buprenorphine and it’s special qualities

Suboxone and generic versions sold in Canada are a combination of two medications – buprenorphine, which is a partial opioid agonist, and naloxone, an opioid antagonist.

Many people will recognize the medication naloxone as it is now readily available to anyone (substance user or not) in Ontario – both through the health unit or a pharmacy. A prescription is not required. It can be used in an opioid overdose to save a persons life by any bystanders with a naloxone kit It works because it occupies opioid receptors in the brain but does not stimulate them.

Some people are confused that naloxone, an opioid antagonist, is included with buprenorphine for the treatment of opioid use disorder (OUD) – wouldn’t it just put people in withdrawal?. The answer is not unless it is injected. It has very poor bioavailability if taken orally or sublingually (under the tongue) so blood levels are too low to cause effects if it is administered by any route other than a needle or intranasally (up the nose). It is considered a safety feature to prevent injection abuse of the medication.

Agonists are compounds that stimulate specific receptors. For example oxycodone, morphine, hydromorphone, fentanyl and methadone are all opioid agonists.

Partial agonists like buprenorphine are drugs which only partially stimulate a receptor. One of the advantages of partial agonists is safety – increasing the dose past a certain point may not cause an additional effect because even if most of the receptors are occupied they are still only partially stimulated. Note that buprenorphine acts as a partial agonist with respect to respiratory depression and preventing withdrawal symptoms but it acts as a full agonist with respect to treating pain. Buprenorphine may be as good as any opioid for treating pain but would need to be used 3-4 times daily for this purpose.

This characteristic is noted with buprenorphine. When 16mg is taken daily 92% of the opiate receptors in a persons brain are occupied. Additional doses have very little additional effect on respiratory depression (all opiates can cause respiratory depression). Therefore it is much less likely to have a life threatening overdose on buprenorphine than with full opioid agonists, including methadone.

There is an additional aspect of buprenorphine’s pharmacology that makes it both useful in the treatment of addiction and at the same time more difficult to use. It has a very high affinity to opiate receptors. This means that it binds more strongly to opiate receptors compared with other opioids.

The high affinity is useful because if a buprenorphine patient tries to use full agonists when they are on buprenorphine the agonists have very little or no effect. Because the patient does not experience euphoria (the “high”) the behavior (using the agonist drug) is not reinforced in the patient’s brain – reinforcement is something that would delay recovery from the addiction. Most patients find this characteristic of buprenorphine helps them quit opiates sooner.

The high affinity of buprenorphine makes Suboxone more difficult to use. The patient must be in moderate withdrawal before Suboxone is administered or the high affinity to opiate receptors coupled with the partial agonist properties of buprenorphine leads to opiate agonists that are present in the brain being replaced with a compound that only partially stimulates the receptor. This leads to the rapid development of withdrawal symptoms – a complication known as precipitated withdrawal. So, if you are in moderate withdrawal buprenorphine can be started and you will soon feel better. If you are not in at least moderate withdrawal, you may feel worse. More about this when we discuss the induction.

How is buprenorphine taken?

Buprenorphine is allowed to dissolve under the tongue (sublingual) – it is not effective if the pill is swallowed. This is also because of bioavailability – anything swallowed and absorbed into blood vessels surrounding the small intestine goes into the portal circulatory system. All this blood goes through the liver where buprenorphine is denatured. Medications that enter into the systemic circulatory system by being absorbed into blood vessels in the oral mucosa (the lining of the mouth) bypasses the liver. In optimal circumstances 60% of the buprenorphine is absorbed into the circulation and 40% is swallowed (because of salivation). There is also a film form of buprenorphine, that after sublingual stabilization is applied to the inside of the cheek. I dissolves faster but at this time (spring 2021) is not covered by ODB or NIHB. In addition there is a depot form of buprenorphine  – see Sublocade on this site.

How buprenorphine helps

Buprenorphine is an opioid and therefore effective in reducing the craving to use opiates and the symptoms of opiate withdrawal. Suboxone is used to treat addiction to other opioids, for example codeine, oxycodone, hydromorphone, fentanyl, morphine and heroin. It is about as effective as methadone. It is not useful in treating an addiction to cocaine or crack, methamphetamine (speed), MDMA (ecstasy), benzodiazepines (valium and others), marijuana or alcohol.

