For the pain-suffering addict, Methadone serves well
As hyperalgesia is minimized, the best we can tell.
Exactly why, we will have to wait to explain -
A divided dose diminishes the pain-fueled flame.

Possibly related to Methadone’s long half-life, it rarely causes hyperalgesia.  The exact underlying brain mechanisms that cause hyperalgesia are yet to be fully understood.  The vast majority of patients with chronic pain and opioid addiction can find a split dose of their Methadone that alleviates their pain, prevents withdrawal, and keeps them in a clear mental state.

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We also know that pain is a very personal matter without a clear yardstick of measurement.  Some people who have been in very serious accidents with multiple fractures and/or anatomic abnormalities deny feeling any significant pain while others with normal anatomy experience severe pain, which is unexplained by current medical science.  The perception and functional disability of pain can respond to good counseling, physical therapy, appropriate medical therapy, mindfulness, anxiety reduction, etc.  Integrating these and non-addicting analgesics can protect the chronic pain patient from becoming addicted to opioids.

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Finding the right dose of Methadone for a person on MOUD is an important early step in the recovery process.  Once achieved, using counseling and other modalities to improve one’s self-awareness helps the pain-suffering patient regain control and improve their day-to-day functioning.

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Buprenorphine was added around 2002,
Soon, the number of trained prescribers grew and grew.
Being safer in overdoses contributed to this growth,
Allowing doctors to treat per their Hippocratic Oath.

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In the midst of the1990-2010 timeframe when doctors were overprescribing opioids for pain and causing addictions, an older long half-life opioid-related medication, Buprenorphine, was studied and found to be an alternate medication for MOUD.  Buprenorphine is called a ‘partial opioid agonist’.  This label is difficult to explain but important to understand.

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All of the opioids that have been mentioned so far are referred to as full opioid agonists.  When they go to the brain, they work by stimulating the opioid receptors.  These receptors do such things as dull pain, slow bowel activity, cause eye pupils to constrict, and other effects to be discussed later.  As the dose of a full agonist is raised, the more potent the effect.  Breathing and heart rate are slowed by the opioid receptors.  Overdoses of opioids can cause respirations to cease and the heart to stop beating, leading to death if not immediately reversed.  

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A partial agonist like Buprenorphine has the interesting property of a tapering off of the opioid effects after a certain dose is achieved.  Buprenorphine’s therapeutic range is between very low dosages in some patients up to 24 mg per day.  In rare circumstances, some patients will have added benefit up to 32 mg per day.  Doses above 32 mg per day offer no added benefit.  It’s as though a blocking effect kicks in at these higher doses. This ceiling effect was very intriguing to the researchers and FDA.  In animal studies, the suppression of breathing and cardiac function with Buprenorphine were significantly less compared to full agonists.  This finding was a major factor in Buprenorphine’s approval for treating opioid addiction.  Overdose deaths caused by Buprenorphine alone are very rare in human adults.

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Methadone does not have that built-in safety feature, and patients can die from too high a dose which could shut off breathing and stop the heart. Legislation in 2000 allowed the FDA to set up an 8-hour training for doctors who wanted to prescribe Buprenorphine for opioid addiction.  Many thousands of doctors have taken this course which has helped reach more patients, especially in rural areas that don’t have access to the more regulated clinics that use Methadone. Safety and diversion risks are the main reason that specialty clinics such as CORE are the only place a person suffering from opioid addiction can receive Methadone.  Around 2018, regulations were changed so that clinics like CORE could also offer Buprenorphine as an option.  This regulation change made Buprenorphine an option for those on Medi-Cal, usually at no cost to the patient.  

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In the early 2000’s, when Buprenorphine was first approved for opioid addiction, the brand name products were Suboxone and Subutex.  Other brand name products such as Zubsolv, Bunavail, and Sublocade have been developed by other pharmaceutical companies, but the active ingredient in all of these is Buprenorphine.  Interestingly, Buprenorphine is well absorbed in the mucous membranes in the mouth, avoiding first pass breakdown by the liver when it is swallowed.  Different preparations seek to maximize absorption and lead to predictable blood levels.  All products, whether tablets, film strips, patches, or injections are equally effective.  The patient’s insurance coverage or the clinic supplies will usually dictate which Buprenorphine preparation the patient will take.  

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Buprenorphine is an excellent choice for a patient who is opioid addicted and also suffers from chronic pain and anxiety.  Its original use in 1966 was as a pain medication following surgery.  It has a high affinity for the Mu receptor leading to excellent pain relief for both acute and chronic pain.  It is also the only Kappa opioid receptor blocker on the market.  The Kappa opioid receptor causes anxiety.  Blocking it relieves anxiety.  Researchers are looking for a Kappa blocker that does not cause opioid dependence.  To date, such a medication has not been discovered.  Studies have been done with a combination of Buprenorphine and a Mu opioid blocker.  This leaves the Kappa blocking effect, which has been effective in treating anxiety in animal models and human trials.   At this time, it has not been approved for anxiety in non-opioid dependent individuals.  The opioid addict, though, can take Buprenorphine for addiction and also have the added benefit of anxiety reduction and alleviation of pain.  The pain and anxiety relief is usually 6-12 hours.  For this reason, addicts with pain and/or anxiety obtain the best results with divided doses, most often two or three times a day.

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Though safer than Methadone, extreme care must be taken to securely and safely store any preparation of Buprenorphine away from children and pets.  Children and pets can die with accidental ingestions and are significantly less protected from the overdose safety referenced above for adults. Though Buprenorphine is much less likely to cause death in an adult overdose as explained above, the same property that makes it safer also makes it more challenging to start in a person who is addicted to opioids.  The next chapter will focus on this challenge.

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