Fall 2002

(London, BBC News, 28 June, 2002) Record numbers of stressed-out Britons are hitting the bottle to overcome their symptoms, according to a survey by the market analyst group Datamonitor. British people spend more money on alcohol to help them cope with stress than any of their European counterparts, almost £21 billion in 2001, compared with just over £90 billion for all the rest of Europe put together.

The researchers at Datamonitor used questionnaires to determine how much of the alcohol consumed by Britons and othe Europeans was bought to alleviate stress. They spoke to 500 consumers in seven European countries and found 47% suffered from stress - ranging from mild to extreme. The survey indicates that more people in each of the seven nations use alcohol than any other drug when they want to wind down. The greatest amount of stress was reported to be work-related, but some was also linked with stresses of family life and socialising.

Andrew Russell, author of the report, said, "Work and commuting are the two most stressful activities in consumers' lives and both of these are set to increase." The report predicted that alcohol sales across Europe would reach £94.8 billion by 2006, and £22.3 billion in the UK.

Interesting though its conclusions are, the Datamonitor report suffers from some serious deficiencies. Its conclusions are based on a sample that is far too small for any confident generalizations. The report seems to predicate much of its interpretation on the assumption that stress relief is the only reason for drinking alcohol. The fact that alcohol also serves social and ceremonial purposes seems to be largely overlooked. From the perspective of the self-medication hypothesis, it would be of great interest to know what differences exist between dependent and non-dependent users of alcohol in their use of alcohol for stress relief. It would also be of great interest to know the relative proportions of alcohol sales to dependent users and non-dependent users.

(Munich, 31 July, 2002) - Natural molecules that act like the primary active ingredient in marijuana apparently play a key part in helping the brain wipe away fearful memories, perhaps averting undue anxiety and panic attacks, report researchers from the Max Planck Institute of Psychiatry in Munich, Germany. The findings reported in the journal Nature may explain part of the reasons why marijuana and hashish have been used for medicinal and recreational purposes for some 3,000 years.

Dr. Beat Lutz, and his German and Italian colleagues, express the hope that their findings could lead to the development of psychiatric drugs for the treatment of such fear-based conditions as phobias and post-traumatic stress disorder. The results of their mouse studies provide clues to the influence on human behavior of so-called "endocannabinoids," naturally occurring molecules related to the delta9-tetrahydrocannabinol or delta9-THC, which is the principal active substance in cannabis.

Delta9-THC affects the nerve cells in the brain, producing its signature mind-altering effects by attaching itself to a protein on the surface of each neuron. This protein, called the CB1 receptor, also provides a critical hook-up point for the endogenous cannabinoids - cannabinoids naturally produced by the body. Without it, the chemicals cannot do their prescribed job.

The five-year study revealed a previously unknown component of that job - snuffing out terrifying memories as part of the body's fear-coping mechanism. "Our work shows an involvement of the endogenous cannabinoid system in extinction of fear memory for the first time," stated Dr. Lutz.

"We really had no idea before that this system might be involved in erasing of particular types of memories," said neuroscientist Pankaj Sah of Australian National University in Canberra, Australia, who wrote an accompanying commentary. "Although we understand how fearful memories are stored in the brain, how they are extinguished remains a mystery. The answers may lie with the cannabinoid compounds our bodies produce," he added. "The finding might have implications for treating anxiety disorders in humans."

Anxiety disorders are the most common of all mental disorders. In the United States, it is estimated that some 5.3 million Americans annually suffer from social anxiety - a persistent, irrational fear of social interactions. Another 5.2 million Americans suffer from post-traumatic stress disorder while more that 3 million suffer from panic disorder. In light of these new findings, it may be the case that such disorders are in part the result of an endocannabinoid deficiency or a deficiency of cannabinoid receptors.

In the experiments, both normal mice and mice with a mutation that caused them to lack the cannabinoid receptor CB1 heard a tone, then felt an electric shock to the foot. Subsequently, both groups of mice "showed a remarkable fear reaction during the first re-exposure to the tone," Lutz explained. "With repeated tone presentations, control mice quickly recovered from this fear reaction. CB1-deficient mice, in contrast, showed only a weak reduction of fear." Over the next several days, as the researchers sounded the tone without administering the shock, the normal rodents soon came to regard the sound as benign, while the mutant mice continued for a much longer time to react to the tone by freezing in fear. To wipe away frightful recollections, endocannabinoids flood the amygdala - the brain's almond-shaped center of threat recognition, fear and aggression - where they dampen the action of its nerve cells, helping to dismantle terrifying associations and potentially providing relief to sufferers of post-traumatic stress disorder, phobias, panic attacks and certain forms of chronic pain.

In the words of Dr. Sah, "the finding that the endocannabinoids contribute to extinction raises the possibility that drugs that target these molecules and their receptors could be useful new treatments for anxiety disorders." Dr. Sah concluded that, "this work tells us that the cannabinoid system is very old and plays roles in evolutionarily quite old behaviors. This, I suppose, fits with the very long history of use of cannabis in human society. It tells us that trying to work out how cannabinoids act is a very useful exercise whose outcome could have important medical benefits in the future."

