Adolescent substance abuse disorders are a predictor of young adult mortality, new research from the University of Pittsburgh concludes. Researchers found that young adult males with substance abuse disorders had a mortality rate far in excess of the norm for their non-addicted contemporaries. For example, 2 percent of the adolescents studied had died by the time the eight-year study period ended, including 23 percent of the African American males in the study.

Teens who abuse alcohol or drugs are more likely to die in early adulthood, according to a study by University of Pittsburgh researchers published in the current issue of the Journal of Adolescent Health.

The study, the first in a sample of U.S. adolescents, found that substance abuse disorders (SUDs) in adolescents significantly predicted young adult mortality. These deaths were linked to specific high-risk behaviors in adolescence, including intoxicated driving and drug trafficking.

“The fact that these were, to an extent, predictable deaths raises additional concerns about the hazards of alcohol and drug problems in teens and young adults,” said Duncan B. Clark, M.D., Ph.D., associate professor of psychiatry and pharmaceutical sciences at the University of Pittsburgh School of Medicine and director of the Pittsburgh Adolescent Alcohol Research Center at the Western Psychiatric Institute and Clinic of UPMC.

The researchers studied 870 white and African-American adolescents, ages 12 through 18, recruited from both clinical and community settings. The subjects were followed for up to eight years, starting in 1990.

Among the 870 adolescents, researchers noted 21 deaths, or about 2 percent of the group, at an average age of nearly 25 years. Fourteen of those deaths occurred in males with SUDs, or more than 10 percent of that group. Among African-American males with SUDs, 23 percent had died by the age of 25. Males with SUDs in this study group had a mortality rate far in excess of the rate of 137 per 100,000 reported for young adult males in the U.S. general population.

Socioeconomic status was not a significant predictor of survival time. Causes of death for the young adults in the study ranged from homicide and suicide to drug overdose and motor vehicle accidents.

Dr. Clark noted that these results need to be confirmed in a larger, nationally representative sample over a longer period of time. Still, he said, “The adolescent characteristics predicting death in young adulthood can be readily identified in clinical evaluations.”

Adolescents may not be oblivious to the risks their behaviors pose. Previous studies have shown that many teens who engage in alcohol and drug use and other high-risk behavior believed they would die within two years. “Unfortunately, this insight on the part of some teens apparently does not eliminate these problem behaviors,” said Dr. Clark. “Effective interventions need to be developed to prevent these predictable deaths in our young adults.”

Co-authors of the study include Christopher S. Martin, Ph.D., and Jack R. Cornelius, M.D., Ph.D., from the University of Pittsburgh. Dr. Clark was supported by funding provided by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.

Source: NEW UNIVERSITY OF PITTSBURGH STUDY IN THE JOURNAL OF ADOLESCENT HEALTH

By LINDSAY McINTOSH

THE antisocial effects of underage drinking are felt by communities across Scotland, with some areas becoming no-go zones on Friday and Saturday nights as a result.
But the real cost of the country’s child drink shame is human, with some youngsters killing themselves with booze.

Just over a year ago, the body of schoolgirl Naomi Thomson was found at a friend’s house in Fraserburgh, Aberdeenshire.
Her death certificate says the fatality is “unexplained”, but it lists “probable acute alcohol intoxication”. It is believed the 14-year-old drank herself to death at a sleepover party.

In February 2002, Craig Ritchie, 13, died after taking part in a secret drinking session with friends. He choked on his own vomit and suffered a heart attack. He was admitted to hospital in a coma and was declared dead ten days later. The pupil at Aberdeen’s Kincorth Academy had been drinking cider with a group of friends in Cove on the city’s outskirts.

In December 2005, two 13-year-old girls were found drunk and unconscious on a snow-covered street after going to an under-18s disco. One was on the brink of death when police officers discovered the scantily clad girls in Westhill, Aberdeenshire. The teenager did not come round for six hours after being treated for hypothermia and alcohol intoxication at Aberdeen Royal Infirmary.

Earlier this month, two girls of the same age were found on the streets in “mortal danger”, according to police. The pair had handed over their pocket money to a man to buy them alcohol from an off- licence in Livingston. Police said they could have lost their way and fallen unconscious which, combined with the cold weather, might have had fatal consequences. During an eight-hour blitz on the town, officers found six “heavily drunk” youths and took them to the police station to sober them up.

The definition of “under-age” sank to a shocking low this October, when community wardens in Cowie, Stirlingshire, caught a boy of seven swigging from a bottle of strong cider. Alcohol campaigners said the youngster could have died if he had drunk the whole one-litre bottle.

Wardens said they found young people openly drinking in the village streets, in flagrant disregard of local by-laws.

Jack Law, chief executive of the Alcohol Focus Scotland charity, said at the time: “Under-age drinking is a massive problem in Scotland, but we are obviously shocked at the age of this child. “There is evidence children find it relatively easy to access alcohol from adults. But these people need to realise there could be serious consequences.”

Under-age drinking is not only a pastime of children from deprived backgrounds. In the summer of 2000, Euan Blair, 16-year-old son of then-prime minister Tony Blair, was held for being drunk and incapable in Trafalgar Square. An ambulance was called for the teenager, as police were worried about his condition. He had been vomiting but did not require hospital treatment. The youngster had been at a post-exam celebration and gave a false name and address to police but was released without charge.
Source: The Scotsman 27 December 2007

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

People with clinical addictions know first-hand the ravages the disease can take on almost every aspect of their lives.
So why do they continue addictive behaviors, even after a period of peaceable abstinence Some answers appear rooted in regions of the brain active during decision making.
“It’s perhaps not just that people are slaves to pleasure, but that they have trouble thinking through a decision,” said Charlotte Boettiger, an assistant professor of psychology at the University of North Carolina at Chapel Hill, and lead author of a study in the December issue of the Journal of Neuroscience that took a novel tack in addiction imaging research. Our data suggest there may be a cognitive difference in people with addictions,” Boettiger said. “Their brains may not fully process the long-term consequences of their choices. They may compute information less efficiently.”
The study also found that a variant of the COMT gene, which controls the level of the neurotransmitter dopamine in the cortex, was associated with a tendency to make impulsive decisions and with high activity in certain brain areas during decision making. Current medications for addictions are not universally effective; many either mimic the addictive substance to help people get through withdrawal periods or block the substance to prevent its effects. For stimulants, such as methamphetamines, there are no therapies yet, Boettiger said.
“What’s exciting about this study is that it suggests a new approach to therapy. We might prescribe medications, such as those used to treat Parkinson’s or early Alzheimer’s disease, or tailor cognitive therapy to improve executive function,” said Boettiger, who led the study as scientist at the University of California, San Francisco’s Gallo Clinic and Research Center. I am very excited about these results because of their clinical implications,” said Dr. Howard Fields, a professor of neurology at UCSF and an investigator in the Gallo Center.
“The genetic findings raise the hopeful possibility that treatments aimed at raising dopamine levels could be effective treatments for some individuals with addictive disorders,” said Fields, who is senior author of the study. Most addiction imaging studies have focused on the brain response to drug-related stimuli.
Boettiger used functional magnetic resonance imaging (fMRI), which shows brain activity while a subject performs a function, to see what happened inside their heads when sober alcoholics and people in a non-alcoholic control group made decisions between immediate and delayed rewards. Boettiger recruited 24 subjects; 19 provided fMRI data, nine were recovering alcoholics in abstinence and 10 had no history of substance abuse. Another five were included in the genotyping analysis.
At the fMRI research facility at the University of California, Berkeley, the subjects were asked to decide between receiving a small monetary award immediately or wait for a larger payoff. The scenarios were hypothetical, but the tasks measured rational thinking and impulsivity; sober alcoholics chose the “now” reward almost three times more often than the control group, reflecting more impulsive behavior. While decisions were being made the imaging detected activity the predicted individual choice in regions associated with decision making — the posterior parietal cortex, the dorsal prefrontal cortex, the anterior temporal lobe and the orbital frontal cortex.
People who sustain damage to the orbital frontal cortex generally suffer impaired judgment; they manage money poorly and act impulsively. Boettiger’s study revealed reduced activity in the orbital frontal cortex in the brains of subjects who preferred “now”over “later,” most of whom had a history of alcoholism. The orbital frontal cortex activity may be a neural equivalent of long-term consequences. “Think of the orbital frontal cortex as the brakes,” Boettiger said. “With the brakes on, people choose for the future; without the brakes they choose for the short-term gain.”

The dorsal prefrontal cortex and the parietal cortex often form cooperative circuits, and this study found that high activity in both is associated with a bias toward choosing immediate rewards.
The frontal and parietal cortex are also involved in working memory — being able to hold data in mind over a short delay. When asked to choose between $18 now or $20 in a month, the subjects had to calculate how much that $18 (or what it could buy now) would be worth in a month and then compare it to $20 and decide whether it would be worth the wait. The parietal cortex and the dorsal prefrontal cortex were much more active in people unwilling to wait. This could mean, Boettiger said, that the area is working less efficiently in those people.
The COMT gene has two common variants with a single amino acid difference at position 158; valine (Val) or methionine. The Val form of the gene is associated with lower dopamine levels, and Boettiger’s study showed that people with two copies of the Val allele (resulting in the lowest dopamine levels) had significantly higher frontal and parietal activity and chose now over later significantly more often.
“We have a lot to learn,” Boettiger said. But the data take a significant step toward being able to identify subtypes of alcoholics, which could help tailor treatments, and may people who are at risk for developing addictions and provide earlier intervention. The bigger picture, Boettiger said, is that her study provides more evidence that addiction is a disease, something even some of her peers do not yet believe.
“It’s not unlike chronic diseases, such as diabetes,” she said. “There are underlying genetic and other biological factors, but the disease is triggered by the choices people make.”
“It wasn’t that long ago that we believed schizophrenia was caused by bad mothers and depression wasn’t a disease. Hopefully, in 10 years, we’ll look back and it will seem silly that we didn’t think addiction was a disease, too.”

Home

Source: News-Med.net 30th Dec. 2007

Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People’s Republic ofChinaThe research reveals that a subject’s brain with low beta-endorphin levels becomes accustomed to the presence of an exogenous surplus, diminishing its own supply and triggering dependence on an external source–in this case, alcohol.
According to a study by the research group “Alcoholism and drug addiction”, of the University of Granada, although there are no specific reasons to become alcoholic, many social, family, environmental, and genetic factors may contribute to its development. Thanks to this study, researchers have shown that the lack of endorphin is hereditary, and thus that there is a genetic predisposition to become addicted to alcohol. Beta-endorphin is a kind of “morphine” released by the brain in response to several situations, such as pain. In this way, beta-endorphins can be considered “endogenous analgesics” to numb or dull pains.
Researchers have focused on the low beta-endorphin levels in chronic alcohol abusers. According to José Rico Irles , professor of Medicine of the UGR, and head of the research group, this low beta-endorphin level determines whether someone may become an alcoholic. When a subjects’ brain with low beta-endorphin levels gets used to the presence of an exogenous surplus, then, when its own production stops, a dependence starts on the external source: alcohol.
Who may become and alcohol abuser?
A total of 200 families of the province of Granada participated in the research. There was at least one chronic alcoholic parent in each family. From birth, each subject presented predetermined beta-endorphin levels. However, children of this population group aged between 6 months and 10 years old, registered lower beta-endorphin levels than other children of the same age. “These levels were even lower in children whose both parents were alcohol abusers”, the researcher states. According to researcher, although alcohol consumption does not affect all people in the same way, differences in endorphin levels make some subjects more vulnerable to alcohol. Therefore, they are more likely to become alcohol dependent.
Beta-endorphins constitute a useful biological marker to identify specifically those subjects who have a higher risk of developing alcohol abuse, the research claims. Regarding the results of this study, professor Rico states the following: “alcohol-abuse prevention must consist of locating and identifying genetically predisposed subjects.” More campaigns for children and teenagers should be launched before these young people make contact with alcohol. Alcohol awareness is fundamental to prevent addiction, the researcher affirms, because alcohol is a drug with reversible effects up to a point.
In relation to the “botellculture” (Botell’s a Spanish custom in which young people congregate in a park, street or any open public place to share alcoholic drinks and converse before entering bars, nightclubs, discos, etc.), José Rico states that some of these “social drinkers” could have low beta-endorphin levels and, therefore, a higher predisposition to become “solitary drinkers” and to develop alcohol abuse.
http://www.ugr.es/
Source:Newa-Medical.net 21st Dec. 2008

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different
technologies have revealed a variety of genes and pathways underlying addiction; however, each individual
technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg. cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

Discussion
The addiction-related genes, (common) pathways, and networks were traditionally studied experimentally. The
explosion of genomic and proteomic data in recent years both enabled and necessitated bioinformatic studies of
addiction. Integration of data from multiple sources could remove biases of any single technology platform, and
statistical and network analysis of the integrated data could uncover high-level patterns not detectable in any individual
study. For instance, our analysis revealed not only many pathways already implicated in addiction [34–38], but also
new ones such as GnRH signaling pathway and gap junction, as well as the coupled positive feedback loops through
CAMKII. They could serve as interesting hypotheses for further experimental testing.

