Part two Deuxième partie Segunda parte st that order)—together accounted for 99 percent(onaverage) of thetotalmanufacturethese facture offivesubstances—phenobarbital, pentobarbital, butalbital,barbitalandamobarbital(in in2012. tion ofbothcategoriesbenzodiazepines stood at27 billion S-DDD calculated consump showing agradualdecreaseover thepastthreeyears.Thecombinedtotal Total calculatedconsumptionofbenzodiazepines followed theoveralltrendinglobalmanufacture, S-DDD. Italycontinuedtobetheleadingmanufacturerofbothgroups of benzodiazepines in 2012. diazepam remained, in thatorder, the mostmanufactured psychotropic substances in termsof not provideitsdataonmanufactureofbenzodiazepines for 2012totheBoard.Alprazolamand in 2012.Thisdecrease may beattributedtothefactthatonemajormanufacturingcountrydid totalreported manufactureofbothgroupsbenzodiazepines decreased type sedative-hypnotics; anxiolyticsand 15Governmentsreported manufacture ofbenzodiazepine- benzodiazepine-type benzodiazepines are listed inScheduleIV. In2012,19Governmentsreportedmanufactureof only benzodiazepineofthe1971Convention, whiletherestof is listedinScheduleIII that isthe Flunitrazepam,asedative-hypnotic, as ananti-epileptic. benzodiazepine isusedmainly that andthe inductionofgeneralanaesthesia.Clonazepamistheonly practice forpre-medication and are usedinmedical classified asanxiolytics,and 12 areclassifiedassedative-hypnotics reported imports ofbuprenorphine. France,and Spain(indescending Switzerland,Italy order). Asinpreviousyears,over60countries The United States remained the leading user ofbuprenorphine in 2012,followed by Germany, substance hasalsocontinuedtogrow.2012. Globalcalculatedconsumptionofthe in S-DDD) lion opioid addicts. Globalmanufactureofbuprenorphine attained anewrecordofover7tons(919 increasingly usedsincethelate1990sintreatmentofpainand in substitutiontreatment for in 2012absoluteterms,aswelltermsofpercapitaconsumption. States duringtheyear.United of amphetamines States remainedthelargestconsumer TheUnited due mainlytoasignificantincreaseinthemanufactureofamfetamineand dexamfetamine inthe in2012.This developmentis (3.4 billiondefineddailydoses for statisticalpurposes (S-DDD)), Schedule II of the 1971 Convention, increased further and attained a new record, of over 50 tons Netherlands, Brazil, Sweden, Israel, SouthAfrica and Australia. methylphenidate in 2012 were, in descending order, Canada, Germany, Spain, Switzerland, the the leading userofmethylphenidatein2012.OutsidetheUnitedStates,main users of facturer, accountingforalmost97percentofthetotaloutput.TheUnitedStatesalsoremained nidate hasincreasedinrecentyears,theUnitedStatesofAmericaremainedleadingmanu- of over 63 tons, in 2012. Although the number of countries reporting manufacture of methylphe ity disorder (ADHD) continuedtoincrease worldwide. Global manufacture reached a newrecord, substances hasdeclinedinrecentyears. schedules. The isolated use of somesubstances in Schedule I forthemanufactureofother scientific researchand, in certaincases, for themanufactureofpsychotropic substances in other on thequalityofdata provided. stances isbaseddata on statisticalfurnishedbyGovernments.Thequalityoftheanalysisdepends The analysis contained in thepresent section ofthetechnicalpublication on psychotropic sub Summary atistics Of the 12 barbiturates listed inSchedules II, IIIand IV ofthe 1971Convention,themanu- A totalof35benzodiazepines are currently under international control.Ofthose,22are of the1971Convention,hasbeen Buprenorphine, anopioidanalgesiclistedinScheduleIII Manufacture of amphetamines, which are the other central nervous system stimulantsin hyperactiv- Manufacture ofmethylphenidateand itsuse for thetreatmentofattention-deficit Use ofsubstancesincludedinScheduleIthe1971Conventionshouldbelimitedto

on comments P sychotropic

on

the S ubstances

reported

mil- - - -

33

English barbiturates during the period 2008-2012. Phenobarbital remained the most widely manufactured barbiturate in 2012, accounting for 79 per cent of total manufacture of all 12 barbiturates. China continued to be the leading manufacturer. Other leading manufacturers in 2012 were Hungary, the United States, Denmark and Germany (in descending order). International trade in most barbiturates has been declining during the past five years.

The 14 central nervous system stimulants listed in Schedule IV of the 1971 Convention are used mainly as anorectics or for the treatment of ADHD. Total reported manufacture of this group of substances has been on the rise during the period 2003-2012, and attained 2.6 billion S-DDD in 2012, the United States accounting for over half of the global total, followed by Germany and Italy. The United States remained the leading user of this group of substances, accounting for 74 per cent of global calculated consumption in 2012. Calculated consumption of stimulants in Schedule IV in the Americas remained the highest in the world. In 2012, the highest consumption rates, expressed in S-DDD per 1,000 inhabitants per day, were reported by the United States, followed by Chile and Brazil. Phentermine continues to be the most used substance in this group, accounting for 83 per cent of calculated consumption.

Substances for which global manufacture or international trade in recent years amounted to less than 1 kg are not mentioned separately in the analysis below; however, the data on those substances are included in the relevant group totals, as applicable.

34 since 2008, stood sinceat 2008, stood 59 grams at endthe of 2012. stocks2007. Global of DMA, have which depleted been demandthe for photographic film, and stopped entirely in DMA to started decline in2002,owing to in adecrease dye, in amounts of tons several year. per Manufacture of sively for manufacture inthe use of anon-controlled film was manufactured United inthe States of exclu America, - However, until 2002,2,5-dimethoxyamphetamine (DMA) manufacture of non-psychotropic substances or products. ­psy 2. paragraphs. limited, with exceptions the noted following inthe substancesas well in,those as trade have extremely been In line with restriction, this manufacture and stocks of, system stimulants limited or with use. very no medical Iarein Schedule hallucinogens and/or central nervous This restriction resultsfrom that the fact all substances control of or specifically approved Governments.their by or by purposes dulymedical authorized persons inmedical Convention,the except for limited scientific and very prohibited,be pursuant to provisions the of article7ofwenty-eight substances are listed Iof inSchedule 1971 Convention.the The those use substancesof should 1.

chotropic substances Iby inSchedule for industry the ­s Th T cientific establishmentsthat are directlythe under e 1971 Convention not does foresee of use the Substances inSchedule I of the1971Convention ingredient that is not under international control. There manufacturethe of tamsulosin, an active pharmaceutical PMA, with quantities ranging from 24to for 71kg, in use past Denmark decade, reported intermittent manufacture of Methoxy-alpha for manufacture the of non-psychotropic substances is para delta (THC) listed Iare inSchedule manufacture inthe used of States. In that country, isomers of tetrahydrocannabinol included inother schedules was reported only by United the Iforule manufacture the of psychotropic substances that are 4. and Unitedthe States manufactured57.5 kg 16 grams. and United the States. In 2012,Denmark manufactured ­co 3. the vastthe majority of which were held in Unitedthe States. end of stocks of 2012,global such isomers at stood 150kg, THC manufactured United inthe States wasAt 60kg. the and 53kgin2010.In total 2012,the amount of isomers of THC listed Ifluctuated inSchedule between 327kgin2005 reported manufacture United inthe States of isomers of manufactured United inthe States. past the decade, During nol is main the substance among isomers the I inSchedule substance listed in II. Schedule

ntinues limited to be manufacture of PMAinDenmark A U -9-tetrahydrocannabinol (delta nother substance Ithat inSchedule by is used se ofse psychotropic the substances included- in Sched -methylphenethylamine the (PMA).During Delta -9-THC), a psychotropic -8-Tetrahydrocannabi- ­ in dustry dustry 35 -

English Substances in Schedule II of the 1971 Convention

5. Listed in Schedule II are 17 substances that have little 8. In 2012, as a result of a significant increase in the to moderate therapeutic usefulness and whose liability to manufacture of amfetamine and dexamfetamine in the abuse constitutes a substantial risk to public health. The United States, the quantity of amphetamines listed in substances belong to the following groups: central nervous Schedule II that was manufactured worldwide rose to a system stimulants, anti-emetics, hallucinogens, sedative- record amount of 50.5 tons (3.4 billion S-DDD) (see fig- hypnotics, antitussives and antidepressants. In addition to ure 2). In 2012, amfetamine comprised 45 per cent and their various applications in human and veterinary medi- cine, some of these substances are used in industry for the manufacture of other psychotropic substances or for Figure 1. Stimulants in Schedule II: total reported ­conversion into non-psychotropic substances. manufacture, by substance, 2003-2012

Millions of S-DDD 5 500 Central nervous system stimulants 5 000 4 500 6. Total manufacture of central nervous system stimu- 4 000 lants in Schedule II fluctuated in the period 2003-2012, as 3 500 can be seen in figure 1. After decreasing for two consecu- 3 000 tive years (2009 and 2010), total reported manufacture of 2 500 this group of substances picked up again, first slightly in 2 000 2011 and then further in 2012, amounting to 5.5 billion S-DDD. This increase is mainly due to a significant increase 1 500 in manufacture of amfetamine, dexamfetamine and methyl­ 1 000 1 phenidate in the United States in 2012. That country 500 accounted for 90 per cent of total output of stimulants in 0 Schedule II during that year. In 2012, methylphenidate’s 2012201120102009200820072006200520042003 share of total output of stimulants in Schedule II was 38 Amfetamine Dexamfetamine Year per cent. Amfetamine and dexamfetamine accounted for Levamfetamine Levomethamphetamine Metamfetamine Metamfetamine Methylphenidate 28 and 27 per cent, respectively, of total output. Together racemate with methylphenidate, these substances accounted for 93 per cent of total combined output in 2012. Figure 2. Amphetamines: total reported manufacture, Amphetamines selected countries, 2003-2012 Tons 7. Both optical isomers of amfetamine (levamfetamine 60 and dexamfetamine) and their racemic mixture (amfeta- 55 mine), as well as both optical isomers of metamfetamine 50 (levomethamphetamine and metamfetamine) and their 45 racemic mixture (metamfetamine racemate), are listed in 40 Schedule II. Statistical reports on amfetamine, dexamfeta- 35 mine and metamfetamine have been received by the Inter- 30 national Narcotics Control Board from Governments since the 1970s. Statistics for levamfetamine and levometham- 25 phetamine have been available since 1986 and statistics for 20 metamfetamine racemate have been available since 1988, 15 reflecting the different dates on which those substances 10 were brought under international control in the context of 5 the 1971 Convention. 0 2012201120102009200820072006200520042003 Year 1 Of the other stimulants in Schedule II (4-bromo-2,5-dimethoxy- France Germany phenethylamine, fenetylline, methylphenidate, phencyclidine and phen- Hungary Switzerland metrazine) only methylphenidate is manufactured and used in signifi- United States Others cant quantities.

36 hexedrine) and antiparkinsonian (selegiline). drugs (benzfetamine, clobenzorex, fenproporex and levopropyl- mainly converted been into substances as anorectics used tured United inthe States. In addition, amphetamines have In 2012,about 11tons of lisdexamfetamine were manufac - dexamfetamine, treatment inthe is which used of ADHD. lisdexamfetamine (l-lysine-d-amfetamine), aprodrug of United States, amfetamine synthesis inthe used of is also into other amphetamines included inthat Schedule. In the IIarein Schedule for inindustry widely used conversion Convention. In France and United the States, amphetamines substance; and substances not controlled under 1971 the including which are those optical isomers of original the intodivided two groups: other psychotropic substances, substances manufactured from amphetamines may be manufacturethe of other substances figure (see 3).new The mphetamines inII Schedule of 1971 the Convention are frequently products as intermediary in industry used for 9. substances intermediate as Use ­co cent and Hungary for most of remainder. the France ufacture of amphetamines, France accounting for 12per States accounting for nearly cent 85 per of totalthe man- represented 6and cent, 3per respectively, with United the amines, metamfetamine while racemate and levamfetamine dexamfetamine cent 43per of total the output of amphet- amfetamine. 2012, where substance the for was used reconversion into narcolepsy

obesity or Levamfetamine ntinued manufacturer sole the to be of levamfetamine in (Has nouse) ADD A (Mixture ofdexamfetamineand

Direct medical use Amfetamine racemate Figure 3. levamfetamine)

1-Phenyl-2-propanone lisdexamfetamine or fenproporex Dexamfetamine Clobenzorex (P-2-P) Manufacture Amphetamines:

ADD Direct medical use Metamfetamine or fenproporex Benzfetamine (Mixture ofmetamfetamineand Norephedrine Manufacture Metamfetamine racemate use inindustry levomethamphetamine) benzfetamine Selegiline or Levomethamphetamine

Manufacture Ove

inhalant counter counter nasal nasal use medical Direct r-the- r-the-

in S-DDD 1,000inhabitants per day, per on basis the of statistics provided for 2012 one, table III, of presentthe publication. three of presentthe publication. tropic substances is explained explanatory inthe note to table IVinpart psychotropic substances. Denmark Finland Chile andmedical industrial byfurnished Governments) consumption and calculated 11. destined for export. amphetamines the as almost all manufactured there are of limited use amphetamines medical very inthat country, amajor been ally manufacturer of amphetamines, there is notably Australia and Canada.While France has tradition- and dexamfetamine in other countries, occurred has also 1990s.Asignificantthe increasethe in use of amfetamine mine United inthe States has increased significantly since countries, of use amfetamine medical the and dexamfeta- have relatively purposes direct medical been inmost small countries. While quantities the of amphetamines for used sity considerably has been reduced or discontinued inmost amphetaminesor purposes, direct medical are used extensive of use amphetamines for treatment the of- obe mainly for treatment the of ADHD and narcolepsy. The 10. use medical Direct Austria Germany Kingdom United Sweden Iceland Island Christmas Netherlands Canada Australia States United Country orterritory 2012. tables 1and 2respectively, inorder of rate their of in use

