Is methadone an effective treatment for heroin addiction? YES!

What is methadone and does it work as a treatment for opioid addiction? Methadone helps treat opioid addiction and keeps addicts off of heroin. Why is it not being used more widely? Derek Simon, Ph.D. helps us explore this issue here.

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Methadone can be a highly effective treatment for heroin addiction.

More here on how it works as a treatment to keep people off stronger opiate or opioid drugs. And, we explore why it’s not being used more widely. As always, your questions or comments are welcomed at the end.

The Opioid Epidemic

The CDC has declared an epidemic of opioid addiction is occurring in the United States (i). Within the last decade, there has been a shocking 500% increase in prescription of opioid pain medications such as oxycodone. This has resulted in a surge of dependence to opioids as indicated by a 900% increase during this same time period of patients seeking treatment for opioid addiction.

Once dependent on a prescription opioid, many addicts then seek out a cheaper and more potent alternative: heroin. Indeed, heroin use has increased dramatically and is accompanied by a disturbing 286% increase in heroin overdose deaths. 4 out of 5 heroin users report that they began by abusing prescription opioids.

Action needs to be taken to prevent addiction to prescription opioids and treatment for people already addicted to either prescription opioids or heroin. What is the solution to this problem? Like many complex public health issues, the approach must be multifaceted targeting prevention and treatment. Fortunately, an effective treatment for prescription opioid and heroin addiction has existed since the 1960’s: methadone.

But what is methadone used for? How does it work and does it actually keep an addict off of heroin? And if so, why isn’t it being used more often? The short answer is that methadone is an incredibly safe and effective treatment for heroin addiction, but widespread stigma and overly tough regulations have prevented its accessibility to people that need it. But let’s start with the pharmacology.

What is Methadone?

Methadone is a synthetic opioid compound originally developed in the 1930s. In general, an opioid is a compound that can bind to the mu opioid receptor (MOPR) and induce its activity. The MOPR is widely distributed throughout the brain but is highly enriched in regions of the brain involved in reward. A compound that activates a receptor is called an agonist while a compound that blocks receptor function is called an antagonist.

Heroin, oxycodone, and morphine are all MOPR agonists, which means they interact with the MOPR and induce its activity (a compound like naloxone is an antagonist and blocks MOPR activity). Opioid addiction occurs due to repeated activation of the MOPR and multiple changes that occur in many brain regions that results in a compulsive craving for the opioid as well as extremely unpleasant physical symptoms in the absence of the drug, known as withdrawal (I discussed how opioid drugs cause addiction in a previous blog post so I will not go into any more detail here). Methadone is also an MOPR agonist but it has very different properties than heroin and oxycodone.

Isn’t methadone a drug replacing a drug?

You may be wondering that if methadone is an MOPR agonist why is it a treatment for another MOPR agonist like heroin? Isn’t this just replacing one drug for another? The answer is an emphatic: NO!

Methadone is long-lasting MOPR agonist. What this means is that is binds to the MOPR, activates it fully, but then sits there on the receptor for a full day.

On the other hand, heroin and oxycodone bind the receptor, activate it, but then fall off the MOPR relatively quickly. This is why heroin addicts need to “shoot-up” several times a day; they need to be repeatedly stimulating the MOPR in order to fight the drug cravings and the withdrawal symptoms that occur in the absence of the drug (repeated use of heroin also results in tolerance, which requires more of the drug to achieve the same effect).

This difference in MOPR binding between heroin and methadone makes all the difference in the world and is the reason why methadone is able to act as an effective treatment. This long-acting function means that methadone is able to satisfy the addict’s craving for heroin (without causing the intense “high” of heroin) for a prolonged period of time. Importantly, methadone can be taken orally and a single dose is usually sufficient for the entire day.

How is methadone prescribed?

Methadone is legally allowed to be administered only in specific clinics and only by trained professionals; federal regulations prevent its administration in primary care clinics (more on this later). Random urine tests are conducted throughout treatment to make sure the patient is staying off of heroin and other illegal drugs. Some clinics also offer psychological counseling to help complement the methadone treatment.

When an addict first seeks treatment for heroin addiction using methadone, they are started on a relatively low dose, which is gradually increased to match the patient’s therapeutic needs. The amazing thing about methadone is that once a stable dose is attained, multiple effects simultaneously act to keep the patient off of heroin.

How methadone keeps you off heroin

First, the methadone blocks the intense psychological craving for heroin as well as prevents the physical withdrawal symptoms. Importantly, methadone delivered to heroin addicts does not elicit the type of intense, pleasurable high that heroin does. This means a heroin addict won’t seek out methadone to get “high” because it does not give them the same sensation; methadone is only useful to satisfy the craving for heroin.