The collection of addiction-related genes and pathways in KARG, the first bioinformatic database for addiction, is the
most comprehensive to date. However, as new technologies continue to be developed and used, more and more genes will
be linked to addiction. In 2004, a paper asked why proteomics technology was not introduced to the field of drug addiction
[5]; since then eleven studies have identified about 100 differentially expressed proteins in drug addiction. Tillingarray
technology, another new strategy for whole-genome identification of transcription factors binding sites, has been
used to identify targets of CREB, an important transcription factor implicated in drug addiction [39]. In addition, as 100 K
and 500 K SNP arrays have been introduced recently, whole genome association studies will also identify more closely
packed and unbiased hypothesis-free vulnerable positions [40]. We will continue to integrate new data and update the
gene list and molecular pathways toward a better understanding of drug addiction.

Source: Li CY, Mao X, Wei L (2008) Genes and (common) pathways underlying drug addiction. PLoS Comput Biuo 4(1):e2. doi:10.1371/journal.p.c

The above article is of extreme interest – and in order to make the details more informative for non-specialist readers Dr. Stuart Reece from Australia has written the following explanations:

The paper means that many addiction have several links in common at the molecular level.

Many major pathways to intracellular signalling are commandeered by the various addictions which have much in common. The addictions documented are tobacco, alcohol, opiates (heroin morphine methadone) and cocaine.

The paper is a computational biology paper which means that supercomputers are used to study 2343 items which have been published in the molecular literature relating to the molecular alterations induced by drug addiction.

Its very essence and principal strongly supports my long-standing contention that molecular research could be much better undertaken in this area, and much more aggressively pursued. This paper is from China.

Of course one of the most difficult parts about addiction is the way in which behaviour which initially is volitional, becomes altered to be habitual and refractory to what would normally be the messages to desist the addictive and destructive behaviours.

What is so revolutionary about the paper -beyond providing a very concise synthesis of several vast scientific literatures – is two things:

1) The way in which the institution of irreversible (or at least refractory) changes are described at the molecular level – in other words the institution of hard core addiction and perturbed memories and behaviours
and
2) The critically important list of molecular pathways which are identified as key components of the cell machinery which are commandeered and effectively pirated or hijacked.

The paper suggests that when fast and slow acting feedback loops interact within the cell (particularly neuron and glial cell) circuitry changes can become irreversible. This is the molecular correlate of the behavioural change which so disturbs the world, addicts and other people.

The list of the major pathways which are perturbed by addiction is absolutely central to any modern understanding of this subject, and strongly expose the terrible fallacies of the legalization arguments. A brief list of some of these and concise notes as to their significance is as follows.

1) CAMKII – Calcium-calmodulin kinase II – this is a key co-stimulating and triggering factor of many of the key cell reactions, particularly relating to synaptic transmission, growth, movement, cell division and growth, coagulation and thousands of reactions in the cell.

2) Synaptic Transmission – this is the basic building block of neural transmission and the molecular substrate of thinking,. remembering, feeling and everything neural. Indeed the article highlights also gap junction formation. These are critical communicating points not only of physical adhesion but also for new synapse formation and cellular cross-talk as occurs between neurons and glial cells in the brain. Important communications have recently been worked out where not only are neurons involved in neural process, but glial cells also have important active and supportive and facilitatory (controlling role). Gap junctions are key features of this regulation and cross talk. synapses are formed subsequent to gap junction formation and intracellular cross talk. If these are disturbed than the key synapses, on which depend memory emotion mood and perception cannot form normally and the neural circuit looses its plasticity. This is particularly true of the new nerve cells entering the circuit and providing key contributions to plasticity which is the molecular substrate of learning.

3) Glutamate and dopamine dependent neural stimulation are also featured which are key transmitters of synaptic information in the brain and long known to be involved in addiction. Importantly they are also involved in age dependent decline in brain function, and this explains the obvious clinical and experimental parallels between brain ageing and the plethora of neuropsychiatric disorders in all the various drug addictions (ie. tobacco, alcohol, cocaine, opiates and especially cannabis).

4) MAP Kinases / ERK kinases (mitogen activated and extracellular related kinases – kinases add a high energy phosphate group to various substrates particularly enzymes which typically up-regulate their activity). These are key pathways long known to be related to cell growth. They are also involved in cancer induction. This fits again with the pro-ageing phenomena mentioned above, and also the incidence of cancer in various addictions (tobacco, alcohol and cannabis).

5) Gonadotrophins releasing hormone. Whilst much work has centred on stress as a trigger for relapse into drug use often focussing on CRH (corticotrophin releasing hormone and the cortisol system in the adrenal cortex) , relatively little has examined the role of the stress system as relates to gonadal function. This is curious to some extent as the loss of the menstrual period in the female, the lowered sperm count in males, loss of libido, osteoporosis (in part gonadally determined in that sex steroids are known in both male and female to be related to maintenance of bone density) and their impact on cardiovascular disease (with females enjoying much greater protection than males, which has long been attributed to the influence of estrogen) have all been recognized for a long period. This finding suggests that just as the general systemic stress system is activated by addiction so is the gonadal one. This might account for several of the findings of addiction, and relate to many of the differences in addiction between the sexes.

6) PKA PKC (protein kinases A and C) are also major intracellular kinases and pivotal points of intracellular cell signalling for a host of pathways. Their implication implies massive pirating of the intracellular transduction cascades.

7) The insulin signalling pathway (Table 1). I had not seen evidence of the involvement of this pathway before in the addiction literature. It is the great star of the ageing literature – more has been written on this pathway in the ageing literature than any other pathway. It is a prime candidate to mediate the pro-ageing effects of addition which my clinic is increasingly documenting, and has also been noted (in part) by studies from the NIH, Johns Hopkins and Boston University hospitals. This is a very important finding and again means the nemesis of the lying legalization juggernaut. It is important to realize that this has tremendous popular appeal. by getting the message out that addiction makes you old ugly decrepit and demented – young people – particularly young females who are normally pre-occupied with beauty – should be warned away from its horrors. This was particularly evident with the interest shown by a north American fashion magazine in the publication of our own work on premature hair graying in drug addiction.

8) VEGF (Vascular endothelial growth factor). This is a key molecule which has an established role in the formation of new blood vessels. It is also involved in cancer development, and stem cell activity. Brain stem cell growth (neurogenesis) has been shown to be blood dependent. Whilst the exact reasons for the blood to be involved in stem cell action, VEGF has been shown to be one of the key factors which facilitates neurogenesis. BDNF (brain derived growth factor ) is another principal determinant of neurogenesis, although many other factors have also been listed). since these new nerve cells are key to memory and mood and brain circuit activity, inhibition or impeding of this process by interfering with VEGF pathways, suggests irreversible damage to these key cells. It should be noted that it is not yet possible to image neurogenesis either clinical or in the living experimental animal, although this is an area of intense investigation in many labs around the world.

9) Protein folding abnormalities . This leads to prion diseases like Jacob Kreuzefeldt disease and mad cow disease. Alzheimer’s disease is also a disease in part of protein misfolding. This is what leads to the development of the senile plaques which are made up of insoluble beta amyloid particles which form macroaggregates and are associated with cell tangles and synaptic dysfunction in Alzheimer’s disease. The exact molecular pathogenesis of this disorder is however not well understood. This is a terrible blow to the legalizers. To suggest that addiction is related to protein folding disorders is a terrible thing, particularly when this is an area of such active investigation globally. There are whole research departments which are devoted to abnormalities of protein folding.

Source: Chuan-Yun Li, Xizeng Mao, Liping Wei*
Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People’s Republic ofChina

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

Patients with chronic hepatitis C (HCV) infection should not use marijuana (cannabis) daily, according to a study published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute. Researchers found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis. The recommendation to avoid cannabis is especially important in patients who are coinfected with HCV/HIV since the progression of fibrosis is already greater in these patients.

“Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise,” according to Norah Terrault, MD, MPH, from the University of California, San Francisco and lead investigator of the study. “It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”

This is the first study that evaluates the relationship between alcohol and cannabis use in patients with HCV and those coinfected with HCV/HIV. It is of great importance to disease management that physicians understand the factors influencing HCV disease severity, especially those that are potentially modifiable. The use and abuse of both alcohol and marijuana together is not an uncommon behavior. Also, individuals who are moderate and heavy users of alcohol may use cannabis as a substitute to reduce their alcohol intake, especially after receiving a diagnosis like HCV, which affects their liver. Researchers found a significant association between daily versus non-daily cannabis use and moderate to severe fibrosis when reviewing this factor alone. Other factors contributing to increased fibrosis included age at enrollment, lifetime duration of alcohol use, lifetime duration of moderate to heavy alcohol use and necroinflammatory score (stage of fibrosis). In reviewing combined factors, there was a strong (nearly 7-fold higher risk) and independent relationship between daily cannabis use and moderate to severe fibrosis. Gender, race, body mass index, HCV viral load and genotype, HIV coinfection, source of HCV infection, and biopsy length were not significantly associated with moderate to severe fibrosis.

Of the 328 patients screened for the study, 204 patients were included in the analysis. The baseline characteristics of those included in the study were similar to those excluded with the exception of daily cannabis use (13.7 percent of those studied used cannabis daily versus 6.45 percent of those not included). Patients who used cannabis daily had a significantly lower body mass index than non-daily users (25.2 versus 26.4), were more likely to be using medically prescribed cannabis (57.1 percent versus 8.79 percent), and more likely to have HIV coinfection (39.3 percent versus 18.2 percent).

The prevalence of cannabis use amongst adults in the U.S. is estimated to be almost 4 percent. Regular use has increased in certain population subgroups, including those aged 18 to 29.

Hepatitis is an inflammation of the liver. Hepatitis C is the most common form of hepatitis and infects nearly 4 million people in the U.S., with an estimated 150,000 new cases diagnosed each year. While it can be spread through blood transfusions and contaminated needles, for a substantial number of patients, the cause is unknown. This form of viral hepatitis may lead to cirrhosis, or scarring, of the liver. Coinfection of hepatitis C in patients who are HIV positive is common; about one quarter of patients infected with HIV are infected with hepatitis C. The majority of these patients, 50 to 90 percent, were infected through injection drug use. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants yearly in the U.S.

Source: http://www.medicalnewstoday.com/articles/95434.php 29.01.08

Singapore — 23 January 2008

A study in a Wiley-Blackwell journal – Respirology – finds that the development of bullous lung disease occurs in marijuana smokers approximately 20 years earlier than tobacco smokers.

A condition often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke, bullous lung disease (also known as bullae) is a condition where air trapped in the lungs causes obstruction to breathing and eventual destruction of the lungs.

At present, about 10% of young adults and 1% of the adult population smoke marijuana regularly.
Researchers find that the mean age of marijuana-smoking patients with lung problems was 41, as opposed to the average age of 65 years for tobacco-smoking patients.

The study “Bullous Lung Disease due to Marijuana” also finds that the bullous lung disease can easily go undetected as patients suffering from the disease may show normal chest X-rays and lung functions.
High-resolution CT scans revealed severe asymmetrical, variably sized bullae in the patients studied. However, chest X-rays and lung functions were normal in half of them.

Lead author Dr. Matthew Naughton says, “What is outstanding about this study is the relatively young ages of the lung disease patients, as well as the lack of abnormality on chest X-rays and lung functions in nearly half of the patients we tested.” He added, “Marijuana is inhaled as extremely hot fumes to the peak inspiration and held for as long as possible before slow exhalation. This predisposes to greater damage to the lungs and makes marijuana smokers are more prone to bullous disease as compared to cigarette smokers.”

Patients who smoke marijuana inhale more and hold their breath four times longer than cigarette smokers. It is the breathing manoeuvres of marijuana smokers that serve to increase the concentration and pulmonary deposition of inhaled particulate matter – resulting in greater and more rapid lung destruction.

Source:http://www.aushealthcare.com.au/news/news_details.asp?nid=10642 23rd January 2008

Study could potentially help clinicians treat marijuana addiction

Research by a group of scientists studying the effects of heavy marijuana use suggests that withdrawal from the use of marijuana is similar to what is experienced by people when they quit smoking cigarettes. Abstinence from each of these drugs appears to cause several common symptoms, such as irritability, anger and trouble sleeping – based on self reporting in a recent study of 12 heavy users of both marijuana and cigarettes.

“These results indicate that some marijuana users experience withdrawal effects when they try to quit, and that these effects should be considered by clinicians treating people with problems related to heavy marijuana use,” says lead investigator in the study, Ryan Vandrey, Ph.D., of the Department of Psychiatry at the Johns Hopkins University School of Medicine.

Marijuana is the most widely used illicit drug in the United States. Admissions in substance abuse treatment facilities in which marijuana was the primary problem substance have more than doubled since the early 1990s and now rank similar to cocaine and heroin with respect to total number of yearly treatment episodes in the United States, says Vandrey.

He points out that a lack of data, until recently, has led to cannabis withdrawal symptoms not being characterized or included in medical reference literature such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV) or the International Classification of Diseases, 10th edition (ICD-10). Since the drafting of the DSM-IV in 1994, an increasing number of studies have surfaced suggesting that cannabis has significant withdrawal symptoms. What makes Vandrey’s recent study unique is that it is the first study that compares marijuana withdrawal symptoms to withdrawal symptoms that are clinically recognized by the medical community – specifically the tobacco withdrawal syndrome.

