Treatment Implications for Intravenous Buprenorphine Use

 

 

During the admission of new patients for opioid use disorder treatment, I ask about prior use of all drugs. I include the medications we use for treatment. I’ve done this since I started working at opioid treatment programs (OTPs) fifteen years ago.

Over the last few years, more patients say they’ve used illicit buprenorphine in the past. At first, I saw patients who were using it sublingually (under the tongue), as recommended, though still illicitly. Most of them wanted to see if this medication would work for them before they committed to the time and expense of entering a treatment program.

Over the past six months, I’m seeing more and more new patients who say they’re using buprenorphine intravenously. This past month, I’d estimate that a fourth of the patients who use buprenorphine illicitly are injecting it. Only a few said they snort buprenorphine.

This presents a big wrinkle to the treatment process.

I see why people use intravenous buprenorphine. It has low sublingual bioavailability, at around thirty percent. That means injecting two or three milligrams gives the same blood level as eight milligrams sublingually. In the short term, people injecting buprenorphine feel like it saves them money. In the long term, I’m certain it will cost more than they can imagine.

Buprenorphine tablets and films were not designed to be injected. Pills and films have fillers in them, and they aren’t sterile. Heating a mixture prior to injection will kill off some of the bacteria, so that’s a harm reduction practice. Using a filter can remove some of the particulate matter, also reducing the potential for harm. However, heat and filters can’t remove all the risk of injecting.

People on the internet insist the bioavailability of snorted buprenorphine is higher than sublingual use, but I doubt that. Either way, you bypass the liver because it crosses to the bloodstream via the veins of the nose or tongue. Plus, alkaline environments increase absorption and bioavailability for this drug, and the mouth is more alkaline than the nose.

Of course there is another reason people with opioid use disorder inject or snort their medication. Their brains associate the act of injecting or snorting with pleasure and euphoria, and can become addicted to the process and feeling of both means of ingestion.

Due to the ceiling on buprenorphine’s opioid effect, it is… arguably… one of the safest opioids a person could inject. But intravenous use is never safe.

Here’s only a partial list of complications from intravenous drug use:

1. Overdose resulting in death, brain damage from low oxygen, stroke or heart attack from prolonged low oxygen
2. Pulmonary edema (lungs fill with fluid)
3. Skin abscesses and cellulitis
4. Endocarditis (infection of heart valve that is life-threatening)
5. Deep vein thrombosis (blood clot)
6. Septic thrombophlebitis (infected blood clot)
7. Contracting infections: HIV, Hep C or B
8. Bacterial infections and abscesses in weird places like the spine, brain, joints, spleen, muscles, or eye
9. Necrotizing fasciitis – rapid, “flesh- eating” infection, also botulism
10. Pneumonia
11. Septic emboli – when infected clots break off and go to the lungs, brain from infected heart valves
12. Fungal blood/eye infections – (seen frequently when pills mixed with saliva are injected)

I have seen patients with every one of these complications. Most of them were in the distant past, when I was an Internal Medicine resident during the late 1980’s, but not all of them. Over the past six months, I’ve seen two patients with spinal abscesses from injecting drugs, though not necessarily buprenorphine.

The last time I posted about intravenous use of buprenorphine (November 2015), Dr. Wartenberg M.D. (pioneer in the addiction treatment field) wrote about the mitochondrial disease, which has caused liver failure, in European IV buprenorphine drug users. This disorder is specific to buprenorphine

So what are the treatment implications for a new patient who has injected buprenorphine?

First of all, these patients aren’t appropriate for office-based practices, even if the physician plans to prescribe the combination product with buprenorphine/naloxone. Clearly there are some patients who inject combination products and monoproducts. Granted, it’s less common, but it still occurs. There’s usually not enough oversight available at office-based practices to treat more complicated patients. I think they should be referred to opioid treatment programs, where they can be offered treatment with methadone.

What if the patient refuses methadone for some reason, or their risk with methadone is at too high from a medical view? Should patients with a history of injecting buprenorphine ever be treated with buprenorphine?

I think they can be – with great caution and daily dosing, on-site at the opioid treatment program.

At our OTP, we ask all buprenorphine patients to sit in a designated area while their dose dissolves. It usually takes around ten minutes, and they are watched by program personnel. Before they leave, each buprenorphine patient shows one of the staff their mouth, to show the medication is completely dissolved. It does feel a little “police-y” but we had a high incidence of diversion until we started this close observation.

