Efficacy of acupuncture for patients with moderate to severe tobacco dependence: study protocol for a randomized controlled trial

Abstract

Background

Tobacco dependence poses significant health and economic burdens globally, with over one billion smokers and eight million deaths annually. Current smoking cessation strategies, including pharmacotherapy and behavioral treatments, often have limited efficacy and potential side effects. Acupuncture, a potential alternative treatment, has shown promise in previous studies, but its mechanism and long-term effects on craving remain unclear.

Methods/design

This two-center, randomized, controlled clinical trial will enroll 192 patients with moderate to severe tobacco dependence and randomly assign them to Acupuncture, sham-Acupuncture, or basic smoking cessation intervention groups in a 1:1:1 ratio. Blinding will be performed on participants in the Acupuncture, sham-Acupuncture groups and statistical analysts. The 12-week trial will involve 8 weeks of treatment and 4 weeks of follow-up. The primary outcome is abstinence rate at week 8. Secondary outcomes include assessment with the following instruments: craving levels via the Visual Analog Scale and Tobacco Craving Questionnaire, withdrawal symptoms via the Minnesota Withdrawal Scale, working memory via the Sternberg paradigm, and response inhibition ability via the Go/NoGo task. Adverse events will be recorded. The study will adhere to SPIRIT guidelines.

Discussion

This trial will investigate the efficacy of acupuncture for tobacco dependence by including a sham control and examining long-term craving effects. Findings will contribute to understanding the potential of acupuncture as a safe and effective treatment option for tobacco dependence.

Trial registration

This trial was registered on the International Traditional Medicine Clinical Trial Registry (Registration number: ITMCTR2024000817) on November 18, 2024.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-025-05223-z.

Background

Tobacco dependence, a major cause of preventable health issues, is a harmful pattern of tobacco use causing significant health and economic burdens. There are over a billion smokers worldwide [1]. Annually, over 8 million die from tobacco use [2]. Besides, the smoking’s total economic cost, including health spending and productivity loss, is about US$ 1.4 trillion, 1.8% of global gross domestic product [3]. In China, over 300 million individuals live with tobacco dependence [4].

The key strategies to quit smoking include pharmacotherapy (nicotine replacement therapy (NRT) and non-NRT, psychological counselling and behavioral treatments, as multiple studies have shown that these approaches boost the smoking cessation success rate to different extents [5]. Nevertheless, such treatments may entail possible adverse effects like chest discomfort, sleeplessness, oral dryness, cutaneous hypersensitivity, and gastrointestinal disturbances [6], potentially diminishing patient adherence and, crucially, the effectiveness of smoking cessation. In addition, over half of the patients with tobacco dependence failed to quit smoking after these treatments [2]. Currently, there is a scarcity of safe and effective intervention measures with little side effects for tobacco dependence.

Acupuncture (Acup) was initially employed in tobacco cessation in Hong Kong in 1973 [7]. This prompted numerous investigations into the effectiveness and safety of Acup for smoking cessation. Our prior researches [8, 9] indicated that Acup serves as a secure and potent therapy for quitting smoking, achieving a 43.00% carbon monoxide (CO)-confirmed 24-hour point abstinence rate at 24 week, comparable to NRT. And a latter study also finds a 40.9% self-reported abstaining rate of participants after 8-weeks Acup treatment [10]. However, despite a wealth of studies providing evidence that Acup can effectively enhance the tobacco abstinence rate, the mechanism behind Acup for smoking cessation remains unclear and these researches did not include sham-Acup as a control group to investigate the potential placebo effect of Acup on tobacco cessation.

Smoking craving, defined as a strong desire to pursue tobacco products [11], is a typical manifestation of tobacco dependence and one of the main symptoms during withdrawal [12]. It often foretells future substance use [13] and is considered a crucial marker for smoking cessation therapies [14]. Smokers with more intense levels of craving during abstinence have increased risk of relapse and reducing craving after withdrawal can increase the quit rate [15]. The results from a previous study [16] indicated a significant immediate effect of Acup on smoking craving, showing that Acup could reduce Minnesota Nicotine Withdrawal Scale (MNWS) and Questionnaire of Smoking Urges and identified salience network as key brain areas, which consists of anterior cingulate cortex and insula, prefrontal cortex, visual cortex and cerebellum. However, the long term-effects of Acup on tobacco craving have yet to be explored.