“Since tobacco withdrawal symptoms are well documented and included in the DSM-IV and the IDC-10, we can infer from the results of this comparison that marijuana withdrawal is also clinically significant and should be included in these reference materials and considered as a target for improving treatment outcomes,” says Vandrey.

Vandrey added that this is the first “controlled” comparison of the two withdrawal syndromes in that data was obtained using rigorous scientific methods – abstinence from drugs was confirmed objectively, procedures were identical during each abstinence period, and abstinence periods occurred in a random order. That tobacco and marijuana withdrawal symptoms were reported by the same participants, thus eliminating the likelihood that results reflect physiological differences between subjects, is also a strength of the study.

Interestingly, the study also revealed that half of the participants found it easier to abstain from both substances than it was to stop marijuana or tobacco individually, whereas the remaining half had the opposite response. “Given the general consensus among clinicians that it is harder to quit more than one substance at the same time, these results suggest the need for more research on treatment planning for people who concurrently use more than one drug on a regular basis,” says Vandrey.

Vandrey’s study, which appears in the January issue of the journal Drug and Alcohol Dependence, followed six men and six women at the University of Vermont in Burlington and Wake Forest University School of Medicine in Winston-Salem, N.C., for a total of six weeks. All were over 18 (median age 28.2 years), used marijuana at least 25 days a month and smoked at least 10 cigarettes a day. None of the subjects intended to quit using either substance, did not use any other illicit drugs in the prior month, were not on any psychotropic medication, did not have a psychiatric disorder, and if female, were not pregnant.

For the first week, participants maintained their normal use of cigarettes and marijuana. For the remaining five weeks, they were randomly chosen to refrain from using either cigarettes, marijuana or both substances for five-day periods separated by nine-day periods of normal use. In order to confirm abstinence, patients were given daily quantitative urine toxicology tests of tobacco and marijuana metabolites. Withdrawal symptoms were self reported on a daily basis Monday through Friday using a withdrawal symptom checklist that listed scores for aggression, anger, appetite change, depressed mood, irritability, anxiety/nervousness, restlessness, sleep difficulty, strange dreams and other, less common withdrawal symptoms. Patients also provided an overall score for discomfort they experienced during each abstinence period.

Results showed that overall withdrawal severity associated with marijuana alone and tobacco alone was of similar frequency and intensity. Sleep disturbance seemed to be more pronounced during marijuana abstinence, while some of the general mood effects (anxiety, anger) seemed to be greater during tobacco abstinence. In addition, six of the participants reported that quitting both marijuana and tobacco at the same time was more difficult than quitting either drug alone, whereas the remaining six found that it was easier to quit marijuana or cigarettes individually than it was to abstain from the two substances simultaneously.

Vandrey recognizes that the small sample size is a limitation in this study, but the results are consistent with other studies indicating that marijuana withdrawal effects are clinically important.

Source: http://www.eurekalert.org/pub_releases/2008-01/jhmi-mwa012408.php :
Eric Vohr evohr1@jhmi.edu Johns Hopkins Medical Institutions

HONG KONG (Reuters) – Smoking a joint is equivalent to 20 cigarettes in terms of lung cancer risk, scientists in New Zealand have found, as they warned of an “epidemic” of lung cancers linked to cannabis.
Studies in the past have demonstrated that cannabis can cause cancer, but few have established a strong link between cannabis use and the actual incidence of lung cancer.
In an article published in the European Respiratory Journal, the scientists said cannabis could be expected to harm the airways more than tobacco as its smoke contained twice the level of carcinogens, such as polyaromatic hydrocarbons, compared with tobacco cigarettes.
The method of smoking also increases the risk, since joints are typically smoked without a proper filter and almost to the very tip, which increases the amount of smoke inhaled. The cannabis smoker inhales more deeply and for longer, facilitating the deposition of carcinogens in the airways.
“Cannabis smokers end up with five times more carbon monoxide in their bloodstream (than tobacco smokers),” team leader Richard Beasley, at the Medical Research Institute of New Zealand, said in a telephone interview.
“There are higher concentrations of carcinogens in cannabis smoke … what is intriguing to us is there is so little work done on cannabis when there is so much done on tobacco.”
The researchers interviewed 79 lung cancer patients and sought to identify the main risk factors for the disease, such as smoking, family history and occupation. The patients were questioned about alcohol and cannabis consumption.
In this high-exposure group, lung cancer risk rose by 5.7 times for patients who smoked more than a joint a day for 10 years, or two joints a day for 5 years, after adjusting for other variables, including cigarette smoking.
“While our study covers a relatively small group, it shows clearly that long-term cannabis smoking increases lung cancer risk,” wrote Beaseley.

“Cannabis use could already be responsible for one in 20 lung cancers diagnosed in New Zealand,” he added.
“In the near future we may see an ‘epidemic’ of lung cancers connected with this new carcinogen. And the future risk probably applies to many other countries, where increasing use of cannabis among young adults and adolescents is becoming a major public health problem.”
(Reporting by Tan Ee Lyn; Editing by Alex Richardson)

Source: http://www.reuters.com/article/healthNews/ Jan. 29 2008

The study’s demonstration of a
strong association between cannabis
use and periodontitis experience by
age 32 years indicates that long-term
smoking of cannabis is detrimental to
the periodontal tissues and that public
health measures to reduce the prevalence
of cannabis smoking may have
periodontal benefits for the population.

To our knowledge, no previous
studies have examined this relationship,
so there are no data with which
to compare the findings. Determining
whether the association exists in other
populations should be a priority for
periodontal epidemiological research.

The nature of the biological mechanism
for the observed association is
currently unclear. The periodontal
effects of tobacco smoke are thought
to occur via the systemic effects of
nicotine and other toxic constituents
on immune function and the inflammatory
response within the periodontal
tissues. Cannabis contains more
than 400 compounds, including more
than 60 cannabinoids; the noncannabinoid
constituents are similar to
tobacco (except for nicotine), and
those have been reported to carry systemic
health risks and have histopathological
effects that are similar to
those of tobacco smoke.

Although definitively establishing the
periodontal effects of exposure to cannabis
smoke we should await confirmation
in other populations and settings,
health promoters and dental and medical
practitioners should take steps to
raise awareness of the strong probability
that regular cannabis users may be
doing damage to the tissues that support
their teeth.

Source: Jama Feb.6 2008 Vol.299 No.5

Although detoxification cannot, in itself, be considered a treatment for addiction, it is one of the most pivotal phases. In order to facilitate entry into recovery and/or rehabilitation programs, a detoxification treatment has to be experienced as easy and safe by the patient. In consideration of the many inconveniences related to standard withdrawal treatments, there is an interest in developing alternative pharmacological strategies. The main rationales for using anticonvulsants in substance-abuse patients are their lack of addiction potential, evidence support a role of kindling mechanisms in withdrawal syndromes and their efficacy in comorbid psychiatric disorders. The available data currently support the utilization of carbamazepine as a treatment for detoxification from benzodiazepines, alcohol and opiates, and as a useful agent to reduce cocaine consumption. The use of valproate is well corroborated for alcohol detoxification and it seems to be a promising treatment for the reduction of cocaine use; however, it has been found to be ineffective against benzodiazepine withdrawal symptoms. Some preliminary data suggest that lamotrigine could be useful in opiate and cocaine dependence. Gabapentin shows potential as a treatment for cocaine dependence, and some case reports have stimulated interest in this agent for alcohol and benzodiazepine detoxification. Due to its particular pharmacological profile, topiramate is one of the most interesting newer anticonvulsants. It has been found to be efficacious in opiate and possibly benzodiazepine detoxification and also has theoretical potential as a preventive therapy.

Source: Drugs Today (Barc). 2004 Jul;40(7):603-19. . Daniele.Zullino@inst.hospvd.ch

A study has found that heavy cannabis smoking is a major cause of gum disease.

The investigation, which tracked a group of 1000 people born in Dunedin in 1972-73, found heavy cannabis use was responsible for more than one-third of the new cases of gum disease by age 32.

The study involved researchers from the University of Otago, King’s College in London, Duke University and the University of North Carolina in the United States. Professor Murray Thomson from University of Otago School of Dentistry said toxins in cannabis smoke were detrimental to periodontal health. “The problem is not the smoke itself – it’s what’s in the smoke,” he said. “In the mouth, there is a fine balance between tissue destruction and tissue healing and the various toxins in cannabis smoke disrupt that.”

Professor Thomson said gum disease was one of the most common diseases of adulthood, and caused problems such as the loss of support for the teeth. There was also emerging evidence it could be a risk factor for heart disease, stroke and pre-term birth.

Heavy cannabis users are those who smoke cannabis 41 times or more per year between the ages of 18 and 32.

The study is the first to have investigated whether smoking anything other than tobacco is detrimental for the gums. The evidence has been published in the prestigious Journal of the American Medical Association.

Source: New Zealand Herald.6 Feb 2008

“Sewages is more than just filth. It’s evidence of our worst habits, everything from caffeine to cocaine, all ingested and flushed down the toilet. Now scientists are using wastewater to drug-test entire cities, and the results are sobering.”

Excerpt:

“In 2001 Daughton proposed the novel ideal of testing for illicit drugs in wastewater…..Sewer epidemiology stalled stateside until 2006, when environmental chemist Jennifer Field of Oregon State University hit upon the idea as a way to help assess Oregon’s growing meth problem…Field began conducting a small proof-of-concept study, analyzing teaspoon-size samples of wastewater from 10 cities left over from an older environmental study. She found that a sample from a popular gambling destination boasted the widest range of drugs, while one from an affluent town tested positive exclusively for cocaine…Her team made headlines last august when they presented these and other findings at the American Chemical Society meeting in Boston. Their results – similar to those of Zuccato and Fanelli – showed cocaine levels highest on the weekends while levels of methamphetamine remained constant. ‘once you’re hooked, you’re hooked,’ field points out.

“Today, Field is heading up the most ambitious community urinalysis test yet. She’s soliciting wastewater samples from 130 treatment plants throughout Oregon, which service approximately 80 percent of its 3.7 million resisdents…Oregon Health Sciences Universitiy, which is footing the $30,000 bill through its Medical Research Fund, stands to gain a trove of data about drug use in individual communities, since Field will have direct estimates from areas in which surveyors have surely never set foot.

“…For marijuana, the target molecule is THC, which is tricky in its owns right. ‘There is a wide variation in the amount of active ingredient in grass,’ Fanelli says. He relies on average potency, which can be gleaned from pot busts. Sewer epidemiologists must factor in all of these variables….And some people worry about how such methods might infringe on their civil liberties. One of the calls Field received after news broke about her proof-of-concept study, for instances, was from High Times magazine. ‘They wanted to know about privacy, she says.”

Source: Popular Science, March 2008

Cannabis use in British teenagers has increased tenfold in the last 20 years
Children who smoke cannabis are twice as likely to get into trouble – both in the classroom and outside the school gates. Boys turn to vandalism, theft and fights, while girls misbehave at school, a four-year study of thousands of pupils aged between 11 and 15 found.
Young males are also up to twice as likely to have committed “delinquent” acts such as vandalism or carrying a knife. And teenage cannabis users have double the chance of developing emotional and psychiatric problems in later life. The finding was released as Gordon Brown comes under pressure to reverse Labour’s downgrading of cannabis.
Calling on the Government to do more to combat drug use in teenagers, researcher Laura Grant said: “Cannabis has been regarded as potentially being a gateway drug to harder drug use, leading to mental health issues, leading to memory loss or impairment and having an impact on learning and social behaviour.
“I have spoken to kids that smoke cannabis every single night, they get up and go to grammar school and get good grades. “This really is a hidden issue that needs to be tackled.”
She added: “These young people are still attending school and are at odds with the general perception of what the typical young person is like who engages in these acts.
“It is no great leap to imagine that this school-attending high risk group may be a further risk of later life problems as a result of their early drug use: mentally, socially and emotionally.” Miss Grant, a sociologist at Queen’s University Belfast, studied data tracking the health and habits of almost 4,000 Northern Irish schoolchildren.
By the age of 15, more than 40 per cent had tried cannabis – a five-fold increase on four years earlier, the British Psychological Society’s annual conference in Dublin heard. She added it was unclear why cannabis had different effects on boys and girls.
A fifth of those studied were judged to be at risk of developing mental health problems in later life, with cannabis users running up to double the risk of other children.
Cannabis use in British teenagers has increased tenfold in the last 20 years. By the age of 16, almost four in ten will have tired cannabis and almost one in ten is a regular user. In 2005, 10,000 youngsters aged between 11 and 17 were treated for cannabis use.
Previous studies have shown a clear link between cannabis use in the teenage years and mental illness in later life. It is thought that used during the developmental years, the drug may do permanent damage to the developing brain.
Source: Daily Mail 5th April 2008

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

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

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

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

Brain scans reveal that cocaine, alcohol and tobacco use during pregnancy can cause changes in the brain scan of developing fetuses, and that these changes can remain detectable for years, HealthDay News reported April 7.
“We found that reductions in cortical gray matter and total brain volumes were associated with prenatal exposure to cocaine, alcohol or cigarettes,” said researcher Michael Rivkin of Children’s Hospital Boston.
Rivkin and colleagues from Children’s Hospital and the Boston Medical Center conducted MRI scans on the brains of 35 children with an average age of 12 who had been exposed to cocaine, tobacco or alcohol before birth. Children with fetal alcohol syndrome were excluded from the study.
Researchers found that the more substances the adolescents had been exposed to, the more brain volume they lost.

