By Julia Sommerfeld/

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.”    © 2009


Methamphetamine Addiction Mechanism Discovered, Explains Why Craving Last so Long

ScienceDaily (Apr. 10, 2008)

Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.  The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.

Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.  They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal — the equivalent of years in humans — did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.

The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.

What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.  After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.  “What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that,” said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children’s Hospital. “We think these changes in the brain may account for at least some of the physiological components of meth addiction.”

If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.  “Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction,” explained Bamford. “We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals.”  Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.

This research was supported by several grants, including two from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. It was also supported by Seattle Children’s Hospital and the Center for Human Development and Disability at the UW. The project included researchers with Columbia University, the New York State Psychiatric Institute, and the University of California at Los Angeles.