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

A typical drug user’s transition to addiction could result from a persistent impairment of synaptic plasticity in a key structure of the brain, suggests a new French study.
The research, by the teams of Pier Vincenzo Piazza and Olivier Manzoni, at the Neurocentre Magendie in Bordeaux, appears in the journal Science.

This study is the first demonstration that a correlation exists between synaptic plasticity and the transition to addiction. The results from the teams at Neurocentre Magendie call into question the hitherto held idea that addiction results from pathological cerebral modifications, which develop gradually with drug usage.

Their results show that addiction may, instead, come from a form of anaplasticity, i.e. from incapacity of addicted individuals to counteract the pathological modifications caused by the drug to all users.

The voluntary consumption of drugs is a behaviour found in many species of animals. However, it had long been considered that addiction, defined as compulsive and pathological drug consumption, is behaviour specific to the human species and its social structure.

In 2004, the team of Pier Vincenzo Piazza showed that the behaviours which define addiction in humans, also appear in some rats which will self administer cocaine. Addiction exhibits astonishing similarities in men and rodents, in particular the fact that only a small number of consumers (humans or rodents) develop a drug addiction. The study of drug dependent behaviour in this mammal model thus opened the way to the study of the biology of addiction.

Today, thanks to a fruitful collaboration, the teams of Pier Vincenzo Piazza and Olivier Manzoni are reporting discovery of the first known biological mechanisms for the transition from regular but controlled drug taking to a genuine addiction to cocaine, characterised by a loss of control over drug consumption.

Chronic exposure to drugs causes many modifications to the physiology of the brain. And researchers wanted to find out which of these modifications is responsible for the development of an addiction.
The addiction model developed in Bordeaux provides a unique tool to answer this question. Thus it allows comparing animals who took identical quantities of drugs, but of which only few become addicted.

By comparing addict and non-addict animals at various time points during their history of drug taking, the teams of Pier Vincenzo Piazza and Olivier Manzoni have demonstrated that the animals which developed an addiction to cocaine exhibit a permanent loss of the capacity to produce a form of plasticity known as long-term depression (or LTD).

LTD refers to the ability of the synapses (the region of communication between neurons) to reduce their activity under the effect of certain stimulations. It plays a major role in the ability to develop new memory traces and, consequently, to demonstrate flexible behaviour.

After short-term usage of cocaine, LTD is not modified. However, after a longer use, a significant LTD deficit appears in all users. Without this form of plasticity, which allows new learning to occur, behaviour with regard to the drug becomes more and more rigid, opening the door to development of a compulsive consumption.

The brain of the majority of users is able to produce the biological adaptations which allow to counteract the effects of the drug and to recover a normal LTD.
By contrast, the anaplasticity (or lack of plasticity) exhibited by the addicts leaves them without defences and hence the LTD deficit provoked by the drug becomes chronic.

This permanent absence of synaptic plasticity would explain why drug seeking behaviour becomes resistant to environmental constraints (difficulty in procuring the substance, adverse consequences of taking the drug on health, social life, etc.) and consequently more and more compulsive. Gradually, control of the taking of the drug is lost and addiction appears.

For Pier-Vincenzo Piazza and his collaborators, these discoveries also have important implications for developing new treatment of addiction.

“We are probably not going to find new therapies by trying to understand the modifications caused by a drug in the brains of drug addicts,” explain the researchers, “since their brain is anaplastic.” For the authors, “The results of this work show that it is in the brain of the non-addicted users that we will probably find the key to a true addiction therapy.

Indeed,” the authors estimate, “understanding the biological mechanisms which enable adaptation to the drug and which help the user to maintain a controlled consumption could provide us with the tools to combat the anaplastic state that leads to addiction”. (ANI)

Source: www.sify.com/news 2010-06-29

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

Marijuana used for medical purposes has the same long term effect on the user as marijuana used for recreation. Marijuana use can cause impairment of short-term memory, attention, motor skills, reaction time, and the organization and integration of complex information.

Marijuana use alters perceptions and creates time distortion and can cause drowsiness and lethargy. Heavy marijuana use can cause apathy, decreased motivation, and impair cognitive performance and can cause mental health problems.

Employees who use marijuana off-duty are still effected by it. Impaired cognition that can cause lapses in judgement can remain for a long period. Memory defects can last as long as six weeks. See: Abbie Crites-Leoni, Medicinal Use of Marijuana: Is the Debate a Smoke Screen for Movement Toward Legalization? 19 J. Legal Med. 273, 280 (1998) (citing Schwartz, et al., Short- Term Memory Impairment in Cannabis-Dependent Adolescents, 143 Am. J. Dis. Child. 1214 (1989)

Employers may be liable for the actions of employee who use marijuana especially those employees in safety sensitive positions. The more chronic the use of “medical” marijuana the higher the risk.

VIOLATIONS OF FEDERAL LAW

Will employers have to accommodate marijuana use that violates federal law? Marijuana, remains illegal under federal law because of its “high potential for abuse,” its lack of any “currently accepted medical use in treatment in the United States,” and its “lack of accepted safety for use … under medical supervision.”Gonzales v. Raich, 545 U.S. 1 (2005); United States v. Oakland Cannabis Buyers’ Cooperative, 532 U.S. 483 (2001)

IF THIS BILL PASSES “MEDICAL” MARIJUANA WILL RESULT IN MORE MARIJUANA USE AMONG EMPLOYEES

As consumers we all pay for lost productivity and job-related accidents in the final costs of the produced goods and higher insurance premiums due to workplace accidents. Drug using employees are not as safe. They are 3.6 times more likely to be involved in a work-related accident than their non-using employee, and 5 times more likely to file workers’ compensation claims. As many as 50% of all workers’ compensation claims may involve substance abuse.[FN1]

The U.S. Postal Service did a study that showed that substance abusers have 55% more accidents, experience 85% more on-the-job injuries, and have a 78% higher rate of absenteeism when compared to non-substance abusing employees.[FN2] A report by the National Safety Council claimed that 80% of those injured in serious drug-related work accidents are not the drug using employees, but innocent employees and others.[FN3]

Drug using employees commit workplace crimes. There is a very significant statistical correlation between drug use and criminal conduct.[FN4]

Substance abuse also causes:
Domestic and financial difficulties for employees;
Poor judgment in employment decision making;
Potential embarrassment to the employer as a result of off-duty conduct, which may be publicized, including criminal charges, diversion of supervisory and managerial time;
Damage to company property; and
Time devoted to discipline and grievance matters.[FN5]

While the studies vary somewhat, it is clear that there is substantial substance abuse in the workplace and it has a powerful negative impact on our economy and productivity. The increased use of “medical” marijuana will magnify all these problems.

References

[FN1] Current, The Truth About Drug Testing: Answers to the Questions Everyone Is Asking, p. 3 (1st Ed., Fort Lauderdale, FL, 1998).

[FN2] “Pre-employment Drug Testing: Association with EAP, Disciplinary, and Medical Claims Information” U.S. Postal Service, Personnel Research and Development Branch, Office of Selection and Evaluation, July 1992.

[FN3] Wisotsky, The Ideology of Drug Testing [Ideology of Drug Testing], 11 Nova L Rev 763, 768 (1987).

[FN4] See Stewart, Proof Positive of Drug Link to Crime, Wall St J, May 28, 1987, at 26, col 3.

[FN5]Alcohol & Drugs in the Workplace: Costs, Control and Controversies, A BNA Special Report [Costs, Control and Controversies], 7 (Bureau of National Affairs, Washington, D.C. 1986)

Source: David Evans sent to DFAF May 2010

A new study from the David Geffen School of Medicine at UCLA suggests that increasing cigarette taxes could be an effective way to reduce smoking among individuals with alcohol, drug or mental disorders.

The study, published online in the American Journal of Public Health, found that a 10 percent increase in cigarette pricing resulted in an 18.2 percent decline in smoking among people in these groups.

The findings demonstrate that increasing cigarette taxes could be a way to curb smoking, which is still the leading preventable cause of death in the United States, according to the study’s lead author, Dr. Michael Ong, an assistant professor of medicine in the division of general internal medicine and health services research at the Geffen School of Medicine.
“Whatever we can do to reduce smoking is critical to the health of the U.S.,” said Ong, who is also a researcher at UCLA’s Jonsson Cancer Center. “Cigarette taxes are used as a key policy instrument to get people to quit smoking, so understanding whether people will really quit is important.

Individuals with alcohol, drug or mental disorders comprise 40 percent of remaining smokers, and there is little literature on how to help these people quit smoking.”

Prior research on the effect of cigarette pricing on smoking, which had been conducted using information from 1991, suggested that individuals with mental illness were less likely than other individuals to quit due to price increases. Unlike that research, however, the current study expanded the research to include people with alcohol and drug disorders.

The researchers based their work on data from 7,530 individuals from the 2000-01 Healthcare for Communities Household Survey. Of those, 2,106 people, or 23 percent, had alcohol, drug or mental disorders during the previous year. Of that group, 43.8 percent were smokers — a much higher proportion than among rest of the population.

Though the researchers found that people with alcohol dependence did not cut down on cigarettes when prices rose, people with binge-drinking problems, substance-use disorders and mental disorders were significantly more likely to quit smoking if prices rose, as would occur with a cigarette tax increase.

While the study does suggest that increasing cigarette prices through taxation could reduce smoking among individuals with alcohol, drug or mental disorders, the authors note that further study is needed to determine if recent cigarette price increases have reduced smoking among individuals with such disorders, and whether the identified association is causal.

Source: http://www.sciencedaily.com/releases June 3, 2010

Neuropharmacologists ran clinical trials to find that a drug called topiramate is an effective therapeutic medication for decreasing heavy drinking and diminishing the physical and psychosocial harm caused by alcohol dependence.

The drug works by blocking the right amount of the feel good effects of alcohol (brought on by increased levels of dopamine), making drinking less enjoyable and thus reducing cravings and helping to stop heavy drinking.

Topiramate was also found to lower blood pressure and cholesterol levels which may lead to a decrease in heart disease in alcohol dependent patients.

Alcoholism affects over 17 million people. Without proper treatment, it’s a devastating disease that can ruin lives and relationships. A new therapy that comes in a pill is bringing new hope to alcoholics.

There was a time in Christine Flemming’s life when alcohol came before her kids.
“I can’t remember when my daughter was very little, because I was drinking so much,” said Flemming. “That affected me a lot.”

Flemming needed help, but traditional treatment methods didn’t work. Now she’s on a new kind of therapy in the form of a pill called topiramate. It has changed her life. “I can tell you that it cuts my cravings, and I don’t feel like I have to drink,” Flemming said. “I don’t feel like that’s something I need in my life and I have to do.”

Alcohol increases levels of dopamine, a chemical in the brain that makes us feel good. The drug works by blocking the right amount of the feel-good effects from alcohol to reduce cravings and help stop heavy drinking. During clinical trials, neuropharmacologists were surprised to learn it also lowers blood pressure and cholesterol levels, which may lead to a decrease in heart disease in alcohol dependent patients.

“Most of the morbidity due to alcoholism is caused by secondary effects of all these other systems, so to have a drug that begins to correct all those other physical abnormalities is extremely helpful,” said Bankhole Johnson, Ph.D., a Neuropharmacologist at the University of Virginia in Charlottesville, Va.

The drug helped improve Fleming’s health and end her dependence on alcohol. She cut her drinking from 15 beers a day to just three, so time with her kids is now a priority.
“It’s made a big difference,” Flemming said. “It’s made a really big difference, and I feel like I’m actually there for my family.”

Qualifying patients can find out how to receive the drug by contacting their primary care doctors.

WHAT IS TOPIRAMATE? Topiramate is a drug originally discovered in 1979. It is prescribed as an epilepsy medication and for migraine headaches. It is also used for a number of other purposes, including as a treatment for people with alcoholism.

Researchers believe that topiramate works in two ways. First, it reduces the release of dopamine that follows the consumption of alcohol. This reduces the positive feeling that people receive from alcohol, and thus reduce the incentive to drink. Second, topiramate interferes with the protein glutamate which normally excites dopamine neurons and again, lessening the ýfeel goodý effect of dopamine from alcohol.

WHAT IS ALCOHOL? Alcohol is created through the natural process of fermentation. This happens when yeast and sugar from vegetables and grains change the sugar into alcohol. When you drink alcohol, it is absorbed into your bloodstream, where it can affect the central nervous system, which is the control center for your entire body.

Alcohol slows down this control center with its sedative effect. In moderation it can reduce anxiety, but it also blocks some of the commands the brain sends to other parts of the body, so it alters your senses. That’s why, when drunk, people often have trouble walking, talking, and some may even “black out,” forgetting what they said or did. Drinking an excessive amount of alcohol can even be fatal.

Source www.ScienceDaily June 2010

Levels of the serotonin transporter are low in the brains of users of ecstasy, according to a US National Institute of Drug Abuse-funded study by Toronto’s Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids) published today in the journal Brain.

Ecstasy (MDMA) is a stimulant drug widely used recreationally that is also being tested in clinical trials for the treatment of post-traumatic stress disorder.
Led by Dr. Stephen Kish at CAMH, this study provides confirmation of a previous finding from Johns Hopkins University that levels of the serotonin transporter (SERT) are low in cerebral cortex of chronic ecstasy users. The subjects were “typical” ecstasy users who used about two tablets of the drug twice a month.

SERT is a protein responsible for regulating levels of serotonin, a neurotransmitter important for mood and impulse control. Ecstasy interacts with SERT to cause the release of serotonin, an action that probably explains some of the behavioral effects of the drug such as increased sociability.

Scientists have long suspected that ecstasy might harm brain cells that use serotonin, but 12 years of brain scan studies have produced contradictory results, even within the same laboratory.
The CAMH study used a large subject size (49 drug users, 50 control subjects), confirmed by hair analysis that ecstasy users actually used the drug, and used an imaging probe that could measure SERT throughout the brain.
“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain, perhaps because serotonin nerves to the cortex are longer and more susceptible to changes. This finding is almost identical to newer data from Johns Hopkins and is the first time that one laboratory has actually been able to replicate results of another independent laboratory in a SERT study of ecstasy users.” said Dr. Kish.

Drug hair analysis indicated that many ecstasy users, probably unknowingly, also used methamphetamine, which might itself damage serotonin cells; however, low SERT was found both in ecstasy users who used and who did not use methamphetamine. Dr. Jason Lerch at SickKids showed that those ecstasy users who also used methamphetamine had a slightly thinner cerebral cortex.

Does low SERT equal “structural brain damage”? “Not necessarily” said co-author Dr. Isabelle Boileau of CAMH. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”
Dr. Kish suggests that low SERT might explain why many ecstasy users need to keep increasing the dose to experience the same effects, since SERT is necessary for the action of ecstasy. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed. The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug,” said Dr. Kish.

Media Contact: Michael Torres, Media Relations, CAMH ; 416 595 6015 or email media@camh.net

Source: www.camh.net 18th May 2010

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.

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

Steroids are linked to manic episodes, depression, suicide, psychotic episodes and increased aggression and hostility, occasionally triggering violent behavior, including murder.

Researchers at Uppsala University in Sweden studied the relationship between crime and steroid use in 1,440 Swedish residents tested for the drugs between 1995 and 2001 from clinics, including substance abuse facilities, as well as police and customs stations.

Of those involved in the study, 241 tested positive, with an average age of about 20.
The research team found those who tested positive for steroid use were roughly twice as likely to have been convicted of a weapons offense and one-and-a-half times as likely to have been convicted of fraud.

When the researchers excluded people from substance abuse facilities from their analysis the connection with armed crime remained, but the link between steroid use and fraud disappeared.
While steroids are linked with outbursts of uncontrolled violence known as “‘roid rage,” they did not appear to be connected with sexual offenses, violent crimes such as murder, assault and robbery, or crimes against property such as theft.

This investigation instead reveals that steroid use may be linked with premeditated crimes—those involving preparation and advance planning.
One explanation the researchers suggest for the findings is that criminals involved in serious crimes such as armed robbery or the collection of crime-related debts might benefit from the muscularity, heavy build and increase in aggression that comes with steroid use.

The scientists report their findings in the November issue of the Archives of General Psychiatry.

Source: Fox News Live Science Monday , November 06, 2006

How serious is the child and teenage alcohol problem in your area?

More than 20 children and teenagers are being treated in hospital every day for alcohol-related illnesses, including mental disorders, poisoning and liver disease, according to newly released official data.

The figures, labelled “staggering” by one of Britain’s most senior doctors, show that in the year 2005-6, during which Labour introduced 24-hour drinking, the number of under-18s seeking treatment for alcohol-related health problems leapt by 13% to 8,894, an average of 24 a day.

The research, released in parliament by Caroline Flint, the health minister, shows that the number treated has gone up by 33% since Labour came to power in 1997.

Professor Ian Gilmore, president of the Royal College of Physicians, said: “This is a staggering rise and it is only the tip of the iceberg.
“Drinks sold by supermarkets and off-licences are cheaper than ever, and those shops have been at the front of the queue for 24-hour licences, so it has never been more available.

“The younger they drink, the more likely they are to have alcohol-related problems later in life. It is now commonplace to see men and women in their twenties with end-stage alcoholic liver damage.”
The disease figures released by Flint do not include those people treated for injuries sustained in incidents such as drunken fights or drink-driving.

Separately, the government has released figures for patients treated for alcohol-related conditions in accident and emergency wards, showing that alcohol-related medical emergencies and hospital treatments have doubled since 1997.

In some parts of the country the rise is even steeper. The worst areas include the region formerly covered by Cheshire and Merseyside Strategic Health Authority, where 742 young people were treated last year, a rise of more than 25% in just a year. In Northumberland, Tyne and Wear, the number went up by a quarter.
By contrast, some southern health authorities experienced an improvement. In Bedfordshire and Hertfordshire, for example, there were only 119 cases, a fall of 30%.

In addition to the figures for children and teenagers, the Department of Health data also show that the number of people aged 18 and over treated for alcohol-related illness has gone up from 124,925 to 253,603 since 1997, a rise of more than 100%.
The data, released in a written answer, appear to contradict the government’s claims that the liberalisation of pub opening and supermarket off-sales time would lead to more responsible drinking.

They bear out research published earlier this year by the British Association for Emergency Medicine, which found an increase in alcohol-related injuries treated in hospital among all age groups since the change to the drinking laws.

Ahead of its launch of 24-hour opening in November 2005, the government assured voters that there would be tougher controls on underage drinking.
It announced on-the-spot fines for children buying alcohol and tougher penalties for staff serving them.
Tessa Jowell, the culture secretary, said at the time: “The result will be more freedom for responsible adults and tougher treatment for the yobbish minority.”

Labour’s approach to teenage drinking has not always lived up to the responsible image that it likes to project.
In the run-up to the 2001 general election, the party sent text messages to first-time voters telling them, “Don’t give a XXXX for last orders? Vote Labour”. This was an allusion to advertisements for Castlemaine XXXX, the Australian beer.

Dr Gray Smith-Laing, a consultant at the Medway Maritime hospital in Gillingham, Kent, who treats patients with liver disease, said last week: “What we’re seeing is the numbers going up, the age coming down.

“The idea that (24-hour opening) just smooths out the drinking and people drink the same amount over a longer period of time is complete rubbish.”
The Department of Health says that levels of binge drinking have peaked and new facilities such as walk-in centres could explain the growth in treatment for drink-related injuries.

The department said yesterday: “The increased attendances at A&E departments, as seen in recently published figures, began some years ago. Evidence suggests that increased rate of growth of attendances predates the change in licensing laws by several years. In fact, this year growth has actually slowed.”

SOURCE: POSTED BY ALCOHOLICS ANONYMOUS UK AT 7:50 AM MON 25.12.06

Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely been studied as a cause. Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person. Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads, how drug use behavior spreads, and how a friend’s sleep behavior influences one’s own drug use. We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation (to one’s friends’ friends’ friends’ friends) in the social network. Prospective regression models show that being central in the network negatively influences future sleep outcomes, but not vice versa. Moreover, if a friend sleeps ≤7 hours, it increases the likelihood a person sleeps ≤7 hours by 11%. If a friend uses marijuana, it increases the likelihood of marijuana use by 110%. Finally, the likelihood that an individual uses drugs increases by 19% when a friend sleeps ≤7 hours, and a mediation analysis shows that 20% of this effect results from the spread of sleep behavior from one person to another. This is the first study to suggest that the spread of one behavior in social networks influences the spread of another. The results indicate that interventions should focus on healthy sleep to prevent drug use and targeting specific individuals may improve outcomes across the entire social network.

Source: Mednick SC, Christakis NA, Fowler JH (2010) The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks. PLoS ONE 5(3): e9775. doi:10.1371/journal.pone.0009775

We know that there are people alive today who find it impossible to quit different kinds of behaviour once they have started it. What is it that makes one person quit cold turkey, and another smoke even while they are being treated for cancer?

Is there an addiction gene? Addiction in the genes is a hotly debated subject among scientists and researchers.

Scientists and researchers are going further back than ever before to unearth present truths. Addiction runs in the family. Again and again, they have found addictive behaviours carried down the family tree. This was their first clue that addiction may be hereditary.

There doesn’t appear to be a single ‘addict’ gene that causes specific types of people to fall into the addiction trap. There are however, several that combine to form a strong susceptibility to the behavioural patterns that addict’s exhibit. This is the addiction and genetics debate.

When a person with these genetic markers is exposed to a drug, or a habit, it can change the chemistry in their brain. This change leads to compulsive behaviour and eventual addiction. We are familiar with the concept that some illnesses – both physical and mental – can be hereditary, but it appears that this can also be applied to addiction.

Naturally, even if addiction is in the genes, there are other external factors that play their part. Why is it, for example, that a man becomes a drug addict, when his sister has never so much as smoked? External circumstances, stimuli and environmental factors also play their part in affecting people who are genetically prone to addiction.

The addiction and the genetic factor discussion will play on for years to come. The science is still quite new, and there are those out there that would prefer to blame addiction on personality disorders instead of genetics. Even if a definitive link is found, there is a still a long way to go before this information can be used to treat addiction sufferers and their families. For the time being at least, traditional addiction treatment and rehabilitation is still the most effective way to proceed.

Alcoholism, gambling, sexual and drug addiction could all be the result of inherited genes and generations of vulnerability. If you believe that addiction runs in the family, analyse yourself honestly. If it appears that you have a vulnerability to addictive behaviour, seek professional assistance. Obtaining assistance early on may help to limit any long-term damage.

Source: www.articlealley.com 5.5.2010

The brain’s nucleus accumbens (NAC) is a core region of the mesocorticolimbic dopaminergic system and is interconnected with the ventral tegmental area (VTA) and the prefrontal cortex. The mesocorticolimbic system is thought to be central to the reinforcing effects of many drugs and plays an important role in addiction. A new study has found that alcohol abuse elevated the expression of a distinct set of genes in the NAC and VTA, while nicotine blunted this effect in the VTA.

Results will be published in the July 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“In spite of their differences in pharmacology, alcohol and tobacco consumption are often intimately linked,” said Traute Flatscher-Bader, a postdoctoral research fellow at The University of Queensland and corresponding author for the study. “Nonetheless, the molecular mechanisms that underlie alcohol and nicotine abuse, and particularly their co-abuse, are still incompletely understood.”

“One thing that researchers have encountered is that it is often difficult to find ‘pure’ alcoholics, that is, alcoholics that only abuse alcohol and nothing else,” agreed Simon Worrall, director of postgraduate coursework programs in molecular biology at The University of Queensland. “Many alcoholics are poly-drug abusers, with the most common other drug being nicotine. Thus, many studies which have studied the effects of alcohol on the brain and other organs have been compromised because they have not taken account of the effects of nicotine addiction which is often superimposed on the effects of alcohol addiction.”

In the first part of the current study, Flatscher-Bader and her colleagues used DNA microarray technique to study the expression of many thousands of genes in the brains of non-smoking and smoking alcoholics and non-drinking smokers.

“We examined the impact of alcoholism and smoking on gene expression in the NAC in 20 chronic alcohol abusers and controls with and without recent smoking history,” said Flatscher-Bader. “The results revealed that in this brain region, the abuse of alcohol and nicotine had distinct effects on the expression of genes. In addition, altered expression of a number of genes was associated with both alcohol and nicotine abuse. Within the latter group was a set of genes which play a crucial role in a molecular pathway regulating cell structure.”

