acupuncture therapy for drug addiction - chinese medicine
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Motlagh et al. Chin Med (2016) 11:16 DOI 10.1186/s13020-016-0088-7
REVIEW
Acupuncture therapy for drug addictionFarid Esmaeili Motlagh1,2,3, Fatimah Ibrahim1,2*, Rusdi Abd Rashid3, Tahereh Seghatoleslam3,4 and Hussain Habil3
Abstract
Acupuncture therapy has been used to treat substance abuse. This study aims to review experimental studies examin-ing the effects of acupuncture on addiction. Research and review articles on acupuncture treatment of substance abuse published between January 2000 and September 2014 were searched using the databases ISI Web of Science Core Collection and EBSCO’s MEDLINE Complete. Clinical trial studies on the efficacy of acupuncture therapy for substance abuse were classified according to substance (cocaine, opioid, nicotine, and alcohol), and their treatment protocols, assessments, and findings were examined. A total of 119 studies were identified, of which 85 research arti-cles addressed the efficacy of acupuncture for treating addiction. There were substantial variations in study protocols, particularly regarding treatment duration, frequency of electroacupuncture, duration of stimulation, and choice of acupoints. Contradictory results, intergroup differences, variation in sample sizes, and acupuncture placebo effects made it difficult to evaluate acupuncture effectiveness in drug addiction treatment. This review also identified a lack of rigorous study design, such as control of confounding variables by incorporating sham controls, sufficient sample sizes, reliable assessments, and adequately replicated experiments.
© 2016 Motlagh et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BackgroundIn 1997, the National Institutes of Health accepted acu-puncture therapy as an acceptable procedure com-plementary to Western medicine [1]. Evidence for its therapeutic effects comes mainly from clinical practice and research into pain control, fibromyalgia, headaches, Parkinson’s disease, schizophrenia, and depression [2]. Acupuncture therapy can be administered using either manual insertion of needles or electroacupuncture (EA), a mild electrical stimulation of acupoints. Extended acu-puncture methods may involve finger pressure (acupres-sure) and laser therapy [3].
In 1985, Dr. M. Smith finalized the National Acupunc-ture Detoxification Association (NADA) protocol that is currently practiced in over 250 hospitals in the United Kingdom and United States [4]. In 1996, the World Health Organization accepted acupuncture as a treat-ment for drug abuse [5]. The latest modification to this treatment protocol was developed in 2005 by Dr. Ji Sheng
from Peking University, Beijing, China [6]. Currently, more than 700 addiction treatment centers use acupunc-ture as an adjunctive procedure [7].
Prominent effects of acupuncture are increases in the levels of enkephalin, epinephrine, endorphin, seroto-nin, norepinephrine, and dopamine in the central nerv-ous system and plasma [8] that might mediate substance abuse. Acupuncture has been used to treat addiction for three decades [2–89]. For example, auricular acupunc-ture (AA) is effective in treating alcohol and drug abuse in both Europe and the United States [4].
However, several clinical trials have indicated that acu-puncture was not effective in treating addiction [2, 3, 31, 67, 69, 78–80]. Thus, the efficacy of the NADA pro-tocol has been reassessed over the last decade [7]. Sev-eral factors have been studied to evaluate the efficacy of acupuncture therapy; for example, treatment proto-col, choice of acupoints, duration of acupuncture, study design diversity, sample size, addiction history, and assessment techniques.
This study aims to review the published research on acupuncture therapy for substance abuse in relation to study type, authors, funding agencies, countries, ago-nist substances, and acupoints used for stimulation.
Open Access
Chinese Medicine
*Correspondence: [email protected] 1 Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, MalaysiaFull list of author information is available at the end of the article
Page 2 of 20Motlagh et al. Chin Med (2016) 11:16
Experimental studies published between January 2000 and September 2014 were systematically reviewed and analyzed to try to resolve the lack of agreement about acupuncture’s efficacy for substance abuse.
ReviewLiterature searchA search of the ISI Web of Science Core Collection and EBSCOHost (MEDLINE Complete) databases for the period January 2000 to September 2014 was conducted to identify acupuncture clinical trials. Keywords, top-ics available in the databases, and titles were searched for the following terms: “acupuncture,” “electroacupunc-ture,” “acupoint stimulation,” “transcutaneous,” and “elec-trostimulation” as single words or combinations (total number of articles: 25 358). The results were refined to exclude non-English language materials. The preliminary findings of the first phase were refined by several paral-lel filters to identify documents relevant to acupuncture treatment of substance abuse. The operator between the filters was the “OR” command. Single, relevant words were selected for each filter and included any combina-tion of the following: “alcohol,” “addict,” “opioid,” “heroin,” “cigarette,” “nicotine,” “tobacco,” “cocaine,” and “sub-stance” as title, topic, keywords, or abstract text (total number of articles: 230) from both searched databases. The search results were collated and filtered to exclude proceedings papers and letters, yielding 161 stud-ies. The abstracts of these documents were reviewed to exclude papers related to other addiction fields such as the Internet, food, or games; 119 documents comprised the refined, selected results. Three authors (FEM, RR, and TS) independently assessed studies for eligibility and crosschecked the material for study relevance. The publi-cation selection process was shown in Fig. 1.
The articles were classified according to their specifi-cations, including publication date, number of citations, source, authors, organization, and funding agencies. All original research papers were examined for their efficacy and method of treating different categories of addiction to agonist substances (e.g., cocaine, opioid and opiate, nicotine, alcohol, morphine). Original clinical trials that investigated the efficacy of acupuncture therapy were divided into six categories based on substance depend-ence (cocaine, opioid and opiate, nicotine, alcohol, mor-phine, and other substances) with a narrative review of their methods and results. Although morphine is an opi-oid, it has been assigned its own section because of the high number of publications on this topic. Heroin, meth-adone, and opiates are discussed in the opioid section.
The findings are discussed and compared according to type of addictive substance. There were 96 articles and 29 review papers; 83 articles were original investigations (76
of which were clinical trials of acupuncture efficacy), with 45 articles involving human beings and 38 involving ani-mals. Figure 2 shows the percentage of all documents in each type of category. Original investigations of humans and animals were classified separately according to type of substance dependence. These articles placed more of an investigative emphasis on morphine and alcohol than on other substances.
The total number of citations for all documents was 1495 (mean = 15.83 and standard deviation = 15.27, cita-tion range 2–87 by excluding 29 articles cited zero times or only once). The top ten most cited articles were shown in Table 1. The United States (43 articles) and China (40 articles) published almost 70 % of all articles. Among the Asian countries, China and South Korea published 59 articles, comprising 50 % of publications. Their funding agencies were also the top supporters in this field. Peking, Kyung Hee, and Daegu Haany Universities were the top three organizations, publishing 40 articles since 2000.
The published articles were associated with various research areas (Fig. 3). About 80 % of the articles focused on neuroscience and neurology, substance abuse, and integrative complementary medicine research areas. Published articles for each year were shown in Fig. 4.
Original experimental research articles were reviewed according to type of substance dependence (Fig. 2); the treatment method, subjects, objectives, and assessments of clinical trials for each group were shown in Tables 2, 3, 4, 5, 6, 7.
CocaineAvants and Margolin have evaluated the efficacy of AA for cocaine addiction treatment in four studies on human subjects. Although promising results were reported in their first study on 82 cocaine-dependent subjects [10], another study on 83 cocaine-dependent subjects found AA to be effective in reducing cocaine in only one of two trials [60]. When the original study was repeated with 620 subjects, no effect was found [61]. These research-ers also conducted a study in 2005 on 40 cocaine abusers who had tested positive for the human immunodeficiency virus and were under methadone maintenance; no dif-ference was found between the standard and reduced NADA protocols for cocaine use [59].
Three studies on rats were conducted to explore the effects of bilateral stimulation at the Shenmen (HT7) points. Modulation of the central dopaminergic sys-tem by acupuncture might be effective in preventing the behavioral effects of cocaine in rats [44]. By regulat-ing neuronal activation in the nucleus accumbens (NAc) shell, acupuncture reduced stress-induced relapse [84]. The effect of acupuncture on the inhibition of cocaine-induced locomotor activity was mediated by A-fiber
Page 3 of 20Motlagh et al. Chin Med (2016) 11:16
activation of the ulnar nerve in rats [42]. See Table 2 for study details.
Opioids and opiatesIn 2002, Montazeri investigated the efficacy of acupunc-ture at Hegu (LI4), Neiguan (PC6), Shenmen (HT7), Tai-chong (LR3), Zusanli (ST36), Dazhui (DU14), and Baihui (DU20) in 40 male adult heroin- or opium-addicted patients. The severity of withdrawal symptoms declined when acupuncture was used in rapid opiate detoxifica-tion [63]. Liu (2007) used functional magnetic resonance imaging to show that hypothalamus activation associated with manual acupuncture at Zusanli (ST36) was more robust in heroin addicts compared with healthy subjects [55]. EA (2 Hz) at Zusanli (ST36) and Sanyinjiao (SP6) was effective in reducing active responses elicited by
discrete cues in rats [56]. The same EA treatment showed promise in treating heroin-seeking behaviors when com-bined with extinction therapy [33]. EA (2 Hz) at the same points—Zusanli (ST36) and Sanyinjiao (SP6)—activated the endogenous opioid cannabinoid and the dopamine systems in rats [81].
An evaluation of the event-related potentials of heroin addicts before and after acupuncture at Neiguan (PC6) and Zusanli (ST36) suggested that EA might potentially lower relapse rates by inhibiting attention bias to heroin [37]. The presentation of heroin cues could induce activa-tion in craving-related brain regions, which are involved in reward, learning and memory, cognition, and emotion. Acupuncture at Zusanli (ST36) rapidly suppressed the activation of these specific brain regions related to crav-ing [17]. Transcutaneous electric acupoint stimulation
searching for acupuncture and addiction related [“acupuncture,” “electroacupuncture,” “acupoint stimulation,” “transcutaneous,” and “electrostimulation” related to “alcohol,” “addict,” “opioid,” “heroin,” “cigarette,”
“nicotine,” “tobacco,” “cocaine,” and “substance” as title, topic, keywords, or abstract text keywords] through ISI web of science core collection database (n1 = 145) and MEDLINE complete from EBSCOHOST database
(n2 = 85).
Scre
enin
g In
clud
ed
Elig
ibili
ty
Iden
�fica
�on
Records after combination of results (n = 230)
Records screened for exclusion of letters, meetings and conference papers
(n = 161)
Letters, meetings and conference papers excluded
(n=69)
Full-text articles assessed for eligibility (n = 119)
Full-text articles excluded: abstracts were reviewed to exclude any paper, which was not related to the topic. Internet and game addiction = 27, food addiction = 15 (n = 42)
Studies included in qualitative synthesis: 83 original clinical investigations on efficacy of acupuncture. (Opioid and opiate=14, cocaine=7, nicotine= 9,
morphine=16, alcohol= 16, other substance= 21) (n = 83)
Studies included in quantitative analysis of publication date, number of citations, source, authors, organization and funding
agencies (n = 119)
Fig. 1 Flow chart of selection process
Page 4 of 20Motlagh et al. Chin Med (2016) 11:16
was a possible adjunctive treatment to pharmacological treatments for heroin detoxification [62]. Acupuncture at Dazhui (GV14) and Baihui (DU20) prevented brain cell apoptosis in heroin-readdicted rats, normalized neuronal ultrastructure in the ventral tegmental area of heroin relapse rats, and protected nerve cells against injury in heroin relapse rats [32, 88].