If a patient tries to spit out their medication, they meet with me. I’m rarely willing to continue to prescribe buprenorphine if it appears they are trying to divert their medication. I meet with the patient and we discuss the option of methadone. If they refuse methadone, we try to refer them to another form of treatment.

If a patient with a history of injecting buprenorphine wants treatment with buprenorphine, I tell him I’m willing to give it a try, but that he can’t expect take home doses for a very long time, after months of observed dosing and stability. So far, this approach seems to be working. These patients are getting counseling, and haven’t attempted to divert their medication, so far as we can see. I’ve checked these patients for track marks, which in all cases appear to be healing, with no new marks.

When/if to grant these patients take homes remains a huge question. I don’t want to unduly burden a patient by insisting he must come every day forever, but I also don’t want to give the patient take home doses that could lead to a relapse back to intravenous use.

Opioid Addicts in Indiana Contract HIV

The New York Times ran an article 5/5/15 about a small town in rural Indiana that is facing a relative epidemic of new cases of HIV.

Austin, Indiana, a town of only 4200, has more than 140 people just diagnosed with HIV. The town is struggling to understand what to do about this epidemic, since the area has had a low HIV rate in the past.

The new cases of HIV were intravenous opioid addicts, and Opana was specifically mentioned by the opioid addicts in the article.

As in many small towns, needle exchange has been met with resistance from citizens who feel giving free needles to addicts only serves to encourage them to use more drugs.

Fortunately, the Indiana governor has authorized a needle exchange program for the area where addicts were sometimes using the same needle as many as three hundred times. Unfortunately, the needle exchange is not being run according to best practices. People must sign up for the service. Obviously, many opioid addicts who could benefit from free new needles are hesitant to register with anyone, due to the shame and stigma associated with addiction in this country.

To add to the difficulty, local police still arrest any addict found with needles, unless they are enrolled with the needle exchange. In other words, if one addict signs up for needle exchange and distributes these new needles to other drug users, those users could still get arrested if the police find their needles. Police say they are doing this to force addicts to register with the needle exchange.

We already know, from decades of studies, that actions like these by the police erode trust in the whole needle exchange program. Studies show needle exchange works best when people aren’t asked to register, and are allowed to procure free needles for other people who won’t come to a needle exchange. These type programs are very effective at halting the spread of HIV

The article only tangentially mentions treatment; it says some intravenous drug users have gone to a residential treatment center about 30 miles away, and others remain on a waiting list.

Sadly, no mention is made of medication-assisted treatment of opioid addiction with buprenorphine and methadone.

I did my own research: residents of Austin can drive to an opioid addiction treatment center less than a half hour away, in Charlestown, Indiana Also, there are at least two OTPs in Louisville,, only a few minutes farther, in Kentucky.

I hope someone is telling all the opioid addicts about this option. We know that after an opioid-addicted person enters medication-assisted treatment, the risk of contracting HIV drops at least three-fold. Thankfully HIV can now be treated, and is more like a chronic disease than the death sentence it was twenty-five years ago, but wouldn’t it be better to prevent HIV in the first place?

I fear Austin, Indiana is a harbinger of things to come in other small towns in our nation. Let’s stop with the politics, and get patients into medication-assisted treatment. Let’s do unrestricted needle exchange, and let’s hand out naloxone kits!

Is Heroin the New Opana?

From CDC data released 3/15

The Center for Disease Control and Prevention (CDC) released new data last month showing a rapid rise in heroin overdose deaths. While total overdose deaths from opioids remained level for the past few years, deaths involving heroin escalated sharply.

The rate has tripled since 2010, and nearly quadrupled since 2000. Males have a four times higher rate than females with the highest rate seen in white males aged 18 to 44. All areas of the country had increased heroin overdose death rates, but the highest were seen in the Midwest, with the Northeast right behind them. The South, for a change, had the lowest rate of heroin deaths, after the West.

Those of us treating patients at OTPs knew heroin was moving into areas where pain pills once dominated, but I had no idea deaths had tripled in three years. That is appalling even to me, and I see appalling things all of the time. I can’t stress enough how bad this is.