The researchers then went on to investigate in more detail the altered expression of six selected genes within the pathway regulating cell structure in two brain regions, using 30 cases comprised again of smoking and non-smoking controls and alcohol abusers. For this part of the study they used the method called “real time polymerase chain reaction.”

“This expanded investigation revealed that one of the genes, called RHOA, was elevated by alcohol abuse and its highest expression was evident in the smoking alcoholics in both brain regions,” said Flatscher-Bader. “The RHOA gene had previously been implicated in the initiation of tobacco smoking. In the NAC, the expression of a further four of the six selected genes was increased by alcohol abuse. Interestingly, the highest expression for each of the genes in the NAC was in the smoking alcoholics. In the other brain region called the VTA, alcohol abuse had a similar effect and elevated the expression of all six selected genes. In contrast to the NAC, however, concurrent smoking dampened the induction of five of these alcohol-sensitive genes in the VTA.”

“Many studies have analyzed the changes in gene expression in this brain system to try to untangle the molecular pathology of alcohol addiction,” said Worrall, “but this is amongst the first to take into account the effect of co-administration of nicotine with alcohol.

Flatscher-Bader stressed that there are several cell types in the brain and there are several steps between gene expression and impact on cell structure and function. “It has to be emphasized that our study is important as a first step in identifying molecular pathways underlying the effects of alcohol abuse and smoking and their co-joint abuse on the human NAC and VTA, “she said. “It now needs to be tested if our findings are, indeed, associated with changes to neuronal structure and function.”

“A better understanding of the molecular basis of withdrawal may help in the development of new treatments to ameliorate the symptoms,” added Dr Worrall. “Not many previous studies took into account the potential effects of nicotine addiction that may be superimposed on top of those from alcohol, so these results may help clinicians better use present therapy/drugs to treat patients abusing both alcohol and/or nicotine and may also lead to the development of new drugs.”

Source: www.medicalnewstoday.com 5.5.2010

Levels of the serotonin transporter are low in the brains of users of ecstasy, according to a US National Institute of Drug Abuse-funded study by Toronto’s Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids) published today in the journal Brain.
Ecstasy (MDMA) is a stimulant drug widely used recreationally that is also being tested in clinical trials for the treatment of post-traumatic stress disorder.
Led by Dr. Stephen Kish at CAMH, this study provides confirmation of a previous finding from Johns Hopkins University that levels of the serotonin transporter (SERT) are low in cerebral cortex of chronic ecstasy users. The subjects were “typical” ecstasy users who used about two tablets of the drug twice a month.
SERT is a protein responsible for regulating levels of serotonin, a neurotransmitter important for mood and impulse control. Ecstasy interacts with SERT to cause the release of serotonin, an action that probably explains some of the behavioral effects of the drug such as increased sociability.
Scientists have long suspected that ecstasy might harm brain cells that use serotonin, but 12 years of brain scan studies have produced contradictory results, even within the same laboratory.
The CAMH study used a large subject size (49 drug users, 50 control subjects), confirmed by hair analysis that ecstasy users actually used the drug, and used an imaging probe that could measure SERT throughout the brain.
“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain, perhaps because serotonin nerves to the cortex are longer and more susceptible to changes. This finding is almost identical to newer data from Johns Hopkins and is the first time that one laboratory has actually been able to replicate results of another independent laboratory in a SERT study of ecstasy users.” said Dr. Kish.
Drug hair analysis indicated that many ecstasy users, probably unknowingly, also used methamphetamine, which might itself damage serotonin cells; however, low SERT was found both in ecstasy users who used and who did not use methamphetamine. Dr. Jason Lerch at SickKids showed that those ecstasy users who also used methamphetamine had a slightly thinner cerebral cortex.
Does low SERT equal “structural brain damage”? “Not necessarily” said co-author Dr. Isabelle Boileau of CAMH. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”
Dr. Kish suggests that low SERT might explain why many ecstasy users need to keep increasing the dose to experience the same effects, since SERT is necessary for the action of ecstasy. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed. The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug,” said Dr. Kish.
Media Contact: Michael Torres, Media Relations, CAMH ; 416 595 6015 or email media@camh.net

Source: www.camh.net 18th May 2010-30-

Researchers have discovered that consuming a very high amount of alcohol in a short time can cause irreversible damage. In the long run youngsters risk becoming absent-minded and forgetful.
Previous research found that high levels of alcohol act as a poison and prevent the brain working properly. Now scientists say that excess alcohol can actually destroy grey matter called the hippocampus, which stores and recalls events and forms mental images, known as spatial reasoning.
A US team gave alcohol for one hour a day to teenage macaque monkeys, who drank until they were drunk. Their brains produced fewer cells and suffered more neural degeneration than a control group. Last year, a survey of 35 countries found the UK had the third highest number of 15 and 16-year-olds with an alcohol problem. Girls were worse than boys.
Don Shenker, chief executive of Alcohol Concern, said the Government needed “to force the drinks industry to ensure consumers are aware of the dangers”.
Source: Daily Express 1st June 2010

The brain’s nucleus accumbens (NAC) is a core region of the mesocorticolimbic dopaminergic system and is interconnected with the ventral tegmental area (VTA) and the prefrontal cortex. The mesocorticolimbic system is thought to be central to the reinforcing effects of many drugs and plays an important role in addiction. A new study has found that alcohol abuse elevated the expression of a distinct set of genes in the NAC and VTA, while nicotine blunted this effect in the VTA.

Results will be published in the July 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“In spite of their differences in pharmacology, alcohol and tobacco consumption are often intimately linked,” said Traute Flatscher-Bader, a postdoctoral research fellow at The University of Queensland and corresponding author for the study. “Nonetheless, the molecular mechanisms that underlie alcohol and nicotine abuse, and particularly their co-abuse, are still incompletely understood.”

“One thing that researchers have encountered is that it is often difficult to find ‘pure’ alcoholics, that is, alcoholics that only abuse alcohol and nothing else,” agreed Simon Worrall, director of postgraduate coursework programs in molecular biology at The University of Queensland. “Many alcoholics are poly-drug abusers, with the most common other drug being nicotine. Thus, many studies which have studied the effects of alcohol on the brain and other organs have been compromised because they have not taken account of the effects of nicotine addiction which is often superimposed on the effects of alcohol addiction.”

In the first part of the current study, Flatscher-Bader and her colleagues used DNA microarray technique to study the expression of many thousands of genes in the brains of non-smoking and smoking alcoholics and non-drinking smokers.

“We examined the impact of alcoholism and smoking on gene expression in the NAC in 20 chronic alcohol abusers and controls with and without recent smoking history,” said Flatscher-Bader. “The results revealed that in this brain region, the abuse of alcohol and nicotine had distinct effects on the expression of genes. In addition, altered expression of a number of genes was associated with both alcohol and nicotine abuse. Within the latter group was a set of genes which play a crucial role in a molecular pathway regulating cell structure.”

The researchers then went on to investigate in more detail the altered expression of six selected genes within the pathway regulating cell structure in two brain regions, using 30 cases comprised again of smoking and non-smoking controls and alcohol abusers. For this part of the study they used the method called “real time polymerase chain reaction.”

“This expanded investigation revealed that one of the genes, called RHOA, was elevated by alcohol abuse and its highest expression was evident in the smoking alcoholics in both brain regions,” said Flatscher-Bader. “The RHOA gene had previously been implicated in the initiation of tobacco smoking. In the NAC, the expression of a further four of the six selected genes was increased by alcohol abuse. Interestingly, the highest expression for each of the genes in the NAC was in the smoking alcoholics. In the other brain region called the VTA, alcohol abuse had a similar effect and elevated the expression of all six selected genes. In contrast to the NAC, however, concurrent smoking dampened the induction of five of these alcohol-sensitive genes in the VTA.”

“Many studies have analyzed the changes in gene expression in this brain system to try to untangle the molecular pathology of alcohol addiction,” said Worrall, “but this is amongst the first to take into account the effect of co-administration of nicotine with alcohol.

Flatscher-Bader stressed that there are several cell types in the brain and there are several steps between gene expression and impact on cell structure and function. “It has to be emphasized that our study is important as a first step in identifying molecular pathways underlying the effects of alcohol abuse and smoking and their co-joint abuse on the human NAC and VTA, “she said. “It now needs to be tested if our findings are, indeed, associated with changes to neuronal structure and function.”

“A better understanding of the molecular basis of withdrawal may help in the development of new treatments to ameliorate the symptoms,” added Dr Worrall. “Not many previous studies took into account the potential effects of nicotine addiction that may be superimposed on top of those from alcohol, so these results may help clinicians better use present therapy/drugs to treat patients abusing both alcohol and/or nicotine and may also lead to the development of new drugs.”

Source: www.medicalnewstoday.com 5.5.2010

Q: How can I tell if my child has been using marijuana?
A: There are some signs you might be able to see. If someone is high on marijuana, he or she might:

• Seem dizzy and have trouble walking;
• Seem silly and giggly for no reason;
• Save very red, bloodshot eyes; and
• Have a hard time remembering things that just happened.

When the early effects fade, the user can become very sleepy.

Parents should be aware of changes in their child’s behavior, although this may be difficult with teens. Parents should look for withdrawal, depression, fatigue, carelessness with grooming, hostility and deteriorating relationships with family members and friends.

In addition, changes in academic performance, increased absenteeism or truancy, lost interest in sports or other favorite activities, and changes in eating or sleeping habits could be related to drug use. However, these signs may also indicate problems other than using drugs.

In addition, parents should be aware of:

• Signs of drugs and drug paraphernalia, including pipes and rolling papers;
• Odor on clothes and in the bedroom;
• Use of incense and other deodorizers;
• Use of eye drops; and
• Clothing, posters, jewelry, etc., promoting drug use.

Source: The National Institute on Drug Abuse 2010

Young men who report an unstable pattern of alcohol consumption including binge drinking have an elevated risk for experiencing hypomania, study results show. Notably, the effect was independent of total alcohol consumption and the presence of clinical alcohol use disorders.
“This fits with the idea that instability in different biological and behavioral systems is a core feature of risk for hypomania and finally risk for bipolar disorders,” say study authors Thomas Meyer (Newcastle University, UK) and Larissa Wolkenstein (University of Tübingen, Germany) in the journal Comprehensive Psychiatry.
Recent studies have suggested that vulnerability to hypomania is related to instability in certain psychologic processes. For example, individuals at risk for hypomania do not generally sleep less than others, but report a much more unstable sleeping pattern. Similarly fluctuations in self-esteem are much more characteristic of vulnerability to hypomania than are consistently low or high levels of self-esteem.
In the current study, the researchers assessed whether alcohol use might show a similar relationship to hypomania. They recruited 120 male students who completed the Hypomanic Personality Scale and were independently interviewed with the FORM 90 to assess alcohol consumption. The latter comprised an interview about a typical weekly drinking pattern and a calendar to assess drinking behavior over the last 90 days, noting special days with unusual drinking behavior.
The researchers found that intra-individual fluctuations in alcohol consumption predicted hypomania after accounting for clinical diagnoses of abuse or dependency. In addition, vulnerability for hypomania was significantly associated with mean standard ethanol content per drinking day.
Discussing their findings, the researchers note a recent theory that bipolar disorder is related to a hypersensitivity to reward-related cues, which is due to a dysregulation of the behavioral activation system.
“To extend this work further, it would be reasonable to look more closely at the motivational and affective processes associated with drinking alcohol and bipolar disorder and how mood and drinking are related,” Meyer and Wolkenstein comment.
Source: MedWire (www.medwire-news.md) 19 March 2010

SMOKERS who suffer damage to a particular part of their brains appear to be able to quit their nicotine habit easily – a discovery that might open new avenues of addiction research.
A study of smokers who had suffered brain damage of various kinds after a stroke showed that those with injuries to a part of the brain called the insula were in many cases able to quit smoking quickly and easily – saying they had lost the urge to smoke altogether.
The insula receives information from the body and translates it into subjective feelings such as hunger, pain and craving, including craving for drugs.
However, the insula has not attracted much attention in studies on drug addiction, according to the research in the latest edition of the journal Science.
Deliberately damaging people’s insulas is not considered a realistic treatment option, because the risks are too great and the insula also has a role in many essential functions, such as the desire to eat.
But in the long term, the authors said, drugs might be developed to target the insula.
Other techniques for affecting the insula might in future also include electrical stimulation, already used in patients with depression. However, current techniques cannot penetrate the brain deeply enough to reach the insula.
The study was inspired by the experience of a man who had smoked 40 cigarettes a day before his insula was damaged in a stroke. He quit smoking immediately after, telling researchers his body “forgot the urge to smoke”.
Additional reporting: The Times

Source: news.com.au January 27th 2007

Research Summary

Background

Despite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia.
Aims To investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56).
Method Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter.
Results Patients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers.
Conclusions A defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.
Philip R. Szeszko, PhD, Delbert G. Robinson, MD and Serge Sevy, MD et al
Correspondence: Dr Philip R. Szeszko, Zucker Hillside Hospital, Psychiatry Research, 75–59 263rd Street, Glen Oaks, NY11004, USA. Tel: +1 718 470 8489; fax: +1 718 343 1659; email: szeszko@lij.edu

Source: The British Journal of Psychiatry (2007) 190: 230-236. doi: 10.1192/bjp.bp.106.024521
© 2007 The Royal College of Psychiatrists

James M. Howard,
Independent Biologist

It is my hypothesis that schizophrenia results from reduced fetal brain growth and development due to low maternal DHEA. This is exposed later in life by hormones that interfere with DHEA availability, that is, cortisol and testosterone, along with the natural decline of DHEA that begins around age twenty. Therefore, schizophrenia often occurs following a stressful event (cortisol) in the late teens or early twenties (testosterone and loss of DHEA) or later in life as DHEA reaches very low levels. Schizophrenia is characterized by low DHEA. Individuals with normal DHEA along with reduced fetal DHEA may not develop schizophrenia.
I suggest that the psychoactive chemicals of cannabis exert their effects by binding to androgen receptors. It has been found that THC and CBN inhibit binding of dihydrotestosterone to the androgen receptor (Endocrinology 1980; 107: 848-50). This binding to receptors in the advanced forebrain would reduce executive function and increase lower brain function by redistributing DHEA. That is, blocking access to upper brain receptors would increase lower brain function and increase lower brain functions such as appetite, etc.
DHEA binds to the androgen receptor. Cannabis use would reduce DHEA binding to the androgen receptor. It is this blocking of DHEA at its upper level receptors and subsequent redistribution of availability for lower brain activity that I think produces the effects of cannabis.
It is known that DHEA directly affects the anterior cingulate cortex (Psychopharmacology (Berl) 2006; 188: 541-51). Interference of DHEA binding in the anterior cingulate cortex of individuals with reduced growth and development in this area may reduce both function and maintenance of this area with the result being the symptoms of schizophrenia.

BY LORI WHITTEN, NIDA Notes Staff Writer

NIDA-supported researchers Dr. Cheryl Kirstein and Ms. Kirstie Stansfield at the University of South Florida have found that higher scores on tests of impulsivity and some behavioral responses to novelty correlate with a heightened biological response to cocaine in adolescent, but not adult, rats. The findings accord well with scientists’ widely shared view that developmental differences in brain systems that use the neurotransmitter dopamine underlie age differences in susceptibility to drug abuse.
Dr. Kirstein and Ms. Stansfield conducted a series of behavioral assays to rate rats’ relative responsiveness to novelty, then compared these results with measures of dopamine release in the reward pathway after an injection of cocaine. First, they put adolescent rats (34 days old, which is roughly equivalent to adolescence in people) and fully mature rats (59 days old, equivalent to human young adulthood) through four behavioral protocols. The tests measured activity in a new environment (how much the rat moved around when put into a new cage); impulsivity (how quickly it approached a new object placed into its cage); exploratory drive in response to a new object (how many times it approached the object in a given period of time); and attraction to new objects (what percentage of a given time interval was spent close to the object).
The researchers then injected the animals with saline and then, 2 hours later, with cocaine 20 mg/kg. Every 10 minutes, starting immediately after the saline injection and continuing until 2 hours after administering the cocaine, they measured the concentrations of the neurotransmitter dopamine and its major metabolite in the rats’ nucleus accumbens (NAc). The measurements were made using the technique of in vivo microdialysis. By the time of the last measurement, the drug had cleared the animal’s system.
ON MOST TESTS, AGE MATTERS
In their analysis, the researchers compared cocaine-induced dopamine release in animals that had responded above the mean level on each test (high responders, HR) to those who had scored below the mean (low responders, LR). The results revealed that among both the adult and adolescent rats, those that exhibited greater activity in a new environment also demonstrated enhanced dopamine release following a cocaine injection. This was the only test, however, in which age did not influence cocaine-induced dopamine release. The other behavioral assays revealed interactions between age and the response to novelty on cocaine-induced dopamine release in the NAc:
• Impulsivity—Adolescent rats with above-the-mean impulsivity scores released more dopamine in response to cocaine than their age mates who were LR. Mature rats exhibited no clear relationship between impulsivity and cocaine-induced dopamine response.
• Exploration of a new object—Adolescent rats with above-the-mean scores on this measure released more dopamine in response to cocaine than their age mates who were LR. Adult rats showed the opposite pattern: Animals with above-the-mean scores showed attenuated cocaine-induced dopamine release compared with age mates who were LR.
• Attraction to a new object—Adolescent rats exhibited no clear relationship between reactivity on this assay and cocaine-induced dopamine release. Mature rats with above-the-mean scores released less dopamine in response to cocaine compared with their age mates who were LR.
Dr. Kirstein’s finding that for all the animals, greater activity in a new environment corresponded with increased sensitivity to stimulants is consistent with earlier research. Her team’s mixed findings on the impulsivity and other novelty response tests indicates, she says, that those behaviors arise from different physiological mechanisms than does locomotor activity. “My colleagues and I think locomotor activity may reflect primarily dopamine activity in a brain circuit involved with generating and controlling movement. Novelty may instead differentially stimulate mesolimbic dopamine—a pathway implicated in attention as well as reward and motivation,” says Dr. Kirstein.
In Vivo Microdialysis
The investigators used In Vivo microdialysis to measure dopamine each animal released from its nucleus accumbens (NAc) in response to cocaine. They implanted a probe into the shell area of the NAc. The probe is a fine tube, about the size of a sewing needle, connected to a mini-pump that continuously perfuses it with artificial cerebrospinal fluid. The membrane tip of the probe captures dopamine and its metabolites. The samples collected by the needle are then analyzed using techniques, such as chromatography, that are able to isolate dopamine and its metabolites from other molecules.
INHIBITION DEVELOPS LATER
The findings on the three tests where age affected the relationship between behavior and cocaine-induced dopamine release may reflect maturation of the brain’s reward circuit. When rats are adolescents, dopamine-producing and releasing cells in this circuit may be particularly sensitive both to novelty and to pharmacological stimulation. As part of normal neurological development, areas of the brain that dampen the activity of this circuit come “online” later, explaining the age-related differences observed in Dr. Kirstein’s study. “The mesolimbic pathway and the cortical areas that inhibit it to regulate dopamine release are not yet fully matured in the adolescent, and this may explain why the adolescent brain responds to drugs differently than the adult brain,” says Dr. Kirstein.
“The results of Dr. Kirstein’s study, along with other animal research on the interaction of drugs and developmental stage, indicate that the adolescent brain is more responsive to drugs than the adult brain—both neurochemically and behaviorally,” says Dr. Nancy Pilotte of NIDA’s Division of Basic Neuroscience and Behavioral Research. Studies that identify the physiological and behavioral processes underlying age-related susceptibility to addiction complement epidemiological work on the individual and social factors contributing to adolescent vulnerability to substance abuse.

SOURCE NIDA Notes Vol. 21, No. 2 (February 2007)
Stansfield, K.H., and Kirstein, C.L. Neurochemical effects of cocaine in adolescence compared to adulthood. Developmental Brain Research 159(2):119-125, 2005.

<span style=”font-size: 10pt; font-family: Verdana;”> Abstract: The use of Cannabis sativa preparations, such as hashish and marijuana, is wide-spread among young people, including pregnant women. Despite this concern, the consequences of cannabis exposure on the brain during periods of active brain development, such as the prenatal phase and adolescence, is not well known. Several epidemiological studies support the cannabis gateway hypothesis, where early cannabis use is suggested to increase the risk of initiating use of other illicit drugs, e.g., amphetamine or heroin. However, the nature of such direct links are unclear. Therefore, the aim of this thesis was to test experimentally the cannabis gateway hypothesis, i.e., to determine whether cannabis exposure during periods of active brain development alters reward-related behavior and neurobiology for psychostimulant and opioid drugs by the use of animal models.
In the first study, we examined the effects of early adolescent exposure (postnatal day; PND; 28-32, one injection per day) with the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 and the main psychoactive substance in C. sativa, Δ9-tetrahydrocannabinol (THC) on amphetamine-induced motor behavior and dopamine release in the nucleus accumbens during adolescence. No alterations were evident in the cannabinoid exposed rats, results which did not support the cannabis gateway hypothesis in relation to subsequent psychostimulant abuse.
Next, we investigated the effects of adolescent exposure on subsequent opioid reward-related behavior and the neurobiology of opioid and cannabinoid systems during adulthood. We studied THC exposure across the full adolescent period (PND 28-49), and administered the drug once every third day in order to better mimic the pattern of intermittent use seen in teenagers. The results revealed discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing (e.g., increased proenkephalin gene expression in the nucleus accumbens and increased mu opioid receptors in the ventral tegmental area). This was coupled to increased heroin intake in a self-administration paradigm and increased morphine conditioned place preference, indicating altered sensitivity to the reinforcing properties of opioids.
Furthermore, in evaluating the adolescent ontogeny of the opioid and cannabinoid systems within limbic-related brain areas, we found that active endocannabinoid- and opioid- related neurodevelopment takes place to a very high extent during this period. Most pronounced were the alterations in endocannabinoid levels in cognitive brain areas, even though alterations were also apparent in reward-related regions.
Finally, we investigated the effects of prenatal cannabis exposure (gestational day 5- PND 2) on subsequent opioid reward-related behavior and neurobiology of the opioid and cannabinoid systems in adulthood. Similar to adolescent cannabis exposure, prenatal exposure induced discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing. Moreover, elevated heroin-seeking observed during extinction and after food deprivation was evident in the THC exposed rats, suggesting an increased motivation for drug use under conditions of stress.
Taken together, this thesis presents neurobiological support for the cannabis gateway hypothesis in terms of adult opiate, but not amphetamine, abuse, with underlying long-term disturbances of discrete opioid-related systems within limbic brain regions.

<em>Source: Ellgren, Maria Karolinksa Institute Sweden ISBN: 978-91-7357-064-0  Feb.2007
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A researcher at the University of Buffalo’s Research Institute on Addictions (RIA) has found a change in the brain that occurs after drug use and that may contribute to drug addiction.
The finding, reported in the January issue of Biological Psychiatry, demonstrates that repeated exposure to different types of drugs of abuse, such as cocaine, nicotine, amphetamine and alcohol, lead to a persistent or long-term reduction in the electrical activity of dopamine neurons in the brain.
Dopamine neurons are the origin of the reward pathway responsible for the “feel good” experience that is such a strong component of drug use and abuse.
“A persistent reduction in dopamine neuron electrical activity after repeated exposure to different types of drugs appears to be the result of excessive excitation of dopamine neurons,” according to Roh-Yu Shen (photo), a neuroscientist and the lead investigator on the study. “This represents a new and potentially critical neural mechanism for addiction and provides a working model that suggests how the reward pathway function is altered and how these changes can be responsible for triggering intense craving and compulsive drug-seeking.”

Source. January 2007 issue of Biological Psychiatry

The brains of alcoholics can show measurable improvement in volume, chemical activity, and functionality after as little as seven weeks of abstinence, a new study published in the journal Brain today reveals.

Researchers from Germany, the UK, Switzerland and Italy collaborated on a study of ten men and five women alcoholics who had achieved an average of 38 days abstinence at the time of the study. Alcoholics who used psychoactive medications or who smoked more than 10 cigarettes a day after they stopped drinking were excluded from the data. Researchers used functional magnetic resonance imaging (fMRI) and proton MR spectroscopy, laboratory tests for levels of brain chemicals that measure nerve integrity and repair, and performance tests for attention and concentration.

