Part two Deuxième partie Segunda parte statistics onPsychotropic Substances and the UnitedStates. tion 54/6) was highest inCanada, Costa Rica, Iceland, Israel, the Netherlands, Norway, Sweden on NarcoticDrugsresolu- by theBoardorreportedGovernments,pursuanttoCommission remains theleadingmanufacturer. In2011,percapitaconsumptionofmethylphenidate(calculated manufacture ofmethylphenidatehasincreasedinrecentyears,theUnitedStatesAmerica ity disorder (ADHD) continuetoincrease worldwide. Although thenumber of countries reporting substances hasdeclinedinrecentyears. schedules. The isolated use of somesubstances in Schedule I forthemanufactureofother scientific research and, in certaincases, the manufactureofpsychotropicsubstances in other data furnishedbyGovernments.Thequalityoftheanalysisdependson provided. The analysis contained in the present section of the technical publication is based on Summary 2011, thehighest valuereportedsince2002, owing toasharpincreasein manufacture of in group ofsubstancesreached2.5billionS-DDD reported manufactureofthis total stimulants, or forthetreatmentofADHD. Despite thelackofdata from Brazil,amajormanufacturerofsuch five years. barbiturates in2011.Internationaltrademosthas been declining duringthepast States, Denmark, Germany and Japan (indescending order) were the leading manufacturers of in 2011,accountingfor72percentoftotalmanufactureall12 barbiturates. China,theUnited rates during2007-2011.Phenobarbital continuedtobethemostwidelymanufacturedbarbiturate together accounted,onaverage, for 99percentoftotalreported manufacture ofthosebarbitu- ­substances—phenobarbital, butalbital, pentobarbital, barbital and amobarbital (in that order)— S-DDD.7.1 billion continued tobetheleadingmanufacturerofallbenzodiazepines Italy in 2011. in2011increasedcomparedwith2010,reaching sedative-hypnotics of benzodiazepine-type Reported manufacture substances in termsofdefined daily doses for statisticalpurposes (S-DDD). anxiolytics alprazolam and diazepam remained, inthatorder, themostmanufactured psychotropic with respecttothedevelopmentsrelatedbenzodiazepines. In 2011,thebenzodiazepine-type in particularBraziland India, affected the analysisofinformationand the resultingfindings Alackofdatafor2011fromsomemajormanufacturingcountries, as ananti-epileptic. mainly used benzodiazepine is and theinductionofgeneralanaesthesia.onlythat Clonazepamisthe ­ and are used in medical practice forpre- classified as anxiolytics and sedative-hypnotics imports ofbuprenorphine in 2011. calculated consumptionofthesubstancehascontinuedtogrow, withover60countriesreporting late 1990s.In2011,global manufacture ofbuprenorphine increased from thepreviousyear. Global treatment foropioidaddicts sincethe increasingly usedinthetreatmentofpainand substitution amphetamines in2011absoluteterms,aswelltermsofpercapitaconsumption. amount reportedaboutadecade ago. The UnitedStatesremainedthelargestconsumerof the combined total ofglobal manufacture ofthesesubstances amounted to onlyhalfofthe in 2011compared with 2010.Nevertheless,in2011 of the1971Convention,increasedslightly Manufacture ofamphetamines,theothercentralnervous system stimulantsinSchedule hyperactiv- Manufacture ofmethylphenidateand itsuse for thetreatmentofattention-deficit Use ofsubstancesincludedinScheduleIthe1971Conventionshouldbelimitedto The 14 stimulants listed in Schedule IV of the 1971 Convention are used mainly as anorectics listed inScheduleIVofthe1971Conventionareusedmainly The14stimulants Of the 12 barbiturates listed inSchedules II, IIIand IV of the 1971 Convention, five A totalof35benzodiazepines are currently under international control. Ofthose,34are of the1971Convention,hasbeen Buprenorphine, anopioidanalgesiclistedinScheduleIII comments on the reported medication statistical ­statistical II

33

English phentermine in the United States. Phentermine continues to be the most used substance in this group. In 2011, the United States accounted for almost 80 per cent of global use. The differences in consumption levels among countries and regions that have been observed for these substances became more pronounced in 2011.

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 at 82 grams at end the of 2011. stocks of DMA, have which depleted since 2008,stood been photographic film, and stopped entirely in2007. Global to decline in2002,owing to demand inthe adecrease for film several dye,tons. exceeded Manufacture of DMA started ­exclusively for manufacture inthe use of anon-controlled amphetamine (DMA) United inthe States of America, However, until 2002,annual manufacture of 2,5-dimethoxy - manufacture of non-psychotropic substances or products. ­psychotropic substances Iby inSchedule for industry the 2. exceptions noted following in the paragraphs. substancesthose have extremely been limited, with the restriction, manufacture and stocks of, as well in, as trade limited orwith use. very In no medical line with this hallucinogens and/or central system nervous stimulants results from that substances fact the all Iare inSchedule ­specifically approved Governments.their by This ­ establishments that are directly under control the of or bypurposes duly authorized persons or inmedical ­ Convention, except for limited scientific andmedical very prohibited, pursuant to provisions the of article7of the 1971 Convention. The those substancesuse of shouldbe 1. The 1971 ConventionThe 1971 not does foresee the use of Twenty-eight substances are listed Iof inSchedule the Substances inSchedule I of the1971Convention restriction scientific the vastthe majority of werewhich held United in the States. endthe of stocks of 2011,global such isomers at stood 538 kg, THC manufactured United in the States reached 288kg. At and 53kgin2010.In total 2011,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 is main the substance among isomers the I in Schedule substance listed II.delta inSchedule 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 I for manufacture the of psychotropic substances that are 4. United States, amounting to 406 grams in total. there was limited manufacture of PMAinDenmark and the ingredient that is not under international control. In 2011, manufacturethe of tamsulosin, an active pharmaceutical PMA, with quantities ranging from 24to for 71kg, in use past Denmark decade, reported intermittent manufacture of manufacturethe of non-psychotropic substances. the During another substance Ithat inSchedule by for is used industry 3. Use of psychotropic the substances included in­ para -9-Tetrahydrocannabinol (delta -Methoxy-alpha -methylphenethylamine (PMA)is -8-­Tetrahydrocannabinol -9-THC), apsychotropic Schedule Schedule 35

English Substances in Schedule II of the 1971 Convention

5. Listed in Schedule II are 17 substances that have ­little Amphetamines to moderate therapeutic usefulness and whose liability to abuse constitutes a substantial risk to public health. The 7. Both optical isomers of amfetamine (­levamfetamine substances belong to the following groups: central nervous and dexamfetamine) and their racemic­ mixture (amfeta- system stimulants; anti-emetics; hallucinogens; sedative- mine), as well as both optical­ isomers of metamfetamine hypnotics; antitussives; and antidepressants. In addition to (levomethamphetamine and ­metamfetamine) and their their various applications in human and/or veterinary racemic mixture (metamfetamine­ racemate), are listed in medicine, some of these substances are used in industry Schedule II. Statistical reports on amfetamine, dexamfeta- for the manufacture of other psychotropic substances or mine and metamfetamine have been received by the for conversion into non-psychotropic substances. ­International Narcotics Control Board from Governments since the 1970s. Statistics for levamfetamine and levometh­ amphetamine have been available since 1986, and ­statistics Central nervous system stimulants for metamfetamine racemate since 1988, owing to the dif- ferent dates on which those s­ubstances were brought under 6. Total manufacture of central nervous system stimulants­ the control of the 1971 Convention. in Schedule II fluctuated in the period 2002-2011, as can be seen in figure 1. After decreasing for two consecutive years 8. In 2011, the quantity of amphetamines listed in Sched- (2009 and 2010), total reported manufacture of this group ule II that were manufactured worldwide increased to of substances picked up again in 2011, amounting to 3 ­billion 20 tons (1.3 billion S-DDD), in contrast with the decline of defined daily doses for statistical purposes (S-DDD), mainly the previous two years (see figure 2). In 2011, dexamfeta- as a result of increased manufacture of both amfetamine and mine and amfetamine comprised almost the same share of dexamfetamine. Nevertheless, manufacture­ of amphetamines total output of amphetamines (34 per cent), while metam- followed a declining trend during the past decade and fetamine racemate and ­levamfetamine represented 15 and ­methylphenidate’s share of total output of stimulants in 13 per cent, ­respectively. In 2011, France accounted for Schedule II increased from 22.5 per cent in 2002 to 54 per 62 per cent of total manufacture of amphetamines, the cent in 2011. In 2011, amfetamine and dexamfetamine United States for 31 per cent and Hungary for the remain- accounted for 16 and 15 per cent, respectively, of total der. France continued to be the sole manufacturer­ of ­output. Together with ­methylphenidate, these substances ­levamfetamine in 2011; the substance was used in that accounted for 85 per cent of total combined­ output in 2011. ­country for reconversion into amphetamines.

Figure 1. Stimulants in Schedule II: total reported Figure 2. Amphetamines: total reported manufacture, manufacture, by substance, 2002-2011 selected countries, 2002-2011

Millions of S-DDD Tons 4500 60 55 4000 50 3500 45 3000 40 35 2500 30 2000 25 1500 20 15 1000 10 500 5 0 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011a 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Amfetamine Dexamfetamine Year Year France Germany Levamfetamine Levomethamfetamine Hungery Switzerland Metamfetamine Metamfetamine Methylphenidate racemate United States Others

a The data for 2011 are incomplete.

36 (selegiline). and levopropylhexedrine) and antiparkinsonian drugs as anorecticsused (benzfetamine, clobenzorex, fenproporex amphetamines have mainly converted been to substances deficit disorderhyperactivity (ADHD). In addition, dexamfetamine, treatment inthe is which used of attention- lisdexamfetamine (L-lysine-d-­ 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 inthe States, ­ substance; and substances not controlled under 1971 the including arewhich those optical isomers of original the intodivided two groups: other psychotropic substances, substancesnew manufactured from amphetamines may be for manufacture the of other substances figure (see 3). The are frequently products as intermediary in industry used 9. substances intermediate as Use although widespread the of substances use those for the In addition, are they to treat used narcolepsy and obesity, mainly for treatment the of ADHD United inthe States. 10. use medical Direct narcolepsy obesity or Levamfetamine (Has nouse) ADD Amphetamines IIof inSchedule 1971Convention the (Mixture ofdexamfetamineand For amphetamines purposes, direct medical are used

Direct medical use Amfetamine racemate Figure 3. levamfetamine)

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

ADD Direct medical use Metamfetamine or fenproporex amphetamine), aprodrug of Benzfetamine (Mixture ofmetamfetamineand Norephedrine Manufacture Metamfetamine racemate levomethamphetamine) benzfetamine Selegiline or Levomethamphetamine

Manufacture amphetamines Over-the- Over-the-

inhalant counter counter nasal nasal use medical Direct

in S-DDD 1,000inhabitants per day, per on basis the of statistics provided for 2011 in these calculationsin these is presented in table IIIof present the publication. present publication. tropic substances is explained explanatory inthe note to table IVof the psychotropic substances. United Kingdom United Austria Denmark Israel Germany Chile Netherlands Sweden Iceland States United Country andmedical industrial byfurnished Governments) consumption and of calculated 11. fordestined 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 continued inmost countries. While France has tradition- treatment of considerably obesity has been reduced or dis- New Zealand Kingdom United Finland 0.08 Belgium 0.18 Norway 0.39 Switzerland 0.40 Australia 1.41 Canada Country in 2011. 1and 2respectively, inorder of rate their of use tables 3 2 1

Table 2. The list of defined daily doses (S-DDD)statisticalfor used purposes for Theused calculating levelsmethod of consumption of psycho- Excluding for use manufacture the of other amphetamines and non- Table 1. The countrieswiththe highest levels of (i.e.reported Amphetamines: calculated consumption rate, selected countries, 2010and 2011 Amphetamines: reported consumption rate, selected countries, 2011 1 uses of uses amphetamines, calculated