Why is this happening? I’ve read and heard various opinions:

 Some people speculate that since marijuana became legal, that crop is less profitable to Mexican farmers, who switched to growing opium poppies. This is just a theory, though the timing supports the premise. I don’t know how it can be proved, short of taking surveys of Mexican farmers, which seems problematic and unlikely to happen.

 As we implemented measures to reduce the availability of prescription opioids, the price increased. Heroin is now cheaper than pain pills in many areas, and heroin’s purity has increased. Many addicts who can’t afford pain pills switch to heroin to prevent withdrawal. NIDA (National Institute for Drug Addiction) estimates one in fifteen people who use prescription opioids for non-medical reasons will try heroin at some point in their addiction.

Maybe that’s why the South still has the lowest heroin overdose death rates: we still have plenty of prescription opioid pain pills on the black market.

 With the increased purity, heroin can be snorted instead of injected. Many people start using heroin by snorting, feeling that’s safer than injection. It probably is safer, but addiction being what it is, many of these people end up injecting heroin at some point.

 Heroin has become more socially acceptable. In the past, heroin was considered a hard-core drug that was used by inner city minorities. Now that rural and suburban young adults are using heroin, it may have lost some of its reputation as a hazardous drug.

Most experts in the field agree that much of the increase in heroin use is an unintended consequence of decreasing the amount of illicit prescription opioids on the street. But we are doing the right thing by making prescription opioids less available. Physicians are less likely to overprescribe and that’s essential to the health of our nation.

Now it’s critical that we provide all opioid addicts with quick access to effective treatment, no matter where they live.

The face of heroin addiction has changed. It is no longer only inner-city minorities who are using and dying from heroin; now Midwestern young men from the suburbs and rural areas are the most likely to be using and dying from heroin.

In the past, when drug addiction was seen as a problem of the poor and down-trodden (in other words, inner-city minorities), the general public didn’t get too excited. But when addiction affected people in the middle classes, there was a public outcry. The Harrison Act of 1914 was passed due to public demand for stronger drug laws.

I think the same thing will happen now. Suburban parents will organize and demand solutions from elected officials for this wave of heroin addiction. Indeed, I think that’s already started to happen.

Let’s make sure a big part of the solution is effective treatment.

Let’s make treatment as easy to get as heroin.

Case Study of an Opioid-addicted Patient: New England Journal of Medicine

A doctor friend of mine sent me an article from the New England Journal of Medicine from November 13. 2014. I subscribe to the NEJM, but somehow overlooked this article, so I’m happy he brought it to my attention. My friend reads my blog and knows I have lamented how I was taught in my Internal Medicine residency to treat endocarditis (potentially life-threatening infection of a heart valve), but not the underlying cause, which was addiction (read in my blog post of December 7, 2014).

The journal article he sent me is a case study of a young woman with endocarditis from intravenous drug use. The case study begins in the usual way, describing her history and physical findings. Nothing was uncommon here: the patient told them she was a drug user, and she had track marks, fever, and a heart murmur. The history and physical findings screamed, “Endocarditis! “ A chest x-ray and then chest CT scan showed multiple septic emboli, commonly seen with endocarditis, sealing the diagnosis.

But this case wasn’t only about the diagnosis and standard treatment with antibiotics. To my delight, the first sentence describing the case management was “Methadone was administered orally.”

Huzzah!

But as it turned out, the patient was only put on a methadone taper while hospitalized. She was started on a protracted course of antibiotics and sent to an extended-care facility, where she quickly relapsed. This relapse illustrated the second point of the article: medication-assisted therapy must be continued to be effective.

As the case discussion points out, “As with other medications for chronic diseases, the benefits, at least in the short term, last only while the patient is taking the medication.” In other words, her relapse was predictable, and not due to failure on the part of the patient. The relapse happened because of failure to continue the medication by the doctor.

A little later in the case study I read these wonderful sentences: “Although making a diagnosis of endocarditis is a crucial first step (emphasis mine), understanding the root cause of the endocarditis is a key feature in the diagnosis and management of this patient’s illness. Endocarditis is only a symptom of her primary illness, which is an opioid-use disorder.”

I loved this case presentation for two reasons: it emphasized treating the entire patient, including the underlying disease of addiction, and it pointed out that short-term medication with methadone or buprenorphine doesn’t work, just like temporary treatments for other chronic diseases don’t cure anything.