Source: April 2008 issue of the journal Pediatrics.

University of Washington researchers say that animal studies show that methamphetamine use causes lasting changes in the brain’s dopamine system, making it especially difficult for users to stop using the drug.
HealthDay News reported April 9 that researcher Nigel Bamford and colleagues found that long-term methamphetamine use depressed the synaptic dopamine-release system in the corticostriatal area of the brain — a condition that gets temporarily reversed when a dose of methamphetamine is administered.
Researchers said that methamphetamine appears to cause long-term changes in certain dopamine receptors and with the neurotransmitter acetylcholine. The findings “might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance,” Bamford and colleagues wrote.
Source: April 10, 2008 issue of the journal Neuron.

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.

Babies born to women who smoke during pregnancy are more likely to have heart defects that are not related to genetics, Reuters reported April 9.
Researcher Sadia Malik of the University of Arkansas for Medical Sciences and colleagues compared more than 3,000 infants born with heart defects to a similar group of infants without heart problems. They found that heart defects were more common among children of women who smoked during the month before they became pregnant or during the first trimester of their pregnancy. Moreover, the risk of babies being born with heart problems was higher when mothers smoked more.
“If even a fraction of congenital heart defects and other birth defects could be prevented by decreasing maternal tobacco use, it would result in improved reproductive outcomes and a saving of millions of health care dollars,” the researchers said.
Source: April 2008 issue of the journal Pediatrics.

A new study found a link between secondhand smoke and sudden infant death syndrome (SIDS), the Toronto Globe and Mail reported Feb. 21.
The study was conducted by researchers at Toronto’s Hospital for Sick Children and the University of Maryland.
In analyzing 44 SIDS deaths, researchers found twice the amount of nicotine levels in the lung tissue of babies whose parents acknowledged that they were smokers than in babies who died of other causes.
“It’s biochemical proof that smoke is associated with SIDS,” said Gideon Koren, lead investigator and senior scientist at the hospital’s research institute. “Some parents may feel guilty, and probably we underestimate the contribution of smoking to the risk of SIDS.”
Koren said additional research is needed to determine which of the toxic substances in tobacco smoke increases the risk for SIDS.
The study’s findings also are raising questions as to whether parents should be held responsible for exposing their babies to tobacco-filled air at home.
“In light of this new research, we and other agencies will be looking at it and rethinking our position to see if a stronger position is more feasible,” said Gail Vandermeulen of the Ontario Association of Children’s Aid Societies.
Source: Journal of Pediatrics February. 2002

The children of women who smoke during pregnancy are at increased risk of suffering strokes or heart attacks later in life, a new study concludes.
Reuters reported March 2 that children of smokers — studied as young adults — were found to have thicker walls around the carotid arteries in their necks, making them more vulnerable to stroke and heart attacks. Children of women who smoked the most during pregnancy had the thickest arterial walls, researchers found.
“There is the possibility that the compounds in tobacco smoke go through the placenta and directly damage the cardiovascular system of the fetus,” said researcher Cuno Uiterwaal at the University Medical Center Utrecht in the Netherlands. “The damage appears to be permanent and stays with the children.”
Source: Findings presented at a recent American Heart Association conference in Orlando. March 5, 2007

A study from the United Kingdom finds that children of mothers who smoke have smaller lung volumes and are more at risk for serious lung disease later in life, Reuters reported Feb. 26.
The study by researchers at the University of Bristol and the University of Glasgow involved 2,000 men and women in their 30s, 40s, and 50s whose parents smoked and took part in a study in the 1970s.
After conducting respiratory tests, the researchers found that children of mothers who smoked had smaller lungs, regardless of whether they also smoked. In addition, these children were more at risk for chronic obstructive pulmonary disease (COPD). If they themselves smoked, the risk was as high as 70 percent.
“Our results suggest that the effects of maternal smoking on lung size are permanent,” said Dr. Mark Upton, lead author of the study.
Children from households where the father smoked, but not the mother, showed poorer lung function, but not as great as those whose mothers smoked.
Source: American Journal of Respiratory and Critical Care Medicine. Feb. 15, 2004

Children exposed to secondhand smoke at home are more likely to carry the streptococcus pneumonia bacteria in their nose and throat, according to Israeli researchers.
A study involving more than 200 children and their mothers found that 76 percent of children exposed to secondhand smoke carried the bacteria in their noses and throats, compared to 60 percent of those not exposed to smoking. The bacteria can cause minor illnesses like ear infections or more dangerous conditions like sinusitis, pneumonia, and meningitis.
Among the mothers, 32 percent of smokers carried the bacteria, compared to 15 percent of nonsmokers exposed to tobacco smoke and 12 percent of nonsmokers not exposed to secondhand smoke.
“Since carriage in the nose is the first step in causing disease, the increased rate of carriage suggests more frequent occurrence of the disease. Indeed, active and passive smoking are associated with increased rate of respiratory infectious diseases,” said lead study author David Greenberg, M.D. “This should definitely encourage the parents not to smoke in the presence of their child, especially if this child has predisposing factors such as asthma.”
Source: Clinical Infectious Diseases. April 1, 2006

Researchers have found that infants as young as three months old accumulate nicotine and carcinogens in their bodies when they are exposed to tobacco smoke, the Guardian reported May 12.
Authors of the study — the first to test smoking exposure on children so young — said that parents who smoking around infants could raise children’s’ risk of addiction, cancer, and other health problems later in life. “The take-home message is that parents should not smoke around their children, because they will suffer from the exposure,” said Stephen Hecht of the University of Minnesota cancer center.
The study of 144 children (ages three months to one year) who lived with family members who smoked found that 98 percent had nicotine in their urine, and 93 percent had cotinine, a marker for nicotine metabolism. Further, 47 percent of the infants had detectable levels of NNAL, a carcinogenic metabolite of cigarette smoke.
“Persistent exposure to environmental tobacco smoke in childhood could be related to cancer later in life,” said Hecht
Source: Cancer Epidemiology Biomarkers and Prevention. May 2006

Infants with at least one parent who smokes have higher levels of a nicotine metabolite in their bodies than the children of nonsmokers, the Guardian reported June 19.
Researchers from the University of Leicester and Warwick Medical School said the study showed that smoking parents are turning their infants into passive smokers, putting them in danger of breathing problems and crib death. “Babies and children are routinely exposed to cigarette smoke by their [caregivers] in the home without the legislative protection available to adults in public places,” the authors stated.
Babies whose mothers smoked had cotinine levels four times higher than children whose parents were both nonsmokers, while babies with fathers who smoked had cotinine levels twice as high.
Cotinine levels were higher among babies who shared a bed with their parents, and during the winter. “Higher cotinine levels in colder times of year may be a reflection of the other key factors which influence exposure to passive smoking, such as poorer ventilation or a greater tendency for parents to smoke indoors in winter,” the authors said.
Source: Archives of Diseases in Childhood. June 2007

Drinking or smoking heavily can speed up the development of Alzheimer’s disease, according to a new study. Scientists found that drinkers developed the disease almost five years earlier and heavy smokers just over two years earlier, after studying 938 people aged 60 or more who had been diagnosed with Alzheimer’s.
Ranjan Duara, of the Mount Sinai Medical Centre in Miami Beach, Florida, said the results were significant “because it’s possible that if we can reduce or eliminate heavy smoking and drinking, we could substantially delay the onset of Alzheimer’s disease for people and reduce the number of people who have Alzheimer’s at any point in time”. He added: “It has been projected that a delay in the onset of the disease by five years would lead to a nearly 50% reduction in the total number of Alzheimer’s cases. In this study, we found that the combination of heavy drinking and heavy smoking reduced the age of onset of Alzheimer’s disease by six to seven years, making these two factors among the most important preventable risk factors for Alzheimer’s disease.”
Researchers gathered evidence of drinking history from family members and also looked at whether the participants had a particular variant of the APOE gene, which predisposes people to get Alzheimer’s earlier than normal. The results, presented yesterday at the American Academy of Neurology’s annual meeting in Chicago, showed that 7% of the participants were heavy drinkers, defined as more than two drinks a day; 20% had a history of heavy smoking, defined as smoking one pack of cigarettes or more a day; and 27% had the Alzheimer’s APOE gene variant.
Heavy drinkers developed Alzheimer’s 4.8 years earlier than those who were not heavy drinkers. Heavy smokers developed the disease 2.3 years sooner than people who were not heavy smokers. People with the APOE variant developed the disease three years sooner than those without it.
The researchers also looked at combined risk factors, and found that people that came into all three risk areas developed Alzheimer’s 8.5 years earlier than those with none of the risk factors.

Source: the Guardian Thursday April 17 2008

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

Almost half of all perpetrators of homicide were intoxicated, while alcohol related hospital discharges increased by 92%
The Health Service Executive (HSE), today, Monday 21st April, published a detailed review entitled “Alcohol Related Harm in Ireland.” The report outlines the recent rising trends in alcohol consumption rates, the harmful effects these rates are having on the user and the damaging results they have on other people.
The report provides an overview of recent studies into alcohol consumption, assesses the most up to date research into their effects and offers recommendations on how best to reduce the unhealthiest consequences.
Following four years of static alcohol consumption, in 2007 there was a rise of 2.7% per capita in individual alcohol consumption.
Some of the key findings of the report include:
Alcohol Related Harm to the Drinker:
• 28% of all injury attendances in Accident and Emergency Departments in acute hospitals were alcohol related;
• Alcohol related hospital discharges, which is an indicator of attendance, increased by 92% between 1995 and 2002;
• Cancer of the liver had the highest increase in cancer incidence rates in comparison to all cancers between 1994-2003;
• Almost half of men and over a quarter of women agreed that drinking alcohol had contributed to them having sex without contraception;
• Between 1995 and 2004, Sexually Transmitted Infections (STIs) increased by 217%;
• Alcohol is a contributory factor in 36.5% of all fatal crashes;
• Between 1996 and 2002, public order adult offences increased by 247% (from 16,284 to 56,822) followed by a decrease in 2003 and 2004 but increased again in 2005;
Alcohol Related Harm to Others:
• Almost half (46%), of those who committed homicide were intoxicated at the time;
• Between 1990 and 2006, 2,462 people were killed on the roads between 9pm-4am, the time most associated with alcohol related driving;
• 44% of all respondents had experienced harm by their own or someone else’s alcohol use;
• In a quarter of severe domestic abuse cases, alcohol was involved;
• The Coombe Women’s Hospital found that 63% of women reported alcohol use during pregnancy, with 7% drinking 6 or more drinks per week;
• IBEC cited that alcohol related illness was cited by 12% of companies as a cause of short-term absence from work for males and 4% for females;
Dr Joe Barry, HSE Population Health Directorate, said; “This report shows that alcohol related harm is not only confined to the negative consequences experienced by the drinker, such as illness and disease, but extends to others as well, which too often can lead to physical injury or even death. Inevitably, this also causes strain on health services and its staff who have to divert resources to treat avoidable alcohol related injuries and conditions.”
“The HSE provides a wide range of responses, from hospital and primary care services, through to specific alcohol and drug initiatives and public awareness and education campaigns. However, improvements in alcohol related harms in Ireland will require a sustained multi-sectoral response.”
Source: www.hse.ie 21st April 2008

PhD [S]; Sarang, Anya [//]; Lewis, Kim MSc [P]; Parry, John PhD [P]
Abstract:
Objective: To measure HIV prevalence and associated risk factors among recent initiates into drug injecting in 2001 and 2004 in Togliatti City, Russian Federation.

Design: Two unlinked, anonymous, cross-sectional, community-recruited surveys of injecting drug users (IDUs) with oral fluid samples for anti-HIV testing.

Methods: IDUs completed an interviewer-administered questionnaire, and oral fluid samples were tested for antibodies to HIV. Demographic characteristics and injecting risk behaviors were compared between subsamples of IDUs who reported injecting for 3 years or less in each of the survey years, 2001 (n = 138) and 2004 (n = 96). Univariable and multivariable analyses explored risk factors with anti-HIV among these new injectors.

Results: Among IDUs overall, although HIV prevalence was high, a lower prevalence was found in 2004 (38.5%, 95% confidence interval [CI]: 34.1 to 42.9) than in 2001 (56%, 95% CI: 51.2 to 60.8). A significantly lower prevalence of HIV was found among new injectors in 2004 (11.5%, 95% CI: 5.0 to 17.9) than in 2001 (55.2%, 95% CI: 46.7 to 63.8). Proportionally, fewer new injectors reported injecting daily, injecting with used needles/syringes, and frontloading in 2004 compared with 2001. Decreased odds of anti-HIV were associated with being recruited in 2004 and with a history of drug treatment. Increased odds of HIV were associated with exchanging sex, duration of injection, and frontloading.