4 3 2 e list of calculations S-DDD in these is presented used inpart for used e method levels calculating of consumption of psycho- xcluding for use manufacture the of other amphetamines and non-

Th Th E Table 1. Th F

e countries with highest the levels of reported (i.e. selected countries and territories, 2010-2012

Amphetamines: 2 uses of uses amphetamines, calculated reported consumption rate, S-DDD per 1,000 inhabitants per day inhabitants per 1,000 S-DDD 15.74 2010 – – – – – 0.02 0.04 0.06 0.08 2.84 0.02 0.29

3 and expressed 4 18.67 are listed in 2011 – – – – – 0.01 0.13 0.07 0.16 0.31 0.51 0.22

11.36 0.09 0.11 0.37 0.01 0.03 0.03 0.41 0.43 0.43 0.66 1.06 1.50 2012 37

English Table 2. Amphetamines: calculated consumption rate, 14. Global reported manufacture of metamfetamine, selected countries and territories, 2012 which amounted to 9.5 tons in 1999, has decreased since that year. The decline has been even more pronounced since (S-DDD per 1,000 inhabitants per day) 2008, after France and Switzerland ceased manufacturing Country or territory 2012 the substance, with total output reaching less than 3 kg in Switzerland 6.09 2010 and 2011. In 2012, global manufacture rose again and Cayman Islands 2.30 stood at 270 kg, almost all of which was manufactured in Czech Republic 1.55 the United States (mainly for industrial purposes). Most Italy 0.46 other countries, which use metamfetamine for medical pur- Norway 0.46 poses, cover their needs through imports. The main France 0.27 importer of metamfetamine in 2012 was Spain (1.4 kg). New Zealand 0.19 Israel 0.11 15. During the period 2003-2012, total reported manu- Belgium 0.07 facture of levomethamphetamine fluctuated between no output (in 2009 and 2010) and 4.6 tons (in 2002). The Czech Republic, France, Germany and the United States have traditionally been the main manufacturers of Comments on amphetamines, by substance ­levomethamphetamine. In 2012, total output was about 1.1 tons, with the United States accounting for 980 kg and 12. The manufacture of amfetamine gradually increased the Czech Republic for 89 kg. In recent years, on average until it reached a peak of 30 tons in 1998, before falling about 470 kg of levomethamphetamine have been used gradually to 4.3 tons in 2010. In 2011, global manufacture annually in the United States for the manufacture of nasal of amfetamine started to rise again, reaching 23 tons in inhalants for domestic use, which are exempted in that 2012, with the United States and France accounting for 88 country from certain control measures in accordance with and 11.7 per cent, respectively. Amfetamine is used mainly article 3 of the 1971 Convention. In 2012, 797 kg of in combination with dexamfetamine in the United States. ­levomethamphetamine were used for that purpose. In 2012, around 2.4 tons of amfetamine were required for such use in the United States, which held about 83 per cent 16. A total of 2.8 tons of metamfetamine racemate was of global stocks of amfetamine in 2012 (9.7 tons). The manufactured in 2012. During the period 2008-2012, United States and France, in that order, remained the main France and Hungary accounted on average for 63 and 37 exporters of the substance. Total exports of amfetamine in per cent of global output, respectively. While in Hungary 2012 amounted to 460 kg, the main importers of which the substance is mainly used in the manufacture of non- were, in descending order, Canada (132 kg), Sweden psychotropic substances, the output by other countries has (14.8 kg) and Switzerland (8.5 kg). mainly been exported to the United States, where it has either been converted into non-controlled substances or 13. The trends in the manufacture of dexamfetamine separated into levomethamphetamine and metamfetamine. reflect developments in the United States. During the 1980s, Global stocks of metamfetamine racemate in 2012 stood at total output was fairly stable, at approximately 350 kg annu- 2.5 tons. International trade in the substance averaged ally. It subsequently increased, although with many fluctu- 1.4 tons during the period 2010-2012, with the United ations, to reach a record level of 11 tons in 2009 and then States accounting for all imports. Levomethamphetamine decreased sharply to less than 5 tons in 2010 and 2011. In has been used mainly for export and has also been 2012, manufacture of dexamfetamine in the United States ­converted, in smaller quantities, into selegiline. Metamfet- increased to a new record level of 21.4 tons. Stocks of dex- amine obtained during the process of separating it from amfetamine held in the United States amounted to 9.6 tons levomethamphetamine has been added to stocks. in 2012. The United States remained the main user of dex- amfetamine for medical purposes, reporting co­ nsumption Methylphenidate of 10.5 tons for 2012. Such use was also reported by a num- ber of other countries, including A­ ustralia (176 kg), C­ anada 17. The use of methylphenidate for medical purposes (155 kg) and the Netherlands (60 kg). Global exports were increased significantly in the 1990s. Methylphenidate is used 813 kg in 2012, of which France accounted for 670 kg and for the treatment of ADHD, primarily in children. the United States for 91 kg. About 25 countries reported It is also prescribed for the treatment of narcolepsy. The imports of dexamfetamine in 2012. Germany became the increase in the manufacture and use of methylphenidate is leading importer in that year, accounting for 41 per cent of mainly the result of developments in the United States, the global total, followed by Canada, Australia and the where the substance is frequently prescribed for the treat- Netherlands, in descending order, which together accounted ment of ADHD and also heavily advertised, including for another 50 per cent of the total. directly to potential consumers. Since 2000, however, the use

38 79 per cent of stocks at global endthe of 2012. 79 per tons in2012.The United States accounted for almost 70 inmanufacture,with rise the increasing to more than stocksGlobal of methylphenidate have increased intandem fromexports that have country increased inrecent years. Unitedthe States continued domestically, used to be although manufacture. Most of methylphenidate the manufactured in bined output accounted for less cent than 4per of global 2012 were Canada(1.2tons) and Spain (1ton); com their - facture of amounts of methylphenidate exceeding 1ton in in 2012to some The 6kg. countriesother manureporting - put of 3 tons of substance,the but that level dropped again again second the largest became manufacturer, with an out- amounted to only afew grams. In United 2011,the however, manufacture of substance the inthat country ­s ­K of output global for that year. Until 2009, Unitedthe level of 61tons represents in2012,which cent almost 97per 1995 and gradually increasing then to itarecord further increasing its output from 1.8tons in1990to 10tons in States leading the manufacturer has been of figureever reported (see 4). thetheSince 1990s, United ing arecord level of 63.2tons highest in2012,the amount rapidly 1990s,although inthe with some fluctuations, reach- 18. arations containing methylphenidate in some countries. concerns have about raised been increasing misuse of prep- rising sharplybeen inmany other countries. In recent years, of methylphenidate for treatment the of ADHD has also econd largest manufacturer of methylphenidate. In 2010, ingdom of Great Britain and Northern Ireland was the 50 55 60 65 10 15 20 25 30 35 40 45 Tons

0 5 Figure 4. G lobal manufacturelobal of methylphenidate to started rise ntdKndmUnitedStates United Kingdom Canada

Methylphenidate: selected countries, 2003-2012 Switzerland total reported manufacture, ­ m ethylphenidate, Others ­ K 2012201120102009200820072006200520042003 ingdom Year South Africa and Australia. South Africa Switzerland, Netherlands, the Brazil, Sweden, Israel, United States were, inthat order, Canada,Germany, Spain, The main users of methylphenidate in2012 from apart the S-DDD in2011to 946million S-DDD in2012. 1.2 billion lated consumption of methylphenidate from decreased tion of methylphenidate in2012.In that country,- calcu accounted for cent 64per consump of global calculated - of methylphenidate for treatment the of ADHD and United States, has which leading traditionallythe user been isdecrease mainly attributable to developments inthe (1.5billion S-DDD) figure in2012(see 5).This 44.2 tons 52.3 tons (1.8 billion S-DDD) in 2011,but dropping to date has followed an upward trend since 2007,reaching 20. phenidate in amounts exceeding 10 kg. ­46 domestic consumption growing. has been In 2012, countries and territories importing methylphenidate for Unitedthe Kingdom, Spain and Germany. The number of countries in 2012 were, in descending order, Switzerland, cent37 per of major total in 2012. Other exports United States leading the exporter, has been accounting for of methylphenidate until 2006.Since 2007, however, the from 980kgto 25tons. Switzerland was main the exporter in methylphenidate 1993-2012 increased during period the continue metto mainly be by imports. International trade ­r has spread other to countries, several medical the 19. approximate global consumption in a given year, expressed in S-DDD. in expressed year, agiven in consumption global approximate

equirements for methylphenidate outside United the States 1 200 1 000 1 400 1 600 1 800 Millions ofS-DDD 200 400 600 800

a ­co tistical data submitted by Governments are used to calculate the the calculate to used are Governments by submitted data tistical St 0 Figure 5. Th D a untries and territories reported imports of methyl- espite that fact the manufacture of methylphenidate e calculated global consumption global e calculated of methylpheni- United States The Netherlands Canada

Methylphenidate: by

countries, United Kingdom Germany Others a 2003-2012 calculated consumption, ­exp 2012201120102009200820072006200520042003 orting Year 39

English 21. The countries and territories with the highest levels Anti-emetics of reported (i.e. furnished by Governments) and calculated consumption of methylphenidate (calculated on the basis of statistics provided for 2011 and 2012) are listed in tables delta-9-Tetrahydrocannabinol and its stereochemical 3 and 4, respectively, in order of their level of consump- variants tion in 2012. 22. During the period 2008-2012, global manufacture of Table 3. Methylphenidate: reported consumption rate, delta-9-THC gradually decreased from 233 kg (7.8 million 2010-2012 S-DDD) in 2008 to 54 kg (1.8 million S-DDD) in 2012, led by a decrease in manufacture by the United States, the S-DDD per 1,000 inhabitants per day largest manufacturer of the substance worldwide. In 2012, Country or territory 2010 2011 2012 the United States manufactured 49 kg of delta-9-THC, the majority of which was for domestic consumption. Ger- Iceland 4.72 14.07 14.80 United States 15.50 19.93 7.94 many remained the second largest manufacturer in 2012, Sweden 4.92 6.22 7.19 reporting 4.5 kg of manufacture. Stocks held in the United Netherlands – 6.63 6.69 States amounted to 965 kg, accounting for 85 per cent of Denmark 5.09 5.88 6.37 the global total (1,338 kg) at the end of 2012, followed by Canada – – 5.51 Austria (12 per cent of global stocks) and Germany (2 per Luxembourg 3.23 0.002 3.59 cent). Norfolk Island – 0.96 2.37 Australia – – 2.33 23. International trade in delta-9-THC grew slightly to 48 Germany 1.98 1.97 2.08 kg in 2012. Germany remained the largest exporter, with Chile 1.10 1.54 1.70 the United States and Austria being the main importers. Finland – – 1.47 The United States, Germany and Austria were the main Sint Maarten – 0.90 1.10 users of the substance, reporting consumption of 103 kg, Saint Helena 0.58 0.77 0.95 Christmas Island – – 0.88 4.8 kg and 2.8 kg, respectively. United Kingdom 0.15 0.50 0.68 Costa Rica – – 0.61 Austria 0.44 0.30 0.51 Turkey – – 0.48 Sedative-hypnotics Brazil – 0.38 0.39 Singapore 0.26 0.27 0.28 24. Of the four substances from the group of sedative- Estonia 0.06 0.15 0.22 hypnotics in Schedule II, three of them, namely, gamma- Lebanon 0.15 0.18 0.21 hydroxybutyric acid (GHB), mecloqualone and Slovenia 0.04 – 0.17 methaqualone, are neither barbiturates nor benzodiaz- Qatar – – 0.16 epines. While mecloqualone has been listed in Schedule II Ecuador 0.06 0.08 0.08 since the adoption of the 1971 Convention, methaqualone, Guatemala – 0.09 0.06 which was initially placed in Schedule IV, was moved to Schedule II in l979 because of new information gathered over the years indicating its increased abuse potential and decreased medical usefulness. Both mecloqualone and Table 4. Methylphenidate: calculated consumption rate, 2012 methaqualone are nowadays no longer used in medical practice. The substance GHB, which was added to Sched- S-DDD per 1,000 inhabitants per day ule IV in 2001, was transferred to Schedule II Country or territory 2012 in 2013. Secobarbital, the only barbiturate in Schedule II, was moved from Schedule III to Schedule II in 1988. Switzerland 14.72 Israel 8.48 Norway 6.94 gamma-Hydroxybutyric acid Dominica 5.53 Cayman Islands 2.98 25. The substance GHB is used in the treatment of narco- Spain 2.82 lepsy and, more rarely, alcoholism. Data for GHB may still New Zealand 2.70 be incomplete, as the substance was moved to Schedule II Belgium 2.54 Andorra 2.51 only in 2013. Reported manufacture of GHB increased Curaçao 1.32 steadily during the period 2006-2010, reaching a peak of 59 South Africa 1.02 tons in 2010. After a significant drop in 2011, to 12.4 tons, global manufacture increased again, to 38.7 tons, in 2012,

