New Medication Formulations Could Quickly Make a Difference for Treating Opioid Addiction

Photo of researcher working with a pipette under a hood

As Francis Collins and I wrote in May, NIH and NIDA are committed to an “all scientific hands on deck” effort to end the opioid crisis in America by halving the time it takes to develop new medications to treat pain and addiction and reverse overdoses. This effort will involve partnerships with pharmaceutical companies and academic institutions, leveraging the diverse benefits that federally funded science, private industry, and academia can bring to bear. Such partnerships have always been important in advancing treatment of addiction, as exemplified by NIDA’s partnership with Lightlake Therapeutics, Inc. (a partner of Adapt Pharma Limited) that led to the approval of nasal Narcan (an intranasal formulation of naloxone) in 2015.

The goals of the new initiative range from innovative and ambitious new treatment approaches that will take some time to develop, such as vaccines or transcranial magnetic stimulation for pain and addiction, to goals that are relatively achievable in the short term, such as improved formulations of existing medications. Effective medications are already available to treat opioid addiction—buprenorphine, methadone, and naltrexone—but only a fraction of people with opioid use disorders are being treated with them, due to limited access and treatment capacity, stigma around their use, lack of provider training, and cost. Also, for those treated, compliance tends to be low and few are retained in treatment for sufficient periods of time. New formulations of these medications that can facilitate access to treatment and improve compliance could be a real game-changer that could quickly make a dent in this crisis.

Buprenorphine and methadone are both highly effective at controlling cravings and withdrawal symptoms when they are administered at sufficient doses for a sufficient length of time. The reality is that these drugs are still not widely available, and are often used at too low a dose and duration when they are available. People who live in rural communities are at particular disadvantage due to logistical challenges associated with accessing treatment. During the first few weeks on the opioid partial agonist buprenorphine, the induction period, the patient must visit the doctor’s office daily or near daily while the dosage is adjusted. Even after the patient’s dosage is adjusted, he or she needs to visit the doctor regularly.

Patients face similar challenges with the opioid agonist methadone, which is only available from opioid treatment programs (OTPs) and is often not covered by insurance. In addition, some states place restrictions on the doses that can be administered or the duration of treatment. Initially, patients are required to visit their OTP daily or, as their treatment progresses, every couple of days. These restrictions are intended to prevent both diversion and overdose. (Methadone overdose is a significant risk for patients who are prescribed it for pain, whose usage is not as closely monitored.) But those who don’t live near an OTP are for this reason not able to take advantage of this medication to treat their addiction.

If extended-release formulations of these drugs were available that allowed patients to get a single injection (depot formulations)—once every few months, or even once a year—it would go a long way toward providing patients a stable, consistent dose and promoting long-term retention in treatment. Developing such formulations is one of the goals for the partnerships NIH is pursuing with industry. A little over a year ago, the FDA approved a six-month buprenorphine implant called Probuphine that Titan Pharmaceuticals had developed with support from NIDA, and this was an important first step. Its dosage is equivalent to 8mg daily, which is relatively low—most people require buprenorphine doses in the 16-24mg range—so the development of higher-dosage formulations, as well as depot injections, would be of great benefit. Multiple pharmaceutical companies are already working to develop new depot formulations of buprenorphine. Implantable formulations of methadone have been evaluated in animal models and also have the potential to be a valuable tool for the treatment of opioid addiction.

Vivitrol, an injectable version of naltrexone that blocks the effects of opioids in the body for four weeks, was approved by FDA in 2006 for treating opioid addiction. Vivitrol makes treatment compliance easier for patients who no longer need to remember to, and choose to, take a pill every day.  The challenge with opioid antagonists like naltrexone is that patients have to be detoxified prior to treatment initiation to avoid withdrawal.  Not all patients tolerate the transition to treatment with an opioid antagonist like Vivitrol, and research is ongoing to evaluate new strategies that can facilitate induction on such medications. Also, patients on naltrexone rapidly lose their opioid tolerance, putting them at risk of overdose if they discontinue treatment—which happens all too often due to lapses in access, insurance coverage, or compliance.   

