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Turning to Drugs to Stop Addiction

From Drug Discovery & Development:

Could a once-a-month alcoholism shot keep some of the highest-risk heroin addicts from relapse? A drug that wakes up narcoleptics treat cocaine addiction? An old antidepressant fight methamphetamine?

This is the next frontier in substance abuse: Better understanding of how addiction overlaps with other brain diseases is sparking a hunt to see if a treatment for one might also help another.

We're not talking about attempts just to temporarily block an addict's high. Today's goal is to change the underlying brain circuitry that leaves substance abusers prone to relapse.

It's "a different way of looking at mental illnesses, including substance abuse disorders," says National Institute on Drug Abuse Director Dr. Nora Volkow, who on Monday urged researchers at the American Psychiatric Association's annual meeting to get more creative in the quest for brain-changing therapies for addiction.

Rather than a problem in a single brain region, scientists increasingly believe that psychiatric diseases are a result of dysfunctioning circuits spread over multiple regions, leaving them unable to properly communicate and work together. That disrupts, for example, the balance between impulsivity and self-control that plays a crucial role in addiction.

These networks of circuits overlap, explaining why so many mental disorders share common symptoms, such as mood problems. It's also a reason that addictions - to nicotine, alcohol or various types of legal or illegal drugs - often go hand-in-hand with post-traumatic stress disorder, depression, schizophrenia and other mental illnesses.

So NIDA, part of the National Institutes of Health, is calling for more research into treatments that could target circuits involved with cognitive control, better decision-making and resistance to impulses. Under way:

-Manufacturer Alkermes Inc. recently asked the Food and Drug Administration to approve its once-a-month naltrexone shot - already sold to treat alcoholism - to help people kick addiction to heroin and related drugs known as opioids.

-Studies at several hospitals around the country suggest modafinil, used to fend off the sudden sleep attacks of narcolepsy, also can help cocaine users abstain.

-An old antidepressant, bupropion, that's already used for smoking cessation now is being tested for methamphetamine addiction, based on early-stage research suggesting it somehow blunts the high.

Medication isn't the only option. Biofeedback teaches people with high blood pressure to control their heart rate. O'Brien's colleagues at Penn are preparing to test if putting addicts into MRI machines for real-time brain scans could do something similar, teaching them how to control their impulses to take drugs.

Combined Sertraline, Naltrexone Treatment May Benefit Depressed, Alcohol-Dependent Patients

From Business Week:

Combined treatment with the antidepressant Zoloft (sertraline) and the alcoholism drug naltrexone improves the likelihood that people with both major depression and alcohol dependence will be able to stop drinking, U.S. researchers report.

Their 14-week study of 170 patients found that 54 percent of those who received the combined treatment were able to stop drinking, compared with 21 to 28 percent for patients who received a placebo, Zoloft only, or naltrexone only.

The patients who received the combined treatment also went for a longer period of time before they started drinking again -- 61 days compared with 15 days for patients in the other groups.

The findings may prove an important advance in the treatment of patients with alcohol dependence and depression, said the University of Pennsylvania researchers.

The study was published March 15 in the The American Journal of Psychiatry.

Posted: 3/16/2010 1:24:00 PM

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Low Dose Naltrexone: The Next Miracle Drug?


Naltrexone is the generic name for a drug, approved by the FDA in 1984, used to treat alcohol and opioid addiction. Opioids are generally pain-management agents such as morphine, codeine, oxycodone, and fentanyl. Opioids also include heroin and methadone, as well as our own naturally occurring endorphins.

Naltrexone is an opiate receptor antagonist; that is, it blocks cellular opiate receptors. As such, it removes the pleasurable feelings associated with alcohol and opioid abuse. In fact, the drug does such a good job of blocking the receptors that many heroin addicts would stop taking naltrexone, since it simply made them feel terrible all the time. As such, methadone became the drug of choice in the treatment of heroin addiction.

Neurologist Bernard Bihari MD, who at the time was treating heroin addicts with naltrexone, discovered that a substantial number of them—who also suffered from AIDS—had extremely low levels of endorphins. He postulated that this may have been the reason they turned to heroin in the first place. While opioid (and thus endorphin) receptors are found throughout the body, they are especially prevalent on immune system related cells.

Since many diseases stem from some sort of immune dysfunction, Bihari wondered if low endorphin levels were a factor. In 1985, Bihari discovered that a low dose of naltrexone (LDN) blocks the endorphin receptors for only about an hour, the net result being that the body responds by secreting much more of the endorphins—often by a factor of five.

Within a few years, he was seeing the therapeutic benefits of LDN in patients with such varied conditions as lymphoma, lupus, and pancreatic cancer. But, as good as these results seemed to be, they were not observed in a controlled clinical study.

The first study of LDN published in a US-based medical journal would come in 2007, with Dr. Jill Smith's article in the American Journal of Gastroenterology entitled "Low-dose naltrexone therapy improves active Crohn's disease" (e-published in January, print published in April). Smith and her team found that 67% of the patients went into remission and fully 89% showed some therapeutic benefit. This encouraging work led to an NIH grant and a Phase II placebo-controlled clinical trial, currently in progress.

In September, 2008, results were published for a Phase II clinical trial in Italy in which LDN was used to combat multiple sclerosis (MS). Again, the results were highly promising. Since MS is thought to result from an autoimmune process whereby T cells mistake myelin—the coating around nerve cell fibers in the brain and spinal chord—for a foreign invader and attack it, many assumed that MS was the consequence of an overactive immune response. These results, though, would argue against that theory.

In 2007, Burton Berkson MD, PhD and associates published an article in Integrative Cancer Therapies entitled "Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone." Berkson's 2006 article in the same journal entitled "The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol" described the incredible turnaround of a patient previously diagnosed as terminal in 2002.

LDN is inexpensive with virtually no harmful side effects. However, since it is no longer a proprietary drug, the pace of rolling out clinical trials for the off-label effects described in this article will probably be slow, as will its acceptance by mainstream medicine. Still, there is nothing to prevent a patient from taking an FDA approved drug for an off-label indication, and this practice goes on all the time.

Posted: 6/1/2009 9:17:00 AM

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