40 in 2012.Italy, United the States, Ukraine, France, the Ukraine (in descending order) were leadingthe exporters (in descending order) remaining main the importers. nearly 16tons, with Italy, United the Kingdom and France 2011 to 2012.In 2012,total reported imports amounted to 26. accounting for cent 76 per of stocks in 2012. global remained two the largest holders of stocks, together those declined to 24tons in2012.Italy and United the States tons). stocks, Global had which attained 41tons in2011, of GHB in 2012 were Germany (8.8 tons) and Ukraine (4.3 United States amounted to 25.6tons. manufacturers Other substance. In 2012,reported manufacture of GHBinthe facture by Unitedthe States, a leading manufacturer of the These fluctuations are mainly due to fluctuations in manu- second-highestthe amount everrecorded for that substance. athine as a stimulant is used and for industrial pur Manufactureposes. of cathine fluctuated considerably 31. Cathine belong to groupthe of analgesics. remaining substances, buprenorphine and pentazocine, pentobarbital), flunitrazepam glutethimide.and The two biturates (amobarbital, butalbital, cyclobarbital and stances belong to group the of sedative-hypnotics: four bar groupthe of central system nervous stimulants. Six sub- therapeutic One substance, usefulness. cathine, belongs to risk to publictial and health have which moderate to great III are liability whose those to abuse constitutes asubstan- ine substances are listed IIIof inSchedule 1971 the by World the Health Organization, substances inSchedule Convention. According to scheduling the criteria adopted 30. ince 2000,Germany major the has accounting been kg, manufac for- over cent 93per of total global 870 turer of secobarbital. In 2012,its output amounted to 27. Secobarbital had highestthe consumption calculated of GHB in 2012. ­R ­G ussian Federation and Germany (indescending order) ermany, Unitedthe Kingdom, Unitedthe States and

C N I S Central nervoussystemstimulants nternational inGHBincreased slightly trade from Substances inSchedule III of the1971Convention - - order, were Germany South Africa, and Switzerland. main importers of cathine during that year, in descending amounted exports 2012, reported global to 1.05tons. The of 3.1tons in2008and aminimum of 872 kgin2011.In stance averaged 1.5tons during that time, with amaximum of exports 2008-2012.Global sub the - cathine period inthe 32. werethese held mainly in Germany and Switzerland. stocks2012. Global of cathine to 263 kgin2012; decreased reported in2011and only some grams were reported in and No 300kginChina. manufacture of substance the was reached of 800 kg, which 500 kg was manufactured in India waswhich reported by In China. output 2010,global manufacture of cathine declined sharply of to all 55kg, in recent years were and China India. From 2007to 2009, stance. countries Other reporting manufacture of cathine 2003, Germany was only the manufacturer of sub the - ofand 5.9tons, apeak was which reached in2007.Until no output between 2003-2012, varying during period the 28. held in Germany. atstood 833kgin2012,with majority the cent) (88per for remainder the (61stockskg). Global of secobarbital manufacture Unitedthe (931 kg), while States accounted descending order) were mainthe users in 2012. Unitedthe States, and Belgium Netherlands the (in main importer. The United Kingdom,Germany, Sweden, substance, United the while Kingdom continued the to be in 2012.Germany remained leading of the exporter the from 830kgin2011to almost 750kg(7.5million S-DDD) and 9.6 kg for 2012. in previous years, reported consumption of 9.1kgfor 2011 tional State main ofthe importer Bolivia, of substance the manufacture of substance the was reported. The Plurina- e Republic of Korea, had which stopped manufac - and 2009mainly for domestic consumption. For 2012,no turing zipeprol in1999,resumed its manufacture in2008 29. Zipeprol

G I Th ndia and Germany were main the exporters of lobal trade volume trade lobal of secobarbital dropped slightly, Antitussives 41

English Sedative-hypnotics listed in Schedule III 35. After reaching a record high level in 2011 (51.4 tons or 514 million S-DDD), global manufacture of pentobarbi- 33. Classified as sedative-hypnotics, barbiturates used to tal edged down slightly to 50.3 tons (503 million S-DDD) be prescribed for the treatment of anxiety and stress and, in 2012, owing to decreased manufacture in the United in some cases, as anaesthetics for short surgery interven- States. Total manufacture in the United States and G­ ermany tions (ultra-short-acting substances). Nowadays, they are accounted for 91 per cent of the global total in 2012. Third used mainly as anti-epileptics or for their selective anticon- came Denmark, followed by Canada and Japan. Total stocks vulsant property. Barbiturates differ in speed of onset, of pentobarbital reached 38 tons (381 million S-DDD) in duration of action and potency. Like benzodiazepines, bar- 2012, with about 41 per cent of them held in the United biturates encountered on the illicit market have usually States, 28 per cent in Germany and 12 per cent in the been diverted from licit circuits rather than synthesized in United Kingdom. In 2012, the largest user of pentobarbital clandestine laboratories. continued to be the United States, followed by Germany, France, Australia, Canada, Denmark and the Netherlands. Amobarbital, butalbital, cyclobarbital and pentobarbital 36. After increasing for two consecutive years in 2009 and 2010, the total volume of international trade in pento- 34. During the period 2003-2012, global manufacture of barbital stabilized at 31 tons (309 million S-DDD) in 2012. amobarbital, butalbital, cyclobarbital and pentobarbital Accounting for 41 per cent of global exports in 2012, fluctuated between 0.82 billion S-DDD and 1.27 billion ­Germany continued to be the top exporter, followed S-DDD. For 2012, a global total of 862 million S-DDD was by the United States (15 per cent) and the Netherlands recorded, the lowest amount since 2006 as a result of (11 per cent). France, Canada and the Netherlands, decreased manufacture in Denmark. While manufacture of together, accounted for half of global imports in 2012. amobarbital has shown a downward trend in recent years, that of pentobarbital has increased (see figure 6). As in pre- 37. Global manufacture of butalbital experienced a sig- vious years, manufacture in China, Denmark, Germany nificant decrease in 2012, down from its record high of and the United States accounted for almost 99 per cent of nearly 40 tons (532 million S-DDD) in 2011 to 23 tons the total. Figure 7 shows the share of the main manufac- (307 million S-DDD) in 2012, owing to decreased manu- turing countries, in total output, during the period facture in Denmark and the United States. Despite a sub- 2008-2012. stantial drop in its manufacture, Denmark remained the

Figure 6. Barbiturates listed in Schedule III: Figure 7. Barbiturates listed in Schedule III: total total reported manufacture, by substance, 2003-2012 reported manufacture, selected countries, 2008-2012

Billions of S-DDD Billions of S-DDD 1.4 1.3 1.2 1.2 1.1 1.0 1.0 0.9 0.8 0.8 0.7 0.6 0.6 0.5 0.4 0.4 0.3 0.2 0.2 0.1 0 0 2012201120102009200820072006200520042003 2008 2009 2010 2011 2012 Year Year

Amobarbital Butalbital China Denmark Cyclobarbital Pentobarbital Germany United States World total

42 12 per cent imported by Georgia and respectively. Latvia, 12 per cent of cyclobarbital, with remaining the cent 13per and Federationthe Russian continued main the to be importer to cent almost 70 per imports of global in2012, the S-DDD), mainly to other countries inEurope. Amounting 2012. Of that amount, Poland 220 kg (1.1 exported ufacture inPoland rose to 484kg(2.4million S-DDD) in (2million S-DDD) of cyclobarbital in2011,man- 393 kg turer of cyclobarbital. After recording a manufacture of substancethe in2003,Poland manufac sole the became - Europe. AfterGermany Latvia and stopped manufacturing 39. S-DDD) of in 2012, almost all it consumed in China. consumptioncalculated at stood 3.3tons (32.8million and United the Kingdom main the being importer. Total about same the level, main withthe being China exporter United Kingdom. Total international remained trade at of were which held and inChina remainder the inthe stocks at stood 950kg(9.5million S-DDD) in2012,most tities manufactured was in China for domestic use. Global amobarbital. As inprevious years, majority the of quan the - Japan, two the main countries manufacturing and using inmanufacturedecrease by and China no manufacture by canbe in 2012.This decrease attributed to a marked (94 million S-DDD) in2011to 5tons (50million S-DDD) 38. in Denmark and Italy. held United inthe States and remainder the held mainly S-DDD) in2012,with around cent 63per of that amount stocks of butalbital dropped to 22.3 tons (297 million largest and exporter Italy main the being importer. Global million S-DDD) in2012,with Denmark remaining the 21.4 tons (286million S-DDD) in2011to 31tons (413 1971Convention.the Total volume of increased from trade controlcertain measures, inaccordance with article3of 2012 for manufacture the of preparations exempted from that country, 3.5tons (47million S-DDD) were in used States was predominately for domestic consumption. In mainlybe for overseas markets, that while United inthe in 2011and 2012.Manufacture inDenmark continued to cant manufacturer, Germany, didnot report manufacture lowed by United the States cent). (37per Another- signifi leading manufacturer cent (61per total), of fol global the - from Schedule IV to Schedule III in 1995. Several from IV to Schedule IIIin1995.Several Schedule diverted andbeen abused, flunitrazepamtransferred was demand for such preparations. it Because had frequently market and smuggled into countries where there is an illicit ing flunitrazepam have been diverted often from the licit unitrazepam remains one of most the frequently from domestic distribution channels. Preparations contain- abused The benzodiazepines. substance is diverted mainly 40. Flunitrazepam

Fl C G yclobarbital was manufactured and mainly used in lobal manufacturelobal of amobarbital fell from 9.4tons ­mi llion 42. cent),(82 per Italy cent) (11 per and cent). Brazil (3 per amounted to 1.3tons in2012,held mainly inSwitzerland (1.6 kg).Stocks of flunitrazepam held by manufacturers output (1.2tons), followed by Italy (303kg)and Germany at 1.5 tons, with Switzerland accounting for cent 80per of graph 84and figures 20 below),and 21 which in2012 stood manufacturetotal global ofpara flunitrazepam- also (see place inthat country. Those fluctuations are in reflected 2010-2011,no manufactureperiod of substance the took some years, such as in2005and 2008and during the manufacturer of substance, the has fluctuated in greatly; manufacture of flunitrazepam in Switzerland,the main reported somealso manufacture of flunitrazepam. The zerland reported its manufacture; in2010and 2011,India tured countries. inseveral After 1996, only Italy and Swit- anaesthesia. Prior to 1996,flunitrazepam was manufac- for used epam, has pre-medication been and for general 41. terfeit products that do not contain that substance. flunitrazepamthat aresold theilliciton market are coun- industry. Most of preparations the containing purportedly nitrazepam, cooperation inclose with pharmaceutical the substance,the have adopted control strict for policies flu- countries, including major manufacturers and importers of (909 million S-DDD) in2012,most of was which by cent 2per compared with 2011and amounted to 909 kg consumption calculated Global of flunitrazepam increased cent26 per ofimports global of substance the in2012. imports ranging from 34to accounting 93kg, together for Brazil and Germany (indescending order) reported imports of substance. the Switzerland, Uruguay, Nigeria, pam in 2012, importing 702 kg or cent 67 per of global 2012. Japan remained leading the importer of flunitraze- imports or of use flunitrazepam 2010- period theduring 2008-2012. More period the than 50countries reported for cent 91per of of exports substance the global during exporters of flunitrazepam, together accounting on average at 1.2tons in2012.Italy and Switzerland were leading the yearper during five-year the 2008-2012, and period stood S-DDD 1,000 inhabitants per day. per rateshighest calculated of consumption measured in S-DDD) had the Japan (15.2S-DDD) and Austria (6.6 S-DDD), in Japan (702million S-DDD). Uruguay (36.7 uprenorphine belongs to family the of opioids used mainly as analgesics. As shown infigure global 8, 43. Buprenorphine

I I B n medical practice, flunitrazepam,n medical similarly - to diaz nternational influnitrazepam trade averaged 1.1 tons Analgesics listed in Schedule III ­ co nsumed 43

English manufacture of buprenorphine started to increase gradu- Czech Republic (526 kg), Australia (431 kg), Switzerland ally beginning in the late 1990s, as the substance began to (239 kg) and France (100 kg) were the major exporters in be used in higher doses for the treatment of pain and opi- 2012, together accounting for 97 per cent of total global oid addiction. After a significant drop in 2010, global man- exports. ufacture increased again and attained a new record, with a total of 7,353 kg (919 million S-DDD) in 2012 reported 45. Global calculated consumption of buprenorphine by 13 countries, including the major manufacturing coun- increased from 5.5 tons (681 million S-DDD) in 2011 to tries: the United Kingdom (4,608 kg), the Czech Republic over 6 tons (756 million S-DDD) in 2012. With 524 mil- (749 kg), Belgium (655 kg), Switzerland (453 kg), Australia lion S-DDD, the United States accounted for 69 per cent (400 kg) and Germany (273 kg). Global stocks of the sub- of global calculated consumption in 2012, followed by stance amounted to about 6.7 tons in 2012, an increase of ­Germany (9 per cent), France (5 per cent), Switzerland almost 96 per cent from 2011. The majority of the stocks (4 per cent) and Spain and Italy (2 per cent each). The cal- were held, in descending order, in the United Kingdom, culated consumption of buprenorphine in S-DDD per the United States, Germany, the Czech Republic, Switzer- 1,000 inhabitants per day is shown in part three, table IV.5, land, Australia and France. of the present publication. Buprenorphine is used in ­several countries in detoxification and substitution treatment pro- 44. The volume of trade in buprenorphine has continued grammes for opioid dependence, including in Australia, to increase since 1993, reaching a total of 7.2 tons in 2012, Austria, Denmark, France, Germany, Hungary, Ireland, with over 60 countries reporting imports of the substance. Malaysia, Switzerland and the United States. Diversions of Major importers in 2012 included the United States (4,749 preparations of buprenorphine, mainly from domestic dis- kg), Germany (886 kg), France (510 kg), the United King- tribution channels, have been reported by a few countries. dom (158 kg), Spain (119 kg) and Italy (104 kg). Among Abuse of the substance, particularly among opioid addicts, those countries, the United States reported a significant has also been reported. increase in imports over the 2011 level. The United King- dom (3,233 kg), Belgium (731 kg), Germany (566 kg), the Pentazocine

46. Pentazocine is an opioid analgesic with properties and uses similar to those of morphine. Global total manufac- ture of the substance fluctuated during the period 2003- 2011 between a low of 2.7 tons (13 million S-DDD) in 2003 Figure 8. Buprenorphine: total reported manufacture, stocks, imports and calculated consumption,a 1993-2012 and a high of 8.5 tons (42 million S-DDD) in 2009, mainly as a result of fluctuations in the total output of India and Tons Italy, the two major manufacturing countries. In 2012, total 8 manufacture of the substance amounted to 685 kg, of which 512 kg was manufactured in the United States. The 7 pentazocine manufactured in the United States was mainly for domestic use. Italy and China, the two other major 6 manufacturers in 2012, reported manufacture of 130 kg 5 and 42 kg, respectively. India, which reported the manu- facture of 6.7 tons of the substance for 2011, did not report 4 manufacture of the substance in 2012. Global reported 3 stocks of the substance decreased by 50 per cent from 2011, to 2,717 kg in 2012, as a result of absence of stock data 2 from India and decreased stocks held in the United States. Major users of the substance in 2012 included, in descend- 1 ing order, the United States, Nigeria, Japan, Canada and 0 Belgium. b

1993 1994 1995 19961997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Year Manufacture Stocks 47. Global trade in pentazocine has been declining since Import Calculated consumption 2009. Total exports further decreased from 2,320 kg in 2011 to 1,072 kg in 2012. The largest exporter in 2012 a Statistical data submitted by Governments are used to calculate the approx- was Italy (800 kg). Major importers in 2012 were the imate global consumption in a given year, expressed in S-DDD. United States, Nigeria, Pakistan and Portugal, in descend- b The data for 2012 are incomplete. ing order.

