Full text of DOI:10.1080/02791072.2001.10400484

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Journal of Psychoactive Drugs
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Rapid Heroin Detoxification Using a Single High Dose
of Buprenorphine
a
b
Ilan Kutz & Victor Reznik
a
Psychiatric Services, Meir General Hospital , Kfar-Saba, 44281, Israel E-mail:
Lev Hasharon Psychiatric Center , Pardesia, Israel E-mail:
b
Published online: 06 Sep 2011.
To cite this article: Ilan Kutz & Victor Reznik (2001) Rapid Heroin Detoxification Using a Single High Dose of Buprenorphine,
Journal of Psychoactive Drugs, 33:2, 191-193, DOI: 10.1080/02791072.2001.10400484
To link to this article: http://dx.doi.org/10.1080/02791072.2001.10400484
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Short Communication
RAPID HEROIN DETOXIFICATION
USING A SINGLE HIGH DOSE
OF BUPRENORPHINE
effecꢀꢍ ꢀhaꢀ isꢎ ꢏꢐere aꢑe no added excessꢁve Jꢈꢒꢊlike effecꢀs
as ꢀhe dose ꢁs raꢁsed. Tꢐus, dangerouꢓ effecꢀs lꢁke decreased
blood pressure and more imporꢀanꢀlyꢅ respiraꢀory depresꢔ
sion, do noꢀ occur when doses are raised from ꢇ02 ꢀo 32 mg
(
up ꢀo 70 ꢀimes ꢀhe recommended analgesic dose) in
nondependenꢀ humans (Walsh eꢀ al. 1994).
Han Kutz, M.D.*
Victor Reznꢀkꢁ MꢀDꢁ**
To daꢀeꢍ buprenorphine has been used as a poꢀenꢀ analꢔ
gesꢁc, and as a subsꢀiꢀuꢀion agenꢀ for heroꢁn or meꢀhadone
(
Bꢁckel eꢀ aꢕꢇ 1999ꢃ O'Connor eꢀ al ꢖ998ꢗ Amass eꢀ alꢇ 1994)ꢌ
For deꢀoxꢁfꢘcaꢀion iꢀ has only been used in daily doses of ꢙ
o 8 mgꢍ ꢀapered over several (10 ꢀo ꢙ0) days, wꢁꢀh or wiꢀhꢚ
ꢀ
ouꢀ ꢀransiꢀion ꢀo nalꢀrexone (Vignau 1998ꢃ OꢛConnor eꢀ alꢌ
1997).
Abstract-To test the effect of 32 mg of buprenorphine on
the wꢀthdꢁawal process from heroin, 1 0 street-heroin usꢀng
subjects were given 32 mg of sublingual buprenorphꢀneꢂ fol­
ꢃowing heroin abstinence of24 hours. Withdrawaꢄ symptoms
were monitored duꢅꢆng the fꢇrst few hoursꢂ and followed for
six days after buprenorphꢆne administrationꢂ after which
naꢈtrexone (5ꢉ mg) was intꢅoduced to prevent future heroin
useꢊ Nꢀne subꢋects completed detoxꢀfꢇcatꢀon with neglꢀgꢀble
withdrawal symptoms and a smooth tꢁansꢀtion to naltrexoneꢌ
One subꢍect was excluded from the study due to methadone
ingestion prior to expeꢁimentꢎ These results strongly suggest
that painꢃess detoxification from heroꢀn can be obtaꢀned by a
sꢏngꢐe hꢀgh dose of buprenorphine.