Conclusions: Findings indicate a decrease in HIV prevalence among new injectors between 2001 and 2004 and emphasize the role of provision of needle/syringes through pharmacies and providing access to voluntary HIV testing. These findings have implications for other cities in which explosive HIV outbreaks have occurred.
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes. 47(5):623-631, April 15, 2008.

A new study published in the Journal of Acquired Immune Deficiency Syndromes finds that HIV prevalence in the city Toggliatti in Russia declined from 56 percent in 2001 to 38.5 percent in 2004, “despite the lack of needle and syringe exchange.” The study found that “a history of drug treatment was associated with a reduced likelihood of testing positive for HIV,” and credits less frequent injection of drugs for the overall reduction in HIV among new injectors, “rather than interventions through services, such as needle exchanges.”
Compare the HIV decline in Toggliatti, Russia—which has no needle exchange program—to the HIV explosion in Vancouver, Canada, which boasts the largest and one of the oldest needle distribution program in North America.
When Vancouver’s needle exchange program (NEP) was established in the late 1980s, the city’s estimated HIV prevalence was 1 to 2 percent. By 1997, one-quarter of the of the drug users in Downtown Eastside were infected with HIV, with a transmission rate of nearly 19 percent, giving Vancouver the distinction of having the highest infection rate of any city in the developed world. By 2003, an estimated 40 percent of the drug using population in Vancouver was infected with HIV. Research has directly linked needle exchange to this trend. A study published in the Journal of Acquired Immune Deficiency Syndromes in 1997 found that “frequent NEP attendance” was one of the “independent predictors of HIV-serostatus” among IDUs. The study found that HIV-positive IDU were more likely to have ever attended NEP and to attend NEP on a more regular basis compared with HIV-negative IDUs. With only one exception, the NEP was the main source of syringes for all of those who became infected during the course of the study.
Source: http:// www.aidsmap.com/en/news/AA1E32BC-20EF-4B93-B811-83CF26FEF1F9.asp April 23, 2008

A significant decline in risky injecting practices and a decline in HIV prevalence in new drug injectors was seen in a Russian city severely affected by HIV between 2001 and 2004, despite the lack of needle and syringe exchange, researchers from the London School of Hygiene report in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes.

The researchers believe that word of mouth, and growing awareness of the rising number of HIV diagnoses, contributed to the shoft, but also note that changes in the drug market during the study period may have driven the change in injecting and equipment sharing practices.

Several major cities worldwide have witnessed explosive outbreaks of HIV due to injecting drug use. In these contexts, some research suggests that new injectors might adopt riskier behaviours, or alternately, within the context of an HIV outbreak, new injectors might adopt safer behaviours than longer term injectors. Thus, measuring behavioural change in targeted populations may help to monitor risks in a changing epidemic.

Therefore investigators from the London School of Hygiene and Tropical Medicine examined two anonymous, cross-sectional community-recruited surveys of injecting drug users in Toggliatti city, which is in the Samara region of Russia. They also conducted a review of new HIV diagnoses in the region since 2000.

Participants in both surveys had used injection drugs in the previous four weeks and consented to HIV testing via oral fluid samples. The participants analysed were injecting drug users who had injected for three years or less (recent injectors): 138 people in 2001 and 96 in 2004.

Participants were identified by respondent-driven sampling, in which those initially recruited act as ‘seeds’ for an expanding chain of referrals. Mathematical modelling was then used to estimate population effects. Injection drug use was estimated to occur in 5.4% of the registered population of the city, but in 2.7% of the assumed genuine population, close to 1 million people.

In 2004, a lower proportion of injecting drug users reported injecting daily, using used needles, syringes or filters, or front-loading – when a solution of drug is passed from a donor syringe into another person by removing the needle. Although fewer injecting drug users in 2004 reported contact with drug treatment services, needle exchange or outreach workers, more had been tested for HIV.

Overall HIV prevalence was high among injecting drug users, but it declined between 2001 and 2004, from 56% to 38.5% A significantly lower prevalence of HIV was found among new injectors in 2004 (11.5%, 95% CI: 5.0 – 17.9) than in 2001 (55.2%, 95% CI: 46.7 – 63.8). A history of drug treatment was associated with a reduced likelihood of testing positive for HIV, while increased odds of HIV were associated with exchanging sex for drugs and sex work, duration of injection (odds ratio 1.4 per year), and front-loading. Most injecting equipment was obtained from pharmacies in both surveys.

Examination of surveillance data revealed that in 2000, 97% of new HIV cases were linked with IDU whereas that figure had fallen to 56.4% by 2005.

The reduction in HIV among new injectors in 2004 seems likely to be related to general risk awareness and changes in injection practice rather than interventions through services, such as needle exchanges. However, the authors suggest that “IDUs, and IDUs involved in sex work specifically, should be targets for sexual risk reduction interventions”.

Given the nature of IDU-related health services in this region, the authors write that “we emphasize the need for increasing access to voluntary and confidential HIV testing in combination with increasing the accessibility of sterile injecting equipment through pharmacies”.

Source: Platt L et al. Changes in HIV prevalence and risk among new injecting drug users in a Russian city of high HIV prevalence. J Acquir Immune Defic Syndr 47: 623 – 631, 2008.

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

Research Summary
Within five years of quitting former female smokers have no greater risk of dying from coronary heart disease than nonsmokers, according to a new study.
HealthDay News reported May 6 that while risk for other smoking-related health problems lingers longer, heart health seems to bounce back more quickly.
Lung-cancer risk persisted 30 years after quitting, however, and former smokers face higher odds of dying from chronic obstructive pulmonary disease for more than 20 years after quitting, the study found.
The study was conducted by researcher Stacey Kenfield of the Harvard School of Public Health and colleagues. “It’s never too early to stop, and it’s never too late to stop,” said Kenfield.
“This shows the power of quitting smoking,” said Jay Brooks, study co-author and chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. “We’ve known this for a number of years, but the beauty of this study is it is a very large and well-studied group of people. When I tell people to quit smoking, I say the effect of the heart precedes that of the lungs. If you’ve smoked, you need to be cognizant that you’re still at an increased risk of lung cancer.”
Source: May 7, 2008 issue of the Journal of the American Medical Association.

Long-term harmful effects of marijuana (MJ) include risk for heart attacks and strokes in addition to impaired learning and memory. The active chemical in MJ called delta-9-tetrahyrdocannabinol (THC) is believed to exert these effects by binding to cannabinoid (CB) receptors located on several cell types in various organs. Scientists have found CB receptors in many organs including the brain, heart, liver, kidney, and spleen.

In this study, researchers investigated if persistent heavy MJ use might be associated with changes in different blood proteins in order to check if the abnormalities in the identified proteins might be related to other side-effects of marijuana.

The study was conducted with 18 long term heavy MJ users and 24 non-drug using volunteers. People with major medical and psychiatric illnesses, hypertension, head injury, HIV positive, alcohol dependency and other drug usage, were excluded from the study. Blood proteins were measured in both control volunteers and MJ users using a new method (protein chip) that has the potential to identify several new target proteins. That approach showed that apolipoprotein C-III (apoC-III) showed significant increases in MJ abusers. ApoC-III belongs to a large family of proteins that interact with lipids and helps lipids to move into and out of cells. ApoC-III is involved in transport of triglycerides and delays the breakdown of triglycerides. Increases in apoC-III levels in the blood occur in parallel with increases in triglyceride levels.

Even though we still don’t understand how heavy MJ use might cause increases in apoC-III levels, this protein might be one of the reasons why some MJ users have increased risks of heart attack and strokes.

Source: Neuroscience Article Date: 13 May 2008

Murat Yu¨ cel, PhD, MAPS; Nadia Solowij, PhD; Colleen Respondek, BSc; Sarah Whittle, PhD; Alex Fornito, PhD;
Christos Pantelis, MD, MRCPsych, FRANZCP; Dan I. Lubman, MB ChB, PhD, FRANZCPContext:

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.
Arch Gen Psychiatry. 2008;65(6):694-701
THERE IS CONFLICTING evidence regarding the long-term effects of regular cannabis use. Although growing literature suggests that long-term cannabis use is associated
with a wide range of adverse health consequences,1-4 many people in the community,
as well as cannabis users themselves, believe that cannabis is relatively harmless and should be legally available.

