due to rounding):
     95.6% Health care/assistance/prosecution
      2.4% Prevention/treatment/research
      1.4% Regulation/compliance
      0.7% Interdiction (federal only)
Source: The National Center on Addiction and Substance Abuse at Columbia University
 
Most of the taxpayer money devoted to combating alcohol and drug abuse goes to cleaning up its consequences, while only about 2% of the funding is used for prevention, says a report from the National Center on Addiction and Substance Abuse (CASA) at Columbia University.
The study found that 96% of the $467.7 billion a year that federal, state and local governments spend on substance abuse is used to deal with consequences such as crime and homelessness.
Of that money, according to the report, governments spend the most on health care costs associated with substance abuse (58%) followed by the costs of prosecuting and jailing the offenders (13.1%).
“The killer finding is that we are spending 96 cents of every dollar we spend on substance abuse and addiction to shovel up the human wreckage,” says Joseph Califano Jr., founder and chairman of CASA. “We’re making this really tiny investment in prevention and treatment when we have enough experience to know that prevention and treatment can reduce the shoveling-up burden.”
Researchers determined spending amounts by analyzing federal, state and local budgets for the year 2005, the most recent year that complete data were available, Califano says.
“These governments have it backwards,” he says. “They’re wasting billions of dollars of taxpayers’ money and not making some relatively simple investments that could sharply reduce the consequences of drug and alcohol addiction.”
Califano says the main reason that federal and state governments aren’t ready to change priorities is because there is a stigma attached to alcohol and drug addiction.
To reduce the amount spent on substance abuse, Califano says, the government needs to “mount major prevention programs,” with a focus on kids.
He adds that increasing taxes on alcohol and training doctors to talk to patients about their substance use also will help decrease associated costs.
“This is a problem we can deal with. We know a lot more about it than we knew years ago,” Califano says.
Source: USA Today 27th May 2009

It seems like such an unlikely finding: In a University of Minnesota study of kleptomania—the compulsion to steal—a popular medicine used to treat both heroin addiction and alcoholism drastically reduced stealing among a group of 25 shoplifters. The drug, naltrexone, blocks brain receptors for opiates. It is one of the few drugs available for the treatment of alcoholism, and continues to gain momentum as a treatment for opiate addiction.

In an article for the April issue of Biological Psychiatry, Jon Grant and colleagues at the University of Minnesota School of Medicine record the results of their work with 25 kleptomaniacs, most of them women. All of the participants had been arrested for shoplifting at least once, and spent at least one hour per week stealing. The 8-week study is believed to be the first placebo-controlled trial of a drug for the treatment of shoplifting.

In the April 10 issue of Science, Grant said that “Two-thirds of those on naltrexone had complete remission of their symptoms.” According to Samuel Chamberlain, a psychiatrist at the University of Cambridge in the U.K., the study strongly suggests that “the brain circuits involved in compulsive stealing overlap with those involved in addictions more broadly.” The study, in short, strengthens the hypothesis that the shoplifting “high” may have much in common with the high produced by heroin or alcohol.

Researchers are also working with the drug memantine as a treatment for compulsive stealing.

The finding lends additional evidence to the theory that shoplifting is a dopamine- and serotonin-driven disorder under the same medical umbrella as drug addiction and alcoholism. Preliminary research has shown that naltrexone may also have an effect on gambling behavior.

If so-called “behavioral addictions” continue to display biochemical similarities with “chemical addictions,” the move to broaden the working definition of addiction will continue to intensify. And the same sorts of questions that plague addiction research will be replayed in the behavioral sphere: What level of shoplifting constitutes the disorder called kleptomania? Isn’t the medicalization of shoplifting just a way to excuse bad behavior? Is medical treatment more effective than jail time? From a legal point of view, what is the the difference between kleptomania and burglary?

In his book, America Anonymous, Benoit Denizet-Lewis quotes lead study author Jon Grant: “With all addictions, a person’s free will is greatly impaired, but the law doesn’t want to entertain that…. Why shouldn’t someone’s addiction be considered as a mitigating factor, especially in sentencing?”
Source: April issue of Biological Psychiatry, published in Addiction Inbox (USA) Monday 8th June 2009

Vigabatrin, an anticonvulsive drug marketed by Ovation Pharmaceuticals, has been “fast-tracked” by the Food and Drug Administration (FDA) and could become the first drug approved by the agency as a treatment for cocaine and methamphetamine dependence, the.
The drug, which would be marketed under the brand name Sabril, is though to work by blocking craving and euphoria by increasing the level of a neurotransmitter called gamma-aminobutyric acid.
Animal testing and two small-scale human trials have shown that the drug inhibits craving and euphoria. Sabril is currently in Phase II drug-safety trials, and the third and potentially final stage of testing before FDA approval should begin next year.
“We believe this fast track designation for Sabril will accelerate our efforts to bring to market a treatment option for the hundreds of thousands of people who suffer from dependence on cocaine and methamphetamine,” said Tim Cunniff, Ovation’s vice president for global regulatory affairs.
Sabril has already been approved by the FDA for treatment of seizures and infantile spasms.
Source: Chicago Sun-Times Jan. 22 2008

New research from Stanford University suggests that a drug used to treat nausea may be effective in combating withdrawal from opioid drugs, U.S. News and World Report reported Feb. 20.
Researchers testing mice found that the drug ondansetron (Zofran) blocks certain 5-HT3 receptors involved in withdrawal. The researchers proceeded to test eight non-opioid-dependent human volunteers.
The subjects were given two doses of morphine, one with and one without ondansetron. The study showed that ondansetron reduced withdrawal symptoms without some of the side effects caused by current treatments for opiate addiction.
The “constellation of symptoms associated with withdrawal” can create a barrier to opiate treatment, said lead author Larry Chu. “What we need is a magic bullet, something that treats the symptoms of withdrawal, does not lead to addiction, and can be taken at home,” Chu said.
The researchers plan to continue testing ondansetron and to conduct a clinical study to investigate the effectiveness of an ondansetron-like drug in treating opioid addiction. “Treating the withdrawal component is only one way of alleviating the suffering,” said Dr. J. David Clark, principal investigator of the study. “With luck and determination, we can identify additional targets and put together a comprehensive treatment program.”
Source: March 2009 issue of the Journal of Pharmacogenetics and Genomics.

For the minority of patients for whom it feasible, acceptable and safe, this meta-analytic review of behavioural couples therapy suggests it reduces substance use relative to other therapies, and the benefits are more likely to extend to the whole family.
Behavioural couples therapy assumes that substance use problems and intimate relationships are reciprocally related, such that substance use impairs relationship functioning, and severe relationship distress combined with attempts by partners to control substance use may prompt craving, reinforce substance use, or trigger relapse. To break this vicious circle and transform the relationship in to a positive force, the therapy aims to build support for abstinence and to improve relationship functioning. It features a ‘recovery contract’ which involves the couple in a daily ritual to reward abstinence, together with techniques for increasing positive activities and improving communication. A requirement for the therapy is that the partner of the problem substance user does not themselves have the same sort of problem.
Descriptive Reviews have concluded that behavioural couples therapy produces better outcomes than individual-based treatment for alcoholism and drug abuse problems. However, the strength and consistency of this effect has not been examined because a meta-analysis of studies of the therapy has not been reported. This meta-analysis combines multiple, well controlled studies to help clarify the overall impact of behavioural couples therapy in the treatment of substance use disorders, and to determine whether this varies across different types of outcomes (such as relationship functioning and substance use) and/or with time after treatment.
A comprehensive search found 12 (eight dealing with drinking problems, four with other substances instead or as well) randomised controlled trials of behavioural couples therapy which could be included in the final analyses, involving altogether 754 couples in intimate relationships. In all but two, couples therapy supplemented other approaches. Eight of the studies compared couples therapy with cognitive-behavioural therapy.
Behavioural couples therapy manuals are available free of charge on request from the web site of the Addiction and Family Research Group. The same site offers a link to a free training program.
Across the studies and amalgamating all outcomes and lengths of follow-up, there was a clear advantage for treatment including behavioural couples therapy versus solely individual-based treatment. At 0.54, the effect size indicated a medium-size impact. Effects were comparable for alcohol studies and for studies including other drugs, for studies which did or did not combine the therapy with medication, which featured more or less extended versions of the therapy, and (but slightly less strongly) when comparison treatments were limited to cognitive-behavioural therapy without a focus on relationships. Across all the studies, effects were slightly greater for measures of the adverse consequences of substance use and for satisfaction with the relationship (0.52 and 0.57 respectively), than for the frequency of substance use (0.36). However, this pattern varied with time. Immediately after treatment ended, couples therapy was superior to comparison treatments only in respect of satisfaction with the relationship. At later follow-ups, it was superior in respect of all three types of outcomes and to roughly the same medium degree of strength. Possibly substance use outcomes were so good immediately after treatment that it was difficult to improve on them, or perhaps relationship benefits from couples therapy took time to impact on substance use.
When the clients are married or cohabiting couples seeking help for substance dependence problems confined to one of the partners, the authors concluded that behavioural couples therapy results in better outcomes than more typical individual-based treatments. The benefits extend beyond substance use to related problems and the quality of the relationship. Immediate improvements in relationships seem to pave the way for later relative gains in substance use outcomes. Though these outcomes were not included in the analyses, studies have also shown that the therapy outperforms individual-based treatments in respect of child adjustment, cost-effectiveness, and reduced interpersonal violence.
Behavioural couples therapy was one of only two psychosocial therapies recommended by Britain’s National Institute for Health and Clinical Excellence (NICE) for the treatment of problems related to illicit drug use. In particular, NICE said it should be considered for problem users of stimulants or opioids who are in close contact with a non-drug-misusing partner. Experts reached a similar conclusion after reviewing the alcohol treatment literature for England’s National Treatment Agency for Substance Misuse.
Both reviews noted the therapy’s limited applicability: the patient must share an intact, live-in relationship with a relative or partner not also experiencing substance use problems, and the relationship must be sufficiently supportive for both to productively engage with the therapy. This will be the case for many (especially male) drinkers, but usually not for long-term dependent users of cocaine or heroin. Care will also be needed to exclude the risk that such therapies, particularly when they engage women in the treatment of male substance users, might perpetuate or aggravate victimisation by abusive partners. Another major limitation is the availability of family therapy of any kind. The dominant paradigm sees addiction as a disorder of the individual and treats it accordingly. Few drug misuse professionals have been trained in family approaches and in the UK there is no appreciable national drive to widen their perspective. The recent emphasis on addressing not just substance use but also other recovery-relevant issues may alter this situation.
The analysis shares the limitations of many meta-analyses. These mean that it is best seen not as an indication of the generalised impact of the therapy, but of how it performed in this set of studies. One assumption underlying the analysis – that the studies were entirely independent of each other – is certainly violated because eight of the 12 involved one or both of the developers of the therapy. Among the remaining four were the three with the least convincing results overall, raising the issue of whether outcomes depend on who is organising the study. Research conducted by teams linked in some way to the intervention they are testing has been found (1 2) to produce more positive findings than fully independent research. In relation to psychosocial therapies for drinking problems, an analysis of relevant studies concluded that therapies were generally equivalent, and that where they were not, the researcher’s allegiance to the therapy accounted for a significant portion of the differences.
What all this means is that it cannot be assumed that fresh applications of the therapy will produce the average advantages over other therapies noted in the featured analysis. Still the analysis offers more support to this therapy than most others can muster, especially since the usual comparator (cognitive-behavioural therapy) was itself a generally effective approach and one relatively hard to better. For the minority of patients for whom it feasible, acceptable and safe, behavioural couples therapy seems a good option relative to other therapies, and one whose benefits are more likely to extend to the whole family.

Source:Clinical Psychology Review: 2008, 28(6), p. 952–962.

Alcohol’s inebriating effects are familiar to everyone. But the molecular details of alcohol’s impact on brain activity remain a mystery. A new study by researchers at the Salk Institute for Biological Studies brings us closer to understanding how alcohol alters the way brain cells work.Their findings, published in the current advance online edition of Nature Neuroscience, reveal an alcohol trigger site located physically within an ion channel protein; their results could lead to the development of novel treatments for alcoholism, drug addiction, and epilepsy.
Ethanol, the alcohol in intoxicating beverages, is known to alter the communication between brain cells. “There’s been a lot of interest in the field to find out how alcohol acts in the brain,” says Paul A. Slesinger, Ph.D., an associate professor in the Peptide Biology Laboratory at the Salk Institute, who led the study. “One of several views held that ethanol works by interacting directly with ion channel proteins, but there were no studies that visualized the site of association.”
Slesinger and his team now show that alcohols directly interact with a specific nook contained within a channel protein. This ion channel plays a key role in several brain functions associated with drugs of abuse and seizures.
Previous research by Slesinger and his group focused on the neural function of these ion channels, called GIRK channels. GIRK channels, short for G-protein-activated inwardly rectifying potassium channels, open up during periods of chemical communication between neurons and dampen the signal, creating the equivalent of a short circuit.
“When GIRKs open in response to neurotransmitter activation, potassium ions leak out of the neuron, decreasing neuronal activity,” says UCSD Biology graduate student and first author Prafulla Aryal. Alcohols had been previously shown to open up GIRK channels but it was not known whether this was a direct effect or whether this was the by-product of other molecular changes in the cell.
Having the location of a physical alcohol-binding site important for GIRK channel activation could point to new strategies for treating related brain diseases. Using this protein structure, it may be possible to develop a drug that antagonizes the actions of alcohol for the treatment of alcohol dependence. Alternatively, “If we could find a novel drug that fits the alcohol-binding site and then activate GIRK channels, this would dampen overall neuronal excitability in the brain and perhaps provide a new tool for treating epilepsy,” says Slesinger.
Epilepsy is a neurological disease characterized by episodic, abnormal electrical activity that affects more than 3 million Americans. Current medications have serious side effects and the search for new, specific mechanisms of treatment is an area of intense research across the globe.
To gain more insight into how alcohols work, Slesinger and Aryal teamed up with Salk colleagues Senyon Choe, Ph.D., a professor in the Structural Biology Laboratory, and Hay Dvir, Ph.D., a postdoctoral researcher in Choe’s lab, to determine whether tiny pockets found in a high resolution, three-dimensional structure of a potassium channel were, in fact, the sites of alcohol action in GIRK channels. The Salk researchers noted the similarity of these candidate alcohol-binding sites with alcohol pockets visualized in two other alcohol-binding proteins: alcohol dehydrogenase, the enzyme that breaks down alcohol in the body, and a fruit fly protein, LUSH, that senses alcohol in the environment.
When Aryal systematically introduced amino acid substitutions that denied alcohol molecules access to the potential alcohol binding site, alcohol could no longer efficiently activate the channel, confirming that they had hit upon an important regulatory site for alcohol. The team further established that this pocket is a trigger point for channel activation since G protein activation was also altered. “We believe alcohol hijacks the intrinsic activation mechanism of GIRK channels and stabilizes the opening of the channel,” says Aryal. “Alcohol may accomplish this by lubricating the activation gears of the channel,” adds Slesinger.