(S-DDD per 1,000 inhabitants perday) per1,000 (S-DDD (S-DDD per 1,000 inhabitants perday) per1,000 (S-DDD 2010 15.74 – 0.22 – 0.51 0.02 0.02 0.06 0.03 0.04 2.84 0.29

2 and expressed 3 are listed in 18.67 0.04 0.06 1.58 0.01 0.07 0.08 0.13 0.16 0.31 2011 2011 – 37

English Comments on amphetamines, by substance ture of nasal inhalants for domestic use, which are exempted in that country from certain control measures in accord- 12. The manufacture of amfetamine gradually increased ance with article 3 of the 1971 Convention. until it reached a peak of 30 tons in 1998, before falling gradually to 4.3 tons in 2010. In 2011, global manufacture 16. A total of 3.1 tons of metamfetamine racemate was of amfetamine rose again to 6.9 tons, with France and the manufactured in 2011. During the period 2007-2011, United States accounting for 65 and 34 per cent, ­respectively. France and Hungary accounted for on average 77 and 23 Amfetamine is used mainly in combination with dexamfe- per cent of global output, respectively. The substance has tamine in the United States. In 2011, about 82 per cent of mainly been exported to the United States, where it has global stocks (7 tons) of amfetamine were held in the either been converted into non-controlled substances or United States; the rest were held in France. The United divided into levomethamphetamine and metamfetamine. States and France, in that order, also remained the main Global stocks in 2011 stood at 2.6 tons. International trade exporters of the substance. Total exports of amfetamine in averaged 1.38 tons during 2007-2011, with the United 2011 amounted to 480 kg, the main importers being, in States accounting for all imports. Levomethamphetamine descending order, Canada, Germany and Chile. has been used mainly for export and has also been ­converted, in smaller quantities, into selegiline. 13. The trends in manufacture of dexamfetamine reflect ­Metamfetamine obtained during the process of separating developments in the United States. During the 1980s, total levomethamphetamine has been added to stocks. output was fairly stable, at approximately 350 kg annually. It increased afterwards, although with many fluctuations, Methylphenidate to 11 tons in 2009 and then decreased sharply to less than 5 tons in 2010. In 2011, however, the United States ­doubled 17. The use of methylphenidate4 for medical purposes has its output, to 4 tons; with the output of France (2.8 tons), increased significantly since the 1990s. Methylphenidate is total manufacture of that substance reached 6.8 tons. The used for the treatment of ADHD, primarily in children. It United States remained the main user of dexamfetamine is also prescribed for the treatment of narcolepsy. The for medical purposes, although such use was also noted in increase in the manufacture and use of methylphenidate is a number of other countries, including, in descending mainly the result of developments in the United States, order, Australia, Canada, Norway, Sweden, Belgium and where the substance is heavily advertised, including directly Switzerland. Global stocks of dexamfetamine increased to potential consumers. Since 2000, however, the use of from 1 ton in 1995 to a little over 10 tons in 2011. Almost methylphenidate for the treatment of ADHD has been 30 countries reported imports of the substance,­ amounting ­rising sharply in many other countries. to 577 kg in total in 2011. Canada, ­Australia and Germany were the main importers, accounting for 40, 28 and 23 per 18. Global manufacture of methylphenidate started to cent, respectively, of the total. increase rapidly in the 1990s, although with some fluctua- tions, reaching 48 tons in 2011, the highest amount ever 14. Global reported manufacture of metamfetamine, reported (see figure 4). Since the 1990s, the United States which amounted to 9.5 tons in 1999, has decreased since has been the leading manufacturer of methylphenidate, that year. The decline has been even more pronounced increasing its output from 1.8 tons in 1990 to 41 tons in since 2008, after France and Switzerland ceased manufac- 2011, which represented 86 per cent of global output. Until turing the substance, with total output reaching less than 2009, the United Kingdom was the second largest manu- 3 kg in 2011. The main regular user of metamfetamine facturer of the substance. In 2010, however, manufacture (mainly for industrial purposes) was the United States. of methylphenidate in that country amounted to only a few International trade in metamfetamine has been limited in grams. In 2011 that country again became the second volume; in 2011, total exports amounted to 362 grams. ­largest manufacturer, with output of 3 tons of the substance.­ The other countries reporting manufacture of amounts of 15. During the period 2002-2011, total reported manu- methylphenidate exceeding 1 ton in 2011 were Canada facture of levomethamphetamine fluctuated between no (1.8 tons), Switzerland (1.1 tons) and Spain (1 ton); their output (in 2009 and 2010) and 4.6 tons (2002). While ­combined output accounted for 8 per cent of global ­Germany, France, the United States and the Czech ­Republic ­manufacture. Most of the methylphenidate manufactured were the main manufacturers of levomethamphetamine in in the United States continued to be used domestically, the past, France was the sole manufacturer of the substance although exports from that country have increased in (624 kg) in 2011. The main user of levomethamphetamine recent years. Global stocks of methylphenidate have for industrial purposes until 2008 was Germany, followed increased in tandem with the rise in manufacture, ­increasing by the United States, France and the Czech Republic. In recent years, about 470 kg of levomethamphetamine have 4 been used annually in the United States for the manufac- The data for 2011 are incomplete.

38 and Australia. Canada, Germany, Spain, Netherlands, the Israel, Sweden methyl worldwide of use methylphenidate. The main users of accounting for, on average, cent 66per of calculated the inthat2009-2011, use averaged country 1billion S-DDD, consumption of methylphenidate. In three-year the period with highest the calculated country ­traditionally the been S-DDD) figure in 2011 (see 5). The UnitedStates has has followed an upward trend, reaching 52 tons (1.7 billion 20. imports of methylphenidate in amounts exceeding 10 kg. 2002-2011. In 2011,40countries and territories reported phenidate continued gradually during to rise period the number of countries and territories importing methyl­ Switzerland, United the Kingdom, Spain and Germany. The countriesexporting in2011were, indescending order, accounted for cent 40 per of major totalOther exports. United States in2011,it leading the exporter; has been of methylphenidate until 2006.Since 2007,however, the from 530kgto 22tons. Switzerland was main the exporter in methylphenidate 1992-2011 increased during period the continue met to mainly be by imports. International trade ­requirements for methylphenidate outside United the States has spread other to countries, several medical the 19. cent of stocks at global end the of 2011. to 43tons in2011.The United States accounted forper 72 a 50 10 15 20 25 30 35 40 45 Tons Figure 4.

0 5 The data for 2011 are incomplete. for 2011are The data The calculated global consumptionglobal Thecalculated of methylphenidate Despite that fact the manufacture of methylphenidate ­phenidate in2011outside of United the States were 2002 United States Switzerland 2003 Methylphenidate: total reported manufacture, selected countries, 2002-2011 2004 2005 2006 Canada United Kingdom 2007 2008 2009 Others 2010 2011 Year a

United States United Country 21. (expressed inS-DDD 1,000inhabitants per day) per in2011. and 4,respectively, inorder of level their of ­ statistics provided for 2010 and 2011)are listed intables 3 consumption of methylphenidate on (calculated basis of the reported (i.e. by furnished Governments) and calculated Iceland Israel Sweden Netherlands Denmark Germany Chile Saint Helena Norfolk Islands United Kingdom United Austria Estonia Palau El Salvador 1200 1000 1400 1600 1800 Millions ofS-DDD 200 400 600 800 Table 3. 0 The countries and territorieswiththe highest levels of Figure 5. 2002 Germany The Netherlands United States consumption, bycountry2002-2011 2003 Methylphenidate: reported consumption rate, Methylphenidate: calculated medical 2004 2010 and 2011 2005 2006

Canada Others United Kingdom (S-DDD per 1,000 inhabitants perday) per1,000 (S-DDD 2007 2008 2010 15.50 14.72 7.38 4.92 5.09 1.98 1.10 0.58 0.15 0.44 0.06 2009 – 6.63 – 0.96 – 0.18 – consumption 2010 2011 Year 19.93 14.07 7.40 6.22 5.87 1.97 1.53 0.76 0.50 0.30 0.15 0.10 2011 39

English Table 4. Methylphenidate: calculated consumption rate, United States were the main users of the substance, report- 2011 ing consumption of 110 kg and 17 kg, respectively.

(S-DDD per 1,000 inhabitants per day) Country 2011 Canada 12.34 Sedative-hypnotics Costa Rica 10.92 Norway 6.51 Portugal 4.04 Secobarbital Spain 3.02 New Zealand 2.61 24. Since 2000, Germany has been the major manufac- Andorra 2.50 turer of secobarbital. In 2011, its output amounted to Belgium 2.47 Australia 2.24 816 kg, accounting for about 80 per cent of total global Chile 1.54 manufacture (1,031 kg). The United States reported ­manufacture of 207 kg, while Japan and Canada accounted for the rest. In 2011, global stocks of secobarbital stood at Anti-emetics 671 kg; the majority (86 per cent) were held in Germany. 25. In 2011, global trade volume of secobarbital reached delta-9-Tetrahydrocannabinol and its stereochemical 830 kg (8.3 million S-DDD), an increase of 30 per cent variants from 2010. Germany continued to be the leading exporter of the substance, while the United Kingdom was the main 22. During the period 2008-2011, global manufacture of importer. The United Kingdom, the United States, Sweden delta-9-THC gradually decreased from 233 kg (7.8 ­million and Germany (in descending order) were the major users S-DDD) in 2008 to 66 kg (2.2 million S-DDD) in 2011, in 2011. led by a decrease in manufacture by the United States, the largest manufacturer of the substance worldwide. In 2011, the United States manufactured 58 kg of delta-9-THC, the majority of which was for domestic consumption. Germany­ Antitussives remained the second largest manufacturer in 2011, ­reporting 8 kg of manufacture. Stocks held in the United States amounted to 127 kg, accounting for 75 per cent of Zipeprol the global total (170 kg) at the end of 2011, followed by Germany (15 per cent of global stocks) and Switzerland 26. The Republic of Korea, which had stopped manufac- (9 per cent). turing zipeprol in 1999, resumed its manufacture in 2008 and 2009 mainly for domestic consumption. For 2011, nei- 23. International trade in delta-9-THC remained at a low ther manufacture nor international trade of the substance level in 2011 (14.4 kg). The largest exporter was Germany, was reported. The Plurinational State of Bolivia, the main with the United Kingdom, Austria, Malaysia, Switzerland importer of the substance in previous years, reported con- and Canada being the main importers. Germany and the sumption of 91 kg for 2011

Substances in Schedule III of the 1971 Convention

27. Nine substances are listed in Schedule III. According of central nervous­ system stimulants. Six substances belong to the scheduling criteria adopted by the World Health to the group of sedative-hypnotics: four barbiturates ­Organization, substances in Schedule III are those whose (­amobarbital, butalbital, cyclobarbital and pentobarbital), ­liability to abuse constitutes a substantial risk to public glutethimide and flunitrazepam. The two remaining health and which have moderate to great therapeutic ­substances, buprenorphine and pentazocine, belong to the ­usefulness. One substance, cathine, belongs to the group group of analgesics.

