Integrative Tobacco Cessation: A Case Study

JULIE RHODES, ND, MS 

Tobacco use is still the leading cause of preventable disease and death in the United States.¹ According to the Centers for Disease Control and Prevention (CDC), approximately 20.8% of Americans (50.6 million) over the age of 18 years were using tobacco in 2019.¹ Worldwide, cigarette smoking remains the most common form of tobacco use and kills more than 8 million people each year, including both smokers and non-smokers who experience second-hand smoke.¹ Alternative forms of tobacco use around the world include smokeless tobacco products, waterpipe tobacco, cigars, cigarillos, roll-your-own tobacco, pipe tobacco, bidis, and kreteks.² No matter what form of tobacco is used, the World Health Organization has been adamant in advising that there is no level of tobacco exposure that is safe.² US medical costs for treating smoking-related disease in adults exceed $225 billion.³ Given these staggering clinical and economic statistics as well as the availability of newer methods of tobacco intake (including combustible, noncombustible, and electronic products), it seems imperative that medical practitioners learn to implement evidence-based, comprehensive strategies to reduce tobacco use and its associated disease burden.    

The reported prevalence of tobacco use among individuals with comorbid substance use disorders (SUD) in various population-based studies ranges from 48.5% to 92%.^4-6 Compared to the general population, premature mortality from smoking-related conditions is more likely in individuals with co-occurring SUD and tobacco dependence, which highlights the importance of offering adjunctive smoking cessation strategies throughout SUD treatment.⁶ Recent population studies of individuals receiving treatment for SUD have identified a concurrent desire to quit smoking, also that nicotine abstinence can improve long-term alcohol and/or drug abstinence.⁷ A desire to engage in smoking cessation strategies may have increased in the context of the recent coronavirus pandemic. However, recent reports also support the hypothesis that increased pandemic-related stress has led to poorer outcomes in females attempting to quit smoking.⁸ The use of tobacco as a coping mechanism to relieve stress, depression, and anxiety can contribute to more severe withdrawal and greater difficulty in quitting among women who use other substances and have a trauma history.⁹ Given the increasing diversity of available tobacco products, impact of environmental stressors, and the recent passage of regulatory policy changes to promote smoking cessation services within SUD detoxification programs, coordinated efforts to overcome barriers to access and provide a variety of tools for smoking cessation should be prioritized by healthcare providers working with this population. 

Case Presentation 

Demographics & History 

A 47-year-old Caucasian female with a history of concurrent alcohol and methamphetamine substance use disorder and tobacco dependence enrolled in an out-patient treatment program through the Volunteers of America InAct program.¹⁰ The woman was residing in public housing with several female cohabitants, the majority of whom were current smokers and also going through an outpatient substance detoxification program. The patient’s past medical history was significant for sleep-onset insomnia as well as seizure disorder, the latter of which was well managed on 125 mg divalproex sodium. She had a significant trauma history that included adverse childhood experiences, instances of domestic violence and sexual abuse in adulthood, incarceration, and housing insecurity. Her mental health history was significant for depression and anxiety, with a diagnosis of post-traumatic stress disorder (PTSD). 

Tobacco Use 

This patient reported smoking approximately 10 cigarettes per day for 32 years (a 16-pack-year history), with a single 5-year duration of tobacco-free status due to incarceration. At her first office visit on February 8, 2021, she was highly motivated to initiate smoking cessation strategies, citing the detrimental impacts of smoking on her overall sense of wellness and respiratory health, and the unsustainable financial burden of the habit.  

She denied previous attempts at smoking cessation and was open to prescription nicotine replacement therapy as well as nutraceutical and lifestyle interventions to reduce cravings and promote nicotine abstinence. She described strong associations between smoking and boredom, and engagement in cigarette use within 30 minutes after morning awakening. Smoking was permitted at the group home in which she resided but was limited to outdoor areas only. 

Laboratory & Diagnostic Data 

Baseline data collection included a formal mental health evaluation, which was executed by a trained counselor associated with the VOA InAct program in which this patient was enrolled. Subjectively-reported severe symptoms of depression, anger, and anxiety had been identified by the provider as fitting within the umbrella of a PTSD diagnosis. The patient reported feeling occasional depressed mood, tearfulness, and low energy, suggesting that her depression was often situational and “related to the trauma of shame and low self-esteem.” Her anxiety was described as “periods of excessive worry that is difficult to control,” which leads to irritability and disruptions to concentration. Her score of 61 (range = 0-80) on the PTSD Checklist for DSM-5, along with a subjective report of moderate-to-extreme trauma, suggested likely benefit from PTSD treatment interventions. 

