Opioids and Naloxone: A Winning Combo for Chronic Pain

Opioids and Naloxone: A Winning Combo for Chronic Pain

OPINION:  By Roger Crystal, M.D.

The national opioid epidemic poses multifaceted challenges for prescribers. One of the central questions involves the sizable population of patients who experience chronic pain: to what extent should they be co-prescribed the medication naloxone alongside opioid-based medications used to manage their pain? Evidence suggests there are advantages to the co-prescription of naloxone as standard practice for pain patients.

Addressing the needs of chronic pain patients

In the U.S., approximately 100 million adults are affected by non-cancer chronic pain, according to the American Academy of Pain Medicine. Of these, approximately 20 to 30 million receive opioid pain prescriptions, including nearly nine million on a long-term (>30-day) basis. With intense current focus on the potential dangers of opioid overdose, safeguarding these patients against accidental overdose is a must. One viable safeguard is naloxone, which has demonstrated its effectiveness as a life-saving opioid overdose antidote.

Increasingly, the medical community is seeing sense in this approach. According to the American Medical Association, in the first eight weeks of 2017, the number of naloxone prescriptions written by physicians has increased 340 percent compared to the same eight-week period in 2016. The number of physicians prescribing naloxone has also increased 475 percent over the same time period.

Although there is as yet no national policy governing the co-prescription of naloxone, certain states have made it a priority. For example, in June 2016, Gov. Peter Shumlin of Vermont signed several new laws including one requiring prescribers to provide all patients with information and education regarding the safe use, storage and disposal of prescription opioids; it also requires the co-prescribing of naloxone.

Meanwhile, a recent study—funded by the National Institute on Drug Abuse (NIDA) and published in Annals of Internal Medicine—found that patients taking opioids for chronic pain, who were given naloxone in a primary care setting, had 63 percent fewer opioid-related emergency department visits after one year compared to those who did not receive prescriptions for naloxone. This study presented the first large published data regarding co-prescribing naloxone for primary care patients on long-term opioid therapy for pain.

A follow-up study by the same researchers, also funded by NIDA and published in Annals of Family Medicine, evaluated chronic pain patients’ attitudes toward being offered a naloxone prescription. Results showed that 82 percent successfully filled the naloxone prescription and 97 percent believed that patients prescribed opioids for pain should be offered naloxone. Most patients (57 percent) had a positive response to being offered naloxone, and 37 percent reported safer opioid use behaviors after receiving the prescription; there were no harmful behavior changes reported.

The naloxone advantage

This positive reception to naloxone from a segment of the chronic pain patient population dovetails with what is known about the unique advantages of naloxone as a therapy for accidental opioid overdose. Opioid antagonists exist in various delivery forms with demonstrated efficacy, including as nasal sprays.

Prior to the development of the nasal spray approved in November 2015, naloxone was only available in approved forms as injectables—whether a syringe-based injection or autoinjector. In general, people don’t like injecting other people and are afraid of needle-stick injuries even amongst trained and qualified professionals, so there was a motivation to develop a nasal spray version.

These advantages are capable of overcoming any residual stigma due to the prominent media portrayal of naloxone as a mere “rescue therapy” for those who have suffered an illegal opioid overdose. As has been previously reported in National Pain Report, the fact is that patients with chronic pain are overwhelmingly responsible users of medications. Statistics suggest that fewer than three percent of all chronic pain patients those who utilize opioids graduate to abuse of their medications.

The co-prescription of naloxone alongside with opioid pain medications—especially given its availability in convenient intranasal delivery form—appears to be a prudent measure for the well-being of chronic pain patients. The expansion of this policy among prescribers is to be encouraged nationwide.

Roger Crystal, M.D. is Chief Executive Officer of Opiant Pharmaceuticals, Inc., a specialty pharmaceutical company developing pharmacological treatments for substance use, addictive and eating disorders. Opiant developed NARCAN® (naloxone HCI) Nasal Spray, marketed by its partner and licensee, Adapt Pharma.