40 Italy, Mexico and South Africa. main importers of cathine during were that same period of 4 tons in 2007 and a minimum of 871 kg in 2011. The stance averaged 2tons during that time, with amaximum of exports 2007-2011.Global sub the - cathine period inthe 29. werethese held mainly in Germany and Mexico. stocksGlobal of cathine to 1,548kgin2011; decreased No manufacture of substance the was reported in 2011. 500 kgwas manufactured inIndia and 300kginChina. by In China. output 2010,global reached of 800kg, which cathine declined sharply of to all was which 55kg, reported were and China India. From 2007to 2009,manufacture of countries reporting manufacture of cathine inrecent years many was only the manufacturer of substance. the Other ofand 5.9tons, apeak reached in2007.Until 2003,Ger no output between 2002-2011, varying during period the Manufacture­purposes. of cathine fluctuated considerably 28. Cathine 2007-2011. ­manufacturing countries, in total output, during period the cent of total. the Figure 7shows share the of main the Germany and United the States accounted for over 96 per As inprevious years, manufacture Denmark, inChina, total of2011, aglobal 1.11billion S-DDD was reported. manufacture reported by and China United the States. For substancesthese has gradually increased, owing to increased S-DDD figure (see 6). manufactureglobal Since 2009, of fluctuatedbetween 0.82 billion S-DDD and 1.69 billion amobarbital, butalbital, cyclobarbital and pentobarbital 31. pentobarbital and cyclobarbital butalbital, Amobarbital, clandestine laboratories. diverted frombeen licit circuits rather than synthesized in biturates encountered on illicit the market have usually duration of action and potency. bar benzodiazepines, Like vulsant property. Barbiturates differof in speed onset, mainlyused as anti-epileptics or for anticon selective their - tions (ultra-short-acting substances). Nowadays, are they in someas anaesthetics cases, for short interven- surgery prescribed forbe treatment the of anxiety and stress, and, 30. Sedative-hypnotics listed in Schedule III Sedative-hypnotics India and Germany were main the exporters of Cathine as astimulant is used and for industrial During 2002-2011,totalDuring reported manufacture of sedative-hypnotics, as Classified barbiturates to used Central nervoussystemstimulants - - manufacture in2011included (indescending order) 94 per cent total. of countries global Other the that reported facture in2011.Their total output accounted for over manufacturers of substance, the reported increased manu - since 2002.The United States Germany,and thetwo major 48.7 tons (487million S-DDD) highest in2011, the level 32. Billions ofS-DDD 1.0 1.1 1.2 1.3 Billions ofS-DDD 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0 0 total reported manufacture, bysubstance,2002-2011 reported manufacture, selected countries, 2007-2011 Total reported manufacture of pentobarbital reached Figure 7. 2002 Figure 6. 2007 Cyclobarbital Germany China Amobarbital 2003 Barbiturates listed in Schedule III: total 2004 Barbiturates listed in Schedule III: 2008 2005 Denmark United States 2006 Butalbital Pentobarbital 2009 2007 2008 2010 2009 2010 World total 2011 2011

Year Year 41

English ­Denmark, Japan and Canada. Global stocks stood at 36. Cyclobarbital continues to be manufactured and used 26 tons in 2011; about 68 per cent of them were held in mainly in Europe, although the quantities manufactured Germany and the United States. In 2011, the largest user decreased considerably after 1998. Poland has been the sole of pentobarbital continued to be the United States, followed manufacturer of cyclobarbital since 2004, after Germany by Germany, France, the United Kingdom, Australia, and Latvia stopped manufacturing the substance in 2003. ­Canada and the Netherlands. In 2011, manufacture by Poland grew considerably, to almost 400 kg (almost 2 million S-DDD), more than dou- 33. Following a declining trend in international trade in ble the quantities manufactured in 2010. Global trade vol- pentobarbital during 2008-2010, the global trade volume ume of cyclobarbital amounted to 286 kg in 2011. Poland of pentobarbital increased from 25 tons in 2010 to 30 tons continued to be the major exporter, while Georgia, Latvia in 2011. As in previous years, Germany, the United States, and the Russian Federation remained the major importers Canada, France and Denmark (in descending order) and users. Global stocks of cyclobarbital stood at 16 kg at remained the major exporters, together accounting for the end of 2011; they were held solely in Germany. about 97 per cent of global exports in 2011. Major importers­ in 2011 continued to be (in descending order) Canada, Flunitrazepam France, the United States, the United Kingdom, Australia and the Netherlands, each of which imported quantities of 37. Flunitrazepam remains one of the most frequently more than 2 tons. abused benzodiazepines. The substance is diverted mainly from domestic distribution channels. Preparations containing­ 34. Following a declining trend during 2002-2005, global flunitrazepam have often been diverted from the licit ­market manufacture of butalbital has picked up since 2006, and smuggled into countries where there is an illicit demand ­reaching nearly 40 tons in 2011. Denmark remained the for such preparations. Because it had frequently­ been largest manufacturer of the substance, followed by the diverted and abused, flunitrazepam was transferred from United States and Canada. Manufacture in the United Schedule IV to Schedule III in 1995. ­Several countries, States increased significantly in the past three years, from including major manufacturers and importers of the 0.6 tons in 2009 to over 11 tons in 2011. Another major ­substance, have adopted strict control ­policies for manufacturer, Germany, did not report manufacture for ­flunitrazepam, in close cooperation with thepharmaceutical ­ 2011. About 77 per cent of the butalbital manufactured in industry. Most of the preparations purportedly containing Denmark in 2011 was for export, whereas the quantities flunitrazepam that are sold on the illicit ­market are ­counterfeit manufactured in the United States were used mainly for products that do not contain that substance. domestic consumption. In that country, some of the ­substance was used for the manufacture of preparations 38. In medical practice, flunitrazepam, similarly to exempted from certain control measures, in accordance ­diazepam, has been used for pre-medication and for ­general with article 3 of the 1971 Convention. In 2011, over 94 per anaesthesia. Prior to 1996, flunitrazepam wasmanufactured ­ cent of global stocks were held in Denmark and the United in several countries. After 1996, only Italy and Switzerland States. Global trade volume remained stable at about reported its manufacture. The manufacture of flunitra­ 21 tons in 2011, with Denmark being the largest exporter zepam in Switzerland, the main manufacturer of the and the United States, Italy and Canada (in descending ­substance, has fluctuated greatly; in some years, such as order) being the main importers. 2010 and 2011, no manufacture of the substance took place in that country. Those fluctuations are reflected in total 35. In 2011, global manufacture of amobarbital continued global manufacture of flunitrazepam (see figures 20 and 21 to increase, to a total of 9.4 tons, an increase of 62 per cent and para. 84 below), which in 2011 stood at 516 kg, with from 2010. This increase can be attributed to the significant Italy accounting for almost the entire output. increase in manufacture by China and Japan, the two major countries manufacturing and using amobarbital. China 39. International trade in flunitrazepam averaged 1,066 kg reported having manufactured 7.2 tons of the substance in per year during the period 2009-2011, and stood at 1 ton in 2011, accounting for 77 per cent of the global total. The 2011. Italy and Switzerland were the leading ­exporters of ­majority of the quantities manufactured in China were for ­flunitrazepam, together accounting on average for 92 per domestic use. Japan reported manufacture of 2.2 tons in 2011, cent of global exports of the substance during the period a considerable increase from 0.8 tons in 2010. Total 2008-2011. More than 50 countries reported imports or use ­international trade in amobarbital also increased significantly of flunitrazepam during the period 2009-2011. Japan from 2010 to 2011, owing mainly to a large increase in exports remained the leading importer of flunitrazepam in 2011, from China and Germany. Thailand, the UnitedKingdom ­ and importing 670 kg, or 81 per cent of global imports of the Belgium (in that order) were the main importers­ of the substance. Mexico, Germany and Switzerland­ reported ­substance in 2011. Total calculated consumption of­ imports ranging from 25 to 50 kg, accounting together for amo­barbital reached 8.4 tons (84 million S-DDD) in 2011. 12 per cent of global imports of the substance in 2011.

42 ­Switzerland, Australia, Czech the Republic and France. order) United the States, Germany, United the 2010. The majority the of stocks were held in(in­ tons in2011,an increase of cent 63per from to about 3 facture for stocks 2011.Global of substance the amounted As for was case the 2010,Australia didnot report manu- Czech Republic kg),the (232kg)and India (72kg). (406 United kg),the Kingdom (739kg),Switzerland (1,250 considerable increase from 147kgin2010),Belgium ­manufacturing countries: United the States a (1,546kg, reported by nine countries, including major the again, with a total of 4,253 kg (532 million S-DDD) phine for that year. In manufacture 2011,global increased United Kingdom, didnot report manufacture of buprenor as some major manufacturers, such as Australia and the addiction. In 2010,total manufacture dropped significantly, for doses inhigher treatmentused the of pain and opioid late inthe beginning 1990s,as substance the beganto be manufacture of buprenorphine to started increase ­ mainlyused as analgesics. As shown infigure global 8, 40. Buprenorphine ntd States (2,872kg), Germany (821kg),France United ­substance. Major importers in 2011included the 2011, with over 60countries reporting imports of the to increase since 1992, reaching atotal of nearly 5 tons in 41. Tons 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 stocks, importsand calculated consumption, 1992-2011 0 Figure 8.

The volume trade in of buprenorphine has ­

1992 Analgesics listed in Schedule III Buprenorphine belongs to family the of opioids 1993 Manufacture Import 1994

1995 Buprenorphine: total reported manufacture,

1996

1997

1998

1999

2000

2001 Stocks Calculated consumption 2002

2003

2004

2005

2006

2007

2008

2009 descending continued ­Kingdom, 2010 gradually

Year 2011 - among opioid reported. been has addicts, also by afew countries. Abuse of substance, the particularly from domestic distribution channels, have reported been States. Diversions of preparations of buprenorphine, mainly Hungary, Ireland, Malaysia, Switzerland and United the including inAustralia, Austria, Denmark, France, ­ substitution treatment programmes for opioid dependence, countriesorphine inseveral indetoxification is used and shown intable IV.5 of present the publication. Bupren­ buprenorphine inS-DDD 1,000inhabitants per day per is and United the States. Thecalculated consumption of ­Iceland, Norway, Portugal, Slovenia, Sweden, Switzerland ­continued France, highest inBelgium, to be Germany, capita per calculated consumption of buprenorphine 5.4 tons (681million S-DDD) in2011.As inprevious years, increased from 4.2tons (531million S-DDD) in2010to 42. exports. together accounting for nearly cent 97per of total global Australia (175 kg) were major the exporters in2011, Czech Republicthe (221kg),Switzerland (202kg)and Kingdom (680kg),Germany (2,617kg),Belgium (507kg), significant increases in importsfrom 2010. The United States, Germany and Islamic the Republic of Iran reported kg) and Spain (105 kg). Among countries, those United the Islamic the Republic of Iran (116kg),Italy(390 kg), (105 2,320 kgin2011.The major exporters continuedbe to 2009. Total from decreased exports 3,166kgin2010to 44. and China. (in descending order) United the States, Slovenia, Japan United States. Major users of substance the in2011included of stock data from India and stocks decreased held inthe cent from 2010,to 2,645kgin2011,as aresult of absence reportedGlobal stocks of substance the by decreased, 46per 2010, didnot report manufacture of substance the in2011. reported ­ the ­manufacture of 406kgand respectively. 106kg, India, which twothe other major manufacturers in2011,reported United States was mainly for domestic use. Italy and China, pentazocine since­country 2002.The manufactured the in Unitedin the States, highest the level reported by that amounted to of 1,369kg, 857kgwas which manufactured of pentazocine. In 2011,total manufacture of substance the put of India and Italy, two the major manufacturing ­ 2002-2011, mainly as aresult of ­ S-DDD) and 8.5tons (42million S-DDD) ­ of substance the fluctuatedbetween 2.7 tons (13 million of similar touses those morphine. total Global ­ 43. Pentazocine Pentazocine is an opioid analgesic with properties and Global calculated consumption calculated Global of buprenorphine Global trade in pentazocine has been declining has inpentazocine since trade been Global manufacture of 4.7tons of substance the for fluctuationsthe in total out- during the period during period the manufacture Germany, countries 43

English India (1,168 kg) and Italy (707 kg). Total imports in 2011 order) remained the major importers in 2011, together also declined, by 47 per cent from 2010, owing mainly to accounting for 60 per cent of total imports. Nigeria and the decrease in imports by the major importing countries. Pakistan, the two other major importers and users, have Japan, Switzerland, Portugal and Canada (in descending not submitted data for 2011 to the Board.

