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Buprenorphine for Opioid Substance Use Disorder (SUD)


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Buprenorphine for Substance Use Disorder (SUD)


The Purpose of Buprenorphine Treatment:

To suppress the debilitating symptoms of cravings and withdrawal, enabling the patient to engage in therapy, counseling and support, so they can implement positive long-term changes in their lives which develop into the new healthy patterns of behavior necessary to achieve sustained addiction remission.


Isn’t buprenorphine treatment just trading one addiction for another?

“No. With successful buprenorphine treatment, the compulsive behavior, the loss of control of drug use, the constant cravings, and all of the other hallmarks of addiction vanish. When all signs and symptoms of the disease of addiction vanish, we call that remission, not switching addictions.


When a patient switches from an addictive opioid to successful buprenorphine treatment, the addictive behavior often stops. In part due to buprenorphine’s long duration of action, patients do not have physical cravings prior to taking their daily dose. The drug seeking behavior ends. Patients; regain control over drug use, compulsive use ends, they are no longer using despite harm, and many patients report no cravings. Thus all of the hallmarks of addiction disappear with successful buprenorphine treatment.


Therefore, one is not trading one addiction for another addiction. They have traded a life threatening situation (addiction) for a daily inconvenience of needing to take a medication (physical dependence), as some would a vitamin. Yes the physical dependence to opioids still remains, but that is vast improvement over addiction, is not life threatening, and it can easily be managed medically. It’s also important to note that the physical depndence pre-existed the buprenorphine treatment and was not caused by it.


Addiction is a brain disease that affects behavior. This addictive behavior can be devastating to the patient and their loved ones. It’s not the need to take a medication that is the problem, many people need to take a medication, but rather it is the compulsive addictive behavior to keep taking it despite doing harm to one’s self or loved ones that needs to stop. Whether or not the person takes a medication to help achieve this shouldn’t matter to anyone. If a medication helps stop the damaging addictive behavior, then that is successful treatment and not switching one addiction for another.”

The National Alliance of Advocates for Buprenorphine Treatment


Buprenorphine is an opioid and, because of some special characteristics, it is useful for treating opiate addiction.


Long Half-Life

Buprenorphine has a long half-life (between 20 and 44 hours), meaning that it takes one to two days for your body to eliminate half of an ingested dose. This allows an appropriate dose of buprenorphine to block withdrawal symptoms up to 24 hours. Importantly, it stops cravings for opioid use with only single daily dosing. For patients with chronic pain and opioid SUD, buprenorphine is an excellent treatment option for both conditions. However, the duration of action of the pain benefit of buprenorphine does not last a full 24 hours, so when treating both conditions it is necessary to take buprenorphine in divided doses, splitting the daily dose into 2 or 3 split doses/day.

See: Buprenorphine for Pain


“Ceiling Effect”

Aside from it’s long duration of action, buprenorphine also has a safety advantage compared to methdone and other opioids. Buprenorphine has a “ceiling effect” related to respiratory depression, the suppression of breathing that occurs with excessive doses of opioids. This means that respiratory depression does not tend to worsen as higher doses of buprenorphine are ingested,  which makes buprenorphine less likely to result in accidental fatal overdose. This  “ceiling effect” is not an absolute protection:  it is still possible to overdose, especially when buprenorphine is taken with other sedatives, including alcohol and benzodiazepines such as Xanax, Valium and Klonopin. This limited respiratory depression may be a particularly valuable characteristic for some people, especially those with COPD or untreated sleep apnea who may be at greater risk for opioid-induced suppression of breathing and oxygenation when sleeping.


