heroin.rtf
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Heroin Heroin (diacetylmorphine or morphine diacetate (INN)), also known as diamorphine (BAN), and colloquially as H, smack, horse, brown, black, tar, and other names,[4 is an opioid anal!esic synthesi"ed by #$%$ Alder &ri!ht in '()4 by addin! two acetyl !roups to the molecule morphine, *ound in the opium poppy$ It is the +,,-diacetyl ester o* morphine$ Heroin itsel* is an acti.e dru!, but it is also con.erted into morphine in the body$[/ &hen used in medicine, it is typically used to treat se.ere pain, such as that resultin! *rom a heart attack or a se.ere in0ury$ 1he name 2heroin2 is only used when bein! discussed in its ille!al *orm$ &hen it is used in a medical en.ironment, it is re*erred to as diamorphine$ 1he white crystalline *orm considered 2pure heroin2 is usually the hydrochloride salt, diacetylmorphine hydrochloride$ Illicit heroin is sometimes a.ailable in *reebase *orm, dullin! the sheen and consistency to a matte-white powder$[, Because o* its lower boilin! point, the *reebase *orm o* heroin is also smokable$ It is pre.alent in heroin comin! *rom A*!hanistan, which as o* 3444 produced rou!hly ()5 o* the world supply in illicit raw opium$[) Howe.er, production in 6e7ico has risen si7 times *rom 344) to 34'', chan!in! that percenta!e and placin! 6e7ico as the second lar!est opium producer in the world$[( 6e7ican cartels are also known to produce a third type o* illicit heroin, commonly called black tar, which results *rom a simpli*ied, quicker synthesis procedure and contains a hi!h percenta!e o* morphine deri.ates other than heroin, such as ,-6onoacetylmorphine (,-6A6)$ As with other opioids, diacetylmorphine is used as both an anal!esic and a recreational dru!$ 8requent and re!ular administration is associated with tolerance and physical dependence$ Internationally, diacetylmorphine is controlled under 9chedules I and I: o* the 9in!le #on.ention on Narcotic ;ru!s$[< It is ille!al to manu*acture, possess, or sell diacetylmorphine without a license in almost e.ery country$ =nder the chemical names diamorphine and diacetylmorphine, heroin is a le!ally prescribed controlled dru! in the =nited >in!dom, and is supplied in tablet or in0ectable *orm *or the same indications as morphine is, o*ten bein! pre*erred o.er morphine due to its lower side-e**ect pro*ile$[citation needed It is also a.ailable *or prescription to lon!-term users as a *orm o* opioid replacement therapy in the Netherlands, =nited >in!dom, 9wit"erland, ?ermany, and ;enmark, alon!side psycho-social care@in the same manner that methadone or buprenorphine are used in the =nited 9tates or #anada['4 ['' @and a similar pro!ramme is bein! campai!ned *or by liberal political parties in Norway$
=sa!e lon!-term e**ects o* intra.enous usa!e, includin! A and indeed primarily because o* A the e**ects o* the contaminants common in ille!al heroin and contaminated needles$['3
9hort-term e**ects o* usa!e['3 1he BB# reported that 2&orldwide, the =N estimates that as o* 344/, there are more than /4 million re!ular users o* heroin, cocaine and synthetic dru!s$2['+ ?lobal users o* diacetylmorphine are estimated at between '/ and 3' million people a!ed '/A,4$['4 6edical use =nder the chemical name diamorphine, diacetylmorphine is prescribed as a stron! anal!esic in the =nited >in!dom, where it is !i.en .ia subcutaneous, intramuscular, intrathecal or intra.enous route$ Its use includes treatment *or acute pain, such as in se.ere physical trauma, myocardial in*arction, postsur!ical pain, and chronic pain, includin! end-sta!e cancer and other terminal illnesses$ In other countries it is more common to use morphine or other stron! opioids in these situations$ In 3444, the National Institute *or Health and #linical B7cellence produced !uidance on the mana!ement o* caesarian section, which recommended the use o* intrathecal or epidural diacetylmorphine *or post-operati.e pain relie*$['/ In 344/, there was a shorta!e o* diacetylmorphine in the =>, because o* a problem at the main => manu*acturers$[', Because o* this, many hospitals chan!ed to usin! morphine instead o* diacetylmorphine$ Althou!h there is no lon!er a problem with the manu*acturin! o* diacetylmorphine in the =>, some hospitals there ha.e continued to use morphine$ 1he ma0ority, howe.er, continue to use diacetylmorphine, and diacetylmorphine tablets are supplied *or pain mana!ement$ ;iacetylmorphine continues to be widely used in palliati.e care in the =nited >in!dom, where it is commonly !i.en by the subcutaneous route, o*ten .ia a syrin!e dri.er, i* patients cannot easily swallow oral morphine solution$ 1he ad.anta!e o* diacetylmorphine o.er morphine is that diacetylmorphine is more *at soluble and there*ore more potent (by in0ection only), so smaller doses o* it are needed *or the same anal!esic e**ect$ Both o* these *actors are ad.anta!eous i* !i.in! hi!h doses o* opioids .ia the subcutaneous route, which is o*ten necessary in palliati.e care$
1he medical use o* diacetylmorphine (in common with other stron! opioids such as morphine, *entanyl and o7ycodone) is controlled in the =nited >in!dom by the 6isuse o* ;ru!s Act '<)'$ In the =>, it is a class A controlled dru! and as such is sub0ect to !uidelines surroundin! its stora!e, administration and destruction$ Cossession o* ;iamorphine without a prescription is an arrestable o**ence$ &hen ;iamorphine is prescribed in a hospital or similar en.ironment, its administration must be super.ised by 3 people who must then complete and si!n a #; re!ister detailin! the patients name, amount, time, date and route o* administration$ In the case o* a doctor administerin! diamorphine, then heDshe may administer the dru! alone, howe.er the rule requirin! two re!istered practitioners (ie$ a nurse, midwi*e or another doctor) to si!n the #; re!ister still applies$ 1he use o* a 2witness2 when administerin! ;iamorphine is to a.oid the possibility o* the dru! bein! di.erted onto the black market$ 8or sa*ety reasons, many => National Health 9er.ice hospitals now only permit the administration o* intra.enous diamorphine in desi!nated areas$ In practice this usually means a critical care unit, an accident and emer!ency department, operatin! theatres by an anaesthetist or nurse anaesthetist or other such areas where close monitorin! and support *rom senior sta** is immediately a.ailable$ Howe.er, administration by other routes is permitted in other areas o* the hospital$ 1his includes subcutaneous, intramuscular, intra.enously as part o* a patient controlled anal!esia setup, and as an already established epidural in*usion pump$ 9ubcutaneous in*usion, alon! with subcutaneous and intramuscular EbolusE administration is o*ten used in the patientEs own home, in order to treat se.ere pain in terminal illness$ ;iacetylmorphine is also used as a maintenance dru! to treat certain !roups o* addicts, normally lon! term chronic I: heroin users, and e.en in these situations it is only prescribed *ollowin! e7hausti.e e**orts at treatment .ia other means$ It is thou!ht that heroin users can walk into a clinic and walk out with a prescription but the process takes many weeks be*ore a prescription *or ;iacetylmorphine is issued$ 1hou!h this is somewhat contro.ersial amon! proponents o* a "ero tolerance dru! policy, it has pro.en superior to methadone in impro.in! the social and health situation o* addicts$ [') 9eeF Heroin prescription *or addicts %ecreational use ;iacetylmorphine, almost always still called by its ori!inal trade name o* heroin in non-medical settin!s, is used as a recreational dru! *or the transcendent rela7ation and intense euphoria it induces$ Anthropolo!ist 6ichael A!ar once described heroin as 2the per*ect whate.er dru!$2['( 1olerance de.elops quickly, and users need more o* the dru! to achie.e the same e**ects$ Its popularity with recreational dru! users, compared to