Substances in Schedule IV of the 1971 Convention

45. Sixty-two substances with various applications in 49. The fluctuations in total calculated globalconsumption ­ medicine are listed in Schedule IV. They belong to the of central nervous system stimulants listed in Schedule IV ­following groups: central nervous system stimulants (see figure 12) mainly reflect changes in the use of phenter- (14 substances); benzodiazepine-type anxiolytics mine in the United States and the use of amfepramone and (22 ­substances); other anxiolytics (1 substance); fenproporex in Brazil. A total of 2.25 billion S-DDD of ­benzodiazepine-type sedative-hypnotics (11 substances); ­central nervous system stimulants listed in Schedule IV benzodiazepine-type anti-epileptics (1 substance); were used in 2011. Of those, phentermine (1.9 billion ­barbiturate-type sedative-hypnotics and anti-epileptics S-DDD) accounted for 84 per cent, followed by mazindol (7 substances); other sedative-hypnotics (5 substances); (188 ­million S-DDD, or 8 per cent), phendimetrazine and analgesics (1 substance). (84 million S-DDD, or 4 per cent), and amfepramone (37 ­million S-DDD, or 1.6 per cent). In the absence of data from Brazil,­ about 80 per cent of global calculated ­consumption of ­stimulants in Schedule IV in 2011 was Central nervous system stimulants accounted for by the United States.

46. Fourteen stimulants are listed in Schedule IV: 50. Calculated consumption of Schedule IV stimulants in amfepramone, aminorex, benzfetamine, etilamfetamine, the Americas remained the highest worldwide, at approx- fencamfamin, fenproporex, mazindol, mefenorex, mesocarb,­ imately the same levels of a decade ago (see figure 13). pemoline, phendimetrazine, phentermine, pipradrol and Decreases in the use of stimulants in Brazil that have been pyrovalerone. The stimulants in Schedule IV are used essentially as anorectics or for the treatment of ADHD. Figure 9. Central nervous system stimulants in 47. Reported manufacture of central nervous system stim- Schedule IV: total reported manufacture, by substance, ulants in Schedule IV has been on the rise during the period 2002-2011 2002-2011, in spite of many fluctuations (seefigure 9). ­ Those Billions of S-DDD fluctuations were mainly a result of ­developments in Brazil, 2.6 Germany and the United States, which were the main 2.4 ­manufacturers during that period. In 2011, global 2.2 ­manufacture of this group of substances amounted to 2.0 2.5 ­billion S-DDD, the highest figure reported during the 1.8 period, in spite of the fact that data for that year have not 1.6 been received from Brazil, one of the traditional 1.4 ­manufacturing countries for this group (see figure 10). 1.2 1.0 48. In 2011, phentermine (2.28 billion S-DDD) accounted 0.8 for 91 per cent of total reported manufacture of all 0.6 ­stimulants in Schedule IV, while the reported manufacture 0.4 0.2 of mazindol (130 million S-DDD) accounted for 5 per cent, 0.0 phendimetrazine accounted for 3 per cent (73 million 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011a Year S-DDD) and amfepramone accounted for 1 per cent Amfepramone Fenproporex (34 million S-DDD) (see figure 11). Reported manufacture Mazindol Pemoline of the other central nervous system stimulants in Sched- Phendimetrazine Phentermine ule IV accounted for about 0.3 per cent of total reported manufacture. a The data for 2011 are incomplete.

44 a mainly as a result of developments in South Africa, increasedalthough markedly and they Oceania, inAfrica 2009-2011 compared 2006-2008, period with period the of consumption inAsia decreased and Europe during the ­consumption United inthe levels observed States. Levels achieved since 2006have nearly been offset risingby Schedule 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

The data for 2011 are incomplete. for 2011are The data 0 Schedule Figure 11. Figure 10. 2002 IV: total reported manufacture, selected countries, Italy Brazil Argentina 2003 IV: share oftotalreported manufacture, Mazindol selected Central nervoussystemstimulantsin 2004 Central nervoussystemstimulantsin 5% 2005 Amfepramone 2002-2011 substances, 2011 Germany United States Belgium 2006 1% 2007 Phendimetrazine 2008 3% 2009 Phentermine World Total 91% 2010 2011 Year a daily doses for statistical purposes (S-DDD). purposes for statistical doses daily given year,in a consumption global ­approximate in defined expressed which is a Republic (3.1) and Hong Kong SAR of (2.4). China (14.6),ArgentinaZealand (9),Australia Czech (8.7),the that didnot report consumption inNew were observed ­inhabitants day, per among countries the and territories consumption rates, expressed inS-DDD 1,000 per ­Australia and New In Zealand. highest 2011,the calculated annual consumption for a three-year period. three-year annual consumptionfora a Schedule 10 11 12 Billions ofS-DDD 0.6 1.0 1.2 1.8 2.0 2.2 2.4 1.4 0.2 0.4 0.8 1.6 Statistical data submitted by Governmentsareusedtocalculate the submitted data Statistical Statistical data submitted by Governments are used to calculate average to calculate used are Governments by submitted data Statistical S-DDD per1,000inhabitantsday S-DDD Schedule 0 1 2 3 4 5 6 7 8 9 0 Figure 12. Figure 13. 2002 Africa IV: calculated global consumption, Pemoline Amfepramone 2003-2005 IV: average national consumption, 2003 2004 Central nervoussystemstimulantsin Central nervoussystemstimulantsin Americas 2005 2002-2011 2003-2011 Fenproporex Phentermine 2006 2006-2008 Asia 2007 2008 Europe 2009 Others Mazindol a 2009-2011 bysubstance, a byregion, 2010 Oceania 2011 Year Year 45

English 51. Phentermine has always been the most manufactured 55. With the exception of 2005 and 2006, when substance in the group of stimulants in Schedule IV, ­manufacture of benzfetamine was reported by Ireland, Italy although its share of total manufacture within this group and Switzerland, the United States was the sole ­manufacturer has fluctuated. Total reported manufacture of the substance of benzfetamine during the decade leading up to 2010. In increased from an average of 9.5 tons annually during the 2011, the United States and Italy reported manufacture of period 1991-1995 to 50 tons in 1996, the highest level ever 318 kg and 136 kg, respectively. International trade in reported. Manufacture of the substance dropped in 1997 ­benzfetamine remained limited in 2011, with only the and ceased in 1998. After 1999, global reported ­manufacture United States reporting imports of the substance, from of the substance picked up again and remained volatile. stocks held by Italy. The United States was also the major Manufacture of 34 tons of phentermine was reported for consumer of benzfetamine in the period 2002-2011; it 2011, with more than 70 per cent of that accounted for by reported consumption of 373 kg for 2011. the United States, followed by Germany and Italy. 56. Global reported manufacture of fenproporex has 52. International trade in phentermine in 2011 amounted declined steadily since 2005, from 9.5 tons in that year to to 13.1 tons, a 20 per cent increase from the average of 11 1.8 tons in 2010, owing to the decrease in manufacture tons reported for the years 2008-2010. In recent years, the reported by Belgium and Brazil, which have been virtually main exporter of the substance has been Germany the only manufacturing countries since 2007. No (­reporting exports of about 7 tons in 2011), ­followed by ­manufacture of the substance was reported for 2011, partly Italy and the United States. In 2011, 25 countries­ reported owing to the fact that Brazil submitted no report for that imports of phentermine in quantities of more than 1 kg. year. Total reported imports of the substance, which had Major importers of phentermine were the United States averaged 3.4 tons per year during the period 2006-2010, (5.66 tons), Australia (2.08 tons), Mexico (572 kg), New dropped to 344 kg in 2011. Whereas Germany and Brazil Zealand (420 kg), South Africa (350 kg), Austria (297 kg) were the leading importers of fenproporex during the and Switzerland (296 kg). Some of those countries period 2005-2009, Mexico was the major importer of the ­re-exported a major share of their imports. substance in 2010 and 2011.

53. Italy was the main manufacturer of phendimetrazine 57. Argentina has been the sole manufacturer of mazin- in the period 2007-2011. Manufacture in that country dol since 2008. It reported an annual average output of 197 amounted to 5.2 tons in 2009, then declined in the kg of the substance during the period 2007-2010. Of the ­following years, reaching 3.3 tons in 2011. Phendimetrazine­ total 130 kg of mazindol manufactured in 2011, 127 kg was manufactured in Italy is mainly destined for export. Inter- manufactured in Argentina, while the United Kingdom national trade reached 4.7 tons in 2011, of which Italy manufactured the remaining 3 kg. Reported global stocks accounted for 88 per cent. Traditionally, the United States, of the substance at the end of 2011 amounted to 42 kg, followed by the Republic of Korea, have been the main mostly held by Switzerland. That country and the United importers and users of the substance. In 2011, the United Kingdom were the main exporters of the substance in 2011, States (3.6 tons), Italy (78 kg) and South Africa (9 kg) were when total reported exports were 6 kg. the only countries reporting imports of phendimetrazine in quantities of more than 1 kg. 58. No manufacture of pemoline was reported from 2005 to 2007. Since 2008, average manufacture of 158 kg annually­ 54. Total reported manufacture of amfepramone has has been reported by the Netherlands and, in much smaller decreased significantly, from 23 tons in 2006 to about 2.6 quantities, Japan. In 2011, total output of the substance fell tons in 2011, owing mainly to a decline in manufacture to 24 kg, all reported by the Netherlands, which has also reported by Brazil until 2010 and the absence of data from been the main exporter. Stocks of pemoline have declined that country for 2011. Three countries reported having steadily, from 7 tons in 2004 to 61 kg at the end of 2011. manufactured amfepramone in 2011: Switzerland (1.6 During the decade ending in 2011, imports of pemoline tons), Italy (746 kg) and the United States (211 kg). Brazil,­ averaged 434 kg yearly. In 2011, total imports reported by which reported the manufacture of 7.9 tons of the Japan, Chile and Switzerland (in descending order) dropped ­substance annually on average in the period 2007-2010, to 101 kg. In addition to being used as a stimulant, pemoline­ submitted no report for 2011. Switzerland was the main is used for the treatment of ADHD. exporter of amfepramone during the decade leading up to 2011, and accounted for 71 per cent of global exports of the substance­ in 2011. The largest imports of amfepramone were reported by the United States (1.2 tons), Germany Benzodiazepines (688 kg) and Chile (298 kg). Eight other countries reported imports of amfepramone in quantities of more than 1 kg 59. Thirty-three benzodiazepines were included in in 2011. ­Schedule IV in 1984. Midazolam was added to Schedule IV