Therefore, this meticulously designed randomized controlled trial is formulated to encompass a sham-Acup group as one of the control cohorts, with the objective of scrutinizing the impact of sham-Acup on tobacco cessation. Additionally, the trial aims to examine the long-term effects of Acup on tobacco craving by systematically assessing the degree of tobacco craving at consecutive visitation points throughout the 8-week intervention period and the subsequent 4-week follow-up phase.

Methods

Study design

This two-center, randomized, controlled clinical trial will be conducted at the Acupuncture and Moxibustion Hospital and Wang Jing hospital, China academy of Chinese Medical Sciences. A planned of 192 patients meeting the inclusion criteria will be enrolled in our study and randomly divided into Acup group, sham-Acup group and basic smoking cessation intervention (BSCI) group in a 1:1:1 ratio. The trial duration will be 12 weeks, comprising 8 weeks of treatment and 4 weeks of follow-up. The study protocol has been approved by The Medical Ethics Committee of Xiyuan Hospital, China Academy of Traditional Chinese Medicine and registered on the International Traditional Medicine Clinical Trial Registry (Registration number: ITMCTR2024000817. Date: November 18, 2024). The reporting of this study protocol will adhere to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) [17] (see Supplementary Material 1). The flowchart is shown in Fig. 1.

Fig. 1.

Flow chart of the study procedure

Recruitment

This trial will be conducted at Acupuncture and Moxibustion Hospital and Wang Jing hospital, China academy of Chinese Medical Sciences. Eligible participants will be recruited through multiple channels, including trial sites, local newspapers, a smoking cessation hotline, community events, websites, and referrals from other medical institutions. The diagnostic criteria for tobacco dependence will be based on the Guideline on China clinical smoking cessation (2015) [18]. Upon arrival at the hospital, participants will first receive informed consent. Subsequently, they will be evaluated by professional researchers and complete a preliminary screening form. Those who pass the initial screening will undergo baseline assessments and additional examinations for further selection. Participants who meet the inclusion criteria will then be confirmed for random assignment to one of three study groups.

Diagnostic criteria

Based on the Guideline on China clinical smoking cessation (2015) [18], the clinical diagnostic criteria for tobacco dependence are as follows: A diagnosis can be made if an individual has experienced or exhibited at least 3 of the following 6 items within the past year.

1. A strong craving for smoking.

2. Difficulty in controlling smoking behavior.

3. The emergence of withdrawal symptoms upon cessation or reduction of smoking.

4. Manifestation of tolerance to tobacco, which means an increased amount of smoking is required to achieve the same level of satisfaction previously obtained from a smaller quantity of tobacco.

5. Giving up or reducing other activities and interests due to smoking.

6. Persisting in smoking despite awareness of the harmful consequences.

Inclusion criteria

1. Meet the diagnostic criteria for tobacco dependence.

2. Age between 18 and 75 years old, no gender restrictions.

3. A smoking history of at least 1 year, with smoking at least 10 cigarettes per day in the past month.

4. Exhaled CO measurement of at least 6 ppm.

5. The Fagerström Test for Nicotine Dependence (FTND) [19] indicates moderate to severe nicotine dependence.

6. No Acup treatment within 30 days prior to entering the study.

7. Willing to participate in this study and sign the informed consent form.

Exclusion criteria

1. Individuals who have received other smoking cessation treatments in the past six months.

2. Pregnant or breastfeeding women.

3. Suffering from severe heart, lung, brain, or hematological disorders.

4. Individuals with substance abuse or dependence other than nicotine.

5. Individuals deemed by the researchers to have other medical or mental conditions that prevent them from meeting the study requirements.

6. Individuals with physical disabilities or medical issues that affect behavioral testing.

7. Individuals who have consumed alcohol within 48 hours prior to the trial.

Withdrawal criteria

1. Occurrence of serious adverse events.

2. Patient withdrawal of informed consent.

3. Discovery during the study that the treatment method is too ineffective to have clinical research value.

4. Poor patient compliance, including self-withdrawal during the course of treatment.

5. Concurrent other diseases and receiving Acup treatment.

Sample size

This study is designed as a superiority trial and the sample size is calculated based on the primary outcome, CO-confirmed abstinence rate. According to the results of the previous studies [20, 21], the abstinence rate for smoking cessation in the Acup group, the sham-Acup group and the BSCI group are 25%, 9% and 3% respectively. We used a two-sided test of difference and calculated the sample size using PASS 15 software. With α = 0.025, β = 0.2, and Power = 0.8, a total of 159 participants are required. Considering a potential dropout rate of 20% and a 1:1:1 ratio for the three groups, each group size will be set at 64.

