Image: 07_Girl_Smoking_Meth_Queens.jpg
Smoking methamphetamine produces a brief, intense "rush" and can result in long-term neurological damage.
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The spread of methamphetamine production and abuse has sparked a flurry of research on the drug’s health effects and possible new ways for treating the addiction.

Until a few years ago, methamphetamine was considered a regional problem. Largely confined to the West Coast and Southwest, it was off the radar of federal drug offices in Washington, D.C. But as the drug swept into rural Midwestern communities in the mid-1990s, catching hospitals and treatment centers unprepared for its devastating effects, steps were taken to gain a better understanding of meth’s toll on the body.

Getting hooked
Methamphetamine, like cocaine, is a powerful stimulant. It produces physiological changes similar to the fight-or-flight response — it boosts heart rate, respiration, blood pressure and body temperature. Some people use it for the brief, intense “rush” it produces when smoked or injected. Others use it for functional reasons — as an appetite suppressant to lose weight or as an energy-booster to enable them to work more. When snorted or taken orally it doesn’t produce an intense “rush” but rather a “high” that can last more than 12 hours.

Both cocaine and meth boost brain levels of the neurotransmitter dopamine, which causes feelings of euphoria and increased energy, but go about it in different ways. Cocaine doesn’t directly stimulate the release of dopamine; it prevents the normal recycling of the chemical messenger once it’s released. Meth goes a step further — it actually gets into the nerve cell where it causes the excessive release of dopamine. Meth users can quickly become addicted to the spike in dopamine.

Abuse of methamphetamine is linked to several serious medical complications such as heart damage, stroke and psychosis. But perhaps the most frightening side effect is long-term neurological damage unlike anything seen with heroin or cocaine.

While high levels of dopamine in the brain usually cause feelings of pleasure, too much can produce aggressiveness, irritability and schizophrenic-like behavior.

“Meth has more long-term, serious effects on the brain than cocaine,” said Dr. Nora Volkow, senior scientist at Brookhaven National Laboratories in Upton, N.Y., who has studied the effects of both cocaine and methamphetamine on the brain for 15 years.

The brain on meth
Using brain-imaging techniques, scientists have discovered that the brains of former chronic users show a significant decrease in the number of dopamine transporters, a crucial component of a functional dopamine system.

The most recent development comes from Volkow who, along with Dr. Linda Chang, collected the first data on what this decline in dopamine transporters means. They performed brain scans on 15 detoxified, former meth users and found a 24-percent loss in the normal number of dopamine transporters. This loss of transporters was linked to slowness in motor skills and poorer performance on verbal and memory tasks.

“We found the subjects with the most profound changes in the transporters were the ones with the most functional disturbances,” said Volkow, whose research will be published in the American Journal of Psychiatry in March. “This is the first time anybody has reported that these neuron losses are functionally significant. It’s not just that you lose brain cells and you keep living happily ever after; it translates into a disruption in your performance.”

Volkow noted that the same association has been reported in Parkinson’s disease patients, although they experience a more drastic loss of transporters.

“We need to look more at how and why it’s having these long-term effects and whether in fact they are permanent,” said Timothy Condon, associate director for science policy at the National Institute on Drug Abuse (NIDA). “As we unravel more about what functional changes are a result of those brain changes, they will impact how you go about treating someone.”

Douglas Anglin, director of the UCLA Drug Abuse Research Center and co-principal investigator of the Methamphetamine Treatment Project, a group that studies addiction therapies, said: “This takes us beyond the model of drug treatment to one of brain damage.”

But Dr. David Smith, founder and president of the Haight Ashbury Free Clinics in San Francisco, wants to draw attention away from methamphetamine’s neurological impact. “Focusing on the brain damage caused by meth is counterproductive to recovery. It makes people pessimistic about whether their brains are going to heal. In treatment, we offer a message of hope, and we have had many meth users who have achieved full recovery.”

Behavioral treatment
Meth addiction gained a reputation as being untreatable when the drug began to spread into small communities in the Midwest. “These rural areas had not been very affected by cocaine or heroin so when they had to start dealing with meth users they had no idea what to do with them,” said Richard Rawson, executive director of the Matrix Institute, a non-profit addiction research organization in Los Angeles, and co-principal investigator at the Methamphetamine Treatment Project along with Anglin. “Patients were coming in psychotic, so you started hearing these horror stories that meth was untreatable. For those of us who’ve been dealing with heroin and crack users, it was more manageable.”

Though not impossible, meth addiction is a difficult disorder to treat, according to Anglin. “There’s not severe physical withdrawal with methamphetamine, but rather a feeling of anhedonia, an inability to experience pleasure, that can last for months and which leads to a lot of relapse at six months,” he said. The anhedonia appears to correspond with the period when the brain is recovering and producing abnormally low levels of dopamine.

“When you think of treatment of drugs like methamphetamine, you have to think of it like fixing a broken leg — treatment provides a structure to allow their brain chemistry to return to normal. Their brain is out of tune, it’s not working very well, and it takes a while to recover,” Rawson said.

Unlike heroin addicts, who can be weaned off the substance with methadone, there are no pharmacological treatments for meth. The only currently available treatment is behavioral therapy.

