IUPAC Name
(2S)-2-[(5R,6R,7R,14S)-17-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Buprenorphine (INN) is chemically 21-cyclopropyl-7-alpha-[(S)-1-hydroxy-1,2,2-trimethylpropyl]-6,14-endo-ethano-6,7,8,14-tetrahydrooripavine CAS 53152-21-9 for the hydrochloride; 52485-79-7 for the free base).
Previous review
In 1989, a decision of the United Nations Commission on Narcotic Drugs placed buprenorphine (INN) in Schedule III of the Convention on Psy- chotropic Substances (1971 Convention). The decision followed the recommendation of the Expert Committee on Drug Dependence at its twenty-fifth meeting (9). During its thirty-second meeting in 2000 (7), the Committee considered the question of the scheduling of buprenorphine and recommended critical review of the substance, taking into account a request by the INCB, as well as questions concerning the rationale for the control of this substance under the 1971 Convention rather than the 1961 Single Convention.
At its thirty-third meeting, the Committee commenced the critical review of the scheduling of buprenorphine on the basis of a review document pro- duced by the Secretariat (3). The Committee considered that buprenorphine met the requirements both for scheduling in the 1961 Convention and for its present scheduling in the 1971 Convention. However, taking any decision was hindered by a lack of authoritative guidance on the choice between the two possibilities. Therefore, the Expert Committee had to seek guidance for its decision from the Conventions, from the existing guidelines and from an appreciation of the impact of changes in the scheduling on public health.
New information since 2002
A document provided by the Secretariat for the thirty-fourth meeting of the Committee indicated an expansion in the therapeutic role of buprenorphine. Buprenorphine (and other medicines used in agonist pharmacotherapy of opioid dependence, such as methadone) is recognized as an efficacious and cost-effective treatment for opioid dependence. Buprenorphine maintenance treatment programmes provide opportunities for human immunodeficiency virus (HIV)/AIDS prevention among opioid-dependent injecting drug users and also support the implementation of directly observed antiretro- viral therapy (ART) for people with opioid dependence who also have HIV/ AIDS. Buprenorphine maintenance treatment programmes can also act as a platform for promoting adherence to medical treatment of opportunistic infections. Buprenorphine maintenance treatment was stated to be available in about 30 countries. In March 2005, WHO included buprenorphine in the 14th WHO Model List of Essential Medicines for use in opioid agonist therapy of opioid dependence (10).
Data were presented to the Committee demonstrating unique pharmaco- logical actions of buprenorphine, which distinguish it from other opioids controlled under the Single Convention. Specifically, buprenorphine is also an agonist at the ORL-1 receptor in the brain, which affects its µ-opioid actions. These new findings suggest that buprenorphine has a unique spec- trum of pharmacological actions.
There have been reports of diversion, seizures and abuse of buprenor- phine in various countries. It was reported that in many instances buprenorphine was being illegally used for alleviating symptoms of opioid withdrawal.
Additional considerations
Additional documents presented to the Committee at its thirty-fourth meet- ing dealt primarily with the possible effects of rescheduling buprenorphine from the 1971 Convention to the 1961 Convention.
The Committee was informed that this question had been discussed during the 115th meeting of the WHO Executive Board. It was indicated during the discussion that the transfer of substances from one convention to the other would result in problems with implementation of the conventions in national laws. A concern was expressed that transfer could consequently give rise to rescheduling at the national level, which would have the unintended effect of restricting access to buprenorphine for use in opioid agonist therapy. Of the 56 countries that responded to the WHO questionnaire, 14 stated that such a rescheduling would result in impeded access to treatment.
The documents presented to the meeting also discussed the legal considerations relating to the transfer of substances between conventions. Taking into account the text of the Single Convention on narcotic drugs and the United Nations Convention on psychotropic substances as well as official commentaries to both Conventions and information included in WHO guidelines for the review of dependence-producing psycho- active substances for international control, it is advisable that a substance should not be under more then one Convention. The WHO guidelines give guidance for the scheduling of new drugs, not yet scheduled, and on the choice between the Conventions for those drugs. They also give guidance for the scheduling of drugs already in the 1988 Convention. However, the guidelines do not give guidance on the transfer of a substance from the 1961 to the 1971 Convention or vice versa. A transfer of a substance from one Convention to the other would demand that the United Nations Commission on Narcotic Drugs take a simultaneous decision on deletion of a substance from one Convention and adding it to the appropriate schedule of another Convention. A procedure for making a deletion from the schedules of the 1971 Convention is included in article 2 para. 6 of the Convention and requires a new assessment by WHO. A similar provision is included in the 1961 Convention article 3 para. 6(b). No provision is included, however, to indicate that these decisions are to be taken simultaneously.
Discussion
In the course of the meeting, members of the Committee expressed their views concerning various aspects of the current scheduling status of buprenorphine and the possible consequences, including legal aspects, of its rescheduling. It became evident that there were divergent views on the legal situation related to the transfer of substances between Conventions. The majority of the members considered however that the Expert Commit- tee on Drug Dependence is not properly constituted to discuss legal issues related to international treaties.
Recommendation
Following review of the documents presented at the present meeting, which expanded the information made available at its thirty-third meeting, the Committee considered the unique pharmacological actions of buprenor- phine, and its expanded role in the treatment of opioid dependence. This pharmacological treatment of opioid dependence also contributes to the efficient prevention and treatment of HIV/AIDS among opioid-dependent injecting drug users. Hence, the Committee did not recommend any change in the present scheduling of the substance in Schedule III of the 1971 Convention.