Recent studies of acupuncture’s effectiveness as an adjunct therapy in methadone maintenance programs have been controversial. In 2009, Bearn demonstrated a lack of effect for adjunctive methadone maintenance treatment with AA upon withdrawal severity or crav-ing [11]. In 2013, Pei Lin showed a lack of AA effective-ness on the number of daily consumed cigarettes, relapse rate, and withdrawal symptoms, and examined patients’ satisfaction and coping with AA as an adjunct treatment
to methadone maintenance treatment among Malay-sian subjects [57, 58]. However, Chan et al. [22] claimed that 2 weeks of acupuncture therapy reduced the daily dose of methadone and was also associated with greater improvement in sleep latency. See Table 3 for study details.
NicotineAcupuncture stimulation at Zusanli (ST36) exerted a therapeutic effect on nicotine detoxification [21] and acupuncture at Zusanli (ST36) or Shenmen (HT7) might attenuate anxiety-like behavior following nicotine with-drawal by modulating corticotrophin-releasing factor in the amygdala [20]. Smoking withdrawal symptoms could be ameliorated by acupuncture treatment [18]. In one study, acupuncture at Shenmen (HT7) attenuated
Original Inves�ga�on on
animals31%
Original inves�ga�on on
human38%
Other ar�cles6%
Review papers
24%
Number of original investigations
Cocaine
Heroin
Nico�ne
Alcohole
Morphine
Other substances
0 5 10 15 20 25
Article type Number
Original investigation on rats 38
Original investigation on human 45
Other articles 7
Review papers 29
Total 119
Fig. 2 Classification of selected articles into review papers and original investigations on humans and animals. The lower diagram shows the number of original clinical investigations according to substance. Morphine and alcohol have the most articles. Each of the columns is described separately in Tables 2, 3, 4, 5, 6, 7
Page 5 of 20Motlagh et al. Chin Med (2016) 11:16
cigarette withdrawal symptoms more than acupuncture at Shousanli (LI10) [19]. Real acupuncture (as opposed to sham acupuncture) at Shenmen (HT7) alleviated cue-induced cravings through the regulation of activity in brain regions (medial prefrontal cortex, premotor cortex, amygdala, hippocampus, and thalamus) related to crav-ing scores in the initial abstinence phase [38].
However, one study failed to find any effect of acupunc-ture on cotinine serum levels, carbon monoxide exha-lation, and smoking quit rate in 59 smokers [83]. It has been suggested that DRD2 gene TaqI A polymorphism was related to AA response in smoking cessation treat-ment [65]. Auricular transcutaneous electrical neuro-stimulation relieved withdrawal symptoms and decreased
Table 1 Top 10 most cited articles from 2000 to 2014
Title First author Source title Publication year
Total citations
Acupuncture: An evidence-based review of the clinical literature [90]
Mayer DJ Annual Review of Medicine 2000 87
A randomized controlled trial of auricular acu-puncture for cocaine dependence [10]
Avants SK Archives of Internal Medicine 2000 67
Acupuncture for the treatment of cocaine addiction—a randomized controlled trial [61]
Margolin A Journal of the American Medical Association 2002 66
Clinical research on acupuncture: Part l. What have reviews of the efficacy and safety of acupuncture told us so far? [91]
Birch S Journal of Alternative and Complementary Medicine
2004 64
Peripheral neuropathy: Pathogenic mechanisms and alternative therapies [92]
Head, Kathleen A Alternative Medicine Review 2006 50
Acupuncture and related interventions for smoking cessation [78]
White AR Cochrane Database of Systematic Reviews 2006 43
A large randomized placebo controlled study of auricular acupuncture for alcohol dependence [16]
Bullock ML Journal of Substance Abuse Treatment 2002 41
Peripheral electric stimulation inhibits mor-phine-induced place preference in rats [75]
Wang B; Luo, F NeuroReport 2000 39
Acupuncture in clinical neurology [67] Rabinstein AA Neurologist 2003 37
Traditional Chinese medicine in treatment of opiate addiction [93]
Shi, Jie Acta Pharmacologica Sinica 2006 34
0
5
10
15
20
25
30
35
40
Num
ber
of p
ublic
atio
n
Fig. 3 Number of research articles in each area. Neuroscience, substance abuse, and complementary medicine are ranked highest
Page 6 of 20Motlagh et al. Chin Med (2016) 11:16
anxiety and stress levels during the detoxification period in a study of six smokers [15]. Auricular transcutaneous electrostimulation therapy might be an acceptable alter-native therapy for smoking cessation [72]. See Table 4 for study details.
AlcoholConflicting results from two large randomized single-blind, placebo-controlled trials suggested that acupunc-ture was not effective in reducing alcohol use [16, 39]. However, promising results have been found using acu-puncture as an adjunctive treatment to carbamazepine
medication to reduce the severity of alcohol withdrawal symptoms [39]. In one study, AA failed to reduce the duration and severity of alcohol withdrawal symptoms [43]; another study found no advantage for laser AA in treating alcohol withdrawal [74]. However, research indi-cated that laser therapy helps to promote the release of endorphins in the body and decreases discomfort accom-panying alcohol withdrawal [87]. It might therefore be a safe and painless beneficial adjunct treatment for alco-holism [87].
Acupuncture at Zusanli (ST36) or Sanyinjiao (SP6) modulated postsynaptic neural activation in the striatum
0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00
201420132012201120102009200820072006200520042003200220012000
Number of publica�on and cita�on in each year
0
50
100
150
200
250
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Yea
r
Year
Num
ber
of c
itatio
n
Number of publication
Fig. 4 Number of publications (top) and citations (bottom) per year. This figure shows that since 2008, the number of citations has increased to 200 per year. Before 2008, it was about 50 per year
Page 7 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 2
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in c
ocai
ne-d
epen
dent
sub
ject
s
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic: i
n th
e de
ltoid
foss
a at
the
junc
tion
of th
e in
fra-
antih
elix
cru
s an
d th
e m
edia
l ord
er o
f the
hel
ix, l
ung:
in th
e ce
nter
of t
he c
avum
con
cha,
live
r: lo
cate
d in
the
post
erio
r to
uppe
r por
tion
of th
e he
lix c
rus,
kidn
ey: i
n th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Publ
icat
ion
year
; fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
(acu
-pu
nctu
re ty
pe, a
cupo
ints
, fr
eque
ncy)
Ass
essm
ents
Out
com
es
2000
Ava
nts
[10]
To e
valu
ate
the
AA
effi
cacy
in
coca
ine
addi
ctio
n tr
eatm
ent
com
pare
d to
nee
dle-
inse
rtio
n an
d no
-nee
dle
rela
xatio
n co
ntro
l con
ditio
ns
82 C
ocai
ne-d
epen
dent
, met
ha-
done
-mai
ntai
ned
patie
nts
Aur
icul
ar a
cupu
nctu
re a
t 4
NA
DA
poi
nts
(sym
path
etic
, lu
ng, l
iver
, and
She
nmen
(H
T7)),
5 ti
mes
a w
eek
for
8 w
eeks
Urin
e to
xico
logy
scr
eens
3-
times
-wee
kly
Acu
punc
ture
sho
wed
pos
itive
re
sults
com
pare
d to
con
trol
gr
oups
for t
reat
men
t of
coca
ine
depe
nden
ce
2002
Mar
golin
[60]
To C
ompa
re tw
o co
cain
e ad
dict
ion
clin
ical
tria
ls o
f AA
to
exp
lore
con
sist
ency
of
trea
tmen
t effe
cts
165
Coca
ine-
depe
nden
t, m
etha
done
-mai
ntai
ned
patie
nts
(Stu
dy 1
, n =
82;
St
udy
2, n
= 8
3)
Aur
icul
ar a
cupu
nctu
re a
t 4
NA
DA
poi
nts
(sym
path
etic
, lu
ng, l
iver
, and
She
nmen
(H
T7)),
5 ti
mes
a w
eek
for
8 w
eeks
Urin
e to
xico
logy
scr
eens
3-
times
-wee
kly,
rete
ntio
n in
tr
eatm
ent,
trea
tmen
t att
end-
ance
, tre
atm
ent c
redi
bilit
y,
ther
apeu
tic a
llian
ce, a
nd
acut
e eff
ects
The
resu
lts o
f tw
o gr
oups
wer
e co
ntro
vers
ial a
nd n
o co
nclu
-si
on c
ould
be
mad
e re
gard
ing
the
effec
tiven
ess
of A
A
2002
Mar
golin
[61]
To e
valu
ate
the
AA
effi
cacy
in
coca
ine
addi
ctio
n tr
eatm
ent
620
Coca
ine-
depe
nden
t m
etha
done
-mai
ntai
ned
patie
nts.