Strong Opioid Receptor Binding Affinity

Buprenorphine has another special characteristic compared with most other opioids: it has a very strong binding affinity to the opioid receptors (mu-receptors) in the nervous system that contribute to opioid effects, including euphoria, analgesia, sedation and other effects. This stronger binding affinity means that it will prevent or displace other opioids in a patient’s system from binding and triggering their effects. This means that while taking buprenorphine, it’s presence blocks the euphoria that might be sought by relapsing on heroin or prescription opioids, thus enhancing abstinence. A note of warning should be heeded here, however. It is possible to overpower buprenorphine’s blockade of other opioids, but to do so may often require high doses to achieve the euphoria, doses that are likely to also cause significant respiratory depression and create a high risk for fatal overdose.


The high receptor binding affinity of buprenorphine is also a major factor in when and how to start taking buprenorphine. If a person has other opioids in their system when they take buprenorphine, this displacement may trigger withdrawal symptoms dependent on a person’s level of physical dependence to their opioids. And this withdrawal will be immediate and full blown, potentially severe, not gradual the way it is experienced when simply discontinuing opioids. For this reason it is important that you discuss with your physician how to make the transition on to buprenorphine and make certain you understand the process before doing so.

See also: Naloxone (Opioid Blocker)


Advantages Compared with Methadone

Methadone is the other opioid agonist used commonly in medication assisted treatment (MAT) of opioid SUD. But, while also very effective in maintaining abstinence from opioid abuse, methadone does not share the “ceiling effect” benefit and has other safety concerns that make buprenorphine a safer choice in MAT. Because the metabolism of methadone by the liver is complex, it is more likely to be affected by drug interactions with other medications, there is greater potential for adverse effects. Furthermore, there are genetic variants in the metabolism of methadone that also make methadone potentially more at risk for unexpected outcomes related to safety.


Additionally, in the event of pregnancy, buprenorphine has growing evidence to support it’s greater safety and improved outcomes for the fetus, particularly as related to neonatal withdrawal complications (Neonatal Withdrawal Syndrome).

See: Methadone



Prescribing Information for Safe Use of Buprenorphine


Different forms and different brands

Buprenorphine is available as a pill or film strip designed to dissolve under the tongue or against the side of the cheek. Buprenorphine is available as a stand-alone medication or in combination with naloxone, a non-therapeutic secondary component added only as an abuse deterrent. The presence of naloxone offers no actual therapeutic benefit but, if the formulation (tablet or film) is snorted or injected in an attempt to abuse the medication, the naloxone will trigger an immediate withdrawal syndrome meant to discourage abuse.


A new form of buprenorphine was approved by the FDA in May, 2016. It is an implantable version of buprenorphine in the form of small 26 x 1 mm rods that are placed under the skin via a minor surgical office procedure. (See below).


Butrans is a transdermal patch form of buprenorphine, designed to be worn for one week then replaced. It is an excellent and convenient means of treating mild to moderate chronic pain. Butrans is FDA approved for pain only, not addiction. Butrans contains only buprenorphine and comes in five dosage strengths ranging from 5 μg/hr to 20 μg/hr in patches designed to be replaced every 7 days.


Belbuca is a buprenorphine film that is applied to the cheek inside the mouth (buccal area). It contains only buprenorphine and comes in seven dosage strengths ranging from 75 μg to 900 μg, to be dosed every 12 hours.  Belbuca provides higher doses than Butrans patches but lower doses than the combination buprenorphine/naloxone tablets and strips (Suboxone, Zubsolv and Bunivail). Belbuca is FDA approved for pain only, not addiction.


Suboxone is the most well-known form of buprenorphine in combination with naloxone because it is commonly used to manage opioid addiction as a safer alternative to the use of methadone, another opioid used for both pain and addiction. Suboxone, like the other brands of buprenorphine tablets or film strips, is FDA approved for addiction treatment and therefore it’s use for pain is considered “off-label.” However, as noted above, buprenorphine as a drug is FDA approved for pain and many medications are commonly used “off-label.” Suboxone is available as a tablet or a film strip in four buprenorphine strengths: 2mg, 4mg, 8mg and 12 mg and is generally dosed every 8-12 hours for pain control.