46 (6.6 61. anxiolytics. cent17 per ofmanufacture global of benzodiazepine-type are missing. In 2010,manufacture inIndia accounted for of result of that fact the data on manufacture of group this 2007-2010.The decline in2011 is a totalthe period inthe together accounted, on average, for cent almost 60per of main­diazepam, the substances group, inthis which ­fluctuationsthe in manufacture alprazolamof and figure2011 (see 14). Those fluctuations mainly reflect to 23.4billion S-DDD in2010and 19billion S-DDD in almost 30billion S-DDD. manufacture Global amounted manufactureglobal fluctuatedbetween 18.9 billion and of 28.8 billion S-DDD. subsequent the During decade, substances rose steadily until it 2001,when reached apeak as anxiolytics. Total reported manufacture of group this of 60. subsequent smuggling and abuse. at least once. are Benzodiazepines frequently diverted for inquantities in benzodiazepines traded of more than 1kg and territories that reported to manufactured Board the or countries ending all decade the During in 2010, practically was transferred from IVto Schedule IIIin1995. Schedule in 1990and brotizolam in1995.Flunitrazepam was added a ­substances from some countries, most importantly India, 20 22 Billions ofS-DDD 14 16 18 24 26 28 30 12 32 10 The data for 2011 are incomplete. for 2011are The data 2 4 8 6 0 total reported manufacture, bysubstance, 2002-2011 In 2011,alprazolam accounted for cent 36per ­billion S-DDD) of total reported manufacture of Twenty-two are benzodiazepines generally classified 2002 Benzodiazepine-type anxiolytics Benzodiazepine-type Figure 14. Chlordiazeproxide Lorazepam Alprazolam 2003 2004 Benzodiazepine-type anxiolytics: Benzodiazepine-type 2005 Bromazepam Diazepam Oxazepam 2006 2007 2008 2009 Others 2010 2011 Year a a reported for 2011. As shown infigureChina, 16, India and manufacture of camazepam, fludiazepam or pinazepam was accounted for cent 6per of total reported manufacture. No 15). The remaining substancesthat in group together over cent 2per each; and clobazam for cent ­ 1per (see S-DDD); oxazepam, chlordiazepoxide and nordazepam for lion S-DDD); bromazepam for cent 5per (0.88 cent (5.1billion S-DDD); lorazepam for cent 19per (3.7bil - anxiolytics; ­benzodiazepine-type diazepam for almost 27 per 12 18 10 14 16 20 22 26 28 24 30 Billions ofS-DDD 32 Lorazepam The data for 2011 are incomplete. for 2011are The data 0 6 2 4 8 Figure 15. reported manufacture, selected countries, 2002-2011 19% Diazepam total reported manufacture, bysubstance,2011 2002 Figure 16. 27% Italy France China 2003 Oxazepam 2% Benzodiazepine-type anxiolytics: share of Benzodiazepine-type 2004 Clobazam Benzodiazepine-type anxiolytics: Benzodiazepine-type 1% 2005 Others 6% Switzerland Germany Finland 2006 Nordazepam 2007 Chlordiazepoxide 2% 2008 2% 2009 Others India Alprazolam 2010 Bromazepam 36% 5% 2011 Year ­billion figure a 47

English Figure 17. Benzodiazepine-type anxiolytics: share of total Figure 18. Benzodiazepine-type anxiolytics: calculated reported manufacture, by country, 2011 global consumption,a 2002-2011

Billions of S-DDD 28 United States 26 13% China 13% 24 22 Switzerland 5% France 20 8% 18 16 Others 14 12% 12 Germany 10 9% 8 6 4 2 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Italy 40% Year

Alprazolam Bromazepam Chlordiazepoxide Diazepam Lorazepam Others

aStatistical data submitted by Governments are used to calculate the approximate global consumption in a given year. These consumption figures are expressed in defined daily doses for statistical purposes (S-DDD).

Figure 19. Benzodiazepine-type anxiolytics: average national consumption,a by region, 2003-2011

S-DDD per 1,000 inhabitants per day 62. Total approximate calculated consumption of 50 ­benzodiazepine-type anxiolytics has been lower than global

45 manufacture, although it has followed the same overall trend. In 2011, the global total calculated consumption for 40 this group of substances amounted to 18.5 billion S-DDD, 35 a decrease from the average of 23.5 billion S-DDD during 30 the five-year period 2006-2010 (see figure 18). The calcu- 25 lated consumption of benzodiazepine-type anxiolytics, expressed in S-DDD per 1,000 inhabitants per day, is 20 shown in table IV.3 of the present publication. Until 2010, 15 Europe was consistently the region with the highest 10 ­calculated average national consumption rates for 5 ­benzodiazepine-type anxiolytics (see figure 19). The sharp increase in consumption levels in Oceania in 2011 is the 0 2003-2005 2006-2008 2009-2011 result of a marked increase in the calculated consumption Year of alprazolam in Australia. Africa Americas Asia Europe Oceania Alprazolam

aStatistical data submitted by Governments are used to calculate the ­average annual consumption for a three-year period. 63. In 2011, total reported manufacture of alprazolam amounted to 6.6 tons, a decline of 11 per cent compared with 2010 because no data on manufacture were ­submitted Italy were the leading manufacturers of benzodiazepine-type­ by India for 2011. In 2010, that country reported a total anxiolytics in the period 2002-2010. Owing to the absence of 2.3 tons of manufacture of alprazolam. The main of data from India, in 2011 Italy, China and the United States ­manufacturers of alprazolam in 2011 were Italy (2 tons), together accounted for 66 per cent of global manufacture of the United States (1.9 tons), Finland (1.1 tons) and France that group of substances (see figure 17). (979 kg), which together accounted for almost 90 per cent

48 Diazepam 2000-2005,reached aning average period the of 8.5 consumption, had which averaged 4.8billion S-DDD dur ­Switzerland (355kg)and Ireland ­ (212kg).Global Iran (431kg),Hungary (420kg),France (314kg), by Japan (508kg), Spain Islamic (463 kg), the Republic of cent of total imports of substance. the They were followed ­Australia (715 kg), togetherwhich accounted for 53 per States (2.8tons), Italy (1ton), (775kg)and Belgium main importers of alprazolam continued United the to be year, of exports alprazolam global at stood 14.3tons. The countries reported import or of use substance. the In that 2009-2011.Induring 2011,more period the than 100 regions. International inalprazolam trade averaged 10tons 64. to illicit markets. diverted from been has domestic also distribution ­ ­Federation (17 kg). Alprazolam has often been abused and kg),Japan (94kg),Canada(44kg)and Russian the (272 of manufacture. global They were followed China by exports ofexports diazepam in excess of 1 kg. cent An additional ofexports. global 42countries reported Republic (1.6tons), together which accounted for 30per Denmark (3.4tons), Germany (1.7tons) and Czech the were followed by Switzerland (5.3tons), India (5tons), 12.7 tons of diazepam and Italy 21.5tons. exported They leading exporters of substance. the In exported 2011,China wereexports 56.6tons, with and China Italy remaining the 2009-2011.In ing three-year the 2011,global period 66. respectively, are missing. still in 2010manufactured 5.4tons and 3.6tons of ­ the Data on manufacture in 2011 from Brazil and India, which were United the States (1.7tons) and Switzerland (1.4 tons). manufacture of diazepam inquantities ­ turers of substance. the The only countriesother reporting (with 20.3tons, or cent) 40per were leading the manufac- or cent almost 53per ofmanufacture) global and China decreasing in2011 to 51.2tons. In 2011, Italy (with 27 tons, increased from 43tons in2009to 66.6tons in2010, often diverted and abused. manufactureGlobal of ­ ­alprazolam, diazepam is among most benzodiazepines the consumed regions in all of world. the Together with groupin the anxiolytics, of benzodiazepine-type and is 65. S-DDD). Hungary (184million S-DDD) and Portugal (119million terms in 2011 were United the States (2.2 billion S-DDD), ­reporting largest the consumption of alprazolam in­ S-DDD 2009-2011.The countries during period the Alprazolam is available inmany countries and all International in diazepam averaged trade 58 tons dur Diazepam continues mostsubstance the to traded be exceeding 1ton substance, calculated calculated diazepam channels absolute ­billion - - S-DDD). France (161 (277 million S-DDD), Argentina (188million S-DDD), (427 S-DDD), Spain (517million S-DDD), Germany of lorazepam was highest United inthe States (896­ to 4.2­ averaged 3.7 consumption calculated 2002-2011,global period the imported ­ imports of substance. the About 50other countries together which accounted for cent 73per of all (420 kg), Hungary (500kg),Argentina (471kg)and Canada Italy(1 ton), (759kg),Germany (659kg),France (613kg), Unitedthe States (1.6tons), Spain (1.3tons), Ireland ­substance. The main importers of lorazepam in 2011 were for approximately cent 90per of of total exports the Ireland and India (inthat order), together which accounted ­lorazepam up decade inthe to 2011were Italy, Germany, 2006-2011(10.6tons).period The main exporters of at 11.3tons, roughly inline with average the value for the 69. Poland (42 (171 kg) kg), andChina Spain (14.5 kg). 2011 were United the States (683 kg), Canada (413 kg), countriesOther reporting manufacture of lorazepam in no manufacture was reported by that for country 2011. year, with output of 1.3 tons reported for 2010;however, ­traditionally reported manufacture of lorazepam every for cent 45per and Italy for cent. 41per India had substancethe was 9.2 tons, of Germany which accounted manufacturers of substance. the In 2011,total output of year.per Italy, Germany and India were three the main stable 2004-2010, averaging during period the 10.7tons 68. Lorazepam ­diazepam in 2011. S-DDD) had consumption highest the calculated of Congothe (407 (757 China S-DDD in2011.The United States (764million S-DDD), ­diazepam continued to decrease, reaching 4.4billion cent ofimports. consumption calculated global Global of tons). Together,(2 countries those accounted for 60per (2.4 tons), Czech Republic the (2.1 tons) and Spain Ghana (2.9tons), United the Kingdom (2.6tons), ­ (4.8 tons), Democratic the Republic of Congo the (4tons), during 2011were United the States (6.9 tons), Switzerland more than 1 kg for 2011. The main importers of countries and territories reported imports of diazepam of ­diazepam at 2009-2011.About least once period inthe 95 67. ­million S-DDD), Italy (336 million S-DDD), Canada Total reported manufacture of lorazepam was fairly In 2011,total reported of exports lorazepam stood Practically all countries all Practically and territories imported billion S-DDD. In consumption calculated 2011,the lorazepam inquantities exceeding During 2kg. ­million S-DDD), Democratic the Republic of ­billion in2011,it S-DDD amounted year; per ­million S-DDD) and Portugal (135million ­million S-DDD) and Ghana (295million ­diazepam Germany million 49