412
Coca
ine
only
an
d 20
8 op
iate
s +
coc
aine
Aur
icul
ar a
cupu
nctu
re a
t 4
NA
DA
poi
nts
(sym
path
etic
, lu
ng, l
iver
, and
She
nmen
(H
T7)),
5 ti
mes
a w
eek
for
8 w
eeks
Urin
e to
xico
logy
dur
ing
trea
tmen
t and
at t
he 3
- and
6-
mon
th p
ost r
ando
miz
atio
n fo
llow
-up,
and
rete
ntio
n in
tr
eatm
ent
acup
unct
ure
was
not
mor
e eff
ec-
tive
than
a n
eedl
e in
sert
ion
or
rela
xatio
n co
ntro
l in
redu
cing
co
cain
e us
e
2005
Mar
golin
[59]
To e
valu
ate
effec
ts o
f acu
punc
-tu
re a
nd s
pirit
ualit
y, th
erap
y in
th
e tr
eatm
ent o
f HIV
-pos
itive
dr
ug u
sers
40 H
IV-s
erop
ositi
ve, c
ocai
ne-
depe
nden
t, m
etha
done
-m
aint
aine
d pa
tient
s
Aur
icul
ar a
cupu
nctu
re a
t 5
NA
DA
poi
nts,
5 tim
es w
eekl
y fo
r 8 w
eeks
Urin
e to
xico
logy
twic
e w
eekl
y,
depr
essi
on a
nd a
nxie
ty a
t pr
e- a
nd p
ost-
trea
tmen
t
acup
unct
ure
and
a sp
iritu
ality
-fo
cuse
d ps
ycho
ther
apy
was
eff
ectiv
e in
redu
cing
the
coca
ine
use
2009
Lee
and
Bom
bi
[44]
To in
vest
igat
e th
e eff
ects
of
acup
unct
ure
on th
e re
peat
ed
coca
ine-
indu
ced
neur
onal
an
d be
havi
oral
sen
sitiz
atio
n al
tern
atio
ns
32 M
ale
Spra
gue–
Daw
ley
rats
, n =
15
acup
unct
ure
Acu
punc
ture
bila
tera
lly a
t She
n-m
en (H
T7) f
or 1
min
Coca
ine-
indu
ced
loco
mot
or
activ
ity a
nd th
e ex
pres
sion
of
tyro
sine
hyd
roxy
lase
(TH
) in
the
brai
n
acup
unct
ure
was
effe
ctiv
e fo
r in
hibi
ting
the
beha
vior
al
effec
ts o
f coc
aine
by
poss
ible
m
odul
atio
n of
the
cent
ral
dopa
min
ergi
c sy
stem
2012
Yoon
[84]
To in
vest
igat
e th
e eff
ects
of a
cu-
punc
ture
on
coca
ine-
seek
ing
and
the
expr
essi
on o
f c-F
os
and
the
tran
scrip
tion
fact
or
cAM
P re
spon
se e
lem
ent-
bind
ing
prot
ein
(CRE
B)
24 M
ale
Spra
gue–
Daw
ley
rats
, n =
6 E
AA
cupu
nctu
re a
t She
nmen
(HT7
) as
stu
dy a
nd Y
angx
i (LI
5) a
s co
ntro
l for
1 m
in
Coca
ine-
seek
ing
beha
vior
, su
rfac
e ex
pres
sion
, and
pho
s-ph
oryl
ated
CRE
B (p
CRE
B)
activ
atio
n in
the
NA
c sh
ell
acup
unct
ure
atte
nuat
ed s
tres
s-in
duce
d re
laps
e by
regu
latin
g ne
uron
al a
ctiv
atio
n in
th
e N
Ac
shel
l
2013
Kim
and
Seo
l Ah
[42]
To e
xplo
re th
e pe
riphe
ral
mec
hani
sms
unde
rlyin
g ac
u-pu
nctu
re tr
eatm
ent f
or d
rug
addi
ctio
n
12 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
at S
henm
en (H
T7)
as s
tudy
and
Yan
gxi (
LI5)
as
cont
rol f
or 1
min
Supp
ress
ion
of c
ocai
ne-
indu
ced
loco
mot
or a
ctiv
ityac
upun
ctur
e in
hibi
ted
the
coca
ine-
indu
ced
loco
mot
or
activ
ity
Page 8 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 3
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in o
pioi
d- a
nd o
piat
e-de
pend
ent s
ubje
cts
Publ
icat
ion
year
, fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
. (ac
u-pu
nctu
re ty
pe, a
cupo
ints
, fr
eque
ncy)
Ass
essm
ents
Out
com
es
2002
Mon
taze
ri, K
amra
n [6
3]To
iden
tify
the
effec
ts o
f bod
y ac
upun
ctur
e on
rapi
d op
iate
de
toxi
ficat
ion
40 O
pioi
d ad
dict
s du
ring
ROD
by
nalo
xone
, n =
20
acup
unct
ure
Bila
tera
lly a
cupu
nctu
re a
t Heg
u (L
I4),
Nei
guan
(PC
6), S
henm
en
(HT7
), Ta
icho
ng (L
R3),
Zusa
nli
(ST3
6), B
aihu
i (D
U20
) and
D
azhu
i (D
U14
) 30
min
for
3 da
ys
Seve
rity
of w
ithdr
awal
reac
tion
(Clin
ical
Inst
itute
Nar
cotic
A
sses
smen
t (C
INA
) sco
re)
acup
unct
ure
redu
ced
the
seve
r-ity
of w
ithdr
awal
sym
ptom
s as
soci
ated
with
rapi
d op
iate
de
toxi
ficat
ion
2007
Liu
[55]
To in
vest
igat
e th
e ac
tivat
ion
in
the
hypo
thal
amus
ass
ocia
ted
with
acu
punc
ture
stim
ulat
ion
Six
heal
thy
men
and
six
her
oin
addi
cts
Acu
punc
ture
at Z
usan
li (S
T36)
w
ith ro
tatio
n fo
r 11
min
fMRI
, Cor
tisol
leve
l and
psy
cho-
phys
ical
resp
onse
s, in
clud
ing
the
deqi
sen
satio
n, a
nxie
ty,
and
shar
p pa
in
Acu
punc
ture
cau
sed
activ
atio
n of
the
hypo
thal
amus
am
ong
addi
cts
2009
Bear
n [1
1]To
inve
stig
ate
AA
effe
cts
as a
n ad
junc
t to
MM
T up
on w
ith-
draw
al s
ever
ity o
r cra
ving
83 O
pioi
d us
ers
unde
r MM
TA
cupu
nctu
re a
t 5 p
oint
s of
ca
rtila
ge ri
dge
area
in th
e ea
r, 30
–40
min
for 1
4 da
ys
Dai
ly m
easu
res
of w
ithdr
awal
se
verit
y an
d cr
avin
g us
ing
the
shor
t opi
ate
with
draw
al
scal
e an
d an
eig
ht-it
em c
rav-
ing
ques
tionn
aire
AA
had
no
effec
t upo
n w
ith-
draw
al s
ever
ity o
r cra
ving
w
hen
prov
ided
as
an a
djun
ct
to a
sta
ndar
d m
etha
done
de
toxi
ficat
ion
trea
tmen
t
2010
Mea
de [6
2]To
eva
luat
e th
e eff
ectiv
enes
s of
TE
AS
as a
n ad
junc
tive
trea
t-m
ent f
or in
patie
nts
rece
ivin
g op
ioid
det
oxifi
catio
n
48 M
en a
nd w
omen
und
er
deto
xific
atio
n w
ith
bupr
enor
phin
e-na
loxo
ne
2 an
d 10
0 H
z TE
AS
at H
egu
(LI4
) an
d N
eigu
an (P
C6)
, 30
min
da
ily fo
r 4 d
ays
The
addi
ctio
n se
verit
y in
dex,
op
ioid
with
draw
al s
cale
, brie
f pa
in in
vent
ory,
the
Pitt
sbur
gh
slee
p qu
ality
inde
x, p
hysi
cal
and
men
tal h
ealth
sta
tus
by
the
med
ical
out
com
es s
urve
y
TEA
S w
as e
ffect
ive
in u
sing
dr
ugs
and
impr
ovin
g th
e pa
in
inte
rfer
ence
and
phy
sica
l he
alth
2011
Xia
[81]
To in
vest
igat
e th
e re
war
ding
eff
ect o
f EA
68 M
ale
Spra
gue–
Daw
ley
rats
2 H
z EA
at N
eigu
an (P
C6)
and
Zu
sanl
i (ST
36),
30 m
in fo
r 5
days
Cond
ition
ed p
lace
pre
fere
nce
(CPP
)EA
was
cap
able
of i
nduc
ing
CPP
in
the
rat v
ia th
e ac
tivat
ion
of th
e en
doge
nous
opi
oid-
, ca
nnab
inoi
d- a
nd d
opam
ine-
syst
ems
2011
Jiang
[37]
To c
ompa
re th
e ch
ange
s of
co
gniti
ve a
tten
tion-
rela
ted
brai
n fu
nctio
n be
fore
and
af
ter E
A
Ten
Her
oin
addi
cts
and
ten
heal
thy
subj
ects
2 H
z bi
late
ral E
A a
t Nei
guan
(P
C6)
and
Zus
anli
(ST3
6)ER
P at
64
elec
trod
e sp
ots
befo
re a
nd a
fter
EA
inte
rven
-tio
n ta
sk o
n th
e po
sitiv
e em
o-tio
nal c
lue
(PEG
), ne
gativ
e em
otio
nal c
lues
(NEC
), an
d he
roin
-rel
ated
clu
e (H
RC).
The
P200
am
plitu
de c
ompo
nent
s on
(Fz,
Cz,
and
Pz)
Elec
troa
cupu
nctu
re e
ffect
ivel
y in
hibi
ted
the
atte
ntio
n bi
as to
he
roin
2012
Cai [
17]
To u
nder
stan
d th
e in
fluen
ce o
f he
roin
cue
exp
osur
e on
bra
in
activ
atio
n
12 H
eroi
n ad
dict
s an
d 12
he
alth
y su
bjec
tsno
n-tw
irled
acu
punc
ture
and
tw
irled
acu
punc
ture
at b
ilat-
eral
Zus
anli
(ST3
6) fo
r 1 m
in
fMRI
dur
ing
hero
in c
ue
expo
sure
Acu
punc
ture
can
rapi
dly
sup-
pres
s th
e ac
tivat
ion
of s
peci
fic
brai
n re
gion
s re
late
d to
cra
v-in
g as
an
inte
rven
tion
for d
rug
crav
ing
2012
Liu
[56]
To in
vest
igat
e th
e be
nefic
ial
effec
ts o
f EA
on
hero
in-s
eek-
ing
beha
vior
40 M
ale
Spra
gue–
Daw
ley
rats
, n =
10
EA2
Hz
EA a
t Zus
anli
(ST3
6) a
nd
Sany
injia
o (S
P6),
once
a d
ay
for 1
4 da
ys d
urin
g he
roin
ab
stin
ence
Cont
extu
al a
nd d
iscr
ete
cue-
indu
ced
rein
stat
emen
t of
activ
e re
spon
ses.
Fos-
posi
tive
nucl
ei d
etec
tion
in th
e nu
cleu
s ac
cum
bens
(NA
Cc)
core
and
she
ll
acup
unct
ure
was
effe
ctiv
e in
pr
even
ting
rela
pse
to d
rug
addi
ctio
n
Page 9 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 3
cont
inue
d
Publ
icat
ion
year
, fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
. (ac
u-pu
nctu
re ty
pe, a
cupo
ints
, fr
eque
ncy)
Ass
essm
ents
Out
com
es
2013
Hu
[33]
To in
vest
igat
e th
e eff
ects
of E
A
on th
e ex
tinct
ion
of h
eroi
n-se
ekin
g be
havi
or
18 M
ale
Spra
gue–
Daw
ley
rats
, n =
6 E
A2
Hz
EA a
t Zus
anli
(ST3
6) a
nd
Sany
injia
o (S
P6),
once
a d
ay
for 7
day
s
The
extin
ctio
n re
spon
se o
f he
roin
ass
ocia
ted
cues
and
ap
plie
d im
mun
ohis
toch
em-
istr
y to
det
ect F
osB-
posi
tive
nucl
ei in
the
nucl
eus
accu
m-
bens
cor
e
Acu
punc
ture
enh
ance
d ex
tinc-
tion
lear
ning
whe
n co
mbi
ned
with
ext
inct
ion
ther
apy
for t
he
trea
tmen
t of h
eroi
n ad
dict
ion
2013
Lua,
Pei
Lin
[57]
To fi
nd th
e eff
ects
of A
A in
nu
mbe
r of c
onsu
med
dai
ly
ciga
rett
es, r
elap
se ra
te, a
nd
with
draw
al s
ympt
oms
40 M
MT,
29
MM
T +
AA
hum
an
subj
ects
Aur
icul
ar a
cupu
nctu
re a
t 5
poin
ts N
AD
A p
oint
s, 3
times
a
wee
k
Mal
ay H
OQ
OLB
REF,
with
draw
al
sym
ptom
sA
cupu
nctu
re a
djun
ct to
MM
T w
as b
enefi
cial
in m
anag
ing
addi
ctio
n be
havi
ors
2013
Lua,
Pei
Lin
[58]
To e
xam
ine
the
patie
nts’
satis
fact
ion
and
copi
ng w
ith
AA
as
an a
djun
ct tr
eatm
ent
to M
MT
40 M
MT,
29
MM
T +
AA
hum
an
subj
ects
Aur
icul
ar a
cupu
nctu
re a
t 5
poin
ts N
AD
A p
oint
s, 3
times
a
wee
k
Patie
nt s
atis
fact
ion
with
pha
r-m
aceu
tical
car
e qu
estio
n-na
ire (P
SPCQ
) and
Mal
ay b
rief
COPE
-27
Acu
punc
ture
adj
unct
to M
MT
did
not i
nflue
nce
patie
nt s
at-
isfa
ctio
n an
d th
eir c
opin
g w
ays
2014
Cha
n [2
2]To
exa
min
e th
e eff
ectiv
enes
s of
acu
punc
ture
for h
eroi
n ad
dict
s on
met
hado
ne
mai
nten
ance
60 H
eroi
n ad
dict
s in
MM
PEA
at H
egu
(LI4
), Zu
sanl
i (ST
36)
and
Shen
men
(HT7
), tw
ice
a w
eek
for 4
wee
ks
Dai
ly c
onsu
mpt
ion
of
met
hado
ne, v
aria
tions
in th
e 36
-item
Sho
rt F
orm
Hea
lth
Surv
ey-3
6 (S
F-36
) and
the
Pitt
sbur
gh S
leep
Qua
lity
Inde
x (P
SQI)
scor
es, a
nd
hero
in c
ravi
ng
Acu
punc
ture
adj
unct
to M
MT
was
use
ful i
n re
duci
ng th
e da
ily d
ose
of m
etha
done
and
gr
eat i
mpr
ovem
ent i
n sl
eep
late
ncy
at fo
llow
-up
2014
Hou
[32]
To o
bser
ve c
ell a
popt
osis
in
the
hipp
ocam
pus
and
front
al
lobe
of h
eroi
n re
addi
cted
rats
by
ele
ctro
n m
icro
scop
y.
