Practical Considerations For The
Clinical Use of  Buprenorphine

 Buprenorphine  is a new and attractive medication option for many opioid-addicted adults and their physicians.  Before initiating buprenorphine treatment, providers must be aware of such critical factors as how the medication works, its efficacy and safety profile, how it is used in opioid withdrawal as well as manintenance treatment, and  how  patients  can  best be selected,
educated about buprenorphine, and monitored throughout treatment. This article reviews these important issues as well as requirements  for physician and staff training  and needs for additional research on this unique medication.

Hendree E. Jones, Ph.D.
John Hopkins University School of Medicine
Baltimore, Maryland

 Buprenorphine was approved by the U.S. Food and Drug Administration (FDA) in October 2002 as a Schedule III narcotic for use in treating opioid-dependent men and opioid-dependent women who are not pregnant. The new medication’s unique pharmacological characteristics provide for less respiratory depression or overdose risk than opioids such as morphine, heroin, methadone, and oxycodone, as well as milder manifestations of withdrawal upon cessation.

This wide safety margin makes buprenorphine suitable for use in new treatment settings, such as office practices, as well as more traditional opioid treatment programs. Further supporting this versatility, buprenorphine can be effective when taken every other day or less frequently, and it is supplied in a combined formulation with naloxone that is designed to reduce its potential for abuse.

The medication is therefore a welcome addition to a restricted treatment armamentarium, especially now that LAAM (levo-alpha-acetylmethadol hydrochloride), another widely used medication, is being discontinued by the manufacturer because of safety concerns (U.S. Food and Drug Administration, 2003). This article reviews buprenorphine’s pharmacology and clinical use, including appropriate dosing; patient selection, education, and monitoring; and physician and staff training; and it identifies important questions for research.

  Buprenorphine Effects   

Buprenorphine is chemically an opioid. Like other opioids, it produces most of its important effects by interacting with a structure on nerve cells called the mu opioid receptor.The special characteristics that distinguish buprenorphine from other opioids and make it useful for helping people overcome opioid addiction result from the unique ways it interacts with this receptor (e.g., Bickel and Amass, 1995; Jasinski, Pevnick, and Griffith, 1978;Martin et al., 1976):

Buprenorphine is a partial agonist at (i.e. stimulator of) the mu receptor. When the mu receptor is stimulated, it sets in motion a chain of nerve cell activities, that underlies most of the familiar opioid effects,for example, pain reduction, feelings of well-being or pleasure,and respiratory suppression. By stimulating the receptor only partially, buprenorphine yields those same effects, but with less intensity than heroin, morphine, or methadone, all of which stimulate the receptor fully (Johnson and Strain, 1999). Whereas those drugs can cause powerful euphoria, motivating continued abuse, buprenorphine provides a positive but moderate psychoactive effect that reduces craving and helps patients comply with their medication regimens (Jasinski, Pevnick, and Griffith, 1978; Walsh et al., 1994).

Buprenorphine has high affinity for the mu receptor. That is, buprenorphine binds tightly to mu receptors, more so than abused opioids and methadone do. Consequently, Consequently, if a patient takes an abused opioid on top of buprenorphine, the medication will block effects. Moreover, if buprenorphine is given to an individual who has already taken another opioid, it displaces the other opioid from the receptors.

 This effect necessitates care when a clinician initiates buprenorphine therapy; depending on the dosage of buprenorphine, the patient’s level of physical dependence, and when he or she last administered an abused opioid, the abrupt stripping of the other opioid from the mu receptor can precipitate withdrawal.

 Buprenorphine disassociates (detaches) from the mu opioid receptor slowly. This characteristic probably accounts for buprenorphine’s long duration of action in the treatment of opioid dependence.While buprenorphine’s manner of interacting with the mu receptor gives rise to its most important attributes and advantages in addiction treatment, the medication also has a significant action at a second receptor:

Buprenorphine is an antagonist (i.e., prevents stimulation) of the kappa opioid receptor (Cowan, Lewis and Macfarlane, 1977). Stimulation of the kappa opioid receptor plays a role in producing some of the major symptoms associated with opioid withdrawal, such as chronic depression. By attaching to the kappa receptor and slowing its activity, buprenorphine may induce positive mood and feelings of wellbeing (Rothman et al., 2000).

There are two formulations of buprenorphine for treating opioid dependence, a buprenorphine hydrochloride (HCl) tablet (Subutex) and a combination tablet (Suboxone) containing buprenorphine HCl plus naloxone HCl in a ratio of 4:1 (Fudala et al., 1998; Mendelson and Jones, 2003; Mendelson et al., 1996, 1997b, 1999; Preston, Bigelow, and Liebson, 1988). Both tablets produce similar clinical effects when administered sublingually (Stoller et al., 2001).

Suboxone was developed because buprenorphine alone has potential for abuse (e.g., Pickworth et al., 1993; Strain et al., 1997) and has been abused in other countries (O’Connor et al., 1988; Singh et al., 1992; Varescon et al., 2002). Unlike buprenorphine, naloxone is poorly absorbed and has little effect when taken sublingually (Chiang and Hawks, 2003; Preston, Bigelow, and Liebson, 1990); however, when injected by an opioid-addicted person, naloxone can precipitate an opioid withdrawal syndrome—a   strong  deterrent  to  diversion  of  Suboxone  and  its  abuse  by
injection (O’Brien et al., 1978).


Reference:  Science Practice Perspectives, Volume 2 No. 2
                      August 2004

Editor: Deborah Shrira                   Date:  September 2008