Authored by: Roger Crystal, M.D.

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Hi Reed, Thank you so much! Excellent explanation!! Wishing you a low pain weekend!


No problem. Sorry for the delay, it’s busy season at work now. The whole agonist, antagonist, as I understand is this: from the NAABT
“Antagonist is a drug that activates certain receptors in the brain. Full agonist opioids activate the opioid receptors in the brain fully resulting in the full opioid effect. Examples of full agonists are heroin, oxycodone, methadone, hydrocodone, morphine, opium and others.
An antagonist is a drug that blocks opioids by attaching to the opioid receptors without activating them. Antagonists cause no opioid effect and block full agonist opioids. Examples are naltrexone and naloxone. Naloxone is sometimes used to reverse a heroin overdose.
Buprenorphine is a partial agonist meaning, it activates the opioid receptors in the brain, but to a much lesser degree than a full agonist.
Buprenorphine also acts as an antagonist, meaning it blocks other opioids, while allowing for some opioid effect of its own to suppress withdrawal symptoms and cravings.
This is why it would be misleading to classify buprenorphine as a replacement therapy. It would be equally misleading to classify it solely as an opioid blocker. Buprenorphine is in a category of its own and therefore should not be seen as “replacement” or “substitution” for anything else.”

So, it still is very much an opioid. It still possesses addictive and certainly dependency risk. For me, the partial antagonist makes it a much “safer” treatment. This is why it was primarily used for addiction treatment. Sadly, the great responsiveness to being a successful chronic pain treatment has led to poor formulations and Subutex being an “off-label” drug for pain. Why they did not apply to receive approval for chronic pain with the FDA is beyond me, but now that they’ve gone after Opana, I see the FDA has an agenda. The naloxone/buprenorphine addition (Suboxone) is almost useless though. It only raises the price, (hence the sales pitch article here for adding it to literally everything). It was meant to deter abuse, which it apparently does not, as people can and are using it IV, as well as every opiate. But I would rather see them do that, than to use heroin or fentanyl because it is far less likely to result in a tragedy.

Jean Price

When any doctor talks about the “opioid epeidemic” as if it’s a real, true issue…I tend think they have been drinking the CDC’s koolaide! And not at all in tune with the real truth and medical sense of the true face of pain care!! I don’t want to take any type of Naloxone…or Narcan! Why add in one more medication that I don’t even need!? Plus why do people think overdoses are a problem anyway…for those with long term pain!? We don’t receive enough medication to even function….let alone overdose! This has to be a joke….and a bad joke at that!

Accidental overdoses just confuse me…is there really such a thing?! It’s easily preventable with a dose strip…and using meds from the bottle isn’t a great idea for any medication…even if a person only takes one pill a day for blood pressure! So I’m can’t see why we would mix in another drug, versus teach people to use strips…or dispense a dosing strip with the prescription! How those who are patients in pain can overdose…especially accidentally…is beyond me!

This seems to be all about marketing…not patient care, and I am disgusted st any attempts to push it off on patients as anything else! I guess there is no shame anymore for some physicians and some officials! If they cared enough to really look for the truth, they would never consider this a great idea…and they would be writing articles instead to help turn the tide BACK TO appropriate pain care! Like in times past when we really cared about our patients comfort and ability to function and also their faster healing when pain was minimized…like I was taught and practiced!! This is just an advertisement, the way I see it! And not about pain care…at all!


Shirley, I am so very sorry about the loss of your daughter. I can’t imagine what you have been through. May God rest her soul and give you peace in your heart. With love and hugs, Maureen

Shirley Gard

My youngest child died from a heroin/fentanyl overdose. I am a chronic pain patient who has been forced to have people think that I am a drug addict because of what my deceased daughter did before she died. I use Suboxone for my pain and they make it clear that they can’t prescribe for pain. It works and why can’t it be an option as pain meds are constantly being thrown down our throats and they don’t last as long as we would think they should. This is all just sickening what we chronic pain patients have to go through. I am not an addict, I have nothing in my records stating anything bad etc. I am sick of all of this, what can we do to be heard? And what’s with these doctors letting everyone, all the way to the insurance companies dictate to how they are to practice? I know what I would tell them, how about all of you? Thank you for listening.