40 W
ista
r rat
s du
ring
the
deto
xific
stio
n by
met
hado
neA
cupu
nctu
re a
t Bai
hui (
GV2
0)
and
Daz
hui (
GV1
4), 3
0 m
in fo
r 5
succ
essi
ve d
ays
Mor
phol
ogy
of n
erve
cel
ls, B
ax
expr
essi
on a
nd B
cl-2
exp
res-
sion
in th
e fro
ntal
cor
tex
and
hipp
ocam
pus
Acu
punc
ture
was
effe
ctiv
e in
pr
even
ting
brai
n ce
ll ap
opto
sis
in h
eroi
n re
addi
cted
rats
2014
Zhan
g [8
8]To
ver
ify th
e re
latio
nshi
p be
twee
n ac
upun
ctur
e,
neur
otro
phic
fact
or e
xpre
s-si
on a
nd b
rain
cel
l str
uctu
ral
chan
ges
32 W
ista
r rat
s, n =
16
acu-
punc
ture
Acu
punc
ture
at B
aihu
i (D
U20
) an
d D
azhu
i (D
U14
) for
30
min
, on
ce a
day
for fi
ve c
onse
cu-
tive
days
The
neur
onal
ultr
astr
uctu
re o
f th
e ve
ntra
l teg
men
tal a
rea,
br
ain-
deriv
ed a
nd g
lial c
ell
line-
deriv
ed n
euro
trop
hic
fact
or e
xpre
ssio
n in
the
vent
ral t
egm
enta
l are
a
Acu
punc
ture
pro
tect
ed b
rain
ne
uron
s ag
ains
t inj
ury
in ra
ts
with
her
oin
rela
pse
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic in
the
delto
id fo
ssa
at th
e ju
nctio
n of
the
infr
a-an
tihel
ix c
rus
and
the
med
ial o
rder
of t
he h
elix
, lun
g in
the
cent
er o
f the
cav
um c
onch
a, li
ver l
ocat
ed in
the
post
erio
r to
upp
er p
ortio
n of
the
helix
cru
s, ki
dney
in th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Page 10 of 20Motlagh et al. Chin Med (2016) 11:16
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic: i
n th
e de
ltoid
foss
a at
the
junc
tion
of th
e in
fra-
antih
elix
cru
s an
d th
e m
edia
l ord
er o
f the
hel
ix, l
ung:
in th
e ce
nter
of t
he c
avum
con
cha,
live
r: lo
cate
d in
the
post
erio
r to
uppe
r por
tion
of th
e he
lix c
rus,
kidn
ey: i
n th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Tabl
e 4
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in n
icot
ine-
depe
nden
t sub
ject
s
Publ
icat
ion
year
; fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
(acu
punc
ture
ty
pe, a
cupo
ints
, fre
quen
cy)
Ass
essm
ents
Out
com
es
2004
Cha
e [2
1]To
inve
stig
ate
the
acup
unct
ure
effec
ts
on th
e fu
nctio
nal a
ltera
tions
of t
he
mes
olim
bic
dopa
min
ergi
c sy
stem
s
35 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
at Z
usan
li (S
T36)
, She
n-m
en (H
T7),
or T
aiyu
an (L
U9)
for
4 da
ys
Nic
otin
e-in
duce
d FL
I in
the
stria
tum
and
the
nucl
eus
accu
mbe
ns
acup
unct
ure
had
a th
erap
eutic
eff
ect o
n ni
cotin
e ad
dict
ion
2005
Park
[65]
To e
xam
ine
whe
ther
the
DRD
2 Ta
qI A
po
lym
orph
ism
is a
ssoc
iate
d w
ith th
e re
spon
se to
acu
punc
ture
231
Hea
lthy
Kore
an m
ale
smok
ers
AA
at l
ung,
thro
at, S
henm
en (H
T7),
and
endo
crin
epo
ints
for 9
6 s,
3 tim
es fo
r a w
eek
Cig
aret
te c
onsu
mpt
ion,
the
desi
re to
sm
oke,
and
Gen
omic
D
NA
ext
ract
ed fr
om b
lood
sa
mpl
es
Acu
punc
ture
was
effe
ctiv
e to
in
fluen
ce th
e D
RD2
TaqI
A
poly
mor
phis
m
2008
Cha
e [2
0]To
inve
stig
ate
the
effec
t of a
cupu
nctu
re
on a
nxie
ty-li
ke b
ehav
ior a
nd c
orti-
cotr
ophi
n-re
leas
ing
fact
or (C
RF) a
nd
neur
opep
tide
Y (N
PY) m
RNA
exp
res-
sion
in th
e am
ygda
la d
urin
g ni
cotin
e w
ithdr
awal
38 M
ale
Spra
gue–
Daw
ley
rats
, n =
18
acup
unc-
ture
Acu
punc
ture
at Z
usan
li (S
T36)
, She
n-m
en (H
T7),
30 s
for 3
day
sTh
e an
xiog
enic
resp
onse
by
usin
g an
ele
vate
d pl
us m
aze.
C
RF a
nd N
PY m
RNA
leve
ls b
y us
ing
reve
rse
tran
scrip
tion
poly
mer
ase
chai
n re
actio
n (R
T-PC
R) a
naly
sis
acup
unct
ure
atte
nuat
ed a
nxie
ty-
like
beha
vior
follo
win
g ni
cotin
e w
ithdr
awal
2008
Bonn
ette
[15]
To e
xplo
re th
e eff
ects
of A
TEN
S in
co
mbi
natio
n w
ith a
ddic
tion
educ
atio
n,
beha
vior
al tr
aini
ng a
nd c
oach
ing
6 Sm
oker
sA
cupu
nctu
re a
t 5 N
AD
A p
roto
col
or 1
-3 p
oint
s, 5
times
a w
eek
for
8 w
eeks
In-d
epth
inte
rvie
ws
for w
ith-
draw
al s
ympt
oms,
anxi
ety
and
stre
ss le
vels
auric
ulot
hera
py re
lieve
d w
ith-
draw
al s
ympt
oms
and
redu
ced
anxi
ety
and
stre
ss le
vels
dur
ing
the
deto
xific
atio
n
2009
Yeh
[83]
To e
valu
ate
the
effec
ts o
f a 6
-wee
k ac
u-po
int s
timul
atio
n pr
ogra
m fo
r qui
ttin
g59
Sm
oker
sA
cuou
nctu
re a
t She
nmen
(HT7
), lu
ng,
stom
ach,
mou
th a
nd e
ndoc
rine
and
Tim
mee
for 2
0 m
in, o
nce
a w
eek
for
6 w
eeks
Dem
ogra
phic
fact
ors,
seru
m
cotin
ine,
car
bon
mon
oxid
e ex
hala
tion,
dai
ly to
bacc
o co
n-su
mpt
ion,
and
qui
t sm
okin
g ra
te o
f par
ticip
ants
bef
ore
and
afte
r the
6-w
eek
inte
rven
tion
Acu
punc
ture
sho
wed
no
stat
isti-
cally
sig
nific
ant e
ffect
on
quit-
ting
smok
ing
2010
Than
avar
o [7
2]To
exp
lore
the
effica
cy o
f ATE
T as
an
adju
nctiv
e tr
eatm
ent t
o in
tens
ive
indi
vidu
al c
ouns
elin
g on
sm
okin
g ce
ssat
ion
29 S
ubje
cts
Aur
icul
ar tr
ansc
utan
eous
ele
ctro
stim
-ul
atio
n th
erap
y at
10
area
s on
the
pinn
a
The
“Fag
erst
rom
Tes
t for
Nic
otin
e D
epen
denc
e,” th
e “W
hat A
re
Your
Trig
gers
Tes
t” an
d th
e “W
hy D
o I S
mok
e Q
uiz.”