Source: ScienceDaily. Retrieved July 5, 2009, from http://www.sciencedaily.com¬ /releases/2009/06/090628171951.htm

Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial.
This unique randomised trial tested what would happen if detoxified opiate addicts were then maintained on a substitute drug, on an opiate-blocking medication, or simply counselled. The results led to the introduction of methadone prescribing programmes in Malaysia.
Abstract As a follow-on treatment after opiate detoxification, this study compared the efficacy of the opiate-blocking medication naltrexone, the opiate substitute buprenorphine, or no treatment other than the drug counselling all patients received. In Malaysia at the time naltrexone was the main long-term pharmacotherapy and maintenance substitute prescribing was not permitted.
Between July 2003 and May 2005, 215 people contacted the study of whom 143 heroin dependent patients began a preparatory 14-day detoxification programme in the study’s inpatient clinic. Most of the remaining contacts did not complete the study’s initial assessments; just 12 were excluded due to complicating conditions. 126 completed detoxification and started 24 weeks of weekly individual and group drug counselling in the study’s outpatient research clinic. For randomly selected patients, counselling was supplemented either by oral naltrexone, sublingual buprenorphine, or placebos. In the first week the medications were given daily, then multiple doses were given on Mondays, Wednesdays and Fridays. All the doses were consumed under supervision at the clinic and all the patients consumed similar tablets and capsules, either active or placebos depending on their assignment. Nevertheless, most on the active medications correctly identified what they were taking, though most on placebos did not. Typically the patients were poorly educated single men with a history of imprisonment who had been using heroin for on average 15 years and had used near-daily in the previous month.
Outcomes were assessed mainly by urine tests three times a week while patients were still in treatment, the credible assumption being made that the few tests missed by retained patients would have been positive for heroin, and that patients who dropped out of treatment had resumed heroin use. When it became apparent that buprenorphine was clearly the best option, the study was terminated early after 103 patients had completed it and 10 remained in treatment.
Supplementing counselling with naltrexone slightly improved treatment retention and heroin use outcomes, but not to a statistically significant degree according to the study’s stringent criteria. In contrast, outcomes on these measures were clearly and universally superior for the buprenorphine patients, significantly better than placebo, and generally also significantly better than naltrexone. For example, of the 24 weeks patients could have stayed in treatment, on buprenorphine they stayed on average for 17 weeks, naltrexone 12, and placebo 10 chart. Corresponding figures for retention without a positive/missed test for heroin use were 7, just over 3, and just under 3 weeks. For retention without relapse to sustained heroin use, the figures were 11, 9, and just under 6 weeks.
For the authors their findings showed the efficacy of maintenance treatment with buprenorphine in sustaining abstinence, delaying time to resumption of heroin use and relapse, and retaining patients in treatment, lending support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public health approach to heroin dependence.
Uniquely the study answered the question: What would happen if continuing care for patients who completed detoxification consisted of low intensity counselling only or with attempts to sustain abstinence using naltrexone, versus effectively accepting that many will relapse and instead prescribing a substitute drug? When these were the only options available, the answer seemed to be that naltrexone offers no substantial advantages, but that substitute prescribing makes a big difference to how long and how many patients are able to live without regular resort to illegal opiates. Without this, for most rapid relapse is the norm even after they have been able to complete detoxification; opiate blocking medication does little to improve the situation.
Though this is the verdict from among the range of options on offer in the study, long-acting forms of naltrexone which last weeks or months might have tipped the balance in favour of abstinence-based therapy, and seamless entry in to (to the patient) acceptable forms of residential rehabilitation or intensive day care might have raised outcomes to the point where the choice of medication was less decisive. In both cases, the caveat is that compared to substitute prescribing, fewer patients are prepared to accept or can access these options, and in the case of residential rehabilitation, the costs per year of heroin use averted are likely to be considerably greater.
The main issue with the study from a UK perspective is its applicability to a country where these are not the only options available, and where even if they were, patients would be expected to be allocated to them on an individual basis in the light of what seems best for that individual. However, there are parallels. As in the featured study, in the UK (and elsewhere) failure to complete detoxification or post-detoxification relapse are the norm, long-acting naltrexone formulations have yet to be licensed and made widely available, and residential rehabilitation remains in short supply. The relevance of the study could be heightened if (as strongly advocated by some political advisers) substitute prescribing is de-emphasised in favour of abstinence-based approaches, especially if the need for economies forces these to take the form of naltrexone or counselling rather than intensive, extensive and expensive psychosocial rehabilitation.
Currently the study usefully reinforces existing guidance on the need for anti-relapse support after detoxification, the limitations of oral naltrexone as a means of providing or reinforcing that support, and the more widespread applicability and more securely established effectiveness of substitute prescribing using methadone or buprenorphine. It also provides an argument for maintenance prescribing to be made rapidly available for the many patients unable to avoid a return to regular opiate use after detoxification.
The implications of the study are supported by other studies of detoxification, oral naltrexone and substitute prescribing, though no other study has within itself compared these options. As commentators on the study put it, this wider research base indicates that “The preferred oral pharmacological treatment for opioid dependence should be agonist maintenance with either methadone or buprenorphine.” This verdict carefully limited itself to “pharmacological” treatments and to “oral” medications, leaving out more intensive or improved psychosocial approaches or long-acting implanted or injected medications.
In Australia, where polarised opinions favoured substitute prescribing or rejected this in favour of naltrexone, the federal parliament reacted by conducting a review of their respective advantages in the Australian context. The conclusion was that both had their place, but that place was much greater for substitute prescribing. Oral naltrexone was seen as a niche option for the minority of opioid-dependent individuals capable of remaining compliant with the treatment, but for most it had been consistently been linked with high rates of non-compliance, a greater risk of death and reduced likelihood of long-term success. In contrast, methadone and other opioid substitution treatments were seen as widely applicable treatments acknowledged as effective in reducing opioid dependence and associated health and social problems.
The featured study seems to support this conclusion, but perhaps not as strongly as it might have done. On one key measure – retention without relapse to sustained heroin use – buprenorphine’s advantage over naltrexone was small (two weeks) and not statistically significant, possible an artefact of the way relapse was defined. Despite its advantages, at best half the patients on buprenorphine stayed in treatment for six months, less than in other studies possibly due to insufficiently supportive psychosocial care, or because the study’s standard dose was at the lower end of what is considered effective. It also seems likely that buprenorphine’s advantage would have been greater had patients not been required to complete detoxification in advance, presumably weeding out those less able or willing to attain abstinence from opiates. On the other hand, the naltrexone patients might have been disadvantaged by the dosing schedule. Both buprenorphine and naltrexone are known to be able to bridge alternate-day dosing schedules, but in studies naltrexone is normally taken daily, providing a daily reminder to the patient that any heroin they try will be more or less wasted. Dosing every two or three days left gaps during which the patients might have been tempted to try heroin. However, this schedule probably reflects how both drugs are commonly prescribed in normal practice.
Source: Schottenfeld R.S., Chawarski M.C., Mazlan M Lancet: 2008, 371, p. 2192–2200.

In a small pilot study, Topiramate – a medication currently used to treat seizure disorders – has helped cocaine-addicted outpatients stay off the drug continuously for 3 weeks or more. That may not seem like a long time, but previous research has shown that outpatients who avoid relapse for 3 to 4 weeks during treatment with behavioral therapy and medication have a good chance of achieving long-term cessation. In other clinical trials Topiramate has helped prevent relapse to alcohol and opiate addiction; these new results with cocaine add to hopes that it may prove a versatile treatment medication for several drugs of abuse.

Dr. Kyle M. Kampman and colleagues at the University of Pennsylvania School of Medicine and the Veteran Affairs Medical Center in Philadelphia treated 40 crack-cocaine-smoking outpatients, mostly African American males, for 13 weeks at the University of Pennsylvania Treatment Research Center (TRC). All participants met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for cocaine dependence. They were typical of the chronic, relapsing abusers who seek treatment at the TRC: They abused cocaine an average of 10 years, preferring crack to the powder form, and demonstrated the average level of drug-related problems. However, participants’ abuse was atypical in one way; they were on the “milder end of the addiction severity spectrum measured by cocaine withdrawal symptom severity and days of abuse and money spent on cocaine,” says Dr. Kampman. On average, participants abused cocaine 6 to 8 days and spent $300 to $500 on the drug in the month before treatment compared with the 10 to 13 days and $400 to $600 reported by most patients at the facility. Because Topiramate exacerbates cocaine withdrawal symptoms, the investigators selected patients who were able to attain at least 3 days of self-reported abstinence immediately before starting the trial and who, based on their level of addiction, were not likely to enter severe withdrawal. Dr. Kampman says that about 40 percent of patients treated at the TRC experience relatively mild withdrawal symptom severity.

After a 1-week baseline period, Dr. Kampman’s team gave Topiramate to 20 study participants, and placebo to the other 20. To avoid potential Topiramate side effects, including sedation and slurred speech, they initiated treatment with 25 mg/d and increased it by 25 mg/d every week to 200 mg/d. They maintained this maximum dose during weeks 8 through 12, then tapered to zero during week 13. The patients also received cognitive behavioral coping skills therapy twice weekly throughout the study. The researchers verified cocaine abstinence two times a week with urine tests.

By the end of the 13th week, almost 60 percent of patients taking Topiramate attained 3 or more weeks of continuous abstinence from cocaine compared with 26 percent of those taking placebo. All 40 patients showed improvement from week 1 to week 13, as reflected by lower Addiction Severity Index (ASI) scores. Patients taking the medication improved more, with average scores in the topiramate group falling by 69 percent, from 0.210 to 0.066, compared with 50 percent, from 0.162 to 0.081, in the placebo group. Dr. Kampman says the improvement in ASI scores reflects fewer days of cocaine abuse and patients’ perceptions of reduced cocaine-related problems. “Patients saw the improvement in their condition, which is an important part of recovery,” he says.

“Based on our findings and other work showing this medication’s effectiveness as a treatment for alcohol and opiate addiction, topiramate appears to have great potential as a relapse prevention medication for people who have achieved initial abstinence from cocaine,” says Dr. Kampman.

Possible Mechanisms

All addictive drugs deliver pleasurable effects by enhancing the neurotransmitter dopamine in the mesocorticolimbic pathway – areas of the brain involved in reward and motivation. Topiramate seems to change the – gamma aminobutyric acid (GABA) and glutamate. Animal studies have suggested to scientists that either activating GABA-producing neurons or blocking glutamate receptors would lessen craving in cocaine-addicted human subjects. “Topiramate does both simultaneously, a unique dual action that appears to underlie its’ promise as a relapse prevention medication,” says Dr. Kampman.

“These are preliminary results, but researchers are very excited about the potential Topiramate has shown as a treatment for a range of problems, including addiction to several drugs and some impulse control disorders,” says Dr. Frank Vocci, director of NIDA’s Division of Pharmacotherapies and Medical Consequences of Drug Abuse. In addition to its initial successes in preventing relapse in patients with alcohol, opiate, and now cocaine addiction, animal studies have suggested it may attenuate nicotine addiction. “Topiramate may prove an effective treatment for patients who are addicted to multiple drugs,” Dr. Vocci adds.

Dr. Kampman plans additional studies to further evaluate Topiramate as a treatment for cocaine addiction. In addition to confirming the present results, obtained with African American male crack smokers, the medication must be tried in other racial groups, women, and powder-cocaine abusers. Dr. Kampman and his colleagues also plan to study Topiramate therapy for patients with coexisting cocaine and alcohol addiction – a group that comprises half of people treated for cocaine abuse.
• Kampman, K.M., et al. A pilot trial of topiramate for the treatment of cocaine dependence. Drug and Alcohol Dependence 75(3):233-240, 2004.

Researchers say that two drug advances may help millions of Americans addicted to alcohol control their cravings, The drug Naltrexone, which was available in capsule form for years, is now offered as a once-a-month injection. “People came in saying that they really wanted to try this because they had a hard time remembering to take the drug on their own,” said lead researcher Dr. Henry Kranzler, a psychiatry professor at the University of Connecticut School of Medicine.

Kranzler’s study, involving 315 patients addicted to alcohol, found that the monthly version of the drug increased the total number of days that the participants abstained from consuming alcohol.

The drug Acamprosate, which is in use in Europe and awaiting approval from the U.S. Food and Drug Administration, also has showed success in studies led by Elizabeth Houtsmuller, a professor of behavioral biology at Johns Hopkins University School of Medicine.

Houtsmuller’s research examined the physiologic and behavioral changes in 10 heavy drinkers who were given daily Acamprosate. The participants were given opportunities to drink during various points in the study period.

The study found that those who took Acamprosate became more sedate than usual. However, it was not clear whether this sedation would discourage repeat alcohol consumption. “It doesn’t work by altering alcohol absorption or elimination,” said Houtsmuller. “And it doesn’t appear to work by changing alcohol’s subjective effects – the alcohol ‘experience’ that people have.”

Kranzler said the medical advances, combined with psychotherapy and assistance from groups like Alcoholics Anonymous, are helping many alcoholics turn their lives around. “We see people getting better all the time,” he said.

Researchers plan to conduct trials to determine whether a skin patch containing the drug mecamylamine can reduce excess drinking by curbing alcohol cravings, Nature reported April 20.

The patch was originally developed as a quit-smoking aid. But preliminary research shows that mecamylamine also may help curb alcohol addiction. An initial study conducted by Jed Rose at Duke University in Durham, N.C., found that people who consumed more than 10 alcoholic drinks a week reduced their intake to six after taking mecamylamine for four weeks.

Mecamylamine, which has been used since the 1950s to reduce high blood pressure, dulls the addictive effects and cravings of drugs by reducing the release of dopamine.

Rose and his team of researchers are applying for funding and ethical approval for a formal trial.

La Jolla, CA. June 21, 2004 — Scientists at The Scripps Research Institute have designed a potentially valuable tool for treating cocaine addiction by creating a modified “phage” virus that soaks up the drug inside the brain.They coated the virus with an antibody that binds to molecules of cocaine and helps to clear the drug from the brain, which could suppress the positive reinforcing aspects of the drug by eliminating the cocaine high.

“Typically one would think of a virus as a bad entity,” says principal investigator Kim D. Janda, Ph.D., who holds the Ely R. Callaway, Jr. Chair in Chemistry and is an investigator in The Skaggs Institute for Chemical Biology at Scripps Research. “But we are taking advantage of a property it has—the ability to get into the central nervous system.”

The structure and design of the virus and its effect in rodent models are described in an article that will be published in an upcoming issue of the Proceedings of the National Academy of Sciences.

The European Agency for the Evaluation of Medicinal Products reports that ten cases of life threatening cardiac rhythm disorders have occurred in young patients taking Orlaam (levacetylmethadol) for opiate addiction, the European Agency for the Evaluation of Medicinal Products (EMEA) reported. The agency believes the risks are serious enough to advise prescribers not to introduce any new patients to Orlaam therapy until a full risk benefit assessment has been completed by its scientific committee.

It is indicated for the substitution maintenance treatment of opiate addiction in adults previously treated with methadone. In a public statement dated December 19, the EMEA said: “ 10 cases of life threatening cardiac rhythm disorders have been reported since 1 July 1997. They include five cases of cardiac arrest associated with ventricular arrhythmias, three cases of cardiac arrhythmia and two cases of syncope.” “Finally three patients required a pacemaker insertion,” the agency added . “This raises a major concern given the fact that these life  cases occurred in young patients (median age 39/ range 23— 57)  a population at low risk of developing these cardiac disorders, and given the relatively low exposure to the product.”  Furthermore, these cardiac disorders might have been under recognised or under reported.”

A new study shows that women receive different types of benefits from prison-based addiction treatment programs and those located off prison grounds. Elizabeth Hall, project director of the Forever Free Substance Abuse Treatment Program Outcomes Study at the University of California, said the study found that women who received prison-based treatment initially did better on parole and with cutting drug use. On the other hand, women in the non-prison program fared better finding jobs. But a year later, when researchers conducted a review of study participants, they found that 35 percent of the prison group had used alcohol or other drugs during the month before the interview, compared with 8 percent of the non-prison group. Also, 75 percent of the prison group reported using alcohol or other drugs at some time during their parole period, compared with half of the non-prison group.