morphine, reportedly stems *rom its percei.ed di**erent e**ects$['< In particular, users report an intense rush, an acute transcendent state o* euphoria, which occurs while diacetylmorphine is bein! metaboli"ed into ,monoacetylmorphine (,-6A6) and morphine in the brain$ 9ome belie.e that heroin produces more euphoria than other opioids upon in0ectionG one possible e7planation is the presence o* ,-monoacetylmorphine, a metabolite unique to heroin A althou!h a more likely e7planation is the rapidity o* onset$ &hile other opioids o* recreational use produce only morphine, heroin also lea.es ,-6A6, also a psycho-acti.e metabolite$ Howe.er, this perception is not supported by the results o* clinical studies comparin! the physiolo!ical and sub0ecti.e e**ects o* in0ected heroin and morphine in indi.iduals *ormerly addicted to opioidsG these sub0ects showed no pre*erence *or one dru! o.er the other$ Bquipotent in0ected doses had comparable action courses, with no di**erence in sub0ectsE sel*-rated *eelin!s o* euphoria, ambition, ner.ousness, rela7ation, drowsiness, or sleepiness$[34 9hort-term addiction studies by the same researchers demonstrated that tolerance de.eloped at a similar rate to both heroin and morphine$ &hen compared to the opioids hydromorphone, *entanyl, o7ycodone, and pethidineDmeperidine, *ormer addicts showed a stron! pre*erence *or heroin and morphine, su!!estin! that heroin and morphine are particularly susceptible to abuse and addiction$ 6orphine and heroin were also much more likely to produce euphoria and other positi.e sub0ecti.e e**ects when compared to these other opioids$[34 9ome researchers ha.e attempted to e7plain heroin use and the culture that surrounds it throu!h the use o* sociolo!ical theories$ In %i!hteous ;ope*iend, Chilippe Bour!ois and He** 9chonber! use anomie theory to e7plain why people be!in usin! heroin$ By analy"in! a community in 9an 8rancisco, they demonstrated that heroin use was caused in part by internal and e7ternal *actors such as .iolent homes and parental ne!lect$ 1his lack o* emotional, social, and *inancial support causes strain and in*luences indi.iduals to en!a!e in de.iant acts, includin! heroin usa!e$[3' 1hey *urther *ound that heroin users practiced 2retreatism2, a beha.ior *irst described by Howard Abadinsky, in which those su**erin! *rom such strain re0ect societyEs !oals and institutionali"ed means o* achie.in! them$[33 Crescription *or addicts 6ain articleF Heroin assisted treatment 1he => ;epartment o* HealthEs %olleston #ommittee %eport[3+ in '<3, established the British approach to diacetylmorphine prescription to users, which was maintained *or the ne7t 44 yearsF dealers were prosecuted, but doctors could prescribe diacetylmorphine to users when withdrawin! *rom it
would cause harm or se.ere distress to the patient$ 1his 2policin! and prescribin!2 policy e**ecti.ely controlled the percei.ed diacetylmorphine problem in the => until '</< when the number o* diacetylmorphine addicts doubled e.ery ', months durin! a period o* ten years, '</<A'<,($[34 In '<,4 the Brain #ommittee recommended that only selected appro.ed doctors workin! at appro.ed specialised centres be allowed to prescribe diacetylmorphine and ben"oylmethylec!onine (cocaine) to users$ 1he law was made more restricti.e in '<,($ Be!innin! in the '<)4s, the emphasis shi*ted to abstinence and the use o* methadoneG until now only a small number o* users in the => are prescribed diacetylmorphine$[3/ In '<<4, 9wit"erland be!an a trial diamorphine maintenance pro!ram *or users that had *ailed multiple withdrawal pro!rams$ 1he aim o* this pro!ram was to maintain the health o* the user by a.oidin! medical problems stemmin! *rom the illicit use o* diacetylmorphine$ 1he *irst trial in '<<4 in.ol.ed +44 users, althou!h enrollment was later e7panded to '444 based on the apparent success o* the pro!ram$ 1he trials pro.ed diamorphine maintenance to be superior to other *orms o* treatment in impro.in! the social and health situation *or this !roup o* patients$[3, It has also been shown to sa.e money, despite hi!h treatment e7penses, as it si!ni*icantly reduces costs incurred by trials, incarceration, health inter.entions and delinquency$[3) Catients appear twice daily at a treatment center, where they in0ect their dose o* diamorphine under the super.ision o* medical sta**$ 1hey are required to contribute about 4/4 swiss *ranc per month to the treatment costs$[3( A national re*erendum in No.ember 344( showed ,(5 o* .oters supported the plan,[3< introducin! diacetylmorphine prescription into *ederal law$ 1he trials be*ore were based on time-limited e7ecuti.e ordinances$ 1he success o* the 9wiss trials led ?erman, ;utch,[+4 and #anadian[+' cities to try out their own diamorphine prescription pro!rams$[+3 9ome Australian cities (such as 9ydney) ha.e instituted le!al diacetylmorphine super.ised in0ectin! centers, in line with other wider harm minimi"ation pro!rams$ 9ince Hanuary 344<, ;enmark has prescribed diamorphine to a *ew addicts that ha.e tried methadone and subute7 without success$[++ Be!innin! in 8ebruary 34'4, addicts in #openha!en and Idense will be eli!ible to recei.e *ree diacetylmorphine$ Jater in 34'4 other cities includin! Krhus and Bsb0er! will 0oin the scheme$ In total, around 3+4 addicts will be able to recei.e *ree diacetylmorphine$[+4 Howe.er, ;anish addicts will only be able to in0ect heroin accordin! to the policy set by ;anish National Board o* Health$[+/ I* the estimated '/44 dru! users who do not bene*it *rom the current oral
substitution treatment, appro7imately <44 will not be in the tar!et !roup *or treatment with in0ectable diacetylmorphine, either because o* 2massi.e multiple dru! abuse o* non-opioids2 or 2not wantin! treatment with in0ectable diacetylmorphine2$[+, In Huly 344<, the ?erman Bundesta! passed a law allowin! diacetylmorphine prescription as a standard treatment *or addictsG a lar!e-scale trial o* diacetylmorphine prescription had been authori"ed in that country in 3443$ [+) ;etection in biolo!ical *luids 1he ma0or metabolites o* diacetylmorphine, ,-6A6, morphine, morphine-+!lucuronide and morphine-,-!lucuronide, may be quantitated in blood, plasma or urine to monitor *or abuse, con*irm a dia!nosis o* poisonin! or assist in a medicole!al death in.esti!ation$ 6ost commercial opiate screenin! tests cross-react appreciably with these metabolites, as well as with other biotrans*ormation products likely to be present *ollowin! usa!e o* street!rade diacetylmorphine such as ,-acetylcodeine and codeine$ Howe.er, chromato!raphic techniques can easily distin!uish and measure each o* these substances$ &hen interpretin! the results o* a test, it is important to consider the diacetylmorphine usa!e history o* the indi.idual, since a chronic user can de.elop tolerance to doses that would incapacitate an opiate-nai.e indi.idual, and the chronic user o*ten has hi!h baseline .alues o* these metabolites in his system$ 8urthermore, some testin! procedures employ a hydrolysis step prior to quantitation that con.erts many o* the metabolic products to morphine, yieldin! a result that may be 3 times lar!er than with a method that e7amines each product indi.idually$[+( Ad.erse e**ects
Jike most opioids, unadulterated heroin does not cause many lon!-term complications other than dependence and constipation$[+< ;ue to increased .ulnerability to in*ectious a!ents, particularly .iruses and intracellular bacteria resultin! *rom the suppression o* .arious cell-mediated immune pathways, the use o* heroin and other opioids, e.en at normal therapeutic le.els, may lead to opportunistic in*ections, which carry their own lastin! e**ects$[44 [4' [43 1he a.era!e purity o* street heroin in the => .aries between +45 and /45 and heroin that has been sei"ed at the border has purity le.els between 445 and ,45G this .ariation has led to people su**erin! *rom o.erdoses as a result o* the heroin missin! a sta!e on its 0ourney *rom port to end user, as each set o* hands that the dru! passes throu!h adds *urther adulterants, the stren!th o* the dru! reduces, with the e**ect that i* steps are missed, the purity o* the dru! reachin! the end user is hi!her than
they are used to and because they are unable to tolerate the increase, an o.erdose ensues$[4+ Intra.enous use o* heroin (and any other substance) with non-sterile needles and syrin!es or other related equipment may lead toF 1he risk o* contractin! blood-borne patho!ens such as HI: and hepatitis by the sharin! o* needles 1he risk o* contractin! bacterial or *un!al endocarditis and possibly .enous sclerosis Abscesses Coisonin! *rom contaminants added to 2cut2 or dilute heroin Chysical dependence can result *rom prolon!ed use o* all opioids, resultin! in withdrawal symptoms on cessation o* use ;ecreased kidney *unction (althou!h it is not currently known i* this is because o* adulterants or in*ectious diseases)[44 6any countries and local !o.ernments ha.e be!un *undin! pro!rams that supply sterile needles to people who in0ect ille!al dru!s in an attempt to reduce these contin!ent risks, and especially the spread o* blood-borne diseases$ 1he ;ru! Colicy Alliance reports that up to )/5 o* new AI;9 cases amon! women and children are directly or indirectly a consequence o* dru! use by in0ection[citation needed $ 1he =nited 9tates *ederal !o.ernment does not operate needle e7chan!es, althou!h some state and local !o.ernments do support needle e7chan!e pro!rams$ Anthropolo!ists Chilippe Bour!ois and He** 9chonber! per*ormed a decade o* *ield work amon! homeless heroin and cocaine addicts in 9an 8rancisco, published in 344<$ 1hey reported that the A*rican-American addicts they obser.ed were more inclined to 2direct deposit2 heroin into a .ein, while 2skin-poppin!2 was a *ar more widespread practiceF 2By the midpoint o* our *ieldwork, most o* the whites had !i.en up searchin! *or operable .eins and skin-popped$ 1hey sank their needles per*unctorily, o*ten throu!h their clothin!, into their *atty tissue$2) Bour!ois and 9chonber! describes how the cultural di**erence between the A*rican-Americans and the whites leads to this contrastin! beha.ior, and also points out that the two di**erent ways to in0ect heroin comes with di**erent health risks$ 9kin-poppin! more o*ten results in abscesses, and direct in0ection more o*ten leads to *atal o.erdose and also to hepatitis # and HI: in*ection$[3' Heroin o.erdose is usually treated with an opioid anta!onist,[citation needed such as nalo7one (Narcan), or naltre7one, which has hi!h a**inity *or opioid receptors but does not acti.ate them$ 1his re.erses the e**ects o* heroin and
