Nicotine Dependence Treatment

Stop Smoking Nicotine Treatment

The gateway theory of addiction describes a sequence and progression of addictive substance use, from tobacco and alcohol to cannabis, then to other illicit drugs like heroin and cocaine. Cigarettes are a powerful gateway drug to diverse illegal drugs, especially among adolescents.

Most U.S. adolescents will experiment with tobacco before age 18, and many will develop a tobacco use disorder by late adolescence. Adolescents tend to overestimate their peers’ use of tobacco products, and peer group imitation is a significant driver of early tobacco use.

Each year, around 70% of tobacco cigarette smokers say they want to quit, and over half of them make a quit attempt. Unfortunately, relapse rates are very high, from 60% to 90% within the first year.

Immediate effects

Nicotine is one of about 4,000 chemicals present in cigarette smoke, but it is the most active psychologically and is responsible for the addictive properties of smoking.

When smoked, the nicotine is quickly absorbed by the lung’s alveoli, reaching the brain within seconds of the first puff. The chemical appears to work by stimulating acetylcholine receptors that are attached to dopamine neurons, which rapidly release dopamine to produce the nicotine buzz. These receptors are sometimes confusingly called “nicotinic receptors,” because they are a subclass of acetylcholine receptors that are stimulated by nicotine. The effects diminish quickly, leading users to want another hit to replicate the feeling.

With regular use, receptor sites are down-regulated, resulting in the smoker needing more nicotine to produce the same effects. The effects of nicotine are similar to the effects of stronger stimulants such as cocaine and amphetamines. Nicotine enhances alertness and focus, but also causes muscle relaxation. As with stimulants, memories of the pleasurable effects are associated with whatever is going on at the time of tobacco use.

Typical times for smoking—such as in the car, while talking on the telephone, with a cup of coffee, after a good meal, or after sex—become strongly associated with the use of nicotine and its pleasurable effects. These then become triggers to smoke again. These are called cue cravings or trigger cravings, and are a large part of the day-to-day habit of smoking.


Another effect of nicotine is appetite suppression, also similar to more potent stimulants. This is one reason cigarettes are popular for weight control among teenage girls. Nicotine’s immediate physiologic effects include mild tachycardia. Long-term effects Nicotine’s dangers in terms of cancer and heart disease risk are well known.

Additionally, from a psychiatric perspective, nicotine is a stimulant and can worsen anxiety and mood disorders. Since it is an inducer of the 1A2 P450 metabolic enzyme, it can complicate dosing of medications, most notably olanzapine and clozapine.

Nicotine Withdrawal Syndrome

Nicotine withdrawal does not have obvious physical symptoms, but rather subjective effects such as reduced alertness, irritability, and headache. This is not as pronounced as the crash from stimulants such as cocaine or methamphetamine, but it is uncomfortable and reduces productivity. The withdrawal syndrome lasts for 7–10 days, then the symptoms drop off sharply and gradually improve from that point.

In addition to the withdrawal symptoms, cravings are prominent and can be intense. Fortunately, an episode of acute craving is fairly short, usually only about 20 minutes. If a patient can hold out that long, the craving will subside. Most smokers who are trying to quit will relapse within a few days due to withdrawal symptoms and cravings. Electronic cigarettes Electronic nicotine delivery systems, or “e-cigarettes,” generally consist of a power source (usually a battery, but adapters can draw power from an electrical outlet, a car’s electrical outlet, or a computer USB port) and heating element (commonly referred to as an atomizer) that vaporizes a solution (known as “e-liquid” or “e-juice”).

The user inhales the vapor, which is called “vaping” instead of smoking. E-liquids contain propylene glycol and/or vegetable glycerin, flavorings, and nicotine. Ask patients specifically about their use of electronic cigarettes in addition to tobacco cigarettes, since patients may not consider them to be a “tobacco product.” E-cigarettes may have the potential for less physical harm compared to tobacco, since they do not deliver carbon monoxide and they expose
the user to fewer carcinogens.