The Matrix model, a method of outpatient cognitive-behavioral therapy backed by the Center for Substance Abuse Treatment (CSAT), a division of the federal Substance Abuse and Mental Health Services Administration, is the only program with evidence of effectiveness for methamphetamine addiction.

The model, which was first developed in the 1980s as a cocaine treatment under a NIDA grant, serves as the primary treatment protocol for a network of clinics in Southern California.

The basic elements of the four- to six-month approach (a two-month approach is also being developed) consist of a minimum of three group or individual therapy sessions per week, where patients are coached through their recovery. They are taught about their addiction and trained to manage cravings and avoid risky activities, like drinking alcohol, that could trigger relapse. The method also uses family therapy, urine testing and 12-step activities.

“We have data from treating several thousand patients [with the Matrix model],” Rawson said. “Treatment of meth addiction appears approximately equal to cocaine treatment. Treatment is about 50 percent to 60 percent drug-free at the end of one year.” That’s superior to recovery after behavioral therapy for heroin addiction (without the use of methadone), but not as good as recovery from alcoholism, according to Rawson. No nationwide statistics on the overall effectiveness of treatment for meth addiction exist, but as the Matrix model is a particularly vigorous, well-studied approach, it’s likely this success rate is higher than average, Rawson noted.

The model is currently being compared to seven other outpatient treatment methods in the first large clinical trial of behavioral treatments for meth addiction. The 800-patient randomized study is being conducted by the Methamphetamine Treatment Project, an organization funded by CSAT in an effort to identify the most effective treatment strategies for meth addiction. CSAT will use the results to issue its national treatment guidelines.

The other treatment approaches being evaluated vary in length (from one month to six months), intensity (from one hour per week to 13), population (two are for women only, and racial makeup varies across centers) and emphasis. All of the programs are based on the underlying assumption that addiction is a chronic disease. Some emphasize life skills such as assertiveness; others focus on spirituality; others on family support. Some are strictly regimented programs; others are more flexible to a patient’s individual needs.

Though the large clinical trial is not evaluating any inpatient treatments, some methamphetamine users do enter 28-day residential programs focused on detoxification and self-help strategies. Originally developed for the treatment of alcoholism in the 1980s, these programs have become a catchall for abusers of various substances. Additionally, other, more long-term residential programs (usually about six months) designed primarily for heroin users referred by the criminal justice system are now being used by meth addicts. CSAT cites a lack of empirical evidence for these programs for stimulant users; however, some experts cite supporting clinical experiences with short-term and long-term residential programs for certain subsets of meth abusers.

In the pipeline
In an effort to expand treatment options, NIDA set up a program last year to develop pharmacological approaches to meth addiction.

“In our pipeline right now, we have about 10 compounds in various stages of clinical trials, most of them very early on, for methamphetamine addiction,” Condon said. “They’re all classic medications used in other areas of medicine that we’re testing as anti-methamphetamine agents.”

Among the drugs being tested: calcium-channel blockers, a class of drugs used to treat high blood pressure that may inhibit the excessive release of neurotransmitters and reduce the “reward” of using methamphetamine; the anti-nausea drug Zofran, which has been shown to work against relapse in alcoholics; tyrosine, an amino acid that’s a precursor of dopamine and may increase production of the neurotransmitter; and several antidepressants.

Antidepressant medications are currently prescribed for some meth addicts to combat the depressive symptoms frequently seen in withdrawal, but they are now being studied as treatments to reduce relapse based on their ability to boost levels of neurotransmitters associated with pleasure, which are abnormally low in people who have stopped using meth.

Research is currently being planned on the anti-smoking/antidepressant drug bupropion, also known as Zyban and Wellbutrin.

Scientists also plan to test medications that may be able to reverse some of the neurological damage and cognitive impairment caused by methamphetamine use. Experts say one of the most promising is selegiline, a treatment approved for some symptoms of Parkinson’s disease. Selegiline has neuroprotective effects and has been shown to reduce HIV-related cognitive deficits. Studies on vitamin E, which is thought to boost natural protective chemicals in the brain, are also planned.

In addition, NIDA is funding research on the development of an antidote for methamphetamine that would be used in overdose situations. The hope is that a compound could leach meth out of the tissues, decreasing concentrations of the drug in the body. Theoretically, this would reduce the duration of the high and some of the adverse effects. However, such a treatment is years away from being tested in people, according to NIDA.

But as researchers churn away on potential treatments of the future, thousands of people are addicted to methamphetamine right now and aren’t taking advantage of the available behavioral treatments, said CSAT director Dr. Westley Clark.

A survey of primary care doctors suggests many of them are reluctant to talk with their patients about drug abuse. The findings, published recently in the Archives of Internal Medicine, showed that about one-third of the 1,080 doctors surveyed said they don’t routinely ask new patients if they use drugs, and 15 percent said they do not generally suggest interventions for drug-abusing patients.

“We need to educate primary-care providers about the early signs of substance abuse. And we need to make sure that treatment is available,” Clark said. “Before treatment can be effective, we need to get people into it.”

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