Simultaneous with blocking the craving and withdrawal, methadone delivered at a stable dose occupies enough of the MOPR in the brain that it can actually out compete heroin for those same receptors while at the same time allowing normal function of the remaining receptors (e.g. pain relief). This means that methadone sits on the MOPR and prevents heroin from binding there too and this in turn prevents heroin from causing an intense, pleasurable effect even if that addict uses heroin during treatment. Yes, you heard that correctly: methadone actually blocks the “high” from heroin!

What is methadone maintenance therapy?

Once a stable dose is found for a patient that accomplishes all the effects that I described above (generally between 60-120mg), the patient can take a single dose of methadone a day indefinitely and still get all of its benefits. This daily, stable dose is known as methadone maintenance therapy (MMT) and is the goal of the treatment (random urine tests are conducted throughout MMT to make sure the patient is staying off of heroin).

Of significance is that once a stable dose is attained, it rarely needs to be increased, which means tolerance to MMT does not develop, unlike with other opioids. MMT basically prevents the behavioral aspects of addiction and allows the addict to live a normal life that is not consumed with seeking out and using heroin.

Does methadone really keep patients off of heroin?

Vincent Dole and Marie Nyswander working at the Rockefeller Medical Institute (now University) in New York City first introduced methadone as a new treatment for heroin addiction in 1964. Since then, many studies have been published considering whether or not methadone actually works to keep addicts in MMT and off of heroin. The answer is an unequivocal YES!

The Cochrane Collaboration did a comprehensive review that included 14 of the largest studies on methadone from the past 40 years and published their results in 2009. Cochrane, a highly regarded non-profit, non-governmental organization, evaluates the scientific evidence for various health interventions and treatments (ii). The Cochrane analysis looked at retention in MMT and off of heroin compared to other non-medication based therapies such as behavioral-only, detoxification, or abstinence-only therapies. The Cochrane report concluded that methadone is much more effective at retaining patients in therapy and off of heroin compared to non-medication based therapies.

However, methadone does not reverse the brain changes that have occurred as a result of heroin abuse. Methadone is a treatment, not a cure, for heroin addiction. This means that MMT may need to be continued daily indefinitely (more on this in a moment).

Importantly, methadone can not only keep addicts off of heroin but is effective at reducing use of cocaine as well in addicts that use both heroin and cocaine. A large analysis of 37 different studies that totaled 3029 patients found that methadone was indeed effective at treating dual cocaine and opioid addiction.

Unfortunately, the withdrawal effects from methadone last for a long period and can be very unpleasant for patients that choose to end therapy, which most likely results in using heroin again for those patients that stop MMT. This suggests that patients may need to remain on MMT indefinitely. However, there is no reason why a patient, once at a stable MMT dose, would need to go off. This may sound controversial but you wouldn’t tell a diabetic he or she needs to get off of insulin. Methadone is a life-long treatment because opioid addiction is a life-long disease.

What are the risks/side-effects of methadone use?

Methadone is a medication and like all medications from aspirin to chemotherapy, there are certain risks and side effects that accompany its use. Thankfully, methadone is extremely safe but does have a few side effects. Like any MOPR agonist (including heroin or morphine), some of methadone side effects may include:

  • chronic sweats
  • constipation
  • loss of sexual function

However, these effects are generally milder with methadone when compared to heroin.

As I explained above, a patient on methadone remains physically dependent to opioids but does not suffer the behavioral problems of addiction. This is important because withdrawal symptoms will occur if a patient ceases MMT. But again, MMT is a daily treatment just like any other medication for any other health problem that requires daily dosage, so this is generally not a problem. However, access to a methadone clinic can be extremely inconvenient, especially if patient does not live in a big city, which is significant problem that needs to be addressed.

Why is methadone not more available?

The scientific evidence supporting the usage of methadone is indisputable and has been for years. So why is it not being used more often when there are millions of opioid addicts that need treatment? This problem can be summed up in a single word: STIGMA.

Methadone clinics have been associated in the mind of the public with criminal activity and other deviant behavior. This is because addicts themselves have been viewed as suffering from a “moral failing” and they view the clinic as just another way for these moral deviants to get their “fix”.

This view is, of course, grossly incorrect. Methadone is a treatment and for a chronic medical condition. Addicts attending a methadone clinic are receiving a life-saving treatment that relieves the constant, compulsive craving for heroin, prevents addicts from resorting to multiple heroin injections a day and the extreme dangers associated with heroin injection, and allows these people a chance to live a normal life.

Stigma causes legal bans of methadone clinics

But because of the stigma around methadone, many cities pass ordinances to ban methadone clinics or restrict them to certain neighborhoods. Indeed, some people need to drive 20 miles (or even more) just to receive their daily dosage, which makes it incredibly inconvenient to attain treatment and is a reason for some patients to drop out of MMT. It’s truly a tragedy that false public attitudes can prevent or impede people from seeking and receiving treatment. This type of situation would never be tolerated for treatments to other diseases like diabetes or HIV.