Shame on you. The CDC’s guidelines clearly state that there is NO EVIDENCE that “nonopioid therapy is preferred for treatment of chronic pain.”



Thank you for filling me in Reed. What are examples of full agonist and partial agonist meds? Thx

Tim Mason

Your have to stop taking current opioids before using Buprenorphine or the antagonist effect will make you violently ill. This statement is in the instructions Buprenorphine is used in patients that have addiction/abuse tendencies or have demonstrated that they cannot manage their own medication.


Subutex (just Buprenorphine alone) was great for my pain. Consistent. I never had any problems. A normal life. With Suboxone and the adverse reaction to naloxone, it is not good. The musculoskeletal pain & chest pains, I believe to be a result of the naloxone, is a major set-back. I may end up switching to full agonists if the effects get worse. I really don’t want to, as I would certainly loose the safety and stability of the partial agonist. I would still recommend trying Suboxone for chronic pain. You might react differently, and it may work great.

William Dorn

I would love to go off pain meds if subutex was legal but do not want to use suboxone.Maybe we all should call our state reps and ask that subutex be allowed for all that want it.


To all, Ditto, ditto, ditto! My thoughts exactly.
I’m curious to know how Reed (or anyone) has done on Suboxone for pain control compared to the regular Oxy/hydrocodone meds??
So, Narcan/Naloxone is strictly used for overdose? And Buprenorphine/Naloxone is for chronic pain?
My pain doc suggested to me a year ago that he may want to try me on the latter. But, he never revisited that idea and I never brought it up because of my fear of my being extremely sensitive of meds and maintain well enough on my hydro.


Gee, a sales pitch. Sure glad your conflict of interest disclosures were posted at the bottom of the article. This content has the same quality of an advertisement in my mind.

I do not need to incur an added cost. This should not be a flat-out requirement – it should be a choice that’s discussed with certain individual patients.


WOW!!! Of course the author of this article wants to push for more “co-prescription of naloxone alongside with opioid pain medications”, he’s the CEO of Opiant Pharmaceuticals, Inc. and he stands to make big bucks off this. This is so wrong. The majority of chronic pain patients are not in danger of over-dosing. They are taking their medications as prescribed by their doctors, they are not addicts using mostly illegal or UN-prescribed medications. SMDH.