Randomization and allocation concealment

Using the random number table (Random sequence generated by the SPSS 26.0 software), patients will be randomly assigned in a 1:1:1 ratio to the Acup group, the sham-Acup group or the BSCI group. The randomization scheme will be securely enclosed in a sealed opaque envelope with a unique code. The envelope will be handed over to the recruiting researcher. At the time of subject enrollment, the envelope corresponding to the subject’s assigned number will be opened to reveal the group allocation information.

Blinding

Blinding will be performed on participants in the Acup group and the sham-Acup group and statistical analysts. Due to the nature of the Acup, the Acupuncturists will not be blinded. Following the conclusion of the intervention, a blind evaluation using Bang’s Blinding Index (BBI) scale will be conducted in the 8th week. The proportion of unblinded participants in the Acup group and the sham-Acup group will be calculated separately, and statistical testing will be performed using Stata 18 software. The BBI index ranges from − 1 to 1, with 0 indicating successful blinding, where the correct rate of guessing is at a random level. A positive BBI index signifies a failure of blinding, with a higher correct rate of guessing than random chance; a negative BBI index indicates successful blinding or a failure of blinding in the opposite direction, which means a higher number of participants incorrectly believe they received the opposite treatment.

Intervention

All three groups of participants receive the 5As model, recommended by the World Health Organization, 10 min each time, once a week [22]. The 5As includes Ask (Systematically identify all tobacco users at every visit), Advise (Persuade all tobacco users that they need to quit), Assess (Determine readiness to make a quit attempt), Assist (Help the patient with a quit plan) and Arrange (Schedule follow-up contacts or a referral to specialist support).

Acup group

1. Acupoints: Baihui (GV 20), Lieque (LU 7), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). Except for GV 20, the other acupoints will be needled bilaterally. The acupoints were selected based on the previous researches [8, 16, 23] and Locations of all the acupoints are in line with the National Standard of the People’s Republic of China’s (GB/T 12346 − 2021) [24]. Details of location of acupoints are provided in the Table 1.

2. Body position: The subjects adopt a supine position with full exposure of the selected acupoints.

3. Procedure: Acupoints will be disinfected with 75% alcohol. Disposable foam pads are applied to all acupoints. Insert a 0.25 mm ´ 25 mm filiform needle through the foam pad at a 45° angle to the back, 5-20 mm deep at Baihui (GV 20). For Lieque (LU 7), insert a 0.25 mm ´ 40 mm filiform needle through the foam pad transversely towards the wrist, 15-20 mm deep, against the direction of the Lung Meridian. For Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6), and Taichong (LR 3), insert 0.25 mm ´40 mm filiform needles through the f oam pad perpendicularly, 20-30 mm deep. The needles will be rotated at a speed of 60 to 90 times per minute at an angle of 90° to 180° to achieve the sensation of “De Qi”,including feelings of soreness, numbness, heaviness, and distention. Connect the KWD-808Ⅰ pulse electrotherapy device (Changzhou Wujin Great Wall Medical Instrument Co., Ltd.) between the same-side Lieque (LU 7) and Zusanli (ST 36). Use continuous wave with a frequency of 15 Hz, and adjust the intensity according to the patient's tolerance. Retain the needles for 30 minutes (other acupoints will not be treated with electroacupuncture). Participants in the Acup group receive treatments for 8 weeks, 3 times per week, every other day.

Table 1.