Routine drug screenings revealed no recent use of alcohol, cannabis, methamphetamine, opioids, benzodiazepines, or cocaine. The patient’s reported alcohol and methamphetamine quit-date was December 25, 2020, and she had remained abstinent, as evidenced by her most recent urinalysis drug-screen results.  

Laboratory results of recent blood testing – including thyroid-stimulating hormone, complete blood count, ferritin, complete metabolic panel, hemoglobin A1c, and vitamin D status – were within normal limits, apart from low ferritin (17 ng/mL; desired range = 40-50), and low vitamin D levels (28.7 ng/mL; desired range = 30-80). 

Medication History 

The patient’s depression and anxiety were currently being treated with venlaxafine (250 mg), and prazosin (4 mg) had been prescribed for managing nightmares related to PTSD. Venlafaxine has been FDA-approved for depression, generalized anxiety disorder, and panic disorder. Its suspected mechanism of action is the potentiation of serotonin and norepinephrine, with weaker inhibition of dopamine reuptake. This medication has clinically been associated with various anticholinergic, sedative, and cardiovascular effects, as seen with other psychotropic drugs. Prazosin is an alpha-1-adrenergic antagonist that is FDA-approved for the treatment of hypertension, but which has also exhibited efficacy in the treatment of nightmares associated with PTSD – likely the reason it had been prescribed to this patient. Dovalproex sodium is broken down within the gastrointestinal (GI) tract to its active metabolite valproate, which is thought to increase the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the brain. Her epilepsy was well controlled on 125 mg of this medication.  

Tobacco Cessation Treatment 

N-Acetylcysteine 

Nicotine replacement therapy (NRT) is the most common first-line treatment for smoking cessation. NRT acts a full agonist at the nicotinic-acetylcholine receptor, and functions to interrupt the reinforcing effects of nicotine in the initiation and maintenance of tobacco smoking. Nicotine intake is known to produce a pleasurable rush and mild euphoria, decreased fatigue, increased arousal, and relaxation.¹¹ Withdrawal of nicotine in nicotine-dependent smokers may manifest as depressed mood, anhedonia, dysphoria, anxiety, irritability, trouble concentrating, and cravings, which may also be accompanied by somatic symptoms of insomnia, bradycardia, GI discomfort, and weight gain.^11,12  

Combining NRT with nutraceutical and herbal medicines may have a synergistically beneficial effect. Providing the nutrient building-blocks for the synthesis of CNS neurotransmitters responsible for mood, behavior, and management of the reinforcing effects of nicotine (mediated by dopamine, glutamate, GABA, serotonin, endogenous opioid and endocannabinoid signaling, and corticotropin-releasing hormone) can result in reduced cravings and fewer symptoms of withdrawal.^12,13  

N-acetylcysteine (NAC) is a potent glutamatergic agent that has exhibited efficacy in reducing cravings and relapse in individuals with tobacco use disorder.^14-16 NAC is a key precursor of glutathione, serves as a source of cystine to promote glutamate signaling in brain areas involved in addiction, and modulates postsynaptic mGlu5 and NMDA receptor activation, which helps curb cue-induced nicotine seeking and anhedonia-like withdrawal states.^12,17 In a double-blind, placebo-controlled study, patients with PTSD and comorbid substance use disorder received NAC (1200 mg twice daily) for 8 weeks along with cognitive behavioral therapy. By the end of the study, patients in the NAC group exhibited reduced depressive symptoms, lower self-reported PTSD symptoms, and a 72-81% reduction in cravings.¹⁸ NAC has also shown efficacy as a therapeutic intervention for COVID-19 due to its mucolytic, antioxidant, and glutathione-producing properties.^19,20 The safety profile, tolerability, and ease of access to NAC favorably supports incorporating this pharmacotherapy into standard-of-care interventions for smoking cessation. 