However, they do deliver nicotine, which is addictive. They also expose the user to other chemicals, pollens, and impurities. When asked whether e-cigarettes are safer than tobacco cigarettes, my response is that e-cigarettes are generally safer than tobacco, but not as safe as air. E-cigarettes are neither designed nor marketed as smoking cessation devices. Their original purpose was to provide a way for users to get around smoking bans in public places (buildings, restaurants, airplanes) by allowing them to vape nicotine instead of exposing others to secondhand tobacco smoke.

Some people have tried to quit smoking by using e-cigarettes, and clinical trials have shown that e-cigarettes can be fairly effective in helping smokers cut down or cease tobacco use. Personally, I do not recommend e-cigarettes to my patients for smoking cessation, since there are several other more successful options available. Even if people use e-cigarettes to quit smoking tobacco, there are risks associated with these devices. As with other drugs of abuse, e-cigarette users may escalate their dose of nicotine due to physical tolerance.

The voltage of newer types of e-cigarettes can be adjusted by the user, and higher voltage increases the nicotine yield of the vapor. Users may also tamper with the e-cigarette delivery system to provide larger doses of nicotine, or change to a higher nicotine concentration in the e-liquid. Bottles containing e-liquid to refill e-cigarette cartridges may contain up to 720 mg of nicotine—if ingested, this is not only toxic, but potentially fatal.

Diagnosis of Tobacco Use Disorder

To officially diagnose tobacco use disorder, a “problematic pattern” of tobacco use must be established, leading to “significant distress” which lasts at least 12 months. DSM-5 lists 11 criteria, which are the same for other substances; the severity guidelines are the same as well (meeting at least 2 criteria is mild, 4 is moderate, and 6 is severe).

First, assess how much you are ingesting and how addicted you are. Answering these questions will help you come up with the best method of attacking the problem.

  1. Determine the daily nicotine load. This includes packs per day of cigarettes, but also e-cigarettes, chewing tobacco, and hookah pipes, all of which are increasingly popular. While the nicotine content of the average cigarette is pretty standard (1 mg), it’s harder to figure out how much you are getting through other options. E-cigarettes used to deliver less nicotine than tobacco cigarettes, but that’s no longer always true. For chewing tobacco, one pouch is generally the equivalent of about a quarter of a pack of cigarettes. Ask yourself, “How many times do I refill my e-cigarette cartridge?” “How many packets of chewing tobacco do I go through per day?”
  2. Determine the usage pattern. Get a feel for your degree of tolerance and addiction. Ask yourself, “When do I have my first cigarette of the day?” If you wake up, take a shower, have breakfast, and then lights up, that’s less concerning than if you shut off the alarm with one hand and light a cigarette with the other. Ask yourself, “Do I smoke when I’m sick?” Those who do are more physically dependent. A good resource is the Fagerström test, which has a list of questions you can ask to assess your degree of tolerance.
  3. Has a quit method worked for you in the past—or not worked? Prior treatment responses will help you and your provider guide your treatment.

What is it about smoking that makes it so addictive?

On one hand, this form of drug delivery is very efficient; inhaled nicotine is absorbed through pulmonary rather than systemic circulation and can reach the brain within 10 to 20 seconds. Once inside the central nervous system (CNS), nicotine stimulates the release of dopamine from the nucleus accumbens, much like the use of cocaine and amphetamines, leading to the feeling of satisfaction and well-being.

Given such rapid central reinforcement, it is not surprising that tobacco can become highly addictive. On the other hand, familial and social influences often play a crucial role in determining who might start smoking, quit, or become dependent.  For example, one study managed to train a small percentage of rhesus monkeys to smoke, but with such difficulty that it concluded that “environmental factors play the primary role in developing smoking behavior.”

Experimenting with smoking usually occurs in the early teen years and is predominantly driven by psychosocial motives. For a first-time user, lighting a cigarette is a symbolic expression of autonomy and independence; acquisition of the desired image is often a sufficient incentive for a novice smoker to tolerate the body’s rejection of the first few cigarettes.