This patient developed endocarditis again after her relapse, and needed a second hospitalization. This time, she left the hospital on buprenorphine maintenance. She relapsed again after two months, had a third episode of endocarditis, this time due to a fungus, and required a third hospitalization.

After that treatment was over, she was maintained on buprenorphine. At the end of the article, the authors reported that the patient had over a year of abstinence from drug addiction, was taking buprenorphine, and going to AA and NA regularly.

In the discussion of appropriate treatment of both the endocarditis and the opioid addiction, I read this delightful sentence::The opioid agonists methadone and buprenorphine are among the most effective treatments for opioid-use disorder.”

Can I get an “Amen!”?

The same paragraph goes on to describe the benefits seen with MAT, which include decreased opioid use and drug-related hospitalizations, and improved health, quality of life, and social functioning. This article also clearly states MAT will reduce the risk of opioid overdose and death. Many references are cited at the end of the article for non-believers in MAT.

This article also included recommendations about educating patients about overdose risk, and providing them with naloxone.

At the end of the article, the patient who was the subject of this case study discussed her perspectives regarding her treatment. She related how each time in the past, she was treated for whatever medical problem she had, and then sent on her way, with little effort to treat her addiction. She says she’s grateful for the second episode of endocarditis, because she met the doctor who treated the addiction and gave her hope that she had a treatable disease. Prior to that, she doubted she could stop her active addiction, because she saw herself as a bad person, not as a sick person.

This article ends with this patient’s words: “To be honest, I never thought I would be standing here, clean for over a year. I thought that I was going to die.” That effectually describes the hopelessness of patients in active addiction.

I hope such endorsement of medication-assisted treatment of opioid addiction by the prestigious New England Journal of Medicine will help convince more doctors of the legitimacy of MAT.

During my training in the 1980’s, I didn’t learn how to treat the underlying cause of the endocarditis. I am delighted and encouraged to find the New England Journal of Medicine has published an article that does just that. This article clearly and overtly states the importance of treating the real problem, not just symptoms of the problem. Today’s doctors have a valuable opportunity to change the lives of many of their future patients.

Project Lazarus in the Huffington Post

In a nice article in the Huffington Post, Project Lazarus, located in Wilkes County, NC, was highlighted as an example of how a community can take action to prevent drug overdose deaths. Please check it out at: http://www.huffingtonpost.com/2014/03/05/project-lazarus_n_4889620.html?1394071210

Many people think Project Lazarus provides naloxone kits to reverse overdoses, and this is true, but they do much more than that. Project Lazarus has sponsored educational programs for doctors to learn to be more cautious when prescribing opioids, has sponsored medication take back days where old prescription meds can safely be disposed, and has worked with agencies and organizations across North Carolina and the nation to better inform doctors, law enforcement, and elected officials about what works to prevent drug overdose deaths.

Project Lazarus helped pass a Good Samaritan law North Carolina (see my post of April 20, 2013). Under this new law, a person who calls 911 to save another person’s life – or their own – won’t be prosecuted for minor drug possession, since they were trying to do the right thing and save a life by calling 911.

The Huffington Post article describes how the opioid overdose death rate has been falling in Wilkes County, while the overdose death rate in other parts of the country has been steadily rising. They credit Project Lazarus for this reduction in overdose deaths.

While I’m sure Project Lazarus has played a huge role in reducing overdose deaths not only in Wilkes County and the state of North Carolina, other factors have helped. Being an opioid addiction treatment provider, of course I believe availability of addiction treatment reduced deaths too.

Project Lazarus also supported the opening of an opioid treatment program in 2011, Mountain Health Solutions. Started by Dr. Elizabeth Stanton, this program initially offered only buprenorphine. As it grew, it became obvious some patients needed methadone treatment, so option became available by late 2011. Mountain Health Solutions was eventually purchased by CRC Health in 2012, and has continued to grow. Located in a small town, we have nearly four hundred patients.

I am honored to be the medical director at this program. It’s one on the best programs I’ve seen, and we work hard to keep improving our quality of care. Our program has done outreach -particularly in the medical community- to try to reduce the stigma of medication-assisted treatment. If you read my blog, you know this can be both a joy and a challenge.

Initially, Project Lazarus paid for an intranasal naloxone kit for every patient entering our opioid treatment program. Now since our patient census has risen, Project Lazarus still pays half of the $50 cost of the kits. The opioid treatment program pays the other half, out of a $33 admission charge for new patients. I feel lucky to be able to partner with Project Lazarus, as I’ve seen these kits save lives.