Burenorphine is widely prescribed in France  used to be THE substitute drug but isn’t any longer in France. Instead som 50.000 opiate addicts use Buprenorphine in France at the moment. Experiments with the drug are also being carried out in Sweden. CSAT( USA)  is  proposing regulatory changes to make buprenorphine more accessible for the treatment of addicts. Unlike  methadone, it is a fairly mild narcotic that should block craving while  having negligible effects. One proposed preparation will mix this with  naloxone which is a narcotic antagonist and which is used to reverse the effects of narcotics abruptly in overdose situations. If the pill is crushed, the Naloxone would be activated.

Buprenorphine is available as a sublingual tablet formulation, and many assorted studies have been performed to determine its effectiveness in the treatment of opiate addiction.
Preliminary studies using low dose Buprenorphine (Temgesic) tablets performed in Belgium and France were the first to demonstrate its effectiveness. Elsewhere in Europe, several studies have been completed that have compared the use of high-dose buprenorphine and methadone.
The major comparison studies have been performed in Switzerland, Italy and Austria and these have confirmed the equivalence of the two agents in all outcome measures, apart from retention rates in some cases probably due to protracted induction phases)
Trials in Spain and Australia have been performed to investigate less than daily dosing, again demonstrating buprenorphines effectiveness in different dosing regimens.
Concerns about misuse/diversion of the product led to studies investigating the injection of doses ranging from 2-6 mg. Results demonstrated the well known ceiling effect of Buprenorphine, in this case maximal effect was seen at approximately the 12 mg dose level.
In summary, Buprenorphine has a wide effective dose range (2—32 mg/day), a wide safety margin, is well tolerated, is widely accepted by addicts, has only mild withdrawal and a low dependence liability, and offers flexibility in dosing.

Jonathan Freedman, Associate Professor of Pharmacology in the Department of Pharmaceutical Sciences at Northeastern University’s Bouve College of Health Sciences, has discovered why people who suffer from drug addictions or chronic severe pain crave larger dosages of drug treatments over time.
The findings of Professor Freedman and his team resulted from a three- year project funded by the National Institute on Drug Abuse in Bethesda, Maryland. Freedman and his team discovered a specific molecular change in the brain using a research method called ‘patch clamp electrophysiology” on the surface of rat brain cells, one molecule at a time. They found that rats treated with morphine eventually needed higher dosages of drugs to achieve the same effect. Freedman and team hope this understanding will later give way to practical applications in human patients.
“Scientists have been looking for almost 30 years for the molecular mechanism of opiate drug tolerance, says Professor Freedman. “I hope that our discovery will be a significant step towards understanding it. Eventually, we may be better able to treat heroin addicts, and better able to help people like cancer patients who have chronic severe pain.”

A study on the effectiveness of the 7-year-old drug court in St. Louis, Mo., finds that the program’s benefits far outweigh its costs, the Associated Press reported Feb. 2.

The study by the independent Institute of Applied Research found that nonviolent drug offenders who are placed in treatment instead of prison generally earn more money and took less from the welfare system than those on probation.

The study compared the 219 individuals who were the program’s first graduates in 2001 with 219 people who pleaded guilty to drug charges during the same period and completed probation.

For each drug-court graduate the cost to taxpayers was $7,793, which was $1,449 more than those on probation. However, during the two years after drug court, each graduate cost the city $2,615 less than those on probation. The savings were realized in higher wages and related taxes paid, as well as lower costs for health care and mental-health services.

“What you learn is that drug courts, which involve treatments for all the individuals and real support — along with sanctions when they fail — are a more cost-effective method of dealing with drug problems than either probation or prison,” said Tony Loman, the lead researcher.

The St. Louis drug court allows addicted individuals who have been arrested to voluntarily enrol in the program. Participants are required to submit to periodic drug and alcohol testing, appear in court during scheduled times, find and keep jobs, and enrol in drug and alcohol treatment. Those who successfully complete the program have their charges dropped.

A team of NIDA-funded researchers from the University of Chicago, Brown University, and Rhode Island Hospital  has found that, in general, the more time a person spends in treatment for addiction, the better. The scientists found that treatment for up to 18 months in residential settings, or almost 14 months in outpatient non methadone treatment, yielded the greatest reductions in illicit drug use. Both overall and primary drug use declined after 18 months in long-term residential programs, at which point peak use measured about one-tenth the pre treatment level. After 18 months in this setting, the amount of improvement began to wane. A similar effect was seen in people treated in non methadone outpatient settings. Individuals in non methadone programs who reduced drug use on their own before entering a treatment program were better able to remain in recovery.

The 4,005 patients in the study were treated for addiction to cocaine, heroin, or marijuana in 62 drug treatment units throughout the United States. As part of the National Treatment Improvement Evaluation Study, they were interviewed at admission, discharge, and one year after therapy ended between 1993 and 1995. Treatment programs included methadone maintenance programs, outpatient non methadone programs, short-term residential programs, and long-term residential programs. There was no significant relationship between treatment duration and overall drug use improvement for individuals in methadone maintenance and short- term residential programs.
WHAT IT MEANS: Remaining in treatment for an extended time has beneficial outcomes for people in residential or outpatient drug treatment programs. Insurers may consider changing their policies to include a longer length of stay so people can be more effectively treated for their addictions.

New research suggests that a family-treatment approach may be effective in preventing children of addicted parents from becoming addicts themselves.

In a collaborative study, researchers from the School of Social Work and the Centre for Addiction and Mental Health (CAMH) in Canada evaluated more than 600 families from New York’s Buffalo-Niagara region and Canada’s southern Ontario area who participated in the Families Working Together program.

The program targets families with a child between the ages of 9 and 12 who has or had a parent with an alcohol problem. The families were selected to either receive an informational booklet on preventing addiction or participate in weekly sessions focusing on family relationships, parenting skills, and children’s coping and competency skills.

The study found that the family-treatment approach, which emphasized communication and skill-building, was effective in preventing children from falling into the same negative patterns that led their parents to alcohol and other drug use.

“Children of alcoholics are at higher risk of certain negative outcomes, including alcoholism, substance abuse, depression, and anxiety,” said Andrew Safyer, interim dean of the School of Social Work and a co-investigator on the project. “Studies show that programs that target parents, children and the family itself are more effective in preventing further substance abuse.”
Source:University of Buffalo Reporter, March 2004

Across the United States, drug treatment courts for adults and juveniles offer an alternative to incarceration for non-violent offenders.

In Rochester, N.Y., the juvenile treatment court is using mentors as aids in recovery, the first treatment court to systematically do so, USA Today reported on September 30. Rochester is a Demand Treatment community.

“There’s the thought in the drug court movement that it’s not programs that influence people — it’s relationships,” says Judge Anthony Sciolino. “We find that where we’re successful with youngsters turning their lives around, it’s because they’ve connected with a caring adult.”

The court finds its mentors through Compeer, Inc., a Rochester-based volunteer organization with national and international affiliate offices. Compeer matches community volunteers with children and adults who are receiving treatment for mental health disorders.

In Rochester, the treatment court coordinators approached Compeer just as the organization was starting a program to match adults with troubled teens. Mentors have been working with 20 adolescents so far, and at least half of the matches have been successful.

Compeer would like to extend mentoring to its chapters in other cities; however, the program has not secured money for next year.
Source:Indiana Prevention Resource Center at Indiana University Bloomington; June 2004.

The Independent reported July 14 that physicians may someday be able to treat addicts by altering neurotransmitters in the brains, and prevent addiction with vaccines such as the one currently under development by the firm Xenova to address cocaine use.

The U.K. Department of Trade and Industry set up the “Foresight” project to consider new technologies and their impact on society in the next 20 years. The group has proposed ideas like a national immunization programme for addiction. It also has predicted that drugs will come to market that are designed to improve mood, intelligence, and memory. Panel members expect pharmaceutical companies to find new ways to deliver medicinal and pleasure-enhancing drugs, such as through impregnated clothing.

“We hope that these findings will give us guidance about what could possibly happen in the future and give us some guidelines about how we can respond to certain issues, like addiction,” said a U.K. health ministry spokesperson.

In an unusual move, city Health Department officials are quietly encouraging physicians, hospitals, methadone clinics and prisons to prescribe the drug buprenorphine to heroin addicts, believing it will lure more addicts into treatment. Buprenorphine — a relatively new drug that goes by the nickname “bupe” and comes in a pill form — offers a new set of treatment options for opiate abusers, said Dr. Lloyd Sederer, executive deputy commissioner of the city Department of Health and Mental Hygiene.

Fewer side effects
Chemically, the drug partially blocks the same brain receptors that heroin and methadone target. But unlike those drugs, it doesn’t produce the same “high” or level of dependence. In addition, withdrawal from buprenorphine produces less severe symptoms and fewer drug cravings.

“The new medicine works differently in two ways,” Sederer said. “Bupe has a ceiling effect and reaches a certain point where it doesn’t get you higher, so it is much less likely to be abused or sold on the streets. With heroin and methadone, the more you take, the higher you get, and your lung function is depressed. The respiratory failure is what results in death.”

Methadone has been the standard for heroin addiction treatment since the early 1970s. But the syrupy, amber liquid is highly habit-forming and by law must be distributed — one dose at a time — at a special clinic. That stricture causes some who would seek treatment to shy away.

“People say that methadone leaves them punchy, and they have difficulty thinking and working,” Sederer said. “The long-term data on people in methadone programs shows that they are more stable, not involved in crime, and that’s a good thing, but only a small percentage are working [in jobs].”

Relatively new drug
Despite the potential benefits of buprenorphine, the drug remains virtually unknown and unused by the city’s heroin addicts. According to city health officials, only about 1,000 people use it, compared with an estimated 34,000 taking methadone.

Sederer and other city health officials want to see a significant change in those numbers. The goal is to have more than 100,000 opiate addicts using buprenorphine for detox maintenance by 2010.

“We are not reaching enough people with the treatments that we have,” Sederer said. “Not everybody should be on methadone.”

Like methadone, buprenorphine is heavily regulated, and may be prescribed only by certified doctors, of which there currently are 345 statewide. In addition, those prescribing the drug are bound by a 30-patient limit, a federal restriction guarding against prescription abuse that Sederer and other health officials hope will be changed so that more patients can be treated.

Some private doctors have been reluctant to prescribe the drug, fearing their offices would be inundated with addicts.

The drug’s pill form would be more attractive to white-collar users trying to avoid methadone clinics, experts said.

Somewhat complicating the picture, there are varying camps in the medical community about how to treat opiate addiction. Some, including Phoenix House, the country’s largest drug-free residential rehabilitation program, use bupe for detoxification; other programs use it solely as a maintenance drug to replace methadone.

Dr. Terry Horton, the medical director of Phoenix House in the city, calls buprenorphine “the most significant development in the treatment of opiate addiction in 40 years.”

“But,” Horton noted, “it is not a replacement for methadone but should be considered another tool we can use to treat opiate addiction.”

Could streamline treatment
The goal, drug treatment experts said, is for more doctors to be able to prescribe buprenorphine and for patients to be able to pick it up at the pharmacy.

Potentially, thousands of people could benefit from the drug. The city spends $50 million annually on treatment of an estimated 200,000 heroin addicts and 200,000 others addicted to prescription painkillers like Vicodin, Percocet and OxyContin. The state Office of Alcoholism and Substance Abuse Services will spend $313.7 million in 2005-06 to treat those battling against alcohol and other drug-related addictions, spokeswoman Jennifer Farrell said.

A review article has outlined the benefits of buprenorphine (Subutex) in the treatment of intravenous drug use. The drug, which was added to the World Health Organization’s (WHO’s) list of essential drugs in July 2005, may be beneficial in reducing HIV transmission through injection practices, as well as treating HIV-infected drug users.

Injection drug use is a major factor in the transmission of HIV internationally. Around 10% of all HIV transmissions can be attributed to the consequences of intravenous drug use including needle sharing or unsafe sex. Drug use has also been linked to the majority of HIV transmissions in central and Eastern Europe and Southeast Asia.

The most commonly used treatment for addiction to opioids, such as heroin and morphine, is replacement therapy with methadone. This drug mimics the effects of opioids by binding to the same receptor molecules as these drugs. These receptors, called mu-opioid receptors, are found on the surface of cells in the brain and spinal cord and trigger the drugs’ sedating, euphoric and pain-killing effects.

Methadone works by preventing the withdrawal symptoms and craving brought about when an addict stops injecting drugs. By reducing the frequency of drug injection, it has been shown to reduce the incidence of HIV infection. However, the use of methadone has a number of problems, including being itself addictive, and its risk of causing breathing problems and overdose. It also interacts with many HIV drugs.

Buprenorphine, in contrast to methadone, is a partial agonist of the mu-opioid receptor. This means that it binds to the receptor less strongly than methadone and is less likely to be abused itself. It is also very difficult to overdose on buprenorphine as its effects plateau at high doses, and it has fewer interactions with HIV drugs, so is easier to use in patients taking antiretroviral therapy.

“The introduction of buprenorphine, a new medication to treat opioid dependence that has fewer restrictions than methadone, holds promise for reducing HIV transmission and improving the care of patients with opioid dependence and HIV disease,” write the review’s authors, Lynn Sullivan and David Fiellin from Yale University School of Medicine. “Methadone has a long history of proven efficacy and benefits in treating opioid dependence, and the addition of buprenorphine serves to expand the treatment options”.

Buprenorphine has become more widely available over the last ten years, and is available alone or in combination with naloxone, a drug that blocks the mu-opioid receptor. It is taken as a tablet dissolved under the tongue daily or three times a week, and was recently added to the WHO’s list of essential drugs. This lists all medicines that should be available in adequate amounts and at an affordable price within all health systems, and are selected according to public health relevance, efficacy, safety and cost-effectiveness.

In their review, the authors summarise the results of cost-effectiveness studies comparing buprenorphine to methadone. These have concluded that buprenorphine treatment programmes may be preferable, both in the treatment of opioid dependence itself, and in its effects on reducing new HIV infections.

However, despite the drug’s benefits, the authors point out that few studies have examined its effects on HIV risk behaviours, such as needle sharing and unsafe sex, although larger scale studies are planned.

In injecting drug users (IDUs) who are already HIV-positive, there is evidence from the French Manif 2000 cohort study that use of buprenorphine improves adherence to antiretroviral drugs. Although this was not associated with a better response to therapy, and over half of the patients reverting to drug use during the study, they point out that, despite limited evidence, buprenorphine is less likely to interact with HIV drugs than methadone.

AZT (zidovudine, Retrovir) and some protease inhibitors may increase buprenorphine levels, but the pharmacological properties of buprenorphine mean that its effects are not increased above a ‘ceiling’ level, so increased buprenorphine levels are unlikely to cause dangerous side-effects. However, the authors write, “as efforts continue with the goal to integrate use of buprenorphine into HIV care, further studies will need to be undertaken to make more than theoretical statements about these interactions.”

In conclusion, there is room for substantial optimism about the inclusion of buprenorphine in the treatment of IDUs for the prevention of HIV transmission and the treatment of IDUs who are already HIV-positive. Although the practicalities of treatment programmes remain to be fully evaluated, many of the questions surrounding the drug’s role will be answered in ongoing and future studies.

“In the meantime, office-based clinicians, for the first time in nearly 100 years, have the opportunity to provide a unique treatment to minimise the adverse impact of opioid dependence,” the authors conclude.

Reference Sullivan LE et al. Buprenorphine: its role in preventing HIV transmission and improving the care of HIV-infected patients with opioid dependence. Clin Infect Dis 41: 891-896, 2005.

Researchers say that the onset, pattern, and duration of the “highs” produced by cocaine and methamphetamine differ significantly — findings that could have implications for development of anti-addiction medications.

