Tobacco Dependence – causes, symptoms, diagnosis, treatment, pathology

There are over a billion people who smoke
tobacco around the world, which makes it one of the most popular psychoactive substances
used in society. The majority of tobacco users smoke cigarettes,
but some smoke cigars or pipes, chew tobacco or practice snuffing which is where ground
up tobacco leaves are pushed up the nose. Given the popularity of tobacco as well as
its negative health consequences, it’s considered one of the leading causes of preventable death
and disease worldwide. Cigarette smoke contains over 4,000 toxic
chemicals. These toxins cause endothelial cell damage
which creates inflammation along the inner lining of arteries. The inflammation increases the risk of having
a myocardial infarction – a heart attack, a stroke, and peripheral vascular disease
which is where there is severe pain in the lower legs. The toxins can also cause pulmonary problems
because the toxins get deposited into the lungs, which damages the lung tissue and makes
them more likely to get infected as well. Finally, the cigarette smoke has a lot of
different carcinogens, including ammonia, formaldehyde, carbon monoxide, which are associated
with cancers of the mouth, throat, lung, bladder, pancreas, and uterus. Combining these effects, a heavy smoker who
smokes two packs of cigarettes each day, for 20 years, loses about 14 years of life. Despite the negative consequences of smoking,
most people continue to smoke because tobacco contains nicotine, a tiny, fat-soluble molecule
that creates pleasurable psychoactive effects and is extremely addictive. Nicotine is considered “responsible” for
the high rates of tobacco dependence and addiction, while the 4,000 other chemicals and compounds
are “responsible” for the negative health effects associated with smoking. When a cigarette is lit, some of the nicotine
gets destroyed by the heat, and some gets into the smoke that gets inhaled. As a result, smokers are able to “self-titrate”
their nicotine dose by inhaling more frequently, more deeply, or for a longer amount of time. Once nicotine is absorbed into the bloodstream,
it binds to a type of acetylcholine receptor, called a nicotinic acetylcholine receptor
– also called a nicotinic receptor – which is found throughout the body and brain. In the central nervous system, nicotinic receptors
are on pre-synaptic axon terminals of neurons, and when nicotine binds to them, it triggers
the release of neurotransmitters like dopamine, acetylcholine, and glutamate, which is why
it’s considered an acetylcholine agonist. The psychoactive effects of nicotine are related
to the locations of nicotinic receptors in the brain and the exact neurotransmitters
that are released when the receptors are stimulated. For example, increased dopamine in the mesolimbic
system, a reward pathway composed of the ventral tegmentum and the nucleus accumbens causes
pleasure, improved attention and mental processing, and working memory. Nicotine directly increases dopamine levels
in the nucleus accumbens, but it also increases glutamate levels which gets the ventral tegmentum
neurons to release more dopamine onto the nucleus accumbens. Nicotine also decreasing the activity of inhibitory
GABA neurons in the ventral tegmentum, so by inhibiting the inhibitory neurons there’s
a double negative, which means that this is one more way to create an increase in dopamine
levels. When nicotine binds to receptors in the peripheral
nervous system, it increases blood pressure, heart rate, cardiac contractility, and gastrointestinal
tract activity. Nicotine also binds to receptors on skeletal
muscles causing relaxed muscle tone. Over time, individuals who consistently use
cigarettes can develop tolerance to the effects of nicotine. This means that with repeated use, they have
a reduced response to nicotine, and therefore an increased dose of nicotine is needed to
achieve the original response. At a cellular level, there are a couple theories
that explain why this might happen. One is that repeated exposure to nicotine
may cause nicotinic receptors to become less sensitive to nicotine. Another theory is that neurons may remove
nicotinic receptors from the cell wall in a process called down-regulation, leaving
fewer receptors available for binding. In either scenario, tolerance leads to the
need for higher and higher doses of nicotine over time. Let’s step back for a moment – and say that
you’re at rest, without anything stimulating your reward pathway. In this situation, your brain keeps your heart
rate, blood pressure, and wakefulness in a normal state, called homeostasis. Now, let’s say that your secret crush sends
you a text. All of a sudden you may feel sweaty and flushed,
your heart rate may jump a bit. You’re now above your normal level of homeostasis,
because something has changed, right? But it doesn’t stay that way for long, and
after the text, your brain brings things back down to this baseline. With repeated cigarette/tobacco use, a few
things start to happen. If you smoke at a specific time and setting,
like on the porch at 6pm after dinner, and being a stimulant, it makes everything speed
up, including heart rate, blood pressure, and wakefulness. Your brain picks up on that pattern! Next time, when you are on the porch at 6pm
after dinner, your brain preemptively decreases the heart rate, blood pressure, and wakefulness
in an effort to create balance, because it knows that when you smoke a cigarette, everything
is going to increase. Now, let’s say that your 6pm after-dinner
porch time rolls around, but you don’t have a cigarette. In that situation, the brain still decreases
heart rate and blood pressure, but the changes aren’t countered with the effects of nicotine,
and so you might feel awful. These awful feelings are called withdrawal
symptoms. Withdrawal symptoms can persist to the point
where a person may need to smoke just to feel normal. Symptoms of nicotine withdrawal include severe
craving for nicotine, irritability, anxiety, anger, poor concentration, restlessness, impatience,
increased appetite, weight gain, and insomnia. Withdrawal symptoms can begin within 2 hours
after the last use of tobacco, and typically peak within 1 or 2 days. While withdrawal tends to decline over the
next few days and weeks, many smokers continue to feel awful for months after their last
cigarette. The withdrawal symptoms associated with stopping
smoking and the intense feelings of craving make it very difficult to stop smoking – in
fact, nearly 70% of those who smoke say that they want to quit, and more than half of smokers
try to quit each year, but of those, only about 5% are successful. The liver is quick to metabolize and eliminates
nicotine from the body; in fact, it’s half-life is only about 1-2 hours. To maintain the positive feelings that nicotine
creates and avoid withdrawal, a person has to smoke a cigarette every 2 hours or so,
to reach a steady state of nicotine in the blood – and that helps explain why individuals
become chain smokers. Also, at night, the liver eliminates the nicotine
that has built up throughout the day, which is why heavy smokers often need a cigarette
first thing in the morning. There are a number of different smoking cessation
treatments. Nicotine replacement therapies include nicotine-containing
gum, lozenges, transdermal patches, nasal sprays, inhalers, dissolvable tobacco, mouth
sprays, and sublingual products. These products are meant to help a person
slowly taper their dose of nicotine and ultimately quit altogether. There are also medications that act on nicotinic
receptors like buproprion and partial nicotine receptor agonists like varenicline which help
reduce withdrawal symptoms and prevent relapse. Both of these can be used in conjunction with
nicotine replacement medications and have been shown to increase the success rates of
individuals trying to quit tobacco. Some smokers turn to electronic cigarettes,
which are battery-powered devices that produce a nicotine vapor that is inhaled. Like some of the other nicotine replacement
medications, they allowing smokers to go outside, enjoy the feeling of holding a cigarette,
and inhaling and exhaling a vapor. Electronic cigarettes offer the same theoretical
advantages of nicotine replacement, but unlike nicotine replacement medications there’s
less research on the safety of e-cigarettes. People trying to quit can also benefit from
simple therapy interventions, for example, simply asking a person about their willingness
to quit, actually increases the likelihood that they will quit. Typically at clinic visits, it’s recommended
to ask about tobacco use, advise to quit or cut back, assess whether a person is willing
to quit, assist with quit attempts by offering counseling and medications, and help arrange
or organize a support network. All right, as a quick recap, the nicotine
in tobacco affects different neurotransmitters and neural systems in the brain, which produces
effects that are initially pleasant or enjoyable, but can become more problematic and unpleasant
if smoking continues over time. Long-term use can cause tolerance, which is
the need for increasing doses to achieve the same effect, as well as dependence, which
is the reliance on the tobacco/nicotine to function normally. The most effective treatments can include
a combination of therapy and medications—with a lot of love and support from family and
friends. Thanks for watching, you can help support
us by donating on patreon, or subscribing to our channel, or telling your friends about
us on social media.