English Bromazepam global consumption of the substance, which decreased from 1.2 billion S-DDD in 2009 to 650 million S-DDD in 70. During the period 2002-2011, total reported manu- 2010, decreased again in 2011, to 396 million S-DDD. facture of bromazepam fluctuated significantly. After reach- ing a peak of 18.3 tons in 2008, it decreased gradually to Oxazepam 8.8 tons in 2011. Italy (5 tons) and Switzerland (3.6 tons) remained the leading manufacturers of the substance in 74. During the period 1992-2011, total reported 2011, accounting for 56 per cent and 41 per cent, respec- ­manufacture of oxazepam was fairly stable, averaging 27.2 tively, of the reported total. No other countries reported tons per year. Global reported manufacture of the substance significant manufacture of the substance in 2011, includ- declined to 23 tons in 2011, partly owing to the lack of data ing Brazil and India (the other major manufacturers of from India, which had reported output of 2.6 tons for 2010. bromazepam in the recent past), for which data on manu­ Italy, which manufactures the substance mainly for export, facture for 2011 are missing. and France remained the main manufacturers of oxazepam in 2011, reporting manufacture of 18.7 tons and 2.4 tons, 71. International trade in bromazepam was stable during respectively. In addition, Canada reported manufacture of the period 2002-2011, with global exports averaging 1.5 tons of the substance in 2011. The volume of trade in 16.3 tons annually. In 2011, as in previous years, the main oxazepam, which had averaged 40 tons per year from 2001 manufacturing­ countries (Italy and Switzerland) were also to 2005, has declined since that time, reaching 22.6 tons in the leading exporters of the substance, together with India 2011. In 2011, 48 countries reported imports of oxazepam. (1.8 tons) accounting for almost 90 per cent of total exports. The main importers, together accounting for almost 67 per Around 80 countries reported imports of bromazepam in cent of total global imports, were France (7.4 tons), ­Germany 2011, with 21 of those countries reporting imports of more (3.8 tons), the Netherlands (1.4 tons), Canada and Australia than 100 kg. The main importers of bromazepam in 2011 (1.1 tons each). Those countries were also the countries with were France (2.2 tons), Switzerland (1.7 tons), Italy (1.2 tons), the highest calculated consumption in 2011. Germany (910 kg), Japan (842 kg), Serbia (760 kg), Spain (477 kg) and Belgium (467 kg), which together accounted Clobazam for 64 per cent of global imports of the substance. Brazil reported imports of 1.2 tons of the substance­ in 2010; 75. Total reported manufacture of clobazam fluctuated ­however, the country did not report any data for 2011. between 3.2 and 6 tons during the decade leading up to ­Calculated global consumption of ­bromazepam was fairly 2011, with France, Germany and India being the main stable during the period 2002-2010, averaging 1.3 billion manufacturers. Data on manufacture of the substance for S-DDD. In 2011, it decreased to 1.0 billion S-DDD. 2011 were missing from India, which had reported manu- facture of 822 kg for 2010. As a result, almost 90 per cent Chlordiazepoxide of total reported manufacture of the substance in 2011 (4.8 tons) was accounted for by France (2.6 tons) and 72. In the period 2001-2010, total reported manufacture ­Germany (1.7 tons). International trade in clobazam also of chlordiazepoxide fluctuated between 28.4 tons in 2002 fluctuated during the period 2002-2011, averaging 5.2 tons and 40 tons in 2009. In 2011, total reported output of that annually. More than 70 countries reported imports of the substance was 13.4 tons, about 98 per cent of which was substance in 2011, including France (801 kg), India accounted for by Italy (11.8 tons) and China (1.4 tons) (697 kg), Bangladesh (452 kg), Canada (292 kg), Japan together. Only two other countries reported manufacture of (250 kg) and the United States (223 kg). the substance in 2011: Canada (148 kg) and Poland (73 kg). Data on manufacture in 2011 were missing from India, Clorazepate which had reported manufacture of 11.6 tons of chlordi­ azepoxide for 2010. China, India, Italy and Switzerland­ 76. Total reported manufacture of clorazepate declined remained the largest exporters of chlordiazepoxide in 2011. from 12 tons in 1992 to 3.9 tons in 2011. France and Italy Global exports of the substance declined from 23.5 tons in were the leading manufacturers during the period 2002- 2002 to 15.8 tons in 2010. They increased slightly in 2011, 2011. In 2011, those two countries accounted for 97 per reaching 17.7 tons, of which Italy exported 10.3 tons. cent of global manufacture of that substance. International trade in clorazepate stood at 4.9 tons in 2011. France, Spain 73. More than 100 countries reported imports of chlor- and Italy, which reported exports of 2.7 tons, 1 ton and diazepoxide in the three-year period 2009-2011. The 902 kg, respectively, together accounted for almost 95 per Islamic Republic of Iran (3.4 tons), Switzerland (2.8 tons), cent of total exports. Spain (2.1 tons), France (492 kg) and Cuba (2 tons) and the United States (1.8 tons) were the the United States (368 kg) remained the largest importers main importers of the substance in 2011, accounting of clorazepate; more than 50 other countries reported together for 67.7 per cent of the global total. Calculated import and use of the substance in 2011.

50 France (28tons), Cuba (21tons), Turkey (15tons) and ers of meprobamate in 2011 included (40 tons), South Africa France (2.2tons) and Switzerland (1.8tons). Major import- majorOther exporters in2011 included India (9tons), accounted for nearly cent 90 per total of in2011. global the and Denmark, major the countries, exporting together which 134 tons in2011,owing to from adecline inexports China fromdecline. decreased exports 259tons Global in2007to 80. (14 tons), France (10tons) and United the States (6.7tons). in Denmark (55tons), (30tons), South Africa Hungary atstood 119tons cent in2011,97per of was which held stocks have continued also to since decrease 2009.They mate, reporting 83tons of manufacture in2011.Global continuedChina amajor to be manufacturer of meproba- hadwhich reported output of nearly 10tons for 2010. 2010, and lack the of data on manufacture from India, reported 40tons for 2011,adecline of cent 56per from the lower reflects decrease outputDenmark, in which in 2009to 125tons (104million S-DDD) in2011.This declined significantly,from 225 tons (187 million S-DDD) average of 230tons. Since 2009,total manufacture has After 2000, total manufacture fluctuated around an annual 1970s to an annual average of 290tons during 1990s. the stantial decline inmanufacture from 750tons late inthe replaced by been ually leading to benzodiazepines, asub- substance as an IVused inSchedule anxiolytic, has- grad 79. Meprobamate oxazolam amounted to 99.5 million S-DDD in 2011. manufacture of medazepam, ketazolam, and halazepam ­substance was reported for 2010or 2011.The combined of 4.6million S-DDD for 2009;no manufacture of the 2002-2011.The most period the recent report of India was India and Italy reported manufacture of pinazepam during million S-DDD, respectively. TheRepublic, Czech 199 ethyl loflazepate amounted to 210 million S-DDD and States. In that year, total manufacture of prazepam and 219 million S-DDD, of all it manufactured United inthe 78. limitedfew countries. to a very largestthe manufacturers. Use of nordazepam remained with Finland (3.4tons) and Switzerland (2.3tons) being of nordazepam amounted to 6.2tons (414million S-DDD), 14.2 tons, reached in 2006. In 2011, total global 1.2tons 2002-2010between of in2002and period apeak reported manufacture of that substance during varied the ­traditionally main the manufacturer of nordazepam, total 77. International inmeprobamate trade has continued to Meprobamate, only the non-benzodiazepine-type In manufacture 2011,global of at tetrazepam stood mainlyOwing to developments inSwitzerland, Other anxiolytics ­manufacture a (see figure(see 21). consumption global calculated at stood 7.7billion S-DDD 8.1 billion S-DDD 2002-2011. In during 2011, period the than manufacture, fluctuating around an annual average of consumption of group this of substances was less volatile cent7.1 per of total manufacture global in2010.Calculated from either Brazil or India, together which accounted for ­figure 20). Fordata 2011, on manufacture were not received sedative-­ reported manufactureglobal of benzodiazepine-type Germany, Switzerland and United the States. In 2011, (in 2009), owing mainly to changes in output reported by 5.5billionbetween S-DDD (in2008) and 9.5billion S-DDD manufacture of 12substances the group inthis fluctuated 82. are provided in paragraphs 37-39 above. was transferred from IVto Schedule IIIin1995, Schedule Comments­triazolam. on flunitrazepam, a substancethat midazolam, nimetazepam, nitrazepam, temazepam and flurazepam, haloxazolam, loprazolam, lormetazepam, ­sedative-hypnotics: brotizolam, estazolam, flunitrazepam, 81. order) major the being users of substance. the with France, Cuba South and Africa, Turkey (indescending of meprobamate amounted to 161tons (135million S-DDD), ­Hungary (12tons). In consumption calculated 2011,global Benzodiazepine-type sedative-hypnotics Benzodiazepine-type Figure 20. Billions ofS-DDD The data for 2011 are incomplete. for 2011are The data 10 0 1 2 3 4 5 6 7 8 9 During the decade leading up decade the During to 2011,total reported Twelve are benzodiazepines generallyas used reported manufacture, bysubstance,2002-2011 2002 hypnotics amounted to 7billion S-DDD (see Flunitrazepam Brotizolam Temazepam 2003 Benzodiazepine-type sedative-hypnotics: total sedative-hypnotics: Benzodiazepine-type 2004 2005 Lormetazepam Estazolam Triazolam 2006 2007 2008 2009 Others Nitrazepam 2010 2011 Year a 51

English Figure 21. Benzodiazepine-type sedative-hypnotics: Figure 22. Benzodiazepine-type sedative-hypnotics: calculated global consumption,a average national consumption,a by region, 2003-2011 2002-2011

Billions of S-DDD S-DDD per 1,000 inhabitants per day 10 28 9 26 24 8 22 7 20 18 6 16 5 14 4 12 10 3 8 2 6 4 1 2 0 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2003-2005 2006-2008 2009-2011 Year Year Brotizolam Estazolam Flunitrazepam Lormetazepam Nitrazepam Africa Americas Asia Europe Oceania Temazepam Triazolam Others

a Statistical data submitted by Governments are used to calculate the approx- aStatistical data submitted by Governments are used to calculate the average imate global consumption in a given year. These consumption figures are annual consumption for a three-year period. expressed in defined daily doses for statistical purposes (S-DDD).

83. The calculated average national consumption of 7 per cent) and estazolam (473 million S-DDD or 7 per cent). ­benzodiazepine-type sedative-hypnotics, expressed in The remaining substances in this group together accounted S-DDD per 1,000 inhabitants per day, has traditionally been for 7 per cent of total ­manufacture in 2011: midazolam­ (267 higher in Europe and in a few non-European countries, such million S-DDD or almost 4 per cent), ­loprazolam (116 ­million as Cuba and Japan, than in other regions. As shown in figure­ S-DDD or 1.6 per cent), flurazepam­ (100 million S-DDD), 22, average calculated levels of consumption of this group nimetazepam (16 million S-DDD) and haloxazolam (13.6 of substances have declined somewhat in Europe, in the million S-DDD) (see figure 23). Americas and in Oceania compared with 10 years ago. ­Calculated consumption levels of benzodiazepine-type Figure 23. Benzodiazepine-type sedative-hypnotics: share ­sedative-hypnotics, expressed in S-DDD per 1,000 ­inhabitants of total reported manufacture, by substance, 2011 per day, in individual countries are shown in table IV.2 of the present publication. Others Estazolam 3% Midazolam Nitrazepam 7% 4% 84. The reported manufacture of individual substances in 8% this group has varied greatly over the years, since manufac- Brotizolam turers tend to produce large quantities of a substance at a Temazepam 21% time to keep stocks of those quantities on hand for future 13% use. There have been significant fluctuations in total manu- facture of brotizolam and flunitrazepam, in particular, which has affected the total for the group as a whole. In 2011, lormetazepam continued to be the most manufactured ­substance in the group of benzodiazepine-type sedative-­ hypnotics, accounting for 1.7 billion S-DDD, or 23 per cent, Triazolam of global manufacture of this group of substances. ­Brotizolam Flunitrazepam 14% 7% was second, with an output of 1.5 billion S-DDD, or 21 per cent of global manufacture in 2011. Triazolam was third (987 million S-DDD or 14 per cent), followed by temazepam Lormetazepam 23% (931 million S-DDD or 13 per cent), nitrazepam (571 ­million S-DDD or 8 per cent), flunitrazepam (516 million S-DDD or

52 a of manufacture global of such substances figure (see 25). data from India and Brazil accounted for cent almost 46per amounting to 3.2billion S-DDD, absence inthe which of Italy manufactured sedative-hypnotics benzodiazepine-type than of manufacture half global of such substances. In 2011, was leading the manufacturer, accounting in2003for more 2011 are shown in figure 24. Throughout that period, Italy diazepine-type sedative-hypnotics during up decade the to 85. reported total manufacture,selected countries, 2002-2011 Figure 25. 10 11 Billions ofS-DDD The data for 2011 are incomplete. for 2011are The data 5 0 2 3 4 6 7 8 9 1 France Figure 24. The main countries manufacturereporting benzo- of 1%

reported manufacture, selected countries, 2011 China

2002 6% Switzerland Switzerland India China 2003 2% Italy 46% Benzodiazepine-type sedative-hypnotics: total sedative-hypnotics: Benzodiazepine-type Benzodiazepine-type sedative-hypnotics: sedative-hypnotics: Benzodiazepine-type 2004 United States 2005 11% United States Italy Germany 2006 2007 Japan 7% 2008 Others 3% 2009 Others 2010 Germany 24% 2011 Year a and Netherlands the (9.4). for ­ expressed inS-DDD 1,000inhabitants per day, per recorded Europe, with rates highest the calculated of consumption, S-DDD). Rates of consumption were in high particularly of lormetazepam amounted to 1.2tons in2011(1.2billion mainly for consumption re-export.global Thecalculated past,the some of countries those imported substance the kg),Finland (200 kg)and (163kg).As Belgium in (242 France (281kg),Germany Netherlands (269kg),the ­importers of lormetazepam in2011were Spain (489kg), Netherlands (159kg)and Spain (110kg).The main zepam, followed by France (211kg),Finland (174kg),the kg)­ (576 almost 1.9tons in2011.Germany (577kg)and Italy in 2011.International inlormetazepam trade reached reported manufacture of amounts small of that substance to main the manufacturers, Canada and Poland also cent from figure the reported for 2010. In addition11 per of lormetazepam amounted to 1.7 tons, of a decrease main manufacturers of substance. the In 2011,­ resultthe of developments inGermany and Italy, two the 2003 (380kg)and in2007(809kg).The fluctuations were of lormetazepam was consistently above 1ton, except in 86. had been the leading the manufacturerhad been of ­ triazolam atstood 247kg(987million S-DDD). The United States 88. Triazolam use. global calculated for cent 70 per of total imports and around cent 65per of was by far largest the importer of substance, the ­ has continued to grow, in2011,as inprevious years, Japan While number the of countries reporting of use brotizolam ­having imported more than 1kgof brotizolam in2011. ofexports substance. the About 10countries reported in 2011,accounting for or 157kg, cent 83per of total ­Germany remained also main the of exporter brotizolam remained main the manufacturers of substance. the to 372kgin2011.Germany (291kg)and Japan (81kg) manufacture of brotizolam increased from 99kgin2010 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 stances (0.25mg). Germany was first the country to report zolam, it has lowest the S-DDD of psychotropic all sub- 87. Brotizolam Lormetazepam Belgium (39.6),SpainBelgium (23.5),Italy (14.4),Andorra (9.8) In the period 2002-2011, total reportedIn manufacture period the In 2011,total reported manufacture of triazolam Brotizolam is apotent hypnotic. Together- with tria continued main the to be exporters of lormeta­ manufacture throughout accounting 53