Brain volume increased an average of two percent, researchers found, and there were major increases in the substances that measured nerve health and regrowth. There were also improvements in performance. However, in one subject, who had the longest history of alcoholism in the study (more than 25 years), the evidence of brain recovery was not visible within the relatively short time span of the study.

The leader of the research, Dr Andreas Bartsch from the University of Wuerzburg, Germany, said:
“The core message from this study is that, for alcoholics, abstinence pays off and enables the brain to regain some substance and to perform better. However, our research also provides evidence that the longer you drink excessively, the more you risk losing this capacity for regeneration. Therefore, alcoholics must not put off the time when they decide to seek help and stop drinking; the sooner they do it, the better.”

Source. Journal ‘Brain’ SUNDAY, DECEMBER 17, 2006

Summary

DURHAM, N.C. — Within the mind of every smoker trying to quit rages a battle between the higher-order functions of the brain wanting to break the habit and the lower-order functions screaming for another cigarette, say researchers at Duke University Medical Center. More often than not, that cigarette gets lit.
Brain scans of smokers studied by the researchers revealed three specific regions deep within the brain that appear to control dependence on nicotine and craving for cigarettes. These regions play important roles in some of the key motivations for smoking: to calm down when stressed, to achieve pleasure and to help concentration.
“If you can’t calm down, can’t derive pleasure and can’t control yourself or concentrate, then it will be extremely difficult for you to break the habit,” said lead study investigator Jed E. Rose, Ph.D., director of the Duke Center for Nicotine and Smoking Cessation Research. “These brain regions may explain why most people try to quit several times before they are successful.”
Understanding how the brain responds to cigarette cravings can help doctors change nicotine cessation treatments to address all three of these components of withdrawal, Rose said. Drugs or therapies that target these regions may help smokers stave off the cravings that often spoil their attempts to quit.
The team’s findings are now online in the journal Neuropsychopharmacology. The research was funded by Phillip Morris USA.
Approximately one in five Americans smokes. Even though 70 percent of smokers report that they would like to quit, only 5 percent do so successfully.
In this study, the researchers manipulated the levels of nicotine dependence and cigarette craving among 15 smokers and then scanned their brains using positron emission tomography, or PET scans, to see which areas of the brain were most active.
Three specific regions of the brain demonstrated changes in activity when the smokers craved cigarettes versus when they did not.
One region that lights up, called the thalamus, is considered to be the key relay point for sensory information flowing into the brain. Some of the symptoms of withdrawal among people trying to quit stem from the inability to focus thoughts and the feeling of being overwhelmed, and could thus be explained by changes in this region, according to the researchers. The researchers found that changes in this region were most dramatic among those who said they smoked to calm down when under stress.
Another region that lights up is a part of the pleasure system of the brain. Changes in this region, called the striatum, were most notable in people who smoked to satisfy craving and for pleasurable relaxation, the researchers said.
A third region that lights up, called the anterior cingulate cortex, is vital to cognitive functions such as conflict, self regulation, decision making and emotion. People whose brain scans showed the most differences in this region also reported that they smoked to manage their weight.
“This knowledge gives us new clues about brain mechanisms underlying addiction to cigarettes and could allow us design better methods to help smokers quit,” Rose said.
Rose and his colleagues are now planning to perform brain scans on smokers undergoing nicotine replacement therapy, such as the nicotine patch, to determine how these treatments affect the same regions of the brain.
Other researchers participating in the study were Frederique M. Behm, Alfred N. Salley, James E. Bates, R. Edward Coleman, Thomas C. Hawk and Timothy G. Turkington.

Source: www.dukemednews March 2007

Summary

Heavy drinking and smoking as teenagers may damage the ability to remember future tasks, according to new research.
The findings are drawn from two studies exploring teenagers’ capacity for prospective memory – the ability to remember something you had intended to do in the future, such as returning a phone call or paying a bill on time.
In one study, 108 students aged 16 to 19 years old were asked to report the number of times that prospective memory had failed them recently. Teenagers who were “excessive” alcohol users were significantly less likely to remember future tasks, the researchers found.
A second study found that teenage smokers reported more memory lapses in general than non-smokers, and also reported fewer items in a prospective memory test.
The findings are being presented today at the British Psychology Society’s annual conference at the University of York.
The society said that although evidence exists suggesting alcohol abuse has a detrimental effect on memory for past events, little was known before now about its impact on prospective memory.
Thomas Heffernan of the University of Northumbria, who led the research, said: “The teenage years are important for structural and functional development of the brain.
“If our findings are confirmed, they suggest that heavy drinking and smoking in the teenage years may impede this important development. This may lead to greater problems with memory later in life.”

Source:Thursday March 22, 2007 SocietyGuardian.co.uk

Research Summary
A pair of new studies find that smokers take many more sick days annually than nonsmokers and perform worse when they are on the job, Bloomberg News reported March 29.
A Swedish study by Petter Lundborg and colleagues from Free University of Amsterdam found that smokers took an average of 34 sick days per year, compared to 20 per year for people who never smoked and 25 per year among former smokers.
Sweden has one of the highest rates of sickness absence in the industrialized world; in the U.S., the average worker takes off nine days annually for illness. “The results suggest that policies that reduce and/or prevent smoking may also reduce the number of days of sick leave,” wrote Lundborg.
In a study of women in the U.S. Navy, San Diego State University researcher Terry Conway and colleagues found that smokers were more likely to be discharged for medical reasons, bad behavior, misconduct, drug misuse and personality disorders. Smokers also were more apt to resign from the Navy before serving their full terms, and were paid less.
However, noted Conway, “Cigarette smoking might simply be a marker for other underlying factors such as nonconformity and high risk-taking, that contribute to poorer performance.”
The research was published in the journal Tobacco Control.

Source: Bloomberg News March 29 2007

Scientists have shown how cannabis may trigger psychotic illnesses such as schizophrenia.
A King’s College London team gave healthy volunteers the active ingredient tetrahydrocannabinol (THC).
They then recorded reduced activity in an area of the brain which keeps inappropriate thoughts at bay. THC levels are thought to have doubled in street cannabis in recent years – at the expense of other ingredients which may have a beneficial effect.

A separate study has shown that one of these ingredients – cannabidiol (CBD) – has the potential to dampen down psychotic symptoms, and could form the basis of new treatments. The research will be discussed at a conference on the impact of cannabis use to be held at the Institute of Psychiatry at King’s College this week.
Dependency
Although figures are not kept, it is estimated that as many as 500,000 people in the UK may be dependent on cannabis. Increasing numbers of people are seeking help for cannabis problems at specialist clinics. In 2005, only heroin users accounted for a greater proportion of patients. Experts are concerned that street cannabis is becoming increasingly potent. It is thought that average THC content has risen from 6% to 12% in recent years.
The Institute of Psychiatry study gave THC, CBD or placebo capsules to adult male volunteers who had not abused cannabis. They then carried out brain scans, and a battery of tests, and found that those who took THC showed reduced activity in an area of the brain called the inferior frontal cortex, which keeps inappropriate thoughts and behaviour, such as swearing and paranoia in check.
The effects were short-lived, but some people appeared more vulnerable than others.
In a second study, a team from Yale University administered THC intravenously. Even at relatively low doses, they found 50% of healthy volunteers began to show symptoms of psychosis. Volunteers who already had a history of psychotic symptoms appeared to be particularly vulnerable.
Side effects
A third study, by the University of Cologne, compared the effect of CBD and a commonly used anti-psychotic medicine, Amisulpride, on 42 patients with a history of schizophrenia.
After four weeks both groups showed a reduction in psychotic symptoms, but the CBD group were less prone to side effects, such as muscle stiffness and weight gain.

The researchers warned that THC and CBD compete with each other biochemically, so a rise in THC levels would blunt any positive impact of CBD. Professor Robin Murray, a consultant psychiatrist at the Institute of Psychiatry, said the research provided the strongest evidence that cannabis had a significant impact on the brain.
He said proving a long-term effect was extremely difficult, as it was not ethical or feasible to stimulate long-term psychosis in volunteers.
However, he said: “If something has an active effect in inducing the symptoms of psychosis after one dose, then it would not be at all surprising if repeated use induced the chronic condition.”
Professor Murray also warned that the high potency cannabis now widely available was likely to pose a much bigger risk to health than the significantly weaker formulations of previous years. “It is similar to comparing the effect of drinking a glass of wine at the weekend with drinking a bottle of vodka every day.”
Marjorie Wallace, of the mental health charity Sane, called the research a “significant contribution” to the understanding of the dangers of cannabis.
“Sane has been saying for years that there is a link between psychosis and the drug, particularly in its more potent forms.
“We strongly urge the government to heed the growing evidence and take urgent action to warn young people that some of them are risking lifelong mental illness – that they are playing Russian roulette with their minds.”

Source: BBC NEWS: 2007/04/30

Analysis of a national sample of individuals with alcohol dependence (alcoholism) revealed five distinct subtypes of the disease. This finding should help dispel the myth that alcoholism is easily categorized and that an individual can be classified as a ‘typical alcoholic’.
Scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH) report their finding in the journal Drug and Alcohol Dependence.
“Our findings should help dispel the popular notion of the ‘typical alcoholic,’” notes first author Howard B. Moss, M.D., NIAAA Associate Director for Clinical and Translational Research.
“We find that young adults comprise the largest group of alcoholics in this country, and nearly 20 percent of alcoholics are highly functional and well-educated with good incomes.
“More than half of the alcoholics in the United States have no multigenerational family history of the disease, suggesting that their form of alcoholism was unlikely to have genetic causes.”
“Clinicians have long recognized diverse manifestations of alcoholism,” adds NIAAA Director Ting-Kai Li, M.D, “and researchers have tried to understand why some alcoholics improve with specific medications and psychotherapies while others do not. The classification system described in this study will have broad application in both clinical and research settings.”
Previous efforts to identify alcoholism subtypes focused primarily on individuals who were hospitalized or otherwise receiving treatment for their alcoholism.
However, recent reports from NIAAA’s National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative epidemiological study of alcohol, drug, and mental disorders in the United States, suggest that only about one-fourth of individuals with alcoholism have ever received treatment.
Thus, a substantial proportion of people with alcoholism were not represented in the samples previously used to define subtypes of this disease.
In the current study, Dr. Moss and colleagues applied advanced statistical methods to data from the NESARC. Their analyses focused on the 1,484 NESARC survey respondents who met diagnostic criteria for alcohol dependence, and included individuals in treatment as well as those not seeking treatment.
The researchers identified unique subtypes of alcoholism based on respondents’ family history of alcoholism, age of onset of regular drinking and alcohol problems, symptom patterns of alcohol dependence and abuse, and the presence of additional substance abuse and mental disorders:
Young Adult subtype: 31.5 percent of U.S. alcoholics. Young adult drinkers, with relatively low rates of co-occurring substance abuse and other mental disorders, a low rate of family alcoholism, and who rarely seek any kind of help for their drinking.
Young Antisocial subtype: 21 percent of U.S. alcoholics. Tend to be in their mid-twenties, had early onset of regular drinking, and alcohol problems. More than half come from families with alcoholism, and about half have a psychiatric diagnosis of Antisocial Personality Disorder. Many have major depression, bipolar disorder, and anxiety problems. More than 75 percent smoked cigarettes and marijuana, and many also had cocaine and opiate addictions. More than one-third of these alcoholics seek help for their drinking.
Functional subtype: 19.5 percent of U.S. alcoholics. Typically middle-aged, well-educated, with stable jobs and families. About one-third have a multigenerational family history of alcoholism, about one-quarter had major depressive illness sometime in their lives, and nearly 50 percent were smokers.
Intermediate Familial subtype: 19 percent of U.S. alcoholics. Middle-aged, with about 50 percent from families with multigenerational alcoholism. Almost half have had clinical depression, and 20 percent have had bipolar disorder. Most of these individuals smoked cigarettes, and nearly one in five had problems with cocaine and marijuana use. Only 25 percent ever sought treatment for their problem drinking.
Chronic Severe subtype: 9 percent of U.S. alcoholics. Comprised mostly of middle-aged individuals who had early onset of drinking and alcohol problems, with high rates of Antisocial Personality Disorder and criminality. Almost 80 percent come from families with multigenerational alcoholism. They have the highest rates of other psychiatric disorders including depression, bipolar disorder, and anxiety disorders as well as high rates of smoking, and marijuana, cocaine, and opiate dependence. Two-thirds of these alcoholics seek help for their drinking problems, making them the most prevalent type of alcoholic in treatment.
The authors also report that co-occurring psychiatric and other substance abuse problems are associated with severity of alcoholism and entering into treatment. Attending Alcoholics Anonymous and other 12-step programs is the most common form of help-seeking for drinking problems, but help-seeking remains relatively rare.

Source: National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism June 2007

For years, scientists described the human brain as a machine with parts, each part dedicated to controlling different activities. If a part was injured, the function it controlled would be lost permanently. But as Norman Doidge shows in his new book, The Brain That Changes Itself, (Viking) new neurological evidence has emerged showing that the brain can be trained to rewire itself after an injury, such as a stroke or ear or eye damage. Through interviews with neuroscientists and neuron-rehabilitation patients, Doidge also finds that the brain is capable of improving learning disabilities and intellectual and even moral performance through techniques such as repetition of learning and implementation of regular habits. The more we know about these processes, the more doctors can help patients to find other ways perform lost functions.

Doidge is a psychiatrist, psychoanalyst, and researcher on the research faculty at Columbia University’s Center for Psychoanalytic Training and Research, in New York, and the University of Toronto’s Department of Psychiatry.

Source: Hudson Institute August 2007

For years, scientists have known that some people are biologically more susceptible to drug addiction than others, but they have only been able to speculate why.
In the August 15, 2007 issue of the Journal of Neuroscience, researchers at the University of Chicago report on a study that may help answer this question.
They discovered that rats most likely to self-administer addictive drugs had a particular receptor in the brain that is more responsive than the same receptor in rats least likely to self-administer addictive drugs.
This receptor, known as the nicotinic acetylcholine receptor (nAChR), increases excitability within in the brain’s reward centers. In the animals that were more likely to take addictive drugs, the effects of these receptors were much stronger, leading to more profound excitation of the cells and pathways associated with reward.
Stress, and the associated increases in stress hormones, will promote drug-taking behavior regardless of whether an animal is more or less susceptible, say the researchers. They showed that stress also increases the responses of nAChRs within the brain’s reward areas.
“We tested the exploratory behavior of rats in an unfamiliar cage. Rats that explore a new environment for a prolonged period of time were more interested in addictive drugs,” says Daniel McGehee, PhD, associate professor and lead researcher on this study. ” Those rats also had stronger nAChR responses, meaning their brains responded differently to the drugs. We measured receptor activity in the brain’s reward centers that are known to be activated by addictive drugs.”
“This study provides valuable insight into the mechanism of addiction,” says McGehee. “It raises the possibility that nicotinic receptors may be important targets for the treatment of multiple addictions, not just nicotine. Unfortunately, blocking these receptors may also interfere with healthy behaviors that depend upon the same brain circuitry. Precisely where these findings will lead drug treatment strategies is unclear, but this work provides insight into the role of nicotinic receptors in the vulnerability to multiple classes of addictive drugs.”

Source: University of Chicago Medical Center. Published on Eureka Alert August 2007

Drug users who can’t kick the habit can blame a dysfunctional brain for their addiction, according to new research.
A study by the University of Melbourne has found long-term drug users have more difficulty controlling impulses because their frontal cortex is impaired.

The two-year study found opiate users needed to use more of their brains to resist impulses in a test of self control than those who were clean. The findings shed new light on why drug addicts find it so hard to quit, despite the health consequences.
“Drugs can capture and hijack some parts of the brain,” said Dr Murat Yucel, a lead researcher in the study. In this study we found the frontal cortex, an area that is essential for exercising control over thoughts and behaviours, was working inefficiently. These findings may help explain why it takes addicted individuals enormous effort to exercise control over their drug taking behaviour in the face of adverse consequences and why they are vulnerable to relapse back into uncontrolled, compulsive patterns of use.”
The study – published in the journal, Molecular Psychiatry, last month – also found drug users’ brain cells in the frontal region were less healthy than normal. The research shows drug taking is not a matter of choice for long-term users, who have a reduced biological capacity to stop, Dr Yucel says.
Researchers will next examine whether reduced brain function is a consequence of addiction or a contributing factor that makes some people more vulnerable to drug abuse. Co-researcher Dan Lubman said the study would likely lead to the development of new strategies for the treatment of addiction.
“These findings tell us that we need to provide a combination of pharmaceutical and psychological treatments that will help bolster the efficiency of the frontal cortex and hence the individual’s ability to stop their urge to use drugs,” he said.

Source: www.yahoo7News.com Aug. 2007

September 7, 2007

Research Summary
Cocaine and amphetamine users appear to develop an abnormal protein in their brains that could play a role in addiction.
Researchers at the Rosalind Franklin University of Medicine and Science in North Chicago, Ill., found that use of these drugs alters a protein that controls how RNA is copied — an anomaly that could cause structural changes in tissues, diseases, and behavior changes.

Reference:
Marinescu V, Loomis PA, Ehmann S, Beales M, Potashkin JA (2007) Regulation of Retention of FosB Intron 4 by PTB. PLoS ONE, 2(9): e828; doi: 10.1371/journal.pone.0000828.
This article summarizes a mainstream media report of research published in a scientific journal. It is not an original analysis of the source material, which is cited in the reference above.

Source: online journal PLoS One. September 2007

Brain volume decreases with age at an estimated rate of 1.9 percent per decade, accompanied by an increase in white matter lesions, according to background information in the article. Lower brain volumes and larger white matter lesions also occur with the progression of dementia and problems with thinking, learning and memory. Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease; because the brain receives blood from this system, researchers have hypothesized that small amounts of alcohol may also attenuate age-related declines in brain volume.
Carol Ann Paul, M.S., of Wellesley College, Mass., and colleagues studied 1,839 adults (average age 60) who were part of the Framingham Offspring Study, which began in 1971 and includes children of the original Framingham Heart Study participants and their spouses. Between 1999 and 2001, participants underwent magnetic resonance imaging (MRI) and a health examination. They reported the number of alcoholic drinks they consumed per week, along with their age, sex, education, height, body mass index and Framingham Stroke Risk Profile (which calculates stroke risk based on age, sex, blood pressure and other factors).
“Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers,” the authors write. “There was a significant negative linear relationship between alcohol consumption and total cerebral brain volume.”
Although men were more likely to drink alcohol, the association between drinking and brain volume was stronger in women, they note. This could be due to biological factors, including women’s smaller size and greater susceptibility to alcohol’s effects.
“The public health effect of this study gives a clear message about the possible dangers of drinking alcohol,” the authors write. “Prospective longitudinal studies are needed to confirm these results as well as to determine whether there are any functional consequences associated with increasing alcohol consumption. This study suggests that, unlike the associations with cardiovascular disease, alcohol consumption does not have any protective effect on brain volume.”

Source: Paul et al. Association of Alcohol Consumption With Brain Volume in the Framingham Study. Archives of Neurology, 2008; 65 (10): 1363 DOI:

Smoking marijuana as a teenager could raise the risk of developing schizophrenia and psychotic symptoms as a young adult, according to a new study that compared the prevalence of mental illness among marijuana users and non-users.
Bloomberg News reported March 2 that researcher John McGrath of the University of Queensland, Australia, and colleagues studied 3,801 young-adult sibling pairs and concluded that those who used marijuana the longest (six or more years) were twice as likely to develop schizophrenia or delusional disorders. They also were four times more likely than non-users to score highly on a test gauging psychotic-like experiences.
Higher scores on the test also were seen among those who used marijuana for less than three years.

Source: www.jointogether.org March 2010

• Marijuana is the most commonly used illicit drug in the United States.
• New research shows that the use and misuse of alcohol and marijuana are influenced by a common set of genes.
Marijuana is the most commonly used illicit drug in the United States. Roughly eight to 12 percent of marijuana users are considered “dependent” and, just like alcohol, the severity of symptoms increases with heavier use. A new study has found that use and misuse of alcohol and marijuana are influenced by a common set of genes.
Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
“Results from a large annual survey of high-school students show that in 2008, 41.8 percent of 12th graders reported having used marijuana,” explained Carolyn E. Sartor, a research instructor at Washington University School of Medicine and corresponding author for the study. “Although many may have used the drug on only a few occasions, 5.4 percent of 12th graders reported using it daily within the preceding month.”
“The active ingredient in marijuana is THC, which mimics natural cannabinoids that the brain produces,” added Christian Hopfer, associate professor at the University of Colorado School of Medicine. “The cannabinoid system is critical for learning, memory, appetite, and pain perception. Most users of marijuana will not develop an ‘addiction’ to it, but perhaps one in 12 will. What is not commonly appreciated about marijuana use is that strong evidence has emerged that it increases the risk of developing mental illnesses and possibly exacerbates pre-existing mental illnesses.”
“Like any drug, marijuana can be used in a way that negatively impacts quality of life, interfering with functioning at school or work or leading to problems with family and friends,” said Sartor. “Although at least three of six symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) are needed to meet full criteria for cannabis (marijuana) dependence … the presence of even one or two of these symptoms could create distress or interfere with day-to-day functioning. There is strong evidence for a genetic component to use and dependence on marijuana as well as alcohol, and the use (and misuse) of these substances frequently occur together.”
Researchers examined 6,257 individuals (2,761 complete twin pairs and 735 singletons) listed in the Australian Twin Registry, 24 to 36 years of age. Alcohol and marijuana use histories were gathered in telephone diagnostic interviews and used to derive levels of alcohol consumption, frequency of marijuana use, and DSM-IV alcohol and cannabis dependence symptoms.
“Our findings indicate that … many of the same genetic factors that contribute to alcohol use also contribute to marijuana use,” said Sartor. “Likewise, alcohol dependence symptoms and cannabis dependence symptoms can be traced to some of the same genetic influences. For both alcohol and marijuana, the majority of genetic factors that contribute to use also contribute to dependence symptoms.”
“In other words,” said Hopfer, “the genetic influences on drug use are not specific to individual drugs, but seem to influence a general tendency to engage in drug use. This is important to note because there is a tendency to study drugs in isolation – alcohol, tobacco, marijuana, cocaine, etc. These findings add support to the notion of common mechanisms underlying all addictions.”
“The fact that very little of the environmental influences on alcohol and marijuana use, or on alcohol and cannabis dependence symptoms, could be traced to common sources indicates that there may be important distinctions between those environmental factors that influence alcohol-related outcomes and those that influence marijuana-related outcomes,” said Sartor. “Identifying alcohol- and marijuana-specific risk factors is an important next step in this line of research.”
“Marijuana research is relatively sparse compared to alcohol or nicotine research,” added Hopfer. “However, if you look at reports of at least adolescents and young people using, it becomes clear that marijuana use, including daily marijuana use, is quite common and the effects of this are not well understood. The mental illness/marijuana connection has not received much press, although I think the evidence has grown substantially that marijuana is a causal risk factor for the development of mental illness.”

Source: http://www.attcnetwork.org/explore/priorityareas/science/tools/asmeDetails.asp?ID=643

 Marijuana use at a young age significantly increased the risk of psychosis in young adulthood, Australian investigators reported.

Young adults who reported a longer duration since first exposure to marijuana had a two- to fourfold greater prevalence of three different psychosis-related outcomes, John McGrath, MD, PhD, of the Queensland Center for Mental Health Research in Wacol, and colleagues concluded in an article published online in Archives of General Psychiatry.

Apart from the implications for policy makers and health planners, we hope our findings will encourage further clinical and animal model-based research to unravel the mechanisms linking cannabis use and psychosis, the researchers concluded.

Several prospective-cohort studies have demonstrated an association between early marijuana use and an increased risk of psychosis. On the basis of such studies, reviews of the issue have generally concluded that early use of marijuana, or cannabis, is a modifiable risk factor for psychosis-related outcomes, the authors wrote.

However, some concern has persisted about potential methodologic biases and unmeasured confounders in the cohort studies. In an effort to address the concern, McGrath and colleagues examined the association between cannabis use and psychosis in 3,800 participants in a long-term evaluation of pregnancy and outcomes. In contrast to prior cohort studies, the authors incorporated a subset analysis involving 228 sibling pairs.

