The Frontal Cortex

A Drug for Drug Addicts

Cerebrum just published an interesting article on the ethical implications of using drugs to treat drug addiction. In particular, the scientists examine the benefits of naltrexone, an opioid receptor antagonist. (This means that the drug blocks receptors that normally bind opiates, like heroin. Methadone, in contrast, activates opioid receptors but appears to be an antagonist for NMDA receptors.) The scientists begin the article by discussing one of the few studies that actually investigated the benefits of naltrexone:

Despite not using opioids for a long period, incarcerated opioid addicts relapse at an alarming rate following their release from custody, even when they are under the supervision of a parole officer. It may be thought that the period of incarceration would “get the opioids out of their system” and “teach them a lesson,” but this is apparently not enough to prevent re-addiction and re-incarceration in a majority of opioid-addicted offenders. The availability of naltrexone may provide real benefits to these individuals, the criminal justice system and the public at large.

Studies conducted in the 1990s suggested that daily ingestion of a naltrexone pill taken by mouth reduced the frequency of relapse in parolees. Naltrexone has a high affinity for opiate receptors and prevents the high from heroin or other opioids by blocking their access to the receptor. In the only randomized, controlled clinical trial of probationers with a history of opioid addiction, Dr. James Cornish and colleagues in Philadelphia found that 59 percent of opioid-addicted parolees who received standard parole supervision–but not naltrexone–relapsed and were re-incarcerated within a year of their release. In contrast, a randomly assigned group of similar parolees who received both standard parole supervision and naltrexone from a research nurse stationed at the parole office had a relapse rate of only 25 percent.

What do you think? Is it wrong to simply substitute one drug for another? Or should extended-release naltrexone (once it’s approved by the FDA) become a mandatory part of drug rehab? Personally, I think the best way to think of these anti-addiction drugs is as a self-control booster. They clearly don’t erase the desire for the opiate – that’s why 25 percent of addicts still relapse – but they make it easier to resist the chemical temptation. And addicts need all the help they can get.

As I’ve argued before, I think the scourge of addiction is one of those rare societal problems that neuroscience can, at least in theory, really help alleviate.


  1. #1 DrugMonkey
    December 1, 2008

    hmm, let’s see here. We have an acquired medical condition that depends (most likely) on the confluence of an adverse genetic endowment, known and unknown environmental influences and yes, behavioral choices made by the individual. It is treatable, but perhaps not curable, with chronic pharmacotherapy.

    hmm, are we talking about drug abuse or

    heart disease? diabetes? HIV/AIDS? HepC? various cancers? emphysema? high blood pressure? …shall we go on?

    Is it wrong to simply substitute one drug for another?

    So why is this a question? Is it because of scientific / medical ignorance? If so, why is it that so many uninformed individuals proudly trumpet their anecdotal and gut feelings about drug abuse when they would never say “boo” about, say, diabetes? or HIV/AIDS?

  2. #2 Emmy
    December 1, 2008

    I have to agree that besides being ironic we should have no qualms about pharmaceutical solutions to drug abuse relapse. However I was reading a review paper on the neural basis of drug addiction this morning and LTP is cited as being culprit in relapse even after many years of being clean. What if drugs were developed that could prevent addiction altogether by interrupting the long term changes in reward circuitry? You could use cocaine but not be addicted. I think this would raise another set of very interesting ethical questions.

  3. #3 crawford
    December 1, 2008

    If you’ve been part of or know a family member who has been helped by AA, NA and their 12-step ilk, then you will appreciate that arresting the compulsion is only a beginning to help the addict learn to live a full, happy, productive life. And it is in this learning to live, this personal rewriting of the individual’s story, that the addict comes to find a solution to his or her coping challenges that is more powerful than the temporary one afforded by the drug.

    So,can a drug be helpful? Sure. I suppose. But it doesn’t really get to the deeper root issues that need to be addressed fo long-term recovery.