Location of acupoints and non-acupoints used in this trial

Intervention group	Acupoints/Non-acupoint	location
Acup	Baihui (GV 20)	The vertex of the head at the sagittal midline of the calp, at the midpoint of the line that connects the apexes of the ears.
	Lieque (LU 7)	On the radial aspect of the forearm, be tween the tendons of the abductor pollicis longus and the extensor pollicis brevis muscles, in the groove for the abductor pollicis longus tendon, 1.5 cun superior to the palmar wrist crease.
	Hegu (LI 4)	Located on the back of the hand, at the midpoint of the second metacarpal bone on the radial side.
	Zusanli (ST 36)	Located on the anterior lateral side of the shank, 3 cun below ST35 (Dubi), one horizontally placed finger distance lateral to the anterior border of the tibia (the middle finger).
	Sanyinjiao (SP 6)	Located on the medial side of the shank, 3 cun above the medial malleolus, by the posterior border of the tibia.
	Taichong (LR 3)	Located on the dorsal side of the foot and sunken behind the first metatarsal space.
Sham-Acup	Non-acupoint 1	The midpoint between the medial epicondyle of the humerus and the styloid process of the ulna.
	Non-acupoint 2	On the anterior medial side of the upper arm, at the junction of the deltoid muscle and the biceps brachii.
	Non-acupoint 3	On the thigh, 0.8 transverse finger width to the medial side from the midpoint of the line connecting the anterior superior iliac spine and the lateral end of the patellar base.
	Non-acupoint 4	On the lateral side of the lower leg, 1 transverse finger width to the lateral side from the Zusanli (ST36) acupoint, between the Stomach Meridian and the Gallbladder Meridian.
	Non-acupoint 5	On the lateral side of the lower leg, 3 transverse finger widths to the upper side from the tip of the lateral malleolus, between the Stomach Meridian and the Gallbladder Meridian.

Sham-Acup group

1. Non-acupoints: Described in the Table 1 and illustrated in Fig. 2. Both side of non-acupoints are needled. The location of these non-acupoints are neither at any meridians nor acupoints.

2. Body position: The subjects adopt a supine position with full exposure of the selected acupoints.

3. Procedure: Non-acupoints will be disinfected with 75% alcohol. The sham needles are designed with a blunt tip, and their packaging and appearance are identical to those of the Acup needles used in the Acup group. Disposable foam pads are applied to all non-acupoint locations. After the sham needle punctures through the foam pad, it merely touches the skin without penetrating it, and no manipulation is performed. At non-acupoint 1 and 5, a pulse electrotherapy device is connected, with the electrical stimulation parameters being the same as those in the Acup group. The needles are retained for 30 minutes before removal. Participants in the shan-Acup group receive treatments for 8 weeks, 3 times per week, every other day.

Fig. 2.

Illustration of acupoints and non-acupoints

Basic smoking cessation intervention group

Participants in the BSCI group receive the 5As only.

Outcome measures

Basic information

1. Demographic information: Gender, age, ethnicity, marital status, educational level, and self-rated physical health score.

2. Smoking-related data: Daily cigarette consumption, duration of smoking, pre-treatment FTND score, and pre-treatment CO concentration.

3. Smoking cessation history: The number of previous quit attempts and confidence in the current quit attempt.

Primary outcome measure

The primary outcome is abstinence rate at week 8 (Abstinence rate: number of individuals who quit smoking (exhaled CO concentration < 6 ppm)/total number of subjects in the group * 100%).

Secondary outcomes measures

Craving

Smoking-related cues, such as various brands of cigarettes, cigarette packs, smoke, ash, ashtrays, individuals smoking, and smoking-related scenes, as well as tobacco retail stores. These diverse forms of smoking cues are presented to the subjects at random in a duration of 1 s each. The Visual Analog Scale (VAS) and the Tobacco Craving Questionnaire are utilized to assess the subjects’ current craving for smoking. This protocol has been extensively validated and widely recognized in numerous studies as an effective method for evaluating the subjects’ craving for nicotine and withdrawal symptoms.

Withdrawal symptoms

The MNWS will be used to assess the severity of withdrawal symptoms.