Longer-acting formulations of naltrexone or other opioid antagonists could provide greater protection against relapse and overdose, the risk of which is particularly high during the first few months of treatment.  Such formulations will make it easier for patients who have difficulty with medication compliance, and thus will help prevent relapse. The benefits of depot formulations for opioid agonists and partial agonists would be just as great, and would also eliminate diversion and misuse, which are concerns with the use of immediate-release opioid medications.   

Bringing an end to the opioid crisis, which continues to claim more than 91 American lives every day, is a top priority for NIDA and NIH. Some solutions are still on the drawing boards and will take many years to come to fruition. But other solutions like improved formulations of existing medications could be developed in a much shorter time frame to help the millions of Americans currently suffering with opioid addiction achieve and maintain a stable recovery. The partnerships that NIH is currently forging between government-funded institutions and private industry aim to accelerate the translation of scientific solutions to help end the opioid crisis.

Dr. Nora Volkow, Director

Here I highlight important work being done at NIDA and other news related to the science of drug use and addiction.

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 Suboxone Abuse

You made no mention of the abuse potential of Suboxone and the fact that the current office-based model lacks the many safeguards built into methadone clinics. Is the widespread distribution of Suboxone by individual providers any different from the office-base pain management model that got us into this mess in the first place?

 While there is some abuse

While there is some abuse potential with Suboxone (buprenorphine-naloxone), it is less than other opioids, and research suggests those risks are outweighed by its great benefits in treating opioid use disorders. Data also suggest that most misuse is for controlling withdrawal and cravings, rather than obtaining euphoria. Research on the question of treatment need versus diversion risk for buprenorphine and methadone is summarized in our report Medications to Treat Opioid Addiction. The depot formulations discussed in the above post (i.e., getting a shot every few months or longer) would further lessen the possibility of misuse and diversion.

 TOO Easy

Opioid deaths drop by 25%+ in areas where cannabis is legal. (Source Johns Hopkins University)
So what's stopping the NIDA from mitigating this "EPIDEMIC" by 1/4?

 The new addiction drugs

This writer is just someone who tries to sound scientific but is really nothing more than a pharmaceutical sales rep. These Bentley compounds being pushed on people have a very serious and problematic profile. I hope people who take these drugs are given accurate, honest information. Is it correct information to say Perdue is highly involved with manufacturing and distributing these drugs? I saw where this was going 15 years ago.

 response to Dr.Boris re The new addiction drugs

No. Purdue is not involved in the manufacture of addiction treatment medications. They make Butrans, a buprenorphine patch which is used for pain control, but not for treatment of opioid use disorder. I agree it is critical that the public receive "honest, accurate" information. Suboxone is a life-saving medication and the best currently available treatment for those addicted to heroin and/or prescription pain medications. NIDA is working hard to educate those who need help and reduce overdose death rates. Please get your facts straight.

 Use of Buprenorphine

It should be approved as a use of a painkiller for those with chronic pain as was it's original purpose. Believe me when I say, it is by the lessor of the two evils.

 Over-Regulations create barriers to effective treatment

As a DEA certified provider with a rural health clinic in South Carolina, it has been difficult to get a "supervising" physician that is also DEA certified to provide suboxone without paying $1000-month... As a health care provider I have had to watch patients forgo treatment because they can't get to another facility and sadly are lost to this disease of despair. South Carolina continues to have draconian laws that prevent access to health care providers. Legislation is slow to change even with conclusive evidence and the vicious cycle continues. We need to bend the cost of healthcare with more providers not less. Competition is good in any industry, why is SC so slow to change its outdated laws?


Perhaps you can move forward on the research of IBOGAINE.
It could go a long way toward ending the "opioid epidemic".

The NIDA says they have "abandoned research because the plant was found to be neurotoxic and thus unsafe".
However, in lower doses of 25mg or less there were "no observable adverse affects" according to the NIH.
Just how "safe" is heroin proving to be?

HOW do you "abandon" research of a possible CURE to opioid addiction and call for "all hands on deck" at the same time?

This absurd stance is like telling a cancer patient that they can NOT use TAXOL to cure their cancer because it is neurotoxic. How much sense would that make?

Further, ibogaine is used just once or twice to rid the patient of their cravings and withdrawals!
So do we continue BURYING our fellow Americans who have overdosed, but have not been given a chance of sobriety using this plant which has shown so much promise? What good are the neurons in a dead body?