The authors from the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA found that cocaine-using research subjects reported a quicker peak and decline of their “high” than methamphetamine users. The body’s cardiovascular system responds quickly to both drugs, but physical responses to cocaine also decline more quickly than with meth use.

“These differences help explain patterns of use by addicts. Methamphetamine users, for instance, report using the drug daily throughout each day, while cocaine users typically engage in binges that occur most often in the evening,” said lead study author Thomas F. Newton. “In addition, the study results may impact development of medication treatments for addiction to these two very different stimulants.”

A compound in the common kudzu weed seems to help drinkers cut back on their alcohol consumption, the Associated Press reported May 17.

Following up on anecdotal evidence from China, researchers at McLean Hospital in Boston, led by Scott Lukas, gave test subjects either kudzu or a placebo and measured their beer consumption. They found that the kudzu group drank an average of 1.8 beers per research session, compared to 3.5 beers consumed by the control group.

Lukas said that it is possible that kudzu raises blood-alcohol levels quickly, so drinkers need to consume less to feel drunk. “That rapid infusion of alcohol is satisfying them and taking away their desire for more drinks,” Lukas said. “That’s only a theory. It’s the best we’ve got so far.”

Animal research conducted in 2003 also suggested that kudzu reduced alcohol intake. “There’s a lot of anecdotal evidence from China that kudzu could be useful, but this is the first documented evidence that it could reduce drinking in humans,” said researcher David Overstreet, who conducted the animal study.

Fourteen men and women in their 20s, who habitually consumed three or four drinks daily, took part in the study, spending four 90-minute sessions drinking beer and watching TV.

Kudzu won’t prevent drinking, researchers said, but could help heavy drinkers cut their consumption.

The report appears in the May 2005 issue of the journal Alcoholism: Clinical and Epidemiological Research.

Lukas, S., et al. (2005). An Extract of the Chinese Herbal Root Kudzu Reduces Alcohol Drinking by Heavy Drinkers in a Naturalistic Setting. Alcoholism: Clinical and Epidemiological Research, 29(5): 756-762.

Source: Alcoholism: Clinical and Epidemiological ResearchAssociated Press May 17 2005

PATIENTS suffering the effects of cannabis abuse are being treated by Tasmanian public hospitals every day, says a leading health authority.

People with short-term drug-induced psychosis and longer-term mental illness, compounded by pot smoking, are seeking medical help at an increasing rate. Mental Health Services clinical statewide director Peter Norrie said the Royal Hobart Hospital was seeing many cannabis cases.

First-time pot smokers were turning up at the Royal with full-blown psychosis — delusional, confused and anxious. Other more regular pot smokers with long-term mental illness were fronting for treatment for episodes likely to have been triggered or related to using cannabis.

“These days it’s close to every day,” said Dr Norrie, who is a senior clinical consultant psychiatrist at the Royal. He said he was talking about “drug-induced psychosis or long-term mental illness associated with pot smoking”. Dr Norrie said it was “very common” for first-time users to present with “floridly psychotic” behaviour.

He said psychiatrists were increasingly concerned with the link between substance abuse and mental illness. Cannabis use had been linked with depression, anxiety and schizophrenia. International studies show modern strains of marijuana are from three to 10 times stronger than those used by previous generations.

“Clinically psychiatrists have suspected a link for many years and the latest research seems to confirm this,” Dr Norrie said.

“The chicken-and-egg debate has raged for years – whether pot causes psychosis or people with a tendency to psychotic illness are predisposed to smoke pot.”

Dr Norrie said the first signs of schizophrenia were often a lack of engagement with society. But those symptoms could also be what is commonly known as “typically teenage” or a sign of the onset of depression.

Disengaged teenagers could then turn to cannabis.

If psychosis did occur it was hard to tell whether smoking pot was a cause or a symptom. Dr Norrie said some pot smokers appeared to be able to continue the habit without serious mental illness but others were prone to individual cases of psychosis or longer-term mental disease.

“There’s a certain group of people who smoke pot who are unlikely to develop mental illness but there’s certainly a significant number of the population who suffer from mental illness and pot smoking adds to the risk,” Dr Norrie said.

Drug-induced psychosis usually consists of paranoia, confusion and anxiety.

Sufferers present with memory problems and delusions. They can believe they have special powers, hear and see things that are not there and are unable to distinguish what is real.

Scientists report that they are inching closer to developing a vaccine that would effectively treat drug addiction. Although the research is several years away from putting a vaccine on the market, the studies are meeting with success. The research suggests that the vaccine is able to activate the immune system to block the effects of substances such as cocaine or nicotine.

The vaccine works by producing antibodies to a certain substance. When that substance is used, the antibodies bind to it as it enters a person’s system. In doing so, the vaccine stops most of the chemical from the drug from crossing into the brain. The substance is then metabolized by the liver and secreted from the body.

The two companies furthest along in the research are Nabi Biopharmaceuticals in Boca Raton, Fla., and Xenova Group PLC of Slough, England.

Nabi Biopharmaceuticals is working on a nicotine vaccine. The company has completed a trial involving 68 smokers to test safety and measure the levels of antibodies produced by the vaccine. The vaccine has also resulted in smoking cessation among a group of participants.

Xenova Group is working on a cocaine vaccine and reports that the vaccine has reduced relapse in a small group of cocaine users.

Orexin (hypocretin), a neurotransmitter recently detected by researchers, is involved in the brain’s pleasure and reward system and could play a role in addiction and treatment.

Researchers at the University of Pennsylvania School of Medicine said that the findings about orexin – previously linked to wakefulness and appetite – could provide new avenues for addiction treatment research. Orexin seems to be involved in communication between the lateral hypothalamus region of the brain and the ventral tagmental area and nucleus accumbens.

“The lateral hypothalamus has been tied to reward and pleasure for decades, but the specific circuits and chemicals involved have been elusive,” said Gary Aston-Jones, Ph.D., one of the study authors. “This is the first indication that the neuropeptide orexin is a critical element in reward-seeking and drug addiction. These results provide a novel and specific target for developing new approaches to treat addiction, obesity, and other disorders associated with dysfunctional reward processing.”

The association between orexin activation and reward seeking for morphine, cocaine, and food was found to be strong in animal studies, the researchers said. Scientists were able to initiate and curb craving by introducing and blocking orexin.

“These findings indicate a new set of neurons and associated neuronal receptors that are critical in consummatory reward processing,” said Aston-Jones. “This provides a new target for developing drugs to treat disorders of reward processing such as drug and alcohol addiction, smoking, and obesity.”

According to one study, almost all adolescents returning to their old school after completing a treatment program were offered drugs on their first day back. Findings such as this sparked a recent innovation in American education: recovery schools, which are high school or college programs designed to support young people in recovery from addiction.

Recovery schools have developed quickly over the past few years, but often in isolation from each other. That’s changing, however. Staff members at recovery schools are making connections with each other, a body of best practices is emerging to guide their work, and formal research to evaluate recovery schools is on the horizon. The bottom line: Parents and students looking for an academic environment that supports sobriety can now rely on more than guesswork and gut feelings when choosing a recovery school.

The need for recovery schools will not go away, as evidenced by the 2003 National Survey on Drug Use and Health from the Substance Abuse and Mental Health Services Administration, which found that:

• Nearly 1 percent of 12-year-olds in the United States either abused or became dependent on alcohol or illicit drugs in 2001

• the percentage of abusing or dependent adolescents increased each year up to age 21, when 22.8 percent fit the abuse or dependence criteria

• in both 2002 and 2003, nearly 2.3 million Americans aged 12 to 17 needed treatment for an alcohol or drug problem. Of this group, only 168,000 received care at a dedicated treatment facility.

Here is where the benefits of recovery schools click in. According to Andrew Finch, director of the Association of Recovery Schools, such programs offer a “protective cocoon” that supports recovery as students work towards graduation.

Since 2002, the number of recovery schools has doubled to 25 high schools and eight college programs. According to Finch, some lessons have emerged from all this activity. If a group is starting a recovery school, Finch recommends that the founders “be patient and persistent and reach out to people who have established schools. Also, be aware of referral sources and funding opportunities. One of the biggest mistakes a new school can make is to open but not have a consistent referral base of local treatment centers, schools, and other resources.”

Finch adds that recovery schools must stay on top of local and state education laws: “These must be followed, and they differ greatly from state to state and district to district.”

According to the ARS, recovery schools should:

• Operate with state approval and be designed specifically for students recovering from chemical dependency.

• Provide academic services and recovery assistance – but not operate primarily as treatment centers or mental-health agencies.

• Require students to be sober and working a program of recovery.

• Offer academic courses for credit and assist students to make transitions to college, a career, or another school.

• Have a plan to handle student crises, including access to counselors on staff, on contract, or available by written referral.

Finch has written a new book, “Starting a Recovery School: A How-To Manual” (Hazelden, 2005), that offers a blueprint for developing an effective recovery school and includes details about existing schools. Related information and a list of sobriety schools in the United States are online at the Association of Recovery Schools website.

A U.K. detox program is using healthy snacks as a way to help addicts overcome anxiety and sleeplessness.

Crack and cocaine addicts going through detox are given snack packs that include brazil nuts and sunflower seeds — natural remedies for relaxation — along with cognitive therapy and acupuncture.

“You’ve got to want to come off crack cocaine or stimulants yourself, but the packs help like mad,” said Joe, an ex-crack cocaine user. “Once you can suppress your cravings you can get on with life. It’s working for me.”

And Karl Sheldon of the Middlesbrough, England drug-action team, added: “When it comes to drug addiction we always think of the usual stuff, opiates and physical addiction. Stimulants like cocaine and crack cocaine are more psychologically addictive, so you are looking at a different way of treating these addicts. For example, the licorice root you chew on is good for sweet cravings and also for liver function. And again with brazil nuts, the chemicals inside attach onto receptors in the brain which deal with opiates and also stimulants.

“You are not going to eat a brazil nut and all your cravings are going to go away,” continued Sheldon. “This is about dealing with your cravings and taking the edge off them.”

Sheldon said about 50 snack packs have been given to addicts over the past two months, and seem to be having a positive effect.

Researchers say that using benzodiazepines — drugs like Valium, Halcion and Xanax — to help ease withdrawal from alcohol addiction works better than a placebo. But benzodiazepines worked no better than other drugs commonly used to help patients through withdrawal.

Dr. Christos Ntais of the University of Ioannina School of Medicine in Greece and colleagues found that patients given benzodiazepines were 84% less likely to suffer withdrawal-related seizures than those given a placebo. “This might suggest that their [benzodiazepines'] current status as first-line treatment for alcohol withdrawal syndrome is justified,” the authors said.

But Ntais and the other researchers noted that other drugs, such as anticonvulsives like carbamazepine, are equally effective. “There was no conclusive evidence or even hints for superiority of specific drugs, but modest differences could have been missed due to limited data,” Ntais said.

The Greek researchers received 57 studies on benzodiazepine use for withdrawal; a separate group of scientists reviewed 48 studies on anticonvulsive use. Both reviews found that cases of death or serious complications were rare. “The extremely small mortality rate in all these studies is reassuring, but data on other harms-related outcomes are sparse and fragmented,” said Ntais.

Sarah Book of the Medical University of South Carolina noted that — unlike anticonvulsives — benzodiazepines have the potential to trigger relapse, and the interaction of benzodiazepine and alcohol can be fatal.

Participation in Alcoholics Anonymous (AA) concurrent with professional treatment appears to improve alcohol outcomes in people with alcohol use disorders. Whether AA alone or the timing of participation (e.g., before or after entering treatment) affects these outcomes is unclear.

In this study, researchers assessed remission (no heavy drinking or related problems in the past 6 months) in 362 people with an alcohol use disorder who entered treatment (inpatient or outpatient), AA, or both in the year after they sought help. Subjects were surveyed at baseline and 4 subsequent times over 16 years.

• Remission was more common in people who had participated in both treatment and AA (e.g., 65 percent at 16 years) followed by AA only (57 percent) and treatment only (50 percent). Differences were significant between the two treatment groups (for 3 of 4 time points).

• Remission did not significantly differ between people in treatment only and those who initially received treatment but later entered AA.

• As duration of AA participation increased, the likelihood of remission significantly increased.

Comments Rosanne Guerriero, MPH Richard Saitz, MD, MPH: This study supports the notion that long-term participation in AA, particularly when begun soon after seeking help, is an important adjunct to professional treatment for alcohol use disorders. Treatment of alcohol dependence should include referral to mutual help groups and encouragement for patients to continue their participation.

The San Francisco Health Department is offering cash rewards to methamphetamine users who quit using the drug and stay clean, the reported.

Payments of up to $40 per week have been given to meth users who quit. Program participants are required to visit a clinic three times weekly for a drug test; clean urines are rewarded with a check, and participants are not even required to go to counselling as part of the deal, even if they fail a drug test.

“Here I am getting clean, I feel better and I’m getting something for it,” said said former meth addict Robert Bowers. “That means something.”

Experts say that many addicts respond very well to rewards, even small ones, that acknowledge their progress toward sobriety. “You’re using the exact same technique that parents use with their children every day,” said Nancy Petry of the University of Connecticut School of Medicine. “It’s behaviour modification and behaviour shaping.”

The 12-week San Francisco program has had 159 participants since November 2004; backers see it as an effective and inexpensive alternative for those who can’t get into treatment or are on waiting lists.

A recent UCLA study found that a cash voucher program for meth addicts was actually more effective in producing clean urine tests than a therapy program lacking a reward component. “Clearly, it wasn’t the money,” said UCLA researcher Steven Shoptaw. “It was the fact that somebody recognized them.”

• Four patterns of AA attendance emerged: low (mainly during the year following treatment entry); medium (about 60 meetings per year with a slight increase by year 5); high (over 200 meetings per year with a slight decrease by year 5); and declining (almost 200 meetings the year following treatment entry and about 6 meetings in year 5).

• Abstinence (past 30 days) in year 5 significantly differed across groups: 79% of patients with high attendance reported abstinence, followed by 73 % with medium attendance, 61% with declining attendance, and 43% with low attendance.

• Patients with medium or high attendance had the largest social networks of people who supported patient abstinence or decreased alcohol use.

• Patients across the groups had similar numbers of dependence symptoms and social consequences of drinking.

Comments by Joseph Conigliaro, MD, MPH:

Patients who attend AA after treatment can be characterized as those who never connect, those who connect briefly, and those who maintain stable (and sometimes quite high) attendance. Even those who connect for a short while appear to benefit years later, though higher attendance was associated with a greater likelihood of long-term abstinence. Providers should reinforce AA attendance as part of a comprehensive effort to improve long-term abstinence.

Reprinted with permission from Alcohol and Health: Current Evidence. March 10, 2006

Cannabis extracts can be harmful because of the unpredictable way the body reacts, New Scientist said.

Research detailed to the Federation of European Neuroscience Societies found boosting levels of some cannabinoids worsened epilepsy and Alzheimer’s.

Experts said it was hard to target the drug at specific parts of the body.

Some compounds in cannabis interfere with a natural signalling system in the brain, nerves and immune system.

The signalling system, which produces its own cannabinoids, plays a role in conditions such as MS, epilepsy, Alzheimer’s disease, schizophrenia and Parkinson’s disease.

Extra cannabinoids, from smoking cannabis or from medications, can therefore have a significant effect, researchers suggest.

Vincenzo Di Marzo, of Italy’s National Research Council, told the conference that he had found boosting the level of one natural cannabinoid, andandamide, in rats initially appeared to protect the animals from memory loss and nerve degeneration.

But if the rise was prolonged, the cannabinoid could be ineffective, or even damaging.

Beat Lutz, of the University of Mainz in Germany, found a another paradox in models of epilepsy in mice.

The same cannabinoid is normally produced by the body during an epileptic seizure to produce a calming effect.