Sternberg paradigm

The working memory task selected for this study is an adapted version of the Sternberg paradigm. The task begins with a fixation cross presented in red for 500 ms, followed by the presentation of the encoding stimulus for 1000 ms. The difficulty of the stimulus is varied, consisting of 1-, 3-, or 5-digit numbers, with one of these number sequences presented randomly. Prior to the task, a set of instructions is displayed on the screen for 10 s to prepare the participants. After the instructions, a blank screen appears for 1000 ms, followed by the presentation of the probe digit. Participants are required to judge whether the presented probe digit was part of the encoding stimulus. The probe digits are composed of 50% digits from the encoding stimulus and 50% digits that are different from the encoding stimulus. If the probe digit is part of the encoding stimulus, participants are instructed to press the “1” key; conversely, if the probe digit is not part of the encoding stimulus, participants are instructed to press the “3” key. The task consists of 60 trials, with the 1-, 3-, and 5-digit encoding stimuli each accounting for one-third of the trials, presented in a random order. Throughout the experiment, participants are required to respond as quickly and accurately as possible. Before the formal task, all participants complete 3 practice trials to familiarize themselves with the experimental requirements. The computer records the reaction results, and the viewing distance for participants is 1 m. Specific operational details are shown in Fig. 3.

Go/NoGo task

The participants’ response inhibition ability is assessed with the Go/NoGo task. The task procedure is programmed using E-prime 2.0, and participants are instructed to understand the content of the task and respond via key presses. Prior to the task, a set of instructions is displayed on the screen for 10 s to prepare the participants. After the instructions, four white letters (A, B, C, D) appear randomly in the center of the screen against a black background, with each letter constituting a stimulus. The letters remain on the screen for 600 milliseconds, followed by a white cross that appears for 300 milliseconds. Participants are required to respond to the appearance of the letters by pressing the “J” key with their index finger, but they should not press the key for consecutive repetitions of the same letter (No-Go stimulus). The computer records the reaction results, and the viewing distance for participants is 1 m. The task consists of 60 trials, with the order of stimulus presentation randomized. Throughout the experiment, participants are required to respond as quickly and accurately as possible. Before the formal task, all participants complete 3 practice trials to familiarize themselves with the experimental requirements. Specific operational details are shown in Fig. 4.

Fig. 4.

Procedure for the Go/NoGo task

Fig. 3.

Procedure for the Sternberg paradigm

Safety evaluation

This study records the occurrence of any adverse events during the treatment process. If an adverse event occurs, the details will be documented, including symptoms of the adverse event, severity of the adverse events, date of occurrence, measures taken to address the adverse event, relationship to the treatment, course of action and outcome.

Adverse Event Categories.

1. Safe: No discomfort experienced, and physiological indicators are normal.

2. Relatively Safe: Mild discomfort due to nervousness, with normal physiological indicators.

3. Safety Concerns: Mild dizziness, vomiting, or slight changes in physiological indicators during the treatment.

4. Severe Adverse Reaction (Immediate Study Termination): Serious conditions such as cerebrovascular accidents, myocardial infarction, or significant changes in physiological indicators.

The details of outcome measurement time points are provided in Table 2.

Table 2.

Details of the planned visit schedule

Task	Baseline period	Treatment period					Follow-up period
	Visit 0	Visit 1	Visit 2	Visit 3	Visit 4	Visit 5	Visit 6
	Week 0	Week 1	Week 2	Week 4	Week 6	Week 8	Week 12
Signing informed consent	√	√	√	√	√	√	√
Random assignment	√
Demographic characteristics	√
Smoking-related data	√	√	√	√	√	√	√
Smoking cessation history	√
Medical history	√
Exhaled CO concentration	√	√	√	√	√	√	√
MNWS		√	√	√	√	√	√
VAS	√	√	√	√	√	√	√
Tobacco Craving Questionnaire		√	√	√	√	√	√
Sternberg Task	√	√	√	√	√	√	√
Go/No-Go Task	√	√	√	√	√	√	√
Adverse event record		√	√	√	√	√	√

Data management

This research employs a combination of Case Report Form (CRF) data collection and electronic data management. The CRF for each participant is promptly completed. Any corrections must not change the original records but should be supplemented with an explanation, signed by the physician involved in the clinical study and dated. Completed CRFs, after being reviewed by clinical monitors, are transferred to the data statistics unit for data entry and management. A designated data manager is responsible for data entry and management. To ensure data accuracy, two data managers independently perform dual data entry and cross-checking. No modifications are made to the data after entry. For any queries arising from the CRFs, the data manager will generate a Data Query Form (DQF) and send inquiries to the researchers through clinical monitors. Researchers should respond promptly and return the answers. The data manager will make data modifications, confirmations, and entries based on the researchers’ responses, and may issue additional DQFs if necessary. Researchers are responsible for answering the questions in the DQFs. A data inspection report is completed. After the completion of the data blind review report, the database is locked and submitted for statistical analysis by the research team.