Buprenorphine can be effective whether you typically inject, smoke, snort or swallow opiates. Several scientific studies have proven that people with substance use disorders on an opioid maintenance program are less likely to have legal or medical problems and are more likely to hold down a job, stay in school and keep their family together. The evidence is overwhelming – the patient benefits but so does their family and society.

How is buprenorphine started?

Starting buprenorphine is termed an Induction. Suboxone Induction should only be attempted by a physician trained in the procedure. Because Suboxone is a partial agonist it may put people dependent on opioids into a precipitated withdrawal. Precipitated withdrawal is a rapid onset and intense withdrawal caused by taking buprenorphine when you have residual opioid drugs in your system. Before the induction the physician will ensure you are in a partial opioid withdrawal state and then instruct you slowly introduce buprenorphine to your system over several hours. In most cases the individual will be offered a home induction which allows you to adjust your dose in the comfort of your own home. Ideally we see you again the next morning to see how much of the buprenorphine you needed over the 24 hours. In most cases, this dose will be provided to you for a week at which time you are reassessed.

How much does buprenorphine cost?

Buprenorphine is covered by the provincial drug plan in Ontario (ODB).

It is also covered by NIHB (Indian Affairs) and most 3rd party drug plans. If you are not eligible for any of this coverage you should discuss this with your pharmacist. The BMC doctor may be able to give you a range of doses you are likely to require.

Effects & Side Effects

Euphoria (feeling high) or sedation or nausea or anorexia (decreased appetite) is possible if too high a dose of buprenorphine is taken. Typically patients feel no effect except a decreased need for opiates. Your stable dose is usually achieved over 24 hours to a few days (compared to a few weeks with methadone). Once stabilized patients do not get “high” and they do not suffer withdrawal or craving for opioids. Patients usually do not get high if they take other opiates because buprenorphine maintenance blocks the euphoric effects of these drugs by occupying the available opioid receptors – this helps to decrease the desire to use opioids.

Buprenorphine is useful to prevent withdrawal because it has a long duration of action. For most people a single dose prevents withdrawal for more than 24 hours. By slowly decreasing the dose over weeks or months (more typical) patients can become opioid free without having to go through withdrawal – this is called a taper. Patients at BMC are never forced to go off buprenorphine and a some do prefer to stay on chronic therapy as it keeps them safer with respect to relapse.

Some people get some side effects but overall buprenorphine is well tolerated. Most common side effects are constipation (typical of all opiates), dizziness or drowsiness or headache (usually resolves over a week or so). Weight gain, sweating and sexual side effects are much less common than with methadone, especially higher dose methadone. Withdrawal symptoms like abdominal cramps, nausea, diarrhea, insomnia, restlessness, irritability, anxiety and muscle or joint pain may be part of the induction phase but resolve quickly once the patient is stabilized.

Taken as directed, buprenorphine is very safe and does not cause long-term damage to organs, even after several years. Some people do get elevations in their liver enzymes which reverse once the drug is stopped. In most cases this is not felt to be of any consequence.

Suboxone is now commonly used in pregnancy.  It is believed that Neonatal Abstinence Syndrome (baby withdrawal) is less severe and requires less treatment for babies born to mothers on buprenorphine vs. methadone. Please see the pregnancy related FAQ’s.

A previous concern about buprenorphine compared with Methadone was with respect to the treatment of  acute pain. It was believed that Suboxone blocked the effect of other opioids. It is now known that increased opioids are required to treat acute pain in patients on any opioid therapy whether it is long term opioids for chronic pain or methadone or buprenorphine for maintenance. The amount of extra opioids needed to treat pain compared with patients that are not on long term opioids is about the same regardless of whether you are on methadone or suboxone. If you have surgery or a procedure booked please discuss this with your BMC physician. We are available to talk with your surgeon, dentist or anesthetist.

Suboxone is a very good pain agent but need to be used 3-4 times per day. This treatment is not covered by ODB, NIHB nor 3rd party drug plans at this time.

Will I become addicted to buprenorphine?

Patients taking buprenorphine are already physically dependent to opioids – stopping it will cause the uncomfortable physical symptoms of withdrawal.  See the section in key concepts.

Buprenorphine Maintenance

In Ontario patients taking Suboxone follow similar rules with respect to clinic visits, urine testing and restrictions in carry home doses as Methadone patients but there are some differences. Overall Suboxone maintenance is probably easier than methadone maintenance in the longer term – talk to the BMC physician. Certainly it is easier to travel with. The CRISM guidelines suggest it should be tried before methadone as it is safer and has less side effects for most people.