indi
vidu
al c
ouns
elin
g m
ay p
ro-
duce
sm
okin
g ce
ssat
ion
rate
s co
mpa
rabl
e to
cou
nsel
ing
with
ph
arm
acot
hera
py
2010
Cha
e [1
8]To
inve
stig
ate
the
effec
t of a
cupu
nctu
re
on th
e se
lect
ive
atte
ntio
n to
sm
okin
g-re
late
d vi
sual
cue
s
29 S
mok
ers
Acu
punc
ture
, She
nmen
(HT7
), (N
A)
The
atte
ntio
nal b
ias
and
ciga
-re
tte
with
draw
al s
cale
Acu
punc
ture
am
elio
rate
d th
e sm
okin
g w
ithdr
awal
sym
ptom
s as
wel
l as
the
sele
ctiv
e at
tent
ion
to s
mok
ing-
rela
ted
visu
al c
ues
2011
Cha
e [1
9]To
inve
stig
ate
effec
ts o
f acu
punc
ture
on
am
elio
ratin
g ci
gare
tte
with
draw
al
sym
ptom
s
29 S
mok
ers,
n =
15
acup
unc-
ture
Acu
punc
ture
at S
henm
en (H
T7) o
r Sh
ousa
nli (
LI10
), 20
min
for 3
day
sTh
e ci
gare
tte
with
draw
al s
cale
(C
WS)
, com
parin
g th
e lo
w-
frequ
ency
/hig
h-fre
quen
cy (H
F/LF
) rat
io in
the
HRV
of t
he R
A
and
SA g
roup
s
acup
unct
ure
atte
nuat
ed w
ith-
draw
al s
ympt
oms
and
smok
ing
cues
-indu
ced
auto
nom
ic
resp
onse
s
2013
Kang
[38]
To in
vest
igat
e ac
upun
ctur
e eff
ects
on
amel
iora
ting
crav
ings
indu
ced
by
smok
ing-
rela
ted
visu
al c
ues
25 M
ale
smok
ers
Acu
punc
ture
at S
henm
en (H
T7) f
or
1 m
infM
RI a
nd c
ravi
ng s
core
s to
sm
okin
g-re
late
d vi
sual
cue
s w
ere
asse
ssed
bef
ore
and
afte
r RA
or s
ham
trea
tmen
t
acup
unct
ure
alle
viat
ed c
ue-
indu
ced
crav
ings
thro
ugh
the
regu
latio
n of
act
ivity
in b
rain
re
gion
s in
volv
ed in
att
entio
n,
mot
ivat
ion,
and
rew
ard
Page 11 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 5
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in a
lcoh
ol-d
epen
dent
sub
ject
s
Publ
icat
ion
year
; fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
(acu
-pu
nctu
re ty
pe, a
cupo
ints
, fr
eque
ncy)
Ass
essm
ents
Out
com
es
2001
Yosh
imot
o [8
6]To
inve
stig
ate
the
effec
t of
EA o
n ch
ange
s in
alc
ohol
-dr
inki
ng b
ehav
ior i
n ra
ts
chal
leng
ed w
ith re
stric
tion
and
imm
obili
zatio
n st
ress
8–12
Mal
e Sp
ragu
e–D
awle
y ra
ts1
Hz
and
100
Hz
EA a
t Zus
anli
(ST
36) a
nd S
hens
hu (B
L 23
) fo
r 10
min
, tw
ice
a w
eek
for
1–3
wee
ks
Tim
e-ac
cess
alc
ohol
-drin
king
be
havi
or, b
rain
dop
amin
e (D
A) l
evel
Acu
punc
ture
at Z
usan
li (S
T 36
) w
as m
ore
effec
tive
for r
educ
-in
g th
e in
crea
sed
alco
hol-
drin
king
beh
avio
r
2002
Bullo
ck [1
6]To
repo
rt th
e cl
inic
al d
ata
on
the
effica
cy o
f acu
punc
ture
fo
r alc
ohol
dep
ende
nce
503
Alc
ohol
ics
AA
at S
henm
en (H
T7),
lung
, sy
mpa
thet
ic, a
nd li
ver f
or
40 m
in, 6
day
s a
wee
k fo
r 3
wee
ks
Alc
ohol
use
, dep
ress
ion,
anx
i-et
y, fu
nctio
nal s
tatu
s, an
d pr
efer
ence
for t
hera
py
acup
unct
ure
was
not
foun
d to
be
effe
ctiv
e in
redu
ctio
n of
al
coho
l use
alo
ne
2002
Kars
t [39
]To
inve
stig
ate
the
acup
unct
ure
effec
ts o
n al
coho
l with
draw
al
ther
apy
with
car
bam
azep
ine
34 A
lcoh
olic
sAA
at S
ympa
thet
ic, S
henm
en
(HT7
), ki
dney
, liv
er, l
ung,
Bai
hui
(GV2
0), e
xtra
1, a
nd H
e G
u (L
i4),
daily
for 1
0 da
ys
Clin
ical
Inst
itute
With
draw
al
Ass
essm
ent (
CIW
A-A
r-sc
ale)
Acu
punc
ture
as
an a
djun
ctiv
e tr
eatm
ent t
o ca
rbam
azep
ine
med
icat
ion
show
s pr
omis
e fo
r the
trea
tmen
t of a
lcoh
ol
with
draw
al s
ympt
oms
2003
Trum
pler
[74]
To c
ompa
re a
uric
ular
lase
r an
d ne
edle
acu
punc
ture
w
ith s
ham
lase
r stim
ulat
ion
in re
duci
ng th
e du
ratio
n of
al
coho
l with
draw
al
48 a
lcoh
olic
s un
derg
oing
al
coho
l with
draw
al w
ith
clom
ethi
azol
e n =
17
lase
r, n =
15
need
le
AA
(2-1
0 ou
t of 2
4 po
ints
) for
30
-45
min
, las
er A
A a
t 24
pint
s (1
min
for e
ach
poin
t),
3-4
days
The
dura
tion
of w
ithdr
awal
sy
mpt
oms
(nur
se-r
ated
sc
ale)
, dur
atio
n of
sed
ativ
e pr
escr
iptio
n
Acu
punc
ture
sho
wed
no
rele
vant
ben
efit f
or a
lcoh
ol
with
draw
al
2004
Zale
wsk
a-Ka
szub
ska
[87]
To in
tens
ify A
A m
etho
d by
ad
ditio
nal b
iost
imul
atio
n of
th
e w
hole
org
anis
m
53 A
lcoh
olic
s un
der d
aily
he
lium
–neo
n la
ser f
or n
eck
bios
timul
atio
n
Lase
r AA
at c
onch
a po
ints
for 4
pe
riods
of t
en ti
mes
app
lied
ever
y 2n
d da
y
The
Beck
Dep
ress
ion
Inve
ntor
y-Fa
st S
cree
n (B
DI-
FS),
beta
-end
orph
in p
lasm
a co
ncen
trat
ion
by u
sing
the
radi
oim
mun
oass
ay (R
IA)
lase
r the
rapy
was
use
ful a
s an
ad
junc
t tre
atm
ent f
or a
lcoh
ol-
ism
2005
Kim
[40]
To in
vest
igat
e th
e eff
ects
of
acup
unct
ure
on a
lcoh
ol
with
draw
al s
yndr
ome
(AW
S)
and
Fos-
like
imm
unor
eact
iv-
ity (F
LI) i
n th
e st
riatu
m a
nd
the
nucl
eus
accu
mbe
ns
(NA
C) o
f rat
s
24 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
at Z
usan
li (S
T36)
an
d Sa
nyin
jiao
(SP6
) for
3
days
Alc
ohol
with
draw
al s
yndr
ome
(AW
S) a
nd F
os-li
ke im
mun
o-re
activ
ity (F
LI) i
n th
e st
riatu
m
and
the
nucl
eus
accu
mbe
ns
(NA
C)
acup
unct
ure
was
use
ful i
n th
e tr
eatm
ent o
f alc
ohol
ism
by
mod
ulat
ing
post
-syn
aptic
neu
-ra
l act
ivat
ion
in th
e st
riatu
m
and
NA
C
2006
Yosh
imot
o [8
5]To
inve
stig
ate
the
neur
opha
r-m
acol
ogic
al m
echa
nism
s of
or
ient
al a
cupu
nctu
re
24 M
ale
Spra
gue–
Daw
ley
rats
, n =
16
acup
unct
ure
unila
tera
l or b
ilate
ral a
cu-
punc
ture
at S
hens
hu (B
U23
) ac
upoi
nt, 6
0 m
in
Dop
amin
e (D
A) a
nd s
erot
onin
(5
-HT)
con
tent
s of
the
mic
ro-
dial
ysat
es in
the
ACC
Acu
punc
ture
was
effe
ctiv
e fo
r tr
eatm
ent o
f em
otio
nal d
isor
-de
rs a
nd la
coni
sm b
y in
crea
s-in
g an
d pr
olon
ging
the
activ
ity
of s
erot
oner
gic
neur
ons
2006
Zhao
[89]
To in
vest
igat
e th
e eff
ects
of
acup
unct
ure
on c
hron
ic
etha
nol-i
nduc
ed c
hang
es in
ex
trac
ellu
lar d
opam
ine
leve
ls
in th
e nu
cleu
s ac
cum
bens
sh
ell
35 M
ale
Spra
gue–
Daw
ley
rats
, n =
21
sham
or r
eal
acup
unct
ure
Bila
tera
l acu
punc
ture
at S
hen-
men
(HT7
) poi
nt o
r Nei
guan
(P
C6)
or t
ail)
for 1
min
Extr
acel
lula
r dop
amin
e le
vels
in
the
nucl
eus
accu
mbe
ns
shel
l (us
ing
in v
ivo
mic
rodi
-al
ysis
in u
nane
sthe
tized
rats
)
Acu
punc
ture
at H
T7 w
as e
ffec-
tive
to n
orm
aliz
e th
e re
leas
e of
do
pam
ine
in th
e m
esol
imbi
c sy
stem
follo
win
g ch
roni
c et
hano
l tre
atm
ent
Page 12 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 5
cont
inue
d
Publ
icat
ion
year
; fir
st a
utho
rO
bjec
tives
Subj
ects
Stim
ulat
ed a
cupo
ints
(acu
-pu
nctu
re ty
pe, a
cupo
ints
, fr
eque
ncy)
Ass
essm
ents
Out
com
es
2007
Kunz
[43]
To c
ompa
re a
uric
ular
nee
dle
acup
unct
ure
with
aro
mat
her-
apy
in re
duci
ng th
e du
ratio
n an
d se
verit
y of
sym
ptom
s of
al
coho
l with
draw
al w
ith c
ar-
bam
azep
ine,
oxc
arba
zepi
ne,
and
benz
odia
zepi
nes
74 a
lcoh
olic
s, n =
36
acup
unc-
ture
, n =
38
arom
athe
rapy
AA
at 5
NA
DA
poi
nts,
45 m
in
for 5
day
sA
lcoh
ol-w
ithdr
awal
syn
drom
e (A
WS
scal
e), s
ubje
ctiv
e vi
sual
an
alog
sca
le o
f cra
ving
and
th
e Se
lf-A
sses
smen
t Man
ikin
(S
AM
)
acup
unct
ure
was
not
mor
e eff
ectiv
e th
an th
e co
ntro
l th
erap
y on
alc
ohol
with
draw
al
sym
ptom
s
2008
Ove
rstr
eet [
64]
To in
vest
igat
e th
e EA
effe
cts
for
redu
cing
vol
unta
ry a
lcoh
ol
inta
ke in
alc
ohol
-pre
ferr
ing
rats
18 in
bred
alc
ohol
-pre
ferr
ing
P ra
ts (I
P), n
= 9
EA
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
and
San
yinj
iao
(SP6
) fo
r 30
min
Alc
ohol
inta
keA
cupu
nctu
re a
ffect
ed o
n al
coho
l int
ake
in th
e al
coho
l-de
pend
ent I
P ra
ts
2009
Dos
San
tos
[28]
To in
vest
igat
e th
e eff
ects
of E
A
over
loco
mot
or s
ensi
tizat
ion
indu
ced
by e
than
ol in
mic
e
12 M
ale
Swis
s m
ice
2 H
z EA
at Z
usan
li (S
T36)
and
/or
Nei
guan
(PC
6) fo
r 10
min
The
loco
mot
or a
ctiv
ity, t
he
expr
essi
on o
f hom
er1A
m
RNA
ass
esse
d by
PC
R
EA m
odul
ated
hom
er1A
ex
pres
sion
and
glu
tam
ater
gic
plas
ticity
2010
Yang
[82]
To e
valu
ate
the
effec
ts o
f HT7
ac
upun
ctur
e on
VTA
GA
BA
neur
on e
xcita
bilit
y, e
than
ol
inhi
bitio
n of
VTA
GA
BA n
eu-
ron
firin
g ra
te, a
nd e
than
ol