  4. #4 Abel Pharmboy
    December 1, 2008

    I recently had the honor of visiting with Dr Mary Jeanne Kreek, the Rockfeller University physician-scientist who in the 1960s led the development of methadone maintenance therapy for opioid addicts. Rather than blocking the reinforcing opioid-induced euphoria with naltrexone, methadone is a long-lived opioid replacement. She uses the example of insulin-dependent diabetes, a chronic disorder with a known biological cause that affects only a subset of the population. Here is a nice exchange during a 2001 radio interview:

    Norman Swan: Which brings us back to methadone and whether it’s a chemical bandaid or a therapy.

    Mary Jeanne Kreek: A better analogy is probably insulin treatment for type 1 or type 2 diabetes. A bandaid, no, but if you’re speaking more correctly as a treatment for the receptor, indeed, just like insulin you’re replacing that which should be there normally. We may in fact be doing the same with beta-endorphin. We are finding that there seems to be evidence for a relative endorphin deficiency, and persons who are now off heroin, off methadone and in this drug-free state.

    Norman Swan: And of course we come now to the key question where prejudice about methadone treatment arises: can you ever get somebody off it?

    Mary Jeanne Kreek: We have to ask why we’d want to get people off a drug if a medication is being helpful. [emphasis mine] I don’t use the word ‘drug’, I use medication if you’ve noticed. In pharmacotherapy I think we should try to change our English language. But having said that, you don’t get people off insulin, you want to maintain their insulin as long as they need it, because they have a relative deficiency. If we had beta-endorphin in a form which would pass the blood/brain barrier, in adequate amounts, we’d be delighted to use beta-endorphin. But on the other hand, methadone is as like beta-endorphin as one can get, and it’s xenobiotic, we were very lucky. It has no toxicity, no long-term side effects, we know that methadone is acting precisely where we want it to be targeted, at the neuro receptor, so we don’t see the need of getting people off treatment any more than you’d try to get people off treatment from insulin or any other medication even if it were synthetic like a medication targeted to manage hypertension or renal problems.

  5. #5 retired
    December 1, 2008

    I think any “recreational drug use” that is more than intermittent is usually self-medication for emotional problems. Ditto for drinking beer more than occasionally (I recently took up the hobby of homebrewing). In short, it’s minor medication for minor personal problems. We all have them. Heavier use indicates less-than-minor problems.

    I was an occasional pot smoker in college, which is an emotionally difficult time. But I didn’t become a heavy user until my mid-40’s, when I ran into some intractable family/emotional problems (massive rejection on all sides). If it wasn’t for “recreational pot use” at that time in my life, I would probably be an alcoholic by now.

    Bottom line: don’t go passing judgement on other peoples’ behavior, unless it harms others directly. It serves no purpose, and is a form of bullying. But bullying of parolees is somehow accepted as part of the War on Drugs.

  6. #6 Percy Menzies
    December 2, 2008

    All drug addicts and alcoholics are in some way ‘incarcerated’ by the addiction. Patients whether being released from jail and prison or residential programs are ‘parolees’ returning home to a cue-rich environment. Naltrexone is a neuroprotective shield that protects the patient from accidently or impulsively using drugs or alcohol and ‘reoffending’and thus risiking ‘reincarcertion’ to the addiction. Few people remember that this was the original reason for the developing naltrexone. The availability of the depot injection is a huge step in protecting ‘parolees’ from relapsing

  7. #7 Estetik
    December 2, 2008

    Not much seems to be working for me — not the YouTube, not the Flickr, not the RSS reader. Not much at all. Am I missing some plugins or something?

  8. #8 Donna B.
    December 3, 2008

    My addiction is smoking. I’m not stupid and I know it’s harmful. That doesn’t mean quitting is easy. The only time I can remember not wanting or craving a cigarette was when I was on morphine after a major surgery.

    I’ve asked myself which would be worse – morphine addiction or lung cancer… for which I might receive morphine for pain.