But he found boosting levels could actually worsen seizures.

Reason

He said he believed the reason for the findings was that there were cannabis receptors on two different types of neuron populations which the drug could affect.

In one group, exposure to cannabinoids increases activity while in the other, it inhibits it.

Dr Lutz said this meant that depending on which one they hit, the effect was different.

Professor David Baker, from University College London, who has studied the impact of cannabis extracts in treating multiple sclerosis, said: “The problem with cannabis is that there’s no way of targeting the drug to any particular place.”

He said the hope was that scientists could manipulate the nervous system by managing the way cannabis compounds are released just as the depression drug Prozac does for serotonin by delaying release.

The only cannabis-based drug which can be used in the UK is a treatment for MS called Sativex.

It has been granted a special licence meaning it can only be used if the doctor takes responsibility for prescribing it.

The drug, produced by GW Pharmaceuticals, is a mouth spray containing two chemicals found in cannabis, THC and cannabidiol.

However, it is made using plant cannabinoids, rather than those found in the body.

QCT Europe: UK findings

Conclusions

Findings from our study reveal that DTTO clients showed considerable and sustained reductions in substance use, injecting risk and offending behaviours, and some improvements in their mental health. Outcomes were similar for those respondents who entered comparable ‘voluntary’ treatment options. The results – which are consistent with those from the other four partner countries involved in the QCT Europe study – suggest that drug treatment that is motivated, ordered or supervised by the criminal justice system can have comparable retention rates and outcomes to drug treatment entered through non-criminal justice routes. The approach should therefore be considered a viable alternative to imprisonment. However, from our qualitative analysis, there appeared to be considerable scope for improving arrangements for aftercare and resettlement for both groups across the UK sites.

More attention should also be paid to issues of treatment process and coordination between health and criminal justice systems in order to provide high quality and consistent treatment that is likely to optimise outcomes for individuals and the wider community. Attention should particularly be focused on:

• Ensuring that treatment is made quickly available to those offenders who are likely to produce the most significant benefits (i.e. those who have high levels of offending) in a manner which enhances motivation and engagement.

• Developing supportive “therapeutic alliances” between offenders and their probation officers and treatment staff.

• Dealing effectively with non-compliance. This does not mean that any lapses in drug use or attendance should be heavily punished; rather that they should be dealt with in a prompt and consistent way, recognising positive as well as negative behaviour changes.

• Making the full range of treatment options available to people who enter treatment as part of a court order, so that they can access support appropriate to their needs.

• Improving access to education, training and employment schemes.

Recent years have seen a rapid expansion in the options available for the criminal justice system to encourage or direct drug-dependent offenders into treatment in England and Wales. Our hope is that the results from the QCT Europe study can be used constructively to inform debate about the appropriate use of these options.

How to get further information

Copies of the full report, The quasi-compulsory treatment of drug-dependent offenders in Europe: Final National Report – England, by Tim McSweeney

The QCT Europe study was funded by the Fifth European Community Framework Programme covering Research, Technological Development and Demonstration activities (Quality of Life programme, contract number QLG4-CT-2002-01446). The authors are solely responsible for the content of this document. It does not represent the opinion of the Community. The Community is not responsible for any use that might be made of data appearing in it.

A British study of the outcome of treatment for drug addiction, published today in the open access journal BMC Public Health, also reveals that drug users were more likely to drop out of treatment if they had been coerced into it by the criminal justice system than if they had entered by other routes.

The authors of the study conclude that efforts to make treatment for drug addiction more accessible have succeeded in getting more people into treatment, but the impact of coercive measures to push drug users into treatment needs further consideration. They write: “recent measures to increase drug treatment participation have speeded up a revolving door both into and out of treatment”.

Dr. Caryl Beynon and colleagues from Liverpool John Moores University, analysed the records of 26,415 anonymous drug users who had entered treatment for drug addiction between 1997 and 2004 in Cheshire and Merseyside (England, UK).

The results of Beynon et al.’s study show that the proportion of individuals who dropped out of treatment increased from 7.2% in 1998 to 9.6% in 2002. Individuals coerced into treatment by the criminal justice system were more likely to drop out of treatment than those referred through other routes. The proportion of drug users who successfully completed treatment decreased from 5.8% in 1998 to 3.5% in 2002, but the proportion of drug users who came back to start treatment again after dropping out of treatment increased from 22.9% in 1998 to 48.6% in 2002.

A plant-derived medication that has been used to treat tobacco dependence in Eastern Europe for 40 years may be effective for smoking cessation, but it remains largely unnoticed in English-language literature, according to a review article in the same issue.

Cytisine is an alkaloid found in a plant known as the golden rain tree, or Cytisus laburnum. It has been used for decades as a smoking cessation drug in Eastern European countries, according to background information in the article.

Jean-Francois Etter, Ph.D., M.P.H., of the University of Geneva, Switzerland, reviewed the literature on the effect of cytisine on smoking cessation. Ten studies were found, and all were conducted in Bulgaria, Germany, Poland and Russia between 1967 and 2005.

“Research conducted during the past 40 years suggests that cytisine is effective for smoking cessation,” Dr. Etter reports. “Thus, an apparently effective smoking cessation drug that has been used for decades in Germany and Eastern European countries remained unnoticed in other countries.”

Most of the articles reviewed by Dr. Etter were never cited in English-language literature. Recent reviews of the efficacy of smoking cessation drugs omitted cytisine, and little research on the drug has been conducted in recent years.

Dr. Etter suggests the omission may be explained because studies on the efficacy of cytisine were not published in English and because the available research is based on studies that do not conform to current standards in conducting and reporting drug trials.

“An apparently effective treatment for the first avoidable cause of death in developed countries remained largely unnoticed, despite research published during the past 40 years,” he concludes. “How many other effective drugs are there for which efficacy remained unnoticed because existing trials were not published in English in Western countries?” (Arch Intern Med. 2006;166:1553-1559. Available pre-embargo to the media at http://www.jamamedia.org.)

Much is known about the rate of relapse after formal alcohol treatment but not after “spontaneous” or “natural” remission. Researchers studied remission and relapse in 461 individuals with an alcohol use disorder who had not received help before study entry. Subjects were interviewed at baseline and then 1, 3, 8, and 16 years later. At each follow-up, they were asked about their alcohol use and whether they had obtained professional treatment or participated in Alcoholics Anonymous at any time since the last follow-up.

• At the 3-year follow-up, remission occurred in 62 percent of subjects who had received help and in 43 percent of subjects who had not received help (P <0.01).

• Among these remitted subjects, relapse by year 16 occurred in 43 percent of those who had received help and in 61 percent of those who had not received help (P <0.05).

Comments by Peter Friedmann, MD, MPH:

Like previous studies, this study found that receiving help improves the chances of short-term remission and decreases the risk of relapse. Therefore, clinicians should emphasize the importance of early help seeking to their patients with alcohol use disorders and should offer ongoing support to help their patients in remission remain remitted.

“Previous studies established that alcoholism runs in families, but this research has given us the most extensive catalogue yet of the genetic variations that may contribute to the hereditary nature of this disease,” says NIDA Director Dr. Nora D. Volkow. “We now have new tools that will allow us to better understand the physiological foundation of addiction.”

The study can be viewed online and will be published in the December 2006 issue of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).

“This is an important contribution to studies of the genetics of alcoholism and co-occurring substance use disorders,” adds Dr. Ting-Kai Li, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). “The findings will open many new avenues of research into common factors in genetic vulnerability and common mechanisms of disease.”

NIDA researchers found genetic variations clustered around 51 defined chromosomal regions that may play roles in alcohol addiction. The candidate genes are involved in many key activities, including cell-to-cell communication, control of protein synthesis, regulation of development, and cell-to-cell interactions. For example, one gene implicated in this study — the AIP1 gene — is a known disease-related gene expressed primarily in the brain, where it helps brain cells set up and maintain contacts with the appropriate neighboring cells. Many of the nominated genes have been previously identified in other addiction research, providing support to the idea that common genetic variants are involved in human vulnerability to substance abuse.

The scientists, led by Dr. George Uhl, included Ms. Catherine Johnson, Ms. Donna Walther, Dr. Tomas Drgon, and Dr. Qing-Rong Liu. Their team developed, validated, and applied a new genetic platform that allowed them to generate the equivalent of more than 29 million individual genotypes and to analyze 104,268 genetic variations from unrelated alcohol-dependent and control individuals. The scientists used DNA samples that were collected by investigators of the Collaborative Study on the Genetics of Alcoholism (COGA), a study funded by NIAAA that included Dr. Howard Edenberg, Dr. Tatiana Foroud, and Dr. John Rice, who are coauthors of the paper. These samples had been analyzed previously to look for genetic associations to alcoholism, but the resolution and coverage achieved in the present study are unprecedented.

Dr. Volkow said finding ways to identify who is most physiologically vulnerable to addiction ‘will be a tremendous step towards more effective prevention and treatment approaches.’

The term ‘genome’ refers to the total genetic information of a particular organism. The normal human genome consists of about 3 billion base pairs of DNA in each set of chromosomes from one parent.

For more information, visit the NIDA home page at www.drugabuse.gov

A drug recently approved by the U.S. Food and Drug Administration as an aid to smoking cessation appears effective both short and long-term for smokers trying to quit, according to two reports in the August 14/28 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Smoking is the leading cause of preventable death in the United States and worldwide. Currently available pharmacotherapies for smoking cessation include nicotine replacement therapy (NRT) – such as gum, skin patches, tablets, nasal spray and inhalers – and the antidepressant drugs bupropion hydrochloride and nortriptyline hydrochloride. These have shown limited success rates, with success at one year averaging approximately seven percent to 30 percent, according to background information in the articles.

The new drug varenicline tartrate mimics the effects of nicotine to help offset cravings, and in the presence of nicotine it helps suppress some of the reinforcing effects of smoking.

Mitchell Nides, Ph.D., of Los Angeles Clinical Trials, and colleagues with the Varenicline Study Group conducted a randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of varenicline for smoking cessation. Healthy smokers aged 18 to 65 years were randomly assigned to receive varenicline in a dosage of .3 milligrams once daily, 1 milligram once daily, or 1 milligram twice daily for six weeks, plus placebo for one week; to 150 milligrams of sustained-release bupropion hydrochloride twice daily for seven weeks; or to placebo for seven weeks.

The authors report that varenicline, in combination with brief behavioral counseling, was more effective for short and long-term smoking cessation than placebo.

“Efficacy improved as the dose increased, with varenicline tartrate, 1 milligram twice daily, providing the highest rates of continuous abstinence across all treatment groups, including bupropion,” they write. Four-week continuous quit rates were 48 percent for varenicline, 1 milligram twice daily; 37.3 percent for varenicline, 1 milligram daily; 33.3 percent for bupropion hydrochloride; and 17.1 percent for placebo. Long-term quit rates from four weeks to one year were 14.4 percent for the group that received varenicline, 1 milligram twice daily, vs. 4.9 percent for placebo.

“In this study, varenicline tartrate, 1 milligram twice daily, effectively helped subjects quit smoking, with response rates three times higher than those for placebo while demonstrating a good tolerability profile in this population of smokers who on average had smoked approximately 20 cigarettes per day for approximately 24 years,” the authors write. “Efficacy was maintained in the non–drug treatment phase through week 52. The significant reductions in craving and in some of the rewarding effects of smoking seen with varenicline tartrate, 1 milligram twice daily, may assist in promoting abstinence and preventing relapse,” they conclude

In an accompanying article, the same research team reports that varenicline taken over 12 weeks was effective in helping smokers quit, and was generally well tolerated.

Cheryl Oncken, M.D., of the University of Connecticut Health Center, Farmington, and colleagues studied 647 patients to evaluate the efficacy, safety and tolerability of four varenicline dose regimens–two with titrated, or progressive, dosing over the first week, and two with a non-titrated, or fixed, dosing schedule, for promoting smoking cessation. Healthy smokers aged 18 to 65 years randomly received varenicline, .5 milligrams twice daily non-titrated, .5 milligrams twice daily titrated, 1 milligram twice daily non-titrated, 1 milligram twice daily titrated or placebo for 12 weeks, then with a 40-week follow-up period to assess long-term efficacy.

“In this study, treatment with varenicline tartrate at doses of .5 milligrams and 1 milligram twice daily, was associated with significantly higher smoking cessation rates compared with placebo,” the authors report. At weeks nine to 52, the abstinence rates were 22.4 percent in the 1-milligram group, 18.5 percent in the .5-milligram group and 3.9 percent in the placebo group.

Among those who were treated with varenicline, 16 percent to 42 percent experienced nausea. Reports of nausea were lower among those who received progressive dosing.

“In summary, varenicline tartrate (.5-milligram and 1-milligram doses taken twice daily for 12 weeks) significantly improved short- and long-term abstinence rates compared with placebo,” the authors conclude. “Future studies are warranted to compare the efficacy of varenicline to other smoking cessation pharmacotherapies and to determine whether a longer duration of medication treatment improves smoking cessation rates.”

The results of the studies by the Varenicline Study Group demonstrate that varenicline is a novel medication to aid in smoking cessation, writes Bankole A. Johnson, D.Sc., M.D., Ph.D., of the University of Virginia, Charlottesville, in an accompanying editorial. Dr. Johnson also summarizes other approaches to treating nicotine addiction now in development, including medications and a vaccine. “In sum, pharmacological and immunological studies are opening up new vistas for safe, efficacious and potent treatments for nicotine dependence,” he writes. “Molecular genetic studies also are investigating how to identify those individuals vulnerable to becoming nicotine dependent and, once they are dependent, the treatments that might work best for them. All these advances will deliver real aid to craving.

To quantify the effect of help seeking on recovery from alcoholism, researchers in the United States analyzed data from 4,422 adults who had participated in a nationally representative survey and developed alcohol dependence at least 1 year before their participation.

• Only 26 percent of subjects had ever sought help for their alcohol problems; 3 percent participated in a 12-step program only, 6 percent in formal treatment only, and 17 percent in both.

• Help seekers drank more and had higher lifetime prevalences of other drug use, mood disorders, and personality disorders than did subjects who had not sought help.

• In analyses adjusted for potential confounders, help seeking significantly increased the likelihood of any recovery (odds ratio [OR] 2.4) and of abstinence (OR 4.0). Any recovery was defined as, in the past year, having no symptoms of alcohol abuse or dependence and either drinking low-risk amounts* or abstaining.

• The odds of recovery were greater for those who had participated in 12-step programs with or without formal treatment than for those who had participated in formal treatment only.

Comments by Peter Friedmann, MD, MPH:

Even though they had more comorbidity and therefore were at risk for worse outcomes, seekers of formal and informal treatment had better odds of recovery from alcohol dependence. This study could not separate the motivation inherent in seeking help from the therapeutic effects of help received. However, help seeking—regardless of the patient’s level of readiness—should be encouraged.

*up to 14 drinks per week and up to 4 drinks on any day for men; up to 7 and up to 3, respectively, for women.

Reference:

Dawson DA, Grant BF, Stinson FS, et al. Estimating the effect of help-seeking on achieving recovery from alcohol dependence.

By Sara Solovitch

When a man and a woman drink too much alcohol — by far the most widely abused substance in the country  they not only do it for different reasons, they also get different results.

Where men may use alcohol to feel “powerful,” women usually drink to fight feelings of hopelessness and anger.

Though women generally drink less than men, the risk of alcoholism kicks in a lot faster: Seven or more glasses a week is considered risky for a woman, compared to 14 or more for a man.

Alcoholism also carries greater risks to women. Heavy drinking increases the chances of a woman becoming a victim of violence and sexual assault. Most women who abuse alcohol and drugs — studies show as many as 80 percent to 90 percent — have a history of physical or sexual abuse.