Stigma alters the way patients see themselves

Beyond accessibility to methadone, stigma can also hurt the patient’s self-esteem or the perception of the treatment to themselves and their friends and family. Studies have shown that stigmatization of methadone actually reduces treatment outcomes and is a reason why some patients drop out of MMT. And the data are very clear, if a patient ceases MMT they are extremely likely to relapse to heroin use. Stigma hurts addicts seeking treatment in multiple ways and a change in attitudes is essential so that policy and regulations can change.

Stigma promotes “abstinence only” ideas

Also, because of the stigma around treating addiction with medications, many patients are forced into expensive rehabilitation or detoxification clinics that only promote abstinence-only therapy. I even found one clinic that actually discourages its patients from even seeking out methadone treatment! (iii).

The problem with abstinence or “detox” is that a patient may be opioid-free while in the rehab facility, but once released, the addict will inevitably start using again. This is because detox or abstinence does not actually address the underlying biology of opioid addiction and does not prevent the powerful psychological craving for the drug, which is practically irreversible.

As described above, the Cochrane study concluded that only methadone is effective at helping the patient to remain off of heroin. A change needs to be made in how addictions are treated: abstinence and behavioral therapies without medications don’t work but methadone does.

What can be done to increase availability of methadone?

Before political action can be taken to reduce overly strict regulations on methadone, public attitudes need to change. The public needs to realize heroin addiction is medical disease and that taking methadone is a treatment that needs to be taken everyday in order to fight the disease. A diabetic needs to take an insulin shot every day in order to live yet no one criticizes a diabetic for taking this treatment (an insulin shot is not a cure either). The same thing goes for a HIV patient who needs to take his or her anti-retroviral medication every day in order to fight the virus.

Patients suffering from opioid addiction take methadone for the same reason as the diabetic taking insulin or the HIV patient taking anti-retrovirals: it gives them a chance to live a normal life. Methadone is a treatment for a devastating disease, opioid and heroin addiction, and needs to be taken daily in order to keep the disease at bay.

Methadone is too strictly regulated

Despite its efficacy and safety, methadone is extremely tightly regulated. Ironically, it is much easier to get a prescription for oxycodone, which can lead to addiction, than methadone, which is the treatment for that very addiction! A recent review of state laws and regulatory policies on addiction concluded that prescribing law “has not kept pace with advancements in medical scientific knowledge about the interface between pain management and addictive diseases.”

Current regulations limit distribution of methadone to clinics so that dosing can properly be controlled and random urine tests can be done to test for heroin. However, a patient must be compliant for two years at a methadone clinic before the patient is allowed to receive their dose at home. Imagine if you needed to drive over 20 miles a day to the doctor’s office for two years just to receive the medication that you need before the doctor agreed to just write you a prescription!

While it is important that methadone administration must be initially supervised for dosage, risk of possible respiratory depression during first use, and to assure retention in treatment but two years is excessive. Furthermore, reduced regulations on how methadone is administered might help to combat resistance from communities that don’t want a clinic in the first place.

What about buprenorphine?

I should also mention that a second treatment for opioid addiction exists as well, buprenorphine, which acts similarly to methadone and is similarly effective. The main difference is that buprenorphine can be prescribed by your primary care physician. But does buprenorphine work better than methadone, is it safe and does it maintain retention in treatment? I’ll address these important questions in a future blog post.

The point is that two effective treatments already exist for opioid/heroin addiction. Attitudes towards methadone need to change and federal policy needs promote expansion of its use so millions of addicts can receive the treatment they need.

Your questions are welcomed

Still have questions about using methadone? Please contact us via the comments section below. We’ll do our best to respond to you personally and promptly.

Reference Sources:
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2. Bart G. Maintenance medication for opiate addiction: the foundation of recovery. Journal of addictive diseases. 2012;31(3):207-25.
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9. Dole VP, Nyswander M. A Medical Treatment for Diacetylmorphine (Heroin) Addiction. A Clinical Trial with Methadone Hydrochloride. Jama. 1965;193:646-50.
10. Mattick RP, et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane database of systematic reviews. 2009(3):CD002209.
11. Castells X, et al. Efficacy of opiate maintenance therapy and adjunctive interventions for opioid dependence with comorbid cocaine use disorders: A systematic review and meta-analysis of controlled clinical trials. The American journal of drug and alcohol abuse. 2009;35(5):339-49.
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i. CDC Vital Signs: Demographic and Substance Use Trends Among Heroin Users — United States, 2002–2013
iii. Novus Detox- Methadone Clinics
About the author
Derek Simon is Postdoctoral Fellow at the Rockefeller University researching the neuroscience of drug addiction using rodent behavioral models. Upon completing his PhD in 2012, Dr. Simon switched from endocrinology to addiction biology and he is currently researching 1) the role of learning and memory in opioid addiction and 2) the interaction between cannabinoids and opioids. He is passionate about increasing public understanding of addiction and is active in science communication and writing. Check out Derek's Addiction Blog and Twitter handle: @derekpsimonphd
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