If, as the NIH claims, there are no observable adverse effects in low doses, let us take action and END THIS CRISIS!
You want to make a difference? HERE IS YOUR CHANCE.



An ongoing, aggressive movement is pushing for marijuana acceptance and legalization across America that seeks all avenues and forms of propaganda to promote its agenda- including the notion that marijuana legalization will mitigate the opioid crisis.

However, these studies cited show links with only medical marijuana legalization. Not general acceptance!

Now there may be some merits to using cannabis for pain relief which might indeed replace the adverse aspects of the opioids. Maybe. More research is needed, and if so, then by all means consider cannabis as a possible substitute to opioid prescription. But clinically only.

Though many point out that overdose deaths from marijuana are virtually non-existent, there appears to be an eerie link with past cannabis abuse, mental derangement and rampage killings (including 9/11,the Boston Marathon bombing), or other violent crime. It might be that we come to accept marijuana only to find out later that this drug leads to psychosis with in turn may lead to homicidal tendencies.

Please note that over the last few years virtually ALL the lone wolf terrorists domestically and abroad have drug abuse history! And few have any serious connections to Islam. It could be we are assuming these senseless rampage killings are merely 'Radical Islam", when in reality the madness may stem from mental derangement derived from months or years of past marijuana abuse!

If that's the case, then we Americans are naively embarking on the path to self-destruction. Be ware of the pro-cannabis lobby and their lies, please!

 All laws are slow to change

Change is always slow. I am a Personal Injury Attorney in South Carolina and I see what Jackie is saying but I am not sure that South Carolina is any slower than anywhere else.


As a recovering addict that began the journey 40 years ago, I see the folly in focusing only on the 12 step program as the cureall. The actual success rate is very low. Ibogaine works, again, for some, actually a whole lot more than program. What freed me was ayhuasca, or DMT. To me it feels as though it "reset" my brain. I do not believe it is as dangerous as Ibogaine. The psychedelics need to be looked at more seriously. 12 step programs are a good start, but the 90 or so percent that do not respond longterm need different. We need more inclusiveness, it cant be black or white anymore. Absinance or replacement (methadone/bupe) still leaves a person "hooked", although in much better terms. That paradigm leaves too many leftover to die. All hands should be all hands, excluding no one. We need to think outside the box until all are included.

 Opiood Crisis Not Caused by the Medical Profession

If we want to solve the opioid crisis, we need to understand its origins. Then we can properly assign blame and strive for solutions.

The current opioid addiction which has taken decades to develop and was not caused by the medical profession, nor by "Big Pharma", as is now commonly portrayed. This crisis developed primarily as a consequence of a couple of generations of middle class Americans who said "Yes" to illegal recreational drugs which mostly started about fifty years ago. People who thought they were "cool", who wanted to be connected to the "in crowd" and who felt they simply 'knew better' are the root cause.

Simply listen to the popular music which in essence has been advertising illicit drug use for decades. Even within the typical 'musak' played at malls and so forth, says over and over again "She's gonna like cocaine". Other songs extol the wonders of "merry jane". All built into our culture now.

We are like a group of blindfolded men touching an elephant unknowing what it is. The giant is our vast illegal recreational drug culture which has spawned a holocaust in Latin America, at the core in one for almost all violent crime, for prostitution, human trafficking, myriads of car accidents, lower productivity, etc. All of which are driven by addiction.

Addiction and insatiable desire for drugs 'caused' the few unscrupulous 'pill farms', not the other way around. Recognize this disaster for what is, and then we can begin to solve it.

 Suboxone Abuse LoL

As a long time Opiate/Opioid addict, I can tell you equivocally that I have never known another Opiate/Opioid addict to take Suboxone to "get high" (and get straight or get right seem to be the more preferred terms). Mostly I'd say because it does not do anything in that regard. Only those truly suffering in withdrawal or someone who had an epiphany or an experience that has convinced them to kick would take it. Or the people who think taking it for a while allows them to forgo withdrawal and re-set the amount of pills or Heroin they need for maintenance.
While my experience is anecdotal, it is more than 20 years worth.
Thank you for the interesting blog and your work on saving lives.