“If a significant association between cannabis use and psychosis-related outcomes was not detected in sibling pairs, it would seriously weaken the argument that cannabis use was a risk-modifying factor for psychosis-related outcomes,” they wrote.

Participants were born between 1981 and 1984 at a single hospital in Brisbane. Mothers and their offspring were followed up at five, 14, and 21 years after birth. At the 21-year follow-up, McGrath and colleagues retrospectively assessed cannabis use among the offspring, whose age averaged 20 and ranged from 18 to 23.

Cannabis use was assessed by means of the young adults’ responses to two questions: In the last month, how often did you use cannabis, marijuana, pot, etc.? At what age did you first use cannabis?
Possible responses to the first question were never, every day, every few days, once or so, and not in the past month.

Investigators separated the cohort into four groups on the basis of self-reported cannabis use. One group included never-users, and the remaining three groups were categorized by duration since first use of cannabis: three years or less, four to five years, six years or more.

Investigators compared participants’ history of cannabis use with three psychosis-related outcomes: non-affective psychosis, hallucinations (assessed by the Computerized International Diagnostic Interview), and the Peters et al Delusions Inventory (PDI) score (Schizophr Bull 2004; 30: 1005-1022).

The authors found that 65 participants met criteria for a diagnosis of non-affective psychosis, and 233 reported at least one hallucination-related incident. The PDI has a score range of 0-21, and participants were grouped into PDI quartiles representing scores of =2, 3 or 4, 5 to 7, and =8.

The authors analyzed the results by means of two statistical models, one adjusted for participant sex and age at testing and the other adjusted for sex, age at testing, presence of hallucinations at the 14-year follow-up, and parental history of mental illness.

Using never-users as the reference, the odds ratio for non-affective psychosis increased from 1.5 to 2.1 or 2.2 in the two models as duration of first cannabis use increased. The odds for hallucinations increased from 1.4 to 2.5 and 1.5 to 2.8.

Comparing the lowest and highest quartiles of PDI scores, the authors found that the odds of a higher score increased from 1.6 to 4.0 or 4.3 as duration since first cannabis use increased.  Associations for all three psychosis-related outcomes were statistically significant in both models (P=0.001 to P<0.001).

The sibling analysis was limited to the PDI scores. For each pair, the authors calculated difference scores for duration since first cannabis use and PDI total score. The association between time since first cannabis use and PDI score remained statistically significant in the sibling subset analysis.

Limitations of the study included: retrospective self-reporting of time since first cannabis use, lack of data on cumulative exposure to cannabis, no clinical validation of non-affective psychosis diagnosis and lack of use of the instrument at the 14-year follow up, and loss of participants at the 21-year mark with significant differences in the group lost to follow up compared with those retained.

Source:. “Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults” Arch Gen Psychiatry 2010; DOI: 10.1001/archgenpsychiatry.2010.6.

My first appointment was with Dr Diana Fishbein, a Senior Fellow in behavioral neuroscience at the Research Triangle Institute (RTI) which is an international not-for-profit research organisation .

Diana is the Director of the Transdisciplinary Behavioural Science Program at RTI. In this role she focuses on bringing interdisciplinary teams of researchers together to try to answer some of the big questions that need to be asked in the behavioural sciences. Her overarching goal is to focus on the nexus between research and practice and to facilitate the “Translation of Research into Evidence Based Practice”. In fact RTI International organisational by line is Turning Knowledge into Practice.    

Diana’s personal research career has been in the area of criminology and drug abuse taking a prevention science approach.  She is particularly interested in why some young people respond well to a prevention approach while others don’t, and ultimately in determining “who responds to what treatment at what time point and why”?

To explore these questions she uses interdisciplinary methods and a developmental approach and sees the plasticity of neurobiological systems as one of the keys to finding the answer. Dr. Fishbein  pointed out that neuroplasticity enables neurobiological systems to be shaped by inputs from the environment and so can be altered for better or worse depending on the nature of these inputs. This is highly relevant to a prevention or early intervention approach and can guide the development of interventions. Research in this area is now beginning to focus on the mechanisms through which developmental risk factors impact on the developing systems and also on the type of interventions which have the most impact, how they are affecting neuroplastic change and when they are having the most effect.  

For instance there is evidence that the neurobiological functions underlying drug misuse and aggression are quite complex and include executive functioning, coping skills and affect regulation. The part of the brain associated with these functions (prefrontal-limbic brain networks) is not consolidated until early adulthood. Therefore is we can understand the type, effect and developmental timing of environmental impact on this brain function we may be able to plan intervention programs that alter negative impact and increase positive impact.  We may also need to tailor interventions to particular risk factors in the young person’s environment. Diana is confident this translational approach promises to eventually offer some direction for the design of effective interventions to prevent drug misuse and associated aggression.

This cutting-edge evidence-based research with the capacity to not only make a difference but to provide us with the scientific evidence to show how change has come about.  The message that again seems to be coming through to me is that one size is not likely to fit all. The other message is one that Professor Alan Hayes a member of the external advisory group for this project has written about in his chapter entitled Why early in life is not enough! (Hayes, 2007. In France, A & Homel, R (Eds) Pathways and crime prevention: Theory policies and practice  Willian (pps 202-225)

Dr Fishbein and I also talked about the need for parent and community involvement in interventions.  She also indicated to me that she and her organisation are very interested in innovative collaborative international research. Perhaps this is something to think about for the future.

Source: http://shapingbrains.wordpress.com  3^rd March 2010

The recreational use of cocaine has rapidly increased in many European countries over the past few years. One cause of this is the fall in the price of the drug on the street from 100 Euros for one gram (about 5 lines) in 2000 to 50 Euros in the Netherlands today. One line of cocaine is, thus, now as cheap as a tablet of ecstasy. This means cocaine is no longer considered an “elite” drug but is affordable for all, especially for recreational use. It is therefore likely that the recreational use of cocaine will become a public health issue in the next few years, which is already the case for the recreational use of ecstasy.
In a study in PLoS One, researchers at Leiden University and the University of Amsterdam, led by Lorenza Colzato, employed the “stop-signal paradigm” to measure the length of time taken by subjects to initiate and suppress a prepared reaction.
The stop-signal task requires participants to react quickly and accurately by pressing a left or right key in response to the direction of a left- or right-pointing green arrow. In 30% of the trials, the green arrow turned red, in which case participants had to abort the go response. The results show that while both recreational users of cocaine and non-users performed similarly in terms of response initiation, users needed significantly more time to inhibit their responses.
The study is the first of its kind to investigate systematically action control, and the inhibitory control of unwanted response tendencies in particular, in recreational users, i.e. those who don’t meet the criteria for abuse or dependency but who take cocaine (usually by snorting) on a monthly basis (1 to 4 grams). The researchers found that the magnitude of the inhibitory deficit in recreational users was smaller than previously observed in chronic users, suggesting that the degree of the impairment is proportional to the level of cocaine use.
Given the seemingly small quantities of cocaine involved, the findings of this study are rather worrying. Many real-life situations require the active inhibition of pre-potent actions, as in the case of traffic lights turning red or of criminal actions. This impairment of inhibitory control has serious implications for personal or societal functioning. This reduced level of inhibitory control may even be involved in the emergence of addiction: the more a drug is used, the less able users are to prevent themselves from using it.

Source: Public Library of Science PLoS One 2(11): e1143.doi:10.1371/journal.pone.0001143 2007, November 7.

Researchers have discovered that even a small amount of MDMA, better known as ecstasy, can be harmful to the brain, according to the first study to look at the neurotoxic effects of low doses of the recreational drug in new ecstasy users. The findings were presented today at the annual meeting of the Radiological Society of North America (RSNA).

“We found a decrease in blood circulation in some areas of the brain in young adults who just started to use ecstasy,” said Maartje de Win, M.D., radiology resident at the Academic Medical Center at the University of Amsterdam in the Netherlands. “In addition, we found a relative decrease in verbal memory performance in ecstasy users compared to non-users.”
Ecstasy is an illegal drug that acts as a stimulant and psychedelic. A 2004 survey by the National Institute on Drug Abuse (NIDA) found that 450,000 people in the United States age 12 and over had used ecstasy in the past 30 days. In 2005, NIDA estimated that 5.4 percent of all American 12th graders had taken the drug at least once.
Ecstasy targets neurons in the brain that use the chemical serotonin to communicate. Serotonin plays an important role in regulating a number of mental processes including mood and memory.
Research has shown that long-term or heavy ecstasy use can damage these neurons and cause depression, anxiety, confusion, difficulty sleeping and decrease in memory. However, no previous studies have looked at the effects of low doses of the drug on first-time users.
Dr. de Win and colleagues examined 188 volunteers with no history of ecstasy use but at high-risk for first-time ecstasy use in the near future. The examinations included neuroimaging techniques to measure the integrity of cells and blood flow in different areas of the brain and various psychological tests. After 18 months, 59 first-time ecstasy users who had taken six tablets on average and 56 non-users were re-examined with the same techniques and tests.
The study found that low doses of ecstasy did not severely damage the serotonergic neurons or affect mood. However, there were indications of subtle changes in cell architecture and decreased blood flow in some brain regions, suggesting prolonged effects from the drug, including some cell damage. In addition, the results showed a decrease in verbal memory performance among low-dose ecstasy users compared to non-users.
“We do not know if these effects are transient or permanent,” Dr. de Win said. “Therefore, we cannot conclude that ecstasy, even in small doses, is safe for the brain, and people should be informed of this risk.”
This research is part of the Netherlands XTC Toxicity (NeXT) study, which also looks at high-dose ecstasy users and aims to provide information on long-term effects of ecstasy use in the general population.

Source: Radiological Society of North America (2006, November 28).

Teens who smoke marijuana are at a greater risk of developing schizophrenia and psychotic symptoms in the future, a new study has found.
After observing more than 3800 youngsters, researchers learnt that people who used the drug for six or more years were twice as likely to suffer from delusional disorders than those who never used it. Researchers from Queensland Brain Institute, at the University of Queensland, quizzed 3801 young adults who were born in Brisbane between 1981 and 1984.
Among the 1272 participants who had never used marijuana, 26 (2 per cent) were diagnosed with psychosis, while the 322 people who had used marijuana for six or more years, 12 (3.7 per cent) were diagnosed with the illness. The average age of the participants was about 20. According to the authors, the study was the first to look at sibling pairs to discount genetic or environmental influence.
“This is the most convincing evidence yet that the earlier you use cannabis, the more likely you are to have symptoms of a psychotic illness,” the Sydney Morning Herald quoted Dr McGrath, a professor at the institute, as saying in a statement.
McGrath added: “The message for teenagers is: if they choose to use cannabis they have to understand there’s a risk involved.” The study noted: “Apart from the implications for policy makers and health planners, we hope our findings will encourage further clinical and animal-model research to unravel the mechanisms linking cannabis use and psychosis.”
The research has been published online by the Archives of General Psychiatry.

Source: Health Wise Feb 28 2009

Teens and young adults who are heavy marijuana users are more likely than non-users to have disrupted brain development, according to a new study that appeared last month in the Journal of Psychiatric Research.

Pediatric researchers found abnormalities in areas of the brain that interconnect regions involved in memory, attention, decision-making, language and executive functioning skills. The findings are of particular concern because adolescence is a crucial period for brain development and maturation.

The researchers caution the study is preliminary and does not demonstrate that marijuana use causes the brain abnormalities. However, “Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari, Ph.D., director of the Diffusion Image Analysis and Brain Morphometry Laboratory in the Radiology Department of The Children’s Hospital of Philadelphia.

Working with child psychiatrist Sanjiv Kumra, M.D., Ashtari and colleagues performed imaging studies on 14 young men from a residential drug treatment center in New York, as well as 14 age-matched healthy controls. All the study subjects were males, with an average age of 19. The researchers performed the imaging studies at Long Island Jewish Medical Center.

The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. Most had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly six marijuana joints daily in the final year before they stopped using the drug.

The study team performed a type of magnetic resonance imaging scan called diffusion tensor imaging (DTI) that measures water movement through brain tissues. The abnormal patterns of water diffusion that were found among the young adults with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells, Ashtari said. Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower.

Myelin gives its color to the white matter of the brain, and covers the nerve fibers that connect different brain regions. The study’s results suggest early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain. Abnormal white matter development could slow information transfer in the brain and affect cognitive functions

Source: the Journal of Psychiatric Research. Reported in CADCA Coalitions online Feb 24 2010

Abstract
The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a
sample of 42 ecstasy/polydrug users and 31 non-ecstasy users. Laboratory-based PM tasks were administered along with self-reported measures of PM to
test whether any ecstasy/polydrug-related impairment on the different aspects of PM was present. Self-reported measures of everyday memory and
cognitive failures were also administered. Ecstasy/polydrug associated deficits were observed on both laboratory and self-reported measures of PM and
everyday memory. The present study extends previous research by demonstrating that deficits in PM are real and cannot be simply attributed to
self-misperceptions. The deficits observed reflect some general capacity underpinning both time- and event-based PM contexts and are not task
specific. Among this group of ecstasy/polydrug users recreational use of cocaine was also prominently associated with PM deficits. Further research
might explore the differential effects of individual illicit drugs on real-world memory.

Source: Journal of Psychopharmacology 0(00) 1–12 2010

Theresa H M Moore, Stanley Zammit, Anne Lingford-Hughes, Thomas R E Barnes, Peter B Jones, Margaret Burke, Glyn Lewis
Summary
Background – Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.
Methods – We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate.
Findings – There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1•41, 95% CI 1•20–1•65). Findings were consistent with a dose-response eff ect, with greater risk in people who used cannabis most frequently (2•09, 1•54–2•84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately.
Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding eff ect was present for both psychotic and aff ective outcomes.
Interpretation The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication eff ects, although evidence for aff ective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now suffi cient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Source: The Lancet Vol.370 pp 319-328 July 2007

New research shows that specific variations in the cannabis receptor gene (CB1) may be associated with the development of one or more symptoms of marijuana dependence in adolescents. This is one of the first studies looking specifically at the link between marijuana dependence and CB1 variations.

Background: Marijuana is the most commonly abused illegal substance among adolescents and young adults, and those who begin using at this stage are about twice as likely as adults to become dependent. Genetic variations in the CB1 receptor—the brain target for the psychoactive ingredient in marijuana—is a logical candidate gene to study as a potential contributor to vulnerability to marijuana dependence. Therefore, researchers examined the associations between specific variants in the CB1 gene and the rates of marijuana dependence.

Study Design: The scientists collected DNA from 541 youths aged 17 or older who had used marijuana at least five times recently. After interviews to identify one or more DSM-IV symptoms of dependence, 327 were established as cases; the remaining 214 had no symptoms and served as controls. All subjects were genotyped for four specific DNA sequence variations of the CB1 gene.

What They Found: One CB1 variant (found in 21 percent of the general population) was associated with a lower rate of having one or more marijuana dependence symptoms, while two others (present in 12 percent of the general population) were linked to increased likelihood of developing dependence symptoms.

Comments from the Authors: Identifying gene variants that may afford some protection against marijuana dependence may have important implications for intervention. However, it is likely that multiple genes and their interactions with environmental events influence marijuana and other drug addictions. Therefore, some level of genetic protection may not necessarily protect an adolescent from becoming dependent on drugs or suffering other related health consequences.

What’s Next: Future studies should examine these genetic variants for other drug-related traits, as well as additional DNA sequence variations for possible drug abuse associations.

Publication: The study, led by Dr. Christian J. Hopfer of the University of Colorado, was published in volume 141B, pages 895-901 (2006) of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).

Source:NIDA Newscan 27th Aug. 2007

The results of this study suggest that many drug abusers may experience similar changes in the patterns of global gene expression in their brains, irrespective of their drug of choice. Whether longtime drug abusers favor cocaine, marijuana, or PCP, their autopsied brains showed a number of common gene changes consistent with diminished brain plasticity— i.e., the ability to learn from new experiences and adapt to new situations. Therefore, brain functions may be similarly impaired as the result of chronically abusing different drugs.

Background: Chronic drug abuse can change the structure and function of several brain regions. Recent advances in genomic technologies allow us to monitor the expression level of thousands of genes simultaneously in specific parts of the brain, including the anterior prefrontal cortex (aPFC), a region that plays an important role in decision making. A dysfunctional aPFC appears to be a characteristic feature of the brains of drug abusers. Researchers wanted to know if different drugs of abuse can compromise the normal patterns of gene expression that converge in common pathways, resulting in similar changes in the brains of drug abusers.

Study Design: NIDA scientists compiled clinical case histories and toxicology reports to establish the primary drug of abuse of 42 deceased drug abusers. The drugs examined included cocaine, marijuana, and PCP. The researchers then measured the level of expression of more than 9000 individual genes in small brain tissue samples obtained from the aPFC.

What They Found: Although many effects were specific to each drug, the scientists also found that nearly 80 percent of the drug abuse cases displayed similar alterations in genetic output compared to the controls. For example, genes involved in calcium signaling were turned down, while genes involved in lipid- and cholesterol-related pathways were turned up.

Comments from the Authors: The aPFC is characterized by a particularly dense and complex network of neural connections. Our results show that cocaine, marijuana, and PCP can alter the function of this critical brain area in similar ways, which could threaten the drug abuser’s ability to make sound decisions.

What’s Next: Many of the gene families identified here point to common downstream pathways that should be studied further in order to understand their specific contributions to the long-term effects of abused drugs on the human brain.

Source: The study, led by Dr. Elin Lehrmann of the Cellular Neurobiology Research Branch in NIDA’s Intramural Research Program in Baltimore, was published in the open access journal PLoS ONE on December 27, 2006 (PLoS ONE 1:e114).

Nicotine addiction relies on brain receptors that have been difficult to fully study and characterize. Scientists at the University of Colorado in Boulder have demonstrated that an immunolabeling technique can effectively analyze receptor subunits.

Background: Nicotine’s effects on the brain are triggered upon its binding to nicotinic acetylcholine receptors, each of which consists of five subunits: two alphas, one beta, one delta and one gamma. Different combinations of these subunits produce different receptor subtypes, which may vary in their pharmacology, biophysical properties, and distribution. To more fully understand how to interfere with nicotine’s effects in the brain, scientists must first understand where these different receptors are and how they work. Two of the most important subunits, a4 and b2, have been hard to study because current study methods can only locate the fully assembled receptor unit. Researchers wanted to know if an alternative strategy of immunolabeling (i.e., using antibodies to tag individual proteins), which has been fraught with technical challenges, would be able to identify, map, and quantify separate subunits.

Study Design: Scientists at the University of Colorado worked with brain sections of mice genetically engineered to express particular a4 and b2 subunit combinations. Using a sensitive immunolabeling technique, they explored the expression of the a4 and b2 subunits at both the gene and protein levels. Additional mice strains, missing the subunits under study, were used as controls.

What They Found: The two predominant nicotinic receptor subtypes (a4 and b2) were reliably detected using immunolabeling. Expression of the a4 subunit protein was almost universally dependent on b2, whereas most, but not all, b2 subunit protein expression was a4-dependent.

Comments from the Authors: Immunolabeling using specific antibodies offers a powerful approach for mapping the distribution of nicotine receptor subunits and can produce reliable quantitative results.

What’s Next: Similar studies can be designed to locate other nicotine receptor subtypes. In many cases, the antibody recognition sites are inside the cell membrane. It will likely take alternative biochemical approaches to uncover these less accessible sites. A better understanding of receptor composition and function may eventually have important implications for developing interventions at the receptor level.

Source: The study, led by Dr. Paul Whiteaker of the Institute for Behavioral Genetics at the University of Colorado, Boulder, with Dr. Jon Lindstrom of the University of Pennsylvania, was published in volume 499, number 6, pages 1016-1038 (2006) of the Journal of Comparative Neurology.

What do suffering a traumatic brain injury and using club drugs have in common? University of Florida researchers say both may trigger a similar chemical chain reaction in the brain, leading to cell death, memory loss and potentially
irreversible brain damage.

A series of studies at UF over the past five years has shown using the
popular club drug Ecstasy, also called MDMA, and other forms of
methamphetamine lead to the same type of brain changes, cell loss and
protein fluctuations in the brain that occur after a person endures a
sharp blow to the head, according to recent findings.

“Using methamphetamine is like inflicting a traumatic brain injury on
yourself,” said Firas Kobeissy, a postdoctoral associate in the College
of Medicine department of psychiatry. “We found that a lot of brain
cells are being injured by these drugs. That’s alarming to society now.
People don’t seem to take club drugs as seriously as drugs such as
heroin or cocaine.”

Working with UF researchers Dr. Mark Gold, chief of the division of
addiction medicine at UF’s McKnight Brain Institute and one of the
country’s leading experts on addiction medicine, and Kevin Wang,
director of the UF Center for Neuroproteomics and Biomarkers Research,
Kobeissy compared what happened in the brains of rats given large doses
of methamphetamine with what happened to those that had suffered a
traumatic brain injury.

The group’s research has already shown how traumatic brain injury
affects brain cells in rats. They found similar damage in the rats
exposed to methamphetamine. In the brain, club drugs set off a chain of
events that injures brain cells. The drugs seem to damage certain
proteins in the brain, which causes protein levels to fluctuate. When
proteins are damaged, brain cells could die. In addition, as some
proteins change under the influence of methamphetamine, they also begin
to cause inflammation in the brain, which can be deadly, Kobeissy said.

Kobeissy and other researchers in Gold’s lab are using novel protein
analysis methods to understand how drug abuse alters the brain. Looking
specifically at proteins in the rat cortex, UF researchers discovered
that about 12 percent of the proteins in this region of the brain showed
the same kinds of changes after either methamphetamine use or traumatic
brain injury. There are about 30,000 proteins in the brain so such a
significant parallel indicates that a similar mechanism is at work after
both traumatic brain injury and methamphetamine abuse, Kobeissy said.

“Sometimes people go to the clubs and take three tablets of Ecstasy or
speed,” Kobeissy said. “That may be a toxic dose for them. Toxic effects
can be seen for methamphetamine, Ecstasy and traumatic injury in
different areas of the brain.”

About 1.3 million people over the age of 12 reported using
methamphetamine in the previous month, according to the 2006 National
Survey on Drug Use and Health. In 2004, more than 12 million Americans
reported having tried the drug, the survey’s findings show.

People often think the effects of drugs of abuse wear off in the body
the same way common medications do, but that may not be the case, Gold
said.

“These data and the previous four years of data suggest some drugs,
especially methamphetamine, cause changes that are not readily
reversible,” Gold said. “Future research is necessary for us to
determine when or if methamphetamine-related brain changes reverse
themselves.”

Gold and Dennis Steindler, director of UF’s McKnight Brain Institute and
an expert on stem cells, are planning studies to find out if stem cells
can be applied to repair drug-related brain damage.

UF researchers are also trying to uncover all the various ways drugs
damage and kill brain cells. During their protein analysis, researchers
discovered that oxidation was damaging some proteins, throwing the
molecules chemically off balance.

“When proteins are oxidized they are not functional,” Kobeissy said.
“When proteins are not working, the cell cannot function.”

Neurologist Dr. Jean Lud Cadet, chief of the molecular neuropsychiatry
branch of the National Institute on Drug Abuse, said analyzing proteins
is important to understanding how drugs such as methamphetamine affect
the brain.

“I think saying the results of methamphetamine abuse are comparable to
the results of a traumatic brain injury is a new idea,” Cadet said. “I
agree with (the findings). Our own work shows that methamphetamine is
pretty toxic to the brains of animals. In humans, imaging studies of
patients who use methamphetamine chronically show abnormalities in the
brain.

“Abuse of methamphetamine is very dangerous.”

This research was presented at a Society for Neuroscience conference
held recently in San Diego.