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,5 there is a clear need to conduct robust investigations that elucidate the long-term sequelae of long-term cannabis
use.
The strongest evidence against the notion that cannabis is harmless comes from the animal literature6-9 in which longterm cannabinoid administration has been shown to induce neurotoxic changes in the hippocampus, including decreases in neuronal volume, neuronal and synaptic density, and dendritic length of CA3 pyramidal neurons. Although such work suggests
that exposure to cannabinoids may be neurotoxic in animals, much less is known about the neurobiologic consequences of long-term cannabis exposure in humans.
Only a handful of brain imaging studies have been conducted in human cannabis users, with inconsistent findings reported.
Early cannabis research using pneumoencephalography10 reported cerebral atrophy in a small sample (N=10) of cannabis users, but further studies using computed tomography11-13 did not detect any abnormalities, despite the potential confounds of polydrug use, comorbid neurologic/
psychiatric diagnoses, and a lack of appropriate comparison groups.
Author Affiliations: ORYGEN
Research Centre (Drs Yu¨ cel,Whittle, and Lubman) and Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health (Drs Yu¨ cel, Whittle, Fornito, and Pantelis), Melbourne, Australia; School of Psychology and Illawarra
Institute for Mental Health, University of Wollongong, Wollongong, Australia (Dr Solowij and
Ms Respondek); and Schizophrenia Research Institute, Sydney, Australia (Dr Solowij).
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©2008 American Medical Association. All rights reserved.
Downloaded from www.archgenpsychiatry.com , on June 3, 2008 recent structural magnetic resonance imaging (MRI) studies have also reported contradictory findings, ranging from
no global or regional changes in brain tissue volume or composition14-16 to gray and white matter density changes, either globally17 or in focal regions, most notably in the
hippocampal and parahippocampal areas.18,19 However, these previous studies used imaging techniques with relatively coarse spatial and anatomical resolution and typically focused on samples with multiple substance use or comorbid psychiatric disorders and on only moderate levels of cannabis use (ie, _2 joints per day). Indeed, despite strong evidence of neurotoxicity in the animal literature, 6-9 to our knowledge, no neuroimaging study has examined the neurobiologic sequelae of long-term heavy cannabis use while controlling for the important confounds of polydrug abuse and co-occurring psychiatric disorders.
In this study, we used high-resolution 3-T MRI to assess volumetric changes in 2 cannabinoid-rich regions of the brain (the hippocampus and the amygdala) known to be susceptible to the neurotoxic effects of cannabis exposure in a sample of long-term heavy users carefully
screened for polysubstance abuse and mental disorders.
Given the growing literature regarding an association between cannabis use and the development of psychosis20 and cognitive impairment,16,21 we also assessed for subthreshold
psychotic symptoms and verbal learning ability in this otherwise psychologically healthy sample.
METHODS
PARTICIPANTS
Male cannabis users with long histories of regular and heavycannabis use (n=15) and nonusing healthy male volunteers (n=16) matched on age, estimated premorbid intelligence (National
Adult Reading Test),22 years of education, and state and trait anxiety (Spielberger State-Trait Anxiety Inventory)23 were recruited from the general community via a variety of advertisements
(Table). Cannabis users had lower Global Assessment of Functioning scale scores and greater depressive symptoms (as measured using the Hamilton Depression Rating Scale)24 than the comparison group; however, there were no current or lifetime histories of diagnosable medical, neurologic, or psychiatric conditions as assessed using the Structured Clinical Interview
for DSM-IV Axis I Disorders, Patient Edition.25 All the control subjects also underwent a Structured Clinical Interview for DSM-IV Axis I Disorders, Non-Patient Edition.25 Subthreshold
psychotic symptoms were probed using the Scale for the Assessment of Positive Symptoms26 and the Scale for the Assessment of Negative Symptoms.27 Regarding alcohol use, the
groups did not differ in levels of current consumption, lifetime use, or history of abuse or dependence; and no participant drank more than 24 standard alcoholic drinks per week.
Significantly more cannabis users were also tobacco smokers (_2=22.9, P_.001) (Table). For all users, cannabis was the primary drug of abuse, with only limited experimental use of other
illicit drugs (generally _10 lifetime episodes).
PROCEDURE
Participants were assessed on 2 occasions, usually 1 week apart. In the first test session, participants completed demographic, clinical, and substance use history assessments. In the second test session, they completed the Rey Auditory Verbal Learning
Test (RAVLT) and underwent structural MRI.
Participants were asked to abstain from using substances for at least 12 hours before each test session, and cannabis users reported abstaining from cannabis for a mean of 21.3 hours before
the first test session (median, 14 hours; range, 10-72 hours) and a mean of 19.8 hours before the second test session (median, 17 hours; range, 12-48 hours). Urine samples were obtained
from users on 4 occasions and from controls on 2 occasions to corroborate self-reported abstinence. Specifically, for cannabis users, samples were obtained on the evening before
each test session and on the day of testing. For controls, samples
were collected only on the day of testing. Examination of these
samples demonstrated that all but 1 cannabis user had cannabinoid
metabolites (11-nor-_9-tetrahydrocannabinol-9-
carboxylic acid creatinine normalized) detected in urine samples
from the first test session, and levels were generally high
(evening: median, 467 ng/mg [range, 0-2320 ng/mg]; day of
testing: median, 447 ng/mg [range, 0-11 293 ng/mg]). From the
second test session, 2 users returned a 0 reading; otherwise,
cannabinoid metabolite levels were again high (evening: median,
456 ng/mg [range, 0-3511 ng/mg]; day of testing: median,
389 ng/mg [range, 0-4470 ng/mg]). The levels of urinary
cannabinoid metabolites generally corroborate the selfreported
patterns of heavy cannabis use in the sample. All but
2 control subjects returned a 0 reading for cannabinoid metabolites
across both test sessions. The 2 controls with positive
urine samples reported only minimal and very occasional
exposure to cannabis. The median level of cannabinoid metabolites
in controls at the first test session was 0 ng/mg (range,
0-184 ng/mg) and at the second test session was 0 ng/mg (range,
0-180 ng/mg).
STRUCTURAL MRI
The MRI data were obtained using a 3-T scanner (Intera; Phillips
Medical Systems NA, Bothell, Washington) at the Symbion
Clinical Research Imaging Centre, Prince of Wales Medical
Research Institute, Sydney. A 3-dimensional volumetric
spoiled gradient–recalled echo sequence generated 180 contiguous
coronal slices. The imaging parameters were as follows:
echo time, 2.9 milliseconds; repetition time, 6.4 milliseconds;
flip angle, 8°; matrix size, 256_256; and 1-mm3 voxels.
Hippocampal, amygdala, whole brain, and intracranial volumes
were measured using established reliable protocols28-31
and were delineated by a trained rater (S.W.) masked to group
information. Specifically, the hippocampal boundaries were as
follows: posterior, the slice with the greatest length of continuous
fornix; medial, the open end of the hippocampal fissure
posteriorly, the uncal fissure in the hippocampal body, and the
medial aspect of the ambient gyrus anteriorly; lateral, the temporal
horn of the lateral ventricle; inferior, the white matter inferior
to the hippocampus; superior, the superior border of the
hippocampus; and anterior, the alveus was used to differentiate
the hippocampal head from the amygdala. The anterior border
was the most difficult to identify consistently and was aided
by moving between slices before and after the index slice. The
amygdala boundaries were as follows: posterior, the appearance
of amygdala gray matter above the temporal horn; superolateral,
the thin strip of white matter that separates the amygdala
from the claustrum and the tail of the caudate; medial, the
angular bundle, which separates the amygdala from the entorhinal
cortex; superomedial, the semilunar gyrus; inferior, the
hippocampus; inferolateral, the temporal lobe white matter and
the extension of the temporal horn; and anterior, the slice anterior
to the appearance of the optic chiasm. Whole brain volumes
were estimated using the Brain Extraction Tool method32
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to separate brain from nonbrain tissue. After brain/nonbrain
segmentation, each voxel was classified into gray matter, white
matter, or cerebrospinal fluid using FAST Model statistical software.
33 Only gray and white matter were used in the estimate
of whole brain volumes. The intracranial cavity was delineated
from a sagittal reformat of the original 3-dimensional data
set. The major anatomical boundary was the dura mater below
the inner table, which was generally visible as a white line.
Where the dura mater was not visible, the cerebral contour was
outlined. Other landmarks included the undersurfaces of the
frontal lobes, the dorsum sellae, the clivus, and the posterior
arch of the craniovertebral junction.
Interrater and intrarater reliabilities were assessed by means
of the intraclass correlation coefficient (ICC) (absolute agreement)
using 15 brain images from a separate MRI database established
specifically for this purpose and that has previously
been delineated by another expert rater. For the hippocampus,
interrater ICC reliabilities were 0.92 (right) and 0.91 (left)
and intrarater ICC reliabilities were 0.98 (right) and 0.95 (left).
For the amygdala, interrater ICC reliabilities were 0.85 (right)
and 0.88 (left) and intrarater ICC reliabilities were 0.93 (right)
and 0.97 (left). Once reliability was established, the rater (S.W.)
delineated the regions of interest for the images acquired from
the present study.
STATISTICAL ANALYSES
Whole brain volume, age, educational level, and estimated IQ
were not significantly different between the 2 groups and were,
therefore, not used as covariates (Table). Regional gray matter
volumes for the hippocampus and amygdala were corrected for
the effect of the intracranial cavity using a previously described
formula34 and were analyzed using analyses of variance,
with hemisphere (left or right) and region (hippocampus
and amygdala) as within-subject factors and group as the
between-subject factor. Main effects and interactions were evalu-
Table. Demographic, Clinical, Drug Use, and MRI Volumetric Measures
Measure
Long-term Cannabis Users
(n=15)
Nonusing Control Subjects
(n=16) P Valuea
Age, mean (SD), y 39.8 (8.9) 36.4 (9.8) .31
IQ, mean (SD) 109.2 (6.3) 113.9 (8.1) .09
RAVLT score, mean (SD)
Sum of 5 learning trials 43.8 (8.8) 57.4 (10.1) _.001
20-min delay 8.9 (4.1) 12.3 (3.7) .009b
Educational level, mean (SD), y 13.4 (3.2) 14.8 (3.7) .28
GAF scale score, mean (SD) 72.0 (11.2) 80.8 (9.4) .02
HAM-D score, mean (SD) 5.87 (3.2) 2.56 (1.9) _.001b
STAI, mean (SD)
State anxiety 34.3 (9.8) 32.9 (9.4) .67
Trait anxiety 39.3 (9.7) 39.0 (8.2) .92
SAPS score, mean (SD) 8.1 (7.9) 0.6 (1.2) _.001b
SANS score, mean (SD) 11.7 (8.5) 1.4 (1.4) _.001b
Cannabis use
Duration of regular use, mean (SD) [range], yc 19.7 (7.3) [10-32] NA NA
Age started regular use, mean (SD) [range], yc 20.1 (6.9) [12-34] NA NA
Current use, mean (SD), d/mod 28 (4.6) NA NA
Current use, mean (SD), cones/mod,e 636 (565) NA NA
Cumulative exposure, past 10 y, mean (SD)f 77 816 (66 542) NA NA
Cumulative exposure, lifetime, mean (SD)f 186 184 (210 022) 12.7 (12.2) _.001
Estimated episodes of use, median (range) 62 000 (4600-288 000) 11 (0-30) _.001
Alcohol use, mean (SD), standard drinks/wk 9.6 (6.1) 6.8 (5.0) .19
Tobacco use, mean (SD), cigarettes/d 16.5 (8.9) 7.5 (9.2) .20
Brain volumes, mean (SD), mm3
Intracranial cavity 1 546 237 (94 018) 1 607 590 (136 386) .14
Whole brain 1 310 780 (90 778) 1 374 123 (105 673) .09
Hippocampus .002g
Left hemisphere 2849 (270) 3240 (423)
Right hemisphere 2949 (244) 3348 (400)
Amygdala .01g
Left hemisphere 1766 (98) 1878 (190)
Right hemisphere 1601 (143) 1744 (158)
Abbreviations: GAF, Global Assessment of Functioning; HAM-D, Hamilton Depression Rating Scale; MRI, magnetic resonance imaging; NA, not applicable;
RAVLT, Rey Auditory Verbal Learning Test; SAPS, Scale for the Assessment of Positive Symptoms; SANS, Scale for the Assessment of Negative Symptoms;
STAI, State-Trait Anxiety Inventory.
aTwo-tailed t test unless otherwise indicated.
bMann-Whitney test.
cRegular use was defined as at least twice a month.
dCannabis users had used at this level for most of their drug-using history.
eA cone is the small funnel into which cannabis is packed to consume through a water pipe in a single inhalation. Without the loss of sidestream smoke, the
quantity of tetrahydrocannabinol delivered by this method is estimated as equating 3 cones to 1 cigarette-sized joint. Thus, the cannabis users in this study
smoked the equivalent of 212 joints per month, or approximately 7 joints per day.
fExpressed as cones for users and as episodes for controls. Estimates of lifetime exposure beyond 10 years in these very long-term users became skewed and
unreliable; hence, the 10-year estimate was used in correlational analyses.
gRegion_group analysis of variance.
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ated using Greenhouse-Geisser–corrected degrees of freedom,
with _=.05. Effect sizes, expressed as Cohen d, are also reported
for pairwise contrasts. Only effects involving group (cannabis
users vs nonusers) and associations with cannabis use
parameters are reported because this was the primary focus of
the present study. Group comparisons of performance on the
RAVLT and measures of subthreshold psychotic symptoms
(using the Scale for the Assessment of Positive Symptoms and
the Scale for the Assessment of Negative Symptoms) were conducted
using independent-samples t tests or Mann-Whitney tests
for nonnormally distributed data. Pearson product moment correlational
analyses were conducted to examine the behavioral
(ie, symptom and cognitive) relevance of any identified group
differences in regional brain volumes and the association
between these brain changes and parameters of cannabis use.
These analyses were necessarily exploratory given the limited
sample size.
RESULTS
GROUP CONTRASTS
In the analysis of regional gray matter volumes, there
was a significant main effect of group (F1,29=12.98,
P=.001) and a region_group interaction (F1,29=6.25,
P=.02). This result and the post hoc pairwise analyses
demonstrated reduced hippocampal volumes in cannabis
users (F1,29=11.14, P=.002 corrected; a reduction of
12.1% in the left and 11.9% in the right hippocampus
relative to controls), with a very large effect size (Cohen
d: left hippocampus, 1.17; and right hippocampus,
1.27) (Figure 1). Cannabis users also had smaller
amygdala volumes (F1,29=7.31, P=.01 corrected; a
reduction of 6.0% in the left amygdala and 8.2% in the
right amygdala relative to controls), with large effect
sizes (Cohen d: left amygdala, 0.80; and right amygdala,
0.99). The region _ group interaction reflects that the
overall reduction in hippocampal volume was relatively
(and significantly) greater than the reduction in amygdala
volume (12.0% in the hippocampus vs 7.1% in the
amygdala). In the analysis of subthreshold psychotic
symptoms, cannabis users reported significantly higher
positive symptoms (Scale for the Assessment of Positive
Symptoms; z=−3.57, P_.001) and negative symptoms
(Scale for the Assessment of Negative Symptoms;
z=−3.66, P_.001) than nonusing controls. Regarding
verbal learning, cannabis users displayed significantly
poorer performance than controls on the RAVLT measures
(sum of words recalled across the 5 learning trials:
z=−3.97, P_.001; and free recall after a 20-minute
delay: z=−2.61, P=.009).
CORRELATIONAL ANALYSES
There was a significant inverse association between left
hippocampal volume and cumulative cannabis exposure
during the previous 10 years (r=−0.62, P=.01; accounting
for 38% of the variance in left hippocampal volume)
(Figure 2A). When 1 participant with relatively
higher cumulative cannabis exposure and small hippocampal
volume was excluded, 22% of the variance was
still accounted for despite falling short of significance in
the reduced sample (r=−0.47, P=.09). There was also an
association between left hippocampal volume and positive
symptoms (r=−0.77, P_.001) (Figure 2B) and between
positive symptoms and cumulative cannabis exposure
(r=0.52, P=.048) (Figure 2C). The associations
between left hippocampal volume and cumulative cannabis
exposure and between left hippocampal volume and
positive symptoms remained after controlling for the effects
of global functioning (Global Assessment of Functioning
scale) and depressive symptoms (Hamilton Depression
Rating Scale). No other associations were found
between other brain volumetric measures, cannabis use,
and psychotic symptoms, and they did not vary as a function
of alcohol or tobacco use. Measures of RAVLT performance
did not correlate with hippocampal or amygdala
volumes in either controls or cannabis users.
COMMENT
To our knowledge, this is the first human study of longterm
heavy cannabis users to demonstrate marked
exposure-related hippocampal volume reductions.
These findings corroborate previous animal research,6-9
suggesting that long-term heavy cannabis use is associated
with significant and localized hippocampal volume
reductions that relate to increasing cumulative cannabis
exposure. In addition, the present findings are consis-
tent with the view that cannabis use increases the risk
of psychotic symptoms and informs the debate concerning
the potential long-term hazardous effects of cannabis
in this regard. The bilateral reduction in amygdala
volume is a novel but not unexpected finding given the
dense concentration of cannabinoid receptors in this
region.35
Although these findings are consistent with those of
a previous study,18 it is difficult to directly compare these
results with those of other human studies given that past
work used MRI with lower magnetic field strength and
spatial resolution and did not conduct region-of-interest–
based analyses (eg, performed whole-brain voxel-based
analyses18). Tzilos et al14 conducted the only other study,
to our knowledge, that investigated cannabis users with
a relatively long history of use (specifically, an average
duration of use of 22.6 years, or 18.9 years of daily use)
and their study is, therefore, most comparable with the
present study. Although they found no effects of longterm
cannabis use on hippocampal volume, the authors
acquired their images at a lower field strength and with
a coarser spatial resolution (1.5 T with 3-mm-thick slices
vs 3 T with 1-mm-thick slices in the present study), an
important consideration given the size of the brain structures
investigated. Moreover, their region of interest was
less specific to the hippocampus relative to the present
measure because they also included the parahippocampal
gyrus. Furthermore, there was a relatively large age
discrepancy between their users and controls (38.1 vs 29.5
years), and the minimum duration of exposure to cannabis
was considerably lower in their sample (as little as
1 year of cannabis exposure), but, overall, their sample
reported an average of 20 100 lifetime episodes of use.
In contrast, the minimum duration of exposure to cannabis
in the present sample was 10 years, with an average
of 62 000 episodes of use. Thus, despite a similar mean
duration of use, the present sample used more than 3 times
as much cannabis, which may explain the finding of a
dose-response relationship between hippocampal volume
and cumulative cannabis use. Further highresolution
MRI work is necessary to characterize precisely
the dosage of cannabis required for significant brain
changes to occur.
The pattern of use in the present sample is consistent
with heavy cannabis use patterns that have previously
been reported in other Australian studies. For example,
Copeland and colleagues36 reported median daily intake
of 8 cones (the small funnel into which cannabis is packed
to consume through a water pipe in a single inhalation)
in an Australian sample of cannabis users seeking treatment
for cannabis dependence, ranging up to 125 cones
per day in the heaviest user, with 11% reporting cannabis
smoking throughout the day. The heaviest user herein
reported smoking 80 cones per day (approximately 25
joints smoked throughout the day). This pattern of cannabis
use is not dissimilar to the heaviest cannabis users
from other studies of non–treatment-seeking samples of
Australian cannabis users.37,38
Despite the large magnitude of effects observed, it remains
unclear whether these volumetric reductions
reflect neuronal or glial loss, a change in cell size, or a
reduction in synaptic density (eg, dendritic arborization),
all of which have been reported in rodent studies.
6-9 For example, Scallet and colleagues9 found striking
tetrahydrocannabinol-induced residual decreases in
the mean volume of hippocampal neurons and their nuclei
and a 44% reduction in the number of synapses up
to 7 months after the last exposure to tetrahydrocannabinol.
Moreover, Landfield and colleagues7 administered
tetrahydrocannabinol 5 times a week for 8 months
(approximately 30% of the rat lifespan, and comparable
in frequency and duration to the present sample) and
found significant tetrahydrocannabinol-induced decreases
in neuronal density in the hippocampus. Such
findings may help explain the mechanisms underlying
gross hippocampal and amygdala volume loss seen in this
sample of long-term heavy cannabis users.
Left Hippocampal Volume, mm3
In the present study, hippocampal volume in the cannabis-
using group was inversely correlated with cumulative
exposure to the drug in the left, but not right, hemisphere.
Previous functional imaging studies16,39 have found
reduced left hippocampal activation during cognitive performance
in cannabis users, and there is evidence to suggest
that hippocampal abnormalities in psychiatric disorders
such as schizophrenia are more prominent in the
left hemisphere.40 These findings converge to suggest that
the left hippocampus may be particularly vulnerable to
the effects of cannabis exposure and may be more closely
related to the emergence of psychotic symptoms. In this
context, it is interesting that we found a significant inverse
correlation between left hippocampal volume and
positive symptoms. Cannabis use was also positively correlated
with positive symptoms, suggesting that there are
complex associations among exposure to cannabis, hippocampal
volume reductions, and psychotic symptoms.
Given these relationships, it is possible that the exposurerelated
hippocampal reduction may reflect heavy cannabis
use in response to preexisting or developing psychotic
symptoms. However, there is limited empirical
support for long-term self-medication of subthreshold psychotic
symptoms with cannabis and stronger support for
the induction of psychotic symptoms subsequent to cannabis
exposure.20 As such, it seems more likely that prolonged
heavy use of cannabis induced subthreshold psychotic
symptoms and that both of these factors are
associated with hippocampal volume loss. These symptoms
were subthreshold because these cannabis-using participants
were carefully screened for current and past history
of mental disorders. Furthermore, the fact that the
mean age of the present cannabis-using sample was nearly
40 years suggests that these symptoms are unlikely to reflect
a prodrome. One speculation is that the present participants
were less genetically vulnerable to developing
a psychotic disorder subsequent to cannabis use,41,42 allowing
them to smoke heavily for many years. Future longitudinal
work assessing the emergence of hippocampal
reductions and psychotic symptoms with continued exposure
to cannabis, and how these are related to polymorphic
variations in susceptibility genes for psychotic
disorders, will prove useful in better characterizing these
relationships.
Given that cannabis users had significantly greater depressive
symptom scores than controls and that there is
an association between depression and hippocampal volume
reduction,43 it could also be argued that depressive
symptoms may be another mediating factor in the relationship
between cannabis use and hippocampal volume
reduction. However, there are a variety of important
considerations that make this unlikely. First, there
was no significant association between hippocampal volumes
and depressive symptom scores. Second, the relationship
between left hippocampal volume and quantity
of cannabis used was maintained after statistically
controlling for depressive symptoms. Finally, the overwhelming
evidence suggests that hippocampal reductions
in major depressive disorder tend to occur in the
more persistent forms of the disorder (eg, multiple episodes,
repeated relapses, or long illness duration).43,44 This
was not the case in the present sample of cannabis users,
who scored less than 6.0 on the Hamilton Depression
Rating Scale, had never been diagnosed as having
major depression, and did not seek treatment for any depressive
disorder.
Cannabis users showed poorer performance on measures
of verbal learning, consistent with previous findings.
Although some functional imaging studies have
found reduced left hippocampal blood flow and activation
during verbal (and visual) learning tasks in cannabis
users, we found no correlation between RAVLT
performance measures and hippocampal volume in either
controls or cannabis users. It is likely that anatomical volume
is a less sensitive measure than brain activation for
identifying correlations with behavioral performance. This
is a particularly pertinent consideration given that the
performance measures on the RAVLT are likely to reflect
the operation of numerous cognitive processes not
necessarily related to hippocampal function. Future work
using experimental tasks designed to more specifically
probe memory functions mediated by the hippocampus
may be useful in this regard.
The bilateral reduction in amygdala volume is a novel
but not unexpected finding given the dense concentration
of cannabinoid receptors in this region.35 There were
no cognitive, psychotic, or depressive symptom associations
with reduced volume in the amygdala. However,
this region has been significantly implicated in cannabinoid-
associated emotional and reward-related learning
and memory processes.47,48 Given that these aspects of
learning have not been examined in human cannabis users,
they would seem to serve as a potentially informative
avenue forward to help elucidate the functional relevance
of such volumetric reduction in the amygdala.
The relationship between long-term cannabis use and
brain abnormalities is complex. Although a limitation of
this study may be the residual effects of cannabis in light
of the fact that the cannabis users in this study were required
to be cannabis free for only 12 to 24 hours before
MRI, such issues are likely to be more pertinent for studies
examining more dynamic aspects of brain functioning
(eg, activations and cognition).49 The present structural
findings are unlikely to relate to the recent effects
of cannabis use because we are unaware of any evidence
that suggests that the hippocampus and amygdala can
change in volume by 6% to 12% in short periods. However,
although we maintain that the present results reflect
brain changes associated with long-term heavy cannabis
use rather than the consequences of recent exposure,
further longitudinal work is required to assess whether
such changes are reversible across more protracted periods
of abstinence.
Another limitation of this study is the relatively small
sample size, although the sample was exceptionally unique
in that participants were very long-term and heavy cannabis
users (mean of 5-7 joints per day for _10 years)
without polydrug use or co-occurring neurologic or diagnosable
mental disorders. As such, we conducted the
first, to our knowledge, “pure” examination of the effects
of heavy and protracted exposure to cannabis in humans.
The large effect sizes of the main findings suggest
that these results are robust and reproducible. These findings
are further strengthened by the observed dose-
response relationships between hippocampal volume reductions
and cumulative cannabis use.
There is ongoing controversy concerning the longterm
effects of cannabis on the brain. 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.
Correspondence: MuratYu¨ cel, PhD,MAPS,ORYGENResearch
Centre, 35 Poplar Rd (Locked Bag 10), Melbourne,

