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Supakit Wongwiwatthananukit1,, Preeda Benjanakaskul2, Thanapat Songsak3,
Somporn Suwanamajo4 and Viroj Verachai4
1Department of Pharmacy Practice, College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii 96720, USA 2Department of Pharmacy, Siriraj Hospital, Bangkok, Thailand 3Department of Pharmacognosy, Faculty of Pharmacy, Rangsit University, Pathumtani, Thailand 4Thanyarak Institute, Pathumtani, Thailand
The aim of this study was to compare the efficacy and safety of Vernonia cinerea
Less. (Compositae) (VC) with placebo. A 24 week, randomized, single-blind, placebo-controlled,
parallel trial was conducted at outpatient smoking cessation clinic at Thanyarak Institute,
Pathumthani, Thailand. A 3-gram of crushed dried whole plant of VC was prepared in infusion tea bag. Sixty-four subjects were equally randomized to receive a 14-day VC tea taken three times daily or placebo. Primary outcomes were continuous abstinence rate (CAR) and the 7- day point prevalence abstinence rate (PAR) which were confirmed by urine cotinine. Adverse events and laboratory data were assessed at baseline and at clinic visits. Results showed that the 12-week CARs were 28.1% with VC versus 12.5% with placebo (p = 0.12). CARs through 24 weeks post-treatment were 18.8% with VC and 9.4% with placebo (p = 0.28). The 7-day PARs at week 12 were 43.8% with VC versus 21.9% with placebo (p = 0.06) and at week 24, 34.4% with VC versus 15.6% with placebo (p = 0.08). VC was well tolerated with no serious adverse events. As expected, the daily cost of VC ($0.30) was lower than that of daily bupropion ($2.42) and nicotine replacement therapy (gum and patch) ($2.72 - $3.65). CARs and PARs tended to be greater than in VC compared with the placebo over 24-week follow-up period, but this difference was not statistically significant. Our results show promise and suggest that VC
may be of potential alternative treatment with cost savings for smoking cessation. Larger scale
trials are needed to verify the efficacy of VC.
Keywords: smoking cessation, Vernonia cinerea Less, effectiveness, safety, tobacco dependence,
placebo-controlled trial

Tobacco smoking is recognized unwanted side effects such as weight gain,
as contributing to a number of acute and chronic nausea, dry mouth and sedation4-6). Long-term
disease processes1). It is the leading preventable abstinence remains difficult and is associated
cause of morbidity and mortality, with enormous with a high rate of relapse3-6). Thus, there is
economic costs for the individual smoker and for clearly a need to search for alternative or new
society in general1,2). This habit globally kills more treatment for smoking cessation to meet the
than 5 million people annually2) and will rise to diverse needs of smokers.
over 8 million deaths per year in 20302). Yet,
VC has been documented and widely used as despite numerous attempts to enlighten people a Thai traditional medicine and in other countries about the dangers of smoking, many begin and for relieving cigarette craving, asthma, cough, continue to smoke. Smokers who try to quit using fever, malaria, arthritis and urinary calculi7-11). It willpower have about 5-7% long-term success3). If is a perennial herbaceous plant distributed in the they use behavioral counseling and/or pharmaco- tropical regions which are commonly found in therapy, the long-term quit rates are approxi- South-East Asia and Hawaii7,8,11,12). A one-group mately double or even trebling the rates of design study has been conducted to determine successful quitting relative to placebo, which is the effectiveness of an infusion tea bag of VC in generally less than 30% 3-5). Despite the benefits of 62 healthy smokers13). A 4-gram tea bag which pharmacotherapy, its major disadvantage is high contained the whole dried crushed plant of cost, which may affect patient affordability, VC 2.86 grams was prepared. Patients were resulting in underutilization of this therapy5). instructed to take a 15-day VC tea taken three Some medications are also associated with times daily with follow-up of smoking status ∗To whom correspondence should be addressed. E-mail:, Tel: +1-808-933-2947, Fax: +1-808-933-2974 J Health Res 2009, 23(1): 31-36
32 Original Article through 4 months. At the end of 4 months, 43 arrhythmias, gastrointestinal bleeding, showed patients (69.6%) were continuous abstinence from hypersensitivity to VC during the treatment smoking and 19 patients (30.6%) failed to quit. period, they would be asked to withdraw from the Reasons for abstinence include tongue numb- ness, decreased appetite, decreased cigarette Interventions
craving, dislike the taste and smell of cigarette