self-
adm
inis
trat
ion
32 M
ale
Wis
tar r
ats
2 H
z EA
at S
henm
en (H
T7) o
r N
eigu
an (P
C6)
for 1
min
Etha
nol-R
einf
orce
d Re
spon
d-in
g, V
TA G
ABA
Neu
ron
Act
ivity
, VTA
GA
BA N
euro
n Fi
ring
Rate
acup
unct
ure
redu
ced
etha
nol
supp
ress
ion
of V
TA G
ABA
neu
-ro
n fir
ing
rate
, and
redu
ced
etha
nol s
elf-a
dmin
istr
atio
n w
ithou
t affe
ctin
g su
cros
e co
nsum
ptio
n
2011
Li [5
0]To
dem
onst
rate
that
SD
rats
es
cala
ted
thei
r eth
anol
inta
ke
and
subs
eque
ntly
dev
elop
ed
etha
nol d
epen
denc
e un
der
the
IE p
roce
dure
26 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
Z EA
at Z
usan
li (S
T36)
for 2
0 m
inIn
take
of a
nd p
refe
renc
e fo
r et
hano
lEA
trea
tmen
ts d
ecre
ased
the
inta
ke o
f and
pre
fere
nce
for
etha
nol,
with
out r
esul
ting
in
a re
boun
d in
crea
se in
eth
anol
in
take
whe
n th
e EA
trea
tmen
ts
wer
e te
rmin
ated
2012
Li [4
9]To
test
the
hypo
thes
is th
at E
A
supp
ress
ion
on a
lcoh
ol c
on-
sum
ptio
n m
ay b
e m
edia
ted
by tr
ansc
riptio
n fa
ctor
s, su
ch
as F
osB/
ΔFo
sB p
rote
in in
re
war
d-re
late
d br
ain
regi
ons
33 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
Z EA
at Z
usan
li (S
T36)
, 30
min
for 6
day
sTh
e ex
pres
sion
of F
osB/
ΔFo
sB
in s
ever
al re
war
d-re
late
d br
ain
regi
ons
usin
g im
mun
o-hi
stoc
hem
istr
y
EA tr
eatm
ent e
ffect
ivel
y re
duce
d et
hano
l con
sum
ptio
n an
d pr
efer
ence
in ra
ts b
y do
wn-
regu
latio
n of
Fos
B/Δ
FosB
in
rew
ard-
rela
ted
brai
n re
gion
s
2012
Esco
steg
uy-N
eto
[29]
To in
vest
igat
e EA
effe
cts
durin
g et
hano
l with
draw
al o
n C
B1R
imm
unor
eact
ivity
12 M
ale
Swis
s m
ice
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
/Nei
guan
(PC
6) o
r D
azhu
i (D
U14
)/Ba
ihui
(DU
20),
10 m
in fo
r 4 d
ays
CB1
R in
the
pref
ront
al c
orte
x,
stria
tum
, hip
poca
mpu
s, am
ygda
la a
nd v
entr
al te
g-m
enta
l are
a
EA in
hibi
ted
CB1
R up
regu
latio
n w
hich
dep
ende
d on
acu
poin
ts
asso
ciat
ion
and
frequ
ency
of
stim
ulat
ion
2012
Fallo
pa [3
0]To
inve
stig
ate
whe
ther
EA
re
vers
es lo
com
otor
sen
sitiz
a-tio
n in
duce
d by
eth
anol
is
para
llel t
o ER
K si
gnal
ing
12 M
ale
Swis
s m
ice
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
/Nei
guan
(PC
6) o
r D
azhu
i (D
U14
)/Ba
ihui
(DU
20),
10 m
in fo
r 4 d
ays
pERK
imm
une-
hist
oche
mis
try
EA in
crea
sed
CB1
R in
the
pref
ront
al c
orte
x, s
tria
tum
, hi
ppoc
ampu
s, am
ygda
la a
nd
vent
ral t
egm
enta
l are
a
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic: i
n th
e de
ltoid
foss
a at
the
junc
tion
of th
e in
fra-
antih
elix
cru
s an
d th
e m
edia
l ord
er o
f the
hel
ix, l
ung:
in th
e ce
nter
of t
he c
avum
con
cha,
live
r: lo
cate
d in
the
post
erio
r to
uppe
r por
tion
of th
e he
lix c
rus,
kidn
ey: i
n th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Page 13 of 20Motlagh et al. Chin Med (2016) 11:16
and NAc in rats [89]. Acupuncture at Shenmen (HT7) normalized dopamine release in the mesolimbic system [89], modulated mesolimbic dopamine release, and sup-pressed the reinforcing effects of ethanol [82]. Activation of the endogenous opiate system might be responsible for Zusanli (ST36) and Sanyinjiao (SP6) stimulation effects on alcohol intake in alcohol-dependent rats [64].
EA applied at Zusanli (ST36) was more effective than EA at Shenshu (BL23) at normalizing alcohol-drinking behavior in rats [86]; the activity of serotonergic neu-rons in the reward system pathway of the brain might be increased and prolonged by acupuncture [85]. EA at the combination Zusanli (ST36) and Neiguan (PC6) (but not at either point alone) prevented sensitization of the mesocorticolimbic pathway induced by ethanol in mice and modulated both the expression of the protein homer1A and glutamatergic plasticity [28]. EA (2 Hz) at Zusanli (ST36) could reduce voluntary intake of ethanol, but not sucrose, in rats [50] and 100 Hz EA treatment at Zusanli (ST36) effectively reduces preference for etha-nol and its consumption in rats [49]. In one study, 2 Hz EA at Zusanli (ST36) and Neiguan (PC6) or 100 Hz EA at Dazhui (DU14) and Baihui (DU20) inhibited CB1R upregulation in ethanol-withdrawn mice [29]. The behav-ioral effects of 2 Hz EA at Dazhui (DU14) and Baihui (DU20), but not 100 Hz EA at Zusanli (ST36) and Nei-guan (PC6), depended on extracellular signal-regulated kinase signaling [30]. See Table 5 for study details.
MorphineCompared with 100 Hz, 2 Hz peripheral electric stimula-tion (PES) at Zusanli (ST36) and Sanyinjiao (SP6) inhib-ited the expression of morphine-induced conditioned place preference (CPP) (see [52] for information on CPP) via activation of opioid receptors [75]. One study found that the release and synthesis of enkephalin in the NAc was accelerated by 2 Hz stimulation of Zusanli (ST36) and Sanyinjiao (SP6) [53]. In addition, EA suppression of opiate addiction might involve the release of endog-enous μ-, δ-, and κ-opioid agonists in the NAc shell [52] and might activate the cannabinoid, endogenous opioid, and dopamine systems to induce CPP in rats [81]. PES (100 Hz) at Zusanli (ST36) and Sanyinjiao (SP6) acti-vated the suprasegmental δ- and κ-opioid receptors in the central nervous system, which cause the anticrav-ing effects of PES in rats [70]. It was also found that the expression of preproenkephalin and preprodynorphin mRNAs in the NAc was mediated by 2 Hz or 100 Hz PES, with the release of endogenous μ-, δ-, and κ-opioid agonists to suppress morphine-induced CPP [71]. Stimu-lation at Zusanli (ST36) and Sanyinjiao (SP6) (100 Hz)
for 30 min normalized the activity of ventral tegmental area dopamine neurons [34], downregulated p-cAMP response element binding, and accelerated dynorphin synthesis in the spinal cord [76].
Some research suggests that 2 Hz EA is a potential complementary therapy for improving immune dysfunc-tion in opiate addicts [51] and that 2 Hz or 100 Hz EA facilitates the recovery of male sexual behavior in rats during morphine withdrawal [27]. Thirty minutes of EA of 2 Hz or 100 Hz at Zusanli (ST36) and Sanyinjiao (SP6) reversed the morphological alterations induced by chronic morphine administration [25]. In addition, by increasing NREM sleep, REM sleep, and total sleep time, EA could be a potential treatment for sleep disturbance during morphine withdrawal [48].
EA at Shenshu (BL23) attenuated the expression of the proto-oncogene c-Fos in the central nucleus of the amygdala [54]. Acupuncture at Shenmen (HT7) inhib-ited neurochemical and behavioral sensitization to mor-phine by decreasing dopamine release in the NAc [41]. Acupuncture at Shenmen (HT7) significantly suppressed morphine-induced increase in locomotor activity and Fos expression in the NAc and striatum [45]. Acupuncture at Yanggu (SI5) can reduce the reinstatement of morphine-seeking behaviors by mediating the gamma-aminobu-tyric acid receptor system [46, 47]. See Table 6 for study details.
Other substancesStudies of methamphetamine, cannabis, illicit/psycho-active drugs, and polydrug users are shown in Table 7. Twelve studies used the NADA 5-point protocol and AA as their treatment method. The findings indicated that people dependent on drugs preferred acupuncture treatment [9], which was associated with a decrease in psychological distress [12] and an increase in confidence [14], but showed no efficacy for drug consumption and withdrawal symptoms [9, 12–14]. However, the conflict-ing nature of the research findings remains a contro-versial issue. Although there was evidence against the effectiveness of acupuncture in drug addiction treatment [7, 35, 36], recent studies have shown an effect for AA [23, 24, 26, 68, 73] and transcutaneous electric acupoint stimulation [66] per se or as adjunct treatments. Issues of safety and placebo effects suggest the need for further research [26, 35, 36, 66]. See Table 7 for study details.