Source: Arch.Gen.Psychiatry. Vol.65 June 2008

WASHINGTON (CNN) — The earlier a young person uses marijuanathe greater the risk for mental health problems later in life, the director of National Drug Control Policy said Tuesday, basing his conclusion on a survey of medical research.

“We’re trying to get out the word that the last 10 years of research have helped to alert us to the use of marijuana in particular is a very dangerous risk for the mental health of our young people,” John Walters said at a news conference.
He said the conclusion runs against popular culture that often considers marijuana a low-risk recreational drug.
Walters cited a government study that found a base rate of mental illness at between 8 percent and 9 percent among Americans 18 and older. For those who use marijuana, he said, “That increases to 12-and-a-half percent.”
And, he added, “For those who have used marijuana prior to age 12, the rate of mental illness jumps to 21 percent.”
The rate was half that, or 10.5 percent, for adults who first used marijuana at age 18 or older.
Those were the findings of the National Survey on Drug Use and Health, an annual survey sponsored by the Substance Abuse and Mental Health Services Administration.
Walters did not directly address the possibility of confusing cause and effect — that is, that people with mental problems might be more inclined to use drugs.
One study he cited was published last year in the Archives of General Psychiatry. It involved 600 pairs of same-sex twins, one of whom was dependent on marijuana and one of whom was not. The twin who was dependent was almost three times as likely to think about suicide and attempt suicide than his brother or sister, the study found.
Neil McKeganey, who heads the University of Glasgow’s Center for Drug Misuse Research, was at the press conference in support of Walters.
“It is leading us to look again at this so-called recreational drug,” he said. “Kids who start to use marijuana at a young age are much more likely to suffer serious, long-term mental health problems.”
The parents of a teenager who committed suicide last year were also at the news conference, and they linked their son’s death to his marijuana use.
Tanya Skaggs, of Colorado Springs, Colorado, said, “He had a severe lack of judgment that was because of the marijuana, this destructive behavior was continuing,” in the months leading up to his death.
The parents were unable to break his marijuana use, Skaggs said, despite counseling, searching his room for pot and random drug tests.
“We just never thought that something like this could happen to us. But it does, and it did,” she said. “We wish we could have helped.”
Agenda ‘detrimental to your children’
Walters downplayed whether the medical use of marijuana undercuts the impact of warnings to young people against pot use.
The question was tied to a decision by Canada last month to approve the prescription drug Sativex, an oral spray that contains the active ingredient of marijuana, to treat the symptoms of multiple sclerosis.
He responded, “We believe that there’s a clear distinction” between validated medical benefits and what he said could be “a bunch of ads where people testify that their mother, dying, smoked a joint and was saved, and that means marijuana is medicine.”
“Your children are being educated,” he said of such advertising. “But they’re being told lies. And they’re being told things that are designed to push a particular agenda which is detrimental to your children, and detrimental to the country.”
Group calls for national discussion
Meanwhile, a Washington-based nonprofit group released a report recommending changes in the way authorities handle drug offenses, citing a “disproportionate” focus on “low-level marijuana users.”
“The ‘war on drugs’ in the 1990s was, essentially, a ‘war on marijuana,’” said the report by the Sentencing Project, which was founded in 1986 to promote alternative sentencing programs.
A national analysis covering 1990 to 2002 found that, of a 450,000 rise in drug arrests during that period, 82 percent of the increase was for marijuana, and 79 percent was for marijuana possession alone.
Marijuana arrests now make up 45 percent of the nation’s 1.5 million drug arrests annually, the report said, and an estimated $4 billion is spent each year on marijuana offenders.
“The growth in marijuana arrests over the 1990s has not led to a decrease in use or availability, nor an increase in cost,” the group said. “Meanwhile, billions are being spent nationally.”
The report calls for “a national discussion regarding the zealous prosecution of marijuana use and its consequences for allocation of criminal justice resources and public safety.”
“Law enforcement has focused disproportionately on low-level possession charges as a result of the nation’s lack of a thoughtful strategy,” it said.
Source:www.WordPress.com June 2008

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

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

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

Being a teenager isn’t as risky as it used to be, but too many teens still put their lives and their health at risk, a CDC survey shows.

Every two years, the CDC conducts its huge Youth Risk Behavior Survey. It contains detailed data from more than 14,000 questionnaires anonymously completed by teens in grades 9 through 12.

Overall, the 2007 results suggest that teens are acting more responsibly. Fewer are sexually active, nearly all wear seat belts, drinking and drug use are down, 80% of kids don’t smoke, and there are fewer suicide attempts.

This is good news to Howell Wechsler, EdD, MPH, director of the CDC’s Division of Adolescent and School Health. In some cases, the new numbers begin to approach the CDC’s Healthy People 2010 objectives. “What we are seeing is from the early to mid-1990s to now, on a large number of health risk behaviors, we are seeing very, very encouraging progress,” Wechsler tells WebMD.