Women are more likely than men to develop liver inflammation and to die from cirrhosis. They are more vulnerable to alcohol-induced brain damage and cardiovascular disease. And heavy drinking appears to increase the risk of breast cancer, as well as cancers of the digestive tract.

The stigma for using drugs and alcohol also is greater, and it’s often one of the biggest obstacles to a woman seeking treatment. She fears — rightly — that she will lose custody of her children if she admits to having a substance abuse problem. Or she’s so busy being the caregiver that she puts off asking for help, often for so long that she develops serious ailments.

The numbers, fairly consistent since the 1990s, say it all: Of the 15.1 million people who abuse alcohol, 4.6 million are women, and only 25 percent of them are in traditional treatment, according to the National Institute on Alcohol Abuse and Alcoholism. Women also tend to go more nontraditional routes for help with addiction, looking to either their doctors, therapists or psychiatrists.

During the past decade, segregated treatment has become a key to success for women, providing a more nurturing environment that encourages patients, often childhood victims of physical and sexual abuse, to open up and talk about the traumas that led to their substance abuse.

A review of hundreds of studies examining substance abuse treatment found that treatment is not only effective in reducing alcohol and drug use, it also helps lower crime and healthcare costs. The report offers a helpful resource for coalitions looking to demonstrate the value of treatment to their community or for coalitions looking to enhance their treatment capacity.

A drug that Duke University Medical Center researchers have successfully used to help some people quit smoking may also help curb cocaine cravings, according to studies conducted in rats.

The drug mecamylamine, used in combination with nicotine to help reduce the urge to smoke cigarettes, has now been shown in animal studies to reduce their self-administration of cocaine.  Rats that were trained to press a lever in order to get cocaine no longer pressed it with the same frequency after they were given mecamylamine, said Edward Levin, lead author of the study.  When injected with mecamylamine, the mice infused cocaine 11 times per hour, versus 19 times per hour when they received a placebo injection of saline – a reduction of more than 40 percent.  “It’s always very exciting when a drug used for one addiction has implications for a broader range of addictive drugs,” said Levin, whose study was funded by the National Institutes of Health.  Mecamylamine is an older medication originally used to treat high blood pressure.  Researchers now know it blocks some of nicotine’s ability, and potentially that of other drugs, to generate feelings of pleasure in the brain.  Levin said it works by occupying specific sites, called “nicotinic receptors,” on nerve cells where nicotine would normally act.  When mecamylamine blocks these receptors, nicotine can no longer exert its full action, that of stimulating the release of dopamine.  Dopamine is the primary brain chemical involved in generating pleasure.  Drugs like nicotine, alcohol and cocaine all increase available amounts of dopamine and thereby increase the pleasure sensation, said Jed Rose, chief of the Nicotine Research Program at Duke and study co-author.  Eventually, the brain may prefer the drug over natural rewards like food or sex, and hence, the person can become addicted.  Mecamylamine blocks the action of nicotine, and potentially cocaine, by lowering the net amount of dopamine available in the brain.  While cocaine still boosts available levels of dopamine, its overall amount is decreased because mecamylamine has plugged up some of the nicotinic receptor sites where the brain would naturally be activating its own dopamine.  “In other words, the brain has its own chemical, acetylcholine, that stimulates the release of dopamine.  Mecamylamine comes along and occupies some of the nicotinic acetylcholine receptor sites and prevents them from activating dopamine,” Rose said.  “So the net effect is that less dopamine is being produced, even when cocaine comes along and boosts dopamine levels through a different pathway.”  Rose said the person still desires nicotine or cocaine, but the desire is weakened because the brain is no longer being flooded with dopamine.  “Mecamylamine reduces desire, but it doesn’t quench it,” he said.  “Yet given how few medications there are to combat serious addictions, even a medication that reduces craving can be of significant benefit.”  Already, mecamylamine has proven to be of significant benefit in helping people quit smoking.

In earlier Duke studies, Rose demonstrated that using a patch with nicotine and mecamylamine together helped 40 percent of smokers quit for at feast one year, while only 15 percent of smokers were able to do so using the patch alone.  The researchers expect mecamylamine to be approved for smoking cessation sometime this year.

Researchers at The Scripps Research Institute have developed a second-generation, long-lived cocaine immunoconjugate that blocks cocaine passage into the brain of rats.
The new immunoconjugate displays two amide groups in the stereochemical configuration found in the cocaine framework, so that antibody affinity to cocaine is optimized, Dr. Janda and associates report in the Proceedings of the National Academy of Sciences.
Rats were immunized with the vaccine and challenged with systemic cocaine.  Compared with unimmunized controls, locomotor activity was significantly reduced, as were stereotypic patterns of behavior, such as sniffing and rearing.  Effects were sustained throughout the 12 days of the study.
“We have been able to tap into the immune system to immobilize antibodies to recognize cocaine as foreign and remove it from the body,” Dr. Janda said.  “The current vaccine provides a much longer lasting effect than our previous vaccines, suggesting that boosting requirements would be minimal and the antibody circulation time would be increased.”
Dr. Janda added that the vaccine would be of most use in addicts who are motivated to stop using cocaine.  “Typically an addict will relapse several times before he or she will ‘kick’ the drug,” he said.  “We believe the vaccine will protect addicts at weak moments when they have the urge to get high.  If we can prevent the high we can prevent relapse and this would speed the process of kicking the addiction.”

More U.S. teens are being admitted to centres to be treated for alcohol and drug abuse, a government report released on Thursday shows. The report, by the Substance Abuse and Mental Health Services Administration (SAMHSA), shows that the number of adolescents aged between 12 and 17 admitted to substance abuse treatment increased by 20 percent between 1994 and 1999.
The survey, which covered 1.6 million cases of adults and youths over age 12 who were admitted for treatment at a centre, found that most were abusing alcohol – 47 %.  16% were users of opiates. mostly heroin, 14% used cocaine and 14% marijuana or hashish. More than half the patients abused more than one substance.
But for teen-agers the numbers were dramatically different. In 1994, 43% of teens treated for substance abuse were marijuana users. In 1999, 60% were. Half of them were sent to treatment by the courts, the report finds.  While we can all be thankful that people who need help are getting it, this report shows some of the real-life consequences of marijuana use,” said John Walters, appointed this month as director of the Office of National Drug Control Policy.

 A New York addiction-treatment provider is seeing positive results using Exposure Response Prevention (ERP) therapy as part of its treatment regimen.
SLS Health in Brewster, has been using the behavioural therapy with a portion of its clients. “We’ve taken the principles of desensitisation and brought it to [illicit] drug and alcohol treatment,” said Robert DeLetis, senior addiction counsellor.  The therapy exposes individuals to alcohol and the other drugs to which they are addicted, to teach them how to deal with their cravings.
“The exposure to these catalysts elicits powerful cravings that the addict is taught how to handle without giving in to them,” said Joseph Santoro, Ph.D., chief operating officer, “in this way, they are exposed to their triggers but prevented from getting high.  This leads to the extinction of their desire to use.”
An internal study found that ERP is having a positive impact when used in conjunction with standard treatment, such as 12-step meetings, cognitive and group therapy, and medication.
For the study, 57 patients, 33 of whom received ERP, were contacted one to two years after completion of treatment.  The study found that those who participated in ERP had a 55% relapse rate, compared to 88% who did not receive the therapy.

Snippets from SAMHSA

In 2000, an estimated 4.7 million people aged 12 or older (2.1 percent of the  total population) needed treatment for an illicit drug abuse problem.
16.6 percent of the people who needed treatment in 2000, received Priority treatment services at a specialty facility.
Among Hispanic male admissions in 1999, alcohol was the most common primary substance of abuse(39%), followed by opiates (32%) and marijuana(14%).
In 1999, the most common primary substance of abuse among Hispanic female admissions was opiates (34%), followed by alcohol (26°/o) and cocaine (16%).
In 1999, opiates were the most common substance of abuse for Hispanic admissions aged 25-44, while alcohol was the most common substance of abuse for non-Hispanic admissions in the 25-44 age group.

Methadone substitution has long been used as a treatment for heroin addiction. But a new 33-year follow-up study has found that equally satisfactory results are possible without recourse to long-term prescribing of opioids.

Until now there has been no long-term study of people addicted to injected heroin who have been treated without the prescribing of methadone substitute.

This study set out to look at the outcome for patients treated for injected heroin 33 years after they were first seen, and 26 years after they were first followed up. Measures included sustained abstinence from heroin, continued maintenance on methadone and deaths.

86 people with heroin addiction first seen in 1966-67 in a small town in the south-east of England were studied. At the time of diagnosis the patients were aged between 16 and 20, were single and living at home with their parents. They all injected heroin.

All the patients were treated in the local general psychiatric service, which differed from most other UK services for heroin addiction in that it did not prescribe methadone substitute for 23 years after recruitment of the patient group (i.e. until 1989).

The main provisions of the service were immediate help in times of crisis; personal counselling; regular follow-up; an ongoing relapse prevention group; and symptomatic relief with drugs other than methadone.

The first follow-up took place after six years. At that assessment 13% of the patient group were judged to have stopped using any illegal drugs, 51% were still injecting, 6% had died and 12% had experienced alcohol-related problems.

For this follow-up study, 45 of the original patient group were located and their clinical state assessed using multiple sources, including personal interviews with some of them.

It was found that 42% of the group had been abstinent for at least 10 years. 10% were taking methadone and were classified as addicted. 22% had died. 8% of the group could not be located.

The authors of this study compared their results with three other British studies. They found the death rates comparable (15%-20%), but the rates of abstinence and methadone dependency differed.

The researchers comment that it is encouraging that trend studies show agreement that the proportion of people maintaining sustained abstinence rises with time, whilst the proportion of those still addicted declines.

One worrying feature, however, is the high proportion of premature deaths, mainly due to overdoses. As overdose with opioid drugs is often mentioned as a cause of death, there is a need for closer monitoring of these drugs, and regular health screening and intervention to reduce premature deaths.

The advantages of long-term substitute prescribing of methadone are obvious in terms of increased social stability and reduction of crime. However, the researchers were struck not only by the number of premature deaths in people taking methadone, but also by the negative perceptions of life among those who are currently prescribed this opioid.

The findings of this study highlight the need to compare outcomes between people prescribed substitute drugs for addictions, and those who are not.

Reference Nehkant H, Rathod R, Addenbrooke WM and Rosenbach AF (2005) Heroin Dependence
in an English town: 33-year follow-up. British Journal of Psychiatry, 187, 421-425

Scientists at the National Institute on Drug Abuse (NIDA) have demonstrated that laboratory animals will self-administer marijuana’s psychoactive component, THC (delta-9-tetrahydrocannabinol), in doses equivalent to those used by humans who smoke the drug.
Self-administration of drugs by animals, long considered a model of human drug-seeking behavior, is characteristic of virtually all addictive and abused drugs.
“This study is simple and its findings are clear,’ says NIDA Director Dr. Alan I. Leshner. ‘Animals will work to get THC. This emphasizes further the similarity between marijuana and other abusable, addicting substances. Both animals and humans will work to acquire access to marijuana in the same way that both animals and humans change their behavior to get other drugs of abuse, like cocaine and heroin.”
“This is the first study in which it has been possible to show that monkeys or other research animals will self-administer THC. There are many factors which may explain this behavior, including the fact that in our study we used doses of THC that are directly comparable to doses in marijuana smoke inhaled by humans,” Dr. Goldberg says.
Before the study began, the scientists first established self-administration behavior in squirrel monkeys that received repeated intravenous injections of cocaine after pressing a lever 10 times for each injection. At the start of the study, the researchers replaced cocaine with saline solution and the animals’self-administration stopped. When saline was replaced with THC in a solution that would rapidly pass from blood to the brain, the animals resumed self-administration, rapidly pressing the lever to obtain on average 30 injections of THC during each of a series of 1-hour sessions. Treatment with a compound that prevented TI-IC from binding to cannabinoid receptors on brain cells almost completely eliminated self-administration of THC, but had no effect in another group of monkeys self-administering cocaine under identical conditions.
“The drug-seeking behavior in these animals was comparable in intensity to that maintained by cocaine under identical conditions, and was obtained from a range of doses comparable to those self-administered by humans smoking a single marijuana cigarette,” Dr. Goldberg says. “This finding suggests that marijuana has as much potential for abuse as other drugs of abuse, such as cocaine and heroin.”

People who begin using marijuana early are more likely than others to become dependent, new findings show.
In a study of over 2700 marijuana users in Ontario, Canada, those who started smoking at 17 years or later were twice as likely to eventually quit compared with those who started at 14 years or younger. “We believe this study has uncovered important information regarding the effects of patterns of marijuana use on the risk of desistance and progression to marijuana- related harm Dr. David J. DeWit, of the Centre for Addiction and Mental Health, in London, Ontario.
“We observed a significant.. relationship between frequency of lifetime marijuana use and marijuana desistance,” the authors say.
Compared with infrequent use, a lifetime frequency of 100 to 199 uses predicted an almost five fold higher likelihood of developing marijuana disorders, they report.
Prevention programs that are effective in delaying initiation of marijuana use until the age of 16 and beyond may greatly diminish the likelihood of prolonged consumption and consequently serve to avert serious problems later in life” DeWit and colleagues conclude.

People who begin using marijuana early are more likely than others to become dependent, new findings show.
In a study of over 2700 marijuana users in Ontario, Canada, those who started smoking at 17 years or later were twice as likely to eventually quit compared with those who started at 14 years or younger. “We believe this study has uncovered important information regarding the effects of patterns of marijuana use on the risk of desistance and progression to marijuana- related harm Dr. David J. DeWit, of the Centre for Addiction and Mental Health, in London, Ontario.
“We observed a significant.. relationship between frequency of lifetime marijuana use and marijuana desistance,” the authors say.
Compared with infrequent use, a lifetime frequency of 100 to 199 uses predicted an almost five fold higher likelihood of developing marijuana disorders, they report.
Prevention programs that are effective in delaying initiation of marijuana use until the age of 16 and beyond may greatly diminish the likelihood of prolonged consumption and consequently serve to avert serious problems later in life” DeWit and colleagues conclude.

SOURCE: Preventive Medicine 2000;31 :455-464

A St. Louis study finds that drug courts and addiction treatment are far more cost-effective than probation over the long run, Alcoholism & Drug Abuse Weekly reported March 8.

The study by the Institute of Applied Research focused on the city’s adult felony drug court. Researchers concluded that drug court costs about $1,449 per offender more up front than probation, but end up saving taxpayers $7,707 within four years of discharge.

“The drug-court client pays for his drug-court experience within about 3.5 years by avoiding costs [such as reinvolvement with the criminal-justice system] and paying taxes,” said Jeffrey N. Kushner, the city’s drug-court administrator.

The complete report is available on the Institute of Applied Research website.

How likely you are to becoming a cocaine addict could well depend on your genetic make up, say researchers from the Institute of Psychiatry. Some people have a gene variation which stops the production of a protein that regulates dopamine in the brain.

The researchers said that if you have two copies of this gene variation, your chances of becoming addicted to cocaine are 50% higher.

You can read about this study in the Proceedings of the National Academy of Sciences. The study was funded by the Medical Research Council (UK).

The researchers studied the DNA of 1550 people. 700 of them were cocaine abusers while 850 were not.

We all produce a protein called DAT. DAT controls the removel of excess dopamine from the brain. Cocaine inhibits the action of DAT leading to dopamine overload. The dopamine overload is what gives the cocaine abuser the “high” feeling.

Part of our genetic code controls the production of DAT. The researchers found that people who had two copies of the variant that controls DAT production were 50% more likely to become cocaine addicts.