Source: Science Daily (Nov. 29, 2007)

Research Summary
Human brain cells can be altered and damaged by low doses of ecstasy, leading to reduced blood flow to the brain, researchers say.
Bloomberg News reported Nov. 27 that a new study finds that even first-time users of ecstasy experience a decrease in verbal memory, and that taking just a few doses of the drug causes brain changes that can be seen 18 months after first use.
“We don’t know if it’s reversible or permanent,” said researcher Maartje de Win of the University of Amsterdam, who presented the findings at a meeting of the Radiological Society of North America this week. “People should know there might be some consequences for them even after incidental use.”
The study included brain scans of 188 young adults considered at risk of ecstasy use; initial scans were taken before any of the group had used the drug. When follow-up scans were taken 18 months later, 64 members of the group had tried ecstasy; 59 of these were reexamined by researchers, as well as 56 members of the group who had not used the drug.
Source: www.jointogether.org Nov.2006

From the founding of National Families in Action during the height of the War on Drugs to Joseph A. Califano’s book, How to Raise a Drug-Free Kid, parents and communities have been touted as the keys to preventing alcohol and other drug problems among youth, and research now shows that environmental and genetic risk factors can be trumped by parental engagement during the critical adolescent years, according to Nora D. Volkow, M.D., director of the National Institute on Drug Abuse (NIDA).
“Parents are incredibly important in raising drug-free kids, but in many instances they are not there or are not involved” — absences that can have measurable effects on brain development as well as other aspects of growing up — said Volkow. For example, studies of orphans have demonstrated that the brains of children who lack connections to parents actually mature more slowly, raising the risk of drug use and other impulsive behaviors. Half of all vulnerability to addiction can be traced to an individual’s genetic background, but that hardly means that a child’s fate is sealed if they have a family history of addiction. Rather, Volkow said that addiction is, in many ways, a developmental disorder that is intimately linked to the maturation of the brain from childhood through adolescence and into early adulthood.
Delivering the keynote address at the Nov. 17 CASACONFERENCESM How to Raise a Drug-Free Kid: The Straight Dope, organized by the National Center on Addiction and Substance Abuse (CASA*) at Columbia University, Volkow compared this brain development to a sculptor taking a block of stone and transforming it into a work of art.
“In childhood the brain is particularly ‘plastic,’” said Volkow. “It is open to stimuli much more than as an adult, and these stimuli affect brain formation both physically and chemically. A child’s cerebral cortex — the brain’s center for memory, attention, perceptual awareness, thought, language, and consciousness — starts out larger than that of an adult, but shrinks as the brain differentiates during the first two decades of life. “The brain of an adult is much more connected than that of a child,” noted Volkow.
The frontal cortex — critical for using cognitive control to regulate desires — is the last part of the brain to fully differentiate, said Volkow, which helps explain why adolescents are especially prone to risk-taking and experimentation. As the brain advances on its “developmental trajectory” it can be strongly influenced by environmental factors, she said. Social stresses are crucially important,” Volkow said, pointing to the Adverse Childhood Experience (ACE) Study research showing that risk of drug abuse rises tenfold among individuals who experience five or more “adverse childhood experiences,” such as recurrent physical or emotional abuse.
“Studies of children raised in orphanages showed that their brain connectivity was much less developed than those with normal parenting,” added Volkow; the effect was most pronounced among the children who had been living in orphanages the longest. The research “directly connected the lack of parenting to delays in the development of the brain,” she said. Children who are genetically predisposed to addiction rarely suffer from drug problems if they have parents who are actively involved in their lives, according to researchers. Those who have both genetic vulnerability and absent or uninvolved parents have a “very significant increase in drug addiction,” however, according to Volkow.
Studies of prevention programs like “Preparing for the Drug-Free Years” (PDF) and “Communities That Care” demonstrate that parents, families and communities can create an environment that is protective against youth drug abuse. Moreover, said Volkow, researchers have found that interventions can actually improve dopamine levels in the brain. Even though kids may be born to very adverse environments, the plasticity of the brain now gives us a path forward in terms of identifying interventions to help reverse the changes caused by these stimuli and increase the likelihood that kids will be able to stay drug-free,” said Volkow.
The NDPA would agree with the comments below – you can be an excellent parent and still have a child who chooses to use drugs…. However, the article ids also correct in stating that parents who know as much about illegal drugs as their children and who parent ‘actively’ (i.e. know where their children are, who are their friends, how are they achieving in school etc.) are less likely to have the problem of drug use in their family.
COMMENTS ON THIS ARTICLE:
Posted by Amy Rosenman, MD on 07 Dec 09 02:07 PM EST
This review is too simplistic.There are still many children brought up in ideal circumstances who develop drug problems. This review still seems to “blame” the family for something beyond their control in many circumstances. However, knowing that family involvement and support is crucial gives many hope that recovery is possible. I too have worked with families of addiction for many years in my medical practice. 12 step programs are very valuable and help keep the family relationships constructive.
Posted by Emily on 07 Dec 09 06:28 PM EST
I agree that parental involvement helps prevent drug abuse, but I know of families that were doing everything right, and their child still became addicted to drugs. In at least one case, the child had no risk factors for substance abuse other than an alcoholic grandparent. I think it is important for parents to know that a family history of alcoholism or drug abuse should not be ignored. In such cases, parents need to be better educated regarding what to do to prevent substance abuse and how to recognize it when it happens.
Posted by Jay Arr on 10 Dec 09 10:35 AM EST
We are the product of our reactions to all the forces of our genes, enviroment, inter-personal relationships,cultural impact, and our reactions to them. Sometimes we are the victims by being stuck in a prison of emotional immaturity. Alcohol and drugs beckon us to escape this life of lies and the lies eventually become our reality. The reality is SAD-S for stigma, A for apathy, and D for denial..I was saved by Alcoholics Anonymous-25 years ago.
Source: CASA Conference. Columbia University Nov. 17th 2009

Long-term cocaine use can alter the function of genes in the brain, leaving “pleasure circuits” stuck in the open position and increasing craving for the drug, according to a new animal study conducted by researchers at the Mount Sinai School of Medicine.
Reuters reported Jan. 9 that researcher Ian Maze and colleagues found that the gene 9A — which produces an enzyme responsible for switching other genes on and off — was repressed in the brains of mice given repeated doses of cocaine. Researchers also found that restoring the activity of gene 9A reversed cocaine preference and craving in lab mice.
“This finding is opening up our understanding about how repeated drug use modifies in long-lasting ways the function of neurons,” said Nora Volkow, director of the National Institute on Drug Abuse.
Source: Science. Jan. 8, 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

A new study funded by NIDA has used brain-imaging technology to show that during a decision game, chronic marijuana users show less activity in an error-processing part of their brains than peers who do not use marijuana. These results provide preliminary evidence in the debate on whether substance abusers willfully ignore their problem or whether cognitive deficits prevent them from fully understanding their addiction and its potential consequences. Functional magnetic resonance imaging (fMRI) of 16 heavy marijuana users and 16 non-drug-using peers provided real-time pictures of brain activity during the decision game. The marijuana abusers in the study did not make more mistakes during the game than participants who did not use the drug, but they were significantly less likely to recognize that they had made the mistakes. Non-marijuana-using participants were aware of 91 percent of their mistakes during the game, and marijuana abusers were aware of only 77 percent of their mistakes. fMRI revealed that when they made errors that they did not consciously recognize, the marijuana abusers showed less activity than the other participants in an area of the brain called the anterior cingulate cortex (ACC). The authors caution that marijuana withdrawal may have played some role in the lack of error awareness, as higher scores in several categories on a marijuana craving questionnaire were associated with poorer error awareness. However, if drug abusers cannot monitor their behavior accurately, this deficit in awareness may contribute to their continued use of a drug despite the consequences or to their continued associations with situations that make them liable to relapse.

Hester R, Nestor L, Garavan H. Impaired Error Awareness and Anterior Cingulate Cortex Hypoactivity in Chronic Cannabis Users. Neuropsychopharmacology. 2009 Jun 24. [Epub ahead of print]

Source: NIDA Addiction Research News December 11, 2009

http://www.drugabuse.gov/newsroom/09/NS-12.html

The daily consumption of cannabis predisposes to the appearance of psychosis and schizophrenia, and those episodes of psychosis which are fruit of this substance present certain specific characteristics, both before their appearance and in the clinical presentation of the psychosis.

This is one of the conclusions of the doctoral thesis “Neurodevelopment and environmental stress in initial psychosis: transversal analysis of the ESPIGAS study”, carried out by researcher Miguel Ruiz Veguilla, of the Institute of Neurosciences of the University of Granada (Spain) and supervised by professors Manuel Gurpegui Fernández de Legaria and Jorge Cervilla Ballesteros. Ruiz Veguilla is also the person in charge fo the Unit of Development Neuropsychiatry of Jaén (Spain).
This work has studied the risk factors associated with schizophrenia, identifying and characterizing in depth those psychosis associated with a continual consumption of cannabis. They carried out a study with 92 subjects, 50 of which had developed a psychosis without presenting signs of an “abnormal neurodevelopment”, this is, they had been doing well academically, they had a group of friends (no social isolation) and they presented a good motor coordination. In addition, these subjects did not show a family history of episodes of psychosis in first or second degree.

Identifying a new type of psychosis
The research work carried out by Miguel Ruiz Veguilla has identified a connection between cannabis consumption and psychosis in subjects with a good premorbid performance, and without signs of minor neurological alterations, which in his opinion might point out “a psychopathological way associated with psychosis in subjects with less predisposition”.
Thus, 66% of the patients with psychosis who participated in the study and had a normal neurodevelopment admitted to have consumed cannabis daily or almost every day, whereas 43% of the participants with markers of an abnormal neurodevelopment (those already indicated: bad previous social and academic behaviour, a family history and a “clumsier” attitude when they carry out tasks of motor coordination and complex motor acts) were drug users too.
In the light of the results of his doctoral thesis, the researcher of the University of Granada says that, after having identified a type of psychosis where the environmental factor plays a more relevant role, we should now answer the question of which is the prognosis, in the long term, of those subjects with a good previous behaviour, whose psychosis is associated with a high consumption of cannabis.
The results of this research work have been published in the journals Schizophrenia Research and European Psychiatry.

Source: December 29, 2009, from http://www.sciencedaily.com/releases/2009/03/090325132328.htm

Canadian teenagers are among the largest consumers of cannabis worldwide. The damaging effects of this illicit drug on young brains are worse than originally thought, according to new research by Dr. Gabriella Gobbi, a psychiatric researcher from the Research Institute of the McGill University Health Centre. The new study, published in Neurobiology of Disease, suggests that daily consumption of cannabis in teens can cause depression and anxiety, and have an irreversible long-term effect on the brain.

“We wanted to know what happens in the brains of teenagers when they use cannabis and whether they are more susceptible to its neurological effects than adults,” explained Dr. Gobbi, who is also a professor at McGill University. Her study points to an apparent action of cannabis on two important compounds in the brain — serotonin and norepinephrine — which are involved in the regulation of neurological functions such as mood control and anxiety.
“Teenagers who are exposed to cannabis have decreased serotonin transmission, which leads to mood disorders, as well as increased norepinephrine transmission, which leads to greater long-term susceptibility to stress,” Dr. Gobbi stated.
Previous epidemiological studies have shown how cannabis consumption can affect behaviour in some teenagers. “Our study is one of the first to focus on the neurobiological mechanisms at the root of this influence of cannabis on depression and anxiety in adolescents,” confirmed Dr. Gobbi. It is also the first study to demonstrate that cannabis consumption causes more serious damage during adolescence than adulthood.
Dr. Gabriella Gobbi is a researcher at the neuroscience axis of the Research Institute of the McGill University Health Centre and also a psychiatrist and associate professor at the Department of Psychiatry, McGill University.

Source:
McGill University Health Centre (2009, December 20). Cannabis damages young brains more than originally thought, study finds. ScienceDaily. Retrieved December 29, 2009, from http://www.sciencedaily.com¬ /releases/2009/12/091217115834.htm

Yes, despite what potheads claim. Doctors in Greece compared the mental abilities of 20 people who had smoked dope four times a week for 15 years with 20 who had used it for less than seven years, and 24 never-smokers. They were given 15 words to learn, and asked to repeat them later. The average score for the long-term smokers was 7; for the shorter-term smokers, 9; for the never-users, 12. It is the latest in many studies showing repeated ‘soft’ drug abuse damages the brain. This isn’t surprising because marijuana’s active ingredient, tetrahydro cannabinol (THC), is highly fat-soluble. As our brain is the organ with the highest concentration of fat, THC makes a beeline for it and stays there for

Source: The Guardian Saturday September 30, 2006

NIDA Research Reveals Subconscious Signals Can Trigger Drug Craving Circuits

Using a brain imaging technology called functional magnetic resonance imaging (fMRI), scientists have discovered that cocaine-related images trigger the emotional centers of the brains of patients addicted to drugs — even when the subjects are unaware they’ve seen anything. The study, published Jan. 30 in the journal PLoS One, was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

A team of researchers at the University of Pennsylvania, led by Dr. Anna Rose Childress and Dr. Charles O’Brien, showed cocaine patients photos of drug-related cues like crack pipes and chunks of cocaine. The images flashed by in just 33 milliseconds — so quickly that the patients were not consciously aware of seeing them. Nonetheless, the unseen images stimulated activity in the limbic system, a brain network involved in emotion and reward, which has been implicated in drug-seeking and craving.

“This is the first evidence that cues outside one’s awareness can trigger rapid activation of the circuits driving drug-seeking behavior,” said NIDA director Dr. Nora Volkow. “Patients often can’t pinpoint when or why they start craving drugs. Understanding how the brain initiates that overwhelming desire for drugs is essential to treating addiction.”

To verify that the patterns of brain activity triggered by the subconscious cues reflected the patients’ feelings about drugs, Childress and her colleagues gave the patients a different test two days later, allowing them to look longer at the drug images. The patients who demonstrated the strongest brain response to unseen cues in the fMRI experiment also felt the strongest positive association with visible drug cues. Childress notes, “It’s striking that the way people feel about these drug-related images is accurately predicted by how strongly their brains respond within just 33 milliseconds.”

Childress and her colleagues also found that the regions of the brain activated by drug images overlapped substantially with those activated by sexual images. This finding supports the scientific consensus that addictive drugs usurp brain regions that recognize natural rewards needed for survival, like food and sex.

According to Childress, these results could improve drug treatment strategies. “We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system. We are looking at the potential for new medications that reduce the brain’s sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges.”

Source: http://www.plosone.org/doi/pone.0001506 29.01.08

Research Summary
Animal studies show that amphetamines are converted into free radicals in the brain, which in turn can cause brain damage, HealthDay News reported April 13.
University of Toronto researchers said the mouse studies could explain how methamphetamine causes brain damage, even after the drug has been metabolized out of the body. The study authors said the enzyme prostaglandin H synthase (PHS) appears to play a role in converting amphetamines into free radicals, which can cause neurodegenerative diseases like Parkinson’s and Alzheimer’s.
Source: April 2006 issue of the FASEB (Federation of American Societies for Experimental Biology) Journal.

People who smoke different strains of cannabis appear to have different psychological symptoms, depending on the cannabinoid combination contained within a particular strain, UK study findings suggest.

Two of the various cannabinoids contained in cannabis – delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) – have almost opposing action, as THC is psychomimetic and CBD is anxiolytic and possesses antipsychotic properties.

To examine the ink between proneness to psychosis and the presence of delusions and the ratio of CBD to THC, Celia Morgan and H Valerie Curran, from University College London, studied 140 individuals from an ongoing longitudinal drug study.

Hair samples were analyzed using gas chromatography/mass spectrometry for the presence of cannabinoids, allowing the identification of 20 individuals with only THC in their hair, 27 with THC+CBD, and 85 with no cannabinoids. The eight individuals who screened positive for CBD only in their hair were excluded due to the small number.

In order to assess psychosis proneness, the team administered the short form of the Oxford Liverpool Inventory of Life Experiences (OLIFE) questionnaire, while Peter’s Delusion Inventory (PDI) was used to examine delusional thinking.

There were no significant differences between the THC and THC+CBD groups in terms of THC levels, and no differences between the three groups in terms of age or drug use other than cannabis. There were no significant differences in the subjective estimates of cannabis use between the THC and THC+CBD groups, aside from the number of days taken to smoke 3.5 g, at 10.2 days versus 5.0 days.

Individuals in the THC group had significantly higher scores on the OLIFE factor of unusual experiences, a marker for positive schizophrenia-like symptoms, than both the THC+CBD and controls groups, while THC+CBD individuals had significantly lower introvertive anhedonia scores than both controls and THC individuals.

Furthermore, THC individuals had significantly higher scores than controls on the PDI, at averages of 8.15 versus 5.48, with THC+CBD patients showing only a trend for greater scores, at an average of 7.22.

The team writes in the British Journal of Psychiatry: “This study is the first to demonstrate that hair analytic techniques can be used to define subsets of cannabis users. The implications of these findings are that people who smoke different strains of cannabis manifest different psychological symptoms.”

They add: “Moreover, this suggests that smoking strains of cannabis containing CBD in addition to THC may be protective against the psychotic-like symptoms induced by THC alone.”

Source : Apr 18, 2008 MedWire News Current Medicine Group

Drinking alcohol at a young age, while the brain is still forming, causes cognitive and structural damage which could be irreversible.
“Studies have proven that alcohol causes brain atrophy,” said Dr. Nicole Gorman, a pediatrician at Village Pediatrics in Westport. “The bottom line is that alcohol stops brain cells from growing.”
Adolescence is the time when the hippocampus, the pre-frontal area of the brain located behind the forehead, is developing significant functions. These include forming its capacity for memory, thinking clearly, impulse control, spatial learning, planning and decision making. After spending more than two decades of analyzing the effects of alcohol on adolescents, the American Medical Association concurs that alcohol can produce both short term and, in many cases, long term damage.
Research studies concluded that teens who drink alcohol score considerably lower on tests involving their cognitive skills. These studies looked at their ability to process general information, including use of vocabulary and verbal and non-verbal information recall.
What is perhaps most alarming is that, according to its Web site, the brain might not be able to “catch up” once this crucial development phase is disrupted and altered by the presence of alcohol.
Dr. Joseph Russo of the Recovery Center of Westport explains that once the brain’s biochemical circuits get “hard-wired,” it’s difficult to alleviate the negative effects of substance abuse.
His colleague, Clarisse Loughrin, a substance abuse counselor, agreed. “The longer someone waits to start treatment the longer it will take,” she said. “And, when you start drinking and drugging at a younger age, the damage is greater and takes even longer.”
Along with physical consequences, alcohol also adversely affects a young person’s emotional growth. “Alcohol has a lot of depressive effects,” said Gorman. “In our practice, we already see many cases of depression in young people.” Teens who are suffering from depression might try to self-medicate themselves by binge drinking. Assuming that they are alleviating unwanted feelings, they are actually adding to their problem because alcohol is, in fact, a depressant.
Conversely, when people are abusing alcohol and drugs, it is more difficult to diagnose clinical depression, anxiety and other mood disorders. Studies have also linked underage drinking with a rise in violent behaviors and suicidal thoughts.
Gorman said that she also has young patients who come to her complaining of sleep disorders. However, this problem, too, is exacerbated by drinking alcohol”Someone might think that a drink or two will help them to sleep better but it’s actually only going to make things worse,” she said.
Characterized by risk-taking behaviors and low impulse control, adolescence is often a time when young people make poor behavioral choices. In attempting to break away from their parents and the embark on process of self actualization, teens could readily view drinking as a benign activity. In their struggle for independence, they defy parental authority with proclamations of “everyone is doing it” and “it won’t hurt me.”
Gorman cautions parents, though, about being “naive” and mistakenly thinking that an honors student or otherwise “good kid” could not be indulging in risky behaviors. “Alcohol should be placed in a locked place where kids do not have access to it,” Gorman said.
Source: www.westport-news.com 2nd Dec. 2009

Conflicting evidence exists regarding the long-term effects of cannabis use, according to background information in the article. “Although growing literature suggests that long-term cannabis use is associated with a wide range of adverse health consequences, many people in the community, as well as cannabis users themselves, believe that cannabis is relatively harmless and should be legally available,” the authors write. “With nearly 15 million Americans using cannabis in a given month, 3.4 million using cannabis daily for 12 months or more and 2.1 million commencing use every year, there is a clear need to conduct robust investigations that elucidate the long-term sequelae of long-term cannabis use.”

Murat Yücel, Ph.D., M.A.P.S., of ORYGEN Research Centre and the Melbourne Neuropsychiatry Centre at the University of Melbourne, Australia, and colleagues from the University of Wollongong performed high-resolution structural magnetic resonance imaging on 15 men (average age 39.8 years) who smoked more than five joints daily for more than 10 years. Their results were then compared with images from 16 individuals (average age 36.4) who were not cannabis users. All participants also took a verbal memory test and were assessed for subthreshold (below the standard of disease diagnosis) symptoms of psychotic disorders, which include schizophrenia and mania.

The hippocampus, thought to regulate emotion and memory, and the amygdala, involved with fear and aggression, tended to be smaller in cannabis users than in controls (volume was reduced by an average of 12 percent in the hippocampus and 7.1 percent in the amygdala). Cannabis use also was associated with sub-threshold symptoms of psychotic disorders. “Although cannabis users performed significantly worse than controls on verbal learning, this did not correlate with regional brain volumes in either group,” the authors write.

“There is ongoing controversy concerning the long-term effects of cannabis on the brain,” the authors write. “These findings challenge the widespread perception of cannabis as having limited or no neuroanatomical sequelae. Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue. Further prospective, longitudinal research is required to determine the degree and mechanisms of long-term cannabis-related harm and the time course of neuronal recovery after abstinence.”

Source: Arch Gen Psychiatry, 2008;65(6):694-701

Francesca M. Filbeya, et alCraving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue.

These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems
related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis
dependence.

The relationship between craving and drug use behavior is an integral piece of the addiction puzzle. Craving is considered the intense desire for a rewarding object or experience. Cue elicited
craving, induced by exposure to alcohol- or drug-related cues, is a particularly potent form of craving. Previous investigators have reported that subjective craving increases after exposure to cues specific to a variety of drugs of abuse, including cocaine (e.g., tactile cues, videos, i.v. administration, images, guided imagery) heroin (e.g., images) alcohol (e.g., alcohol taste, images, alcohol-related words), and tobacco (e.g., visual and tactile presentations) .

Cue-elicited craving for alcohol and tobacco in particular have important clinical implications and have been the focus of psychosocial and pharmacological intervention efforts.

The advent of functional neuro-imaging has allowed studies of cue-elicited craving to elucidate the neurobiological mechanisms that accompany increased craving. Such neuro-imaging studies
have associated craving with increased activation of reward pathways . The reward circuits involve the dopamine projection from the ventral tegmental area (VTA) to striatal areas (e.g., nucleus accumbens) and the prefrontal cortex (PFC), the repeated activation of which underlies the attribution of incentive salience to otherwise neutral stimuli . Other reward-related areas, including the insula and cingulated gyrus show increased activity with the presentation of drug-related stimuli. Presentation of these stimuli is also associated with increased activity in brain structures that underlie reward and emotion regulation, such as the thalamus and amygdala.

The few published studies of cue-elicited craving for marijuana suggest that it is a reliable and valid phenomenon, analogous to cue-elicited craving for other drugs of abuse. Marijuana-related cues presented in a variety of sensory modalities, elicit increases in self-reported craving. For example, auditory-presented imagery scripts induce craving in marijuana smokers, and the magnitude of this craving varies as a function of the amount of marijuana-related content presented in the script . Craving also increases when abstinent frequent marijuana users are exposed to an auditory script that is paired with a tactile cue, such as a used marijuana pipe or bong .

Importantly, in this paradigm, cue presentation increases craving beyond the effects induced by abstinence. Additionally, marijuana related visual cues elicit greater craving in chronic heavy users than in controls; physiologically, users demonstrate greater skin conductance and larger late positivity of visual event-related brain potentials than controls in response to these stimuli .

The present study was designed to examine the effects of marijuana-related cues on the activation of reward circuitry, and to examine the relationship between these effects and the behavioral symptoms of cannabis dependence. We hypothesized that among regular marijuana users, marijuana-related cues compared with neutral cues, would elicit greater blood oxygen level dependent (BOLD) activity in reward structures (i.e., VTA, striatum, anterior cingulate, and insula). Furthermore, we hypothesized that the magnitude of this response would be associated with the number of problems related to marijuana use.