other opioid a!onists and causes an immediate return o* consciousness but may precipitate withdrawal symptoms$ 1he hal*-li*e o* nalo7one is much shorter than that o* most opioid a!onists, so that anta!onist typically has to be administered multiple times until the opioid has been metaboli"ed by the body$ ;ependin! on dru! interactions and numerous other *actors, death *rom o.erdose can take anywhere *rom se.eral minutes to se.eral hours because o* ano7ia resultin! *rom the breathin! re*le7 bein! suppressed by a!onism o* L-opioid receptors$ An o.erdose is immediately re.ersible with an opioid anta!onist in0ection$ ;iacetylmorphine o.erdoses can occur because o* an une7pected increase in the dose or purity or because o* diminished opioid tolerance$ Howe.er, many *atalities reported as o.erdoses are probably caused by interactions with other depressant dru!s like alcohol or ben"odia"epines$[4/ It should also be noted that since heroin can cause nausea and .omitin!, a si!ni*icant number o* deaths attributed to heroin o.erdose are caused by aspiration o* .omit by an unconscious .ictim$ 9ome sources quote the median lethal dose (*or an a.era!e )/ k! opiate-nai.e indi.idual) as bein! between )/ and +)/ m!$[4, Illicit heroin is o* widely .aryin! and unpredictable purity$ 1his means that the user may prepare what they consider to be a moderate dose while actually takin! *ar more than intended$ Also, tolerance typically decreases a*ter a period o* abstinence$ I* this occurs and the user takes a dose comparable to their pre.ious use, the user may e7perience dru! e**ects that are much !reater than e7pected, potentially resultin! in a dan!erous o.erdose$ It has been speculated that an unknown portion o* heroin related deaths are the result o* an o.erdose or aller!ic reaction to quinine, which may sometimes be used as a cuttin! a!ent$[4) A *inal *actor contributin! to o.erdoses is place conditionin!$ ;iacetylmorphine use is a hi!hly rituali"ed beha.ior$ &hile the mechanism has yet to be clearly elucidated, lon!time heroin users display increased tolerance to the dru! in locations where they ha.e repeatedly administered$ &hen the user in0ects in a di**erent location, this en.ironment-conditioned tolerance does not occur, resultin! in a !reater dru! e**ect$ 1he userEs typical dose o* the dru!, in the *ace o* decreased tolerance, becomes *ar too hi!h and can be to7ic, leadin! to o.erdose$[4( A small percenta!e o* heroin smokers, and occasionally I: users, may de.elop symptoms o* to7ic leukoencephalopathy$ 1he cause has yet to be identi*ied, but one speculation is that the disorder is caused by an uncommon adulterant that is only acti.e when heated$[4< [/4 [/' 9ymptoms include slurred speech and di**iculty walkin!$ #ocaine is sometimes used in combination with heroin, and is re*erred to as a
speedball when in0ected or moonrocks when smoked to!ether$ #ocaine acts as a stimulant, whereas heroin acts as a depressant$ #oadministration pro.ides an intense rush o* euphoria with a hi!h that combines both e**ects o* the dru!s, while e7cludin! the ne!ati.e e**ects, such as an7iety and sedation$ 1he e**ects o* cocaine wear o** *ar more quickly than heroin, thus i* an o.erdose o* heroin was used to compensate *or cocaine, the end result is *atal respiratory depression$[citation needed
Creppin! heroin *or in0ection
6odi*ied syrin!e *or suppository administration
Ine stamp o* heroin
#hunky 2No$+2 heroin
&ithdrawal 6ain articleF Ipioid withdrawal 1he withdrawal syndrome *rom heroin (the so-called 2cold turkey2) may be!in within , to 34 hours o* discontinuation o* the dru!G howe.er, this time *rame can *luctuate with the de!ree o* tolerance as well as the amount o* the last consumed dose$ 9ymptoms may includeF[/3 sweatin!, malaise, an7iety, depression, akathisia, priapism, e7tra sensiti.ity o* the !enitals in *emales, !eneral *eelin! o* hea.iness, e7cessi.e yawnin! or snee"in!, tears, rhinorrhea, sleep di**iculties (insomnia), cold sweats, chills, se.ere muscle
and bone aches, nausea, .omitin!, diarrhea, cramps, watery eyes,[/+ *e.er and cramp-like pains and in.oluntary spasms in the limbs (thou!ht to be an ori!in o* the term 2kickin! the habit2[/4 )$ Charmacolo!y
Black tar heroin &hen taken orally, heroin under!oes e7tensi.e *irst-pass metabolism .ia deacetylation, makin! it a prodru! *or the systemic deli.ery o* morphine$[/ &hen the dru! is in0ected, howe.er, it a.oids this *irst-pass e**ect, .ery rapidly crossin! the bloodAbrain barrier because o* the presence o* the acetyl !roups, which render it much more *at soluble than morphine itsel*$[// Ince in the brain, it then is deacetylated .ariously into the inacti.e +monoacetylmorphine and the acti.e ,-monoacetylmorphine (,-6A6), and then to morphine, which bind to M-opioid receptors, resultin! in the dru!Es euphoric, anal!esic (pain relie*), and an7iolytic (anti-an7iety) e**ectsG heroin itsel* e7hibits relati.ely low a**inity *or the M receptor$[/, =nlike hydromorphone and o7ymorphone, howe.er, administered intra.enously, heroin creates a lar!er histamine release, similar to morphine, resultin! in the *eelin! o* a !reater sub0ecti.e 2body hi!h2 to some, but also instances o* pruritus (itchin!) when they *irst start usin!$[/) Both morphine and ,-6A6 are M-opioid a!onists that bind to receptors present throu!hout the brain, spinal cord, and !ut o* all mammals$ 1he Mopioid receptor also binds endo!enous opioid peptides such as N-endorphin, Jeu-enkephalin, and 6et-enkephalin$ %epeated use o* heroin results in a number o* physiolo!ical chan!es, includin! an increase in the production o* M-opioid receptors (upre!ulation)$[citation needed 1hese physiolo!ical alterations lead to tolerance and dependence, so that cessation o* heroin use results in a set o* remarkably uncom*ortable symptoms includin! pain, an7iety, muscle spasms, and insomnia called the opioid withdrawal syndrome$ ;ependin! on usa!e it has an onset *our to 34 hours a*ter the last dose o* heroin$ 6orphine also binds to O- and P-opioid receptors$ 1here is also e.idence that ,-6A6 binds to a subtype o* M-opioid receptors that are also acti.ated by the morphine metabolite morphine-,N-!lucuronide but not morphine itsel*$[/( 1he third substype o* third opioid type is the mu+ receptor, which may be a commonality to other si7-position monoesters o* morphine$ 1he contribution o* these receptors to the o.erall pharmacolo!y o*
heroin remains unknown$ A subclass o* morphine deri.ati.es, namely the +,, esters o* morphine, with similar e**ects and uses, includes the clinically used stron! anal!esics nicomorphine (:ilan), and dipropanoylmorphineG there is also the latterEs dihydromorphine analo!ue, diacetyldihydromorphine (Caralaudin)$ 1wo other +,, diesters o* morphine in.ented in '()4-/ alon! with diacetylmorphine, diben"oylmorphine and acetylpropionylmorphine, were made as substitutes a*ter it was outlawed in '<3/ and, there*ore, sold as the *irst 2desi!ner dru!s2 until they were outlawed by the Jea!ue o* Nations in '<+4$ Btymolo!y
In '(</, the ?erman dru! company Bayer marketed diacetylmorphine as an o.er-the-counter dru! under the trademark name Heroin$[/< 1he name was deri.ed *rom the ?reek word 2Heros2 because o* its percei.ed 2heroic2 e**ects upon a user$[/< It was de.eloped chie*ly as a morphine substitute *or cou!h suppressants that did not ha.e morphineEs addicti.e side-e**ects$ 6orphine at the time was a popular recreational dru!, and Bayer wished to *ind a similar but non-addicti.e substitute to market$ Howe.er, contrary to BayerEs ad.ertisin! as a 2non-addicti.e morphine substitute,2 heroin would soon ha.e one o* the hi!hest rates o* dependence amon! its users$[,4
9ynthesis o* heroin *rom opium History
Bayer Heroin bottle 1he opium poppy was culti.ated in lower 6esopotamia as lon! a!o as +444 B#B$[,' 1he chemical analysis o* opium in the '<th century re.ealed that most o* its acti.ity could be ascribed to two alkaloids, codeine and morphine$ ;iacetylmorphine was *irst synthesi"ed in '()4 by #$ %$ Alder &ri!ht, an Bn!lish chemist workin! at 9t$ 6aryEs Hospital 6edical 9chool in Jondon$ He had been e7perimentin! with combinin! morphine with .arious acids$ He