ConclusionAA and NADA protocols failed to show a strong thera-peutic effect for cocaine, nicotine, and alcohol addic-tion treatment. However, some studies discussed here
Page 14 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 6
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in m
orph
ine-
depe
nden
t sub
ject
s
Publ
icat
ion
year
; firs
t au
thor
Obj
ectiv
esSu
bjec
tsSt
imul
ated
acu
poin
ts (a
cupu
nc-
ture
type
, acu
poin
ts, f
requ
ency
)A
sses
smen
tsO
utco
mes
2000
Wan
g [7
5]To
obs
erve
the
effec
t of p
erip
hera
l el
ectr
ic s
timul
atio
n (P
ES) o
n m
orph
ine-
indu
ced
Cond
ition
ed
plac
e pr
efer
ence
CPP
57/8
2 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
z PE
S at
Zus
anli
(ST3
6)
and
Sany
injia
o (S
P6) f
or 3
0 m
inCo
nditi
oned
pla
ce p
refe
renc
e2
Hz
PES
coul
d sp
ecifi
cally
inhi
bit
the
expr
essi
on o
f mor
phin
e-in
duce
d C
PP
2003
Shi [
70]
To e
xam
ine
the
effec
t of 1
00 H
z pe
riphe
ral e
lect
ric s
timul
a-tio
n (P
ES) o
n th
e ex
pres
sion
of
mor
phin
e-in
duce
d C
PP
48 M
ale
Spra
gue–
Daw
ley
rats
100
Hz
PES
at Z
usan
li (S
T36)
and
Sa
nyin
jiao
(SP6
), 30
min
a d
ay
for 3
day
s
Cond
ition
ed p
lace
pre
fere
nce
Repe
ated
100
Hz
PES
had
anti-
crav
ing
effec
ts b
y ac
tivat
ing
supr
a-se
gmen
tal δ
- and
κ-o
pioi
d re
cept
ors
2004
Shi [
71]
To e
luci
date
if p
repr
oenk
epha
lin
(PPE
) and
pre
prod
ynor
phin
(P
PD) m
RNA
s in
the
nucl
eus
accu
mbe
ns (N
Ac)
pla
y a
role
in
PES
sup
pres
sing
mor
phin
e-in
duce
d C
PP
48 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
z PE
S at
Zus
anli
(ST3
6)
and
Sany
injia
o (S
P6),
30 m
in a
da
y fo
r 3 d
ays
Cond
ition
ed p
lace
pre
fere
nce
PES
supp
ress
ed b
oth
the
expr
essi
on
of m
orph
ine-
indu
ced
CPP
and
th
e re
inst
atem
ent o
f ext
ingu
ishe
d C
PP
2004
Cui [
27]
To in
vest
igat
e th
e eff
ect o
f EA
on
the
sexu
al b
ehav
ior o
f mal
e ra
ts u
nder
goin
g m
orph
ine
with
draw
al
41 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
an
d Sa
nyin
jiao
(SP6
), 30
min
a
day
for 7
day
s
Tota
l ser
um te
stos
tero
ne (T
ST)
conc
entr
atio
nsEA
faci
litat
ed th
e re
cove
ry o
f mal
e se
xual
beh
avio
r and
incr
ease
d TS
T co
ncen
trat
ions
2005
Kim
[41]
To in
vest
igat
e th
e eff
ect o
f ac
upun
ctur
e on
repe
ated
m
orph
ine-
indu
ced
chan
ges
in
extr
acel
lula
r dop
amin
e le
vels
31 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
at S
henm
en (H
T7)
for 1
min
Dop
amin
e re
leas
e in
the
nucl
eus
accu
mbe
ns a
nd b
ehav
iora
l hy
pera
ctiv
ity
Acu
punc
ture
dec
reas
ed b
oth
dopa
min
e re
leas
e in
the
nucl
eus
accu
mbe
ns a
nd b
ehav
iora
l hy
pera
ctiv
ity
2005
Liu
[54]
To e
valu
ate
the
effec
t of E
A o
n m
orph
ine
with
draw
al s
igns
an
d c-
Fos
expr
essi
on o
f the
am
ygda
la
21 M
ale
Spra
gue–
Daw
ley
rats
100
Hz
EA a
t She
nshu
(BL2
3) fo
r 30
min
Cort
icos
tero
ne le
vels
and
be
havi
oral
resp
onse
s du
ring
EA
stim
ulat
ion
EA s
igni
fican
tly re
duce
d th
e si
gns
of
mor
phin
e w
ithdr
awal
2008
Chu
[25]
To o
bser
ve th
e eff
ect o
f EA
on
chro
nic
mor
phin
e-in
duce
d ne
u-ro
nal m
orph
olog
ical
cha
nges
in
the
vent
ral t
egm
enta
l are
a (V
TA)
12 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
an
d Sa
nyin
jiao
(SP6
), 30
min
for
3 da
ys
The
roug
h en
dopl
asm
ic re
ticu-
lum
, mem
bran
e co
nfigu
ratio
n of
the
nucl
eus
and
mito
chon
-dr
ia, a
nd s
truc
ture
of m
yelin
sh
eath
EA re
vers
ed th
e m
orph
olog
ical
al
tera
tions
indu
ced
by c
hron
ic
mor
phin
e ad
min
istr
atio
n
2009
Hu
[34]
To e
xam
ine
alte
ratio
ns in
the
firin
g ra
te o
f Dop
amin
e ne
uron
s in
10
0 H
z EA
trea
tmen
t
40 M
ale
Spra
gue–
Daw
ley
rats
100
Hz
EA a
t Zus
anli
(ST3
6) a
nd
Sany
injia
o (S
P6),
30 m
in fo
r 10
day
s
Cond
ition
ed p
lace
pre
fere
nce
EA w
as e
ffect
ive
for t
he tr
eatm
ent
of o
piat
e ad
dict
ion
by n
orm
aliz
-in
g th
e ac
tivity
of V
TA D
A n
euro
ns
2010
Lian
g [5
3]To
find
the
Role
of e
nkep
halin
in
the
nucl
eus
accu
mbe
ns m
edia
t-in
g th
e eff
ects
of E
A
218
Mal
e Sp
ragu
e–D
awle
y ra
ts2
Hz
EA a
t Zus
anli
(ST3
6) a
nd S
any-
injia
o (S
P6),
30 m
in fo
r 1-3
day
sCo
nditi
oned
pla
ce p
refe
renc
eEA
up-
regu
late
d th
e m
RNA
leve
l of
prep
roen
keph
alin
in th
e N
Ac
2010
Lee
[45]
To in
vest
igat
e th
e eff
ect o
f acu
-pu
nctu
re o
n m
orph
ine-
indu
ced
beha
vior
al s
ensi
tizat
ion
and
the
neur
onal
cha
nges
in N
Ac
and
stria
tum
14 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
at S
henm
en (H
T7),
1 m
in fo
r 3 d
ays
Mor
phin
e-in
duce
d ch
ange
s of
lo
com
otor
act
ivity
and
Fos
ex
pres
sion
acup
unct
ure
supp
ress
ed th
e m
orph
ine-
indu
ced
incr
ease
s in
the
loco
mot
or a
ctiv
ity a
nd
Fos
expr
essi
on in
the
NA
c an
d st
riatu
m
Page 15 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 6
cont
inue
d
Publ
icat
ion
year
; firs
t au
thor
Obj
ectiv
esSu
bjec
tsSt
imul
ated
acu
poin
ts (a
cupu
nc-
ture
type
, acu
poin
ts, f
requ
ency
)A
sses
smen
tsO
utco
mes
2011
Li [4
8]To
obs
erve
whe
ther
EA
cou
ld
mod
ulat
e th
e im
mun
e st
atus
of
mor
phin
e de
pend
ence
and
w
ithdr
awal
mic
e
40 M
ale
BALB
/c m
ice
2 H
z EA
at Z
usan
li (S
T36)
and
San
y-in
jiao
(SP6
), 30
min
for 5
day
sSp
leni
c T
Lym
phoc
yte
Prol
if-er
atio
n, IL
-2 P
rodu
ctio
n, C
D4+
/C
D8+
Rat
io
EA ra
ised
IL-2
and
nor
mal
ized
ch
roni
c m
orph
ine
expo
sure
-in
duce
d im
mun
e dy
sfun
ctio
ns
2011
Li [5
1]To
inve
stig
ate
the
effec
t of 2
an
d 10
0 H
z EA
of t
he s
leep
di
stur
banc
e du
ring
mor
phin
e w
ithdr
awal
15 M
ale
Spra
gue–
Daw
ley
rats
2 an
d 10
0 H
z EA
at Z
usan
li (S
T36)
an
d Sa
nyin
jiao
(SP6
), 30
min
tw
ice
a da
y fo
r 3 d
ays
Elec
troe
ncep
halo
gram
and
ele
c-tr
omyo
gram
EA d
ecre
ased
NRE
M/R
EM a
nd to
tal
slee
p tim
e, w
hile
the
slee
p la
tenc
y pr
olon
ged
sign
ifica
ntly
dur
ing
acut
e m
orph
ine
with
draw
al
2011
Wan
g [7
6]To
find
the
optim
um p
roto
col
for E
A e
ffect
ive
for a
llevi
atin
g w
ithdr
awal
syn
drom
e
40 M
ale
Spra
gue–
Daw
ley
rats
100
Hz
EA a
t Zus
anli
(ST3
6) a
nd
Sany
injia
o (S
P6) f
or 3
0 m
inCo
nditi
oned
pla
ce p
refe
renc
eEA
dow
n-re
gula
ted
of p
-CRE
B an
d ac
cele
rate
d of
dyn
orph
in s
ynth
e-si
s in
spi
nal c
ord
2011
Xia
[81]
To in
vest
igat
e w
heth
er E
A b
y its
elf
will
pro
duce
som
e re
war
ding
eff
ect
44 M
ale
Spra
gue–
Daw
ley
rats
2 H
z EA
at Z
usan
li (S
T36)
and
Sa
nyin
jiao
(SP6
) for
30
min
Cond
ition
ed p
lace
pre
fere
nce
EA w
as c
apab
le o
f ind
ucin
g C
PP in
th
e ra
t via
the
activ
atio
n of
the
endo
geno
us o
pioi
d-, c
anna
bi-
noid
- and
dop
amin
e-sy
stem
s
2012
Lee
[47]
To in
vest
igat
e th
e ro
le o
f acu
-pu
nctu
re in
the
rein
stat
emen
t of
mor
phin
e se
ekin
g
15 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
, Yan
ggu
(SI5
) or
Yang
xi (L
I5) f
or 1
min
Mor
phin
e re
inst
atem
ent
acup
unct
ure
atte
nuat
ed th
e re
in-
stat
emen
t of m
orph
ine
seek
ing
beha
vior
by
bloc
king
the
GA
BA
rece
ptor
ant
agon
ists
2013
Lee
[46]
To in
vest
igat
e w
heth
er a
cupu
nc-
ture
cou
ld s
uppr
ess
the
rein
-st
atem
ent o
f mor
phin
e-se
ekin
g be
havi
or
28 M
ale
Spra
gue–
Daw
ley
rats
Acu
punc
ture
, Yan
ggu
(SI5
) or
Yang
xi (L
I5) o
r Zus
anli
(ST3
6) fo
r 1
min
Mor
phin
e-se
ekin
g be
havi
orac
upun
ctur
e su
ppre
ssed
mor
phin
e in
ject
ion
perf
ectly
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic: i
n th
e de
ltoid
foss
a at
the
junc
tion
of th
e in
fra-
antih
elix
cru
s an
d th
e m
edia
l ord
er o
f the
hel
ix, l
ung:
in th
e ce
nter
of t
he c
avum
con
cha,
live
r: lo
cate
d in
the
post
erio
r to
uppe
r por
tion
of th
e he
lix c
rus,
kidn
ey: i
n th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Page 16 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 7
Ori
gina
l inv
esti
gati
ons
of a
cupu
nctu
re th
erap
y eff
ects
in p
oly-
drug
and
oth
er s
ubst
ance
abu
sers
(NA
not a
vaila
ble)
Publ
icat
ion
year
; firs
t aut
hor
Obj
ectiv
esSu
bjec
tsSt
imul
ated
acu
poin
ts (a
cu-
punc
ture
type
, acu
poin