Obviously, if you have two copies of this variant and never touch cocaine your chances of becoming addicted to it are zero. Everyone will eventually become addicted to cocaine, if they take it often enough and for long enough. People with this gene variant are more likely to become addicted sooner.

Dr Gerome Breen, head researcher, said “This study is the first large scale search for a genetic variant influencing the risk of developing cocaine addiction or dependence. The target we investigated, DAT, is the single most important in the development of cocaine dependence. It made sense that variation within the gene encoding DAT would influence cocaine dependence.”

It was found that people who had the genetic variant were more likely to inhibit the DAT response when taking cocaine.

Hopefully, this new finding may eventually help in the designing of new drugs for the treatment of cocaine addiction, say the researchers.

Written by: Christian Nordqvist, Editor: Medical News Today

Source: http://www.medicalnewstoday.com/healthnews.php?newsid=39415

LONDON (Reuters) British scientists are closer to developing drugs based on cannabis that will take away pain but also take away the “high”.

Researchers from Imperial College in London have separated cannabinoids, the active components of the popular the recreational drug, and shown that they act on both the brain and spinal cord.

The findings will allow scientists used receptors for cannabinoids on the spinal cord, particularly the areas concerned with pain processing.

By delivering drugs directly to the spinal cord to relieve pain they bypass the brain so there are no psychoactive effects.

New drugs based on cannabis are still years away but the findings are an important first step.

Source: Reuters Report July 2000.

“Drug abuse treatment can have important positive public health benefits even if the outcomes are less than perfect,” lead study author DL George Woody told Reuters Health. “The 12-step oriented combination of group and individual counselling worked the best, though all patients reduced their risk.”

Woody urged everyone to “support substance abuse treatment. It can do a lot of good both in the short and long term.”

In an article in the Journal of Acquired Immune Deficiency Syndromes, Dr. Woody who is at the University of Pennsylvania in Philadelphia and his colleagues report on changes in HIV risk among 487 people undergoing treatment for cocaine addiction.

Treatment was associated with an average reduction of cocaine use from 11 days per month to one day per month after six months, the authors report, with participants who received both individual and group drug counselling faring best.

Treatment participation was also associated with significant reductions in risky sex and the total risk of HIV infection, the report indicates.

Those who completed treatment showed a trend toward less sex risk and significantly less total risk than did patients who dropped out before completing their program, the researchers note.

HIV risk reduction corresponded to reductions in drug use and to improvements in psychiatric symptoms, the results indicate. This improvement was similar regardless of race, gender, sexual orientation or the presence of antisocial personality disorder.

“The fact that all treatments consisted of no more than three weekly outpatient sessions that included risk reduction counselling is worth noting,” the authors conclude, “because it suggests that reductions in cocaine use and HIV risk can be achieved at a relatively low cost, at least for a portion of the patients who seek treatment for cocaine dependence.”

SOURCE: Journal of AIDS (news -web sites) 2003;33:82-87.

(The Substance Abuse and Mental Health Services Administration’s Drug Abuse Warning Network ( DAWN ) found that the most common single-drug suicide deaths involved opiates, followed by antidepressants and then cocaine, sedatives and anti-anxiety medications.

DAWN information showed that 7 out of 10 of the suicide deaths involved multiple drugs. The highest rates included combinations of alcohol and antidepressants, anti-anxiety medications and opiates, alcohol and opiates, and then antidepressants with opiates. One quarter of the overall deaths in the metropolitan areas and states involved multiple antidepressants.

“What this data shows is what we teach in our education presentations,” comments a supervisor at Narconon Arrowhead, which is one of the nation’s largest and most successful drug rehabilitation and education programs, “that all drugs are basically poisons and that enough of any drug can cause extreme adverse reactions and even death.”

The DAWN study of 32 metropolitan areas and six states also looked for mortality rates for drug abuse. Of the cities that were examined, Baltimore and Albuquerque had the highest rates with more than 200 deaths per million people. Another 14 metropolitan areas had drug misuse death rates that exceeded 100 per 1,000,000.

In the six states, the number of deaths related to drug misuse or abuse ranged from 74 to 697. After adjusting for population differences, the rates of drug misuse/abuse deaths ranged from 88 deaths per 1,000,000 in Maine and New Hampshire to 162 deaths per million in New Mexico.

The Drug Abuse Warning Network is a public health surveillance system that monitors drug-related hospital emergency department visits and drug-related deaths to track the impact of drug use, misuse, and abuse in the U.S.

This survey did not include any deaths from adverse reactions to drugs. Such cases would include the consequences of using a prescription or over-the-counter pharmaceutical for therapeutic purposes and include deaths related to adverse drug reactions, side effects, drug-drug interactions, and drug-alcohol interactions.

Source: I-Newswire.com Jan.2006

Over 160,000 people admitted for drug addiction treatment in 2003 started using drugs before the age of 13.

The Substance Abuse and Mental Health Services Administration (SAMHSA) recently released a report from ongoing monitoring of the Treatment Episode Data Set (TEDS) showing an increase in the number of people in treatment for drug addiction who started at an earlier age.

The report tracked treatment admissions from 1993 to 2003 and the percentage of people in treatment who started using drugs before the age of 13 had increased from 12% to 14% during that time span. The total number of people jumped from about 114,000 to more than 162,000.

In a SAMHSA release, Administrator Charles Curie exclaimed, “Age at first use is an important predictor of the potential for serious substance abuse problems later in life. The increase in the proportion of the admissions for drug use before age 13 should be a wake-up call to parents to speak with their children early and often about the dangers of drug use.”
Source: (PRWEB) February 1, 2006

Methadone substitution has long been used as a treatment for heroin addiction. But a new 33-year follow-up study has found that equally satisfactory results are possible without recourse to long-term prescribing of opioids.

Until now there has been no long-term study of people addicted to injected heroin who have been treated without the prescribing of methadone substitute.

This study set out to look at the outcome for patients treated for injected heroin 33 years after they were first seen, and 26 years after they were first followed up. Measures included sustained abstinence from heroin, continued maintenance on methadone and deaths.

86 people with heroin addiction first seen in 1966-67 in a small town in the south-east of England were studied. At the time of diagnosis the patients were aged between 16 and 20, were single and living at home with their parents. They all injected heroin.

All the patients were treated in the local general psychiatric service, which differed from most other UK services for heroin addiction in that it did not prescribe methadone substitute for 23 years after recruitment of the patient group (i.e. until 1989).

The main provisions of the service were immediate help in times of crisis; personal counselling; regular follow-up; an ongoing relapse prevention group; and symptomatic relief with drugs other than methadone.

The first follow-up took place after six years. At that assessment 13% of the patient group were judged to have stopped using any illegal drugs, 51% were still injecting, 6% had died and 12% had experienced alcohol-related problems.

For this follow-up study, 45 of the original patient group were located and their clinical state assessed using multiple sources, including personal interviews with some of them.

It was found that 42% of the group had been abstinent for at least 10 years. 10% were taking methadone and were classified as addicted. 22% had died. 8% of the group could not be located.

The authors of this study compared their results with three other British studies. They found the death rates comparable (15%-20%), but the rates of abstinence and methadone dependency differed.

The researchers comment that it is encouraging that trend studies show agreement that the proportion of people maintaining sustained abstinence rises with time, whilst the proportion of those still addicted declines.

One worrying feature, however, is the high proportion of premature deaths, mainly due to overdoses. As overdose with opioid drugs is often mentioned as a cause of death, there is a need for closer monitoring of these drugs, and regular health screening and intervention to reduce premature deaths.

The advantages of long-term substitute prescribing of methadone are obvious in terms of increased social stability and reduction of crime. However, the researchers were struck not only by the number of premature deaths in people taking methadone, but also by the negative perceptions of life among those who are currently prescribed this opioid.

The findings of this study highlight the need to compare outcomes between people prescribed substitute drugs for addictions, and those who are not.

Reference Nehkant H, Rathod R, Addenbrooke WM and Rosenbach AF (2005) Heroin Dependence
in an English town: 33-year follow-up. British Journal of Psychiatry, 187, 421-425

Need for meth treatment programs growing dramatically

Two new surveys released today by the National Association of Counties (NACo) show that methamphetamine abuse continues to have a devastating effect on America’s communities.

One survey, “The Effect of Meth Abuse on Hospital Emergency Rooms,” revealed that there are more meth-related emergency visits than for any other drug and the number of these visits has increased substantially over the last five years. The second survey, “The Challenge of Treating Meth Abuse,” showed that the need for treatment programs for meth addiction is growing dramatically and lack of funding is an obstacle in meeting this demand.

“There is no question that meth abuse is having a devastating effect on America’s communities,” said Bill Hansell, President of NACo and Commissioner in Umatilla County, Ore. “Some states have enacted legislation that has been effective in reducing the number of local labs that produce meth. But officials in two of those states have said that the number of users has not been reduced. We still have a fight on our hands. The vast majority of meth being used today is being imported into our country. We have to find a way to treat those people that have become addicted and prevent others from becoming addicted.”

Both surveys were conducted in late 2005. The results of the emergency room survey are based on 200 responses from hospital emergency room officials in 39 states. Most of the hospitals participating in the survey are either county owned or operated. The second survey asked 200 county behavioral health officials in 26 states about drug treatment programs and how they have been affected by the meth epidemic.

A factor affecting treatment programs is that treatment for meth addiction is different from other drugs. 54% of the officials reported that the success rate is different and 44% said that the length of time in the program is longer for meth addicts. Meth users seeking treatment require special protocols and longer treatment periods than users of other drugs. said. “We hope that he will recognize the need for more funding for treatment.”

This is the second set of surveys that NACo has released on meth abuse. In July 2005, NACo released the results of two surveys it conducted on the impact of meth. The surveys reported responses from county sheriffs and police departments and from child welfare officials. The survey of 500 sheriffs and police departments showed that meth abuse is the top drug problem facing counties in America.

In an alarming number of meth arrests, there is a child living in the home. Often, these children suffer from neglect and abuse. 40% of the counties where child welfare activities are the responsibility of the county reported that out of home child placements have increased because of meth, according to the second survey released in July.
Source: www.naco.org January 18, 2006

Inbred strains of rats differ in how aggressively they seek cocaine after a few weeks of use, researchers say. The finding, posted online Jan. 18 by Psychopharmacology, is another piece of evidence that genetics plays a role in the relapse of drug-seeking behavior in humans, says Dr. Paul J. Kruzich, behavioral neuroscientist at the Medical College of Georgia and lead study author.

It also fingers glutamate, a neurotransmitter involved in learning and memory, as an accomplice in stirring the cravings and uncontrollable urges that drive some drug users to use again, he says.

“Given the right environmental stimuli, all persons addicted to psychostimulants can relapse, but potentially some people are a little more susceptible than others * it’s all about gene-environment interaction,” says Dr. Kruzich.

He took two strains of inbred rats – Fischer 344 and Lewis – with known genetic differences, enabled each to self-adminster cocaine for 14 days, then took the drug away for a week but not the levers the animals used to access it. During that hiatus, he adminstered a drug that stimulates glutamate receptors, possible targets for drugs of abuse.

He found that the F344 strain worked harder to get cocaine than the Lewis rats following treatment with the glutamate drug, suggesting they were more susceptible to relapse.

“Maybe 12-step programs and faith-based programs will be enough to keep some people from relapsing,” says Dr. Kruzich. “For others we may have to come up with medical treatments we can use on top of those to keep them from taking drugs again.”

He says there are many different versions of the hundreds of genes that may play a role in increasing the risk of relapse.

It’s known that some people become addicted more quickly than others, some literally with their first use, he says. The hardest part is not getting people to stop taking drugs: that happens when they are checked in a clinic or put in jail. The real work is keeping them from relapsing when they are out of such restricted environs, he says.

“Something happens, either they see an old colleague they have used with, they go into an old environment, they have a huge stressor in life and they start to want the drug. They have drug hunger, what we call drug craving,” says Dr. Kruzich. “When it gets bad enough, they engage in drug-seeking behavior.” His lab is working to identify the relapse trigger to use as a target for developing ways to curb craving and subsequent relapse.

His studies focus on an area of the brain called the nucleus accumbens core, a target for drugs of abuse long considered a pleasure center, Dr. Kruzich says. Drugs such as cocaine and methamphetamine stimulate release of dopamine in the nucleus accumbens. Dopamine is a neurotransmitter believed responsible for the euphoria that come with drug use. In fact, animals given dopamine blockers won’t self-adminster drugs of abuse, and dopamine has long been a focus of drug-abuse studies.

“These drugs impinge upon the reward centers of the brain that normally food, sex, survival and adaptation impinge upon,” says Dr. Kruzich. “When you are having that great piece of cheesecake and thinking, ‘Oh man,’ that is the kind of response these drug of abuse are evoking but much more so than that cheesecake could ever do.”

Glutamate, also released in the nucleus accumbens core, may play an equally important role in drug relapse, he says. Drugs such as cocaine appear to alter glutamate neurotransmission in the core, which may contribute to the rewiring of the brain that occurs with drug use. “It’s not that these drugs just damage neurons, which they can, but they rewire the circuitry of the brain so no longer is your spouse or your job or other things in your life important to you. Your brain is tricked into thinking that drugs are the most important thing for your survival,” Dr. Kruzich says.

Unfortunately, drugs that restore glutamate function also produce seizures, so scientists are looking for an indirect approach to restore the misdirected rewiring.

Source: mcg.edu/news/2006NewsRel/Kruzich011806.html

Smoking cannabis is strongly associated with delinquent and aggressive behaviour in young teenagers, a major study has found.

Researchers in the Netherlands revealed the link after surveying more than 5,500 adolescents aged 12 to 16.

The results showed that “externalising” problem behaviour, such as criminality and aggression, increased with higher use of cannabis. No similar association was found with “internalising” problems of withdrawal and depression.

The scientists, led by Ms Karin Monshouwer, from the Trimbos Institute in Utrecht, accounted for confounding influences including social background, regular smoking and alcohol consumption.

They wrote in the British Journal of Psychiatry: “This study shows that at young ages the use of cannabis is already strongly associated with delinquent and aggressive behaviour, even after controlling for strong confounders such as alcohol use and smoking.

“The strength of the associations increased with higher frequency of use, and significant associations were only present among those who had used cannabis recently.”

Cannabis users who had not taken the drug in the preceding year did not show any more signs of delinquency than teenagers who had never smoked a joint. “Heavy” cannabis use was also associated with thought and attention problems.

Marjorie Wallace, chief executive of the mental health charity Sane, said: “In the past, it has been claimed that cannabis is of less concern than it might be because it can make people withdrawn rather than aggressive.

“Some recent studies, however, have been linking aggressive behaviour with heavy use of cannabis, particularly among young people.

“Aggression can worsen the symptoms and outcomes of those who may be developing mental illness.”
Source: www.Scotsman.com 6.2.06

Do smokers crave nicotine to self-medicate their depression? The question has prompted much discussion since a study concluded that smokers are more depressed than nonsmokers, “We thought understanding the smoker’s mind would help us end tobacco use,” said Gerald Markle, an author and sociology professor at Western Michigan University. “But, in some respects, we’ve raised as many new questions as we’ve answered.”

In addition to being nearly five times as likely to suffer from major depression as nonsmokers, smokers also have been found to be more apt to have anxiety disorders, schizophrenia, attention-deficit disorders, or alcohol and other drug addiction problems. Smokers also are seen as more neurotic, greater risk-takers, and having poor impulse control.

Such research has led some employers and even the military to begin viewing smokers as possible problem cases. But others say the findings should be seen as reinforcing the need for treatment. “Smokers are socially isolated and so less likely to search out help,” says David Gilbert, a nicotine researcher at Southern Illinois University. “But these studies suggest that better treatments are out there.”