44 of ADHD. IVareule as anorectics essentially used or for treatment the mine, pipradrol and pyrovalerone. The stimulantsSched- in mefenorex, mesocarb, pemoline, phendimetrazine, phenter ourteen central system nervous stimulants are listed etilamfetamine, fencamfamin, fenproporex, mazindol, IV:in Schedule amfepramone, aminorex, benzfetamine, 49. ics (5 substances); and analgesics (1 substance). and anti-epileptics (7substances); other sedative-hypnot- epileptics (1substance); barbiturate-type sedative-hypnotics tive-hypnotics (11substances); anti- benzodiazepine-type other anxiolytics- (1substance); seda benzodiazepine-type anxiolyticsstances); benzodiazepine-type (22substances); ixty-two substances with various applications in lowing groups: central system nervous stimulants (14sub- medicine are listed IV. inSchedule belong They the to fol- 48. Billions ofS-DDD 1.4 0.2 0.4 0.6 0.8 1.0 1.2 1.6 1.8 2.0 2.2 2.4 2.6 2.8

Schedule 0 F S Central nervoussystemstimulants Figure 9. Phendimetrazine Mazindol Amfepramone

IV : total reported manufacture, bysubstance,

Central nervoussystemstimulantsin Substances inSchedule IV of the1971Convention 2003-2012 Phentermine Pemoline Fenproporex 2012201120102009200820072006200520042003 Year - mefenorex, mesocarb, pipradol and pyrovalerone). IV(aminorex,in Schedule etilamfetamine, fencamfamine, No manufacture reported for has been other the stimulants each for less cent than 1per of total reported manufacture. IV(benzfetamine,ule fenproporex and pemoline) accounted ture of other the central system nervous stimulants- inSched accounted for cent figure 1per manufacReported (see 11). - for cent 5per and phendimetrazine (25 million S-DDD) cent,10 per amfepramone (131million S-DDD) accounted manufacture of mazindol (269 million S-DDD) accounted for facture of stimulants all IV, inSchedule reported the while S-DDD) accounted for cent 84per of total reported manu- 51. followed by Germany and Italy figure (see 10). Unitedthe States accounting for over total, of half global the of group this of substances amounted to 2.6billion S-DDD, main the manufacturers.been In manufacture 2012,global Germany and United the States, have which traditionally fluctuations were mainlythe result of developments in manufactureeported of central system nervous stim- 2003-2012, inspite of many fluctuations figure (see 9). Those ulants during on IVhas inSchedule rise period the the been 50. Schedule Billions ofS-DDD 1.4 2.8 1.0 1.2 1.6 1.8 2.0 2.2 2.4 2.6 0.2 0.4 0.6 0.8

0 I R n 2012, manufacture of phentermine (2.2billion Figure 10.

IV Italy Brazil Argentina : total reported manufacture, selected countries,

Central nervoussystemstimulantsin 2003-2012 Germany United States Belgium World Total 2012201120102009200820072006200520042003 B ­ Year razil, razil, 45

English Figure 11. Central nervous system stimulants in Figure 13. Central nervous system stimulants in a Schedule IV: share of total reported manufacture, Schedule IV: average national consumption, by region, selected substances, 2012 2004-2012

S-DDD per 1,000 inhabitants per day Mazindol 12 10% Phendimetrazine Amfepramone 11 1% 5% 10 9 8 7 6 5 4 3 2 1 0 2004-2006 2007-2009 2010-2012 Phentermine Year 84% Africa Americas Asia Europe Oceania

aStatistical data submitted by Governments are used to calculate average annual consumption for a three-year period.

Figure 12. Central nervous system stimulants in Schedule IV were used in 2012. Of those, phentermine Schedule IV: calculated global consumption,a by substance, (1.58 billion S-DDD) accounted for 82.9 per cent, followed 2003-2012 by mazindol (192 million S-DDD, or 10 per cent), fenpro­ porex (59.5 million S-DDD, or 3.1 per cent), amfepramone Billions of S-DDD (52 million S-DDD, or 2.7 per cent) and phendimetrazine 2.4 (13.2 million S-DDD, or 0.7 per cent) (see figure 12). About 2.2 74 per cent of global calculated consumption of stimulants 2.0 in Schedule IV in 2012 was accounted for by the United 1.8 States (1.41 billion S-DDD), followed, in descending order, 1.6 by Argentina, Australia and Brazil. 1.4 1.2 53. Calculated consumption of stimulants in Schedule IV 1.0 in the Americas remained the highest in the world, at 0.8 approximately the same levels as a decade ago (see 0.6 ­figure 13). Decreases in the use of stimulants in Brazil 0.4 achieved since 2006 have been almost offset by rising con- 0.2 sumption levels observed in the United States. Levels of 0 2012201120102009200820072006200520042003 consumption decreased in Asia and Europe during the Year Amfepramone Fenproporex period 2010-2012 compared with the period 2006-2008, Mazindol Pemoline but increased markedly in Africa and, in particular, Phendimetrazine Phentermine Others ­Oceania, where consumption of anorectics has increased significantly in some countries. In 2012, the highest con- aStatistical data submitted by Governments are used to calculate the approx- sumption rates, expressed in S-DDD per 1,000 inhabitants imate global consumption in a given year, expressed in S-DDD. per day, were reported by the United States (11.6 S-DDD), followed by Chile (1.2 S-DDD) and Brazil (0.5 S-DDD). 52. The fluctuations in total calculated global consump- Among the countries and territories that did not report tion of central nervous system stimulants listed in Sched- consumption data, the highest calculated consumption ule IV (see figure 12) mainly reflect changes in the use of rates, expressed in S-DDD per 1,000 inhabitants per day, phentermine in the United States and the use of amfepra- were observed in Argentina (12.1 S-DDD), Australia mone and fenproporex in Brazil. A total of 1.9 billion (9.1 S-DDD) and China, Hong Kong Special Administra- S-DDD of central nervous system stimulants listed in tive Region, and Singapore (3.4 S-DDD each).

46 zerland, United the States wasmanufacturer sole the of ture of benzfetamine was reported by Ireland, Italy and Swit- 58. quantities of more than 1 kg in 2012. Nine other countries reported imports of amfepramone in United(816 kg),the Kingdom (402kg)and (289kg). Chile were reported by United the States (5.3tons), Germany substance inthat year. Thelargest imports of amfepramone 7 tons, accounting for cent 83 per of of exports the global 2008-2011. In 2012, Switzerland period the almost exported up to 2.5 tons 2012,exporting year per on average during main of exporter amfepramone during leading decade the 2011, submitted no report for 2012. Switzerland was the Brazil, had which reported manufacture the of 4.8tons for (6.9 tons), Italy (2.4 tons) and United the States (570 kg). having manufactured amfepramone in2012:Switzerland mone amounted to 10tons. Only three countries reported on average. In 2012,total reported manufacture of amfepra- in2008to beginning about2007, decreased 9tons year per had averaged 22tons 2003- year per during period the 57. Republicthe of Korea for 2011 and 2012. than No 1kg. imports of phendimetrazine were reported by reporting imports of phendimetrazine in quantities of more kg)and Switzerland (4kg)were only the countries (26 kg),South Africa of substance. the In 2012,Germany (43 Republic of Korea, have mainthe importersbeen and users cent.58 per Traditionally, United the States, followed by the to 1.1tonsdecreased in2012,of Italy which accounted for factured inItaly is mainly for destined exports Global export. in2009to 733kgin2012.Phendimetrazine manu - 5.2 tons phendimetrazine inthat declinedgradually from country 2007-2011.Manufacturephendimetrazine period inthe of reflects developments in Italy,the main manufacturer of from 7.6tons in2010to 1.8tons in2012.This decrease 56. 23 countries and territories. in quantities of more than 1kgwere reported in2012by importing almost 8tons in2012.Imports of phentermine main the importerbeen of phentermine inrecent years, Italy, United the States and Australia. The United States has almost 7tons in2012),followed, indescending order, by of substance the Germany has been (reporting of exports reaching 17tons in2012.In recent years, main the exporter 55. followed by Germany (7.22 tons) and Italy (4.7 tons). in 2012,with United the States accounting for 20.7tons, 9 tons in2003to 34.4tons in2011,and at stood 32.6tons manufacture of substance the gradually increased from hentermine has always most the widely been man- IV.ule 2003-2012,total reported period the During ufactured substance group inthe of stimulants- inSched 54.

G W T I P nternational in phentermine trade increased, also otal reported manufacture of amfepramone, which lobal manufacturelobal of phendimetrazine decreased ith exception the of 2005and manufac 2006,when -

59. 2003-2012, reporting consumption of 137 kg for 2012. major the was also consumer of benzfetamine period inthe United States and United the Kingdom. The United States countries reporting imports of substance, the including the in benzfetamine remained limited in2012,with only three total manufacture of 454kgand International 104kg. trade and United 2012,the States and Italy together reported a benzfetamine during leading up decade the to 2010.In 2011 as astimulant, for pemoline is used treatment the of ADHD. Netherlandsthe for remainder. the In addition to used being atstood of 360kg, Japan which accounted for 320kgand averaged 338 kgayear. In 2012, total imports of pemoline ending decade the in2012,importsDuring of pemoline steadily, from 7.5tons in2004to 188kgat end the of 2012. main the exporter.been Stocks of pemoline have declined reportedto by all 387kg, Netherlands, the has which also since 2008. In 2012,total output of substance the amounted only the manufacturing virtually country has been pemoline in 2009,reflecting developmentsthe in Netherlands, which stance has fluctuatedbetween 392kgin2008 grams and 4 2005 and manufacture 2007.Since 2008,global of sub the - 61. Switzerland and Unitedthe Kingdom for remainder.the amounted to with 39kg, Brazil accounting for 23kgand at end the of 2012(135kg).Total of exports mazindol Brazil held most of stocks of global the substancethe 91 kg. Argentina manufactured 178 kg and Brazil manufactured mazindol, inamounts averaging annum. 50kgper In 2012, tion to Argentina, Brazil has intermittently manufactured kg of substance the 2003-2012.In during addi- period the dol since 2003.It reported an annual average output of 160 60. ofalmost all that amount imported by Brazil. 2006-2010,droppeding to period the 313kgin2012, substance,the had which averaged 3.4tons year per dur was manufactured by Australia. Total reported imports of total output of fenproporex dropped of to all 6 kg, which major manufacturing countries In inthat 2012, period. facture reported by and Belgium Brazil, were which the 1.4 tons in2011,owing mainly to inmanu decrease the - declined steadily since 2003,from 10tons inthat year to and territories that reported to manufactured Board the or countries ending decade the all During in 2012, practically were benzodiazepines ty-three included- in Sched was transferred from IVto Schedule IIIin1995. Schedule 1990 and brotizolam in1995.Flunitrazepam was added IVin1984.Midazolamule to was IVin added Schedule 62.

A N G Thir rgentina mainthe has manufacturerbeen of mazin- o manufacture of pemoline was reported between lobal reportedlobal manufacture of fenproporex has Benzodiazepines 47 -

English traded in benzodiazepines in quantities of more than 1 kg each (see figure 15). The remaining substances in that group at least once. Benzodiazepines are frequently diverted for together accounted for 6 per cent of total reported manufac- subsequent smuggling and abuse. ture. Up to 2007, fludiazepam had been intermittently man- ufactured in Japan; in the first reported manufacture since then, Switzerland reported manufacture of 7 grams of that Benzodiazepine-type anxiolytics substance in 2012. No manufacture of camazepam or pina­ zepam was reported for 2012, small quantities of which were last manufactured in 1991 and 2011, respectively. As shown 63. Twenty-two benzodiazepines are generally classified as anxiolytics. In the past decade, total reported manufacture of this group of substances fluctuated in the range of Figure 15. Benzodiazepine-type anxiolytics: share of 19.4 ­billion and 29.9 billion S-DDD, averaging 23 billion total reported manufacture, by substance, 2012 S-DDD per year during the period 2003-2011 (see figure Others 14). Those fluctuations mainly reflect fluctuations in the 6% Nordazepam manufacture of alprazolam and diazepam, the main sub- Oxazepam 1% stances in this group, which together accounted, on average, 3% for almost 60 per cent of the total in the period 2008-2012. Global manufacture of this group of substances amounted Lorazepam Alprazolam 29% to 16.1 billion S-DDD in 2012, which is 40 per cent lower 21% than in 2011. The decline in 2012 is a result of the fact that data on manufacture of this group of substances from some countries, most importantly India, are missing. In 2011, manufacture in India accounted for 27 per cent of global manufacture of benzodiazepine-type anxiolytics.