boiled anhydrous morphine alkaloid with acetic anhydride *or se.eral hours and produced a more potent, acetylated *orm o* morphine, now called diacetylmorphine or morphine diacetate$ 1he compound was sent to 8$ 6$ Cierce o* Iwens #olle!e in 6anchester *or analysis$ Cierce told &ri!htF ;oses $$$ were subcutaneously in0ected into youn! do!s and rabbits $$$ with the *ollowin! !eneral results $$$ !reat prostration, *ear, and sleepiness speedily *ollowin! the administration, the eyes bein! sensiti.e, and pupils constrict, considerable sali.ation bein! produced in do!s, and sli!ht tendency to .omitin! in some cases, but no actual emesis$ %espiration was at *irst quickened, but subsequently reduced, and the heartEs action was diminished, and rendered irre!ular$ 6arked want o* coordinatin! power o.er the muscular mo.ements, and loss o* power in the pel.is and hind limbs, to!ether with a diminution o* temperature in the rectum o* about 4Q$[,3
Ad.ertisement *or Bayer Heroin &ri!htEs in.ention did not lead to any *urther de.elopments, and diacetylmorphine became popular only a*ter it was independently resynthesi"ed 3+ years later by another chemist, 8eli7 Ho**mann$ Ho**mann, workin! at the Aktien!esellscha*t 8arben*abriken (today the Bayer pharmaceutical company) in Blber*eld, ?ermany, was instructed by his super.isor Heinrich ;reser to acetylate morphine with the ob0ecti.e o* producin! codeine, a constituent o* the opium poppy, pharmacolo!ically similar to morphine but less potent and less addicti.e$ Instead, the e7periment produced an acetylated *orm o* morphine one and a hal* to two times more potent than morphine itsel*$ 8rom '(<( throu!h to '<'4, diacetylmorphine was marketed under the trademark name Heroin as a non-addicti.e morphine substitute and cou!h suppressant$ Bayer marketed the dru! as a cure *or morphine addiction be*ore it was disco.ered that it rapidly metaboli"es into morphine$ As such, diacetylmorphine is in essence a quicker-actin! *orm o* morphine$ 1he company was embarrassed by the new *indin!, which became a historic blunder *or Bayer$[,+ In the =$9$A$, the Harrison Narcotics 1a7 Act was passed in '<'4 to control the
sale and distribution o* diacetylmorphine and other opioids, which allowed the dru! to be prescribed and sold *or medical purposes$ In '<34, the =nited 9tates #on!ress banned its sale, importation, or manu*acture$ It is now a 9chedule I substance, which makes it ille!al *or non-medical use in si!natory nations o* the 9in!le #on.ention on Narcotic ;ru!s treaty, includin! the =nited 9tates$ 1he Health #ommittee o* the Jea!ue o* Nations banned diacetylmorphine in '<3/, althou!h it took more than three years *or this to be implemented$ In the meantime, the *irst desi!ner dru!s, .i"$ +,, diesters and , monoesters o* morphine and acetylated analo!ues o* closely related dru!s like hydromorphone and dihydromorphine were produced in massi.e quantities to *ill the worldwide demand *or diacetylmorphine@this continued until '<+4 when the #ommittee banned diacetylmorphine analo!ues with no therapeutic ad.anta!e o.er dru!s already in use, the *irst ma0or le!islation o* this type$ [,4 Jater, as with Aspirin, Bayer lost some o* its trademark ri!hts to heroin under the '<'< 1reaty o* :ersailles *ollowin! the ?erman de*eat in &orld &ar I$[,/ %outes o* administration
%ecreational usesF Buphoria 1ranscendent rela7ation 6edicinal usesF Cower*ul anal!esic (pain killer) #ou!h suppressant Anti-diarrheal #ontraindicationsF Alcohol Barbiturates and ben"odia"epines 9timulants Ither opioids #entral ner.ous systemF
;rowsiness ;isorientation ;elirium Neurolo!icalF Anal!esia 1olerance Addiction (physical dependence) Csycholo!icalF Addiction (psycholo!ical dependence) An7iolysis #on*usion Buphoria 9omnolence #ardio.ascular R %espiratoryF Bradycardia Hypotension Hypo.entilation 9hallow breathin! %espiratory depression ?astrointestinalF Nausea Crotracted .omitin! #onstipation ;yspepsia (heartburn) 6usculoskeletalF Anal!esia
Ata7ia 6uscle spasticity 9kinF Itchin! 8lushin!D%ash 6iscellaneousF ;ry mouth (7erostomia) 6iosis (pupil constriction) =rinary retention
;iamorphine ampoules *or medicinal use 1he onset o* heroinEs e**ects depends upon the route o* administration$ 9tudies ha.e shown that the sub0ecti.e pleasure o* dru! use (the rein*orcin! component o* addiction) is proportional to the rate at which the blood le.el o* the dru! increases$[,, Intra.enous in0ection is the *astest route o* dru! administration, causin! blood concentrations to rise the most quickly, *ollowed by smokin!, suppository (anal or .a!inal insertion), insu**lation (snortin!), and in!estion (swallowin!)$ In!estion does not produce a rush as *orerunner to the hi!h e7perienced with the use o* heroin, which is most pronounced with intra.enous use$ &hile the onset o* the rush induced by in0ection can occur in as little as a *ew seconds, the oral route o* administration requires appro7imately hal* an hour be*ore the hi!h sets in$ 1hus, with both hi!her the dosa!e o* heroin used and *aster the route o* administration used, the hi!her potential risk *or psycholo!ical addiction$ Jar!e doses o* heroin can cause *atal respiratory depression, and the dru! has been used *or suicide or as a murder weapon$ 1he serial killer ;r Harold 9hipman used diamorphine on his .ictims, and the subsequent 29hipman Inquiry2 led to a ti!htenin! o* the re!ulations surroundin! the stora!e, prescribin! and destruction o* controlled dru!s in the =>$ ;r Hohn Bodkin Adams (see his .ictim Bdith Alice 6orrell) is also known to ha.e used heroin as a murder weapon$
Because si!ni*icant tolerance to respiratory depression de.elops quickly with continued use and is lost 0ust as quickly durin! withdrawal, it is o*ten di**icult to determine whether a heroin lethal o.erdose was accidental, suicide or homicide$ B7amples include the o.erdose deaths o* 9id :icious, Hanis Hoplin, 1im Buckley, Hillel 9lo.ak, Jayne 9taley, Bradley Nowell, 1ed Binion, and %i.er Choeni7$[,) #hronic use o* heroin and other opioids, has been shown to be a potential cause o* hyponatremia, resultant because o* e7cess .asopressin secretion$ Iral Iral use o* heroin is less common than other methods o* administration, mainly because there is little to no 2rush2, and the e**ects are less potent$[,( Heroin is entirely con.erted to morphine by means o* *irst-pass metabolism, resultin! in deacetylation when in!ested$ HeroinEs oral bioa.ailability is both dose-dependent (as is morphineEs) and si!ni*icantly hi!her than oral use o* morphine itsel*, reachin! up to ,4$35 *or hi!h doses and 4/$,5 *or low dosesG opiate-nai.e users showed *ar less absorption o* the dru! at low doses, ha.in! bioa.ailabilities o* only up to 33$<5$ 1he ma7imum plasma concentration o* morphine *ollowin! oral administration o* heroin was around twice as much as that o* oral morphine$[,< In0ection In0ection, also known as 2slammin!2, 2ban!in!2, 2shootin! up2, 2di!!in!2 or 2mainlinin!2, is a popular method which carries relati.ely !reater risks than other methods o* administration$ Heroin base (commonly *ound in Burope), when prepared *or in0ection will only dissol.e in water when mi7ed with an acid (most commonly citric acid powder or lemon 0uice) and heated$ Heroin in the Bast coast =nited 9tates is most commonly *ound in the hydrochloride salt *orm, requirin! 0ust water (and no heat) to dissol.e$ =sers tend to initially in0ect in the easily accessible arm .eins, but as these .eins collapse o.er time, users resort to more dan!erous areas o* the body, such as the *emoral .ein in the !roin$ =sers who ha.e used this route o* administration o*ten de.elop a deep .ein thrombosis$[)4 Intra.enous users can use a .arious sin!le dose ran!e usin! a hypodermic needle$ 1he dose o* heroin used *or recreational purposes is dependent on the *requency and le.el o* use, thus a *irst-time user may use between / and 34 m!, while an established addict may require se.eral hundred m! per day$ As with the in0ection o* any dru!, i* a !roup o* users share a common needle without sterili"ation procedures, blood-borne diseases, such as HI: or hepatitis, can be transmitted$ 1he use o* a common dispenser *or water *or the use in the preparation o* the in0ection, as well as the sharin! o* spoons andDor *ilters can also cause the spread o* blood borne diseases$ 6any countries now supply small sterile spoons and