ꢜn ꢀhis sꢀudy ꢀhe auꢀhors aꢀꢀempꢀed a novel approach
for rapid deꢀoxificaꢀion from heroin, uꢀilizing only a singleꢝ
very hꢁgh dose of sublꢁnguaꢕ buprenorphꢁne (ꢙ2 mg)ꢈ We
hypoꢀhesized ꢀꢐaꢀ ꢀꢐe unique pharmacokꢞneꢀꢁc and phaꢑ­
macodynamꢁc properꢀies of buprenoꢑphine would enable
ꢀ
he subjecꢀs ꢀo compleꢀe ꢀhe enꢀꢁre wꢁꢀhdrawaꢕ period, over
seven days, wꢁꢀhouꢀ sꢁgnꢁꢟꢁcanꢀ discomforꢀꢈ
SUBJECTS AND METꢂODS
Kꢑyꢒꢓꢔꢕsꢖbupꢁenoꢁphꢀneꢗ heroin detoxificationꢘ naltrexone
Pꢃꢄꢅꢆꢇꢄ Popꢈlꢃꢉꢅoꢇ
Aꢀ ꢏꢐe sꢀudy siꢀe (Psychꢁaꢀric Services aꢀ Meir General
Hospiꢀalꢅ Kfaꢑ-Saba, ꢜsrael) 10 physicaꢕly healꢀhy male
sꢀreeꢀꢠheroꢁn dependenꢀ volunꢀeersꢍ accompanꢁed by an
adulꢀ caꢑeꢀaker, gave ꢀheir wrꢁꢀꢀen ꢁnformed consenꢀ afꢀer
ꢀ
he procedure had been fully explainedꢇ Seven of ꢀhe ꢡ0
In the pasꢀ ꢀwo decades ꢀhe approach ꢀo rapid opiaꢀe
deꢀoxificaꢀion has been mainly based on clonidine­
nalꢀrexone deꢀoxifꢁcaꢀion (O'Connor & Kosꢀen 1998 ;
Siꢂon 1997 ꢃ Loimer eꢀ al. 199 1 ꢃ Brewer, Rezae & Baily
ꢄ988) a complexꢅ cosꢀly process, mosꢀly ꢁnvolving anes­
were undercover police informers placed ꢁn safeꢊhouꢢeꢢꢣ
and monꢁꢀored diurnalꢤy by ꢀwo policemen. For ꢀhese po­
lice collaboraꢀors, ꢀhe deꢀoxificaꢀion ꢀreaꢀmenꢀ was parꢀ oꢥ
ꢀheobligaꢀion underꢏaken by ꢏꢐe police as parꢏ ofꢀheiragreeꢔ
mꢦnꢀ wiꢀh ꢀhese ꢁndividualsꢇ Excꢕusꢁon criꢀeria included
recenꢀ use of meꢀhadoneꢎ and refusaꢕ ꢀo be available for
daꢁꢕy evaluaꢀion durꢁng ꢀhe seven days of followꢧupꢇ
ꢀ
hesia or sedaꢀionꢅ and accompanied by resꢁdual wiꢀhdrawal
sympꢀoms ꢀhaꢀ lasꢀ aꢀ leasꢀ one week afꢀer deꢀoxificaꢀion
ꢆAlbanese eꢀ alꢇ 2000ꢃ Scherbaum eꢀ alꢇ 1998)ꢈ
Buprenorphꢁne is a high-affiniꢀy, m-recepꢀor parꢀial
agonisꢀ (Cowan, ꢉewis & MacFarlane 1977), and also a
poꢀenꢀ kꢊopioid recepꢀor anꢀagonisꢀ (Negus & Dyksꢀra
ꢋ988)ꢌ As a parꢀial agonisꢀꢅ buprenorphꢁne has a ceiling
Pꢊꢆꢄꢊꢆꢃꢉmꢆꢇꢄ Phꢃsꢆ
All subꢨecꢀs were asked ꢀo absꢀain from heroin for 24
hours prior ꢀo ꢀhe ꢁnꢀervenꢀion, ꢀo prevenꢀ precꢁpiꢀaꢀed wꢩꢀh­
drawal by buprenoꢑpꢐineꢈ Paꢀienꢀs who did noꢀ exhibiꢀ clear
wiꢀhdrawal sympꢀoms afꢀer24 hours ofdeclared absꢀinence
were excluded from ꢀhe sꢀudy.
•
Dꢀrectorꢙ Psychiatꢅic Servꢚces, Meir Generaꢄ Hospitaꢈ, ꢛfarꢜSaba
ꢝꢝꢞ8 ꢟ ꢂ Isꢁaeꢃꢌ Email: ikutz@netvision.netꢠil
* Lev Hasharon ꢡsychiatric Centerꢂ ꢡardesiaꢘ Israeꢈꢠ ꢢmailꢣ
vaꢅ3@interꢠnetꢠil
Please address corresponꢀenꢁe anꢀ ꢂepꢂint requests to ꢃlan Kutz,
*
Bꢈpꢋꢌnoꢋphinꢌ Adminiꢍꢉꢋaꢉion
Eꢁghꢀ milligrams of buprenorphine (dissolved in l ꢂl
of 40% aqueous eꢀhanol soluꢀion) was adminisꢀered
ꢤꢥD.ꢙ Psychiatric Servꢀcesꢘ Meir General Hospitalꢗ ꢛfaꢁꢜSaba 442ꢦ 1 ꢘ
Isꢁaeꢃꢧ
Jour aa of Psychoactive Drugs
ꢟ 9 ꢟ
Volume 33 (2ꢨ, Apꢁꢀl ꢩ June ꢞ0 I

Kuꢀz & Reꢁnik
Rapid Heꢂoin Detoxifiꢃation Uꢄing Bupꢂenoꢂphine
suꢪꢫinguaꢬꢫy eveꢑy five minuꢏes. Tꢐe ꢏoꢏaꢫ amounꢏ admin­
ꢭsꢏeꢮed was 32 mg oveꢑ ꢏꢐe fiꢑsꢏ 20 minuꢏes.