ts,
freq
uenc
y)
Ass
essm
ents
Out
com
es
2000
Russ
ell [
68]
To c
ompa
re th
e be
havi
or o
f ad
dict
s in
a tr
eatm
ent c
ente
r w
ith a
rchi
ved
info
rmat
ion
from
no
-acu
punc
ture
(NA
) pat
ient
s
86 P
atie
nts
(Met
ham
phet
a-m
ine
was
the
prim
ary
drug
of
cho
ice
for 4
4)
AA
at 5
NA
DA
poi
nts,
45 m
in
for 9
wee
ksPr
ogra
m re
tent
ion,
new
ar
rest
s in
curr
ed, d
rug-
pos-
itive
urin
alys
is re
sults
, and
nu
mbe
r of d
ays
need
ed
to p
rogr
ess
from
ent
ry
leve
l to
seco
ndar
y le
vel
trea
tmen
t
Acu
punc
ture
impr
oved
pr
ogra
m re
tent
ion
up to
30
day
s am
ong
met
h-am
phet
amin
e-ad
dict
ed
patie
nts
2000
Song
Ber
nste
in [1
4]To
exp
lore
the
mea
ning
of
subs
tanc
e ab
user
s’ ex
perie
nce
whi
le re
ceiv
ing
acup
unct
ure
as a
par
t of t
he tr
eatm
ent f
or
subs
tanc
e de
pend
ence
8 H
uman
Sub
ject
sA
A, (
NA
), on
ce a
wee
kIn
terv
iew
s, re
sear
cher
’s fie
ld
note
s, an
d de
mog
raph
ic
data
obt
aine
d fro
m th
e pa
rtic
ipan
ts’ m
edic
al
reco
rds
Acu
punc
ture
cau
sed
antic
ipa-
tion
of p
ain,
app
rehe
n-si
on c
once
rnin
g a
new
ex
perie
nce,
moo
d el
evat
ion,
in
abili
ty to
des
crib
e th
e ex
perie
nce,
phy
sica
l se
nsat
ion,
rela
xatio
n, a
nd
impr
oved
sle
ep
2004
Berm
an [1
3]To
com
pare
the
expe
rimen
tal
NA
DA
-Acu
deto
x pr
otoc
ol w
ith
a no
n-sp
ecifi
c he
lix c
ontr
ol
prot
ocol
in a
rand
omiz
ed tr
ial
174
Inm
ates
Aur
icul
ar a
cupu
nctu
re a
t 5
NA
DA
poi
nts,
40 m
in fo
r 4
wee
ks
A s
impl
e dr
ug u
se q
uest
ion-
naire
, the
Acu
punc
ture
Tr
eatm
ent A
sses
smen
t Sc
ale
(ATA
S), a
Sw
edis
h re
sear
ch v
ersi
on o
f the
Sy
mpt
om C
heck
Lis
t 90
Acu
punc
ture
had
no
sig-
nific
ant e
ffici
ency
ove
r the
pl
aceb
o
2005
Jans
sen
[36]
To e
xam
ine
the
utili
ty o
f ac
upun
ctur
e tr
eatm
ent i
n re
duci
ng s
ubst
ance
use
in
the
mar
gina
lized
, tra
nsie
nt
popu
latio
n
261
Hum
ans
AA
at 5
NA
DA
poi
nts
for
40 m
inQ
uest
ionn
aire
, Dru
g us
e sy
mpt
omat
olog
y, s
ever
ity
of w
ithdr
awal
sym
ptom
s
Acu
punc
ture
cau
sed
redu
ctio
n in
ove
rall
use
of
subs
tanc
es a
nd d
ecre
ase
in in
tens
ity o
f with
draw
al
sym
ptom
s
2006
Tian
[73]
To e
xam
ine
the
effica
cy o
f AA
in
add
ition
to u
sual
car
e in
su
bsta
nce
abus
e tr
eatm
ent
17 H
uman
sA
A a
t 5-p
oint
s N
AD
A, o
nce
a w
eek
for 6
con
secu
tive
wee
ks
The
Hop
kins
Sym
ptom
C
heck
list (
SCL-
20) d
epre
s-si
on s
cale
, brie
f sub
stan
ce
crav
ing
scal
e
ther
e w
as a
pos
itive
resp
onse
to
the
spec
ific
auric
ular
ac
upre
ssur
e tr
eatm
ent o
n ps
ycho
logi
cal d
istr
ess,
crav
-in
g, a
nd d
rug/
alco
hol u
se
mea
sure
s
2007
Cour
bass
on a
nd C
hris
tine
[26]
To e
valu
ate
the
bene
fits
of a
dd-
ing
AA
to a
21-
day
outp
atie
nt
stru
ctur
ed p
sych
oedu
catio
nal
trea
tmen
t pro
gram
185
Wom
en w
ith c
oncu
rren
t su
bsta
nce
use
prob
lem
s, an
xiet
y, a
nd d
epre
ssio
n
AA
at 5
poi
nts
NA
DA
for
45 m
in, 3
tim
es a
wee
kPh
ysio
logi
cal c
ravi
ngs
for
subs
tanc
es, d
epre
ssio
n,
and
anxi
ety
AA
as
an a
djun
ct th
erap
y to
a
com
preh
ensi
ve p
sych
oe-
duca
tiona
l tre
atm
ent w
as
effec
tive
and
mor
e vi
able
tr
eatm
ent a
ltern
ativ
e to
an
xiol
ytic
s
Page 17 of 20Motlagh et al. Chin Med (2016) 11:16
Tabl
e 7
cont
inue
d
Publ
icat
ion
year
; firs
t aut
hor
Obj
ectiv
esSu
bjec
tsSt
imul
ated
acu
poin
ts (a
cu-
punc
ture
type
, acu
poin
ts,
freq
uenc
y)
Ass
essm
ents
Out
com
es
2009
Ash
ton
[9]
To d
escr
ibe
the
char
acte
ristic
s of
cl
ient
s ch
oosi
ng A
A o
r cou
n-se
ling
to tr
eat d
epen
denc
e at
a
UK
self-
refe
rral
cen
ter
162
Hum
ans,
n =
36
acup
unct
ure,
n =
126
co
unse
lling
AA
at 5
-poi
nts
NA
DA
, 45
min
, on
ce a
wee
k fo
r 11
wee
ksPs
ycho
met
ric v
aria
bles
(anx
i-et
y, d
epre
ssio
n, d
epen
d-en
ce s
ever
ity, r
eadi
ness
to
chan
ge),
and
alco
hol a
nd
drug
con
sum
ptio
n
Acu
punc
ture
was
pre
ferr
ed b
y cl
ient
s an
d fo
llow
up
asse
ss-
men
ts s
how
ed a
sig
nific
ant
decr
ease
in p
sych
olog
ical
di
stre
ss a
nd re
duct
ion
of
alco
hol c
onsu
mpt
ion
2014
, 20
10C
hang
and
Bei
-Hun
g [2
3,
24]
Exam
ine
the
effec
ts o
f acu
punc
-tu
re a
nd re
late
d re
spon
se (R
R)
on re
duci
ng c
ravi
ng
23 A
cupu
nctu
re, 2
3 RR
, 21
cont
rols
(hom
eles
s m
ilita
ry
vete
rans
)
AA
at 5
-poi
nts
NA
DA
, 45
min
tw
ice
a w
eek
Deg
ree
of c
ravi
ng a
nd a
nxi-
ety
leve
lsac
upun
ctur
e an
d th
e re
laxa
-tio
n re
duce
d cr
avin
g an
d an
xiet
y le
vels
2011
Blac
k, S
. [7]
To te
st th
e hy
poth
esis
if A
A
redu
ces
the
anxi
ety
asso
ciat
ed
with
with
draw
al fr
om p
sych
o-ac
tive
drug
s.
101
Patie
nts
recr
uite
d fro
m
an a
ddic
tion
trea
tmen
t se
rvic
e
AA
at 5
-poi
nts
NA
DA
45
min
fo
r 3 d
ays
Anx
iety
sta
te b
y us
ing
a pr
etes
t–po
stte
st tr
eatm
ent
desi
gn
The
NA
DA
pro
toco
l was
not
m
ore
effec
tive
than
sha
m o
r tr
eatm
ent s
ettin
g co
ntro
l in
redu
cing
anx
iety
2012
Jans
sen
[35]
To te
st th
e ab
ility
of m
ater
nal
acup
unct
ure
trea
tmen
t am
ong
mot
hers
who
use
illic
it dr
ugs
to re
duce
the
frequ
ency
and
se
verit
y of
with
draw
al s
ymp-
tom
s am
ong
thei
r new
born
s
50 W
omen
usi
ng a
cupu
nc-
ture
, 39
wom
en s
tand
ard
care
AA
at 5
-poi
nts
NA
DA
for
45 m
inD
ays
of n
eona
tal m
orph
ine
trea
tmen
t for
sym
ptom
s of
neo
nata
l with
draw
al.
Neo
nata
l out
com
es
incl
uded
adm
issi
on to
a
neon
atal
ICU
and
tran
sfer
to
fost
er c
are
leng
th o
f tre
atm
ent f
or n
eo-
nata
l abs
tinen
ce s
yndr
ome
show
ed n
o effi
cien
cy o
f ac
upun
ctur
e
2012
Pene
tar [
66]
To in
vest
igat
e th
e eff
ects
of T
EAS
on d
rug
addi
ctio
n9
Coca
ine-
depe
nden
t, 11
Ca
nnab
is-d
epen
dent
2 an
d 10
0 H
z at
Nei
guan
(P
C6)
/Wai
guan
(TH
5) a
nd
Heg
u (L
I4)/
Laog
ong
(PC
8)
stim
ulat
ion,
Tw
ice-
daily
30
-min
ute
sess
ions
of f
or
3.5
days
Dru
g us
e an
d dr
ug c
ravi
ngs,
cue-
indu
ced
crav
ing
EEG
ev
alua
tion,
and
P30
0 ER
P
TEA
S di
d no
t red
uce
drug
use
or
dru
g cr
avin
gs, o
r alte
r the
ER
P pe
ak v
olta
ge o
r lat
ency
bu
t mod
ulat
ed s
ever
al s
elf
repo
rted
mea
sure
s of
moo
d an
d an
xiet
y
2014
Berg
dah
[12]
To d
escr
ibe
patie
nts’
expe
ri-en
ces
of re
ceiv
ing
AA
dur
ing
prot
ract
ed w
ithdr
awal
15 H
uman
sub
ject
sA
A a
t 5-p
oint
s N
AD
A 4
0 m
in,
twic
e a
wee
k fo
r 5 w
eeks
Inte
rvie
wA
A re
info
rced
sen
se o
f re
laxa
tion
and
wel
l-bei
ng,
peac
eful
ness
and
har
mon
y,
and
new
beh
avio
rs
Acup
oint
s in
NA
DA
pro
toco
l are
loca
ted
at (s
ympa
thet
ic: i
n th
e de
ltoid
foss
a at
the
junc
tion
of th
e in
fra-
antih
elix
cru
s an
d th
e m
edia
l ord
er o
f the
hel
ix, l
ung:
in th
e ce
nter
of t
he c
avum
con
cha,
live
r: lo
cate
d in
the
post
erio
r to
uppe
r por
tion
of th
e he
lix c
rus,
kidn
ey: i
n th
e cl
eft b
etw
een
the
uppe
r pla
teau
, and
the
helix
)
Page 18 of 20Motlagh et al. Chin Med (2016) 11:16
indicate that acupuncture at Shenmen (HT7), Zusanli (ST36), and Sanyinjiao (SP6) acupoints can affect drug-induced physiological activities.
Authors’ contributionsFEM, FI, RAR, and TS designed and conceived the study. FEM, RR, TS, FI, and RAR carried out the article searches. FEM performed the statistical analysis. FEM and TS wrote the manuscript. FI, RAR, and HH revised the manuscript. All authors read and approved the final manuscript.
Author details1 Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia. 2 Centre for Innovation in Medical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia. 3 Centre of Addiction Sciences, University of Malaya, 21st Floor, Wisma Research and Development, Jalan Pantai Baru, 59200 Kuala Lumpur, Malaysia. 4 Shahid Beheshti University of Medical Sciences, Tehran, Iran.
AcknowledgementsWe would like to acknowledge and thank the University of Malaya and Min-istry of Higher Education for providing High Impact Research Grant, account codes E000007-20001 to fund this project.
Competing interestsThe authors declare that they have no competing interests.
Received: 12 September 2014 Accepted: 29 March 2016
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