A screening visit was conducted 2 weeks prior smoke, and decreased coughing. However, there to the baseline visit (week 0). During the screening are some limitations in this study, such as no visit, we obtained a medical history, physical comparison group, lack of randomization, self- examination, chest x-ray, 12-lead electrocardio- report smoking status without biochemical gram, vital signs (blood pressure, heart rate, body verification, lack of safety and adherence data, weight), laboratory data including complete blood and short-term follow-up. To our knowledge, this cell count (CBC), fasting blood glucose (FBG), liver study was the first trial designed to evaluate the enzyme levels (aspartate aminotransferase [AST], efficacy and safety of VC for smoking cessation alanine aminotransferase [ALT]), renal function compared with placebo in healthy smokers. test (blood urea nitrogen [BUN], creatinine (Cr). A MATERIALS AND METHODS:
smoking history, demographic data, and the Fagerström Test for Nicotine Dependence A randomized, single-blind, placebo-controlled, (FTND)14)score were also obtained. During parallel trial was conducted between November baseline visit, we obtained baseline characteristics 2006 to August 2007 at the outpatient smoking on subjects and enrolled subjects based on cessation clinic, Thanyarak inclusion and exclusion criteria. All eligible Institute, Pathumthani, Thailand. The study protocol was approved by the subjects were randomly assigned to VC or placebo Human Subjects Research Committee of Faculty using block randomization (i.e., block size = 4). of Pharmaceutical Science, Chulalongkorn Subjects were blinded to treatment assignments. University with the consent of the Director of Adherence to treatment was assessed by counting Thanyarak Institute. leftover tea bags and interviewing subjects at clinic visit during the treatment period. Patients Smokers were at least 18 years of age, smoked were instructed to leave any missed doses in the > 5 cigarettes/day in the past 6 months, box and were examined by the investigators at the motivated to quit smoking in the preparation or end of the 2-week treatment period. Good action stages of Transtheoretical Model3,6), signed adherence to follow-up was defined as patients an informed consent form, and had no period of take the tea bag at least 90% of the total tea bags. abstinence > 3 months in the past year. Subjects The whole plant of VC was prepared at Rangsit were excluded if they had a history of diseases University, Pathumtani, Thailand by washing, air including cardiovascular, cerebrovascular, gastro- drying, and incubating in hot air oven set at 50- intestinal, endocrine, cancer, pulmonary disease, 70 degree celsius. Subsequently, the plant were significant hepatic and renal impairment, crushed and sieved to a smaller size and packed neurologic and psychiatric disorder and those in a 3-gram of infusion tea bag. The aqueous with clinically significant laboratory abnormal- soluble extract of the crushed dried whole plant of ities. Other exclusion criteria were pregnancy or VC was standardized for the content of luteolin by lactation, history of alcohol or drug abuse in the thin layer chromatography. Subjects in VC group past year, previous use of smoking cessation received a 3-gram of VC tea bag. They were products within a month (e.g., nicotine replacement, instructed to use 14 days of treatment with VC bupropion, nortriptyline, clonidine), and use of tea taken three times daily by pouring 150 mL other forms of tobacco products other than boiling water over tea bag, stirring well, covering cigarettes. If the subjects experienced an cup for 15-20 minutes before drinking. Placebo intolerable or serious adverse event such as group receive a 3-gram of Morus alba Linn. (MA) J Health Res 2009, 23(1): 31-36
Original Article 33 infusion tea bag and received instruction to inferential statistics were determined for outcome
use similar to those in the VC group. The reasons variables. Baseline characteristics were compared
to use MA were that the tea provides the same using the χ2 test or Fisher's exact test or
color similar to VC tea and there is no smoking independent t-test, as appropriate. The odds ratio
cessation effect. Subjects were asked to completely and the difference of CAR and PAR variables
stop smoking on their target quit date which was between the 2 groups was compared using the χ2
scheduled for day 8 after their baseline visit. Both test. Adverse events were summarized using
groups were given standardized, individual brief frequencies and percentages and χ2 test or
10-minute counseling based on the US Agency for Fisher's exact test was used for each type of
Healthcare Research and Quality Guidelines5) by adverse events to compare the percentage of
a clinical pharmacist at each clinic visit. The subjects who experienced an event between the 2
follow-up period was 24 weeks with 5 clinic visits groups.