Despite an admitted awareness of at least some of the deleterious effects of smoking, in 2018, 1 in 4 high school students and 1 in 14 middle school students admitted to using a tobacco product in the past 30 days.  Almost all people (90%) who will smoke as adults have started doing so by 18 years of age, and the earlier a person begins, the more likely they are to continue.

Within a year, adolescents inhale the same amount of nicotine per cigarette as adults, and they too experience the craving and withdrawal symptoms associated with nicotine addiction. By 20 years of age, 80% of smokers regret ever having started.

Much research has been dedicated to uncovering the reasons for the development of a smoking habit. Risk factors include:

  • Presence of a smoker in the household
  • Single parent home and/or strained relationship with a parent
  • Comorbid psychiatric disorders
  • Low level of expressed self-esteem and self-worth
  • Poor academic performance
  • In boys, high levels of aggression and rebelliousness
  • In girls, preoccupation with weight and body image
  • Increased adolescent perception of parental approval of smoking
  • Affiliation with smoking peers
  • Availability of cigarettes

In addition, twin studies revealed a significant genetic contribution to both smoking initiation and dependence.

In practice, many find the very act of smoking a cigarette ritualistic and calming. The process of “packing” cigarettes by tapping the box on the palm of a hand, removing a cigarette, lighting it, inhaling, and watching the smoke as it is exhaled all contribute to the perceived need to smoke.

Some go so far as to claim that they “would not know what to do with their hands” if they were to stop smoking. An investigation using denicotinized cigarettes illustrated that the sensorimotor experience of smoking makes a significant contribution to perceived satisfaction.

Mass media is another factor that contributes to the learning of smoking behavior. Historically, the tobacco industry recruited new smokers by associating its products with fun, excitement, sex, wealth, power, and a means of expressing rebellion and independence. Such promotional efforts have proven to be especially effective on teenagers, a particularly lucrative market with a lifetime of cigarette consumption ahead of them.

Although at present tobacco companies can no longer directly advertise to teenagers, they retain the most potent form of marketing: movies. Smoking in films is a “more powerful force than overt advertising,” perhaps because the audience is generally unaware of any sponsor involvement. Philip Morris, one of the world’s leading tobacco companies, stated in their 1989 marketing plan, “We believe that most of the strong, positive images for cigarettes and smoking are created by cinema and television”.

Although television is taking a more socially responsible stance on the subject of on-air tobacco use, movies continue to model smoking as a socially acceptable behavior, portraying it as a social behavior or a way to relieve tension. A study exploring the connection between a child’s professed favorite movie star and that actor’s on-screen smoking history revealed “a clear relation between on-screen use and the initiation of smoking in the adolescents who admire them.” Tobacco use in movies, albeit falling through the 1970s and 1980s, increased significantly after 1990.

Furthermore, despite declining tobacco use and increasing public understanding of the dangers of nicotine, smoking in movies returned to the levels observed in the 1950s, when it was nearly twice as prevalent in society as in 2002. A study analyzing the content of the top 25 grossing films each year from 1988 to 1997 found that 87% of movies depicted tobacco use, with an average of 5 occurrences per film.

The vast majority of tobacco use was portrayed as experienced use (91.5%) and rarely did it represent a character’s first use (0.3%) or a relapse from a previous quit attempt (0.5%). Despite the fact that R-rated movies contained most tobacco exposure and were more likely to feature a major character using tobacco, about 60% of the total coverage of smoking occurred in youth-rated films (G, PG, and PG-13).

It has been suggested that high genetic vulnerability to cigarette smoking may explain why some people begin and continue to smoke despite associated risks. Twin studies found significant heritability for the persistence of smoking versus quitting. Heritability estimates for smoking persistence ranged from 27% to 70% and were greater for older than younger cohorts.

Madden et al. examined cross-cultural differences in the genetic risk of becoming a regular smoker and of persistence in smoking in men and women. They found strong genetic influences on smoking behavior, 46% for women and 57% for men, consistent across country and age group. In a U.S. study, estimates of the genetic contribution to risk of becoming a smoker were 60% in men and 51% in women.