Even so, the new numbers are enough to take a parent’s breath away:
• 7% of teens say they’ve attempted suicide (down from nearly 9% in
2001).
• 35% of teens say they’re sexually active (down from 37.5% in 2001).
• 18% of teens say they carry a gun, knife, or club (no significant change from 2001).
• 20% of teens say they smoke cigarettes (down from 36.4% in 1997).
• Nearly 45% of teens say they use alcohol (down from 50% in 1999).
• About 20% of teens say they use marijuana (down from nearly 27% in 1999).
• Only about 21% of kids eat five or more servings of fruits and vegetables (down from 24% in 1999).
• 25% of teens play video games or use the computer for three or more hours a day (up from 21% in 2005).
• More than 65% of kids don’t get enough exercise , and 25% of teens say they don’t even get an hour of exercise on any day of the week.

“We are gratified that there is progress being made,” Wechsler says. “But my take on it is this: I have a bunch of kids myself and I am not going to be satisfied until we meet our goals — and in most areas we are still not meeting our Healthy People 2010 objectives. So I see no cause to be overly
satisfied.”

(Which teens are most at risk? Find out from guest blogger Howell Wechsler on WebMD’s News Watch blog.)

Best States/Cities, Worst States/Cities

In some cases, the overall numbers conceal states and localities where teen behavior is much better — and much worse — than average:
• 62.2% of Kentucky kids have tried smoking cigarettes, compared with only 24.9% of Utah teens (national average: 50.3%).
• 34.5% of West Virginia teens use tobacco products, compared with only 8.9% of kids in Vermont (national average: 25.7%).
• 44.7% of Alaska teens have tried marijuana, compared with only 17.4% of Kentucky kids (national average: 38.1%)
• 90.8% of kids in New York attend physical education classes at least once a week vs. 28.4% of kids in South Dakota (national average: 53.6%).
• 49.7% of Baltimore teens are sexually active, compared with 17.5% of San Francisco teens (national average: 35%).
• 39.2% of ninth to 12th graders in Dallas have been offered, sold, or given an illegal drug, compared with 13.5% of teens in Baltimore (national average: 22.3%).

Wechsler says the survey data don’t show exactly why teens in some areas take fewer health risks than teens in other areas. But he says that state and local efforts to reduce specific risk behaviors pay off. He points to anti-tobacco efforts as an example.

“One thing that is instructive is the tremendous difference in resources different states put into this,” Wechsler says. “In some states, teen tobacco use is much lower than the national rate. And we see this in exactly those states where they have made substantial investments in tobacco
reduction.”

Even Good Teens Take Risks — What Parents Must Do

If none of this sounds like your teenager, listen to Nancy Cahir, PhD, a child/adolescent/adult psychologist in private practice in Atlanta.

“What I have seen in my practice is even parents who think it couldn’t happen to their child — well, it can,” Cahir tells WebMD. “Even with the ‘perfect child,’ there may be hidden issues; even in good families, bad things can happen. There is no discrimination when it comes to high-risk behavior for teens.”

Parents have a responsibility to involve themselves in their children’s lives, Cahir says. They cannot assume their teen is doing fine because they haven’t had calls from the school or because their teen’s grades are good.

“Parents, I say stay close to your children. Know your kids the way you know your best friend, and keep in touch with them,” she says. “Spend time with them, know their friends, and know the parents of the children your children hang out with. Say to them every day, ‘Did you have a difficult day? What’s going on with you? How are you doing?'”

It’s probably not news that teens can be moody, even surly at times. Your teen may respond to your inquiries with something like, “My life is none of your business.”

Not so, says Cahir.

“Every parent has the right to say, ‘It is too my business,'” she says. “Parents sometimes shy away from being more involved because they don’t want to seem intrusive. But it is their business to know whom their child hangs out with, to know whether the child is in distress, and to help their children through these difficult times. Sometimes kids don’t like hearing that, and may respond in defiant ways, but parents must toe the line and say, ‘We have a right to know.'”

But Wechsler agrees with Cahir that communication is not only what your children need, but what they truly want.

“As a parent of two teens myself, you tend to believe them when they walk out of the room and don’t express any interest in hearing from you,” Wechsler says. “But kids really do want that communication with parents. They really do want to hear their parents’ values. They really need their parents to monitor their whereabouts and stay in touch and stay a very strong part of their lives.”

Cahir says the key to communicating with teens is developing mutual respect.

“Each member of a family should treat the others members like a best friend or at least as a guest in the house,” she says. “If you are angry with your teen, or your teen is angry with you, you have to talk it out in a way that is not hostile or aggressive. I’ve seen some families go after each other tooth and nail and they end up really harming each other.”

If communication breaks down, it may be time for the family to sit down with a professional to learn how to express disagreements in a constructive way.

The full CDC report, “Youth Risk Behavior Surveillance — United States, 2007,” is available on the CDC’s web site. For comparison, earlier years’ reports are also available.

Source:CBS News Web 4 June 2008

Drug policy public hearing – a revivalist meet for the disciples of dope.

A Brussels Parliament sketch by Peter Stoker – Director, National Drug Prevention Alliance
_____________________________________________________________

In the comfortable and prestigious surroundings of the European Parliament, a ‘Public Hearing’ was – in the event – heard by very few of The Public. Perhaps this is just as well, for the average citizen might have torched this expensive building, built from his tax money, had they heard what was being said.

Under the name of the Civil Liberties, Justice and Home Affairs Committee, the hearing concerned what was euphemistically called the ‘Anti-Drug’ Strategy, 2005 – 2012, and its attendant ‘Action Plans’ (2005 – 2008 and 2009 – 2011). Enthusiasts of drug policy will know the special significance of 2008; this is the year in which the UN is set to review its Conventions on Drugs, for which more than 100 nations have signed up, thereby generating an enormous and positive influence on drug policy around the world. It is precisely because the Conventions have a positive influence, a bulwark against legalisation, that they are hated by the pro-legalisation crowd. They would kill them today if they could but meanwhile they are working behind and in front of every available screen to administer a death blow as soon as they can.

Deep concern for the public health, social cohesion and safety of European society was cited as the drive for the ‘Anti-Drug’ Strategy – surely matters of interest to The Public, but this meeting was populated by a rather different variety of human being.

Instead of the public there was a collection of around 150 people – of which more than 100 came ‘on a mission from Gomorrah’, bearing banners and leaflets, and demanding a Europe of free drugs – not a Europe free of drugs. Largely in harmony with this aspiring cluster were some 15 MEPs who, if they spoke at all, spoke in terms which garnered the applause of the 100. Also on hand were around 25 EU officials who maintained at discreet silence – in all but one noteworthy case. Mathematicians amongst you will note that this leaves about five people are not accounted for? Who they? The prevention platoon – including yours truly.

Known drug legalisers and liberalisers were greeted like old friends – which maybe they were – and were given reserved seating plus arranged speaking slots in the agenda. Thus were we treated to presentations by ENCOD, TNI, IAPL and others who would not be given house room in any self-respecting house.

Looking on benevolently but keeping a low profile was Mike Trace, the disgraced former Deputy Drugs Tsar for the UK who, on the eve of his elevation to head of Demand Reduction for the UN, was spectacularly exposed by the London Daily Mail as running covert operations with legaliser bodies, notably those bankrolled by George Soros. Trace was obliged to resign his seat at the UN even before he had begun warming it, but he remains a force on the UK and European scene, the beneficiary of a determined rehabilitation scheme by those who feel there is still some useful mileage in him. He is a top cat in Drug Treatment Limited, in the Beckley Foundation, and in RAPt – the Rehabilitation of Addicted Prisoners Trust – the breadwinner job he has held since before his heady days of Drug Tsardom.

The meeting was chaired by Belgian MEP Antoine Duquesne, and did little to diminish his reputation as a strange person. A welcome was offered by the Health Minister for Luxemburg, who promised that of all present today had left their dogmas leashed up outside the front door, and that no preachers had been admitted. Our main goal, he suggested, should be free to reduce Harm … not only the physiological harm drug-users suffer but also the harm of their social exclusion (presumably users should be set on a pedestal in society). The minister concluded by entreating all present to not stick to a static view; there are many approaches, he said, witness the contents of the Action Plan produced by the splendidly named Horizontal Drug Group on the 23rd of February this year.

Next up was a spokesman for the Pompidou Group, Bob Kaiser, who did his best to maintain gravitas in presenting a predictable and unimaginative series of recommendations, ending with the plea that money should not be spent on new organisations (the implication being that it was better to spend it on old organisations – like his).

Paul Griffiths, spokesman for the Lisbon-based monitoring centre, EMCDDA, uttered the recurrent plea for more and better data, not withstanding what he saw as improvements in recent years. We needed, he said, to get much better at collecting evidence, if – that is – evidence-based policy (as distinct from policy-based evidence) is the goal.

A sanguine spokesman from the International Red Cross made new friends in the audience when he asserted that the notion of a drug-free world is unrealistic and that it was in the nature of man to swallow psychoactive substances – much in the way he had evidently swallowed this rhetoric. He lost one friend, however, when he dismissed the concerns of of Madame Roure, MEP for Lyon, France, who spoke of young children in deprived areas being drawn into drug use; that – said the Red Cross man – was a South American or Eastern Europe problem i.e. nothing for us civilised types over here to get excited about. Madame R gave him a short shrift; she was, she said, talking about the fair city of Lyon – not Bogota or Bucharest.

Luc Beauman, spokesman for ENCOD, knew he was preaching to the converted. From his position on the top table he presented a relaxed and intellectually stylish restatement of their position. At this, the 100 erupted into thunderous and extended applause, holding aloft colourful if modestly-sized banners (possibly designed to fit comfortably inside one’s jacket).

It was then that the assembled drug freedom fighters in the cheap seats became restless. Surely, the first cautiously suggested, it is the system of making drugs illegal which just makes prevention harder to appear: wouldn’t a bright new day dawn and everything be super if we just legalised them all?. Others quickly followed over this rickety bridge head: A man from Bologna complained that he couldn’t get a drink after 9pm or smoke cigarettes in shops – this is Prohibitionism even with legal drugs, so it’s just part of the same problem, and we must recognise that prohibitionists are dangerous animals. The appropriately-named ‘Freek’ Polack claimed that he had just one question for the Parliament – then proceeded to ask five; the gist of it was that policies which don’t enable drug use are failures, so why are we silent on this failure? He was received in silence.

An impassioned plea from a hirsute young German drug user took the form of a velvet trap – “You say we need your help, I say you need our help, so when will you stop isolating and demonising us?” (as in ‘When did you stop beating your wife?’).

An Italian plaintiff said he knew of five people, arrested for drug possession who, when their names were published in the media, committed suicide.The notion of an early death during this meeting was perhaps growing in the minds of some, who were by now finding the whole affair life-threatening.

In the name of balance, a Belgian prevention centre worker was invited to speak. He remarked that the discussions “seemed to getting very polemical” – perhaps unintentionally implying that they had not been polemical from the kick-off.

ENCOD’s Luc Beauman took another bite at the cherry; if cannabis is demonised, he opined, then kids don’t take any drug information seriously. Ergo, unreliable prevention messages damage all prevention messages, so his argument went.
( Unreliable libertarian messages did not, it seemed, qualify for the same criticism). ‘Regulation’ – the new buzzword for Legalisation – would usher in a new dawn of ‘ sincere and and honest information’. This would be best achieved by involving citizens, a pious hope of politicians since the 1980s but sadly a hope yet to be realised. 2008 or 2012 were, said Luc, intolerably far away … “What do we want? Regulation! When do we want it? Now!” … and so on …

It was left to the one civil servant who did speak to administer a cold douche of reality. Carel Edwards, Head of the Anti-Drugs Coordination Unit at the EC, told it how it was – and is likely to remain. He was given just six minutes to speak; and said “If you think I can, or will state that the EC position in six minutes, think again”. If today had demonstrated anything, he said, it had demonstrated once again the enormous confusion over the whole subject. The notion that opinions from street level would reach to and direct the top of government is the kind of dream that only comes from those smoking unusual tobaccos. In support of this he cited how few MEPs were here today – and the fact that no of single member state has yet reached what can be called a consenus on drug policy.

He made a somewhat bizarre reference to the Institute for Global Drug Policy Conference held in the European Parliament building about a month ago, characterising this as “Americans expressing a very repressive policy” (It seems that an attendance register, showing the wide variety of European and worldwide delegates at that meeting might helpfully enlighten him). In closing, he said the EC’s aim was to produce an ‘ideology-free, evidence-based’ policy. Those who wanted to debate ideology should go elsewhere; coming as it did after three and a half hours of almost unceasing ideology-pushing, this remark fell on stoned and stony ground alike.

***************

• Compared to 12- and 13-year olds who have frequent family dinners, those who have infrequent family dinners are six times likelier to use marijuana, four times likelier to use tobacco, and three times likelier to use alcohol.
• Compared to teens who attend religious services at least weekly, those who never attend services are more than twice as likely to try cigarettes, and twice as likely to try marijuana and alcohol.
• Compared to teens who have frequent family dinners, those who have infrequent family dinners are one and a half times likelier to report getting grades of C or lower in school. 

Source: www.casacolumbia.org   Sept.2009

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