(weeks 2, 4, 8, 12, and 16) and 1 telephone RESULTS: Of the 75 subjects screened, 64 were
contact (week 24). eligible, randomized to receive VC or placebo (32 Measures
subjects in each group), and included in the The primary outcomes were self-report of analysis. Of the 64 subjects, 42.2% (27/64) continuous abstinence rate (CAR) and the 7-day completed the study. The 24-week completion point prevalence abstinence rate (PAR) which were rates were 47% (15/32) for VC and 38% (12/32) confirmed by the measurement of urine cotinine. for placebo. The reasons for discontinuation in CAR was defined as no cigarette smoking, not both 2 groups were loss to follow-up (53.1%) and even a puff since target quit date. PAR was refusal to participate further (4.7%). We treated defined as no cigarette smoking, not even a those lost to follow-up and refusal (20.3%) as puff for the previous 7 days. Subjects who smokers. Adherence of 100% for the subjects discontinued the study or who were lost to follow- who completed the 2-week treatment period was up were classified as smokers for the remainder of demonstrated by counting leftover tea bags at the the study. The urine cotinine confirmed self- end of week 2 clinic visit. report of CAR and PAR for 5 clinic visits was There were no statistically significant measured qualitatively by using GC 5890/ differences in the baseline characteristics and MS5972 Injector HP6890 series, USA. Vital signs smoking history between those receiving VC were measured at all clinic visits and laboratory versus placebo except gender, which percentage data were measure at the screening visit, week 2, of male was significantly higher in the VC group and week 12. All observed or self-reported adverse (Table 1). Overall, the majority of subjects were events during the treatment period were male, 100% in the VC group and 78.1% in the documented in case report forms at week 1 using placebo group. Subjects were aged 18 to 65 years telephone contact and at the end of week 2 and and the mean ages were 40.1 and 41.7 years for followed up until they resolved or to the end of VC and placebo groups, respectively. Subjects study. had smoked for 4 to 50 years with the overall Analyses
means of 23.6 years and smoked a mean of 19.1 Based on the previous study13), an estimated cigarettes/day over the past 6 months. The sample of 54 subjects was calculated to detect a overall mean score on the FTND was 5.31 out of a difference of 35% abstinence rate between the VC possible total of 10. and placebo groups13) at an α significance level of The urine cotinine-confirmed CARs were not 0.05 and a power of 80%. The statistical analyses significantly higher for VC compared with placebo were performed on an intention-to-treat basis. at all clinic visits (weeks 4, 8, 12, and 16) and at Statistical analyses were performed using the week 24 (Figure 1). The odds ratios, which were Statistical Package for Social Sciences (SPSS) the likelihood of subjects treated with VC software, version 15.0. Both descriptive and abstinence compared with placebo, tended to be J Health Res 2009, 23(1): 31-36
34 Original Article at doubling or nearly trebling a subject's odds at each group at week 2 and week 12 from baseline quitting smoking from week 8 through week 24. visit. All laboratory data were also no significant The 7-day PARs (Figure 2) were higher for VC difference between VC and placebo groups at than for placebo at all assessment points, but the baseline visit, week 2, and week12. Table 2 shows differences in abstinence rate between the 2 the percentages of subjects who reported adverse groups were not significantly different. The odds events during the treatment period. There were ratios of the PAR at week 8, 12, 16, 24 no significant differences in adverse events demonstrated that about twice as many subjects between the groups except percentage of subjects in VC were abstinent in the previous 7 days than who disliked the taste and smell of cigarette in the placebo. smoke, which was significantly higher in VC No significant difference in the average change group. No serious adverse event was reported of blood pressure and heart rate was observed during the treatment period. There were no between the 2 groups at all clinic visits. Blood significant differences in the mean body weight pressure and heart rate in each group at all clinic between VC and placebo groups at baseline visit, visits were not significantly different from baseline weeks 2, 4, and 12 (all p>0.05). The mean (SD) visit. There were no significantly different weight change from baseline visit to week 12 was changes in CBC, FBG, AST, ALT, BUN, and Cr in 2.30 (0.19) kg for subjects who received VC versus
