Working out may help prevent substance abuse

WASHINGTON - Sure, exercise is good for your waistline, your heart, your bones — but might it also help prevent addiction to drugs or alcohol?

There are some tantalizing clues that physical activity might spur changes in the brain to do just that. Now the U.S. government is beginning a push for hard research to prove it.

This is not about getting average people to achieve the so-called runner's high, a feat of pretty intense athletics.

Instead, the question is just how regular physical activity of varying intensity — dancing, bicycling, swimming, tae kwan do — might affect mood, academic performance, even the very reward systems in the brain that can get hijacked by substance abuse.

What first caught the attention of National Institute on Drug Abuse chief Dr. Nora Volkow: A study found youngsters and teens who reported exercising daily were half as likely to smoke as their sedentary counterparts, and 40 percent less likely to experiment with marijuana.

Volkow knows — from her own 6-mile daily runs and from her scientific experiments — that the brain literally likes physical activity. Exercise seems to invigorate neurochemicals that sense and reinforce pleasure.

"In children, it's innate," she notes. "Children want to move."

But U.S. children are becoming more sedentary, as illustrated by the obesity epidemic, "screen time" replacing outdoor play and a drop in school physical education. And as youngsters approach adolescence, the run around the yard that used to be fun too often becomes a chore — the dreaded jog around the school track or the nagging to get off the couch. The sedentary teen turns into the sedentary adult.

"Why do we lose the ability to experience pleasure from physical activity?" asks Volkow.

Last week she brought more than 100 specialists in exercise and neurobiology to a two-day conference to explore physical activity's potential in fighting substance abuse, and announced $4 million in new research grants to help.

Drug treatment programs often include exercise, partly to keep people distracted from their cravings, but there's been little formal research on the effects.

The best evidence: Brown University took smokers to the gym three times a week and found adding the exercise to a smoking-cessation program doubled women's chances of successfully kicking the habit. The quitters who worked out got an extra benefit: They gained half as much weight as women who managed to quit without exercising, says lead researcher Dr. Bess Marcus.

She now is working on a larger study to prove the benefit.

Marcus cautions that people trying to kick an addiction have a powerful incentive to exercise. Could that possibly translate into prevention? Among the clues:

• Rats were less likely to ingest amphetamines if their cages had running wheels, suggesting exercise stimulated a reward pathway in the brain to leave them less vulnerable to the drug's rush.
• In people, exercise acts as a mild antidepressant and relieves stress. Depression, anxiety and stress increase risk of alcoholism, smoking or drug abuse.
• Volkow is intrigued that attention deficit disorder and obesity both involve problems with the brain chemical dopamine, one system that drugs hijack to create addiction.
• Baby monkeys who do not play enough in childhood have problems controlling aggression when they're older. The most aggressive tend to have defects involving the feel-good brain chemical serotonin — and binge-drink when researchers offer them alcohol.
• Back to rats, physical activity increases production of growth factors and stem cells in key brain regions important for learning and mood; increases formation of blood vessels; and strengthens communication networks between brain cells.

Together, that is far too little research to know if exercise really matters for substance abuse, scientists at the National Institutes of Health meeting cautioned.

Copyright 2008 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Could Exercise Regenerate Alcohol-Damaged Neurons?

Aaron Levin

Genetics and alcohol-induced inflammation appear to combine in complex ways to cause dependency, but in rats, at least, exercise reduces long-term damage to the brain.

Rats that drink like college students at a frat party are teaching researchers about how alcohol affects the growth and death of brain cells and providing insight into how alcohol produces addictive behavior. They may even point to ways to help alcoholics reach sobriety.

Alcohol's effects on the brain occur through a mixture of genetics and inflammation, Said Fulton Crews, Ph.D., a professor of pharmacology and psychiatry and director of the Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill.

Crews delivered the annual Mark Keller Honorary Lecture at the National Institute on Alcohol Abuse and Alcoholism in November.

His alcoholism research for several decades has been based on the fact that neural stem cells continue dividing in adulthood and give rise to new neurons in the dentate gyrus of the hippocampus and the subventricular zone of the anterior lateral ventricles.

However, ethanol blocks development of new adult neurons, decreasing neural stem cell proliferation, reducing cell survival, and altering maturation of new neurons. Part of that effect is due to genetics, since rats bred to prefer alcohol exhibit greater brain damage after drinking than do controls.

Age is another factor. Adolescent rats are less sensitive to the intoxicating effects of alcohol, but are more likely to sustain brain damage.

A family history of alcoholism and lower age at drinking onset are known to increase the prevalence of alcohol dependence, said Crews. Adolescent rats show more damage in the forebrain from alcohol, and other studies have shown that damage in the orbitofrontal cortex leads to maladaptive decision making.

Crews' recent research has concentrated on how immune regulatory and transcription factors affect neurogenesis. For instance, CREB (cAMP response element-binding) proteins are transcription factors that increase or decrease the transcription of certain genes. Given the equivalent of binge-drinking doses of alcohol, rats show a dose-dependent decrease in CREB binding, which protects neurons, and an increase in necrosis factor-kB (NF-kB) DNA binding activity, a proinflammatory agent.

