DDN December 2021 December 2021 | Page 6


In the first of a three-part series , Dr Georges Petitjean and Deanne Burch take a look at the history of buprenorphine prescribing


This article is the first in a series examining the past , present and future of buprenorphine in the treatment of opioid dependence . Buprenorphine is a medication used in opioid substitution treatment ( OST ), and it has also been used extensively for the management of pain . The surge of buprenorphine prescribing during the COVID-19 pandemic triggered a reflection of its journey , and with the recent introduction of long-acting

injectable buprenorphine we question what its future is within drug treatment services .
DEVELOPMENT In the USA , the Committee on Drug Addiction was created in the 1920s where it studied the morphine molecule , searching for medicines which would not cause addiction . It was hoped that they would find a medicine which could be used in the place of opium based medicines .
The search to find a nonaddictive analgesic began in
the 1920s following increasing concerns that opioid addiction was resulting from iatrogenic prescribing . The opioid agonist methadone was initially developed during World War II and it was prescribed minimally in the 1950s . Due to the lack of agreement on its safety and its inability to produce the desired effect without addiction , the search for opioid antagonists commenced .
The concept of ‘ substitution treatment ’ was first developed in response to the opium and morphine addiction epidemic in
The concept of ‘ substitution treatment ’ was first developed in response to the opium and morphine addiction epidemic in the USA .


Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa receptor :
μ-opioid receptor
Buprenorphine has a very high affinity , a low intrinsic activity , and a slow dissociation at the mu receptor .
It has unique and clinically desirable pharmacological properties : lower misuse
potential , milder withdrawal symptoms on dose reduction than methadone and a ceiling effect at higher doses ( meaning that an overdose of buprenorphine is less likely to cause fatal respiratory depression than an overdose of a full mu opioid agonist like methadone ).
Buprenorphine produces a doserelated blocking of drug ‘ high ’ from ‘ ontop ’ use of heroin , making it particularly appealing to well-motivated patients .
However , if taken too soon in opioiddependent patients , buprenorphine can displace heroin and other opioids from the receptors , yet not provide the equivalent degree of receptor activation , thereby leading to a rapid drop in opioid effect and the onset of opioid withdrawal symptoms (‘ precipitated withdrawal ’).
κ-opioid receptor
The high-affinity kappa receptor antagonism of buprenorphine is involved in reducing stress-induced drug-seeking behaviour . Also , kappa antagonism has demonstrated antidepressant properties .