*ilters *or sin!le use in order to pre.ent the spread o* disease$[)' 9mokin! 9mokin! heroin re*ers to .apori"in! it to inhale the resultin! *umes, not burnin! it to inhale the resultin! smoke$ It is commonly smoked in !lass pipes made *rom !lassblown Cyre7 tubes and li!ht bulbs$ It can also be smoked o** aluminium *oil, which is heated underneath by a *lame and the resultin! smoke is inhaled throu!h a tube o* rolled up *oil, 1his method is also known as 2chasin! the dra!on2 (whereas smokin! methamphetamine is known as 2chasin! the white dra!on2)$ Insu**lation Another popular route to intake heroin is insu**lation (snortin!), where a user crushes the heroin into a *ine powder and then !ently inhales it (sometimes with a straw or a rolled up banknote, as with cocaine) into the nose, where heroin is absorbed throu!h the so*t tissue in the mucous membrane o* the sinus ca.ity and strai!ht into the bloodstream$ 1his method o* administration redirects *irst pass metabolism, with a quicker onset and hi!her bioa.ailability than oral administration, thou!h the duration o* action is shortened$ 1his method is sometimes pre*erred by users who do not want to prepare and administer heroin *or in0ection or smokin!, but still e7perience a *ast onset$ 9nortin! heroin becomes an o*ten unwanted route, once a user be!ins to in0ect the dru!$ 1he user may still !et hi!h on the dru! *rom snortin!, and e7perience a nod, but will not !et a rush$ A 2rush2 is caused by a lar!e amount o* heroin enterin! the body at once$ &hen the dru! is taken in throu!h the nose, the user does not !et the rush because the dru! is absorbed slowly rather than instantly$ 9uppository
=sa!e lon!-term e**ects o* intra.enous usa!e, includin! A and indeed primarily because o* A the e**ects o* the contaminants common in ille!al heroin and contaminated needles$['3
9hort-term e**ects o* usa!e['3 1he BB# reported that 2&orldwide, the =N estimates that as o* 344/, there are more than /4 million re!ular users o* heroin, cocaine and synthetic dru!s$2['+ ?lobal users o* diacetylmorphine are estimated at between '/ and 3' million people a!ed '/A,4$['4 6edical use =nder the chemical name diamorphine, diacetylmorphine is prescribed as a stron! anal!esic in the =nited >in!dom, where it is !i.en .ia subcutaneous, intramuscular, intrathecal or intra.enous route$ Its use includes treatment *or acute pain, such as in se.ere physical trauma, myocardial in*arction, postsur!ical pain, and chronic pain, includin! end-sta!e cancer and other terminal illnesses$ In other countries it is more common to use morphine or other stron! opioids in these situations$ In 3444, the National Institute *or Health and #linical B7cellence produced !uidance on the mana!ement o* caesarian section, which recommended the use o* intrathecal or epidural diacetylmorphine *or post-operati.e pain relie*$['/ In 344/, there was a shorta!e o* diacetylmorphine in the =>, because o* a problem at the main => manu*acturers$[', Because o* this, many hospitals chan!ed to usin! morphine instead o* diacetylmorphine$ Althou!h there is no lon!er a problem with the manu*acturin! o* diacetylmorphine in the =>, some hospitals there ha.e continued to use morphine$ 1he ma0ority, howe.er, continue to use diacetylmorphine, and diacetylmorphine tablets are supplied *or pain mana!ement$ ;iacetylmorphine continues to be widely used in palliati.e care in the =nited >in!dom, where it is commonly !i.en by the subcutaneous route, o*ten .ia a syrin!e dri.er, i* patients cannot easily swallow oral morphine solution$ 1he ad.anta!e o* diacetylmorphine o.er morphine is that diacetylmorphine is more *at soluble and there*ore more potent (by in0ection only), so smaller doses o* it are needed *or the same anal!esic e**ect$ Both o* these *actors are ad.anta!eous i* !i.in! hi!h doses o* opioids .ia the subcutaneous route, which is o*ten necessary in palliati.e care$
1he medical use o* diacetylmorphine (in common with other stron! opioids such as morphine, *entanyl and o7ycodone) is controlled in the =nited >in!dom by the 6isuse o* ;ru!s Act '<)'$ In the =>, it is a class A controlled dru! and as such is sub0ect to !uidelines surroundin! its stora!e, administration and destruction$ Cossession o* ;iamorphine without a prescription is an arrestable o**ence$ &hen ;iamorphine is prescribed in a hospital or similar en.ironment, its administration must be super.ised by 3 people who must then complete and si!n a #; re!ister detailin! the patients name, amount, time, date and route o* administration$ In the case o* a doctor administerin! diamorphine, then heDshe may administer the dru! alone, howe.er the rule requirin! two re!istered practitioners (ie$ a nurse, midwi*e or another doctor) to si!n the #; re!ister still applies$ 1he use o* a 2witness2 when administerin! ;iamorphine is to a.oid the possibility o* the dru! bein! di.erted onto the black market$ 8or sa*ety reasons, many => National Health 9er.ice hospitals now only permit the administration o* intra.enous diamorphine in desi!nated areas$ In practice this usually means a critical care unit, an accident and emer!ency department, operatin! theatres by an anaesthetist or nurse anaesthetist or other such areas where close monitorin! and support *rom senior sta** is immediately a.ailable$ Howe.er, administration by other routes is permitted in other areas o* the hospital$ 1his includes subcutaneous, intramuscular, intra.enously as part o* a patient controlled anal!esia setup, and as an already established epidural in*usion pump$ 9ubcutaneous in*usion, alon! with subcutaneous and intramuscular EbolusE administration is o*ten used in the patientEs own home, in order to treat se.ere pain in terminal illness$ ;iacetylmorphine is also used as a maintenance dru! to treat certain !roups o* addicts, normally lon! term chronic I: heroin users, and e.en in these situations it is only prescribed *ollowin! e7hausti.e e**orts at treatment .ia other means$ It is thou!ht that heroin users can walk into a clinic and walk out with a prescription but the process takes many weeks be*ore a prescription *or ;iacetylmorphine is issued$ 1hou!h this is somewhat contro.ersial amon! proponents o* a "ero tolerance dru! policy, it has pro.en superior to methadone in impro.in! the social and health situation o* addicts$ [') 9eeF Heroin prescription *or addicts %ecreational use ;iacetylmorphine, almost always still called by its ori!inal trade name o* heroin in non-medical settin!s, is used as a recreational dru! *or the transcendent rela7ation and intense euphoria it induces$ Anthropolo!ist 6ichael A!ar once described heroin as 2the per*ect whate.er dru!$2['( 1olerance de.elops quickly, and users need more o* the dru! to achie.e the same e**ects$ Its popularity with recreational dru! users, compared to
morphine, reportedly stems *rom its percei.ed di**erent e**ects$['< In particular, users report an intense rush, an acute transcendent state o* euphoria, which occurs while diacetylmorphine is bein! metaboli"ed into ,monoacetylmorphine (,-6A6) and morphine in the brain$ 9ome belie.e that heroin produces more euphoria than other opioids upon in0ectionG one possible e7planation is the presence o* ,-monoacetylmorphine, a metabolite unique to heroin A althou!h a more likely e7planation is the rapidity o* onset$ &hile other opioids o* recreational use produce only morphine, heroin also lea.es ,-6A6, also a psycho-acti.e metabolite$ Howe.er, this perception is not supported by the results o* clinical studies comparin! the physiolo!ical and sub0ecti.e e**ects o* in0ected heroin and morphine in indi.iduals *ormerly addicted to opioidsG these sub0ects showed no pre*erence *or one dru! o.er the other$ Bquipotent in0ected doses had comparable action courses, with no di**erence in sub0ectsE sel*-rated *eelin!s o* euphoria, ambition, ner.ousness, rela7ation, drowsiness, or sleepiness$[34 9hort-term addiction studies by the same researchers demonstrated that tolerance de.eloped at a similar rate to both heroin and morphine$ &hen compared to the opioids hydromorphone, *entanyl, o7ycodone, and pethidineDmeperidine, *ormer addicts showed a stron! pre*erence *or heroin and morphine, su!!estin! that heroin and morphine are particularly susceptible to abuse and addiction$ 6orphine and heroin were also much more likely to produce euphoria and other positi.e sub0ecti.e e**ects when compared to these other opioids$[34 9ome researchers ha.e attempted to e7plain heroin use and the culture that surrounds it throu!h the use o* sociolo!ical theories$ In %i!hteous ;ope*iend, Chilippe Bour!ois and He** 9chonber! use anomie theory to e7plain why people be!in usin! heroin$ By analy"in! a community in 9an 8rancisco, they demonstrated that heroin use was caused in part by internal and e7ternal *actors such as .iolent homes and parental ne!lect$ 1his lack o* emotional, social, and *inancial support causes strain and in*luences indi.iduals to en!a!e in de.iant acts, includin! heroin usa!e$[3' 1hey *urther *ound that heroin users practiced 2retreatism2, a beha.ior *irst described by Howard Abadinsky, in which those su**erin! *rom such strain re0ect societyEs !oals and institutionali"ed means o* achie.in! them$[33 Crescription *or addicts 6ain articleF Heroin assisted treatment 1he => ;epartment o* HealthEs %olleston #ommittee %eport[3+ in '<3, established the British approach to diacetylmorphine prescription to users, which was maintained *or the ne7t 44 yearsF dealers were prosecuted, but doctors could prescribe diacetylmorphine to users when withdrawin! *rom it