"To my mind [the study] raises issues about why people use cannabis in the first place," Sah remarked. "We all take aspirin for headaches and toothaches - of course, aspirin does not have the same gamut of cognitive actions as cannabis. But it's worth considering that people (who) constantly use cannabis may be doing it for other reasons than just to 'get high' - perhaps they are experiencing some emotional problems which taking cannabis alleviates. Much the same way as some people drink alcohol to relieve anxiety." In brief, Dr. Sah appears to have rediscovered the self-medication hypothesis - apparently unaware of the extensive literature already supporting it.

A recent analysis of the rates of comorbidity among adolescents with substance abuse disorders in a community-based sample from the Methods for the Epidemiology of Child and Adolescent Mental Disorders Study (MECA) provides further support for the self-medication hypothesis.

Denise Kandel and her colleagues compared the rates of comorbidity in the MECA group with findings from other community-based studies of adolescents and adults. Three-quarters of the adolescents with a substance abuse disorder had a comorbid anxiety, mood or behavior disorder, compared with one quarter of adolescents without a substance abuse disorder.

The relationship with disruptive behavior disorders was strongest and remained significant after controlling for other co-occurring disorders. Rates of comorbidity were comparable with those found in other studies of adolescents and adults, including some studies of adolescent treatment populations.

Source: Kandel, D.B.; Johnson, J.G.; Bird, H.R.; Weissman, M.M.; Goodman, S.H.; Lahey, B.B.; Regier, D.A.; and Schwab-Stone, M.E. Psychiatric comorbidity among adolescents with substance use disorders: Findings from the MECA Study. Journal of the American Academy of Child and Adolescent Psychiatry, 1999, vol. 38, pp. 693-699.

A number of studies have shown that Attention Deficit/Hyperactivity Disorder may play a causal role in dependence on a number of drugs, including marijuana and cocaine, as predicted by Duncans model of the self-medication hypothesis. A new study suggests that attentional difficulties that do not rise to the level of ADHD may also contribute to the causation of substance abuse disorders.

Tapert et al. examined the influence of adolescent attention functioning on the development of substance use problems in 66 high-risk youths over an 8-year period. Participants were community youths who were free from any history of substance use disorders, other mental disorders, or neurological illness at intake and were administered neuropsychological tests and substance involvement interviews from ages 15 through 23. Substance involvement was assessed by self-report, resource person reports, and randomly sampled toxicology screens.

Attention/executive functioning scores obtained at the pretest neuropsychological assessment significantly predicted substance abuse and dependence symptoms 8 years later, even after controlling for intake substance involvement, gender, education, conduct disorder, family history of substance use disorders, and learning disabilities. These results suggest that adolescents with limited attentional abilities are also at risk for developing drug abuse or dependence. Thus, prevention and treatment efforts should target youths with attentional difficulties by using programs that are effective for those with compromised concentration and processing abilities.

Source: Tapert, S.F.; Baratta, M.V.; Abrantes, A.M.; and Brown, S.A. Attention dysfunction predicts substance involvement in community youths. Journal of the American Academy of Child and Adolescent Psychiatry, 2002, vol. 41(6), pp. 680-6

The authors conducted a comparative test of the hypotheses that (a) stress is an etiological factor for smoking and (b) cigarette smoking causes increases in stress. Participants were a sample of 1,364 adolescents, initially surveyed at mean age 12.4 years and followed at three yearly intervals. Measures of negative affect, negative life events, and cigarette smoking were obtained at all four assessments.

Latent growth modeling showed negative affect was related to increase in smoking over time; there was no path from initial smoking to change in negative affect. Comparable results were found for negative life events, with no evidence for reverse causation.

This study investigated internalizing and externalizing symptoms as potential mediators of the relationship between perceived discrimination and early substance abuse among 195 American Indian 5th through 8th graders from three reservations that share a common culture. It was found that perceived discrimination increased both internalizing and externalizing symptoms among the youth.

Perceived discrimination contributed significantly to internalizing symptoms, particularly among female and younger adolescents, but did not contribute to early onset substance abuse. Instead, perceived discrimination acted through externalizing symptoms to increase its likelihood. That is, American Indian early adolescents who experienced discrimination were likely to respond with anger and delinquent behaviors, which in turn were strongly associated with early substance abuse.

The authors examined early psychopathology as a predictor of trajectories of drug use from ages 13-18 years. Six years of annual data were analyzed for 506 boys using a mixed effects polynomial growth curve model. They tested whether distinct measures of psychopathology and behavioral problems (i.e., attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, depression, and violence) assessed in early adolescence could prospectively predict level and change in alcohol and marijuana use.

Higher levels of all of the types of psychopathology predicted higher levels of alcohol use, and higher levels of attention-deficit/hyperactivity disorder, conduct disorder, and violence predicted higher levels of marijuana use. Only conduct disorder predicted linear growth in alcohol use, and none of the measures predicted growth in marijuana use. The results suggest that drug use prevention programs should target youths with early symptoms of psychopathology.