Table 1
Baseline Subject Characteristics
Vernonia cinerea
Gender, N (%)
Age, y mean ± SD (range)
40.13±11.86 (18-65) 41.72±11.29 (18-64) Weight, kg (mean ± SD)
Body mass index, kg/m2 (mean ± SD)
Blood pressure, mm Hg (mean ± SD)
No. of years smoked
mean ± SD (range) 23.44 ± 11. 79 (4-50) 23.81 ± 9.52 (5-44) No. of cigarettes/day in past 6 months
mean ± SD (range) 19.88 ± 10.57 (8-60) 18.83 ± 10.31(10-60) No. of previous quit attempts
mean ± SD (range) 2.31 ± 1.33 (1-5) 2.50 ± 1.69 (1-5) Fagerström Test for Nicotine Dependence score
a statistical significance set at α < 0.05.
b χ2 test used to compare the number of patients between the 2 groups.
c Independent t-test used to compare the mean between the 2 groups.
d Score range from 0 to 10, with higher score representing a higher degree of nicotine dependence.
Table 2 Adverse Events Occurring of VC-treated Subjects Compared with Placebo
Placebo Group
Adverse Events
p valuea,b
Upper abdominal pain Craving reduction Dislike the taste and smell of a statistical significance set at α < 0.05
2 test used to compare the number of patients between the 2 groups
J Health Res 2009, 23(1): 31-36
Original Article 35 1.54 (0.25) for placebo subjects. The daily cost of the inclusion criterion was limited to the relatively VC ($0.30) was lower than that of daily bupropion motivated healthy smokers, excluding smokers ($2.42) and nicotine replacement therapy (gum with concurrent medical illnesses. This may and patch) ($2.72 - $3.65). probably limit the generalizability of the results to DISCUSSION: This study is the first, randomized, the majority of smokers in a typical primary care
placebo-controlled trial to evaluate the efficacy VC population.
compared with placebo in healthy smokers. VC
Few female smokers were enrolled in the study group tended to produce higher CAR and PAR and there is a significant difference in gender than placebo group at all follow-up periods. The between VC and placebo group. One might argue smokers' odds at quitting smoking for VC were that gender may affect the abstinence rate, but about 2.0-3.0 times that for placebo from week several smoking cessation trials have indicated 8 to week 24. This is consistent with results that the abstinence rates were not significantly of most current pharmacotherapies for smoking different between male and female15,16). We cessation5). However, our findings did not reach observed no serious adverse events and abnormal statistical significance due probably to the laboratory data across two groups. The dropout relatively small number of participants to detect rate was higher in the placebo than VC. This the effect of at least 9.4 – 22.0% difference in CAR provides reassurance the tolerability of VC. or PAR between the VC and placebo groups. Large Craving reduction and dislike the taste and smell scales trials with longer duration of treatment and of cigarette smoke were higher in VC compared follow-up are needed to verify the efficacy of VC with placebo. From this result, we hypothesize VC versus placebo. One limitation of our study is that may decrease the reinforcing effect of cigarette Figure 1 Continuous
abstinence rates (CAR)
in Vernonia cinerea group
compared with placebo
Figure 2 7-Day point
prevalence abstinence
rates (PAR) in Vernonia
group compared
with placebo
J Health Res 2009, 23(1): 31-36
36 Original Article smoking. A translational opportunity for research guideline. Rockville, MD: U.S.Department of to discover the active compounds of VC as Health and Human Services.