64. In 2012, alprazolam accounted for 29 per cent (4.6 ­billion S-DDD) of total reported manufacture of benzo- diazepine-type anxiolytics; diazepam for 26 per cent (4.3 bil- Diazepam Bromazepam 26% lion S-DDD); lorazepam for 21 per cent (3.3 billion S-DDD); 8% bromazepam for 8 per cent (1.3 billion S-DDD); chlordiaz- Chlordiazepoxide Clorazepate Clobazam 3% epoxide and oxazepam for 3 per cent each; clobazam for 1% 2% 2 per cent; and clorazepate and nordazepam for 1 per cent

Figure 14. Benzodiazepine-type anxiolytics: Figure 16. Benzodiazepine-type anxiolytics: total reported manufacture, by substance, 2003-2012 reported manufacture, selected countries, 2003-2012

Billions of S-DDD Billions of S-DDD 32 32 30 30 28 28 26 26 24 24 22 22 20 20 18 18 16 16 14 14 12 12 10 10 8 8 6 6 4 4 2 2 0 0 201120102009200820072006200520042003 2012a 201120102009200820072006200520042003 2012a Year Year Alprazolam Bromazepam China Finland Chlordiazeproxide Diazepam France Germany India Lorazepam Oxazepam Others Italy Switzerland Others

aThe data for 2012 are incomplete. aThe data for 2012 are incomplete.

48 expressed in defined daily doses for statistical purposes (S-DDD). purposes for statistical doses daily in defined expressed global consumptioninagivenyear.approximate Theseconsumptionfiguresare ­m S-DDD) together accounted for cent 76per of global S-DDD), Finland (1.8billion S-DDD) and France (1.5 for that year, Italy (7billion S-DDD), (1.9 billion China 2003-2011. In 2012,owing to absence the of data from India facturers anxiolytics of period benzodiazepine-type inthe in figureChina, 16, India and Italy werethe leading manu-

Billions ofS-DDD 10 12 14 16 18 20 22 24 26 28 anufacture of that group of substances figure (see 17). Figure 17. 0 2 4 6 8 b a Statistical data submitted by Governments are used to calculate the to calculate used are by Governments submitted data Statistical The data for 2012 are incomplete. for 2012are The data Figure 18. Others 6% Diazepam Alprazolam Switzerland reported manufacture, bycountry, 2012 Italy 43%

Benzodiazepine 4% global consumption, Benzodiazepine United States 2% Lorazepam Bromazepam -type anxiolytics: share oftotal Brazil -type anxiolytics: calculated 6% a Germany 2003-2012

6%

China 12% Others Chlordiazepoxide 201120102009200820072006200520042003 France 10% Finland 11% 2012 Year ­ b illion illion b

annual consumptionfora accounted for cent 92per ofmanufacture. global They were France (989 kg) and (251 kg), which together China zolam in2012were Finland (1.7 tons), Italy (1.3tons), outputglobal in 2011. The main manufacturers alpraof - submitted by India, had which contributed 5.4tons to United States and no because data on manufacture were with 2011due to significantly lower manufacturethe in amounted to 4.6tons, adecline of cent 62per compared 66. tion of alprazolam in Australia for 2011. marked increase imports inthe and consump calculated - 2010-2012is result the duringOceania period the of a figure 19). The sharp increase in consumptionlevels in sumption rates for anxiolytics benzodiazepine-type (see region withaverage highest the calculated national con- highest rates. Until 2010, Europe was consistently the Finland (107 S-DDD) and Portugal (99 S-DDD) having the (984 S-DDD), (360S-DDD), Belgium Ireland (177S-DDD), three, table IV.3, of present the publication, with Slovenia S-DDD 1,000inhabitants per day, per is shown inpart sumption anxiolytics, of benzodiazepine-type expressed in ­s ing order) were largestthe consumers of group this of ­B 20.4 sumption for group this of substances amounted to otal approximate consumption calculated of- benzo manufacture.global con In calculated - global 2012,the diazepine-type anxiolytics followed overall the trend in 65.

ubstances, inabsolute terms, in2012.Thecalculated con - razil, Belgium, France,razil, Belgium, Spain, Japan and Italy- (indescend

S-DDD per1,000inhabitantsday S-DDD a 15 20 25 30 35 40 45 50 10 Statistical data submitted by Governments areusedtocalculatethe submitted data Statistical 0 5 average national consumption, I T ­b n 2012,total reported manufacture of alprazolam illion S-DDD figure (see 18). The UnitedStates, Figure 19. Africa 2004-2006

Americas three-year period. three-year Benzodiazepine 2007-2009 Asia a byregion,2004-2012 -type anxiolytics: Europe 2010-2012 Oceania Year ­ average 49

English followed by Brazil (132 kg), Pakistan (90 kg), the United 69. International trade in diazepam, which averaged States (90 kg, down from almost 2 tons in 2011), Canada 57.2 tons annually during the 10-year period 2003-2012, (41 kg), Argentina (30 kg) and the Russian Federation amounted to 54.7 tons in 2012. Italy (19.4 tons) and China (5 kg). Global stocks of the substance have been relatively (9.5 tons) remained the leading exporters of the substance stable in the past five years, averaging 6.1 tons per year in 2012, followed by Switzerland and Denmark (5.6 tons during the period 2008-2012. In 2012, the main ­stock‑ each) and India (4 tons); together, those countries accounted ­holders, in descending order, were the United States, for 81 per cent of global exports in 2012. ­Finland, ­Canada, Italy and Brazil. 70. Practically all countries and territories imported diaz- 67. Alprazolam is available in many countries and all epam at least once in the period 2008-2012. About 100 regions. Global exports have shown an upward trend dur- countries and territories reported imports of diazepam of ing the past 10 years, rising from 4.9 tons in 2003 to more than 1 kg for 2012, the main importers being Ghana 11.8 tons in 2011. In 2012, global reported exports fell to (5.8 tons), the United States (4.7 tons) and the Democratic 10.8 tons. India, the United States, Italy, Finland, France Republic of the Congo (3.9 tons). Switzerland, Denmark and Belgium, in descending order, were the main countries and Spain imported 3.4 tons, 3.2 tons and 3 tons, respec- reporting exports of the substance in 2012, their combined tively, mainly for re-export. Global calculated consumption total accounting for 87 per cent of global exports. More of diazepam continued to decrease, standing at 4.6 billion than 100 countries reported imports of the substance dur- S-DDD in 2012. Brazil (734 million S-DDD), the United ing 2012. The main importers of alprazolam continued to States (648 million S-DDD), Ghana (579 million S-DDD), be the United States (4.4 tons), Belgium (2 tons) and Italy the Democratic Republic of the Congo (392 million (1.2 tons), mainly for re-export. Those countries were fol- S-DDD) and the United Kingdom (387 million S-DDD) lowed, in descending order, by Slovenia, Argentina, Brazil, had the highest calculated consumption of diazepam in Hungary and Switzerland. Global calculated consumption, 2012. Measured in S-DDD per 1,000 inhabitants per day, which had averaged 10.3 billion S-DDD per year during Ghana (65.1 S-DDD), Croatia (35.8 S-DDD), the former the period 2008-2011, decreased to 8.9 billion S-DDD in Yugoslav Republic of Macedonia (23.2 S-DDD) and 2012. The countries having the largest calculated consump- ­Uruguay (18.9 S-DDD) had the highest calculated rates of tion of alprazolam in absolute terms in 2012 were the consumption in 2012. United States (2.8 billion S-DDD), Belgium (1.2 billion S-DDD), Slovenia (727 million S-DDD) and Argentina Lorazepam (542 million S-DDD). Measured in S-DDD per 1,000 inhabitants per day, Slovenia (984 S-DDD), Belgium (309 71. Total reported manufacture of lorazepam was fairly S-DDD), Ireland (132 S-DDD), Hungary (57 S-DDD), stable during the period 2009-2011, averaging 10.9 tons Uruguay (44 S-DDD) and Argentina (37 S-DDD) had the per year. In the recent past, Italy, Germany and India were highest rates of calculated consumption. the three main manufacturers of the substance. In 2012, total reported output of the substance stood at 8.4 tons, of which Italy accounted for 64 per cent and Germany for Diazepam 25 per cent. India had traditionally reported manufacture of lorazepam every year, with an output of 1.2 tons reported 68. Diazepam continues to be the most traded substance for 2011; however, no manufacture was reported by that in the group of benzodiazepine-type anxiolytics and is con- country for 2012. Other countries reporting manufacture sumed in all regions of the world. Together with alpra- of lorazepam in 2011 were the United States (296 kg), zolam, diazepam is among the benzodiazepines most often ­Canada (276 kg), Poland (209 kg), Israel (68 kg), China diverted and abused. Global reported manufacture of diaz- (49 kg), Spain (34 kg) and Costa Rica (23 kg). Global epam, which in the past decade had fluctuated between reported stocks of lorazepam stood at 8.3 tons in 2012, 43.5 tons in 2009 and 113 tons in 2004, fell to mainly held, in descending order, in Germany, Italy, the 43 tons in 2012, its lowest level in the past decade, mainly United States and Ireland. because no data on manufacture for 2012 were submitted by India, a major manufacturer and exporter of this sub- 72. In 2012, total reported exports of lorazepam stood at stance, which in 2011 manufactured 7.1 tons of the sub- 10.9 tons, 4 per cent lower than in 2011. The main export- stance. In 2012, Italy (17.7 tons), China (16.1 tons), Brazil ers of lorazepam in 2012 were Italy, Germany, India, ­Ireland, (6.9 tons) and the United States (1.4 tons) accounted for Belgium and Hungary (in that order), which together 98 per cent of total reported manufacture. Global reported accounted for approximately 94 per cent of total exports of stocks of diazepam stood at 35.8 tons in 2012, held mainly the substance. About 60 countries and territories reported in China, Italy, Brazil, Switzerland and the United King- imports of lorazepam of more than 1 kg for 2012, the main dom, in descending order. importers being the United States (2.2 tons), Ireland

50 highest levels, in absolute terms. S-DDD) and Pakistan (73million S-DDD) having the S-DDD), Italy (85million S-DDD), Japan (74million 2012, with France (251 million S-DDD), Brazil (153 from 1.4billion S-DDD in2011to 1.2billion S-DDD in 1.3 fairly stable 2003-2012,averaging during period the consumption calculated 2012. Global of bromazepam was kg), accounted for cent 26per ofimports global during (750kg)and(799 kg),Brazil (750kg),Serbia Japan (739 countries,Five further namely Pakistan (951kg),Germany jointly accounting for cent 43 per of total reported imports. remained main the importers of bromazepam in2012, tons, for re-export) and Italy (1.4tons, for re-export) tons, mainly for domestic consumption), Switzerland (2.1 reporting importstries of more than France 100kg. (3.2 imports of bromazepam in 2012, with 23 of coun those - cent78 per of Ninety-four total exports. countries reported leading exporters of substance, the jointly accounting for ufacturing countries (Italy and Switzerland) were the also tons annually. In 2012, as inprevious years, main the man- averaging exports 2003-2012, with global 16.8 period the 74. in that order. in 2012 were held in Switzerland, Italy, France and Brazil, 2008-2012. Most yearper during period the of stocks the fairly stable during past the five years, averaging 14.1 tons are missing. reported Global stocks of bromazepam were recentthe past), for data which on manufacture for 2012 including India other (the manufacturer of bromazepam in reportedcountry manufacture of substance the in2012, lowed by Brazil (931kg)and Canada(108kg).No other remaining Italy (5.9tons) and Switzerland (5.8tons), fol- bromazepam at stood 12.7 tons, mainthe manufacturers 13.8 tons year. per In 2012,total reported manufacture of 2003-2012,total reported manuuring period the - range of 7.3tons (2005)and 18.3tons (2008),averaging facture of bromazepam fluctuated significantly the within 73. Bromazepam measured in S-DDD 1,000 inhabitants per day. per (21.6 S-DDD) hadrates highest the calculated of S-DDD), Austria (22.6S-DDD) and Serbia (23.1 ­B ­C (382 million S-DDD), Italy (346million S-DDD) and recorded for United the States (783million S-DDD), Spain amounted to 3.3billion S-DDD, with highest the levels being sumption averaged 3.8billion S-DDD year. per In 2012,it con calculated - 2003-2012,global stance. period the During accounted for cent 60 per of reported imports all of sub the - (1 ton) and Italy for (758kg, re-export), togetherwhich tons), (1.1 tons, Belgium mainly for re-export), Spain (1.2 elgium (27.7 S-DDD), Portugal (24.9 S-DDD), Spain anada (238million S-DDD). Ireland (33.6S-DDD),

­b illion S-DDD. Total consumption slightly, decreased I D nternational inbromazepam trade was stable during ­ co nsumption, ­mi llion S-DDD) and Islamicthe Republic of Iran (1.6 S-DDD). S-DDD), Iceland (2.5S-DDD), Ghana (2.4 Jordan (4.9 in S-DDD 1,000inhabitants per day per were recorded for S-DDD); highest the rates while of consumption measured United States (28.9million S-DDD) and Italy (23.9million Islamicthe Republic of Iran (45.2million S-DDD), the with highest the levels oftries consumption in2012were S-DDD in2011to 300million S-DDD in2012.The coun- 2009, continued to and decrease fell from 660million substance,the after having peaked at 1.2 billion S-DDD in cent consumption total. of global global Calculated the of ers of substance the in2012,accounting together for 48per Republic of Iran (1.4tons), United the States (1.2tons), 2008-2012.Switzerlandyear period (2tons), Islamic the countries reported imports of chlordiazepoxide in five-the accounting for cent 88per More ofexports. global than 100 largest exporters of chlordiazepoxide in 2012,jointly India (2.5tons each)and Switzerland (1.6tons) were the tons in 2011 to 16.9 tons in 2012. Italy (8.3 tons), andChina ­B in 2012,held mainly inItaly, United the China, States, reportedGlobal stocks of substance this at stood 12.5tons reported manufacture of 7.7tons of substance the for 2011. major manufacturer of chlordiazepoxide, had which manufacture in2012were missing from India, another and Poland and United the States (147kgeach).Data on manufacture of substance the in2012:Canada(160kg) put. Only three other countries reported significant stance, accounted for cent 97per of total the reported out- (1.8 tons), traditionally main the manufacturers of sub the - in2009atince peaking 40.4tons, total reported tofalling 13.6tons in2012.Italy (11.3tons) and China manufacture of chlordiazepoxide steadily, has decreased 75. Chlordiazepoxide 27.5 tons in 2012. Italy (21.7 tons), Germany and India (1.9 41 tons in2003 to 17.3 tons in2009,before increasing to pam has gradually declined during pastthe from decade, annual level of 18.4tons. The volume trade in of oxaze- stocks were stable 2011-2012, at during an period the accounting for cent almost 99per ofoutput. global Global mainthe manufacturers of oxazepam in2012,jointly Canada(1.2tons)export, and France (1.1tons) remained (20.1 tons), manufactures which substance the mainly for India, had which reported output of 1.6tons for 2011.Italy to 22.7 tons owing in2012, partly to lackthe of data from year. reported Global manufacture of substance the declined 2003-2012,total reported manuuring period the - tons in2007and 34.4tons in2003,averaging 25.1tons per facture of oxazepam fluctuatedwithinthe range of 20.3 77. Oxazepam ­B 76. razil (770kg)andrazil Ghana (645kg)were main the import - razil andrazil Switzerland, in that order.