Mindfulness 

Habits are formed through the repetitive activation of our brain’s reward system following a specific behavior. A variety of triggers and associated mood states can ignite the habitual chain of events that leads one to reach for that soothing object or activity that results in a sense of reward. It is a natural tendency for us to form habits, as these behaviors allow us to be more efficient without wasting time and energy on deliberating about what to do. However, this tendency toward default or reactionary thought and behavioral patterns can backfire, especially when the resultant behavior is harmful to health. A “habit loop” describes the essential elements of a habitual behavior, and includes the cue (or trigger), the routine behavioral response, and the reward. Our brains are capable of associating anything with everything, which can make it challenging to recognize and disentangle the cues or triggers that drive our habits. Mindfulness is the act of maintaining attention on the immediate, present-moment experiences with an attitude of acceptance, curiosity, and non-judgment toward that experience. Practicing mindfulness can enable one to recognize triggers and interrupt the habitual behaviors by replacing them with new, more meaningful, behavioral patterns. Mindfulness can also be a valuable tool for learning and adopting alternative routine behaviors that are more aligned with one’s values and goals, and which can replace less healthy behaviors, while being equally rewarding.  

Daily practices of mindfulness to interrupt the “addictive loop” include the following: 

• Keep a cravings journal. This can include jotting down details such as the environmental cues, emotions, physical sensations, and a rating of the strength of the craving (0-10, 10 being “I need this right now”). One may also wish to write down whether smoking occurred after noting the craving cue, the replacement activity that was substituted, and/or how long it took for the craving to subside. 
• Establish a new routine. Since smoking is often connected with other regular daily activities, changing one’s routine will help break up old habit patterns associated with smoking. 
• Incorporate new daily activities. Examples include starting a diary or blog, reading, sewing, gardening, remodeling, learning a new skill or craft, engaging in creative arts, listening to music, taking music lessons, joining clubs, taking classes, or other social activities. 

• Use a phone app for quitting smoking. One of the more popular apps is a 21-day program that provides daily instruction through audio and video tracks, goal-setting tools, and daily reminders for gradually quitting smoking.²¹ The first 4 daily modules are free, after which the program is billed monthly.   

Patient Treatment & Follow-up 

Via telemedicine, the patient was seen in an outpatient setting with practitioners from a medical clinic associated with the facility providing oversight of her SUD program. A new-patient appointment focused on addressing several health concerns, including a desire to quit smoking. She was prescribed NRT in the form of 24-hour patches (21 mg) and lozenges (2 mg), along with N-acetylcysteine (600 mg twice daily) for reducing cravings and easing withdrawal symptoms.  

A follow-up visit 3 weeks later revealed that the patient had adhered to smoking cessation treatment recommendations and successfully reduced her tobacco use by 50%. She reported ease with utilizing treatment recommendations and that the main barrier to complete cessation was exposure to housemates who were active smokers with no interest in quitting. Fifteen minutes of smoking cessation counseling and motivational interviewing was provided at this follow-up visit. The patient identified alternative behavioral strategies to avoid smoking triggers, and was able to team up with a housemate who expressed a mutual desire to quit smoking.  

Continuity of care has been established with the patient, and subsequent appointments will include additional smoking cessation counseling and lifestyle interventions to improve overall physical and mental well-being. 

Discussion 

Tobacco use in individuals with alcohol and/or drug use disorder and certain mental health conditions remains markedly higher compared to the general population.^4,22 A commonly held belief that it is too difficult for individuals with SUD to reduce or totally quit tobacco consumption in coordination with active SUD treatment has been deemed as “unfounded” in the United Kingdom’s 2017 Department of Health Clinical guidelines.²³ Recent changes to regulatory policies have prompted SUD treatment facilities to be more proactive at offering smoking cessation support to individuals engaged in in-patient and out-patient activities. The availability of practitioners able to prescribe NRT and recommend natural therapies for addressing cravings and withdrawal symptoms remains difficult to determine. Identified barriers to the broad implementation of smoking cessation programs into SUD treatment facilities include staff reluctance to deal with patient smoking, lack of skilled providers of smoking cessation intervention, and facility staff’s own smoking habits.⁵  

We described here a 47-year-old client with a history of substance use, mental illness, and trauma who was able to achieve and maintain abstinence from tobacco smoking through the integrated use of NRT, NAC, and mindful self-awareness practices. The absence of objective measures of depression, anxiety, cravings, and withdrawal symptoms for monitoring treatment response in this patient makes it difficult to fully understand the impact and efficacy of these interventions. Standardized patient-reported frequency of the use of NRT and adherence to recommended dosing of NAC would contribute to the understanding of how to individualize therapy and/or make additional recommendations for improving outcomes. This case report draws attention to the integrative strategies that can be applied by healthcare practitioners providing service to patients with complex medical and mental health histories who wish to successfully achieve and maintain smoking cessation. 