Buprenorphine (INN) is chemically 21-cyclopropyl-7-alpha-[(S)-1-hydroxy-1,2,2-trimethylpropyl]-6,14-endo-ethano-6,7,8,14-tetrahydrooripavine CAS 53152-21-9 for the hydrochloride; 52485-79-7 for the free base).
Previous review
In 1989, a decision of the United Nations Commission on Narcotic Drugs placed buprenorphine (INN) in Schedule III of the Convention on Psy- chotropic Substances (1971 Convention). The decision followed the recommendation of the Expert Committee on Drug Dependence at its twenty-fifth meeting (9). During its thirty-second meeting in 2000 (7), the Committee considered the question of the scheduling of buprenorphine and recommended critical review of the substance, taking into account a request by the INCB, as well as questions concerning the rationale for the control of this substance under the 1971 Convention rather than the 1961 Single Convention.
At its thirty-third meeting, the Committee commenced the critical review of the scheduling of buprenorphine on the basis of a review document pro- duced by the Secretariat (3). The Committee considered that buprenorphine met the requirements both for scheduling in the 1961 Convention and for its present scheduling in the 1971 Convention. However, taking any decision was hindered by a lack of authoritative guidance on the choice between the two possibilities. Therefore, the Expert Committee had to seek guidance for its decision from the Conventions, from the existing guidelines and from an appreciation of the impact of changes in the scheduling on public health.
New information since 2002
A document provided by the Secretariat for the thirty-fourth meeting of the Committee indicated an expansion in the therapeutic role of buprenorphine. Buprenorphine (and other medicines used in agonist pharmacotherapy of opioid dependence, such as methadone) is recognized as an efficacious and cost-effective treatment for opioid dependence. Buprenorphine maintenance treatment programmes provide opportunities for human immunodeficiency virus (HIV)/AIDS prevention among opioid-dependent injecting drug users and also support the implementation of directly observed antiretro- viral therapy (ART) for people with opioid dependence who also have HIV/ AIDS. Buprenorphine maintenance treatment programmes can also act as a platform for promoting adherence to medical treatment of opportunistic infections. Buprenorphine maintenance treatment was stated to be available in about 30 countries. In March 2005, WHO included buprenorphine in the 14th WHO Model List of Essential Medicines for use in opioid agonist therapy of opioid dependence (10).
Data were presented to the Committee demonstrating unique pharmaco- logical actions of buprenorphine, which distinguish it from other opioids controlled under the Single Convention. Specifically, buprenorphine is also an agonist at the ORL-1 receptor in the brain, which affects its µ-opioid actions. These new findings suggest that buprenorphine has a unique spec- trum of pharmacological actions.
There have been reports of diversion, seizures and abuse of buprenor- phine in various countries. It was reported that in many instances buprenorphine was being illegally used for alleviating symptoms of opioid withdrawal.
Additional considerations
Additional documents presented to the Committee at its thirty-fourth meet- ing dealt primarily with the possible effects of rescheduling buprenorphine from the 1971 Convention to the 1961 Convention.
The Committee was informed that this question had been discussed during the 115th meeting of the WHO Executive Board. It was indicated during the discussion that the transfer of substances from one convention to the other would result in problems with implementation of the conventions in national laws. A concern was expressed that transfer could consequently give rise to rescheduling at the national level, which would have the unintended effect of restricting access to buprenorphine for use in opioid agonist therapy. Of the 56 countries that responded to the WHO questionnaire, 14 stated that such a rescheduling would result in impeded access to treatment.
The documents presented to the meeting also discussed the legal considerations relating to the transfer of substances between conventions. Taking into account the text of the Single Convention on narcotic drugs and the United Nations Convention on psychotropic substances as well as official commentaries to both Conventions and information included in WHO guidelines for the review of dependence-producing psycho- active substances for international control, it is advisable that a substance should not be under more then one Convention. The WHO guidelines give guidance for the scheduling of new drugs, not yet scheduled, and on the choice between the Conventions for those drugs. They also give guidance for the scheduling of drugs already in the 1988 Convention. However, the guidelines do not give guidance on the transfer of a substance from the 1961 to the 1971 Convention or vice versa. A transfer of a substance from one Convention to the other would demand that the United Nations Commission on Narcotic Drugs take a simultaneous decision on deletion of a substance from one Convention and adding it to the appropriate schedule of another Convention. A procedure for making a deletion from the schedules of the 1971 Convention is included in article 2 para. 6 of the Convention and requires a new assessment by WHO. A similar provision is included in the 1961 Convention article 3 para. 6(b). No provision is included, however, to indicate that these decisions are to be taken simultaneously.
Discussion
In the course of the meeting, members of the Committee expressed their views concerning various aspects of the current scheduling status of buprenorphine and the possible consequences, including legal aspects, of its rescheduling. It became evident that there were divergent views on the legal situation related to the transfer of substances between Conventions. The majority of the members considered however that the Expert Commit- tee on Drug Dependence is not properly constituted to discuss legal issues related to international treaties.
Recommendation
Following review of the documents presented at the present meeting, which expanded the information made available at its thirty-third meeting, the Committee considered the unique pharmacological actions of buprenor- phine, and its expanded role in the treatment of opioid dependence. This pharmacological treatment of opioid dependence also contributes to the efficient prevention and treatment of HIV/AIDS among opioid-dependent injecting drug users. Hence, the Committee did not recommend any change in the present scheduling of the substance in Schedule III of the 1971 Convention.
ECDD Recommendation
No change in scheduling
Link to full TRS
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