would cause harm or se.ere distress to the patient$ 1his 2policin! and prescribin!2 policy e**ecti.ely controlled the percei.ed diacetylmorphine problem in the => until '</< when the number o* diacetylmorphine addicts doubled e.ery ', months durin! a period o* ten years, '</<A'<,($[34 In '<,4 the Brain #ommittee recommended that only selected appro.ed doctors workin! at appro.ed specialised centres be allowed to prescribe diacetylmorphine and ben"oylmethylec!onine (cocaine) to users$ 1he law was made more restricti.e in '<,($ Be!innin! in the '<)4s, the emphasis shi*ted to abstinence and the use o* methadoneG until now only a small number o* users in the => are prescribed diacetylmorphine$[3/ In '<<4, 9wit"erland be!an a trial diamorphine maintenance pro!ram *or users that had *ailed multiple withdrawal pro!rams$ 1he aim o* this pro!ram was to maintain the health o* the user by a.oidin! medical problems stemmin! *rom the illicit use o* diacetylmorphine$ 1he *irst trial in '<<4 in.ol.ed +44 users, althou!h enrollment was later e7panded to '444 based on the apparent success o* the pro!ram$ 1he trials pro.ed diamorphine maintenance to be superior to other *orms o* treatment in impro.in! the social and health situation *or this !roup o* patients$[3, It has also been shown to sa.e money, despite hi!h treatment e7penses, as it si!ni*icantly reduces costs incurred by trials, incarceration, health inter.entions and delinquency$[3) Catients appear twice daily at a treatment center, where they in0ect their dose o* diamorphine under the super.ision o* medical sta**$ 1hey are required to contribute about 4/4 swiss *ranc per month to the treatment costs$[3( A national re*erendum in No.ember 344( showed ,(5 o* .oters supported the plan,[3< introducin! diacetylmorphine prescription into *ederal law$ 1he trials be*ore were based on time-limited e7ecuti.e ordinances$ 1he success o* the 9wiss trials led ?erman, ;utch,[+4 and #anadian[+' cities to try out their own diamorphine prescription pro!rams$[+3 9ome Australian cities (such as 9ydney) ha.e instituted le!al diacetylmorphine super.ised in0ectin! centers, in line with other wider harm minimi"ation pro!rams$ 9ince Hanuary 344<, ;enmark has prescribed diamorphine to a *ew addicts that ha.e tried methadone and subute7 without success$[++ Be!innin! in 8ebruary 34'4, addicts in #openha!en and Idense will be eli!ible to recei.e *ree diacetylmorphine$ Jater in 34'4 other cities includin! Krhus and Bsb0er! will 0oin the scheme$ In total, around 3+4 addicts will be able to recei.e *ree diacetylmorphine$[+4 Howe.er, ;anish addicts will only be able to in0ect heroin accordin! to the policy set by ;anish National Board o* Health$[+/ I* the estimated '/44 dru! users who do not bene*it *rom the current oral
substitution treatment, appro7imately <44 will not be in the tar!et !roup *or treatment with in0ectable diacetylmorphine, either because o* 2massi.e multiple dru! abuse o* non-opioids2 or 2not wantin! treatment with in0ectable diacetylmorphine2$[+, In Huly 344<, the ?erman Bundesta! passed a law allowin! diacetylmorphine prescription as a standard treatment *or addictsG a lar!e-scale trial o* diacetylmorphine prescription had been authori"ed in that country in 3443$ [+) ;etection in biolo!ical *luids 1he ma0or metabolites o* diacetylmorphine, ,-6A6, morphine, morphine-+!lucuronide and morphine-,-!lucuronide, may be quantitated in blood, plasma or urine to monitor *or abuse, con*irm a dia!nosis o* poisonin! or assist in a medicole!al death in.esti!ation$ 6ost commercial opiate screenin! tests cross-react appreciably with these metabolites, as well as with other biotrans*ormation products likely to be present *ollowin! usa!e o* street!rade diacetylmorphine such as ,-acetylcodeine and codeine$ Howe.er, chromato!raphic techniques can easily distin!uish and measure each o* these substances$ &hen interpretin! the results o* a test, it is important to consider the diacetylmorphine usa!e history o* the indi.idual, since a chronic user can de.elop tolerance to doses that would incapacitate an opiate-nai.e indi.idual, and the chronic user o*ten has hi!h baseline .alues o* these metabolites in his system$ 8urthermore, some testin! procedures employ a hydrolysis step prior to quantitation that con.erts many o* the metabolic products to morphine, yieldin! a result that may be 3 times lar!er than with a method that e7amines each product indi.idually$[+( Ad.erse e**ects
Jike most opioids, unadulterated heroin does not cause many lon!-term complications other than dependence and constipation$[+< ;ue to increased .ulnerability to in*ectious a!ents, particularly .iruses and intracellular bacteria resultin! *rom the suppression o* .arious cell-mediated immune pathways, the use o* heroin and other opioids, e.en at normal therapeutic le.els, may lead to opportunistic in*ections, which carry their own lastin! e**ects$[44 [4' [43 1he a.era!e purity o* street heroin in the => .aries between +45 and /45 and heroin that has been sei"ed at the border has purity le.els between 445 and ,45G this .ariation has led to people su**erin! *rom o.erdoses as a result o* the heroin missin! a sta!e on its 0ourney *rom port to end user, as each set o* hands that the dru! passes throu!h adds *urther adulterants, the stren!th o* the dru! reduces, with the e**ect that i* steps are missed, the purity o* the dru! reachin! the end user is hi!her than
they are used to and because they are unable to tolerate the increase, an o.erdose ensues$[4+ Intra.enous use o* heroin (and any other substance) with non-sterile needles and syrin!es or other related equipment may lead toF 1he risk o* contractin! blood-borne patho!ens such as HI: and hepatitis by the sharin! o* needles 1he risk o* contractin! bacterial or *un!al endocarditis and possibly .enous sclerosis Abscesses Coisonin! *rom contaminants added to 2cut2 or dilute heroin Chysical dependence can result *rom prolon!ed use o* all opioids, resultin! in withdrawal symptoms on cessation o* use ;ecreased kidney *unction (althou!h it is not currently known i* this is because o* adulterants or in*ectious diseases)[44 6any countries and local !o.ernments ha.e be!un *undin! pro!rams that supply sterile needles to people who in0ect ille!al dru!s in an attempt to reduce these contin!ent risks, and especially the spread o* blood-borne diseases$ 1he ;ru! Colicy Alliance reports that up to )/5 o* new AI;9 cases amon! women and children are directly or indirectly a consequence o* dru! use by in0ection[citation needed $ 1he =nited 9tates *ederal !o.ernment does not operate needle e7chan!es, althou!h some state and local !o.ernments do support needle e7chan!e pro!rams$ Anthropolo!ists Chilippe Bour!ois and He** 9chonber! per*ormed a decade o* *ield work amon! homeless heroin and cocaine addicts in 9an 8rancisco, published in 344<$ 1hey reported that the A*rican-American addicts they obser.ed were more inclined to 2direct deposit2 heroin into a .ein, while 2skin-poppin!2 was a *ar more widespread practiceF 2By the midpoint o* our *ieldwork, most o* the whites had !i.en up searchin! *or operable .eins and skin-popped$ 1hey sank their needles per*unctorily, o*ten throu!h their clothin!, into their *atty tissue$2) Bour!ois and 9chonber! describes how the cultural di**erence between the A*rican-Americans and the whites leads to this contrastin! beha.ior, and also points out that the two di**erent ways to in0ect heroin comes with di**erent health risks$ 9kin-poppin! more o*ten results in abscesses, and direct in0ection more o*ten leads to *atal o.erdose and also to hepatitis # and HI: in*ection$[3' Heroin o.erdose is usually treated with an opioid anta!onist,[citation needed such as nalo7one (Narcan), or naltre7one, which has hi!h a**inity *or opioid receptors but does not acti.ate them$ 1his re.erses the e**ects o* heroin and