Treatment could involve using nicotine to treat depression, researchers said.
Source: the Los Angeles Times reported April 26.2006

Inbred strains of rats differ in how aggressively they seek cocaine after a few weeks of use, researchers say.

The finding, posted online Jan. 18 by Psychopharmacology, is another piece of evidence that genetics plays a role in the relapse of drug-seeking behavior in humans, says Dr. Paul J. Kruzich, behavioural neuroscientist at the Medical College of Georgia and lead study author.

It also fingers glutamate, a neurotransmitter involved in learning and memory, as an accomplice in stirring the cravings and uncontrollable urges that drive some drug users to use again, he says.

“Given the right environmental stimuli, all persons addicted to psychostimulants can relapse, but potentially some people are a little more susceptible than others … it’s all about gene-environment interaction,” says Dr. Kruzich.

He took two strains of inbred rats – Fischer 344 and Lewis – with known genetic differences, enabled each to self-adminster cocaine for 14 days, then took the drug away for a week but not the levers the animals used to access it.

During that hiatus, he adminstered a drug that stimulates glutamate receptors, possible targets for drugs of abuse.

He found that the F344 strain worked harder to get cocaine than the Lewis rats following treatment with the glutamate drug, suggesting they were more susceptible to relapse.

“Maybe 12-step programs and faith-based programs will be enough to keep some people from relapsing,” says Dr. Kruzich. “For others we may have to come up with medical treatments we can use on top of those to keep them from taking drugs again.”

He says there are many different versions of the hundreds of genes that may play a role in increasing the risk of relapse.

It’s known that some people become addicted more quickly than others, some literally with their first use, he says. The hardest part is not getting people to stop taking drugs: that happens when they are checked in a clinic or put in jail. The real work is keeping them from relapsing when they are out of such restricted environs, he says.

“Something happens, either they see an old colleague they have used with, they go into an old environment, they have a huge stressor in life and they start to want the drug. They have drug hunger, what we call drug craving,” says Dr. Kruzich. “When it gets bad enough, they engage in drug-seeking behavior.”

His lab is working to identify the relapse trigger to use as a target for developing ways to curb craving and subsequent relapse.

His studies focus on an area of the brain called the nucleus accumbens core, a target for drugs of abuse long considered a pleasure center, Dr. Kruzich says. Drugs such as cocaine and methamphetamine stimulate release of dopamine in the nucleus accumbens. Dopamine is a neurotransmitter believed responsible for the euphoria that come with drug use. In fact, animals given dopamine blockers won’t self-adminster drugs of abuse, and dopamine has long been a focus of drug-abuse studies.

“These drugs impinge upon the reward centers of the brain that normally food, sex, survival and adaptation impinge upon,” says Dr. Kruzich. “When you are having that great piece of cheesecake and thinking, ‘Oh man,’ that is the kind of response these drugs of abuse are evoking but much more so than that cheesecake could ever do.”

Glutamate, also released in the nucleus accumbens core, may play an equally important role in drug relapse, he says. Drugs such as cocaine appear to alter glutamate neurotransmission in the core, which may contribute to the rewiring of the brain that occurs with drug use. “It’s not that these drugs just damage neurons, which they can, but they rewire the circuitry of the brain so no longer is your spouse or your job or other things in your life important to you. Your brain is tricked into thinking that drugs are the most important thing for your survival,” Dr. Kruzich says.

Unfortunately, drugs that restore glutamate function also produce seizures, so scientists are looking for an indirect approach to restore the misdirected rewiring.
Source: Psychopharmacology, posted online Jan. 18 2006. Toni Baker Medical College of Georgia http://www.mcg.edu

Cocaine may be one of the toughest addictions to cure because it triggers a build up of a protein that persists in the brain and stimulates genes that intensify the craving for the drug, new research suggests. Scientists at the Yale School of Medicine were able to isolate the long-lived protein, called Delta-FosB, and show that it triggered addiction when released to a specific area of the brains of genetically engineered mice. The protein (pronounced fawz-bee) isn’t produced in the brain until addicts have used cocaine several times, or even for several years. But once the build up begins, the need for the drug becomes overpowering and the user’s behaviour becomes increasingly compulsive.
“It’s almost like a molecular switch,” said Eric Nestler, who led the research. ‘Once it’s flipped on, it stays on, and doesn’t go away easily.” The findings were called “elegant” and “brilliant’ by other researchers who said it offered the first concrete proof that drug use triggers a specific long-term change in brain chemistry.

Nestler and his colleagues combined genetic and biochemical research to isolate the Delta-FosB protein and the area of the brain it affected, then did behavioural studies on the mice. Once the level of Delta-FosB accumulates, it begins to regulate genes that control a region of the brain called the nucleus accumbens. an area involved in addictive behaviour and pleasure responses. They speculated that Delta-FosB also activates other genes that produce biochemical compounds called glutamates, which carry messages in brain cells. Receptors in the brain cells become highly sensitive to glutamate, particularly in the nucleus accumbens. To test the theory, they inserted a gene associated with glutamate into the nucleus accumbens of experimental mice. Those mice showed a ‘dramatic increase in cocaine sensitivity, they reported. “This is a major advance in our understanding of addiction,’ said Francis White, chairman of cellular and molecular pharmacology at Finch University of Health Sciences in Chicago.

Other researchers were more cautious, noting that addiction is a complex process in humans because it is linked to learning and multiple chemical pathways in the brain. “It’s not clear to me that there’s a separate molecular pathway that’s going to be assignable to drug abuse and not interfere with other learning,’ said Gary Aston-Jones of the University of Pennsylvania School of Medicine. The craving for cocaine can be so powerful, a recovered addict who has avoided the drug for years may start feeling his or her heart race just by seeing something associated with drug use, such as a $100 bill or a familiar street corner, Aston-Jones said. “You want to knock out the memory for the drug but you don’t want to knock out the memory for the way home,” he said. Steve Hyman, director of the National Institute of Mental Health, said the study also indicated the build up of the Delta-FosB protein might be a factor with other drugs, including amphetamine, morphine, heroin and nicotine.

Source: Yale school of Medicine published in Nature Sept 1999

Long-term abstinence from alcohol reverses some of the structural changes in the brain associated with heavy consumption, according to a report in the November issue of Alcoholism: Clinical and Experimental Research. Chronic alcohol abuse brings changes in the grey and white matter of the brain readily visible by magnetic resonance imaging, as well as possible metabolic consequences discernible through magnetic resonance spectroscopy (MRS), the authors explain.

Dr. Dieter J. Meyerhoff and colleagues from the Veterans Affairs Medical Center and the University of California at San Francisco compared quantitative MRI and MRS results from 12 recovering alcoholics and eight actively heavy drinking (AHD) subjects. Recovering alcoholics had significantly greater white matter volume in the frontal lobes than did the AHD subjects, the authors report, whereas white matter volumes in the other regions examined were lower. Among recovering alcoholics, frontal white matter volume percentages showed a positive correlation with duration of abstinence from alcohol.

In contrast, the report indicates, white matter lesions occupied lower volumes in recovering alcoholics than in AHD subjects in all areas except the frontal lobes. Cortical grey matter volume was higher in the orbital frontal pole and somatosensory cortex of recovering alcoholics, the researchers note, but lower in the anterior cingulate. As measured by MRS, the metabolites of N-acetyl-aspartate, creatine, and choline did not differ between the two groups.

Source: Author Dr. Dieter J Meyerhoff University of California Reported in Alcohol Clin Exp Res 25: 1673-1682. 2001

A recent study on the in-prison drug treatment program at the Richard J. Donovan Correctional Facility in San Diego County found that only 16% of its inmates who also completed an after-care program came back into the system within two years of their release. State wide, the recidivism rate is about 70%.

“You’ll get a lot of complaining in the first 30 to 60 days, then things will settle down, if the programme is good,” said Douglas Anglin, director of the UCLA Drug Abuse Research Centre. When you follow them up five years later, coerced clients, in every well-designed study, they do better than voluntary clients. These are very well-established findings.”

Source: Reported in Join Together May 1999

Research published in the journal, Forensic Science International (2001), noted that the profile of individuals dying from the use of illicit substances has changed considerably since the 1960’s, when the use of psychoactive and addictive substances began to find its way into the mainstream population.

The researchers looked at the physical condition of IO individuals whose deaths, attributable to the use of illicit drugs, occurred consecutively from 1995 to 1997, as we as the circumstances at the scene of death. They noted that though the general public and scientific literature has tended to believe that drug users are always neglected, untidy, down-and-outs, found mainly in public restrooms after having died from intoxication, that was not the case with most of these 100 victims. The researchers found that often signs of drug use are not present at death and suggested that ‘Death from drug consumption should be taken into account even it there are no drug-addiction utensils found at the scene, no visible injection marks and no signs of physical neglect.’
On autopsy, 86% were found NOT to be undernourished, and only 11% were found in public places. Interestingly, 63% were tattooed, including seven depicting cannabis leaves, and 95% showed signs of previous injection drug use.

Source: Authors: Michael Bohnert, Minou Hafez Stefan Pollak. Institute Forensic Medicine, University of Freiburg, Germany. ‘The changing phenomenology of drug death over the year’. Forensic Science International 124(2001) 117-123

New research clearly shows that longer-term methadone maintenance therapy (MMT), combined with some psychosocial counselling, is a far more effective treatment for heroin addiction than is simply the temporary use of methadone to detoxify patients and reduce drug craving, even when the detoxification is coupled with much more intensive psychosocial therapy.

“The findings from this study clearly indicate that methadone maintenance is an effective treatment for heroin addiction,” says Dr. Alan I. Leshner, NIDA Director. “This is yet another indication that MMT should be used more widely as a treatment option for heroin addicts. Currently, only about 20 percent of the 810 000 diagnosed heroin addicts in the U.S. receive this treatment.” Study director Dr. Sharon Hall says, “The goal of this study was to determine whether short-term methadone-assisted detoxification, when enriched with intensive psychosocial services and aftercare, could provide an effective alternative to MMT. Our results show that no matter how ideologically attractive the notion of a time-limited methadone treatment for heroin abusers, longer-term methadone maintenance treatment is far more effective.”

The researchers interviewed 179 heroin- or cocaine-dependent volunteers monthly, for 12 month after their admission to the study. The volunteers were randomly divided into two groups methadone maintenance treatment group and a methadone detoxification group. The MMT group was eligible for 14 months of methadone maintenance, followed by a 2-month detoxification. Participants in this group were required to attend substance abuse group therapy 1 hour per week for the first 6 months of maintenance, and 1 hour per month of individual therapy.

Patients in the detoxification group received methadone only for the first 180 days of their treatment. During their first 6 months of treatment, the detoxification group was required to attend 2 hours per week of substance abuse group therapy; 1 hour per week of cocaine group therapy (if they had tested positive for cocaine when admitted to the study); a series of 14 1- hour, weekly substance abuse education classes; and 4 weekly individual therapy sessions. This group also received 6 months of aftercare services that included weekly individual and group psychotherapy and liaison services with the criminal justice system, medical clinics, and social service agencies, but no additional methadone after the first 180 days of their treatment.

Study results showed that more patients in the MMT group remained in treatment for longer periods of time (438.5 days vs. 174 days) and had lower heroin use rates than did shorter-term methadone detoxification patients. Of the MMT group, 77 out of 91 patients were still in the study at the 12-month mark, while only 57 of 88 methadone detoxification patients were still in the study. MMT also resulted in a lower rate of drug use-related HIV-risk behaviours and a lower level of criminal activity.

Source: Study Director Dr. Sharon Hall, “ Methadone Maintenance versus 180-day Psychosocially-Enriched Detoxification for Treatment of Opioid Dependence: A Randomized, Controlled Trial,”
The Journal of the American Medical Association (JAMA 2000;283 :1303-13 10) March 2000.

Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioural intervention, a pharmacological intervention, and a combination of both interventions.

Methods
Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counselling.
Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions:
(1) contingent vouchers for opiate-negative urine specimens (n29 patients);
(2) methadone hydrochloride dose increase to 70 mg/d (n=31 patients);
(3) combined contingent vouchers and methadone dose increase (n=32 patients); and
(4) neither intervention (comparison standard; n=28 patients). Methadone dose increases were double blind.

Vouchers had monetary value and were exchangeable for goods and services.
Groups not receiving contingent vouchers received matching vouchers independent of urine test results.
Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis).

Results
Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention.
Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings.
Methadone dose increase, with or without contingent vouchers, reduced frequency of use and self-reported craving.

Conclusions
In patients enrolled in a methadone-maintenance program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use.  When combined, they did not dramatically enhance each other’s effects on any one outcome measure, but they did seem to have complementary benefits.
Source: Author Kenzie et al published in Arch Gen Psychiatry. 2000;57:395-404

Scientist have found powerful evidence suggesting that genetics plays a dominant role in making some people particularly susceptible to nicotine addiction.

A comparison of the smoking habits of more than 2,000 pairs of twins, showed much greater similarity on smoking behaviour between identical (same gene) twins than non-identical twins.

A member of the team, Dr. Pamela Madden said “Our evidence indicates that strong genetic effects are responsible for both starting smoking and for long-term smoking.  Innate differences in initial sensitivity to nicotine may play an important role, with many individuals who experience a strong adverse reaction  giving up smoking after the first or second attempt”. The Health Education Authority said “If convincing evidence of a genetic effect emerges, then we may consider targeting children of smoking parents”.

Madden, P et al.Washington University School of Medicine, Missouri.
Report ‘Behaviour Genetics’ June95

Message from Secretary-General Kofi Annan on the Occasion of the International Day
against Drug Abuse and Illicit Trafficking
26 June 2004

One of the most damaging misconceptions about drug use is that it is a permanent problem. The truth is that treatment for drug abuse can work, and can restore value and dignity to a person’s life. The theme for this year’s International Day against Drug Abuse and Illicit Trafficking, ‘Drugs: Treatment Works’, aims to correct this misconception, and convey the facts about drug abuse treatment, based on the latest and most reliable evidence and research. Millions of people worldwide have been directly affected by drug problems – those who are dependent, as well as their families. Their lives have been disrupted, their health undermined, their education interrupted, their jobs lost, their families broken. People with drug-related problems, and their families and friends, need to know that there is a way out, and that effective help is available in different forms, depending on the needs and situation of each individual.

Today we have a better understanding of the mechanism of dependence. We know that dependence is a chronic and, in many cases, relapsing disorder. We know that, like many other chronic disorders, there are effective interventions that can help those affected to adopt productive lifestyles, avoid and reduce physical and mental health problems, improve family relationships, regain and retain child custody, and find better housing and employment opportunities. We also know that drug-abuse treatment helps communities, by reducing criminality and the risks of transmission of blood-borne infectious diseases, particularly HIV/AIDS, and by allowing them to benefit from the contributions of healthier, more productive and better-integrated individuals and families.

Policy makers need to bear in mind that treatment is a cost-effective way to tackle not only the health and social consequences of drug abuse, but also to reduce the associated costs of medical care, social welfare and criminal justice interventions. The United Nations Office on Drugs and Crime has a variety of tools available at www.unodc.org to help clarify the facts about drug-abuse treatment. On this International Day against Drug Abuse, I call on everyone to examine and take into account the strong evidence about drug-abuse treatment and its effectiveness. When treatment works, it benefits us all.

The National Drug Prevention Alliance would concur with the sentiments above – but would add that as well as supporting drug treatment, drug prevention should have a much higher priority. Prevention Works! has been the strap line for our organisation for eleven years. Proof that prevention works can be found in an article from The Weekly – between 1979 and 1992 drug prevention programmes in the USA cut use by 50% – from 25 million to 11 million users – as a result crime, drug related hospital admissions and road deaths also declined.