References: 

1. Centers for Disease Control and Prevention. Tobacco Product Use Among Adults — United States, 2019. November 20, 2020. CDC Web site. https://www.cdc.gov/mmwr/volumes/69/wr/mm6946a4.htm. Accessed August 25, 2021. 

2. World Health Organization. Tobacco. July 26, 2021. Newsroom Fact Sheets. WHO Web site. https://www.who.int/news-room/fact-sheets/detail/tobacco. Accessed March 5, 2021. 

3. Centers for Disease Control and Prevention. Smoking & Tobacco Use: Data and Statistics. Last reviewed June 2, 2021. CDC Web site. https://www.cdc.gov/tobacco/data_statistics/index.htm. Accessed March 5, 2021. 

4. Fine DR, Bearnot BI, Rigotti NA, Baggett TP. Smoking status and quit behaviors among health center patients with substance use disorders: A national study. Drug Alcohol Depend. 2019;202:6-12.  

5. Campbell BK, Le T, Tajima B, Guydish J. Quitting smoking during substance use disorders treatment: Patient and treatment-related variables. J Subst Abuse Treat. 2017;73:40-46.  

6. Hayhurst KP, Jones A, Cairns D, et al. Tobacco Smoking Rates in a National Cohort of People with Substance Use Disorder Receiving Treatment. Eur Addict Res. 2021;27(2):151-155.  

7. Tsoh JY, Chi FW, Mertens JR, Weisner CM. Stopping smoking during first year of substance use treatment predicted 9-year alcohol and drug treatment outcomes. Drug Alcohol Depend. 2011;114(2-3):110-118.  

8. Elling J, Crutzen R, Talhout R, de Vries H. Tobacco smoking and smoking cessation in times of COVID-19. Tob Prev Cessat. 2020;6:39.  

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10. InAct Treatment and Prevention Servs Volunteers of America Oregon. 2021. SoberNation. Available at: https://sobernation.com/listing/inact-treatment-and-prevention-servs-volunteers-of-america-oregon-portland-or/. Accessed August 25, 2021. 

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14. Machado RCBR, Vargas HO, Baracat MM, et al. N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial. Braz J Psychiatry. 2020;42(5):519-526.  

15. Schulte MHJ, Goudriaan AE, Kaag AM, et al. The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2017;31(10):1377-1379.  

16. Duailibi MS, Cordeiro Q, Brietzke E, et al. N-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis. Am J Addict. 2017;26(7):660-666.  

17. Natural Medicines. Professional. Therapeutic Research Center. N-Acetyl Cysteine (NAC). 2020. Available with subscription at: https://naturalmedicines-therapeuticresearch-com.nunm.idm.oclc.org/databases/food,-herbs-supplements/professional.aspx?productid=1018#scientif. Accessed March 5, 2021. 

18. Back SE, McCauley JL, Korte KJ, et al. A double-blind, randomized, controlled pilot trial of N-acetylcysteine in veterans with posttraumatic stress disorder and substance use disorders. J Clin Psychiatry. 2016;77(11):e1439-e1446.  

19. Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047-1055.  

20. de Flora S, Balansky R, la Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J. 2020;34(10):13185-13193.  

21. Craving to Quit. Program Reviews. Center for Technology and Behavioral Health. Geisel School of Medicine, Dartmouth College. Available at: https://www.c4tbh.org/program-review/craving-to-quit/. Accessed August 26, 2021. 

22. Creamer M, Wang T, Babb S, et al. Tobacco Product Use and Cessation Indicators Among Adults – United States, 2018. MMWR Morb Mortal Wkly Rep. 2019;68(45):1013-1019. 

23. Department of Health and Social Care. Drug misuse and dependence: UK guidelines on clinical management. Last updated December 15, 2017. Available at: https://www.gov.uk/government/publications/drug-misuse-and-dependence-uk-guidelines-on-clinical-management. Accessed March 5, 2021.  

Julie Rhodes, ND, MS is a recent graduate of the National University of Natural Medicine, where she undertook dual-degree studies to obtain her MS in Integrative Mental Health and a doctorate in Naturopathic Medicine. Her 8 years of biomedical research at the University of Pittsburgh, coalescing with the past 5 years of doctoral education, has expanded her passion for learning about the dynamic interplay between our physiology and consciousness and the environment in which we live. Dr Rhodes is an advocate for integrative medicine and aspires to serve her patients effectively by cultivating her abilities in applying naturopathic medical principles and the Therapeutic Order.