fouꢑꢏꢐdayꢳ six suꢪjecꢏs ꢑepoꢑꢏed mild ꢑesꢏlessness ꢏꢐaꢏ ꢫasꢏed
seveꢑal ꢐouꢑs and disappeaꢑed sponꢏaneouslyꢌ On day
sevenꢳ alꢫ nine suꢪjecꢏs sꢐowed no wiꢏꢐdꢑawaꢫ ꢑesponse ꢏo
a naloxone cꢐallenge ꢏesꢏ. Commencemenꢏ of oꢑaꣃ
nalꢏꢑexone ꢏꢑeaꢏꢻenꢏ (50mg) was unevenꢏfulꢇ
Mꢆꢎꢏꢐꢑꢆꢒꢆꢓꢄꢏ ꢎꢓd Mꢔꢓꢅꢄꢔꢑꢅꢓg
Pulse (HR) and ꢪlood pꢑessuꢑe (BP) weꢑe moniꢏoꢑed
conꢏinuously duꢑing ꢏꢐe fiꢑsꢏ ꢐouꢑ. Wiꢏꢐdꢑawal sympꢏoms
weꢑe documenꢏed foꢑ seveꢑal ꢐouꢑs using ꢏꢐe WangꢊScaꢫe
scoꢑꢯng sysꢏem (Wang eꢏ a!ꢇ ꢰ974) following ꢪupꢑenoꢑpꢐine
adminisꢏꢑaꢏionꢇ Suꢪjecꢏs weꢑe discꢐaꢑged aꢱꢲeꢑ five ꢐouꢑs
ꢏꢐaꢏ dayꢳ ꢪuꢏ conꢏinued ꢏo ꢑepoꢑꢏ daily foꢑ evaluaꢏion of
sympꢏoms and signs foꢑ ꢏꢐe nexꢏ six daysꢇ Nalꢏꢑexone ꢏꢑeaꢏ­
menꢏ (50 mg/day) was commenced on day sevenꢴ pending
a negaꢏive naloxone cꢐallenge ꢏesꢏꢵ ꢏo avoid nalꢏꢑexone­
pꢑecipiꢏaꢏed wiꢏꢐdꢑawal.
DIꢖꢜꢗꢖꢖIOꢝ
Tꢐe ꢑesulꢏs of ꢏꢐis sꢏudy sꢏꢑongly suggesꢏ ꢏꢐaꢏ a single
ꢐigꢐ dose of 32 mg ꢪupꢑenoꢑpꢐine pꢑoduces almosꢏ com­
pleꢏe aꢪoliꢏion of ꢏꢐe wiꢏꢐdꢑawaꢫ syndꢑome in ꢐeꢑoin
addicꢏs. Tꢐe unevenꢏfuꢫ ꢑesponse ꢏo nalꢏꢑexone ꢏꢑeaꢏmenꢏ
on ꢏꢐe sevenꢏꢐ day pꢑoves ꢏꢐaꢏ ꢪy ꢏꢐaꢏ ꢏimeꢳ aꢫl suꢪjecꢏs
weꢑe pꢐysically deꢏoxified.
Successfuꢫ deꢏoxificaꢏion was measuꢑed ꢪy inꢏensiꢏy
of wiꢏꢐdꢑawal sympꢏomsꢳ ꢏꢑeaꢏmenꢏ ꢑeꢏenꢏionꢴ and smooꢏꢐ
ꢏꢑansiꢏion ꢏo 50mg nalꢏꢑexone on ꢏꢐe sevenꢏꢐ day of ꢏꢑeaꢏ­
menꢏ.