Treatment for Nicotine Dependence

Non-pharmacologic treatment
Studies have shown that simply discussing your intentions to quit along with agreeing on a quit date can be helpful. Even more effective are behavioral therapy and motivational interviewing—but that may not be available to certain patients, depending on where they live and what kind of insurance you have.

Fortunately, there are several free resources, some of which are paid for by manufacturers of smoking cessation treatments. The best portal is the
phone number 1-800-QUIT-NOW, and there are various affiliated websites.

One is, maintained by the U.S. Department of Health and Human Services. You can get diaries and calendars to support
your efforts, and you can sign up for a phone call or text message on your quit date, as well as follow-up calls or texts.

The site also has information on using diaries and calendars to support quitting efforts. While these programs are designed to be used in conjunction with nicotine replacement therapy or other pharmacologic treatment, they are helpful for anyone.


Motivational Interviewing to Persuade a Patient to Quit

Doctor: Have you thought about quitting smoking?

Patient: Smoking relaxes me.

Doctor: Yes, it can help people relax. What else do you like about smoking?

Patient: Like? No doc has asked me that before. Let’s see . . . I like taking a break during the day. I like talking with people who are also outside smoking. That first cigarette of the day is the best. I used to look pretty cool lighting up and puffing away in front of my friends, but that got kind of old after a while.

Doctor: So the excuse to take a break during the workday is good, and the first cigarette of the day is the best one, but lighting up isn’t as cool now as it used to be. Is anything else not as much fun as it used to be?

Patient: Well, it costs real money, that’s for sure. And going outside all the time gets old, too. If I knock over an ashtray in the house, cleaning
it up is a pain. I also don’t like that I can’t give it up, even for a while. But if I didn’t have my cigarettes, I couldn’t make it through my day.

Doctor: So it’s expensive, it takes some time in your day away from other things, and cleaning up is a hassle. Anything else?

Patient: My mother quit when she was younger, so she’s on my case about me smoking. I swear, she brings it up all the time. I’ve taken to hiding the ashtrays when she comes to visit, and I sneak out of my own house to take a drag, just to avoid the hassle.

Doctor: So your mother would support you if you would try to quit, and she would be proud of you if you did?

Patient: I guess so.

Doctor: That sounds like something to think about.

Patient: Yeah, I’m sure I’ll try to quit again someday. I’m not ready now.

Doctor: You’re right; it’s worth thinking about quitting again. You might find you can relax without a cigarette. It might even help your depression.

Patient: I suppose so. I’ll think about it—especially if it could help my depression.

Doctor: Is it all right if I ask about that at our next visit?

Patient: Okay. I’ll let you know.

Pharmacologic Treatment for Nicotine Dependence

Nicotine replacement therapy (NRT)

NRT supplies an alternative source of nicotine to help your patients decrease and ultimately quit smoking. It is typically recommended to start with NRT before moving to bupropion or varenicline, because it’s widely available and readily acceptable to most smokers.

Which NRT to choose?

There are lots of options, but generally, people begin with the patch, because it delivers a constant nicotine level throughout the day, hopefully preventing episodes of craving. (Really light smokers can start with nicotine gum—see below.) Patches used to be expensive, but prices have come down as more chain pharmacies have created their own products. At this point, a month’s supply will generally cost about $1 per day.

Which dose of the patch is for you?

It depends on your current nicotine consumption. A typical pack-per-day smoker is consuming about 20 mg of nicotine per day, so in this case you would need the 21 mg patch. If you smoke 2 packs per day, 2 patches may be needed, but this (and even lesser doses) may be too much, and sometimes
you will simply discontinue the patch if you have adverse effects. It’s recommended to counsel patients that they can reduce the dose if needed.