Subutex is buprenorphine only, in tablet form and like Suboxone it is available in four strengths: 2mg, 4mg, 8mg and 12 mg.  Subutex is generally dosed every 8-12 hours for pain control. It is used almost exclusively in pregnancy.


Zubsolv is buprenorphine in combination with naloxone. It is a film strip designed to dissolve under the tongue and comes in two buprenorphine strengths: 1.4mg (a comparable dose to the 2mg Suboxone dose) and 4.2mg (a comparable dose to the 8mg Suboxone dose). The difference in dosing is due to the different bioavailability associated with the different proprietary formulation. Due to the equivavent bioavaiable dose with Zubsolv. It ihas been shown that Zubsolv dissolves more quickly than Suboxone and there is less buprenorphine being swallowed where it contributes to risk for constipation.


Bunavail is buprenorphine in combination with naloxone. It is a film strip designed to adhere to the cheek, then dissolve. It comes in three buprenorphine strengths: 2.1 mg (a comparable dose to the 4 mg Suboxone dose), 4.2 mg (a comparable dose to the 8mg Suboxone dose) and 6.3 mg (a comparable dose to the 12mg Suboxone dose. The difference in dosing is due to the different bioavailability associated with the different proprietary formulation.


Advantages of Bunavail

Bunavail is designed differently from Suboxone and Zubsolv. Rather than the single layer design, it is a bilayered film that promotes unidirectional drug flow across the buccal mucosa (lining of the cheek), allowing for less buprenorphine dissolving into saliva and more of it going into the blood through the cheek. Consequently, because less buprenorphine is wasted into saliva and swallowed, a smaller dose strip can be used with equal amounts of buprenorphine entering the blood.


Thus, while an equal amount of buprenorphine enters the blood compared with the other formulations, less buprenorphine enters the stomach and intestines. When buprenorphine enters the stomach and intestine, it is absorbed and transported to the liver which metabolizes the buprenorphine into norbuprenorphine, its primary metabolite. In a recent 2016 study, it was determined that norbuprenorphine blood levels were 40% lower with Bunavail compared with the sublingual preparations.


Norbuprenorphine is bioactive like buprenorphine but with different characteristics. Because it is a full mu-opioid agonist unlike the partial mu-opioid agonist, buprenorphine, norbuprenorphine has greater activity related to the mu-opioid receptor resulting in greater constipation effect. For this reason, the higher norbuprenorphine levels associated with Suboxone and Zubsolv compared with Bunavail are associated with more likelihood of constipation.  Therefore, if one experiences constipation with Suboxone or Zubsolv, a trial of Bunavail is warranted.


Another advantage of the buccal adherence to the cheek is the relative immediacy one can proceed to speak without waiting for a tab or strip to dissolve under the tongue.


Disadvantage of Bunavail

Because blood levels of norbuprenorphine are lower at comparable blood levels of buprenorphine with Bunavail compared with Suboxone and Zubsolv, it is likely that Bunavail does not have as much analgesic benefit due to the analgesic contribution of norbuprenorphine. This conclusion is speculative, however, with no definitive studies comparing analgesic benefits between the three versions.


Each proprietary formulation tastes different, with each taste appealing more or less to the individual.


Probuphine is an implantable form buprenorphine that consists of four rods, each measuring 1 inch, that are implanted under the skin on the inside of the upper arm. It provides a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses (2-8 mg/day) of other forms of buprenorphine. The procedure is relatively simple and is performed under local anesthesia, the same as when placing stitches. It can be performed in 20-30 minutes or less and is relatively painless.


The advantage to this approach, aside from convenience, is that it maintains compliance with treatment, offering the promise of less likelihood of relapse.  This procedure can only be performed by a physician certified to do so. Please note that Dr. Ehlenberger is certified to perform the procedure, please contact the office for more information.


What is the most important information I should know about taking Buprenorphine?