other opioid a!onists and causes an immediate return o* consciousness but may precipitate withdrawal symptoms$ 1he hal*-li*e o* nalo7one is much shorter than that o* most opioid a!onists, so that anta!onist typically has to be administered multiple times until the opioid has been metaboli"ed by the body$ ;ependin! on dru! interactions and numerous other *actors, death *rom o.erdose can take anywhere *rom se.eral minutes to se.eral hours because o* ano7ia resultin! *rom the breathin! re*le7 bein! suppressed by a!onism o* L-opioid receptors$ An o.erdose is immediately re.ersible with an opioid anta!onist in0ection$ ;iacetylmorphine o.erdoses can occur because o* an une7pected increase in the dose or purity or because o* diminished opioid tolerance$ Howe.er, many *atalities reported as o.erdoses are probably caused by interactions with other depressant dru!s like alcohol or ben"odia"epines$[4/ It should also be noted that since heroin can cause nausea and .omitin!, a si!ni*icant number o* deaths attributed to heroin o.erdose are caused by aspiration o* .omit by an unconscious .ictim$ 9ome sources quote the median lethal dose (*or an a.era!e )/ k! opiate-nai.e indi.idual) as bein! between )/ and +)/ m!$[4, Illicit heroin is o* widely .aryin! and unpredictable purity$ 1his means that the user may prepare what they consider to be a moderate dose while actually takin! *ar more than intended$ Also, tolerance typically decreases a*ter a period o* abstinence$ I* this occurs and the user takes a dose comparable to their pre.ious use, the user may e7perience dru! e**ects that are much !reater than e7pected, potentially resultin! in a dan!erous o.erdose$ It has been speculated that an unknown portion o* heroin related deaths are the result o* an o.erdose or aller!ic reaction to quinine, which may sometimes be used as a cuttin! a!ent$[4) A *inal *actor contributin! to o.erdoses is place conditionin!$ ;iacetylmorphine use is a hi!hly rituali"ed beha.ior$ &hile the mechanism has yet to be clearly elucidated, lon!time heroin users display increased tolerance to the dru! in locations where they ha.e repeatedly administered$ &hen the user in0ects in a di**erent location, this en.ironment-conditioned tolerance does not occur, resultin! in a !reater dru! e**ect$ 1he userEs typical dose o* the dru!, in the *ace o* decreased tolerance, becomes *ar too hi!h and can be to7ic, leadin! to o.erdose$[4( A small percenta!e o* heroin smokers, and occasionally I: users, may de.elop symptoms o* to7ic leukoencephalopathy$ 1he cause has yet to be identi*ied, but one speculation is that the disorder is caused by an uncommon adulterant that is only acti.e when heated$[4< [/4 [/' 9ymptoms include slurred speech and di**iculty walkin!$ #ocaine is sometimes used in combination with heroin, and is re*erred to as a
speedball when in0ected or moonrocks when smoked to!ether$ #ocaine acts as a stimulant, whereas heroin acts as a depressant$ #oadministration pro.ides an intense rush o* euphoria with a hi!h that combines both e**ects o* the dru!s, while e7cludin! the ne!ati.e e**ects, such as an7iety and sedation$ 1he e**ects o* cocaine wear o** *ar more quickly than heroin, thus i* an o.erdose o* heroin was used to compensate *or cocaine, the end result is *atal respiratory depression$[citation needed
Creppin! heroin *or in0ection
6odi*ied syrin!e *or suppository administration
Ine stamp o* heroin
#hunky 2No$+2 heroin
&ithdrawal 6ain articleF Ipioid withdrawal 1he withdrawal syndrome *rom heroin (the so-called 2cold turkey2) may be!in within , to 34 hours o* discontinuation o* the dru!G howe.er, this time *rame can *luctuate with the de!ree o* tolerance as well as the amount o* the last consumed dose$ 9ymptoms may includeF[/3 sweatin!, malaise, an7iety, depression, akathisia, priapism, e7tra sensiti.ity o* the !enitals in *emales, !eneral *eelin! o* hea.iness, e7cessi.e yawnin! or snee"in!, tears, rhinorrhea, sleep di**iculties (insomnia), cold sweats, chills, se.ere muscle
and bone aches, nausea, .omitin!, diarrhea, cramps, watery eyes,[/+ *e.er and cramp-like pains and in.oluntary spasms in the limbs (thou!ht to be an ori!in o* the term 2kickin! the habit2[/4 )$ Charmacolo!y
Black tar heroin &hen taken orally, heroin under!oes e7tensi.e *irst-pass metabolism .ia deacetylation, makin! it a prodru! *or the systemic deli.ery o* morphine$[/ &hen the dru! is in0ected, howe.er, it a.oids this *irst-pass e**ect, .ery rapidly crossin! the bloodAbrain barrier because o* the presence o* the acetyl !roups, which render it much more *at soluble than morphine itsel*$[// Ince in the brain, it then is deacetylated .ariously into the inacti.e +monoacetylmorphine and the acti.e ,-monoacetylmorphine (,-6A6), and then to morphine, which bind to M-opioid receptors, resultin! in the dru!Es euphoric, anal!esic (pain relie*), and an7iolytic (anti-an7iety) e**ectsG heroin itsel* e7hibits relati.ely low a**inity *or the M receptor$[/, =nlike hydromorphone and o7ymorphone, howe.er, administered intra.enously, heroin creates a lar!er histamine release, similar to morphine, resultin! in the *eelin! o* a !reater sub0ecti.e 2body hi!h2 to some, but also instances o* pruritus (itchin!) when they *irst start usin!$[/) Both morphine and ,-6A6 are M-opioid a!onists that bind to receptors present throu!hout the brain, spinal cord, and !ut o* all mammals$ 1he Mopioid receptor also binds endo!enous opioid peptides such as N-endorphin, Jeu-enkephalin, and 6et-enkephalin$ %epeated use o* heroin results in a number o* physiolo!ical chan!es, includin! an increase in the production o* M-opioid receptors (upre!ulation)$[citation needed 1hese physiolo!ical alterations lead to tolerance and dependence, so that cessation o* heroin use results in a set o* remarkably uncom*ortable symptoms includin! pain, an7iety, muscle spasms, and insomnia called the opioid withdrawal syndrome$ ;ependin! on usa!e it has an onset *our to 34 hours a*ter the last dose o* heroin$ 6orphine also binds to O- and P-opioid receptors$ 1here is also e.idence that ,-6A6 binds to a subtype o* M-opioid receptors that are also acti.ated by the morphine metabolite morphine-,N-!lucuronide but not morphine itsel*$[/( 1he third substype o* third opioid type is the mu+ receptor, which may be a commonality to other si7-position monoesters o* morphine$ 1he contribution o* these receptors to the o.erall pharmacolo!y o*
heroin remains unknown$ A subclass o* morphine deri.ati.es, namely the +,, esters o* morphine, with similar e**ects and uses, includes the clinically used stron! anal!esics nicomorphine (:ilan), and dipropanoylmorphineG there is also the latterEs dihydromorphine analo!ue, diacetyldihydromorphine (Caralaudin)$ 1wo other +,, diesters o* morphine in.ented in '()4-/ alon! with diacetylmorphine, diben"oylmorphine and acetylpropionylmorphine, were made as substitutes a*ter it was outlawed in '<3/ and, there*ore, sold as the *irst 2desi!ner dru!s2 until they were outlawed by the Jea!ue o* Nations in '<+4$ Btymolo!y
In '(</, the ?erman dru! company Bayer marketed diacetylmorphine as an o.er-the-counter dru! under the trademark name Heroin$[/< 1he name was deri.ed *rom the ?reek word 2Heros2 because o* its percei.ed 2heroic2 e**ects upon a user$[/< It was de.eloped chie*ly as a morphine substitute *or cou!h suppressants that did not ha.e morphineEs addicti.e side-e**ects$ 6orphine at the time was a popular recreational dru!, and Bayer wished to *ind a similar but non-addicti.e substitute to market$ Howe.er, contrary to BayerEs ad.ertisin! as a 2non-addicti.e morphine substitute,2 heroin would soon ha.e one o* the hi!hest rates o* dependence amon! its users$[,4
9ynthesis o* heroin *rom opium History
Bayer Heroin bottle 1he opium poppy was culti.ated in lower 6esopotamia as lon! a!o as +444 B#B$[,' 1he chemical analysis o* opium in the '<th century re.ealed that most o* its acti.ity could be ascribed to two alkaloids, codeine and morphine$ ;iacetylmorphine was *irst synthesi"ed in '()4 by #$ %$ Alder &ri!ht, an Bn!lish chemist workin! at 9t$ 6aryEs Hospital 6edical 9chool in Jondon$ He had been e7perimentin! with combinin! morphine with .arious acids$ He
boiled anhydrous morphine alkaloid with acetic anhydride *or se.eral hours and produced a more potent, acetylated *orm o* morphine, now called diacetylmorphine or morphine diacetate$ 1he compound was sent to 8$ 6$ Cierce o* Iwens #olle!e in 6anchester *or analysis$ Cierce told &ri!htF ;oses $$$ were subcutaneously in0ected into youn! do!s and rabbits $$$ with the *ollowin! !eneral results $$$ !reat prostration, *ear, and sleepiness speedily *ollowin! the administration, the eyes bein! sensiti.e, and pupils constrict, considerable sali.ation bein! produced in do!s, and sli!ht tendency to .omitin! in some cases, but no actual emesis$ %espiration was at *irst quickened, but subsequently reduced, and the heartEs action was diminished, and rendered irre!ular$ 6arked want o* coordinatin! power o.er the muscular mo.ements, and loss o* power in the pel.is and hind limbs, to!ether with a diminution o* temperature in the rectum o* about 4Q$[,3