I know of four occasions when a naloxone kit saved a person’s life. Three of these four times, that person saved wasn’t even in treatment for opioid addiction.

Most recently, a parent used a kit to reverse an opioid overdose in a child who accidently ingested the parent’s medication. The parent called 911 and while waiting for EMS to arrive, used one of the two vials in the kit. The child partially woke, and started breathing better. Then EMS arrived and took the child to the hospital. This child survived a potentially fatal overdose and is back to normal with no lasting damage, thanks in part to that naloxone kit and a parent who knew how to use it.

Naloxone kits can be obtained much more cheaply, but contain Narcan vials, a more dilute form of naloxone that is meant to be injected. Those kits, which cost a few dollars, contain a syringe and needle instead of the Project Lazarus kit for nasal administration. Trying to inject naloxone into a vein is technically much more difficult than spraying the more concentrated form of naloxone up into the nose.

And unfortunately, a kit containing a needle and syringe would meet resistance from the public. I can imagine all sorts of angry phone calls to our opioid treatment program: “My son came to you people to get off the needle and you GAVE him a needle and syringe??” Politically, the public would more likely oppose distribution of a naloxone kit with a needle than a kit for intranasal use.

Fifty dollars for an intranasal naloxone kit to save a life is a pittance in the overall picture. Some insurance companies will cover these kits, as will Medicaid, but most of our patients have no insurance. They pay for their buprenorphine/methadone treatment out of their own pocket. Fifty dollars is a big sum for these patients.

I am blessed to work for an opioid treatment program that gets financial help from Project Lazarus for these kits. And I am very blessed to work for a for-profit company, CRC Health, which is willing to bear half the cost of the kits, since this comes out of their profits. Most opioid treatment programs do charge patients an admission fee, but unlike Mountain Health Solutions, don’t put that money towards buying a naloxone kits for their patients.

This is an example of the success that can happen when agencies work together toward a common goal.

Warning Warning Warning

If you are still using heroin, or know someone using heroin, please heed this caution. SAMHSA (Substance Abuse and Mental Health Services Administration) sent out a notification last week, warning people that a deadly form of heroin is causing deaths in the Northeast.

Since the first of the year, thirty-none overdose deaths occurred in Pittsburgh and Rhode Island from heroin contaminate with fentanyl. Fentanyl is a powerful opioid, and kills opioid addicts accustomed to using heroin alone. Trends like these can spread rapidly, so if you are reading this and know someone who uses IV heroin, warn them about this deadly heroin.

When I first read SAMHSA’s notification, I wondered if I should put the warning on my blog. Being realistic, I know some addicts will think, “How can I get some of that? It sounds like good stuff!” That’s the insanity of addiction…people are dying from a variety of heroin and other addicts want to try the deadly substance, believing they can use without harm.

In the interest of harm reduction, I’m going to describe precautions that addicts, still in active addiction, can take to reduce the risk of overdose death. This information can be accessed at: http://harmreduction.org/wp-content/uploads/2011/12/getting-off-right.pdf