Apply the patch at the same time each day, usually in the morning. One potential exception is if you wake up with a strong craving to smoke. Such patients can try applying the patch close to bedtime, following the theory that the residual morning nicotine will prevent their initial craving. A common problem with nighttime administration is vivid dreams or nightmares, so be aware that you may have some unusual dreams.

In terms of where to place the patch,  start by placing it just above the heart (the upper anterior chest), then the next day move it left to the upper arm, then the left upper back, right upper back, right shoulder, right chest, and finally back above the heart. This rotation helps prevent skin irritation due to the adhesive. If there is any irritation, 0.5% cortisone cream helps.

Usually, no shaving is required. Swimming with the patch is fine and patches are clear now and pretty hard to spot.

Stay on the initial dose for 4–6 weeks, then use the next-lower strength for 4 weeks, and so on. Some patients need a longer taper—for example, you may need 3 months on the initial dose, and then a very slow taper thereafter.

Do not smoke while taking the patch.

If you do smoke, you may develop nausea, which is the first symptom of nicotine toxicity.


Indication Tobacco cessation
Dosages available: 7 mg, 14 mg, 21 mg
Target dose: Start 14 mg–21 mg daily, then gradually taper over several weeks

nicotine patches as potential coronavirus treatment | Coronavirus | The Guardian

Several other forms of NRT are available, including gum, lozenge, and spray

Combination NRT
Some patients find that they have cravings throughout the day even while using the patch—if so, recommend one of the short-acting NRT agents,
such as the gum, lozenge, or spray, in combination with the patch. In fact, light smokers may do well starting with one of these agents and skipping the patch entirely.

A word on nicotine gum: Its chewing technique is different from regular gum. Patients should start by chewing a few times to activate the release of
the nicotine; they’ll know it’s releasing because the gum will start tasting bad and peppery. At that point, they should park it between the cheek
and the gums, and switch sides every several minutes or so. One piece of gum releases a total of either 2 mg or 4 mg of nicotine, and it lasts about
30 minutes.

While the gum is the most popular short-acting treatment, some patients will prefer other options, such as the lozenge or the spray. The lozenge is
easy to use—patients just pop one in like a piece of hard candy when they have the urge to smoke. Nicotine nasal spray is available by prescription and
involves frequent dosing of small amounts of nicotine. Its use is limited to six months to prevent development of physical dependence on nicotine
(obviously counterproductive given the goal of tobacco cessation).

Varenicline (Chantix)
Chantix acts as a partial agonist at nicotinic receptors, so its mechanism is physiologically closer to nicotine—which is our rationale for choosing it
over other medications, such as bupropion. Some patients will move on to Chantix after an unsuccessful trial of NRT, but others want to start with the
pill right away, which is reasonable.

Pfizer Recalls All Lots of Chantix Due to Potential Cancer-Causing Impurity | Everyday Health

While Chantix’s manufacturer has a dosing recommendation, different clinicians have their own preferences based on experience. Some start patients with 0.5 mg per day for 7–10 days, at which point they should stop smoking and increase to 1 mg BID, then continue at that dose for 3 months. However, a recent study found that patients don’t have to quit that soon after starting Chantix to respond to the drug.

In the study, smokers were asked to reduce their smoking gradually over 3 months while taking Chantix, and their long-term abstinence rates were robust—27% at one year vs. 9.9% on placebo.

This is good news because some patients panic when told they have to try quitting in a week. Chantix’s potential psychiatric side effects have been widely covered.  A recent meta-analysis of 39 randomized controlled trials covering 10,761 patients found that there was no difference
between Chantix and placebo in rates of depression, suicidal ideation, or aggression.

However, Chantix did cause more insomnia and abnormal dreams in these studies. Be aware of the possibility of vivid dreams and nightmares (though nightmares aren’t very common). If this is a problem,  take the pills in the morning.

Indication Tobacco cessation
Dosages available 0.5 mg, 1 mg
Target dose 1 mg twice daily

Bupropion (Wellbutrin, Zyban)
One large study reported that bupropion SR led to a 23% one-year quit rate vs. 12% for placebo (Hurt, 1997). While the manufacturer recommends starting at 150 mg per day for 3 days then increasing to 150 mg BID, studies have shown that continuing with 150 mg/day is just as effective as the higher dose—and has fewer side effects.