Ad.ertisement *or Bayer Heroin &ri!htEs in.ention did not lead to any *urther de.elopments, and diacetylmorphine became popular only a*ter it was independently resynthesi"ed 3+ years later by another chemist, 8eli7 Ho**mann$ Ho**mann, workin! at the Aktien!esellscha*t 8arben*abriken (today the Bayer pharmaceutical company) in Blber*eld, ?ermany, was instructed by his super.isor Heinrich ;reser to acetylate morphine with the ob0ecti.e o* producin! codeine, a constituent o* the opium poppy, pharmacolo!ically similar to morphine but less potent and less addicti.e$ Instead, the e7periment produced an acetylated *orm o* morphine one and a hal* to two times more potent than morphine itsel*$ 8rom '(<( throu!h to '<'4, diacetylmorphine was marketed under the trademark name Heroin as a non-addicti.e morphine substitute and cou!h suppressant$ Bayer marketed the dru! as a cure *or morphine addiction be*ore it was disco.ered that it rapidly metaboli"es into morphine$ As such, diacetylmorphine is in essence a quicker-actin! *orm o* morphine$ 1he company was embarrassed by the new *indin!, which became a historic blunder *or Bayer$[,+ In the =$9$A$, the Harrison Narcotics 1a7 Act was passed in '<'4 to control the
sale and distribution o* diacetylmorphine and other opioids, which allowed the dru! to be prescribed and sold *or medical purposes$ In '<34, the =nited 9tates #on!ress banned its sale, importation, or manu*acture$ It is now a 9chedule I substance, which makes it ille!al *or non-medical use in si!natory nations o* the 9in!le #on.ention on Narcotic ;ru!s treaty, includin! the =nited 9tates$ 1he Health #ommittee o* the Jea!ue o* Nations banned diacetylmorphine in '<3/, althou!h it took more than three years *or this to be implemented$ In the meantime, the *irst desi!ner dru!s, .i"$ +,, diesters and , monoesters o* morphine and acetylated analo!ues o* closely related dru!s like hydromorphone and dihydromorphine were produced in massi.e quantities to *ill the worldwide demand *or diacetylmorphine@this continued until '<+4 when the #ommittee banned diacetylmorphine analo!ues with no therapeutic ad.anta!e o.er dru!s already in use, the *irst ma0or le!islation o* this type$ [,4 Jater, as with Aspirin, Bayer lost some o* its trademark ri!hts to heroin under the '<'< 1reaty o* :ersailles *ollowin! the ?erman de*eat in &orld &ar I$[,/ %outes o* administration
%ecreational usesF Buphoria 1ranscendent rela7ation 6edicinal usesF Cower*ul anal!esic (pain killer) #ou!h suppressant Anti-diarrheal #ontraindicationsF Alcohol Barbiturates and ben"odia"epines 9timulants Ither opioids #entral ner.ous systemF
;rowsiness ;isorientation ;elirium Neurolo!icalF Anal!esia 1olerance Addiction (physical dependence) Csycholo!icalF Addiction (psycholo!ical dependence) An7iolysis #on*usion Buphoria 9omnolence #ardio.ascular R %espiratoryF Bradycardia Hypotension Hypo.entilation 9hallow breathin! %espiratory depression ?astrointestinalF Nausea Crotracted .omitin! #onstipation ;yspepsia (heartburn) 6usculoskeletalF Anal!esia
Ata7ia 6uscle spasticity 9kinF Itchin! 8lushin!D%ash 6iscellaneousF ;ry mouth (7erostomia) 6iosis (pupil constriction) =rinary retention
;iamorphine ampoules *or medicinal use 1he onset o* heroinEs e**ects depends upon the route o* administration$ 9tudies ha.e shown that the sub0ecti.e pleasure o* dru! use (the rein*orcin! component o* addiction) is proportional to the rate at which the blood le.el o* the dru! increases$[,, Intra.enous in0ection is the *astest route o* dru! administration, causin! blood concentrations to rise the most quickly, *ollowed by smokin!, suppository (anal or .a!inal insertion), insu**lation (snortin!), and in!estion (swallowin!)$ In!estion does not produce a rush as *orerunner to the hi!h e7perienced with the use o* heroin, which is most pronounced with intra.enous use$ &hile the onset o* the rush induced by in0ection can occur in as little as a *ew seconds, the oral route o* administration requires appro7imately hal* an hour be*ore the hi!h sets in$ 1hus, with both hi!her the dosa!e o* heroin used and *aster the route o* administration used, the hi!her potential risk *or psycholo!ical addiction$ Jar!e doses o* heroin can cause *atal respiratory depression, and the dru! has been used *or suicide or as a murder weapon$ 1he serial killer ;r Harold 9hipman used diamorphine on his .ictims, and the subsequent 29hipman Inquiry2 led to a ti!htenin! o* the re!ulations surroundin! the stora!e, prescribin! and destruction o* controlled dru!s in the =>$ ;r Hohn Bodkin Adams (see his .ictim Bdith Alice 6orrell) is also known to ha.e used heroin as a murder weapon$
Because si!ni*icant tolerance to respiratory depression de.elops quickly with continued use and is lost 0ust as quickly durin! withdrawal, it is o*ten di**icult to determine whether a heroin lethal o.erdose was accidental, suicide or homicide$ B7amples include the o.erdose deaths o* 9id :icious, Hanis Hoplin, 1im Buckley, Hillel 9lo.ak, Jayne 9taley, Bradley Nowell, 1ed Binion, and %i.er Choeni7$[,) #hronic use o* heroin and other opioids, has been shown to be a potential cause o* hyponatremia, resultant because o* e7cess .asopressin secretion$ Iral Iral use o* heroin is less common than other methods o* administration, mainly because there is little to no 2rush2, and the e**ects are less potent$[,( Heroin is entirely con.erted to morphine by means o* *irst-pass metabolism, resultin! in deacetylation when in!ested$ HeroinEs oral bioa.ailability is both dose-dependent (as is morphineEs) and si!ni*icantly hi!her than oral use o* morphine itsel*, reachin! up to ,4$35 *or hi!h doses and 4/$,5 *or low dosesG opiate-nai.e users showed *ar less absorption o* the dru! at low doses, ha.in! bioa.ailabilities o* only up to 33$<5$ 1he ma7imum plasma concentration o* morphine *ollowin! oral administration o* heroin was around twice as much as that o* oral morphine$[,< In0ection In0ection, also known as 2slammin!2, 2ban!in!2, 2shootin! up2, 2di!!in!2 or 2mainlinin!2, is a popular method which carries relati.ely !reater risks than other methods o* administration$ Heroin base (commonly *ound in Burope), when prepared *or in0ection will only dissol.e in water when mi7ed with an acid (most commonly citric acid powder or lemon 0uice) and heated$ Heroin in the Bast coast =nited 9tates is most commonly *ound in the hydrochloride salt *orm, requirin! 0ust water (and no heat) to dissol.e$ =sers tend to initially in0ect in the easily accessible arm .eins, but as these .eins collapse o.er time, users resort to more dan!erous areas o* the body, such as the *emoral .ein in the !roin$ =sers who ha.e used this route o* administration o*ten de.elop a deep .ein thrombosis$[)4 Intra.enous users can use a .arious sin!le dose ran!e usin! a hypodermic needle$ 1he dose o* heroin used *or recreational purposes is dependent on the *requency and le.el o* use, thus a *irst-time user may use between / and 34 m!, while an established addict may require se.eral hundred m! per day$ As with the in0ection o* any dru!, i* a !roup o* users share a common needle without sterili"ation procedures, blood-borne diseases, such as HI: or hepatitis, can be transmitted$ 1he use o* a common dispenser *or water *or the use in the preparation o* the in0ection, as well as the sharin! o* spoons andDor *ilters can also cause the spread o* blood borne diseases$ 6any countries now supply small sterile spoons and
*ilters *or sin!le use in order to pre.ent the spread o* disease$[)' 9mokin! 9mokin! heroin re*ers to .apori"in! it to inhale the resultin! *umes, not burnin! it to inhale the resultin! smoke$ It is commonly smoked in !lass pipes made *rom !lassblown Cyre7 tubes and li!ht bulbs$ It can also be smoked o** aluminium *oil, which is heated underneath by a *lame and the resultin! smoke is inhaled throu!h a tube o* rolled up *oil, 1his method is also known as 2chasin! the dra!on2 (whereas smokin! methamphetamine is known as 2chasin! the white dra!on2)$ Insu**lation Another popular route to intake heroin is insu**lation (snortin!), where a user crushes the heroin into a *ine powder and then !ently inhales it (sometimes with a straw or a rolled up banknote, as with cocaine) into the nose, where heroin is absorbed throu!h the so*t tissue in the mucous membrane o* the sinus ca.ity and strai!ht into the bloodstream$ 1his method o* administration redirects *irst pass metabolism, with a quicker onset and hi!her bioa.ailability than oral administration, thou!h the duration o* action is shortened$ 1his method is sometimes pre*erred by users who do not want to prepare and administer heroin *or in0ection or smokin!, but still e7perience a *ast onset$ 9nortin! heroin becomes an o*ten unwanted route, once a user be!ins to in0ect the dru!$ 1he user may still !et hi!h on the dru! *rom snortin!, and e7perience a nod, but will not !et a rush$ A 2rush2 is caused by a lar!e amount o* heroin enterin! the body at once$ &hen the dru! is taken in throu!h the nose, the user does not !et the rush because the dru! is absorbed slowly rather than instantly$ 9uppository
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