  1. Buprenorphine can cause death from overdose, especially if you take them with alcohol or sedatives such as Xanax, Valium or Klonopin (the benzodiazepines). Studies indicate that the toxicity of respiratory depression combining benzodiazepines and buprenorphine are more than additive, they are synergistic. This means that the sum danger of their combined effects is greater than predicted by the sum of their individual combinations. Use Buprenorphine exactly the way your doctor tells you to with medicines used to treat depression or anxiety.
  2. Use Buprenorphine only for the condition for which it was prescribed.
  3. Buprenorphine can cause drug dependence. This means that you can get withdrawal symptoms if you stop using it too quickly. Buprenorphine is not for occasional (“as needed”) use.
  4. Getting off buprenorphine can be accomplished without serious difficulty. The reason it sometimes has the reputation of being difficult to taper off is that the tapering is not done correctly. Buprenorphine is a potent opioid and must be tapered slowly and you cannot simply stop taking it abruptly when you get down to a 1 or 2mg/day dose. Use of alternative buprenorphine formulations and tapering regimens can be engaged to make the final taper smooth and well tolerated. There is growing research to suggest that the use of gabapentin (Neurontin) may ease opioid withdrawal symptoms (See: Gabapentin). Additionally, the use of Synaptamine during the tapering process may make the tapering better tolerated.
  5. Prevent theft and misuse. Buprenorphine is a narcotic painkiller that can be a target for people who abuse prescription medicines or street drugs. Keep your Buprenorphine locked in a safe place, to protect them from theft. Never give them to anyone else. Selling or giving away this medicine is against the law.
  6. In an emergency, have family members tell emergency room staff that you are being treated with buprenorphine, especially if being treated for a severely painful condition. Buprenorphine binds very tightly to the opioid receptors (see: Neurobiology of Opioids) that provide pain relief, more than most other opioids including hydrocodone, oxycodone and morphine. This means that in the event of an emergency that demands pain medicines for pain not controlled by currently prescribed buprenorphine, the emergency physician must use the correct opioid for pain or the buprenophine will block the second opioid and it will be ineffective. This ineffectiveness may be misinterpreted as drug-seeking by a physician not well informed regarding treating pain in patients who take buprenorphine. The best two medications for emergency use for managing pain in this emergency circumstance, either orally or intravenously, are hydromorphone (Dilaudid) or fentanyl. These two opioids have greater affinity for the opioid receptor than buprenorphine and will be effective for pain. That being said, caution is advised to avoid unintentional overmedication/overdose and careful monitoring should be employed. Whenever possible, always contact Dr. Ehlenberger (24/7) should you need to go to the emergency room for any condition, but especially for a painful condition.


Who Should Not Take Buprenorphine?

Do not take buprenorphine if:


  1. Your doctor did not prescribe buprenorphine for you.
  2. You are allergic to buprenorphine, or any of the inactive ingredients in the medicines. See the end of this leaflet for a complete list of ingredients.


Your doctor should know about all your medical conditions before deciding if buprenorphine is right for you or what dose is best. Tell your doctor about all of your medical problems, especially the ones listed below:


  1. Trouble breathing or lung problems  
  2. Head injury or brain problem
  3. Liver or kidney problems
  4. Gallbladder problems
  5. Adrenal gland problems, such as Addison’s disease
  6. Low thyroid (hypothyroidism
  7. Enlarged prostate gland (men)
  8. Problems urinating
  9. A curve in your spine that affects your breathing
  10. Severe mental problems or hallucinations (seeing or hearing things that are not really there  
  11. Alcoholism


Tell your doctor:

  1. if you are pregnant or plan to become pregnant. Buprenorphine may not be right for you. It is not known whether buprenorphine could harm your baby.
  2. if you are breast feeding, buprenorphine will pass through your milk and may harm your baby.
  3. Tell your doctor about all the medicines you take, including prescription and non­prescription medicines, vitamins, and herbal supplements. They may cause serious side effects when taken with buprenorphine. Sometimes, the doses of certain medicines and buprenorphine need to be reduced if used together.
  4. Do not take any other medicine, herbal, or over-the-counter medicine while using buprenorphine unless your doctor has told you it is okay.