Results

Compared with the neutral cue, presentation of the marijuana cue elicited significantly greater BOLD activation in a large cluster encompassing several areas, including the VTA, dorsal anterior cingulate cortex, cerebellum, thalamus, pre- and postcentral gyri, inferior frontal gyrus/insula, thalamus, amygdala,

fusiform gyrus, pre- and postcentral gyri, inferior parietal lobe, and superior temporal gyrus (cluster-corrected z_2.3, P_0.05)

BOLD response in several of these differentially activated areas was also significantly positively correlated with total marijuana problem scale (MPS) score (cluster-corrected z _ 2.3, P _ 0.05). These areas included the orbitofrontal cortex (OFC) and nucleus accumbens (NAc) The analyses of correlations with the Structured Clinical Interview for DSM Disorders (SCID) total symptom count, subjective urge ratings, frequency, and duration of use did not meet the significance threshold.

Source: 13016–13021 _ PNAS _ August 4, 2009 _ vol. 106 _ no. 31 www.pnas.org_cgi_doi_10.1073_pnas.0903863106

A tiny genetic mutation is the key to understanding why nicotine–which binds to brain receptors with such addictive potency–is virtually powerless in muscle cells that are studded with the same type of receptorBy all rights, nicotine ought to paralyze or even kill us, explains Dennis Dougherty, the George Grant Hoag Professor of Chemistry at Caltech and one of the leaders of the research team. After all, the receptor it binds to in the brain’s neurons–a type of acetylcholine receptor, which also binds the neurotransmitter acetylcholine–is found in large numbers in muscle cells. Were nicotine to bind with those cells, it would cause muscles to contract with such force that the response would likely prove lethal. Obviously, considering the data on smoking, that is not what happens. The question has long been: Why not?

“It’s a chemical mystery,” Dougherty admits. “We knew something subtle had to be going on here, but we didn’t know exactly what.” That subtlety, it turns out, lies in the slight tweaking of the structure of the acetylcholine receptor in muscle cells versus its structure in brain cells.
The shape of the acetylcholine receptor, and the way the chemicals that bind with it contort themselves to fit into that receptor, is determined by a number of different weak chemical interactions. Perhaps most important is an interaction that Dougherty calls “underappreciated”–the cation-π interaction, in which a positively charged ion and an electron-rich π system come together.

Back in the late 1990s, Dougherty and colleagues had shown that the cation-π interaction is indeed a key part of acetylcholine’s ability to bind to the acetylcholine receptors in muscles. “We assumed that nicotine’s charge would cause it to do the same thing, to have the same sort of strong interaction that acetylcholine has,” says Dougherty. “But we found that it didn’t.”
This would explain why smoking doesn’t paralyze us; if the nicotine can’t get into the muscle’s acetylcholine receptors, it can’t cause the muscles to contract.

But how, then, does nicotine work its addictive magic on the brain? It took another decade for the scientists to be able to peek at what happens in brain cells’ acetylcholine receptors when nicotine arrives on the scene. Turns out that in brain cells, unlike in muscle cells, nicotine makes the exact same kind of strong cation-π interaction that acetylcholine makes in both brain and muscle cells. “In addition,” Dougherty notes, “we found that nicotine makes a strong hydrogen bond in the brain’s acetylcholine receptors. This same hydrogen bond, in the receptors in muscle cells, is weak.”

The cause of this difference in binding potency, says Dougherty, is a single point mutation that occurs in the receptor near the key tryptophan amino acid that makes the cation-π interaction. “This one mutation means that, in the brain, nicotine can cozy up to this one particular tryptophan much more closely than it can in muscle cells,” he explains. “And that is what allows the nicotine to make the strong cation-π interaction.”

Dougherty says the best way to visualize this change is to think of the receptor as a box with one open side. “In muscle cells, this box is slightly distorted, so that the nicotine can’t get to the tryptophan,” he says. “But in the brain, the box is subtly reshaped. That’s the thing: It’s the shape, not the composition, of the box that changes. This allows the nicotine to make strong interactions, to become very potent. In other words, it’s what allows nicotine to be addictive in the brain.”

“Several projects in our labs are converging on the molecular and cellular mechanisms of the changes that occur when the brain is repeatedly exposed to nicotine,” adds study coauthor Henry Lester, the Bren Professor of Biology at Caltech. “We think that the important events begin with the rather tight and selective interaction between nicotine and certain receptors in the brain. This Nature paper teaches us how this interaction occurs, at an unprecedented level of resolution.”
Dougherty notes that these findings might one day lead to better drugs to combat nicotine addiction and other neurological disorders. “The receptor we describe in this paper is an important drug target,” he says. “It might help pharmaceutical companies develop a better drug than nicotine to do the good things nicotine does–enhance cognition, increase attention–without being addictive and toxic.”

Source: Xiu et al. Nicotine binding to brain receptors requires a strong cation–π interaction. Nature, March 26, 2009; DOI: 10.1038/nature07768 Science Daily 29.03.09

Ian Sample, science correspondent
The Guardian
Tuesday June 3 2008

Smoking cannabis for long periods of time may shrink parts of the brain that govern memory, emotion and aggression, according to researchers in Australia. Scientists used magnetic resonance imaging to scan the brains of people who admitted to smoking more than five joints a day for at least 10 years and compared them with brain images taken from non-drug users.

Those who smoked cannabis regularly had on average a 12% smaller hippocampus, the part of the brain which is thought to be involved with emotion and memory, and a 7% smaller amygdala, which plays a role in regulating fear and aggression.

For the study, researchers imaged the brains of 15 cannabis smokers and 16 individuals who did not use the drug. The scientists, led by Murat Yücel at the University of Melbourne and colleagues at the University of Wollongong, said scans on larger numbers of people were needed to confirm the extent of the effect.

“Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue,” the scientists report in the journal Archives of General Psychiatry.

Cannabis users also fared worse in tests of verbal memory and were more likely to have low-level symptoms of psychotic disorders such as schizophrenia and mania.

Last month, a team at New York University scanned the brains of a group of 17- to 30-year-olds who had smoked cannabis two to three times a week for at least a year. In that study, the brains of drug users looked no different from those who had never taken cannabis.

In 2004, Cyril D’Souza, a professor of psychiatry at Yale University, reported that THC, the active ingredient in cannabis, caused fleeting schizophrenia-like symptoms in users, ranging from suspiciousness and delusions to poor memory and attention span.

Source: http://www.guardian.co.uk/science/2008/jun/03/drugs.drugsandalcohol

It  was fascinating to note in the opening line of one of the recent papers on Alzheimer’s Disease that hippocampal atrophy (or wasting) is completely accepted as a hallmark feature!
 
You will recall the recent Australian Study (abstract below) which demonstrated unequivocally even in quite small samples (of 15 patients in control and THC groups) that cannabis atrophies the hippocampus!
 
Sounds like we need to tell the world!Dr.Stuart Reece, Australia.

 
Alzheimer’s disease (AD) is a genetically heterogeneous disorder characterized by early hippocampal atrophy and cerebral amyloid-β (Aβ) peptide deposition. Using TissueInfo to screen for genes preferentially expressed in the hippocampus and located in AD linkage regions, we identified a gene on 10q24.33 that we call CALHM1. We show that CALHM1 encodes a multipass transmembrane glycoprotein that controls cytosolic Ca2+ concentrations and Aβ levels. CALHM1 homomultimerizes, shares strong sequence similarities with the selectivity filter of the NMDA receptor, and generates a large Ca2+ conductance across the plasma membrane. Importantly, we determined that the CALHM1 P86L polymorphism (rs2986017) is significantly associated with AD in independent case-control studies of 3404 participants (allele-specific OR = 1.44, p = 2 × 10-10). We further found that the P86L polymorphism increases Aβ levels by interfering with CALHM1-mediated Ca2+ permeability. We propose that CALHM1 encodes an essential component of a previously uncharacterized cerebral Ca2+ channel that controls Aβ levels and susceptibility to late-onset AD.
Source: Cell, Vol 133, 1149-1161, 27 June 2008
 
Regional brain abnormalities associated with long-term heavy cannabis use.
CONTEXT: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain. OBJECTIVE: To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala. DESIGN: Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging. SETTING: Participants were recruited from the general community and underwent imaging at a hospital research facility. PARTICIPANTS: Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years). MAIN OUTCOME MEASURES: Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured. RESULTS: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group. CONCLUSIONS: These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.

Source:  Arch Gen Psychiatry. 2008 Jun;65(6):694-701

Alterations in a molecular brain pathway activated by marijuana may contribute to the cognitive symptoms of schizophrenia, according to a report in the July issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Expression of the cannabinoid 1 receptor (CB1R), the site of action of the main chemical ingredient of marijuana, is significantly reduced in the brains of individuals with schizophrenia. Activation of CB1R impairs signaling by gamma-aminobutyric acid (GABA), an important neurotransmitter essential for core cognitive processes such as working memory. The use of marijuana in individuals with schizophrenia appears to worsen this deficit in GABA synthesis.
Since reduced GABA is known to be present in schizophrenia, these findings suggest possible new drug targets that could help to improve function in people with the mental illness, University of Pittsburgh School of Medicine researchers report.
“Heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia, and the course of illness is worse for people with schizophrenia who use marijuana,” said David A. Lewis, M.D., corresponding author of the study and UPMC Endowed Professor in Translational Neuroscience, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. “We wanted to understand the biological mechanisms that could explain these observations, and with this study, I believe that we can narrow down at least part of the ‘why’ to CB1R, the receptor for both tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and the brains own cannabinoid chemical messengers.”
Dr. Lewis and his colleagues examined specimens of brain tissue collected after death from 23 people with schizophrenia and 23 normal comparison subjects matched for a number of factors, including age and sex. The researchers evaluated levels of CB1R messenger RNA and protein, and also measured levels of glutamic acid decarboxylase (GAD-67), an enzyme that makes GABA, and cholecystokinin (CCK), a neuropeptide released from GABA neurons that, among other actions, regulates the production of the brain’s own cannabinoids.
“CB1R levels were significantly 15 percent lower in the subjects with schizophrenia,” Dr. Lewis said. “We measured these biochemical messengers using three techniques, and each time got the same answer — less CB1R in people with schizophrenia.” This reduction, he noted, appears to be the brain’s way of compensating for lower levels of GABA, and the use of marijuana defeats this compensation.
“These findings may provide insight into the biological basis of why cannabis use worsens schizophrenia, and, as a result, identify a novel target for new drug development that could improve treatments available for schizophrenia,” said Dr. Lewis.
Other authors include Stephen M. Eggan, Ph.D., and Takanori Hashimoto, M.D., Ph.D., both of the Department of Psychiatry, University of Pittsburgh School of Medicine.
The study was funded by the National Institutes of Health. Additional funding support for Dr. Eggan came from the University of Pittsburgh’s Andrew Mellon Predoctoral and Scottish Rite fellowships.Source: University of Pittsburgh Schools of the Health Sciences (2008, July 8). Schizophrenia Linked To Dysfunction In Molecular Brain Pathway Activated By Marijuana. ScienceDaily. Retrieved July 18, 2008, from http://www.sciencedaily.com¬ /releases/2008/07/080707161411.htm

Scientists at the National Institute on Drug Abuse’s (NIDA) Intramural Research Program in Baltimore, MD, have confirmed for the first time in humans that chemically blocking the body’s cannabinoid receptors can significantly reduce the effects of smoked marijuana. The study appears in the April 14th issue of the Archives of General Psychiatry.Cannabinoid receptors – proteins on the surface of brain cells — are most dense in brain regions involved in thinking and memory, attention and control of movement. Their exact role in humans is not well understood, but animal studies have shown that cannabinoid receptor agonists – compounds that activate the receptor sites – impair learning and memory and increase appetite and food intake. Previous studies in animals have shown that the major effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. These effects appear to be lessened when cannabinoid receptors are blocked by an antagonist.
 
“This research helps point the way toward possible treatment for those addicted to marijuana and perhaps may be useful in finding effective treatments for other disorders related to the cannabinoid system, ” says NIDA director Dr. Alan I. Leshner.
In the study, Dr. Marilyn Huestis and her NIDA colleagues used a cannabinoid receptor antagonist – a compound that binds to the receptor and blocks agonist compounds from activating it. The antagonist, SR141716, was discovered by Sanofi-Synthelabo of Paris, France, and was used in this study with NIDA under a Cooperative Research and Development Agreement (CRADA).
Participants in the study were given either SR141716 or a placebo and two hours later smoked one marijuana cigarette. Those who received SR141716 showed significantly reduced marijuana effects, while those who received the placebo showed typical marijuana intoxication.
The results of the study are an important step in understanding the complex role of the cannabinoid receptor system in the human brain.
“Our findings of a significant blockade of marijuana’s effects after treatment with SR141716, which is highly selective for the CB1-cannabinoid receptor sites, demonstrates for the first time in humans that these receptors play a major role in mediating the effects of marijuana,” Dr. Huestis says.
In their investigation of the role of the cannabinoid system in humans, Dr. Huestis and her colleagues gave increasing doses of SR141716 or placebo to 63 adult men with histories of marijuana use. When individuals received SR141716 before smoking marijuana, there was a dose-dependent reduction in psychological and physical effects of marijuana. At the highest dose of SR141716 (90 mg), volunteers reported a 43% reduction in how “high” they felt, a 38% reduction in how “stoned” they were, and a 43% reduction in “drug effect” as compared to those who received active marijuana and no antagonist. In addition, they had a 59% less increase in heart rate, one of the primary physical effects of marijuana.
The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world’s research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish by calling NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov.

Source: . ScienceDaily. Retrieved July 23, 2008, from http://www.sciencedaily.com¬ /releases/2001/04/010413080431.htm

ScienceDaily (Aug. 16, 2008) — A possible future way to prevent relapses into drug dependence has been discovered by researchers at Linköping University and the German cancer research center DKFZ. The target is the dopamine-producing nerve cells in the midbrain.Earlier research has shown that these cells become more excitable when a person takes drugs. To find out the functional meaning of this, these researchers used a mouse model for cocaine dependence. When they blocked the cells’ receptors for glutamate ¬- the brain’s most important signal substance -¬ the risk of relapsing into addiction vanished. The findings are being published in Neuron.
Dopamine-producing nerve cells are central to the brain’s reward system. Dependence-inducing drugs cause concentrations of dopamine to rise in the surroundings, which in turn affects other nerve cells and brings about various physical and mental reactions.
Cocaine has a very rapid impact on dopamine levels, which explains why it is one of the most addictive drugs.
“When you take cocaine, the number of glutamate receptors increases, rendering the cell more excitable. When we block this process, we prevent relapses into addiction. This is interesting clinically since that is the phase when we can get hold of patients,” says David Engblom, a neurobiologist at Linköping University and the study’s lead author.
An addict who wants to give up drugs could thus be offered a ‘vaccination’ against relapsing. But much more research remains to be done before such treatment can become a reality.

Source: Vetenskapsrådet (The Swedish Research Council) (2008, August 16). Mechanism Behind Cocaine Craving Identified. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2008/08/080815073522.htm

Scientists at Oregon Health Sciences University have discovered that mice lacking a certain brain cell receptor for the chemical messenger dopamine are supersensitive to alcohol, cocaine and methamphetamine. Their findings appear in the September 19, 1997, issue of the journal Cell and detail the increased locomotor activity of mice who lack the D4 receptor.”Branching nerve cells communicate with each other by secreting chemical messengers like dopamine that bind to receptors on neighboring nerve cells in a lock-and-key fashion,” explains, David Grandy, Ph.D., OHSU scientist and senior author of the article. “Dopamine is one of the primary chemical messengers, or neurotransmitters, and plays numerous complex roles in both movement and emotional states. Disturbances in the dopamine system are known to be associated with human disorders such as Parkinson’s disease, schizophrenia and addiction. Dopamine producing neurons continue to be the focus of research because of their widespread importance in regulating complex locomotor, emotional and motivational states.”
Grandy further explains that dopamine producing neurons are involved in mediating some of the positive reinforcing properties shared by drugs of abuse such as alcohol, cocaine, methamphetamine and opiates.
“We examined mice that were genetically engineered to lack the D4 dopamine receptor to investigate the role of this receptor in mediating the effects of various drugs,” says Grandy. “We discovered that mice given either alcohol, cocaine or methamphetamine displayed a dramatic increase in locomotor activity compared to normal mice. Prior to their treatment with these drugs, the mutant mice tended to be less active than normal mice. Following treatment their activity level increased greatly compared to normal mice.
“Based on the observation that mice lacking the D4 receptor show a supersensitivity to certain drugs of abuse, we speculate that the D4 receptor is implicated in modulating the effects of such drugs,” says Grandy. “Consequently, the D4 receptor may be a new target for the treatment of drug abuse.”
Grandy explains that humans show a wide variability in the gene that encodes the D4 receptor, and there are reports that some forms of the D4 gene may predispose an individual to drug taking and novelty seeking behaviors. The D4 receptor has been the focus of intense interest since its discovery in 1990 because of its high affinity for the antipsychotic drug clozapine, which is used to treat schizophrenia. Recently, several new D4-selective drugs that are similar to clozapine have been developed and are currently undergoing clinical trials for the treatment of schizophrenia. In addition to shedding light on the role that the D4 receptor plays in an organism*s response to drugs like alcohol, cocaine and methamphetamine, the new research reported by Grandy and his colleagues underscores the relevance of this receptor to antipsychotic drug development.

Source: Oregon Health Sciences University (1997, September 23). OHSU Scientists Discover Mice Lacking Dopamine Receptor Are Supersensitive To Alcohol, Cocaine And Methamphetamine. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/1997/09/970923034045.htm

Scientists have identified a brain mechanism in rats that may play a central role in regulating anxiety and alcohol-drinking. The finding, by researchers supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), could provide important clues about the neurobiology of alcohol-drinking behaviors in humans..”This is an intriguing finding,” notes NIAAA Director Ting-Kai Li, M.D. “These experiments, conducted in rats selectively bred to have a high affinity for alcohol, help us address questions about the potential role that anxiety might play in human alcoholism. These molecular studies also may reveal potential targets for therapy of anxiety and alcoholism.”
Some researchers have suggested that high levels of anxiety may predispose some individuals to becoming alcoholic.
Researchers led by Subhash C. Pandey, Ph.D., Associate Professor and director of neuroscience alcoholism research in the Department of Psychiatry at the University of Illinois and Jesse Brown VA Medical Center in Chicago, found that “P” rats, a strain bred to prefer alcohol, showed more anxiety-like behaviors and drank more alcohol, than non alcohol-preferring “NP” rats. They measured anxiety in the rats with an apparatus known as an elevated plus-maze, which consists of two open arms and two closed arms connected to a central platform. Anxiety is gauged as a function of the amount of time a rat spends in the closed versus the open arms of the maze during a 5-minute testing period — the greater an animal’s level of anxiety, the less open-arm activity it displays.
Dr. Pandey and his colleagues also found that levels of CREB, a protein involved in a variety of brain functions, were lower in certain brain areas of P rats compared with NP rats. Levels of neuropeptide Y (NPY), a molecule that regulates the function of several neurotransmitters and is known to play a role in anxiety and alcohol-drinking behaviors, also were lower in P rats. One function of CREB is to regulate the production of NPY.
“Compared to NP rats, levels of CREB and NPY were innately lower in the central amygdala and medial amygdala of P rats,” explains Dr. Pandey, “brain areas which play a crucial role in anxiety behaviors and which have been shown previously to be involved in rewarding, reinforcing, and motivational aspects of alcohol drinking behaviors. And turning off CREB function in the central amygdala of NP rats makes them look like P rats — more anxious and thus more likely to drink.”
Alcohol intake reduced anxiety-like behaviors in the P rats, an effect that was associated with increased CREB function and NPY production in the central and medial amygdala. And by administering compounds that promote CREB function and NPY production in the central amygdala, researchers were able to reduce anxiety — and alcohol intake — in P rats. On the other hand, by disrupting CREB function (and the concomitant NPY production) in the central amygdala of NP rats, the researchers were able to provoke anxiety-like behavior and promote alcohol intake in those animals.
Dr. Pandey and his colleagues proposed that decreased CREB-dependent NPY production in the central amygdala might be a pre-existing condition for anxiety and alcohol-drinking behaviors.
“Our findings implicate this pathway in genetic predisposition to high anxiety and alcohol-drinking behaviors of P rats,” says Dr. Pandey. “Future studies should explore the relationship of other CREB-related compounds to these phenomena in P rats or other animal models.”

Source: NIH/National Institute on Alcohol Abuse and Alcoholism (2005, October 5). Researchers Shed Light On Anxiety And Alcohol Intake. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2005/10/051005080853.htm

Reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to stop using alcohol.The finding is reported by researchers at the University of Illinois at Chicago and the Jesse Brown VA Medical Center in the April 2 issue of the Journal of Neuroscience.
DNA can undergo changes in function without any changes in inheritance or coded sequence. These “epigenetic” changes are minor chemical modifications of chromatin — dense bundles of DNA and proteins called histones.
“This is the first time anyone has looked for epigenetic changes related to chromatin remodeling in the brain during alcohol addiction,” said Dr. Subhash C. Pandey, professor and director of neuroscience alcoholism research at the UIC College of Medicine and the Jesse Brown VA Medical Center in Chicago, the lead author of the study.
Chemical modification of histones can change the way DNA and histones are wound up together. Histone acetyltransferases (HATs) are enzymes that add acetyl groups to histones and loosen the packing, promoting gene expression. On the other hand, histone deacetylases (HDACs) remove acetyl groups from histones, causing them to wrap with DNA more tightly, decreasing gene expression.
The UIC researchers had previously shown in an animal model that levels of neuropeptide Y in the amygdala modulate anxiety and alcohol-drinking behavior. In the new study, they looked at the HDAC activity, acetylation of histones, and expression of the genes for NPY in the amygdala and the anxiety-like behaviors associated with withdrawal from chronic alcohol use.
Pandey and his colleagues found that acute exposure to alcohol decreases HDAC activity; increases the acetylation histones; increases levels of NPY — and reduced anxiety in the animals.
Conversely, anxiety-like behaviors during withdrawal in animals with chronic alcohol exposure was associated with an increase in HDAC activity and decrease in histones acetylation and NPY levels.
Importantly, blocking the observed increase in HDAC activity using an HDAC inhibitor during alcohol withdrawal brought up histone acetylation and NPY expression levels in the amygdala and prevented the development of anxiety-like behaviors.
“Our findings suggest that HDAC inhibitors may have potential as therapeutic agents in treating alcoholism,” Pandey said.
The researchers also found that levels of a protein known as CREB binding protein, which has HAT enzymatic activity, were increased by acute alcohol but were decreased during ethanol withdrawal.
They concluded that the enzymes that are involved in remodeling of chromatin play an important role in the anxiety that accompanies alcohol withdrawal as well as in the anti-anxiety effects of acute alcohol use.
“We need new strategies to treat alcoholism that are directed toward the prevention of withdrawal symptoms,” Pandey said. “Anxiety associated with withdrawal from alcohol abuse is a key factor in the maintenance of alcohol addiction.”