Indications Major depression, SAD, tobacco cessation
Dosages available 75 mg, 100 mg, 150 mg, 200 mg
Target dose 300 mg for smoking cessation

Most psychiatric prescribers are quite familiar with bupropion’s common side effects of insomnia and anxiety. A potentially good side effect is weight
loss, since people trying to quit smoking often substitute food for cigarettes. Note that bupropion is contraindicated in patients with a seizure disorder or with a history of bulimia or anorexia nervosa.

Off-label meds
Two medications, nortriptyline and clonidine, are effective second-line agents for smoking cessation, though this is an off-label use for both. Nortriptyline is usually started at 25 mg daily 10–28 days before the quit date, then gradually increased to 75 mg–100 mg daily. Treat for 3 months at this
dose; the treatment can be extended to a total of 6 months depending on response. Nortriptyline should be tapered off instead of stopped abruptly due to possibility of withdrawal effects.

Clonidine is dosed starting with 0.1 mg daily, then increased gradually as tolerated by 0.1 mg/day to a 0.15 mg–0.75 mg total daily dose. Clonidine should also be tapered off to avoid rebound effects.

Unfortunately, most patients relapse, even with the fanciest of meds and behavioral therapy; let them know that there’s no shame in failing to quit.
I say things like, “You may have to try this several times—and that’s okay.” Often I’ll invoke the Mark Twain quote that leads off this chapter. The first week after quitting is the hardest in terms of craving. A typical smoker gets about 10 puffs out of a cigarette, meaning that a pack-per-day smoker gets 200 doses of nicotine over the course of a day. That’s a lot of habituation and reinforcement the patient must overcome.

Triggers for craving are everywhere—seeing the ashtray, having coffee, having a drink, going to the corner store, etc. Distraction techniques can work well, because nicotine cravings generally only last 10–20 minutes. Patients can do things like drink a large glass of cold water or play a video game to get their minds off the urge.

I recommend warning patients that they are likely to cough temporarily after they quit—this is a normal response as the cilia of the lungs “wake
up” and get rid of mucus. If not alerted to this, some patients will worry unnecessarily. In my experience, even with the high rate of relapse, patients who are willing to stick it out with you over time will have at least a 50% chance of prolonged abstinence.

Here are some practical tips for successful quitting and relapse prevention.
• Set a quit date. Have the patient set a significant quit date, such as a birthday or anniversary, to enhance motivation. Conversely, a quit date can be set during a time when the patient has less stress and can deal with the difficulties of a quit attempt. Before setting a quit date, I recommend patients immediately start gradually reducing their daily number of cigarettes. This way, they will be smoking less before they stop completely, which can help with the severity of early nicotine withdrawal symptoms. They will also start to get used to those symptoms, at least to a degree.

• Tell friends and family. If other people know the patient is quitting, they can provide support. Family, friends, or coworkers can also help keep the patient accountable—if the patient lights up a cigarette around them, they can say, “I thought you were quitting!”
• Have everyone try to quit together. If the patient has a partner or roommate who is a smoker, the patient is much more likely to relapse. If
both try to quit, they can support one another and are much more likely to be successful.
• Reduce the prevalence of cigarettes. Here are a few ways:
– Limit smoking to outside the home. This helps the patient to think twice about automatically lighting up. It makes smoking intentionally less convenient. If smoking an individual cigarette becomes more of a hassle, the patient is more likely to say, “Forget it; I’ll just smoke later.”
– Get rid of all but one ashtray in the home. Then get rid of the last ashtray on the quit date.
– Switch to a different brand of cigarettes. The difference in taste from a new brand can help reduce the number of cigarettes smoked per day and remind patients that they are not supposed to be smoking as much. However, switching to “light” (lower-nicotine) cigarettes doesn’t work—patients just smoke more cigarettes to make up the difference.