How should I take Buprenorphine?

  1. Follow your doctor’s directions exactly. Your doctor may change your dose after seeing how the medicine affects you. Do not change your dose unless your doctor tells you to change it. Do not take buprenorphine more often than prescribed.
  2. Put the tablets or film under your tongue or against the cheek as directed and let them melt. This will take 2 to 10 minutes. Do not chew or swallow the tablets. The medicine will not work this way and you may get withdrawal symptoms.
  3. If your doctor tells you to take more than 1 tablet/film, you will be told to:
  4. take all tablet/films at the same time together under your tongue, or
  5. take 2 tablet/films, put them under your tongue. After they melt, put the next tablet/film under your tongue right away
  6. hold the tablet/film under your tongue until they melt completely. The medicine will not work if swallowed and you may get withdrawal symptoms.
  7. Do not change the way you are told to take your medicine or you may get too little or too much medicine.
  8. Do not inject (“shoot-up”) buprenorphine. Shooting-up is dangerous and you may get bad withdrawal symptoms.
  9. Buprenorphine can cause withdrawal symptoms if you take them too soon after using opiate drugs like morphine, oxycodone, hydrocodone or methadone.
  10. If you miss a dose of buprenorphine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once unless your doctor tells you to.
  11. Before discontinuing buprenorphine, ask your doctor how to avoid withdrawal symptoms.
  12. If you take too much buprenorphine or overdose, call your local emergency room or poison control center ASAP.
  13. If you discontinue taking buprenorphine, flush the unused tablets or strip down the toilet.


What Should I Avoid While Taking Buprenorphine?

  1. Do not drive, operate heavy machinery, or perform other dangerous activities until you know how this medicine affects you.
  2. Do not drink alcohol or take tranquilizers or sedatives (medicines that help you sleep) while using buprenorphine. You can die when you use these products with buprenorphine..
  3. Do not take other medicines without talking to your doctor. Other medicines include prescription and non-prescription medicines, vitamins, and herbal supplements. Be especially careful about medicines that may make you sleepy.
  4. When in early remission, only recently abstaining from opioids and early in buprenorphine treatment do not take on the added challenge of quitting smoking. Not only does this add greater stress and potentially amplify withdrawal symptoms, studies indicate that nicotine withdrawal/abstinence dysregulates the mu-opioid receptors and makes buprenorphine less effective.


Potential Drug Interactions

There may also be a potential for a buprenorphine interaction with other drugs and compounds that induce or inhibit the cytochrome P-450 3A4 system, the enzyme system in the liver that metabolizes buprenorphine. There are many agents in this category and they include erythromycin, zileuton, and grapefruit juice and starfruit (inhibitors of metabolism), as well as carbamazepine, phenobarbital, phenytoin, and rifampin (inducers that enhance metabolism). In a study of the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac) and fluvoxamine (Luvox), were both shown to inhibit buprenorphine metabolism, suggesting they may increase blood levels of buprenorphine if started on someone already taking buprenorphine.


What are the Possible Side Effects of Buprenorphine?

Some of the common side effects of buprenorphine are headache, drowsiness, problems sleeping, nausea, sweating, stomach pain, and constipation.These are not all the possible side effects of buprenorphine, just some of the most common.


Call your doctor or get medical help right away if:

  1. You feel faint, dizzy, confused, or have any other unusual symptoms.
  2. Your breathing gets much slower than is normal for you. These can be signs of an overdose or serious problem.
  3. Buprenorphine can cause your blood pressure to drop, causing dizziness if you get up too fast from sitting or lying down.
  4. Buprenorphine can cause allergic reactions that can make it hard for you to breathe. Other symptoms of a bad allergic reaction include hives, swelling of your face, asthma (wheezing) or shock (loss of blood pressure and consciousness).