Source: University of Illinois at Chicago (2008, April 4). Brain DNA ‘Remodeled’ In Alcoholism. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2008/04/080402084340.htm

Doctors may one day be able to control alcohol addiction by manipulating the molecular events in the brain that underlie anxiety associated with alcohol withdrawal, researchers at the University of Illinois at Chicago College of Medicine and the Jesse Brown VA Medical Center report in the March 5 issue of the Journal of Neuroscience.”The association of anxiety with increased alcohol use is a key factor in the initiation and maintenance of alcohol addition,” says Dr. Subhash Pandey, UIC professor of psychiatry and director of neuroscience alcoholism research, the lead author of the study.
Previous research has shown that people with inherently high levels of anxiety are at an increased risk of becoming alcoholics. In addition, withdrawal of alcohol in chronic users is often accompanied by extreme anxiety.
“Alcoholics may feel a need to continue to drink alcohol in an attempt to self-medicate to reduce their anxiety and other unpleasant withdrawal symptoms,” said Pandey.
Pandey and his colleagues have discovered the molecular basis for the link between anxiety and alcohol addiction, which may help in identifying new therapeutic strategies for the treatment of alcohol addiction.
The researchers found that a protein within neurons in the amygdala — the area of the brain associated with emotion and anxiety — controls the development of alcohol withdrawal symptoms and drinking behaviors in laboratory animals by changing the shape of the neurons. This change in shape affects the communication between neurons, leading to changes in behavior.
Neurons communicate by sending signals through branches called dendritic spines. The researchers found that short-term alcohol exposure increased the number of dendritic spines in certain regions of the amygdala, producing anti-anxiety effects. Alcohol-dependent animals eventually developed a tolerance to the anxiety-lowering effects of alcohol.
The researchers traced the anti-anxiety effect to the production of a particular protein, Arc, in response to a nerve growth factor called BDNF that is stimulated by alcohol exposure. BDNF is vital in the functioning and maintenance of neurons.
When alcohol was withheld from animals that had been chronically exposed, they developed high anxiety. Levels of BDNF and Arc — and the number of dendritic spines — were decreased in the amygdala. But the researchers were able to eliminate the anxiety in the alcohol-dependent animals by restoring BDNF and Arc to normal levels.
Pandey suggested that an initial easing of anxiety may encourage people to begin to use alcohol, while for chronic users, a lack of alcohol provokes high anxiety, creating a need to continue drinking to feel normal.
The researchers blocked Arc production in normal rats by injecting a complementary sequence to Arc gene DNA into the central amygdala. They found that when levels of Arc in the central amygdala were lowered, the spines decreased and anxiety and alcohol consumption increased. When levels of Arc were returned to normal three days post-injection, anxiety and alcohol consumption also returned to normal. In a previous study, researchers found that lowering BDNF in amygdala promoted anxiety and alcohol drinking.
“This is the first direct evidence of the molecular processes occurring in the neurons that is responsible for the co-morbidity of anxiety and alcoholism, which we believe plays a major role in the addictive nature of alcohol,” said Pandey.
“This offers the possibility of new therapeutic target — BDNF-Arc signaling and associated dendritic spines in the amygdala — or new drug development.”
“These observations by Dr. Pandey’s research group provide an insight into the link between alcohol and anxiety and could be used to identify new targets for developing medications that alleviate withdrawal-induced anxiety and potentially modify a motivation for drinking,” said Antonio Noronha, director of neuroscience and behavior research at the National Institute on Alcohol Abuse and Alcoholism.
The work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the Department of Veterans Affairs. Huaibo Zhang, Rajesh Ugale, Anand Prakash, Tiejun Xu and Kaushik Misra of the UIC College of Medicine and the Jesse Brown VA Medical Center also contributed to the study.

Source: University of Illinois at Chicago (2008, March 5). Brain Chemistry Ties Anxiety And Alcoholism. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2008/03/080304173356.htm

Research SummaryA brain imaging study conducted by researchers at Massachusetts General Hospital revealed that abnormalities appearing in the cerebral cortex of cocaine addicts correlate with dysfunction in regions of the brain responsible for attention and reward-based decision-making. 
While some of these abnormalities may reflect a predisposition to drug use, others may result from long-term cocaine exposure. “These data point to a mixture of both drug effects and predisposition underlying the structural alterations we observed,” said Hans Breiter principal investigator of the Phenotype Genotype Project in Addiction and Mood Disorder.
Magnetic resonance imaging studies of 20 cocaine addicts and 20 control participants were used to determine variations in cortical thickness. Compared to the healthy controls, the cocaine addicts had significantly less overall cortical volume. The difference was markedly apparent in areas that control reward functioning and decision-making. In addition, typical differences in thickness in the frontal regions of the cortex was reversed for the addicts compared to non-addicts.
“The severity of these cortical alterations point to the potential importance of prevention efforts to keep susceptible individuals from beginning to use cocaine,” Breiter said. He suggested that further large-scale testing of individuals with different addictions is needed “to see if these findings are limited to cocaine users.”

Source The report appears in the Oct. 9, 2008 issue of the journal Neuron.

DAZED AND CONFUSED: Marijuana muddles memory, and it may be because THC disrupts the synchronous firing of brain cells.
Marijuana–and its active ingredient, Δ9-tetrahydrocannabinol (THC)–has muddled memories for millennia. But how exactly the wacky weed interferes with remembrance of things past–as well as attention span and speech, among other things–has never been clear. Now neuroscientists have discovered that cannabinoids diminish the brain waves of rats–and disrupt the symphony of synchronous brain cell firing that may be essential for memory.
Neuroscientist David Robbe of Rutgers University and his colleagues tested the impact of THC and a synthetic cannabinoid on rats that had their heads restrained. The drugs affected certain brain waves: the theta (four to 12 hertz) and fast ripple (100 to 200 hertz) waves diminished significantly, whereas the drug had a slightly lesser impact on gamma (30 to 80 hertz) waves. Because theta and gamma oscillations are thought to play a critical role in creating and storing short-term memories–and fast ripple oscillations may allow such short-term memories to be moved into long-term storage–this suppression could mean missing memories for the rats.
In fact, rats that had been trained to follow a specific series of turns to get water–and did fine on the test before being intravenously injected with the drug–found themselves wandering in a daze under its influence. And when the researchers injected the synthetic cannabinoid directly into three rats’ brains, it completely disrupted the otherwise synchronized pattern of the firing of their neurons: they fired as much as before, but in a more random pattern. And other types of brain cells, such as interneurons and pyramidal cells, fell out of step as well, although, interestingly, their overall activity actually increased (perhaps an explanation for the random nature of thoughts generated by use of the drug).
The finding suggests that this disruption of synchronized brain cell firing might be responsible for marijuana’s memory distortions. “Overall, our findings indicate that under the influence of cannabinoids, neurons are liberated from population control,” the researchers write in the paper presenting the finding published in the December issue of Nature Neuroscience. This, they argue, is the direct cause of memory impairment. But the research also reveals that at the highest doses of synthetic cannabinoid, the rats failed to discover the right sequence of turns altogether. In other words, there may be a threshold level of the drug that entirely prohibits learning, and that is something worth remembering very clearly.
Source:  Scientific American. Nov.2006

Two recently published research papers have used functional MRI (fMRI) to show how the two main constituents of cannabis Tetrahydrocannabinol (THC) and Cannabidiol (CBD) act on the brain to modulate cognitive function and psychiatric  symptoms.
Cannabis is the world’s most widely used illicit drug and has a wide range of psychological and symptomatic effects.  In the short term cannabis can induce psychotic symptoms and anxiety, while regular use is associated with cognitive impairments and an increased risk of schizophrenia.  
Talking about the latest research published by the Institute of Psychiatry at King’s College London, into the effects of cannabis, Professor Philip McGuire one of the authors said: “The Institute has been at the forefront of research into the adverse psychiatric effects of cannabis use.  These new findings further develop scientific understanding in this area by indicating how the two main psychoactive constituents of cannabis act on the brain to alter cognitive function and induce psychiatric symptoms.
The studies were initiated by Philip McGuire and Zerrin Atakan from the Institute of Psychiatry at King’s, Jose Crippa from Ribeirão Preto, Brazil and Rocio Martin-Santos in Barcelona, Spain.   They and a team of researchers at the Institute used functional magnetic resonance imaging and behavioural measures to assess the impact on brain function in healthy male volunteers.  Each subject was scanned on three occasions at monthly intervals, with each scan preceded by the administration of either THC, CBD or a placebo.
In the first paper published in Biological Psychiatry in December 2008, ‘Neural Basis of Δ-9-Tetrahydrocannabinol and Cannabidiol: Effects During Response Inhibition’ the researchers considered the effects of THC and CBD on brain function during a Go/No Go task which requires subjects to over-ride a regular button pressing response.  They found that THC reduced activation in the part of the prefrontal cortex that is normally critical for this ‘response inhibition’ process.  Please refer to the journal for a full copy of the paper. (Biological Psychiatry 64 (11), pp. 966-973) doi:10.1016/j.biopsych.2008.05.011)
In the second paper published in the Archives of General Psychiatry (12 January 2009) ‘Distinct Effects of _9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing’  the researchers investigated the neurophysiological basis of the effects of cannabis on anxiety, using faces that had fearful expressions.  Normally viewing fearful faces provokes anxiety, activates the amygdala, and increases skin conductance (a measure of autonomic arounsal).  Administration of CBD reduced the response of the amygdale to fearful faces, and this effect was correlated with its effect on skin conductance.  Please refer to the Archives of General Psychiatry, January 2009 issues for full copies of this paper.  (Arch Gen Psychiatry, 2009;66 (1): 95-105.)
Professor Philip McGuire concludes, “These studies show that THC and CBD have distinct effects on brain function in humans, and these may underlie their correspondingly different effects on cognition and psychiatric symptoms.  Determining how the constituents of cannabis act on the brain is fundamental to understanding the role of cannabis use in the aetiology of psychiatric disorders.”
Source:  Institute of Psychiatry  20th Jan 2009 

Drug addicts find it harder than non-addicts to derive pleasure from everyday life, new Australian research shows.
The study took in 33 heroin addicts on opiate replacement, whose brain activity was measured as they looked at pictures of drug and non-drug related scenes.
Associate Professor Dan Lubman said the addicts showed elevated responses to drug-related images compared with a control group of non-drug users, but the key finding was their disinterest in otherwise pleasurable non-drug scenes.  “Looking at pictures of heroin, needles, people injecting heroin, and social drug use … the heroin group found the drug pictures much more pleasant and rewarding, it lit up the brain activity,” said Dr Lubman, of Melbourne University’s Orygen Youth Health Research Centre.  “Whereas they were under-responsive and found the emotionally pleasant pictures much less pleasant.”
Dr Lubman said the alternative images included attractive people engaged in fun activities, delicious food, and “things that people normally rank as being quite pleasurable … there were also a few puppy dogs in there”.
The same drug addicts were assessed again six months later to see who had kicked their habit, with surprising results as the critical factor was not those who enjoyed drug-related pictures the most.  “It was actually the under-responsiveness to emotional positive pleasurable stimulus that predicted who was using the most heroin,” Dr Lubman said.
He said the findings held implications for drug treatment programs and the public, who often grappled with an addict’s inability to stop using.  Dr Lubman said the results suggested drug users had a reduced ability to enjoy everyday pleasures, and their brains remained excited by the prospect of continued drug use.
It also showed why threats of punishment, which Dr Lubman calls the “big stick” approach, may not work in discouraging addicts. “They haven’t got anything else in their lives to turn to,” he said.
“Our research shows the focus should be not only just the drugs but getting them (addicts) to be passionate about something else in some way, because that’s the best predictor about whether they will stop using.”
Dr Lubman said he expected similar results to be associated with all drugs of addiction, including alcohol, and further research was needed to explain a possible “chicken and egg” problem.  Which came first, addiction leading to less pleasure in life or drug taking to overcome a pre-existing lack of enjoyment?
“There is evidence to suggest that people who are vulnerable to addictions already have an underlying emotional problem,” Dr Lubman said.
The research findings were published in the journal Archives of General Psychiatry.

Source:  www.theage.com.au  Feb. 3rd 2009

Adolescents and young adults who are heavy users of marijuana are more likely than non-users to have disrupted brain development, according to a new study. Pediatric researchers found abnormalities in areas of the brain that interconnect brain regions involved in memory, attention, decision-making, language and executive functioning skills. The findings are of particular concern because adolescence is a crucial period for brain development and maturation.
The researchers caution that the study is preliminary and does not demonstrate that marijuana use causes the brain abnormalities. However, “Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari, Ph.D., director of the Diffusion Image Analysis and Brain Morphometry Laboratory in the Radiology Department of The Children’s Hospital of Philadelphia.  The study appeared early last month in the Journal of Psychiatric Research. The current research builds on previous work by Ashtari and colleagues, who used the same imaging technology to analyze normal brain development in adolescent subjects.
In the current study, working with child psychiatrist Sanjiv Kumra, M.D., now at the University of Minnesota, Ashtari and colleagues performed imaging studies on 14 young men from a residential drug treatment center in New York State, as well as 14 age-matched healthy controls. All the study subjects were males, with an average age of 19. The researchers performed the imaging studies at Long Island Jewish Medical Center.  The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. On average, they had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly 6 marijuana joints daily in the final year before they stopped using the drug.
The study team performed a type of magnetic resonance imaging scan called diffusion tensor imaging (DTI) that measures water movement through brain tissues. “The abnormal patterns of water diffusion that we found among the young men with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells,” said Ashtari. Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower.
Myelin gives its color to the white matter of the brain, and covers the nerve fibers that connect different brain regions. “Our results suggest that early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain,” said Ashtari. “Abnormal white matter development could slow information transfer in the brain and affect cognitive functions.”
Ashtari added that the findings are preliminary. Among other limitations of the study, such as a small sample size, five of the 14 subjects with heavy cannabis use also had a history of alcohol abuse, which may have contributed an effect. Also, it is possible that the brain abnormalities may have predisposed the subjects to drug dependence, rather than drug usage causing the brain abnormalities.
“Further research should be done to investigate the relation between repeated marijuana use and white matter development,” said Ashtari. “However, our work reinforces the idea that the adolescent brain may be especially vulnerable to risky behaviors such as substance abuse, because of crucial neural development that occurs.
Source: Science Daily 5th Feb 2009

There is growing evidence suggesting that
adolescence is a key period for neuronal maturation. The
results of the current study support that heavy cannabis
use during adolescence is related to brain damage in areas
known to be involved in ongoing development during late
adolescence, particularly in the fronto-temporal connection
via arcuate fasciculus. These results suggest that earlyonset
substance use may affect the development of fronto-
temporal white matter circuits, potentially resulting in
disturbed memory, and deficits in executive and affective
functioning (Lubman et al., 2007). Since five of the HCU
subjects were alcohol abusers, conclusions from our report
should be considered preliminary as the DTI findings
reported here may be due to combination of alcohol and
marijuana use. Adolescence, however, being marked as a
critical time for brain maturation and development, may
be a vulnerable period to partake in risky behaviors, such
as marijuana or alcohol use, for both physiological

Source: extract from  Journal of Psychiatric Research 43 (2009) 189–204

Adolescents and young adults who are heavy users of marijuana are more likely than non-users to have disrupted brain development, according to a new study. Pediatric researchers found abnormalities in areas of the brain that interconnect brain regions involved in memory, attention, decision-making, language and executive functioning skills. The findings are of particular concern because adolescence is a crucial period for brain development and maturation.
The researchers caution that the study is preliminary and does not demonstrate that marijuana use causes the brain abnormalities. However, “Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari, Ph.D., director of the Diffusion Image Analysis and Brain Morphometry Laboratory in the Radiology Department of The Children’s Hospital of Philadelphia.
The study appeared early last month in the Journal of Psychiatric Research. The current research builds on previous work by Ashtari and colleagues, who used the same imaging technology to analyze normal brain development in adolescent subjects.
In the current study, working with child psychiatrist Sanjiv Kumra, M.D., now at the University of Minnesota, Ashtari and colleagues performed imaging studies on 14 young men from a residential drug treatment center in New York State, as well as 14 age-matched healthy controls. All the study subjects were males, with an average age of 19. The researchers performed the imaging studies at Long Island Jewish Medical Center.
The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. On average, they had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly 6 marijuana joints daily in the final year before they stopped using the drug.
The study team performed a type of magnetic resonance imaging scan called diffusion tensor imaging (DTI) that measures water movement through brain tissues. “The abnormal patterns of water diffusion that we found among the young men with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells,” said Ashtari. Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower.
Myelin gives its color to the white matter of the brain, and covers the nerve fibers that connect different brain regions. “Our results suggest that early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain,” said Ashtari. “Abnormal white matter development could slow information transfer in the brain and affect cognitive functions.”
Ashtari added that the findings are preliminary. Among other limitations of the study, such as a small sample size, five of the 14 subjects with heavy cannabis use also had a history of alcohol abuse, which may have contributed an effect. Also, it is possible that the brain abnormalities may have predisposed the subjects to drug dependence, rather than drug usage causing the brain abnormalities.
“Further research should be done to investigate the relation between repeated marijuana use and white matter development,” said Ashtari. “However, our work reinforces the idea that the adolescent brain may be especially vulnerable to risky behaviors such as substance abuse, because of crucial neural development that occurs during those years.”
Source:  www.ScienceDaily.com  3rd Feb 2009

Abstract Achieving abstinence in the treatment of cannabis dependence has been difficult. To date the most successful treatments have included combinations of motivational enhancement treatment plus cognitive–behavioural coping skills training and/or contingency management approaches rewarding abstinence. Although these approaches are theoretically based, their mechanisms of action have not been explored fully. The purpose of the present study was to explore mechanisms of behaviour change from a cannabis treatment trial in which cognitive–behavioural and contingency management approaches were evaluated separately and in combination. A ‘dismantling’ design was used in the context of a randomised clinical trial. 240 dependent adult cannabis smokers who responded to advertisements attended an out-patient treatment research facility located in a university medical centre. They were randomly assigned to one of four nine-week treatment conditions:
• supportive case management, the control condition used as a benchmark for the other treatments;
• motivational enhancement therapy plus cognitive–behavioural coping skills training;
• standalone contingency management procedures rewarding cannabis abstinence with vouchers for retail goods or services, with no other therapeutic inputs;
• and a combination of contingency management with the motivational and cognitive–behavioural therapies.
The main outcome measure was total abstinence over the past 90 days based on the patients’ own accounts and verified by urinalysis. These measures were recorded every 90 days for the 12 months after treatment ended. Standalone contingency management led to the highest in-treatment abstinence rate, but the lowest in the last six months of the follow-up. Regardless of the treatment, abstinence in near-term follow-ups was predicted most clearly by abstinence during treatment, but long-term abstinence was predicted by use of coping skills and especially by post-treatment self-efficacy for abstinence.
 Though an exploration of the mechanisms of change in cannabis treatment in general, the study’s innovation This seems the first study to establish how contingency management works by linking it to psychological and behavioural changes, and then linking these to abstinence outcomes using a methodology which can tease out potential causal mechanisms. Inclusion of motivational and cognitive–behavioural approaches in the same study makes it possible to compare these mechanisms against those of probably the most influential and widespread structured therapies for substance use problems. (and the focus for this commentary) was to probe the psychological processes underlying contingency management, building on previously reported abstinence outcomes from the same study. The key message is that these procedures do not produce lasting change simply by mechanically reinforcing the habit of non-use. More important is whether the experience fosters confidence that one can resist relapse, along with the motivation to transform ‘can’ in to ‘will’, and strategies to effectively implement this resolution. In other words, what the patient makes of their spell on the contingencies and how they interpret it determines whether it will result in a transient, reward-driven spell of reduced substance use, or more lasting change. What the patient makes of the contingencies can in turn be influenced by integrating test results and rewards in to accompanying therapy, leading to greater longer term success than either on its own.
On the basis of the study, this message can only be considered a tentative working hypothesis. But it is consistent with other studies (1 2 3 4 5) which also found that the in-treatment boost Interestingly, in several studies this boost was deflated somewhat when contingency management was combined with cognitive-behavioural therapy, yet once the rewards ended this combination was at least as or more effective. to abstinence provided by rewards does not persist, leaving contingency management with longer term outcomes at best equivalent to cognitive-behavioural approaches, and sometimes slightly worse. More generally, when rewards end, patients often quickly revert to their previous behaviours. Even during the rewards period, typically impacts are limited to the targeted behaviours and/or the targeted drugs. This is what would be expected if patients interpret the procedures as a chance to do what it takes (and no more) to make some money or win some prizes. In particular, the authors suggest that lasting change is less likely if patients see abstinence as foisted on/enticed out of them by the rewards, rather than something they have shown they can achieve by their own efforts.
Within the study, this hypothesis emerged from an analysis which showed that the way contingency management enhanced cannabis abstinence after treatment, was by having enhanced it during treatment. However, when other variables were taken in to account, the distinct contribution of in-treatment abstinence was relatively weak. More significant were variables contingency management did not directly affect – the individual’s growing confidence in their ability to resist cannabis use and their deployment of strategies to help them do so. Each bolstered the other, especially when growing motivation to change gave impetus to the process. These variables were directly impacted by the treatments which included motivational and cognitive–behavioural elements, especially when combined with contingency management.
The upshot it seems was that though it led to the highest abstinence rates Both in terms of the average number of days abstinent and the number of patients who remained completely abstinent. during treatment, by the final follow-up a year later patients subject only to the rewards were least likely to have sustained abstinence over the past three months. After the other three This applied even to the case management option, one deliberately devoid of structured therapeutic content. treatments, abstinence rates improved, culminating in a final rate of around 20% or more. After standalone contingency management ended, the abstinence rate rapidly fell to barely more than half the level during treatment.
This transience did not apply when contingency management was combined with motivational/cognitive-behavioural therapy – in the longer term, the most effective of the options. Contingency management brought these patients in to contact with qualified and specially trained and supervised therapists who melded the urinalysis results and the rewards in to the therapeutic encounter, and who were in a position to influence the patient’s interpretation of and response to the contingencies. In contrast, standalone contingency management involved relatively fleeting contact with a research assistant who administered tests and rewards.
When contingency management and cognitive-behavioural therapy have merely run in parallel no longer term advantage from combining the two has materialised. But when, as in the featured study, therapists have integrated the contingency programme in to their sessions, the combination has proved the most powerful intervention in the longer term.
Though this study breaks new ground, others have also indicated that contingency management may not work in the same way as other therapies. Most relevant is a study which used vouchers to reward drug-free urine tests and consumption of the opiate blocking medication naltrexone to maintain abstinence from opiates after detoxification. As expected, during the 12 weeks of treatment the rewards encouraged patients to take their medication The difference was substantial but fell just short of statistical significance. and stay free of opiate drugs. But this did not presage lasting change. Within 12 weeks of the rewards ending, there was little difference between these patients and those not offered vouchers, by another 12 weeks, virtually none. A clue to the reason came in the observation that across the 12 weeks of treatment, motivation and readiness to change drug use behaviour increased slightly among patients not offered vouchers, but were significantly eroded Tests showed that this was not due to patients who had attained abstinence no longer feeling the need to change. among those rewarded for abstinence.
In other studies, motivation has not been eroded relative to other treatments, but neither has it been enhanced by reinforcing abstinence, indicating that the greater abstinence rates ‘bought’ by the rewards do not reflect increased motivation to remain abstinent. In one, supplementing motivational and coping skills therapy with rewards actually halved what without the rewards was a substantial increase in confidence in ability to refrain from smoking cannabis.
The potential for contingency management type rewards to erode motivation is well recognised outside the substance misuse sector. An analysis aggregating results from 128 studies found that tangible rewards offered for engaging in, completing, or doing well at a task undermined intrinsic motivation. The effect was greatest when represented by what people actually did after the rewards ended, the equivalent of post-treatment substance use in contingency management studies. However, the same analysis found that it is possible for rewards – and especially verbal recognition – to be given in such a way that they acknowledge the individual’s achievements and bolster feelings of mastery rather than of being controlled. In these cases the undermining effect can be reversed and intrinsic motivation enhanced.
Such findings help explain why in several studies contingent rewards or punishments for engaging in treatment did improve attendance and compliance, but, contrary to the usual pattern, ‘engagement’ elicited in this way did not improve substance use or other outcomes. It also helps explain why occasionally this does not happen, for example, when rewards are experienced as a non-controlling signal of the individual’s own achievements, and are embedded in a caring therapeutic environment which accompanies them with verbal and public recognition. Another exception is a study which achieved greater and more lasting abstinence by rewarding recovery-oriented activities rather than directly rewarding abstinence. In this case the rewards were delivered within a collaborative therapeutic relationship and empowered rather than controlled the patient. With their therapist, they could select activities to be rewarded in line with their own recovery plan and ability to complete the task. The broader findings referred to above also help us understand the oft-reported power of the verbal praise delivered by drug court judges to offenders, precisely the sort of unexpected, non-controlling verbal recognition which the analysts would expect to enhance motivation by reinforcing the offender’s sense of control.
Current British trials have absorbed the lessons of this US research and at least one Personal communication from Dr John Marsden of the National Addiction Centre, March 2008. is attempting to extend the substance use reductions gained by contingency management by exploring this experience in accompanying therapy. The trial is also using a newly developed questionnaire Marsden J., Mitcheson L., Stillwell G., Litt M., Shoptaw S. Treatment Incentives Experiences Scale. 2008. to track how patients interpret the contingencies, including whether they attribute their successes to the rewards or to themselves, and impacts on their confidence in their recovery.