  1. Great concised Information, Clear narration and very helpful visualization.
    Great work!
    You are making a tremendous impact on the learning systems of today!
    Many thanks!

  2. and thats why i want all smokers expelled to Syberia

    i always say that: "another one way ticket to Syberia sold" when im passing by a smoker

  3. Isn't tolerance related to an increase of of nicotinic receptors on neurons, so more nicotine is required to bind to the receptors to achieve the same effect? Anyways, great video!

  4. Can you provide any evidence that Carbon Monoxide is a carcinogen (as stated at 1:15 in the video)? Although CO is certainly toxic, it is not generally considered a carcinogen.

  5. Amazing work guys 🙂
    Understood the concepts In less than 10 minutes that I haven't been able to understand slogging with medical textbooks since 2 years .

  6. Really really awesome way of providing information! Fell in love with your channel. Going to recommend to everyone i meet!

  7. There must be a group of geniuses out there making these videos. You have made learning medicine most pleasurable job for me. Thank you 🙂

  8. This was good info! Thanks. I'm on day number 15. My coach (thru texts) thinks I should not want a cigarette at this point. I still want a cigarette. Walked by someone at the store today, they were smoking it smelled like a great dinner. Holy shit!!! Not sure I can do this. Does anybody really know how long it will be before I don't think they're yummy? I really want to quit. This is so bloody hard.

  9. I hope this isn't to weird to say, but, I really like the sound of Tanner Marshall's voice. Thanks for all the info, I've been watching these videos a lot for Nursing School!!

  10. I don't quite get how nicotine (which has sympathomimetic effects) causes muscular relaxation and increase in gastrointestinal activity. I thought it was supposed to be increase in contractility (therefore muscular rigidity) and decrease of gastrointestinal activity. Can anyone enlight me in this?

  11. Ciggarettes is not a problem. Nicotine is a problem. if someone is addictive to Marijuana or ciggarretes then somebody surely told him a lie and he is lving from that persepective or point of view/understanding
    try to change it and beleive that Nicotine is jsut a 10 min craving addiction. and i need to quit it.
    now mail me all you Marlboros to my address

  12. Science needs to step it up already and figure out a drug that will inhibit the over expression of deltafosB as that is the primary cause of nicotine, amphetamine, methamphetamine and most psychostimulant addictions. They already have viral vectors that can inhibit deltafosB and modulate deltaJunD and G9a which would virtually abolish the addiction so there is zero excuse why no pharmacotherapy is available. We’re going on what 30+ years now with no pharmacotherapy yet opiates, alcohol and benzodiazepines have a whole plethora of pharmacotherapy 🤦🏻‍♂️

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