Call a doctor or get emergency help right away if you get any of these symptoms.


Buprenorphine may cause liver problems. Call your doctor right away if:

  1. Your skin or the white part of your eyes turns yellow (jaundice).
  2. Your urine turns dark.
  3. Your bowel movements (stools) turn light in color.
  4. You don’t feel like eating much food for several days or longer.
  5. You feel sick to your stomach (nausea).
  6. You have lower stomach pain.


Your doctor will do blood tests while you are taking buprenorphine to make sure your liver is okay.


Other considerations:

  1. You may get withdrawal symptoms when you start treatment with buprenorphine. To avoid this, be sure other opiates are out of your system before starting buprenorphine.
  2. Like with all opiates, you can develop dependence from taking buprenorphine, so you may get withdrawal symptoms when you stop taking buprenorphine. There is also a chance that you may abuse or get addicted to buprenorphine.


Genetic Testing

At Accurate Clinic we highly recommend genetic testing for our opioid management patients. Through testing our patient’s DNA with a simple oral swab of saliva from the cheek, an individual’s ability to metabolize opioids and other medications by the liver can be evaluated. This information provides important insights as to how a patient may respond to various medications, including buprenorphine, and where side effects or drug interactions may be predicted, offering substantial safety benefits in prescribing opioids.


Buprenorphine and Psychiatric Comorbidities


Overall, psychiatric disorders are common in opiate-dependent people, particularly depression, with some studies indicating that approximately 20% of opioid SUD patients in treatment with buprenorphine have a history of depression. It has been shown that depression often subsides or improves within the first weeks of buprenorphine treatment. Consequently, it is generally recommend to wait for at least 1 week after starting buprenorphine before treating with antidepressants.


Buprenorphine is considered to be a possible antidepressant, both in patients with depressive disorder and in opiate SUD patients. A possible pharmacological explanation for an antidepressive effect of buprenorphine is that it is not only a partial opioid agonist at the mu-opioid receptor but also a partial agonist and effective antagonist at the kappa-opioid receptor. The kappa-receptor appears to play a role in the development of addiction, as well as in the development of depression. Kappa antagonists have been shown to have antidepressive and anxiolytic effects.  Buprenorphine’s combination of opioid mu-agonistic and kappa-antagonistic characteristics results in less depressed mood than methadone.


When treating buprenorphine-dependent patients, a number of studies have shown that  tricyclic antidepressants are particularly effective in treating depressive symptoms and doxepin is slightly more effective than imipramine.

See: Antidepressants



Buprenorphine Constipation

  1. Opioid-induced constipation_ rationale for the role of norbuprenorphine in buprenorphine-treated individuals – 2016


Buprenorphine Management of Chronic Pain in Opioid SUD

  1. a-clinical-trial-comparing-tapering-doses-of-buprenorphine-with-steady-doses-for-chronic-pain-and-co-existent-opioid-addiction-2010


Buprenorphine Probuphine (Implant)

  1. FDA OKs Buprenorphine Implant (Probuphine) for Opioid Dependence – 2016


Buprenorphine – Zubsolv

  1. Effects of a Higher-bioavailability Buprenorphine:Naloxone Sublingual Tablet Versus Buprenorphine:Naloxone Film for the Treatment of Opioid Dependence During Induction and Stabilization – 2015


BuprenorphineDrug Interactions

  1. Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine



  1. Root Causes, Clinical Effects, and Outcomes of Unintentional Exposures to Buprenorphine by Young Children – 2013
  2. buprenorphine-and-midazolam-act-in-combination-to-depress-respiration-in-rats-2002


Buprenorphine – Microinduction

  1. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use – the Bernese method – 2016


Emphasis on Education


Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.


For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.


Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.


For more information, please contact Accurate Clinic.


Supplements recommended by Dr. Ehlenberger may be purchased commercially online or at Accurate Clinic.

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