G S D lobal exports of exports lobal chlordiazepoxide declinedfrom 18 51

English tons each) and Hungary (1.2 tons) remained the main reported manufacture of that substance varied during the exporters. A total of 47 countries reported imports of oxaz- period 2003-2011 between 1.3 tons in 2003 and a peak of epam in 2012. The main importers of oxazepam, together 14.2 tons in 2006. In 2012, total global manufacture of nor- accounting for 66 per cent of total global imports, were dazepam amounted to 2.5 tons (164 million S-DDD), with France (10.3 tons), Germany (2.8 tons), Canada (1.7 tons) Finland (2 tons) and France (437 kg) being the largest and the Netherlands and Australia (1.5 tons each). Those manufacturers. Switzerland did not manufacture nordaze- countries were also the countries with the highest calcu- pam in 2012. Use of nordazepam remained limited to a lated consumption in 2012, in absolute terms. Norway (7.6 very few countries, namely, Finland, France, Morocco, Italy S-DDD), Finland (7.3 S-DDD), Croatia (7.1 S-DDD), and Singapore, in descending order. France (7 S-DDD) and Austria (5.8 S-DDD) were the coun- tries with the highest rates of calculated consumption in 81. In 2012, global manufacture of tetrazepam stood at 2012, measured in S-DDD per 1,000 inhabitants per day. 21.8 tons (218 million S-DDD), manufactured mainly in France, Italy and Germany. In 2012, total reported manu- facture of prazepam dropped to 1.4 tons (48 million Clobazam S-DDD), as a result of no manufacture being reported by Switzerland. Total reported manufacture of ethyl loflaze- 78. Total reported manufacture of clobazam fluctuated pate amounted to 417 kg (208 million S-DDD), Japan and between 3.3 tons in 2009 and 6.8 tons in 2011 and stood France being the only manufacturers in the past decade. at 5.8 tons in 2012. Germany (2.9 tons) and France (2.5 Since 2004, India has been the only country reporting tons) remained the main manufacturers, and exporters, of manufacture of pinazepam; since no data on manufacture the substance in 2012, while data on manufacture were were submitted by India for 2012, global output for that missing from India, which had reported an output of 2 tons year was recorded as zero. Similarly, there was no manu- for 2011. Global reported stocks had increased over the facture of camazepam and halazepam in 2012. The com- past three years, reaching 4.7 tons in 2012, mainly held in bined manufacture of clotiazepam, cloxazolam, France, Germany, Canada, Brazil and the United States, in delorazepam, fludiazepam, ketazolam, medazepam and that order. International trade in clobazam was fairly sta- oxazolam amounted to 511 million S-DDD in 2012. ble in the past 10 years, global reported exports averaging about 5.2 tons per year during the period 2003-2012. Seventy-six countries reported imports of the substance Meprobamate in 2012, including France (1.1 tons), Brazil (663 kg), Japan (300 kg), Pakistan (280 kg), Canada (260 kg), Spain 82. Meprobamate, the only non-benzodiazepine-type (212 kg) and the United States (201 kg). substance in Schedule IV used as an anxiolytic, has grad- ually been replaced by benzodiazepines, leading to a sub- stantial decline in manufacture from 750 tons in the late Clorazepate 1970s to an annual average of 290 tons during the 1990s. During the period 2000-2009, total manufacture of mepro- 79. Total reported manufacture of clorazepate declined bamate fluctuated around an annual average of 220 tons. from 8.4 tons in 2003 to 4.1 tons in 2011. In 2012, global Since then, total reported manufacture has declined con- manufacture recovered slightly and stood at 4.6 tons. tinually, to 128 tons (107 million S-DDD) in 2012. China France and Italy were the leading manufacturers of this and Denmark were traditionally the main manufacturers substance during the period 2003-2012. In 2012, those two of the substance, their combined output accounting for countries accounted for almost the entire output (except over 93 per cent of global manufacture in the past five for 86 grams manufactured in Canada) and for 78 per cent years. India, which has also manufactured meprobamate in of global exports. International trade in clorazepate has significant quantities, did not report such manufacture for been stable in the past two years and averaged about 2012. The observed decline in global manufacture is pri- 5.1 tons per year during the period 2011-2012. Spain marily due to lower outputs in Denmark, which dropped (2.4 tons), the United States (548 kg), France (302 kg, for from 40 tons in 2011 to 375 kg in 2012. China remained re-export), Switzerland (274 kg) and Thailand (223 kg) the leading manufacturer of meprobamate, reporting were the largest importers of clorazepate in 2012, while 127 tons of manufacture in 2012 (a 53 per cent increase about 40 other countries reported import and use of the over 2011). Global stocks have also continued to decrease substance during that year. since 2009. They stood at 47.1 tons (39.3 million S-DDD) in 2012, 93 per cent of which were held in South Africa (25 tons), France (9 tons), Hungary (4.8 tons), Denmark Other anxiolytics (2.9 tons) and the United States (2 tons).

80. Owing mainly to developments in Switzerland, tradi- 83. International trade in meprobamate has also gradu- tionally the main manufacturer of nordazepam, total ally declined, from 259 tons in 2007 to 134 tons in 2011,

52 consumption at stood 6.6 billion S-DDD figure (see 21). 2003-2012.In during global 2012,calculated period the fluctuating around an annual average of 8 billion S-DDD group of substances was less volatile than manufacture, States consumption cent). (12per global Calculated of this Switzerland cent), (17per Italy cent) (15per and United the S-DDD in2012,mainly held inGermany cent), (33per cent). per stocksGlobal held by manufacturers were (5 remained Italy cent), (40per Germany cent), (20per major2012, the manufacturers of group this of substances reported manufacture of lormetazepam and triazolam. In lower than in2011,mainly of because inglobal adecrease amounted to 6.5billion S-DDD figureper cent (see 20),12 manufacture sedative-hypnotics of benzodiazepine-type Switzerland and United the States. In reported 2012,global mainly to changes inoutput reported by Germany, Italy, lion S-DDD in2008and 9.5billion S-DDD in2009,owing S-DDD year, per on average, fluctuatingbetween 5.5 - bil diazepine-type sedative-hypnotics was 7.2billion manufacture of 12substances the group inthe of- benzo 85. are provided in paragraphs 40-42 above. was transferred from IV to Schedule IIIin1995, Schedule midazolam, nimetazepam, nitrazepam, temazepam and welve are benzodiazepines - as generally seda used flurazepam, haloxazolam, loprazolam, lormetazepam, tive-hypnotics: brotizolam, estazolam, flunitrazepam, 84. States (6.1 tons). Denmark (45.3tons), Hungary (9.6tons) and United the mate, with 117.6tons (98million S-DDD), followed by leading the consumer became South Africa of meproba- to increased consumption In inSouth Africa. that year, 2011 to 196tons (164million S-DDD) in2012,mainly due meprobamate rose from 162tons (135million S-DDD) in mainly for re-export. consumption calculated Global of Switzerland imported 1.8tons and 1ton, respectively, tons), (3tons) Egypt and Turkey (2.4tons). and Belgium (114 tons), Democratic the Republic of Congo the (5.4 mate in2012,major importers South being Africa kg). Atotal of 34countries reported imports of meproba- France (910kg)and (891 (959kg),SouthBelgium Africa major exporters in2012included Switzerland (1.7tons), ing for cent 97per inthat ofexports year. global Other countries meprobamate exporting in2012,jointly account- India (13.3tons) and Denmark (7.3tons) were main the before increasing to 172tons (146tons), in 2012. China ­s ­S ­t riazolam. Comments on flunitrazepam, a substancethat table past inthe three years, at level the of 6.4billion witzerland cent), (19per Japan cent) (9per and China Benzodiazepine-type sedative-hypnotics Benzodiazepine-type

D T uring the decade leading upuring decade the to 2012,total reported

expressed in defined daily doses for statistical purposes (S-DDD). purposes for statistical doses daily in defined expressed year.given in a global consumption imate are figures consumption These ditionally inEurope higher and inafew non-European arlier average calculated the decade, inthe annual expressed inS-DDD 1,000inhabitants per day, per - was tra consumption sedative-hypnotics, of benzodiazepine-type 86. 10 Billions ofS-DDD Billions ofS-DDD 10 Figure 20.

a b a 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 The data for 2012 are incomplete. for 2012are The data data submitted by Governments are used to calculate the approx to calculate used are by Governments submitted data The data for 2012 are incomplete. for 2012are The data Statistical Figure 21. E reported manufacture, bysubstance,2003-2012 calculated global consumption, Flunitrazepam Brotizolam Temazepam Flunitrazepam Brotizolam Temazepam

Benzodiazepine

Benzodiazepine Lormetazepam Estazolam Triazolam Lormetazepam Triazolam Estazolam -type sedative-hypnotics: total -type sedative-hypnotics: -type sedative-hypnotics: -type sedative-hypnotics: a 2003-2012 Others Nitrazepam Nitrazepam Others 201120102009200820072006200520042003 201120102009200820072006200520042003 2012 2012 Year Year a b 53 -

English countries, such as Japan and Cuba, than in other regions. sedative-hypnotics, accounting for 1.8 billion S-DDD, or In recent years, however, there have been significant 28 per cent, of global manufacture of this group of sub- changes in average annual consumption rates across regions stances (see figure 23). Flunitrazepam was second, with an (see figure 22). While average consumption rates in Europe, output of 1.5 billion S-DDD, or 24 per cent of global man- the Americas and Oceania have been relatively stable in ufacture in 2012. Nitrazepam was third (716 million the past six years, standing at about 20, 9 and S-DDD, or 11.1 per cent), followed by temazepam (702 10 S-DDD per 1,000 inhabitants per day, respectively, this million S-DDD, or 10.9 per cent), lormetazepam indicator increased markedly in Asia, from 13.4 S-DDD to (608 ­million S-DDD, or 9.4 per cent), estazolam (398 18.7 S-DDD, mainly owing to a 29 per cent increase in the consumption rate of Japan, which stood at 63 S-DDD in 2012. It is also notable that the average annual rate of con- Figure 23. Benzodiazepine-type sedative-hypnotics: share sumption of benzodiazepine-type sedative-hypnotics, of total reported manufacture, by substance, 2012 although still low, almost doubled in Africa, and averaged 1.6 S-DDD per 1,000 inhabitants per day during the period Estazolam Others Midazolam 2010-2012. In 2012, South Africa and Nigeria had the high- 6% 4% 4% Nitrazepam est rates of consumption in this region, with 1.8 and 1.5 11% S-DDD per 1,000 inhabitants per day, respectively. Calcu- lated consumption levels of benzodiazepine-type sedative- Brotizolam hypnotics in individual countries, expressed in S-DDD per 28% 1,000 inhabitants per day, are shown in part three, table IV.2, of the present publication.

87. The reported manufacture of individual substances in this group has varied greatly over the years, since manu- facturers tend to produce large quantities of a substance at Temazepam a time in order to keep stocks on hand for future use. There 11% Triazolam have been significant fluctuations in total manufacture of 3% brotizolam, flunitrazepam and lormetazepam, in particu- Flunitrazepam Lormetazepam lar, which has affected the total level for the group as a 24% whole. In 2012, brotizolam was the most manufactured 9% substance in the group of benzodiazepine-type

Figure 22. Benzodiazepine-type sedative-hypnotics: Figure 24. Benzodiazepine-type sedative-hypnotics: average national consumption,a by region, 2004-2012 reported total manufacture, selected countries, 2003-2012

S-DDD per 1,000 inhabitants per day Billions of S-DDD 28 11 26 10 24 9 22 20 8 18 7 16 6 14 5 12 10 4 8 3 6 2 4 2 1 0 0 2004-2006 2007-2009 2010-2012 201120102009200820072006200520042003 2012a Year Year China Germany Africa Americas Asia Europe Oceania India Italy Switzerland United States Others aStatistical data submitted by Governments are used to calculate the average annual consumption for a three-year period. aThe data for 2012 are incomplete.