potential use for smoking cessation, evaluate its Fiore MC, Jaen CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, et al. 2008. Treating mechanism of action and potential as therapeutic tobacco use and dependence: 2008 update. agents, develop alternative dosage formulations of clinical practice guideline. U.S. Department of VC to enhance the convenience and adherence, Health and Human Services. and replicate clinical trials with larger sample 6. Prochazka AV. 2000. New developments in
size, optimal duration of treatment and longer smoking cessation. Chest 117: 169-75.
follow-up period are warranted. Lack of afford- Bunyapraphatsara N. 2000. Medicinal plants indigenous to Thailand volume 5, Bangkok: ability or health insurance to cover for smoking Department of Pharmacognosy, Faculty of cessation pharmacotherapy can reduce smoker Pharmacy, Mahidol University: 72-4. adherence, which may result in failure to quit 8. Lin KW. 2005. Ethnobotanical study of
smoking. VC produces a saving in the cost medicinal plants used by the Jah Hut people in spent compared with other currently approved Malaysia. Indian J med Sci 59: 156-61.
9. Lhieochaiphant S. 1985. A Phytochemical
pharmacotherapy for smoking cessation. This study of Vernonia cinerea Less. [Master's thesis]. could greatly lower the substantial costs of health Chiangmai: Graduate School. Chiangmai care for smokers who desire to quit smoking. CONCLUSION: Our preliminary study shows
10. Yamsup N. 1998. Vernonia cinerea: another
alternative treatment for smokers who want to
promise and VC could be an alternative thera- quit smoking. Smoking and Health Newsletter 8: peutic target with low cost for the treatment of tobacco dependence. VC was generally well 11. Chea A, Hout S, Long C, Marcourt L, Faure
tolerated. Unpleasant taste and smell of cigarette R, Azas N, et al. 2006. Antimalarial activity of smoke and craving reduction were the most sesquiterpine lactones from Vernonia cinerea. common report for VC. While our CAR and PAR Chem Pharm Bull 54: 1437-39.
results did not reach statistical significance due to Starr F, Starr K. 2008. Plants of Hawaii. Available at: the relatively small number of subjects, we hope that VC may be of potential use for smoking 5 December 2008). cessation and stimulate interest in future 13. Chaisawad S, Makanuntachote M. 1996. A
smoking cessation research. study of smoking cessation therapy model using Vernonia cinerea Less. and natural cure at Theng ACKNOWLEDGEMENT: The authors wish to
Hospital, Chiangrai. Nonthaburi, Thailand: Office express special thank to the Thai Pharmacy of the alcohol beverage and tobacco committee, Network for Tobacco Control and the Thai Health Department of Diseases Control. Ministry of Promotion Foundation for supporting this study. REFERENCES:
14. Heatherrton TF, Kozlowski LT, Frecker RC,
Fagerstrom KO. 1991 The Fagerstrom test for Mackay J, Eriksen M, Shafey O. 2006. The tobacco atlas. 2nd ed. Atlanta, GA: American Nicotine Dependence: a revision of the Fager- strom Tolerance Questionnaire. Br J Addict 86: World Health Organization. 2008. WHO report on the global tobacco epidemic 2008: the 15. Killen JD, Fortmann SP, Varady A, Kraemer
MPOWER Package. Geneva, Switzerland: WHO. HC. 2002. Do men outperform women in smoking cessation trials? Maybe, but not by Wongwiwatthananukit S. 2003. Role of phar- macists in smoking cessation program. In: much. Exp Clin Psychopharmacol 10: 295-301. Jindavijag B, ed. Ambulatory pharmaceutical 16. Jorenby DE, Hays JT, Rigotti NA, Azoulay S,
care. 1st ed. Bangkok: Thai Hospital Pharmacist Watsky EJ, Williams KE, et al. 2006. Efficacy of Association: 153-74. varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained- Fior MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein MG, Gritz ER, et al. 2000. Treating release bupropion for smoking cessation: a tobacco use and dependence: clinical practice randomized controlled trial. JAMA 296: 56-63. J Health Res 2009, 23(1): 31-36
Original Article 37 J Health Res 2009, 23(1): 31-36



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