    Does methadone reduce cravings for cigarettes? As a side-effect, would it make my arthritis less painful?

    Just asking… as I’m certainly not a drug expert. I do suspect that the self-medication benefits of cigarettes has not been fully explored.

  9. #9 whitewhale
    December 3, 2008

    you ask stupid questions like,
    “Is it wrong to simply substitute one drug for another?”

    There are no ethical questions when substituting one drug for another, it only matters which drug is more effective, and why?

    another stupid question,
    “should extended-release naltrexone (once it’s approved by the FDA) become a mandatory part of drug rehab?”

    you must have no regard for issues of our cognitive freedom and infringement of personal liberties. It would be very frustrating to be forced to ingest a drug that prevents a person from getting high. I doubt that you would be in line for a drug that prevented the enjoyment of a wine/cheese party.

  10. #10 Crusty Dem
    December 3, 2008

    One of the best features of the variety of drugs being tested/used now for addicts is their ability to alter the reward response, which could reverse the LTP-type neurophysiological response (LTD been demonstrated in the striatal circuit, it required cannabinoids. Insert ironic and gratuitous marijuana joke here.) in the DA system that triggers reward. Repeated administration that fails to stimulate a satisfying response (due to naltrexone, methadone, or other drugs) could result in habituation of craving. Which would be helpful for addicts, although I doubt it’s truly possible to eliminate craving (without very harmful side effects), given it’s complexity.

    “Is it wrong to simply substitute one drug for another?”

    No. No No No No No. Not in a million years*.

    A better question would be “Is it wrong to implant a drug delivery system in these patients to improve outcome?”.

    * unless you’re secretly a scientologist, Jonah.

  11. #11 gboone
    December 12, 2008

    @whitewhale his questions are not stupid and you did not answer them. Try again.

    To address the topic:
    The ethical question really at the fore of this discussion should be “What is the essence of the drug problem, and what are the goals of drug rehabilitation?” If a person is addicted to heroine and the essence of the problem is one of chemical dependence then it is absolutely wrong to “cure” that dependence by switching chemicals. When the patient leaves the hospital, the patient has the same problem it was admitted with; it would seem to make more sense to eliminate the chemical dependency altogether instead of replacing the chemical on which the patient depends. Unless, of course, the patient is admitted with a heroine addiction–-a much more specific condition–in which case there is no problem in replacing the drug, especially if the new drug keeps the patient from enjoying heroine again.

    Addiction to a specific drug and chemical dependence are two separate conditions in my mind–though the former is a subset of the latter–and I would hope the goal of a rehabilitation program would be to eliminate chemical dependency rather than correcting one individual addiction at a time. Treating a heroine addiction isolated from the greater dependency issue is a bit of a cheat in my book; a more honest rehabilitation program would try, not only to keep patients from relapsing on the same drug, but from other drugs and substances as well.

  12. #12 aldovillasenor1979
    February 12, 2009

    Now, I am by no means an expert, but I believe that Crawford may be on the right track…

    Physiological dependence to any substance is usually null after the acute withdrawl period(7-10-15 days or so). What usually drives addicts to relapse after a substantial enough period of abstinence could be described as more of an psychological lack of coping mechanisms. Counter conditioning, and the development of healthy ways in which to cope with emotional and psychological states, would further facilitate the probability of long term abstinence.

    Use of medically monitored drugs to aid in easing symptoms of acute withdrawl is not unethical, in my opinion.
    Longterm use of such drugs and not adressing the psychological, emotional or behavioral aspects of addiction, is just plain irresponsible.

    Also, has anyone considered the fact, that incarceration does not necessarily result in abstinence from mood or mind altering substances? Drug culture and substance abuse runs rampant in America’s correctional institutions. To not consider this factor is just plain naive. If an inmate continues to engage in substance abuse while incarcerated, he has not technically “relapsed”, after his release from prison because there was never a long enough period of abstinence to be catagorized in this way…

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