54 manufacture of brotizolam has increased by cent, 20per much extent, lesser by Italy and Japan. reported Global amounts hundred of several year kilograms per and, to a substance manufactured has usually been by Germany in manufacture of brotizolam, in1997.Since that year, the rotizolam is apotent hypnotic. Together- with tria stances (0.25mg). Germany was first the country to report zolam, it has lowest the S-DDD of psychotropic all sub- 89. Brotizolam figure 25). cent ofmanufacture global of such substances (see cent30 per lower accounted than in2011,still for 40per hypnotics amounting to 2.6billion S-DDD, although which, 2012, Italy manufactured sedative- benzodiazepine-type than ofmanufacture half global of such substances. In was leading the manufacturer, accounting in2003for more 2012 are shown in figure 24. Throughout that period,Italy diazepine-type sedative-hypnotics during up decade the to 88. haloxazolam was reported. nimetazepam (16million S-DDD); no manufacture of cent), loprazolam (124million S-DDD, or cent) 1.9per and ture in2012:flurazepam (141million S-DDD, per or 2.2 together accounted for about cent 4per of total manufac- or cent). 3.4per The remaining substancesgroupthis in S-DDD, or cent) 3.6per and (218million triazolam S-DDD, million S-DDD, or cent), 6.2per midazolam (231million Figure 25.

France

2% China

B Th 5% reported manufacture, selected countries, 2012 e main countries reporting manufacture of- benzo

Benzodiazepine Switzerland Italy 40% 19% -type sedative-hypnotics: total -type sedative-hypnotics: Japan 9% Others 5% Germany 20% (23 per cent).(23 per S-DDD in2012,mainly inJapan cent) (69per and for cent 71per of total imports. calculated Global Japan biggest the being importer (144kg)and accounting having imported more than 1kgof brotizolam in2012, of of total exports substance. the Nine countries reported brotizolam in2012,accounting for or 162kg, cent 80per S-DDD) cent in2012,79per of were which held in substance. stocks at Global stood 383kg(1.5billion and Japan (91kg)remained main the manufacturers of the from 372kgin2011to 446kgin2012.Germany (320kg) ­co ­G and Herzegovina (4.4 S-DDD), Croatia (3.3 S-DDD), 1,000inhabitantsper day, per Japan (8.8S-DDD), Bosnia annually 2011-2012.Measured during period the inS-DDD 3.4 tons (684million S-DDD) of substance the consumed (by cent) 44per past inthe two years, with an average of significantly 2008-2010,has decreased during period the on average to almost 6tons (1.2billion S-DDD) annually consumptioncalculated of nitrazepam, amounted which were main the importers of nitrazepam in2012.Global cent), Germany cent) (4.7per and cent) Canada (4per cent), United the Kingdom cent), (8per Nigeria (5per ing past 1kginthe five years (2008-2012). Japanper (51 countries have imported nitrazepam inquantities- exceed ing for cent 94per of nitrazepam in2012.Forty all exports main the be exporters of substance, the together account - (3.6 tons), (850kg)and China India (358kg)continued to increased from 3.2tons in 2011 to 5.1 tons in 2012. Italy annually during precedingthe nine years (2003-2011), ofExports nitrazepam, had which averaged about 4.2tons recent years, from 4.6 tons in 2009 to 1.4 tons in 2012. stocks of nitrazepam have gradually decreasing been in kg).Following trend the inmanufacture, global the (6 Russian the Federation (38kg)and New Zealand (50 kg), 2012 were (850kg),Canada(92Germany China other countries reporting manufacture of nitrazepam in turer of only 2003-2010,the nitrazepam during period the data reported by India, amajor had which been manufac- Italywhich accounted for cent. 71per In absence the of ufacture increased to 3.6tons (716million S-DDD), of reported outputs of Italy and India. In man 2012,global - nitrazepam fell to 2.9 tons, owing to sharp inthe decreases annual average of 5.2tons. In 2011,total manufacture of substance ranged 4and between 6.8tons year, per with an reported manufacture 2003-2010,global taly, period the of this and China India, indescending order, were the main manufacturers of nitrazepam past In inthe decade. 90. Nitrazepam highest rates of consumption calculated in 2012. ­A ustralia (3.1S-DDD)ustralia and Canada(3S-DDD) had the ermany. Germany remained also main the of exporter nsumption of brotizolam at stood about 1.4billion

I G ­ ermany 55

English Temazepam mainly for re-export. The calculated global consumption, which had fluctuated in the past decade between 790 kg 91. During the period 2003-2012, Italy was the leading in 2003 and 2 tons in 2010, stood at 1.2 tons (1.2 billion manufacturer and exporter of temazepam and Canada, S-DDD) in 2012. Rates of consumption continued to be India, Poland, the United Kingdom and the United States particularly high in Europe, with the highest calculated reported intermittent manufacture of the substance for rates of consumption, expressed in S-DDD per 1,000 some of those years. In the past three years, global reported inhabitants per day, recorded for Belgium (48), Spain (18), manufacture of temazepam gradually decreased from Italy (17) and Finland (10). 21.6 tons in 2010 to 14 tons in 2012, with Italy accounting for about 93 per cent (13 tons) of the total. The only other Estazolam manufacturers of the substance in 2012 were Canada (987 kg), the United States (23 kg) and Germany (6 grams). 93. After staying fairly stable during the period 2008- Global stocks of temazepam held by manufacturers stood 2010 at an average annual level of 2.5 tons, global reported at 10.4 tons in 2012 (a 28 per cent decrease compared with manufacture of estazolam gradually decreased in the fol- 2011), held mainly in Italy, the United States, the United lowing two years, to less than 1.2 tons (398 million S-DDD) Kingdom, Canada and Hungary, in descending order. in 2012, as a result of lower outputs reported by China, Global exports of temazepam were stable in the past three which was the major manufacturer of the substance dur- years, averaging 19 tons per year during the period 2010- ing the period 2003-2011. In 2012, China reported manu- 2012. Nineteen countries imported temazepam in quanti- facture of 501 kg of estazolam, which represents a 37 per ties exceeding 1 kg in 2012, with the United States cent reduction on the year before. Other countries report- remaining the largest importer (10.9 tons) and consumer ing manufacture of estazolam in 2012 were, in descending of the substance. The other major importers of temazepam order, Japan, Poland, Italy, the United States and Israel. The in 2012 were Finland (1.2 tons), the Netherlands and Aus- reported total stocks of the substance increased by more tralia (about 1.1 tons each), and Canada and the United than five-fold in 2012 and amounted to 702 kg (234 mil- Kingdom (with about 1 ton each). Global calculated con- lion S-DDD), 81 per cent of which were held in China. sumption of temazepam stood at 17.9 tons (897 million Use of the substance outside the manufacturing countries S-DDD) in 2012. The United States accounted for 51 per has increased steadily since the 1980s, with international cent of the total, while Canada, Italy, Australia and the trade in 2011 reaching the highest level ever reported Netherlands, in that order, together accounted for 39 per (405 kg). In 2012, global exports decreased slightly, to cent. According to reported statistics, measured in S-DDD 384 kg. The leading exporters of estazolam have tradition- per 1,000 inhabitants per day, Finland (17.4 S-DDD), ally been Japan and Italy; in 2012, those two countries ­Canada (10.2 S-DDD) and the Netherlands (8.5 S-DDD) accounted for 63 and 29 per cent of global exports, respec- had the highest calculated rates of consumption in 2012. tively. About 15 countries reported imports of estazolam in quantities exceeding 1 kg during the period 2008-2012. Lormetazepam In 2012, Italy (57 kg), the Netherlands (36 kg), Japan and Portugal (30 kg each), France (27 kg) and the United States (18 kg) jointly accounted for 87 per cent of total imports 92. In the period 2003-2011, total reported manufacture of the substance. Global calculated consumption of of lormetazepam was consistently above 1 ton, except in ­estazolam has continued its downward trend in the past 2003 (380 kg) and in 2007 (809 kg). The fluctuations were three years, decreasing from over 2.5 tons (848 million the result of developments in Germany and Italy, the two S-DDD) in 2009 to 533 kg (178 million S-DDD) in 2012. main manufacturers and exporters of the substance. In Measured in S-DDD per 1,000 inhabitants per day, in 2012 2012, global output of lormetazepam fell again, to 608 kg Portugal (2.6 S-DDD), Japan (2.4 S-DDD) and Poland (608 million S-DDD), reflecting the output of Italy, which (1.4 S-DDD) had the highest rates of calculated was the only country reporting manufacture of the sub- consumption. stance that year. Global stocks held by manufacturers decreased to 1.3 tons (1.3 billion S-DDD) in 2012, mainly held in Germany (65 per cent), Italy (13 per cent) and Fin- Midazolam land (10 per cent). The volume of reported international trade decreased from 1.9 tons in 2011 to 1.5 tons in 2012. 94. Global reported manufacture of midazolam, which Italy (582 kg), Germany (382 kg), Finland (197 kg) and had fluctuated significantly in the past decade within the Spain (158 kg) jointly accounted for 90 per cent of global range of 2.7 tons (2006) and 8.7 tons (2005) per year, exports in 2012. Twenty countries reported imports of dropped from 7.2 tons in 2011 to 4.6 tons in 2012. Brazil, lormetazepam in 2012, the main importers being Spain India, Israel, Italy and Switzerland have been the main (456 kg), Finland (220 kg) and Belgium (195 kg). As in the manufacturers of the substance. However, data on manu- past, some of those countries imported the substance facture of midazolam for 2012 have not been received from

56 2012, measured in S-DDD 1,000 inhabitants per day. per highest rates of consumption calculated of midazolam for and Hungary (1.5S-DDD) were countries the with the (2.3 S-DDD), Portugal (1.8S-DDD), Uruguay (1.6S-DDD) Maarten (2.4S-DDD), (2.6S-DDD), Rica Curaçao Costa million S-DDD) in2012.Switzerland (2.7S-DDD), Sint consumptionglobal of midazolam at stood 5.7tons (285 for cent 62per ofimports global of midazolam. Calculated and Brazil (486 kg). Together, countries those accounted United States and Germany (949kgeach),France (496kg) zerland (1.2tons, entirely for re-export), followed by the 2008-2012.The main importerperiod in2012was Swit- imports of midazolam inquantities above 1kginthe inmanyis used countries; over 80countries reported accounting for cent 89per total. of global Midazolam the tinued main the to be exporters of midazolam, jointly India (654kg),Italy (639kg)and Germany (576kg)con- previous years, Switzerland (3.1tons), Israel (1.8tons), represents cent a20per increase on year the before. As in reported of exports substancethe at stood 7.6 tons, which outputs2012, their ranging from 1to In 8kg. 2012,global Unitedthe States reported manufacture of midazolam in (305 kg).In and Ecuador addition, Rica, Canada, Costa tons, followed by Brazil (1.4tons), Italy (1ton) and China largestthe manufacturer of midazolam in2012,with 1.9 accountsin 2012,which for drop the inoutput. Israel was India and Switzerland didnot manufacture substance the calculated consumptioncalculated rates of triazolam. Austria (9S-DDD) and Italy (4.4S-DDD) had highest the S-DDD 1,000 inhabitants per day, per Japan (14S-DDD), main consumers in absolute terms. In 2012,measured in million S-DDD) and Austria (27million S-DDD) the being S-DDD in2012,with Japan (651million S-DDD), Italy (96 consumptioncalculated of at stood triazolam 821million ing in2012for cent almost 60 per ofimports. global Total 2012, Japan was largest the importer of account triazolam, - 2008-2012. Throughoutperiod leading the decade up to than 40 countries reported imports of inthe triazolam Switzerland (15kg),France (12kg)and India (11kg).More main exporter, followed by Italy (22kg), (85kg),Belgium to The 288kg. United States (141kg)continued the be to (6grams).ada Total of exports in2012amounted triazolam azolam in2012were Italy (48kg),Japan (6.5kg)and Can- S-DDD). The only countries manufacturereporting - tri of S-DDD), compared withor 2011(267kg, over 1billion total droppedglobal by cent, 80per to 55kg (218million not report manufacture of and, triazolam as aresult, the throughout past In the decade. United 2012,the States did leading the manufacturer hadwhich been of triazolam reportedlobal manufacture of fluctuated triazolam manufacturedthe quantities reported by United the States, significantly 2008-2012, mainly period theduring reflecting 95. Triazolam

G Spain (15 kg). France (49kg),Poland (17kg)and (43kg),South Africa main2008-2012, the importing countries in2012being 2012. About 25countries loprazolam used period inthe increased by cent 10per over 2011and at stood 189kgin United States. reportedof Global exports loprazolam manufacturedally by India, United the Kingdom and the (68 kg).In quantities small past the decade were occasion- of substancethe and held cent also 92 per of stocks global otal reported manufacture of loprazolam in2012 ditionally main the manufacturer been and leading exporter amounted reported toby all 124kg, France, has which - tra 97. Loprazolam S-DDD each). and Italy (1.7S-DDD each)and Spain and Switzerland (1.2 ants day, per recorded for Ireland (2.8S-DDD), Belgium sumption in2012,expressed inS-DDD 1,000inhabit per - in Europe,higher with highestthe rates calculated of con- substance in2012.Rates of consumption continued to be together accounted for cent 63per of total imports of the Germany (355kg)and United the States (318kg),which epam continued Spain to be (1.1tons), Canada(378kg), (3.8tons).of exports global The main importers of fluraz- ofexporter flurazepam in2012,accounting forper cent 73 stance in2012.Italy (2.8tons) remained also largest the Noada. other countries reported manufacture of sub the - for cent 80per of total output, followed by Brazil and Can- reportedlobal manufacture of flurazepam stood at Italy continued largest the to be manufacturer, accounting 4.2 tons cent is in2012,which 21per than higher in2011. 96. Flurazepam output at stood 10.2tons (1.3billion S-DDD), owing to tons in2003 to arecord of 12tons in2011.In 2012,total lonazepam that is abenzodiazepine mainly is used manufacture of clonazepam gradually increased, from 3.9 as an anti-epileptic. In reported past global the decade, 99. Clonazepam in haloxazolamtrade was reported. of nimetazepam; no manufacture of80 kg or international e remaining substances group, inthis nimetazepam in Japan. In 2012,that reported country manufacture of and haloxazolam, are manufactured and almost solely used 98. sedative-hypnotics Other benzodiazepine-type