Source: Litt M.D., Kadden R.M., Kabela-Cormier E. et al. Request reprint
Addiction: 2008, 103(4), p. 638–648

Students who regularly combine ecstasy and cannabis may harm their academic results, a recent research project has shown. The research was conducted in Barcelona and followed 120 cannabis and ecstasy users for three years. The results suggested that regular poly-drug users obtained half the marks of the non-user control group, writes Ruth Evans.
Scientists are divided over the effects of ecstasy, but there is general agreement that regular use can negatively affect long-term memory. The Spanish study contradicts previous research which suggested that people who took ecstasy alone had worse memory problems.
Dr de la Torre, who conducted the study, said that the risk of affecting their degrees should deter students from mixing drugs.
Source:  www.Nouse.co.uk    February 12, 2005

People who smoked marijuana had changes in the blood flow in their brains even after a month of not smoking, according to a study published in the February 8 issue of Neurology, the scientific journal of the American Academy of Neurology.

The findings could explain in part the problems with thinking or remembering found in other studies of marijuana users, according to study authors Ronald Herning, PhD, and Jean Lud Cadet, MD, of the National Institute on Drug Abuse in Baltimore, Md.

The study involved 54 marijuana users and 18 control subjects. The marijuana users volunteered to take part in a month-long inpatient program. The blood flow velocity in brain arteries was tested with transcranial Doppler sonography in all participants at the beginning of the study and again at the end of the month for the marijuana users.

The blood flow velocity was significantly higher in the marijuana users than in the control subjects, both at the beginning of the study and after a month of abstinence from marijuana use. The marijuana users also had higher values on the pulsatility index (PI), which measures the amount of resistance to blood flow. This is thought to be due to narrowing of the blood vessels that occurs when the circulation system’s ability to regulate itself is impaired.
“The marijuana users had PI values that were somewhat higher than those of people with chronic high blood pressure and diabetes,” Herning said. “However, their values were lower than those of people with dementia. This suggests that marijuana use leads to abnormalities in the small blood vessels in the brain, because similar PI values have been seen in other diseases that affect the small blood vessels.”

The PI values for light and moderate marijuana users improved over the month of abstinence. There was no improvement for heavy marijuana users. The light users smoked two to 15 joints per week. The moderate users smoked 17 to 70 joints per week, and the heavy users smoked 78 to 350 joints per week.

Source:. American Academy Of Neurology (2005, February 13). Marijuana Use Affects Blood Flow In Brain Even After Abstinence. ScienceDaily. Retrieved May 12, 2009

Alcoholics who smoke appear to lose more brain mass than alcoholics who don’t smoke, according to a study at the San Francisco VA Medical Center.

It is already well-known that the brains of long-term alcoholics atrophy and shrink, the study authors say, but the new findings are the first evidence that cigarette smoking might contribute to that atrophy, particularly in grey matter of the parietal and temporal lobes.
Fifty to 90 percent of alcoholics also are smokers, according to Dieter Meyerhoff, PhD, a radiology researcher at SFVAMC and the principal investigator of the study
“Just looking at the amount of tissue mass lost due to either drinking or smoking, alcoholics who smoke show a greater loss in some regions of the brain compared to alcoholics who don’t smoke,” says Meyerhoff, who also is a professor of radiology at the University of California, San Francisco.
The study, which was published in the August 2005 issue of Alcoholism: Clinical and Experimental Research, compared 37 recovering alcoholics between the ages of 26 and 66 with a control group of 30 healthy light drinkers. The researchers used magnetic resonance imaging, a safe, non-invasive imaging technique, to measure brain volumes of the study participants.
They discovered that the more severe the tobacco habit, the greater the brain injury. “In smoking alcohol-dependent individuals, smaller regional [brain] volumes are related to greater cigarette-smoking severity,” according to the study findings, with severity measured by level of nicotine dependence, cigarettes smoked per day, and years of smoking.
The alcoholics (24 smokers and 13 non-smokers) averaged around 400 drinks per month for three years prior to the study; the light drinkers (seven smokers and 23 non-smokers) averaged between four and 11 drinks per month before the study and had no history of alcohol abuse or dependence. The alcoholics were sober for approximately one week before the study began.
The study uncovered no apparent differences in brain volume between smoking and non-smoking light drinkers.
Another key finding was that among non-smoking alcoholics, there was a direct relationship between brain volume and cognitive function: the higher the volume, the better the function. However, no such relationship was apparent among smoking alcoholics, according to co-author Timothy Durazzo, PhD, an associate radiology researcher at SFVAMC. Nor has such a relationship been measured before in previous studies on alcohol abuse and brain volume, he says.
“And this makes us wonder if what has been reported in the literature of alcoholism could have been obscured or distorted by combining smokers and non-smokers in the same studies,” Durazzo adds.
In their paper, the researchers speculate that smoking “disrupts these [brain] structure-function relationships,” possibly through its detrimental effects on brain volume or on brain neurochemistry.
Meyerhoff and his co-authors emphasize that their results are retrospective — that is, they discovered the apparent effects of smoking during statistical analysis of the participants in an earlier study they conducted on alcoholism and its effects on the brain. They then went back, re-classified each study participant as smoking or non-smoking, and analyzed brain volumes accordingly.
The authors say that if replicated in other studies, their results will raise several potentially important questions. The first is whether recovering alcoholics should also be treated for smoking — and if so, at what point during their treatment. At present, alcohol treatment programs such as Alcoholics Anonymous do not discourage smoking or even address the issue, they say.
Beyond that, says Durazzo, there is the potential effect of smoking on cognitive dysfunction, which is common among older long-term alcoholics. “Right now, our study participants are relatively young, around 50,” he notes. “But will the combination of smoking and drinking, or continued smoking during abstinence from alcohol, put them at greater risk for cognitive dysfunction as they age?” Finally, says Meyerhoff, there is the question of whether smoking has an effect on physical recovery from alcohol abuse. “In alcoholics who stop drinking, we know that there is recovery from at least some of these injuries to the brain — but is this recovery affected by continued smoking?” Meyerhoff and his team are conducting a study to explore that question right now.
In the future, the researchers plan a prospective study that will use MRI to compare brain volumes between smoking and non-smoking light drinkers and smoking and non-smoking alcoholics, with the hope of replicating the results of their current retrospective study.

Source: University of California – San Francisco (2005, September 29). Smoking Seems To Increase Brain Damage In Alcoholics. ScienceDaily. Retrieved May 31, 2009, from http://www.sciencedaily.com¬ /releases/2005/09/050929081514.htm

Researchers have demonstrated that a naturally occurring brain protein known as Brain Derived Neurotrophic Factor (BDNF) can be manipulated to produce increased activity in the brain similar to when opiates are ingested, the Deseret News reported May 28.
Neurobiologist Hector Vargas-Perez and colleagues at the University of Toronto and Brigham Young University (BYU) found that an increased presence of BDNF is associated not only with greater brain activity, such as when an epileptic fit occurs, but also with chronic exposure to drugs of abuse. The increase in BDNF – known to be involved in the release of dopamine in the brain — occurs within a specific area of the brain known as the ventral tegmental area (VTA).
The researchers found that repeatedly increasing BDNF levels in the brains of non drug-dependent lab rats changed their behavior to resemble that of drug-dependent rats.
“If we can understand how the brain’s circuitry changes in association with drug abuse we can find ways to medically counteract the effects of dependency” in humans, said researcher Scott Steffensen of BYU. Lead author Hector Vargas-Perez of the University of Toronto said that the study “reveals the mechanism behind drug addiction.”
Source: online edition of the journal Science. May 28, 2009

Research Summary
Researchers from the Brookhaven National Laboratory and the National Institute on Drug Abuse (NIDA) have demonstrated that an area of the brain called the Anterior Cingulate Cortex (ACC) shows differences in levels of activity between cocaine users compared with non-users when performing a series of tasks, even though both groups are evenly matched demographically (socially, cognitively, educationally, etc.).
The study suggests that this difference in brain activity is not due to prior variance in cognitive ability or lack of motivation on the part of drug users, but rather because drug-users’ brains act differently from non-users’, Medical News Today reported May 26.
The researchers took 17 individuals with current cocaine-use disorders (CUD) and 17 demographically matched healthy controls and gave them several tasks to perform while the subjects underwent functional magnetic resonance imaging.
Both groups performed equally well at all the tasks. However, the levels of ACC activity differed between the two groups as the tasks were performed. In tasks that required monitoring behavior, activity in the ACC increased among the healthy non-drug users, but for the cocaine users this did not happen. Also, among the cocaine users the level of ACC activity was lowest in those who had used cocaine more frequently.
In other tasks in which emotion needs to be suppressed (emotion-monitoring), another part of the ACC becomes less active, but in the cocaine users this activity was not suppressed to the same extent as among non-drug users. 
The major functions of the ACC (behavior-monitoring and emotion-monitoring) are located in a pair of regions in the same area of the brain. When the researchers measured the subjects’ responses to stimuli, these two regions of the brain behaved differently between the non-drug users and the drug users. Among the non-addicted subjects, the researchers found that the two parts of the ACC communicated with each other whereas among the cocaine users such communication did not take place. The researchers suggest that this was because the drug users experienced a disruption between the two functions of the ACC.
Lead author Rita Z. Goldstein, a psychologist at Brookhaven National Laboratories, said the study, “gives us some clues as to what happens when drug users are unable to suppress craving — and how that might work together with a decreased ability to monitor behavior … to make some people more vulnerable to taking drugs.”
Source: online Proceedings of the National Academy of Science. May 2009

In a study published online by the Journal of Substance Abuse Treatment, UC Davis researchers report that it takes at least a year for former methamphetamine users to regain impulse control. The results tell recovering substance abusers, their families and drug-treatment specialists that it can take an extended period of time for the brain functions critical to recovery to improve.

“Recovery from meth abuse does not happen overnight,” said Ruth Salo, lead author of the study and a UC Davis assistant professor of psychiatry and behavioral sciences. “It may take a year – or even longer – for cognitive processes such as impulse control and attentional focus to improve. Treatment programs need to consider this when monitoring recovering addicts’ progress during their early periods of abstinence.”

Salo specializes in the behavioral, neuropsychiatric and cognitive outcomes of methamphetamine addiction – a particularly difficult condition to treat, primarily due to prolonged, intense cravings for the drug. During her career, she has worked with hundreds of methamphetamine addicts.

“All of them want to know if there is hope,” Salo said. “We used to think most, if not all, effects of meth addiction were permanent. This study adds to the growing evidence that this assumption is not true. I can confidently tell patients that the longer they stay in a structured rehabilitation program and remain drug free, the more likely it is that they will recover some important brain functions.”

For the current study, Salo used the widely-validated, computer-based Stroop attention test to measure the abilities of 65 recovering methamphetamine abusers to use cognitive control – or direct their attention to specific tasks while ignoring distractors. Study participants had been abstinent for a minimum of three weeks and a maximum of 10 years, and they had previously used the drug for periods ranging from 24 months to 28 years. The data for the 65 individuals were compared to Stroop attention test data from 33 participants who had never used methamphetamine.

“The test taps into something people do in everyday life: make choices in the face of conflicting impulses that can promote a strong but detrimental tendency,” Salo explained. “For meth users, impairments in this decision-making ability might make them more likely to spend a paycheck on the immediate satisfaction of getting high rather than on the longer-term satisfaction gained by paying rent or buying groceries.”

The study analyzed cognitive control in terms of the amount of time since methamphetamine was last used as well as total time spent using the drug. The researchers found that those who were recently abstinent (three weeks to six months) performed significantly worse on the Stroop test than those who had been abstinent one year or longer. In addition, there was no statistical difference between test results for those abstinent at least one year and non-drug using controls. Longer-term methamphetamine use was associated with worse test scores. Similarly, longer-term abstinence was connected to improved test performance.

According to Salo, the new study mirrors previous magnetic resonance imaging (MRI) studies she and her colleagues published in 2005 showing a partial normalization of chemicals in selected brain regions after one year of methamphetamine abstinence.

“Together, the studies provide strong evidence that, eventually, meth abusers in recovery may be able to make better decisions and regain the impulse control that was lost during their drug use period,” she said.

Salo said that more research is needed to determine just how the brain recovers from methamphetamine addiction and if behavioral treatments can hasten that recovery. She plans to continue neuroimaging studies to further define the brain functions affected by the drug. Her ultimate goal is to provide information essential to refining treatment programs for this population of drug users.

“Meth use worldwide is pandemic,” she said, referring to the estimated 35 million people who have used the neurotoxic stimulant or similar drugs. “Recovery is difficult, but possible. The point of my research is to better understand the neural and behavioral consequences of this toxic drug along with the brain and behavior changes that are possible with long-term abstinence.”
Source: Journal of Substance Abuse Treatment, Ruth Salo et al 1st July 2009

Yellow areas in the brain of a heavy marijuana user show brain regions with the most significant abnormalities. These areas correspond with those under development during normal adolescent years. Credit: Ashtari et al., Children’s Hospital of Philadelphia

The term pot-head takes on new meaning with a study that suggests adolescents and young adults who smoked a lot of marijuana are more likely than non-users to have disrupted brain development.
Using brain scans, researchers found abnormalities in areas of the brain that interconnect brain regions involved in memory, attention, decision-making, language and executive functioning skills.
The findings are of particular concern because adolescence is a crucial period for brain development and maturation, the researchers note.
“Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari of the Children’s Hospital of Philadelphia.
The findings are considered preliminary, however, and more research is needed to confirm the work.
This is not the first research to suggest marijuana damages the brain. In previous reseach involving memory skill stests, subjects who’d smoked too much did poorly. But brain imaging can reveal specifics.
In an admittedly small study, Ashtari and colleagues performed imaging studies on 14 young men (average age 19) from a residential drug treatment center in New York State, as well as 14 healthy men of the same age.
The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. On average, they had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly 6 marijuana joints daily in the final year before they stopped using the drug.
The brain scans measureed water movement through brain tissues.
“The abnormal patterns of water diffusion that we found among the young men with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells,” Ashtari said.
Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower. Myelin gives its color to the white matter of the brain, and covers the nerve fibers that connect different brain regions.
“Our results suggest that early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain,” Ashtari said. “Abnormal white matter development could slow information transfer in the brain and affect cognitive functions.”
Study shortcomings
Ashtari pointed out shortcomings in the study, however.
For one, it involved a small number of subjects. Also, five of the 14 subjects with heavy cannabis use also had a history of alcohol abuse, which may have contributed an effect. Also, it is possible that the brain abnormalities may have predisposed the subjects to drug dependence, rather than drug usage causing the brain abnormalities.
“Further research should be done to investigate the relation between repeated marijuana use and white matter development,” Ashtari said. “However, our work reinforces the idea that the adolescent brain may be especially vulnerable to risky behaviors such as substance abuse, because of crucial neural development that occurs during those years.”
The work was funded by the National Institute of Mental Health.
Source: Journal of Psychiatric Research Feb. 2009

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

Nicotine is thought to exert its effects on the brain by binding to receptors in the brain called nicotinic acetylcholine receptors (nAChRs). However, tobacco smoke contains thousands of chemicals besides nicotine, some of which may also bind to the nAChRs or cause molecules normally found in the body to bind to these receptors. To study the effects of denicotinized cigarettes—cigarettes from which nicotine has been removed—on a specific type of nAChR (a4b2* nAChRs), researchers funded in part by NIDA used a brain imaging technique known as positron emission tomography (PET) to visualize these receptors in the brains of smokers during withdrawal and after smoking either low-nicotine or denicotinized cigarettes. Before the PET imaging, all volunteers stopped smoking for approximately 2 days. The volunteers underwent an hour of PET imaging while still undergoing withdrawal and then were assigned to perform one of three activities: smoke a low-nicotine cigarette, smoke a denicotinized cigarette, or not smoke; they then underwent approximately 4 more hours of PET imaging. Withdrawal symptoms were monitored during all imaging sessions. The imaging results showed not only that “inhalation of nicotine during cigarette smoking is solely responsible for occupancy of brain a4b2* nAChRs,” but also that the imaging “demonstrated significant a4b2* nAChR occupancy from smoking a denicotinized cigarette,” state the authors. This result challenges the assumption that denicotinized cigarettes do not affect the brain’s nicotine receptors, the authors further explain. Interestingly, whether or not the receptors were occupied did not correlate with withdrawal symptoms, indicating that factors other than nicotine binding to the receptors play a role in the relief of withdrawal symptoms provided by smoking.

Source: Brody et al. Brain nicotinic acetylcholine receptor occupancy: Effect of smoking a denicotinized cigarette. Int J Neuropsychopharmacol. 2009;12(3):305–316.

By Patrick Zickler
NIDA NOTES Staff Writer

Smokers who want to quit can get help with a variety of treatments, including counselling, nicotine replacement therapy (patches, gum, lozenges, or inhalers and medications. Some smokers use these treatments and succeed; for many. however, the discomfort of withdrawal and craving for nicotine lead to relapse. Recent NIDA funded research suggests that our genes may partly explain this variable success.

The research evaluated the effect of an enzyme, designated CYP2B6, on craving and relapse. This enzyme breaks down nicotine in the brain. Some peoples’ genes produce a more active form of the enzyme. while others have a less active form. Dr. Caryn Lerman at the NIDA- and NCI supported Transdisciplinary Tobacco Use Research Centre (TTURC) at the University of Pennsylvania, found that among smokers enrolled in a smoking cessation program, those with the genetic variant that decreases activity of CYP2B6 reported greater craving than did those with the more active form of the enzyme. Moreover, those with the less active enzyme were 1.5 times more likely to resume smoking during treatment.

The same enzyme helps break down bupropion, an antidepressant medication that acts on the brain’s dopamine system—where nicotine exerts much of its addictive influence—and helps some smokers quit. Dr. Lerman, along with colleagues at Georgetown University in Washington, DC., the State University of New York at Buffalo, and Brown University in Providence, Rhode Island, also investigated the relationship of CYP2B6 activity with bupropion treatment. They found that bupropion nearly tripled the success rate for women with the less active enzyme.

These findings provide initial evidence that smokers who have decreased CYP2B6 activity experience greater craving for nicotine than those with the more active form of this enzyme,” Dr. Lerman says. “Perhaps of greater interest is the preliminary evidence that, among women, bupropion may overcome the effect this genetic predisposition has on relapse.”

Genes, Treatment, and Abstinence

Most people—about 70 percent of the U.S. population—inherit two copies of the ‘C’ variant of the gene that influences CYP2B6 activity. The rest of the population inherits from one or both parents the less common form of the gene—the “T’ variant associated with decreased CYP2B6 activity. Among the 426 participants (232 men, 194 women) in the TTURC study, 128 (29.6 percent) had one or two copies of the T form of the gene. All participants received counselling to quit smoking; 229 received bupropion (300 mg/day) and 197 received placebo throughout the 10-week study. The participants provided weekly reports on craving and smoking rates. Abstinence (7 consecutive days without smoking) was verified with blood tests. At the end of treatment, participants who received counselling and bupropion had higher abstinence rates than those who received counselling and placebo. With one exception. participants with the less active enzyme had lower abstinence rates than those with the more active enzyme. Women with the less active enzyme who received bupropion showed the largest treatment effect, with 54 percent achieving abstinence, up from a 19-percent rate among women in the placebo group, notes Dr. Lerman.

This study suggests that properly selected treatment matched to a patient’s characteristics can improve a smoker’s chance of quitting

Theories To Explain Outcomes

The higher abstinence rate with bupropion for women with the lower activity enzyme may he due, in part, to reduced susceptibility to low moods that accompany nicotine withdrawal; overall. women reported more negative feelings than did men when asked to rate their mood during withdrawal. “This rate may reflect better management of the negative moods and craving that abstinence can create. But more study is needed to clarify the mechanisms by which bupropion influences smokers’ success in quitting”, Dr. Lerman says.
Researchers theorize that the association between the less active enzyme and increased craving could be the result of nicotine’s remaining longer in the brains of smokers with the less active enzyme. When nicotine lingers in the brains of these smokers, it may change their brain cells more profoundly than those of smokers with the more active enzyme. If so, the changes might produce more severe addiction marked by more intense craving during abstinence and increased risk of relapse.

“This study offers additional evidence of the important role genes play in smoking and treatment,” says Dr. Joni Rutter of NIDAs Division of Neuroscience and Behavioural Research, ‘While illustrating the increased craving and vulnerability to relapse that may be associated with inherited traits, it also suggests that properly selected treatment matched to a patient’s characteristics in this case, Bupropion for some women can improve a smoker’s chance of quitting.’

Source:Lerman, C., et al. Pharmacogenetic investigation of smoking cessation treatment, Pharmacogenetics
12(8):627-634, 2002.

 By Patrick Zickler, NIDA NOTES Staff Writer

Many genetic, biological, and environmental factors can influence whether and when an individual initiates drug abuse or develops drug dependence or addiction. One tool that helps scientists isolate and evaluate the effect of different factors is research on twins, who share many inherited biological traits and environmental influences. In a study of more than 300 pairs of same-sex twins, NIDA-supported investigators found that smoking marijuana before age 17 is linked to a greater likelihood of proceeding to serious problems with marijuana or other drugs.

“This finding underlines the significance of early drug initiation,” says Dr. Wilson Compton, director of NIDA’s Division of Epidemiology, Services and Prevention Research. “Identical twins had the same inherited biological characteristics, and fraternal twins shared half their genes. All the twins had common family influences and social environments. Even though they had so much in common, something influenced one twin to take drugs earlier than the other, and that difference had a profound impact on later experience with drugs.”

The same-sex twin pairs grew up in the same households and attended the same schools. In each pair, one twin smoked marijuana before his or her 17th birthday and the other did not. “When we interviewed the twins as adults, the early users were more than twice as likely to have taken other illicit drugs. They also were from two to five times more likely to move on to abuse or dependence on alcohol, marijuana, stimulants, opioids, or sedatives,” says Dr. Michael Lynskey, who conducted the study with colleagues at the Washington University School of Medicine in St. Louis, Missouri; the Queensland Institute of Medical Research in Brisbane, Australia; and the University of Missouri in Columbia.

The researchers asked both members of 2,765 twin pairs included in the Australian Twin Register if they had ever smoked marijuana and, if so, how old they were when they smoked it for the first time. The researchers identified 311 pairs of same-sex twins (average age 30) in which one twin first smoked marijuana before age 17 and the other twin had either never smoked the drug (77 pairs) or did so for the first time at age 17 or older (234 pairs). Of the 311 twin pairs, 136 (74 female, 62 male) were identical and 175 (84 female, 91 male) were fraternal. The interviews were conducted by phone in Australia and the data analyzed by scientists at Washington University and the University of Missouri.

The investigators defined “use” as drug taking on one or more occasions for a nonmedical reason. The researchers defined “abuse” and “dependence” according to criteria adapted from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Abuse was understood to involve taking the drug in physically hazardous situations or circumstances that interfered with major obligations. According to the DSM-IV criteria, twins described as drug- or alcohol-dependent had two or more of the following symptoms: needing increasingly larger amounts to achieve drug effect, using for longer periods or more frequently than intended, and continuing to use despite associated emotional problems or recurrent desire to cut down use.

Overall, the researchers found, twins who smoked marijuana before age 17 were more than twice as likely as their sibling to use opioids, three times as likely to use sedatives, three times as likely to use cocaine or other stimulants, and nearly four times as likely to use hallucinogens. Those who smoked marijuana before age 17 also were from 1.6 to 6 times as likely to have reported abuse or dependence on alcohol or an illicit drug. Nonetheless, Dr. Lynskey points out, the majority (52 percent) of twins who smoked marijuana before age 17 did not go on to develop abuse or dependence. The increased odds of using other drugs or for developing abuse or dependence were not greater for identical than for fraternal twins, nor for males or females.

“While these study findings indicate that early marijuana use is associated with increased risk of progression to other illicit drug use and possibly to drug abuse or dependence, it is not possible to draw strong causal conclusions solely on the basis of these associations,” Dr. Lynskey cautions. Additional research in other cultures, using a range of research designs, will be needed to determine the causes of the association, he says.

“Given that early initiation of marijuana smoking appears to be associated with increased risks,” says Dr. Lynskey, “there is a need for greater physician awareness of those risks. Focused interventions also are needed to prevent escalation to use of other drugs among young people identified as being at risk.”