Introduction: legislation and pharmacological action

Figure 1 Effects of buprenorphine, heroin and naloxone on the mu opioid receptor

Figure 1

NB: The mu receptor is one of the primary sites for the reward effects of opiate drugs in the brain. The opiate binds to the affinity zone of the receptor and stimulates the activity zone, thereby producing an effect. In the diagram, heroin, buprenorphine and naloxone are represented by blue polygons, and the receptors by yellow polygons. The stimulatory effect of each chemical is related to how it interacts with the affinity zone (represented here as filling a proportion of the affinity zone). Heroin, classified as a full receptor agonist (stimulator), almost fills the activity zone while buprenorphine, a partial receptor agonist, fills a smaller proportion of it and naloxone does not stimulate the receptor at all. The substances also differ in how strongly they bind to the receptors. A substance that binds more strongly to the receptor can displace a substance that binds less strongly. Thus, buprenorphine can displace both naloxone and heroin, and naloxone can displace heroin.

Source: Adapted from Jones, H. E. (2004), 'Practical considerations for the clinical use of buprenorphine', Science & Practice Perspectives 2, no. 2, pp. 4-20.

Buprenorphine is classified under Schedule III of the United Nations Convention of Psychotropic Substances of 1971, requiring all countries to place it under control. By comparison, methadone is classified under Schedule I of the 1961 Convention, which places more restrictive measures on its control, distribution and use.

Buprenorphine is a derivate of the morphine alkaloid thebaine and, in contrast to methadone, which is a full opiate agonist, it is a mixed agonist/antagonist. This means that buprenorphine only partially activates the opiate receptors within the nervous system, producing a milder effect with both less euphoria and less sedation (Ridge et al., 2004).

Buprenorphine is often described as a partial agonist (receptor stimulator)/antagonist (prevents receptor stimulation) (Jones, 2004) (Figure 1) because it has important actions on two types of opiate receptors in the brain. Many of the most common opioid effects, such as euphoria, respiratory effects and reduced pain sensation, are caused by stimulation of the mu receptor. Buprenorphine produces these effects because it stimulates the mu receptor, albeit at lower intensity than other opiates such as heroin or methadone. Additionally, however, as buprenorphine binds more strongly to the receptor than these drugs, it can displace them. As a result, an individual who takes buprenorphine while dependent on another opioid risks the development of withdrawal symptoms due to a reduction in stimulation of the receptor. In addition, disassociation of buprenorphine from the receptor is slow, accounting for the drug’s long duration of action, one of the factors that makes it a versatile treatment option.

Buprenorphine is also an antagonist of another receptor associated with opioid effects. The kappa opioid receptor is associated with some of the negative effects experienced in withdrawal, particularly depression. As buprenorphine inhibits stimulation of this receptor it may produce feelings of well-being.

Studies have shown that buprenorphine can be effective for the treatment of opiate dependence. In addition, it has been argued that the pharmacology of buprenorphine provides a number of benefits: its mixed opioid stimulating/blocking action makes it a relatively safer option in terms of the risk of overdose; its properties make it a less attractive drug to the illicit user and it may therefore be less likely than other opiates to be diverted onto the illicit market; cessation of the drug is associated with milder levels of withdrawal distress; and the long duration of its action permits more flexible dispensing options. Taken together, these factors may make buprenorphine a versatile therapeutic agent and provide clinicians with an important additional prescribing option, although questions about which client groups are best treated with buprenorphine and which clients may be better suited to a different treatment option remain unanswered. In particular, it has been suggested that the pharmacological action of buprenorphine may make it less attractive to some client groups and that other benefits have to be weighed carefully against the cost of the drug.