T G C Th Benzodiazepine-type anti-epileptics Benzodiazepine-type 57

English the fact that data from India, which had reported output 2012, global calculated consumption stood at 1.3 billion of over 3 tons for 2011, had not been received. Switzerland S-DDD. The seven countries with the highest levels of cal- was the leading manufacturer of clonazepam in the world culated consumption of clonazepam were the United States during the two decades leading up to 2010. In 2011, Italy (321 million S-DDD), Brazil (281 million S-DDD), Italy became the largest manufacturer of the substance and, in (137 million S-DDD), Argentina (97 million S-DDD), 2012, its share of global output reached 43 per cent China (65 million S-DDD), the Islamic Republic of Iran (4.4 tons). The other major manufacturers of clonazepam (59 million S-DDD) and Israel (42 million S-DDD). The in 2012 were Switzerland (2.7 tons), Brazil (1.8 tons), China rates of calculated consumption of clonazepam, measured (720 kg) and Poland (284 kg) (see figure 26). in S-DDD per 1,000 inhabitants per day, in individual countries are shown in part three, table IV.4, of the pre- 100. Total reported stocks of clonazepam almost doubled, sent publication. increasing from 10.6 tons in 2011 to 20.5 tons in 2012, 76 per cent of which were held in Canada (10.8 tons) and Switzerland (4.9 tons). Global exports of clonazepam also followed an upward trend until 2011. After a record of Barbiturate-type sedative-hypnotics and 12.9 tons exported in 2011 however, total exports decreased anti-epileptics listed in Schedule IV to 11.7 tons in 2012. Switzerland, India and Italy remained the main exporters of clonazepam in 2012, together accounting for almost 80 per cent of the global total. More Allobarbital, barbital, butobarbital, than 100 countries reported imports of clonazepam in methylphenobarbital, phenobarbital, secbutabarbital 2012. Of those, eight countries imported more than 400 kg and vinylbital of the substance, both for domestic use and for re-export, namely, the United States (2.2 tons), Switzerland (1.2 tons), 101. The seven barbiturates in Schedule IV are pharma- Brazil (904 kg), Spain (902 kg), Israel (901 kg), Argentina cologically related to those in Schedule III. Five of the (838 kg), Canada (645 kg) and the Islamic Republic of Iran seven substances, namely allobarbital, barbital, butobarbi- (475 kg). Use of clonazepam expanded from about 50 tal, secbutabarbital and vinylbital, are intermediate-acting countries in 1995 to more than 140 countries in the period barbiturates and are mainly used as hypnotics (to induce 2008-2012. Global calculated consumption of the substance sleep). They are no longer used as daytime sedatives. The remained stable in the past five years and averaged other two substances, methylphenobarbital and phenobar- 1.2 ­billion S-DDD annually in the period 2008-2012. In bital, have additional properties and are also used as anti- epileptics (long-acting barbiturates). Phenobarbital continued to be the most commonly used substance in this group in 2012, followed by barbital. More information on Figure 26. Clonazepam: total reported manufacture, calculated consumption of phenobarbital is shown in part selected countries, 2003-2012 three, table IV, of the present publication.

Millions of S-DDD 102. Total reported manufacture of the seven barbiturates 1 600 in Schedule IV (for both direct medical use and the man- 1 500 1 400 ufacture of non-psychotropic substances) rose from 1 300 4 billion S-DDD in the period 1999-2000 to an average of 1 200 5.1 billion S-DDD in 2006. After that year, reported global 1 100 manufacture started to decline, with fluctuations, to a total 1 000 900 of 3.3 billion S-DDD in 2012. Changes in the quantities of 800 phenobarbital manufactured, which continued to be the 700 most widely manufactured substance in this group, 600 accounted for the changes in output. In 2012, the share of 500 400 phenobarbital in total manufacture (expressed in S-DDD) 300 was 98.6 per cent. Barbital, butobarbital and secbutabarbi- 200 tal together accounted for the remainder. No manufacture 100 0 of allobarbital or methylphenobarbital was recorded in 201120102009200820072006200520042003 2012a 2012 and no manufacture of vinylbital has been reported Year Brazil China since 1996. India Italy Poland Switzerland Others 103. In 2012, the countries with the highest calculated consumption rates of barbiturate-type sedative-hypnotics aThe data for 2012 are incomplete. in Schedule IV were, in descending order, Italy, Georgia,

58 Ukraine, in that order. Russianzil, the Federation, Japan, United the States and major users of phenobarbital in2012included Bra China, - in descending order. In terms of consumption, calculated Switzerland, Hungary, France, Philippines the and Ukraine, around cent 78per of held being them Brazil, inChina, stayed at about same the level as in2011(163tons), with countries, figure see 27. Global stocks of phenobarbital in 2012.For details on reported manufacture inselected manufactured 26tons in2011,didnot report manufacture 84 tons and 9tons, respectively, in2012.India, had which to 32tons Hungary in2012,while and Japan manufactured 2012 and Russian inthe Federation from 53.7tons in2011 from in China decreased 262 tons in 2011 to 201 tons in manufacturers of that substance. Total manufacture facture and inChina Russian the Federation, leading the Thatcanbe decrease attributed the in decrease manuto - 2003-2011, fell to 329tons (3.3billion S-DDD) in2012. fluctuatedbetween 360 and 480 tons period theduring 104. shown three, in part table IV, of presentthe publication. Brazil. More information on consumption calculated is day,per were, indescending order, Bulgaria, Ukraine and lated consumption levels, inS-DDD 1,000inhabitants per listed IV, inSchedule countries the - with highest the calcu ants day. per As for barbiturate-type the anti-epileptics ranging 0.13and between 0.03S-DDD 1,000inhabit per - ­D Thailand, Israel, France, Turkey,Lebanon, Albania,

enmark, Hungary and Lithuania, with consumption rates a 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Billions ofS-DDD The data for 2011 are incomplete. for 2011are The data Figure 27.

0 G lobal manufacturelobal of phenobarbital, which had Japan China

selected countries, 2003-2012 Phenobarbital: Russian Federation Hungary total reported manufacture, Others India 201120102009200820072006200520042003 2012 Year a and Italy, inthat order, were main the users of the 2012. Major importers of substance the included the than 120countries reported imports of phenobarbital in together accounted for cent 91per of More total exports. in 2012. 108. 2011, imported only 16 kg in 2012. 1971 Convention. Japan, had which imported 4tons in tain control measures inaccordance with article3of the imported to manufacture preparations exempted from cer Thailand. The UnitedStates someused the of amounts of 4.1tons was imported by Italy, United the States and and re-exported 7.2tons during that year. Acombined total 8.3tonsexported in2012and Germany imported 8.3tons level leading as of the exporter in2011.China, barbital, tional inbarbital trade remained more or less at same the 107. order, continued major the to be users of substance.the tion, Italy, China, United the States and Thailand,that in of barbital in2012.In terms of total consump calculated - just 7tons reported in2012.China consumption of 58 tons sumption of barbital from decreased 122tons in 2011to manufacture, global decreased the total con calculated - manufacture of non-psychotropic substances. Parallel to mainly for domestic consumption, including for in the use 2 tons eachyear.barbital The manufactured in Japan was put inthat inrecent country years has remained at about tons in 2011. Japan was otherthe major manufacturer; out - manufacture of only 21tons in2012compared with 120 leadingthe China, manufacturer of barbital, which reported This a decrease reflects majordecrease in manufacture by S-DDD) lowest in2012,the amount recorded since 1980. (245 million S-DDD) in2011to 23tons (47million 106. cent)(5 per and Japan cent). (4 per cent), Ukraine cent), (8per Germany cent), (6per France cent), Switzerland cent), (10per United the States (8per Federation cent (18 per of total imports), Brazil (11 per ­S total2011, the volume of international in trade countries year. trading substance the every Compared with psychotropictraded substances, with an average of 140 105. Based on total consumption,Based calculated Croatia, 4.9 tons cent in 2012, with 94per held inSwitzerland. of methylphenobarbital dropped from 5.6tons in2011to methylphenobarbital was reported stocks in2012.Global Switzerland and United the States. No manufacture of put reported by manufacturing the countries, namely India, and 22tons, owing10 kg to significant changesthe in out- siderably 2003-2011,ranging during between period the to 242tonsdecreased in2012.Hungary, India, China, witzerland, United the States and Germany, inthat order,

P G M A henobarbital continues one to be of most the widely t almost 17tons volume in2012,the of interna- lobal manufacturelobal of barbital fell from 122tons anufacture of methylphenobarbital fluctuated con- ­ p henobarbital ­S witzerland ­ s ubstance ­ R ussian 59 -

English 109. With 2.1 tons in 2012, the volume of international total manufacture of the entire group of barbiturates, fol- trade in methylphenobarbital remained at around the same lowed by Hungary (20 per cent), the United States (9 per level as in 2011 (1.8 tons). Croatia and Germany imported cent), Denmark (6 per cent), Germany (5 per cent) and 900 kg of the substance each, together accounting for Japan (2 per cent) (see figure 29). 86 per cent of total imports in 2012. Germany, which ­re-exported 900 kg during that year, India (500 kg) and Figure 28. Barbiturates in Schedules II, III and IV: share Switzerland (250 kg) were the main exporters during 2012. of total reported manufacture, by substance, 2012

110. During the past 10 years, allobarbital has been man- ufactured intermittently by Germany and Belgium, in Pentobarbital 12% Barbital amounts of several tons per year. Since 2010, no manufac- Amobarbital 1% ture of allobarbital has been reported. Global stocks of the 1% substance continued to decrease steadily, from 1.3 tons in Butalbital Phenobarbital 7% 2009 to 740 kg in 2012. Of these stocks, 59 per cent was 79% held in Germany and the remainder, in descending order, in Ireland, Switzerland, Turkey and Israel. With only ­Switzerland reporting an export, of 200 kg of allobarbital to Turkey during 2012, global trade in that substance fell to 200 kg, just half of its volume in 2011.

111. Secbutabarbital has been manufactured intermittently during the past decade. After Germany stopped manufac- turing the substance in 2003, the United States became the sole manufacturer. In 2012, the United States manufactured 94 kg of secbutabarbital. Global stocks of the substance went up from 56 kg in 2011 to 139 kg in 2012. Half of them were held in the United States, 34 per cent in Lebanon and 11 per cent in Germany. The United States and Lebanon were the Figure 29. Barbiturates in Schedules II, III and IV: total main users in 2012. Lebanon was the only country that reported manufacture, selected countries, 2012 reported importing the substance (25 kg) in 2012.

Others 112. No manufacture of butobarbital was reported 8% Hungary between 2000 and 2011, with the exception of Germany 20% reporting manufacture of 117 kg in 2008. In 2012, how- ever, the United States manufactured 94 kg of that sub- stance and consumed 25 kg of that amount. The other main consumer in 2012 remained Jordan, reporting total imports of 6 kg during that year. Global stocks of butobarbital Denmark increased to 106 kg in 2012, with 76 kg held by the United 6% States and 26 kg by Germany. Germany 5% Barbiturates in Schedules II, III and IV United States 9%

113. Of the 12 barbiturates listed in Schedules II, III and China IV of the 1971 Convention, five substances, phenobarbital, 50% Japan pentobarbital, butalbital, barbital and amobarbital, in that 2% order, together accounted, on average, for 99 per cent of total reported manufacture of those barbiturates during the period 2008-2012. The shares of total manufacture of the 12 substances in 2012 are shown in figure 28. Phenobar- Other sedative-hypnotics listed in bital remained the most widely manufactured barbiturate Schedule IV in 2012, accounting for 79 per cent of the total manufac- ture of the 12 barbiturates, followed by pentobarbital (12 114. Four substances from the group of sedative-­hypnotics per cent) and butalbital (7 per cent). China continued to in Schedule IV are neither barbiturates nor benzodiaz- be the leading manufacturer, accounting for 50 per cent of epines: ethchlorvynol, ethinamate, methyprylon and

60 factured 13.2tons in2011,didnot report concerning for 12.6tons and Israel for 12.3tons; India, manu which - 32.3 tons (3.2billion S-DDD) in2012.France accounted dem was stable, output with global amounting to In past the two years, total reported manufacture of zolpi- for cent 83per ofmanufacture global past inthe five years. turing countries, France, India and Israel, accounted which havethe reflected changing outputs the of main manufac- around a10-year average of 34tons. Those fluctuations substancethe fluctuatedwidely, between 24 and 50 tons, manufacture 2003-2012,global period the During nia. of control mainly in 2001, is used for treatmentthe of insom- 115. to II Schedule of 1971 the Convention. to IVin2001,wasadded Schedule rescheduled and moved ­N zolpidem. Following a decision of Commissionthe on arcotic inMarch Drugs 2013,GHB, was which initially

Z olpidem, was which brought under international

the highestthe levels of consumption calculated in 2012. Japan, Uruguay and Czech Republic, the inthat order, had cent76 per The ofexports. global United States, France, (5.3 tons) were mainthe exporters in 2012, accounting for France (9.9tons), Czech Republic the (7.4tons) and Israel substancethe to about 100countries. India (16.6tons), to 52tons in2012,with 34 countries reporting of exports psychotropic substances. reportedamounted Global exports 116. in descending order. of were which held inIsrael, France and United the States, attained 29.1tons (2.9billion S-DDD) cent in2012,75per dem have increased steadily during past the five years and icant quantities of zolpidem in2012.Total stocks of zolpi- and Brazil, in descending order, manufactured also - signif ing Czech Republic, the Japan, Argentina, Canada,Italy manufacture of zolpidem countries, in2012.Other includ-

Z olpidem is one of most the and widely traded used 61

English