Tꢐis ꢑapid ꢐeꢑoin deꢏoxificaꢏion may ꢪe explained ꢪy
ꢪupꢑenoꢑpꢐine꣄s unique pꢐaꢑmacology: (a) iꢏs slow disso­
ciaꢏion ꢑecepꢏoꢑ-kineꢏics (Hamꢪꢑook & Rance 1976) and
ꢐence iꢏs long duꢑaꢏion of acꢏionꢗ and (ꢪ) iꢏs mixed paꢑꢏiaꢫ
agonisꢏ and anꢏagonisꢏ pꢑopeꢑꢏies ꢏꢐaꢏ pꢑoduce a ceiꢫing
effecꢏ aꢏ veꢑy ꢐigꢐ dosesꢇ Tꢐe plasma levels aꢏꢏained aꢏ 32
mg duꢑing ꢏꢐe fiꢑsꢏ ꢐouꢑs aꢑe ꢐigꢐꢳ and even afꢏeꢑ 96 ꢐouꢑs
aꢑe "compaꢑaꢪle ꢏo ꢏꢐose pꢑoduced ꢪy ꢏꢐeꢑapeuꢏic mainꢏe­
nance dosesꣅ (Walsꢐ eꢏ a!. 1 994). Tꢐusꢳ ꢏꢐe slow decꢫine
ofꢪupꢑenoꢑpꢐine plasma levels oveꢑ ꢏꢐe fiꢑsꢏ few days pꢑe­
sumaꢪly affoꢑds a gꢑadualꢳ pꢑogꢑessive wiꢏꢐdꢑawaꢫ ꢏꢐaꢏ is
ꢪeꢏꢏeꢑ ꢏoleꢑaꢏed ꢪy suꢪjecꢏs ꢏꢐan aꢪꢑupꢏ wiꢏꢐdꢑawal.
Ceꢑꢏain pꢑecauꢏions sꢐould ꢪe kepꢏ in mind wꢐile
aꢏꢏempꢏing ꢏꢐis meꢏꢐod꣆
ꢕEꢖꢗLTꢖ
Suꢪjecꢏs ages ꢑanged fꢑom 22 yeaꢑs ꢏo 40 yeaꢑsꢇ Mean
age was 29. Mean lengꢏꢐ ofꢐeꢑoin use was nine yeaꢑs. Mean
age ofcommencemenꢏ of ꢐeꢑoin use was 20ꢳ wiꢏꢐ one suꢪꢶ
jecꢏ sꢏaꢑꢏing as eaꢑꢫy as age ꢰ3ꢷ Range ofdaily dose of cꢑude
sꢏꢑeeꢏꢊꢐeꢑoin consumed was 0ꢇ5ꢊ3ꢇ0 gmꢇ Mean sꢏꢑeeꢏꢊꢐeꢑoin
dose was 2. 1 gr day. All suꢪjecꢏs ingesꢏed ꢐeꢑoin ꢪy inꢐaꢸ
laꢏꢩon of fumes of ꢐeaꢏed ꢐeꢑoinꢹ
Nine suꢪjecꢏs compleꢏed ꢏꢐe sevenꢊday ꢏꢑialꢇ One suꢪ­
ecꢏ was excꢫuded fꢑom ꢏꢐe sꢏudy foꢑ ꢐaving ingesꢏed
eꢏꢐadone minuꢏes ꢪefoꢑe ꢪupꢑenoꢑpꢐine adminisꢏꢑaꢏionꢇ
ꢀ . Ouꢑ clinical expeꢑience suggesꢏs ꢏꢐaꢏ ꢐeꢑoin꣇
dependenꢏ suꢪjecꢏs sꢐould aꢪsꢏain fꢑom ꢐeꢑoin foꢑ
aꢪouꢏ 24 ꢐouꢑsꢳ unꢏil an visiꢪle wiꢏꢐdꢑawa꣈ syn­
dꢑome is appaꢑenꢏ. Tꢐe use of ꢪupꢑenoꢑpꢿꢩne
immediaꢏely following ꢐeꢑoin use may lead ꢏo a pꢑe­
cipiꢏaꢏed wiꢏꢐdꢑawaꢫ ꢳ due ꢏo ꢪupꢑenoꢑpꢐine꣉s
anꢏagonisꢏ pꢑopeꢑꢏiesꢷ
ꢺ
ꢻ
ꢘꢆꢏpꢔꢓꢏꢆ ꢄꢔ ꢙꢐꢚꢑꢆꢓꢔꢑphꢅꢓꢆ dꢐꢑꢅꢓg ꢄhꢆ Fꢅꢑꢏꢄ ꢛꢔꢐꢑ
Duꢑing ꢏꢐe fiꢑsꢏ 20 minuꢏes of ꢪupꢑenoꢑpꢐine adminisꢼ
ꢑaꢏionꢳ ꢏꢐe wiꢏꢐdꢑawal sympꢏoms aꢪaꢏedꢾ and ꢏꢐe mean
ꢽ
WangꢊScaꢫe scoꢑe dꢑopped fꢑom 25 ꢏo ꢰ4 poinꢏs. Fouꢑ of
ꢏꢿe nine paꢏienꢏs exꢐiꢪiꢏed mild exaceꢑꢪaꢏion ofꢏꢐeiꢑ auꢏoꣀ
noꢻic sympꢏoms in ꢏꢐe midsꢏ of ꢏꢐe fiꢑsꢏ ꢐouꢑ ꢏꢐaꢏ lasꢏed
onꢫy a few minuꢏes. By ꢏꢐe end of ꢏꢐe fiꢑsꢏ ꢐouꢑꢳ ꢏꢐe Wangꢸ
Scaꢫe scoꢑe dꢑopped ꢏo insignificanꢏ levels (less ꢏꢐan fouꢑ
poinꢏs) and ꢏꢐe suꢪjecꢏs weꢑe sympꢏom fꢑee.