English the period 2000-2009, accounting for over 90 per cent of countries reported manufacture of the substance in 2011, global manufacture of the substance in 2009. In 2010, the including India, which had been a major manufacturer of United States did not report manufacture of triazolam and, nitrazepam during the period 2002-2010. Exports of nitra­ as a result, the global total dropped to 90 kg. In 2011, the zepam, which had averaged about 4.2 tons annually during United States was again the largest manufacturer of the the period 2008-2010, also fell in 2011, to 3.2 tons. Italy substance by far, with output of 185 kg. The other coun- (1.9 tons) and China (705 kg) continued to be the main tries reporting manufacture of triazolam in 2011 were Italy exporters of the substance, together accounting for 84 per and Canada, which reported 57 kg and 5 kg, respectively. cent of all nitrazepam exports in 2011. More than 30 More than 40 countries reported use of triazolam in the ­countries imported nitrazepam in quantities exceeding 2 kg period 2009-2011. Total global calculated consumption of in the period 2009-2011. Imports reported by Japan and triazolam stood at 1.9 billion S-DDD in 2011, with the Cuba, traditionally­ the largest importers and users of the United States (1.1 billion S-DDD) and Japan (545 million substance, increased, with some fluctuations, during the S-DDD) being the main consumers in absolute terms. Total period 2002-2010. Both countries, however, reported a exports of triazolam in 2011 amounted to 220 kg. The decline in total imports of nitrazepam compared with 2010; United States (115 kg) continued to be the main exporter, in 2011, imports were 1 ton for Japan and 550 kg for Cuba. followed by Italy (56 kg), Switzerland (15 kg), India (14 kg) and Belgium (14 kg). Throughout the decade leading up to Estazolam 2011, Japan was the largest importer of triazolam, account- ing in some years for over 50 per cent of global imports. 91. During the period 2008-2010, unlike in previous In 2011, Japan remained the country with the highest cal- ­periods, global reported manufacture of estazolam was fairly culated per capita consumption rate of triazolam, followed stable, varying between 2.4 and 2.6 tons. In 2011, global out- by the United States. put of the substance declined to 1.4 tons, owing to developments in China, which was the major manufacturer Temazepam of the substance during the period 2002-2011. Other ­countries reporting manufacture of estazolam in 2011 were, 89. During the period 2002-2011, Italy was the leading in descending order, Japan, Italy, Poland and the United manufacturer and exporter of temazepam, and Canada, States. Use of the substance outside the manufacturing India, Poland, the United Kingdom and the United States ­countries has increased steadily since the 1980s, with inter- reported intermittent manufacture of the substance for some national trade in 2011 reaching the highest value ever years. In 2011, global reported manufacture of temazepam reported (405 kg). The leading exporters of estazolam have amounted to 18.6 tons, a decline from 21.6 tons in 2010, traditionally been Italy and Japan. About 15 countries with Italy accounting for about 92 per cent of the total. In reported use of estazolam in quantities exceeding 10 kg 2011, Canada, which reported manufacture of temazepam ­during the period 2008-2010. In 2011, Poland (33 kg), Japan for the first time in 2010, manufactured 1.3 tons of the (30 kg), the United States and Italy (24 kg each), Mexico ­substance. Poland and the United States manufactured (19 kg) and France and the Netherlands (18 kg each) together 123 kg and 41 kg, respectively. The United States continued accounted for 87 per cent of total imports of the substance. to be the largest importer of temazepam in 2011 (9.1 tons). The second largest importer was Australia (1.18 tons), Midazolam ­followed by Finland (1.10 tons), Canada (1 ton), the ­Netherlands (928 kg), the United Kingdom (907 kg), Ireland 92. Total reported manufacture of midazolam decreased (750 kg), Hungary­ (652 kg), Switzerland (595 kg) and from 6.6 tons in 2009 to 5.4 tons in 2011. Brazil, Israel, India, ­Germany (561 kg). Global calculated consumption of tema­ Italy and Switzerland have been the main manufacturers of zepam stood at 822 million S-DDD in 2011. The United States the substance; however, data on manufacture for 2011 have accounted for almost 58 per cent of the total, while Canada, not been received from Brazil and India, which may account Italy, Australia, the ­Netherlands, Finland and ­Germany, in that for the drop in output. Switzerland reported 3.1 tons of order, together accounted for about 37 per cent. ­manufacture of midazolam in 2011, followed by Israel (1.2 tons), Italy (662 kg) and China (284 kg). Midazolam is used Nitrazepam in many countries; over 80 countries reported imports of midazolam in quantities above 1 kg in the period 2009-2011. 90. In the period 2002-2010, global reported manufacture In 2011, global exports of the substance stood at 6 tons. As of nitrazepam ranged between 4 and 6.8 tons per year. In in previous years, Switzerland continued to be the main 2011, that figure dropped to 2.86 tons, of which Italy exporter, accounting for 2.4 tons, or almost 39 per cent of accounted for 68 per cent. China (805 kg), Canada (126 kg) the global total. The main importer in 2011 was the United and the Russian Federation (7 kg) were the other countries Kingdom (1.4 tons), followed by Germany (936 kg), reporting manufacture of nitrazepam for that year. No other ­Switzerland (604 kg), France (514 kg) and the United States

54 between 150 andbetween 300 kg during 2011. (in that order) imported flurazepam in quantities ranging Japan, Ireland Belgium, and Islamic the Republic of Iran of substance, the at stood which 3.5tons in2011.Italy, together accounted for about cent 57per of total imports (537 kg),Germany (345kg)and Canada(315kg),which razepam continued Spain to be United (773kg),the States ofexporter flurazepam in2011. The main importers of flu- substancethe in2011.Italy remained also largest the by Canada.No other countries reported manufacture of turer, accounting for cent 90per of total output, followed 3 tons in2011.Italy continued largest the to be manufac - 94. Flurazepam and Italy (12 kg). for by Poland (86kg),France (14kg) (48kg),South Africa amounted cent to 85per 188kg, of were which accounted 2008-2011.Total period the imports of loprazolam in2011 Unitedthe States. About 25countries loprazolam used in reported bybeen India, Spain, United the Kingdom and of substance, the although manufacture has occasionally ditionally main the manufacturer been and leading exporter amounted reported to by all 116kg, France, has which - tra 93. Loprazolam rates of reported consumption of midazolam for that year. and (inthat Chile order) were countries the with ­ the United States, Hungary, Colombia, Portugal, Netherlands the tion of midazolam at stood 258million S-DDD in2011.The of imports global of consump midazolam. global Calculated - (470 kg).Together, countries those accounted for cent 60per as an anti-epileptic. 1992-2009,global period the During 96. Clonazepam of nimetazepam and output of 102 kg of haloxazolam. in Japan. In 2011,that reported country manufacture of 79 kg and haloxazolam, are manufactured and almost solely used 95. The remaining substancesgroup,this in nimetazepam Global reportedGlobal manufacture of flurazepam stood at Total reported manufacture of loprazolam in2011 Clonazepam that is abenzodiazepine mainly is used Benzodiazepine-type anti-epileptics Benzodiazepine-type Other benzodiazepine-type Other benzodiazepine-type sedative-hypnotics sedative-hypnotics highest highest (200 kg) (see figure(200 kg) (see 26). (2.7 tons), (590 kg), Canada(251kg)and China Poland or cent 45per total, of global followed the by Switzerland manufacturer of substance, the reporting output of 3.5tons ades leading up to 2010.In 2011,Italy largest the became leading manufacturer of clonazepam during two- the dec for 2010,had not received. been Switzerland was world’s the had reported output of 702kgand 2.4tons, respectively, owing that to fact the data from Brazil and India, which of clonazepam declined to 7.8tons (975million S-DDD), kgto 9.6tons. In reported manufacture 2011,global 735 reported manufacture of substance the increased from S-DDD), Italy (109million S-DDD), Argentina (87million azepam in2011were United the States (233million countries with consumption highest the calculated of clon- 2008-2010. In 2011,it at stood 1.01 billion S-DDD. The averaged to close 1.1billion S-DDD annually period inthe consumption calculated 2008-2011. Global of substance the countries in1995to more than 140countries period inthe kg).Use of clonazepam expanded from about 50 (408 Republic of Iran (430kg)and (625kg),Chile Canada (948 kg),Mexico (802kg),Argentina Islamic (760kg),the ing more than 400kgof substance the in2011were Spain Israel, imported which 1.3tons. countries Other import- of clonazepam; however, inthat year were they joined by and Switzerland (1.7tons) remained largest the importers cent total. of global In the United 2011,the States (1.9tons) land, Italy and India together accounting for almost 90per increasing trend, reaching 12.5tons in2011,with Switzer 97. a Millions ofS-DDD 1 000 1 100 1 200 1 300 100 200 300 400 500 600 700 800 900 The data for 2011 are incomplete. for 2011are The data Figure 26. 0 Global exports of exports Global clonazepam have followed also an 2002 Poland India Brazil 2003 selected countries, 2002-2011 Clonazepam: total reported manufacture, 2004 2005 Switzerland Italy China 2006 2007 2008 2009 Others 2010 2011 Year a 55 -