My previous comment was lacking what I really needed to say. I don’t see this as a “win win” for all CP patients. I will admit, some may greatly benefit. Others, will most certainly not. I’m very familiar with Naloxone, as after the ill-conceived 2016 CDC guidelines, my physician put me on Suboxone (Buprenorphine-Naloxone), after being successfully treated on Subutex (Buprenorphine-Mono). I experienced several adverse reactions. Another patient went into anaphylactic shock. While one could argue, there are no adverse reactions “documented”, they are very real. Long term (and short term) exposure to Naloxone needs to be more thoroughly researched. Originally on Suboxone, I was at 90mg per day, and when prescribed Subutex, I went to 45mg, on my own, finding my lowest effective dose. My physician was surprised and the only rational explanation, was that due to no naloxone, my receptors were finally producing endorphins, having been suppressed for such a long time by Naloxone. Now, back on Suboxone for over a month, my side effects are increasing. Sharp stabbing pains in limbs, lack of concentration/memory. Persistent chest pains. itching, rashes, full body spasms, etc. In April, the Virginia Board of Medicine met to address the issue of a law recently passed that makes Subutex illegal (but for ONLY pregnancies). The ramifications of the law were profound as Doctors, Patients and Advocates reported multiple incidences of Naloxone reactions. They held another meeting to discuss revising. One Doctor even went so far as to prescribe epi-pens, after several patients went into anaphylactic shock. Interestingly, the first two public comments were from Adept Pharmaceuticals, and they were very obvious in their interests, stating that they wanted the law to remain as strict as possible, enforcing Naloxone as much as possible. Go figure. The law passed in Virginia was a textbook law that indicates the influence from the radical anti-opioid group PROP (or Physicians for the responsible prescribing of Opioids), aka Propaganda. Instrumental in the drafting of the 2016 CDC guidelines. In researching the board members, I found one who cc’d an executive board member of PROP. In his e-mail that was a bit too derogatory towards his patients. He insinuated that those with reactions were liars, and that these were CP patients that were basically “addicts”. I can tell you first hand, the reactions are VERY REAL. Others will also. So, the state of Virginia is attacking a drug used to treat addiction and chronic pain and it is the safest drug of them, being only a partial agonist, a schedule II not III. Not very smart. I agree that patients need to carry Naloxone, and have friends and family members trained to use it, however; forcing it into every opioid medication will not be a good thing for everyone. Being the CEO of a company that manufactures a Narcan/Naloxone, product (Opiant & Adept) your interests likely lie in the financial gain of your company. For example, an Rx for a drug with only 1mg of naloxone is twice as expensive.… Read more »


I tried this after being cold turkeyed after 20 years of long-acting Opioids. Just got out of hospital with pancreatitis and hepatitis. They’re suspicious of it for why it happened, though I was just diagnosed with complex regional pain disorder and also have fibromyalgia, levels fused, and extensive nerve damage in my pelvis and obturator nerve. A was stupidly put on a benzo plus Oxycontin originally, was switched to Methadone and Clonazepam when I had Alopecia Totalis. I went to a dependency doctor who has been tapering me down since I was dropped from my pain clinic of 9 years for accidentally recycling my script, yet I could go back for injections. Sure buddy! Anyhow, after 3 months when I saw the doctor, she encouraged me to try it for pain. I WAS on way less than with Methadone and it did help my pain. I’m pretty sure I’m sensitive to Naloxone, I have almost every symptom despite it being rare. In sum, I DO think it’s a good option for pain control, just be careful if you’re real sensitive to meds like I am. You also don’t get the drug addict treatment by the ER when on it, surprisingly. I had trouble with liver enzymes after going off Methadone and cutting Clonazepam in half and actually called back to the ER. The numbers were a few hundred higher than normal whereas my first ER trio they were up to 3000 higher than normal. Good luck to those who try it! I used strips that I sectioned and they were sublingual.


Naloxone has side effects. You work for Adapt Pharma who has a financial interest in Naloxone. You, of all people should know, need MORE RESEARCH on long term and short term adverse effects and reactions.. Adding Naloxone to all opioids is dangerous and driving prices sky high as well.


Again pain patients are being compared to addicts. The pain patients taking the Naloxone are doing so because it is being forced upon them if they want to continue to receive their pain medication. I don’t like reading articles written by people with an invested interest in addiction. Chronic pain patients are not addicts and abusers. This is where this whole problem of losing our medications began. With someone saying “Let’s not study it, why don’t we fix what isn’t broken because we want to see what happens.” I also noticed that the fact that most are responsible with their meds. and fewer than 3% abuse their meds. is well hidden and not really explored in this article. Although I have read that fewer than .08% abuse their meds. I think these are the types of articles that are damaging to the plight of chronic sufferers.


I was given a prescription for the auto injection delivery system and was very pleased to have it! The evening that I got it, I showed it to my husband and son and instructed them on how and when to use it. I go to great lengths to ensure that I don’t accidentally take too much medication but with a systemic disease the possibility of my body doing something stupid is always present. I feel safer knowing that my family has a tool to help keep me safe in an emergency. Now if I could just get my doctors to bring my prescriptions back up to a level that actually controls my pain somewhat…