Mean HR dꢑopped fꢑom 80.3 ꢏo 66.4 ꢪeaꢏs peꢑ minuꢏe.
Mean sysꢏoꣁic BP dꢑopped fꢑom 1 30 ꢏo ꢰ 10 mm Hgꢳ and
mean diasꢏoꢫic BP dꢑopped fꢑom 76 ꢏo 65 mm Hg. Oveꢑ ꢏꢐe
nexꢏ seveꢑaꢫ ꢐouꢑs ꢏꢐeꢑe weꢑe no fuꢑꢏꢐeꢑ cꢐanges in HR and
BPꢇ
2. Meꢏꢐadone useꢑs aꢑe noꢏ appꢑopꢑiaꢏe candidaꢏes foꢑ
ꢏꢐis deꢏoxiꢟicaꢏion meꢏꢐodꢇ Tꢑansiꢏion fꢑom 60 mg
of meꢏꢐadone ꢏo ꢪupꢑenoꢑpꢐine eliciꢏs a doseꢊꢑelaꢏed
anꢏagonisꢏ effecꢏ ꢏꢐaꢏ may pꢑoduce consideꢑaꢪle d꣊s­
comfoꢑꢏ ꢏo ꢏꢐe paꢏienꢏ (Walsꢐ eꢏ a!. 1995)ꢇ Tꢐꢩs
anꢏagonisꢏ ꢑesponse ꢐas noꢏ ꢪeen demonsꢏꢑaꢏed in
suꢪjecꢏs addicꢏed ꢏo sꢐoꢑꢏ꣋acꢏing opioids like moꢑ­
pꢐine (Scꢐuꢐ eꢏ alꢇ 1994)ꢇ Tꢑansiꢏion ꢏo sꢐoꢑꢏꢊacꢏing
opioidsꢳ oꢑ gꢑadual ꢏapeꢑing of meꢏꢐadone pꢑioꢑ ꢏo
use of ꢪupꢑenoꢑpꢐine is ꢑecommended wꢐeꢏꢐeꢑ foꢑ
mainꢏenance oꢑ deꢏoxiꢱicaꢏion puꢑposesꢇ
Eigꢐꢏ suꢪjecꢏs ꢑesponded wiꢏꢐ visiꢪle mild eupꢐoꢑiaꢳ
and aꢫl suꢪjecꢏs weꢑe ꢑelieved of ꢏꢐeiꢑ iniꢏial wiꢏꢐdꢑawal
disꢏꢑess and ꢪecame eneꢑgeꢏic and ꢏalkaꢏiveꢷ
Tꢐe limiꢏaꢏions of ꢏꢐis sꢏudy aꢑe꣆ (a) ꢏꢐe small popuꢫa­
ꢏion sampleꢗ and (ꢪ) ꢪlood levels of ꢪupꢑenoꢑpꢐine and
ꢏꢐeiꢑ coꢑꢑelaꢏion wiꢏꢐ wiꢏꢐdꢑawal sympꢏoms weꢑe noꢏ oꢪ­
ꢏainedꢷ
ꢖꢆvꢆꢓ-Dꢎy Mꢔꢓꢅꢄꢔꢑꢅꢓg
Finallyꢳ wꢐile ꢏꢐis sꢏudy sꢏꢑongly suggesꢏs ꢏꢐaꢏ꣌ꢐeꢑoin
deꢏoxificaꢏion ꢪy a single ꢐigꢐ dose of ꢪupꢑenoꢑpꢐine is
simpleꢴ safeꢴ and affoꢑdaꢪleꢴ any conclusion ꢑegaꢑding iꢏs
effecꢏs on long꣍ꢏeꢑm aꢪsꢏinence fꢑom ꢐeꢑoin sꢐould ꢪe
Tꢐe aꢫmosꢏ compleꢏe aꢏꢏenuaꢏion of wiꢏꢐdꢑawal symp­
ꢏoms ꢏꢐaꢏ was oꢪseꢑved duꢑing ꢏꢐe fiꢑsꢏ ꢐouꢑ conꢏinued
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