English S-DDD), the Islamic Republic of Iran (77 million S-DDD), 100. The countries with the highest calculated consump- China (68 million S-DDD), Mexico (59 million S-DDD), tion rates of barbiturate-type sedative-hypnotics in Sched- Japan (45 million S-DDD), Israel (42 million S-DDD), ule IV in 2011 were (in descending order) China, Japan, Bangladesh (37 million S-DDD) and France (37 million Turkey, Italy, Albania, Thailand and France, which had S-DDD). Calculated consumption levels of clonazepam, consumption rates ranging between 0.065 and 0.464 measured in S-DDD per 1,000 inhabitants per day, in indi- S-DDD per 1,000 inhabitants per day. With respect to the vidual countries are shown in table IV.4 of the present barbiturate-type anti-epileptics listed in Schedule IV, the publication. countries with the highest calculated consumption levels, in S-DDD per 1,000 inhabitants per day, were (in descend- ing order) Bulgaria, Ukraine, Cuba, Vanuatu, the Russian Federation, Benin and Belarus. More information on cal- Barbiturate-type sedative-hypnotics and culated consumption levels is shown in table IV. anti-epileptics in Schedule IV 101. Total reported manufacture of phenobarbital ­fluctuated between 330 and 480 tons during the period 2002-2011. In 2011, total output of phenobarbital amounted Allobarbital, barbital, butobarbital, to 330 tons (3.3 billion S-DDD), a significant decrease from methylphenobarbital, phenobarbital, 461 tons (4.6 billion S-DDD) in 2010. That decrease can be attributed to the decrease in manufacture in China, the secbutabarbital and vinylbital leading manufacturer of the substance. Total output in that country decreased from 355 tons in 2010 to 262 tons in 2011; nevertheless, China still accounted for nearly 80 per 98. The seven barbiturates in Schedule IV are pharmaco- cent of global manufacture in 2011 (see figure 27). The logically related to those in Schedule III. Five of the seven ­second largest manufacturer in 2011 was the Russian substances, namely allobarbital, barbital, butobarbital, sec­ ­Federation (54 tons), followed by Japan (9.6 tons). The butabarbital and vinylbital, are intermediate-acting barbi- other two major manufacturers of phenobarbital, Hungary turates and are mainly used as hypnotics (to induce sleep). and India, did not report manufacture of the substance in They are no longer used as daytime sedatives. The other 2011. Total stocks amounted to about 119 tons in 2011, two substances, methylphenobarbital and phenobarbital,5 the majority of which were held (in descending order) in have additional properties and are also used as anti-epilep- Switzerland, the United States, Denmark, Hungary, Costa tics (long-acting barbiturates). Phenobarbital continued to Rica, France, Ukraine, Italy and Germany. The major users be the most commonly used substance in this group in 2011, followed by barbital. Figure 27. Phenobarbital: total reported manufacture, 99. Total reported manufacture of those seven barbitu- selected countries, 2002-2011 rates (for both direct medical use and the manufacture of Billions of S-DDD non-psychotropic substances) rose from 4 billion S-DDD 5.0 in the period 1999-2000 to an average of 5.1 billion S-DDD in 2006. After that year, reported global manufacture 4.5 started to decline, with fluctuations, to a total of 3.6 billion 4.0

S-DDD in 2011, a decrease of 20 per cent from 2010. 3.5 Changes in the quantities manufactured of phenobarbital, which continued to be the most widely manufactured sub- 3.0 stance in this group, accounted for the changes in output. 2.5 In 2011, the share of phenobarbital in total manufacture 2.0 (expressed in S-DDD) was nearly 92 per cent. Barbital 1.5 accounted for approximately 7 per cent of total manufac- ture, and methylphenobarbital and secbutabarbital together 1.0 accounted for about 1 per cent. No manufacture of buto- 0.5 barbital or vinylbital was reported for 2011. The most 0 recent manufacture of butobarbital was reported by 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011a ­Germany (117 kg) in 2008. No manufacture of vinylbital Year has been reported since 1996. China Hungary India Japan Russian Federation Others 5 See table IV for details of the calculated consumption levels of phe- a nobarbital. The data for 2011 are incomplete.

56 ­traditionally another major manufacturer of methylpheno- report any data on manufacture for 2011.Switzerland, manufactured 21.7tons of substance the in2008,didnot waswhich reported by United the States. India, which amounted to 10kg(0.1million S-DDD), of almost all Switzerland and United the States. In 2011,total ­ put reported by manufacturing the countries, namely India, 0.8 and 22 tons, owing to significant changesthe in out- ­considerably 2002-2010,ranging during between period the 105. States, France, Thailand and Italy. ing importers of barbital in2011,followed by United the Japan (1.1tons).two Those countries - thewere lead also exporters in2011continued Germany to be (4.9tons) and from 11.5 tons in 2010 to 7.6tons major in2011.Other leading of exporter substance, the declined significantly, tons (28million S-DDD) from in2011.Exports the China, approximately 19 tons (38 million S-DDD) in 2010 to 14 104. order) continued main the to be users. Italy, United the States, Thailand and France (in­ at 269tons (539million S-DDD) Japan, in2011.China, ­Convention. Total consumption calculated of barbital stood measures inaccordance with article 3of 1971 the substances and preparations exempted from ­ certain including for manufacture inthe use of non-psychotropic factured inJapan was mainly for domestic consumption, remained around 2tons eachyear.barbital The manu­ manu­ centper total. of global Japan the was other the major 120 tons (240million S-DDD) in2011,accounting for 98 increasinghas been steadily since 2008,and amounted to Manu­ million S-DDD) highest in2011,the level since 2002. 103. Ukraine and Japan. Unitedthe States, Germany, Russian the Federation, importers continued (indescending to order) be ­ reported imports of phenobarbital in 2011. The major cent per More of exports. global than 120countries 97 Total from countriesexports those accounted for about (in descending order) remaining largest the exporters. Hungary,China, India, Switzerland, Germany and ­ barbital amounted to 321 tons (3.2 billion S-DDD), with year. substancethe every In of 2011,total exports pheno- during 2007-2011,with an average of 140countries ­ in phenobarbital ranged 321tons between and 381tons psychotropicwidely traded substances. International trade 102. order). ­Federation, United the States, Japan and Ukraine (inthat of phenobarbital in2011included Russian the China, facturer; outputfacturer; inthat inrecent country years has facture leading the manufacturer inChina, of ­ Manufacture of methylphenobarbital fluctuated International in barbital trade from decreased Total manufacture of barbital reached 122 tons (245 Phenobarbital continues one to be of most the manufacture Switzerland, descending Denmark barbital, trading control 107. remained two the major exporters in 2011. total imports. Switzerland and India (inthat order) largest the being importers, accounting for cent 98per of with Croatia, Switzerland and Italy (in descending order) since volume 2007.In trade 2011,global reached 1.8tons, ated 2002-2006and declining during has been period the 106. were main the users of substance the in 2011. Italy and and Herzegovina Bosnia (indescending order) over cent 94per of were them held inSwitzerland. ­ stocks atin 2011.Global stood 5.6tons at end the of 2011; barbital, did not also report manufacture of that substance of substance the in 2011. were reported by and Belgium Jordan, two the main users remained limitedtrade in2011.Only 4 kg of very imports mostly held inGermany and Netherlands. the International butobarbital at stood 31kgat end the of were 2011;they ­substance reported sincestocks has Global then. been of Germany in 2008 (117 kg). No manufacture of that 109. substance,the totalling with exports 50 kg. United2011, the States was only the that country exported were held inGermany and United inthe half States. In stocks of substance the amounted to 28kgin2011;half ture of for 61kg, domestic both and use Global export. output since 2006of In 45kg. 2011,it reported manufac- manufacturer, sole the became reporting an average annual manufacturing substance the United in2003,the States yearsthe 2000,2004and 2005.AfterGermany stopped during past No the decade. manufacture was reported for 108. substance. the (200 kg).Poland and Turkey remained main the users of in 2011continued Switzerland to be (201kg)and Turkey cent from 2010.The major50 per importers of ­ quantities by exported Germany declinedby more than accounted for nearly in2011,although exports the all in 2011.Germany (226kg)and Switzerland (200kg) to significantly decrease since 2008, amounting to 428kg land. International inallobarbital trade continued has also werein 2011;these held mainly inGermany and Switzer continued to decrease, from 2.6tons in2009to 0.7tons reported bybeen any country. As aresult, stocks global S-DDD). Since 2010, no manufacture of allobarbital has resumed manufacture in 2009 (1.1 tons or 11.3 million million S-DDD) in2007,mainly for Germany export. of 2.5 tons (25 million S-DDD) in 2006 and 1.4tons (14 began manufacturing substance; the it reported an output 2006-2008.In substancethe 2006,Belgium period inthe ranging 393kgand between 4tons, didnot manufacture 1996-2005,with quantitiesing period the manufactured Germany, manufacturer sole the of allobarbital dur International inmethylphenobarbital trade fluctu- Manufacture of butobarbital was last reported by Secbutabarbital was manufactured intermittently allobarbital Croatia, 57 - -

English Barbiturates in Schedules II, III and IV facture of GHB increased steadily during 2006-2010, reach- ing a peak of 59 tons in 2010. In 2011, global manufacture 110. Of the 12 barbiturates listed in Schedules II, III and declined significantly, to 12.4 tons, owing mainly to IV of the 1971 Convention, five substances — phenobar- decreased manufacture in the United States, a leading bital, butalbital, pentobarbital, barbital and amobarbital (in manu­facturer of the substance. In 2011, reported manu­ that order) — together accounted, on average, for 99 per facture of GHB in the United States amounted to 1.3 tons, cent of total reported manufacture of those barbiturates which represented only 3 per cent of its manufacture in during 2007-2011. The shares of total manufacture of those 2010. Other manufacturers of GHB in 2011 were Germany five substances in 2011 are presented in figure 28. (9.8 tons) and Ukraine (1.2 tons). Global stocks have ­Phenobarbital remained the most widely manufactured ­continued to rise in recent years, reaching 41 tons in 2011. barbiturate in 2011, accounting for 72 per cent of total Italy and the United States were the two largest holders of manufacture of the 12 barbiturates. China (63 per cent), those stocks, together accounting for 88 per cent of global the United States (9 per cent), Denmark (8 per cent), stocks in 2011. ­Germany (5 per cent) and Japan (3 per cent) together accounted for 88 per cent of total manufacture of the entire 113. International trade in GHB declined slightly from group of barbiturates (see figure 29). 2010 to 2011. In 2011, total reported imports amounted to nearly 14 tons, with Italy, the United Kingdom and France (in descending order) being the main importers. Germany, the United States, the United Kingdom and Ukraine (in Other sedative-hypnotics listed in descending order) remained the leading exporters in 2011. Schedule IV France, Germany and Ukraine (in descending order) had the highest calculated consumption of GHB in 2011. 111. Five substances from the group of sedative-­hypnotics in Schedule IV are neither barbiturates nor benzodiaz- 114. Zolpidem is used to induce sleep. Global manufacture epines. While ethchlorvynol, ethinamate and methyprylon fluctuated during the period 2002-2011 between 18 tons and have been listed in Schedule IV since the adoption of the 51 tons, reflecting the changing output of the major manu- 1971 Convention, gamma-hydroxybutyric acid (GHB) and facturers, including India, Israel and France. In 2011, zolpidem were added to Schedule IV in 2001. reported global manufacture of zolpidem amounted to 19.6 tons (1.96 billion S-DDD), 83 per cent of which was 112. GHB is used in the treatment of narcolepsy and, accounted for by France (14 tons) and the Czech Republic more rarely, alcoholism. Data for GHB may still be incom- (2.3 tons). India, another key manufacturer, which accounted plete, as some countries have not extended import and for nearly 36 per cent of global manufacture in 2010, had export control measures to this substance. Reported manu­ not yet reported any data on manufacture for 2011. Other

Figure 28. Barbiturates in Schedules II, III and IV: share Figure 29. Barbiturates in Schedules II, III and IV: total of total reported manufacture, by substance, 2011 reported manufacture, selected countries, 2011

Pentobarbital 10% Barbital Others Amobarbital 12% Denmark 2% 5% 8% Germany Butalbital 5% Phenobarbital 11% 72%

United States 9%

Japan 3%

China 63%

58 Israel and Canada (in descending order). were held inFrance, United the States, Czech Republic, the In stocks at stood 2011,global 22tons, majority the of which fluctuated between 14 tonsduring 2007-2011 and 37 tons. reported manufacture of zolpidem stocks in 2011. Global Canada, Israel, Spain and (indescending China order), also countries, including Argentina, Japan, United the States, Uruguay had highestconsumption the calculated in 2011. cent TheRepublic, Czech ofexports. global Slovenia and twothe major exporters in2011,accounting for nearly 70 per stance to nearly 100countries. France and India remained 2011, with about 30countries reporting of exports sub the - psychotropic substances. reached trade Global 57tons in 115. Zolpidem is one of most the and widely traded used 59

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