Statistical analysis

This study employs an Intention-to-Treat analysis, where all dropouts are considered as treatment failures.

Statistical analyses are conducted using SPSS version 26.0. For the behavioral data analysis in the Sternberg task, a 3 (group: Acup, sham-Acup, basic intervention) × 3 (task category: 1-digit, 3-digits, 5-digits/red, green, blue) repeated measures ANOVA is used to assess the accuracy and reaction times of participants under different experimental conditions. In the Go/NoGo task behavioral data analysis, independent samples t-tests are first conducted to determine if there are differences in Go task reaction times between groups. Subsequently, a 3 (group: Acup, sham-Acup, basic intervention) * 2 (task category: Go task accuracy/NoGo accuracy/location task and number matching task) repeated measures ANOVA is used to compare the accuracy of participants under different experimental conditions. For the analysis of data from scales such as the VAS, Tobacco Craving Questionnaire, and MNWS, repeated measures ANOVA is used to compare differences in craving levels under different experimental conditions. In the statistical analysis process, post-hoc analyses with Bonferroni correction are conducted for significant main effects. For simple effects analysis in significant interactions, the Greenhouse-Geisser correction is applied to adjust the degrees of freedom and p-values when the sphericity assumption is violated. A p-value of less than 0.05 is considered statistically significant.

Missing data will be handled using multiple imputation by chained equations (MICE) with 20 imputations (R’s mice package, v3.15). Key variables including baseline covariates, longitudinal measures (VAS, Tobacco Craving Questionnaire, and MNWS), and dropout timing will be included in the imputation model. Results from imputed datasets will be pooled using Rubin’s rules. Sensitivity analyses with complete-case analysis and last-observation-carried-forward approaches will be conducted to assess robustness.

Categorical data are described using counts and percentages (%), and analyzed using chi-square tests or Fisher’s exact tests. Continuous data are described using “mean ± standard deviation” (). For data that do not meet the assumptions of normality or have unequal variances, the median and interquartile range [M(IQR)] are used for description. For normally distributed continuous data, independent samples t-tests are used for between-group comparisons, and paired samples t-tests are used for within-group pre-post comparisons. For data that do not meet the assumptions of normality, non-parametric rank-sum tests are used, with Wilcoxon rank-sum tests comparing the average ranks of samples between groups and paired samples rank-sum tests used within groups. A p-value of less than 0.05 is considered statistically significant.

Quality control and confidentiality

Develop standard operating procedures for smoking cessation counseling using the 5 A/5R approach [22], Acup, and sham-Acup techniques. Establish standard operating and quality control procedures for all observational indicators required for the study, such as the protocol for exhaled CO detection. Physicians are responsible for guiding patients in filling out self-report content and for measuring and scoring primary observational indicators; researchers review the completed clinical observation forms for diagnostic accuracy, basis of medical judgment, completeness of CRFs, and adherence to clinical operation standards.

Behavioral tests are conducted in a controlled environment shielded from external noise and light, maintained at a constant temperature of (20 ± 3)°C. Prior to the formal test, each participant is given several practice opportunities. Only when the participant fully understands the operational requirements and achieves an accuracy rate of 50% can the formal testing proceed. During the test, a researcher supervises the participant to ensure compliance with the testing protocol.

The research team is composed of relatively stable members who possess professional expertise, qualifications, and capabilities in clinical research. These individuals are selected after a qualification review. Before the start of the clinical study, all personnel involved in the research are organized for training to ensure a thorough understanding and recognition of the clinical research protocol and the specific connotations of each indicator, and to implement all technical standards.

An independent quality control officer will be appointed to oversee data quality, prioritizing remote data monitoring supplemented by on-site verification. Remote monitoring will be conducted every 4 weeks to ensure the timeliness, completeness, and accuracy of clinical data entry. For issues identified during remote monitoring, on-site quality control will be promptly initiated. On-site audits will occur at the following stages: after enrollment of the first 1–3 cases, at 1/4, 1/2, mid-term, 3/4 of enrollment, and before study closure, with a planned frequency of twice annually to ensure overall research quality.