1. Don’t use alone. Use a buddy system, to have someone who can call 911 in case you stop breathing. Do the same for another addict. Obviously you shouldn’t inject at the same time. Stagger your injection times.
Many states now have Good Samaritan laws that protect the overdose victim and the person calling 911 for help, so that police don’t give criminal charges to people who do the right thing by calling for help for an overdose.
Take a class on how to give CPR so that you can revive a friend or acquaintance with an overdose while you wait on EMS to arrive.
2. Get a naloxone kit. I’ve blogged about how one patient saved his sister with a naloxone kit. These are easy to use and very effective. You can read more about these kits at the Project Lazarus website: http://projectlazarus.org/
3. Use new equipment. Many pharmacies sell needles and syringes without asking questions. Your addict friends probably can tell you which pharmacies are the most understanding.
Don’t use a needle and syringe more than once. Repeated use dulls the needle’s point and causes more damage to the vein and surrounding tissue. Don’t try to re-sharpen on a matchbook – frequently this can cause burrs on the needle point which can cause even more tissue damage.
4. Don’t share any equipment. Many people who wouldn’t think of sharing a needle still share cottons, cookers, or spoons, but hepatitis C and HIV can be transmitted by sharing any of this other equipment. If you have to share or re-use equipment, wash needle and syringe with cold water several times, then do the same again with bleach. Finally, wash out the bleach with cold water. This reduces the risk of transmitting HIV and Hepatitis C, but isn’t foolproof.
5. Use a tester shot. Since heroin varies widely in its potency, use small amount of the drug to assess its potency. You can always use more, but once it’s been injected you can’t use less. The New England overdose deaths described by SAMHSA may have been avoided if the addicts had used smaller tester shots instead of shooting up the usual amount.
6. Use clean cotton to filter the drug. Use cotton from a Q-tip or cotton ball; cigarette filters are not as safe because they contain glass particles.
7. Wash your hands thoroughly before preparing your shot, and clean the injection site with an alcohol wipe if possible. Don’t use lemon juice to help dissolve heroin, as it carries a contaminant that can cause a serous fungal infection.
8. Opioid overdoses are much more likely to occur in an addict who hasn’t used or has used less than usual for a few days, weeks, or longer. Overdose risks are much higher in people just getting out of jail and just getting out of a detox. Patients who have recently stopped using Suboxone or Subutex may be more likely to overdose if they resume their usual amount of IV opioids.
9. Don’t mix drugs. Many opioid overdoses occur with combinations of opioids and alcohol or benzodiazepines, though overdose can certainly occur with opioids alone.
10. Don’t inject an overdosed person with salt water, ice water, or a stimulant such as cocaine or crystal methamphetamine – these don’t work and may cause harm. Don’t put the person in an ice bath and don’t leave them alone. Call for help, and give mouth-to-mouth resuscitation if you can.

To people who believe I’m giving addicts permission to use, I’d like to remind them that addicts don’t care if someone gives them permission or not. If an addict wants to use, what other people think matters little. But giving people information about how to inject more safely may help keep the addict alive until she wants to get help.

The Harm Reduction Coalition has excellent information on its website: http://harmreduction.org

On the Horizon: Heroin Vaccine

In a May issue of the Proceedings of the National Academy of Sciences, scientists at the Scripps Research Institute in California reported their success using a heroin vaccine in rats. The lead author of the study, Joel Schlosburg, works with Dr. George Koob, renowned and accomplished scientist who heads the team at Scripps.

This vaccine is still only in the animal phase of study. Scientists have developed a vaccine that stimulates the rat body immune system to recognize heroin and its metabolic byproducts. The immune system sees these substances as pathogens which must be got rid of, and manufactures antibodies against the compounds. After the antibodies bind to the heroin and its active metabolites, it gets further metabolized into harmless compounds that are eliminated from the body without ever crossing the blood brain barrier. In other words, the vaccine binding prevents this powerfully reinforcing opioid from ever getting into the pleasure centers of the brain to cause euphoria, or a “high.”

The first studies in rats are promising. This vaccine is postulated as a way to prevent heroin overdoses, since vaccinated addicts will no longer get euphoria from the drug. However, similar studies have been done with cocaine, and some human subjects could over-ride that vaccine by taking more cocaine, and were still able to get high. Dr. Koob says that with this new heroin vaccine, it would take a very large amount of heroin to over-ride the vaccine, or to cause an overdose. The rats in this heroin vaccine study didn’t try to load themselves with more heroin, a positive sign.

The vaccine wouldn’t affect opioid medications like methadone or buprenorphine, and so the heroin vaccine could theoretically be used along with these standard opioid addiction treatments.

Researchers took pains to make clear this vaccine is not a magic bullet. Once a vaccinated addict is subjected to cues associated with past heroin use, like being back in an old neighborhood, craving will still occur and the vaccinated addict may still use heroin in response to that craving, despite a lack of euphoria once it is used.

Also, it won’t be effective on most opioids contained in prescription pain pills. This means other opioids can still be useful if a vaccine-treated patient needs pain control… but it also means a vaccine-treated patient could still get high from non-heroin opioids. My fear is that a heroin addict would just switch to misusing prescription opioids.

Even with the vaccine, addicts still must have the psychosocial aspects of treatment in order to overcome addiction. It should be used as a part of a comprehensive treatment program.

Human trials may begin as early as the end of this year.

Schlosburg et.al., “Dynamic vaccine blocks relapse to compulsive intake of heroin,” Proceedings of the National Academy of Sciences of the United States of America, 2013 110 (22) 8751-8752.