"Ethanol intoxication decreases neurogenesis, and cell death occurs during intoxication, not withdrawal," said Crews.

Crews and his colleagues also found that butylated hydroxytoluene (BHT)—an antioxidant used as a food preservative— blocks tumor necrosis factor-a (TNF-a), an inflammatory cytokine, in brain slice cultures and in vivo by blocking NF-k B activation. That observation led them to look more closely at the effects of inflammation. Giving BHT with ethanol produced some reversal of neuronal death bysuppressing the inflammatory reaction, leading Crews to speculate about whether diet plays a role in this process. Perhaps the BHT—much reviled by health-food advocates—might protect neurogenesis.

"Natural foods may not be as good for you in this case," he joked.

To test the role of TNF-a, he gave rats a dose of lipopolysaccheride, a bacterial toxin that produces inflammation. in an hour, the toxin produced a 1,000-fold increase in TNF-a in liver, serum, and brain. Levels in liver and serum dropped within hours, but brain levels stayed up, said Crews.

"Cytokines stay in the brain a long time," said Crews. "Ten months after a single dose of the toxin, brain levels remained high." Further study found that alcohol potentiated the toxin's effect in producing long-lasting effects of TNF-a, indicating a similar pathway. At the same time, alcohol also reduces brain levels of IL-10, an anti-inflammatory cytokine.

In another experiment, rats given high doses of alcohol for four days exhibited cognitive deficits associated with neurotoxicity in the dentate gyrus, which is involved with memory and learning. In a water-maze test, both control and alcohol-drinking rats learned equally well, but even three weeks into abstinence the alcoholic rats were much worse at relearning the task. They kept making the same mistake over and over again.

"Such perseveration in rats only brings to light how difficult therapy is for the human alcoholic," said crews. "They have to regenerate to relearn."

The implication, said Crews, is that neurons must be regenerated to provide a substrate for recovery. Yet that does seem possible once the extended, harmful inflammatory effects of alcohol fade.

"Within 20 weeks of stopping alcohol, the damage can be reversed," he said. "So if brain regrowth is useful for the return of executivefunction, how do we make the brain grow?"

Crews has an answer for the rats and maybe for humans, one that doesn't even require approval by the Food and Drug Administration.Heavy physical exercise is known to increase neurogenesis, he said, so he and his colleagues tried an experiment with three groups of rats. One group drank alcohol, but got no exercise. A second drank water and exercised.

"The third drank huge amounts of alcohol and also ran huge amounts," said Crews. The sedentary, alcoholic rats lost neurons, but running increased neurogenesis equally in both the water-drinking rats and the exercising, alcoholic animals, he said. Perhaps an exerciseregimen could reverse neurodegeneration, improve executive function, and help alcoholics along the path to recovery.

"Therapists should challenge their patients to engage in vigorous physical exercise and see if it helps recovery," he said.

An abstract of "Cytokines and Alcohol" is posted at <www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2006.00084.x>.

Exercise: the 13th Step to Beat Addiction!

Todd Crandell was 20-something and an up and coming hockey player with a promising future when he lost it all to substance abuse. After 13 years of drug and alcohol addiction, Crandell decided to enter recovery the traditional way — detox, support groups, AA meetings, the 12 steps etc. — but he, like many others, felt something was missing.

We are learning that one size does not fit all when it comes to addiction recovery programs. The 12-step programs have and will continue to help millions successfully recover from addictions. However, many recovery programs are now taking a more holistic approach when treating addictions — not just alcohol and drugs — but other addictions like cigarette smoking and binge eating.

The holistically oriented programs supplement the traditional approach of beating an addiction with lifestyle changes including exercise, nutrition, stress management and optimal rest. That’s why as a fitness trainer, I am now talking about addictions, because exercise can play a central role.

Exercising every day has been proven to positively impact an addict in many ways. For example, an active addict can lose structure and meaning to his/her day, but exercise immediately provides this. Exercise fills time and keeps the mind busy. The process of getting fit or actually training for a specific event builds confidence and gives the recovering addict a goal to work toward.

Exercise can also be beneficial in easing symptoms of anxiety and depression, which go hand-in-hand with addiction. An imbalance of neurotransmitters in the brain produces the anxiety and depression. Exercise not only impacts endorphins, but also increases levels of serotonin and dopamine, creating more balance. This produces the famous “runners high,” decreases anxiety, and provides an overall feeling of “calm.”

These were the benefits for Crandell, and they helped him overcome his addiction for good and get his life back on track. He is now helping others overcome addiction with the organization he founded called Racing for Recovery.

He says the holistic approach to recovery helped him “not only physically, but spiritually, emotionally, and intellectually, as well.”¹ In other words, the whole person. You can learn more about the organization at www.racingforrecovery.com.

Research shows that 75% of Americans know someone who has an addiction.² If you are struggling with addiction now, I urge you to seek out programs that encourage exercise. It has helped many others like Todd Crandell, and it could be just what you need to finally overcome your addiction.