Discussion

Tobacco dependence is widespread, severely impairing, and linked to substantial adverse outcomes. Cognitive and behavioral changes following tobacco withdrawal can decrease self-control, induce cravings, which often lead to relapse [6]. Effective control of post-withdrawal cravings can enhance the rate of successful cessation. A meta-analysis study has shown that Acup can effectively suppress post-withdrawal drug cravings in addictive disorders [25]. including for substances such as methadone [26], heroin [27], alcohol [28] and tobacco [9]. Our previous research indicated that short-term Acup can inhibit tobacco cravings and modulate the functional connectivity of craving-related brain areas [16]. However, the long-term effects of Acup on tobacco cravings are not clear. Therefore, this study was designed to extend the treatment and follow-up period to observe the long-term effects of Acup on tobacco cravings and explore the potential mechanisms of Acup for smoking cessation.

The placebo effect plays a potential role in Acup for smoking cessation, which can affect the evaluation of the efficacy of Acup in this context. To date, there have been no randomized controlled trial that have employed sham Acup as a control group to more accurately assess the effectiveness of Acup for smoking cessation. Therefore, in addition to setting up smoking cessation counseling, which is clinically recommended [2], as a control group, we have also included a sham- Acup group as a control to better investigate the clinical efficacy of Acup for smoking cessation. Moreover, to better blind the participants, we have chosen a one-time use foam pad attached to acupoints/non-acupoints with a blunted sham needle design that produces a sensation upon contact without penetrating the skin. On the other hand, the non-acupoints selected in the sham-Acup group locates neither on any meridians nor acupoints rather than simply using non-penetrating blunted needles at the same acupoints as the Acup group, which can further reduce the likelihood of false-positive results due to stimulation at the acupoints.

The limitations of this trial must be acknowledged. Firstly, partial blinding (blinding of participants in the sham-Acup and Acup groups and statisticians only) may introduce performance bias. We mitigated this risk by employing biochemical outcome (exhaled CO concentration) to measure the primary endpoint which are less susceptible to observer bias and organizing all personnel involved in the research for training to implement all technical standards. Secondly, the research is mainly carried out in two Beijing, China-based centers, which may result in participant recruitment that does not entirely reflect the demographics of other cities in China or Western nations. This constraint potentially reduces the broader applicability of the study’s conclusions to a more diverse population. Thirdly, volunteer-based recruitment within clinical environments risks self-selection bias. Fourthly, unmeasured psychosocial confounders (e.g., motivation, socioeconomic support, stress) remain uncontrolled. Finally, the 4-week follow-up period may inadequately capture relapse patterns, a critical consideration in smoking cessation trials. These limitations could influence generalizability and validity of the proposed research. Future studies should recruit both clinic-referred and community-based smokers with baseline matching on key confounders and ≥ 6-month follow-up periods.

Abbreviations

NRT

Nicotine replacement therapy

Acup

Acupuncture

MNWS

Minnesota Nicotine Withdrawal Scale

BSCI

Basic smoking cessation intervention

FTND

Fagerström Test for Nicotine Dependence

BBI

Bang's Blinding Index

CO

Carbon monoxide

VAS

Visual Analog Scale

CRF

Case Report Form

DQF

Data Query Form

Authors’ contributions

Conceptualization: WYY and YY; Data Curation: ZM; Funding Acquisition: WYY; Investigation: TCM, ZM and CSM; Methodology: YY and GJW; Project Administration: TCM, ZM and GJW; Resources: ZM and LMH; Software: HY and WTR; Generation of the random number table: WTR; Supervision: WYY and YY; Visualization: TCR; Writing – Original Draft Preparation: TCR; Writing Review & Editing: TCR, WYY and YY.

Funding

This study is funded by the Capital’s Funds for Health Improvement and Research (No. 2024-2-4372).

Data availability

No datasets were generated or analyzed during the current study.

Declarations

Ethics approval and consent to participate

The study protocol has been approved by the Medical Ethics Committee of Xiyuan Hospital, China Academy of Traditional Chinese Medicine (2024XLW003-2). Participants provide written informed consent. Findings of the proposed trial will be published in a peer-reviewed journal and/or disseminated through conference presentations.

Competing interests

The authors declare no competing interests.