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

Cocaine, sometimes called coke, is a powerful
psychoactive stimulant that alters how the brain functions – specifically how we perceive
our surroundings. Cocaine comes from the leaves of the South
American coca plant, and has been used for over a thousand years. In modern times, it’s become a popular “party
drug” because cocaine reduces inhibitions and creates a feeling of euphoria or pleasure
that lasts between fifteen to ninety minutes, depending on how it’s taken. Around 18 million people worldwide use cocaine,
and this is because of its strong potential for addiction and overdose, and also for that
reason the drug is heavily regulated in a lot of countries. To understand how cocaine works, let’s zoom
into one of the synapses of the brain. Normally, electrical signals, or action potentials,
travel down the axon to the axon terminal, where they trigger the release of chemical
messengers called neurotransmitters from synaptic vesicles into the synapse. The neurotransmitters travel across the synapse
and bind to receptors on the postsynaptic neuron, where they give the cell a message. After the neurotransmitters have done their
job, they unbind from the receptors, and can just diffuse away, get degraded by enzymes,
or get picked up by proteins and returned to their release site in a process called
reuptake. Cocaine increases the release of certain neurotransmitters,
but it’s biggest effect is blocking reuptake receptors on presynaptic axon terminals, and
both actions keep neurotransmitters like dopamine, norepinephrine, and serotonin in the synapse
longer and increases their effects. For example, increased concentrations of dopamine
in the brain’s reward pathway, which includes the nucleus accumbens, ventral tegmentum,
and prefrontal cortex, produce intense feelings of euphoria, pleasure, and the emotional “high”
associated with cocaine. The physical “high” or feeling of hyper-stimulation
is caused by increased norepinephrine concentrations throughout the brain, which produces a variety
of effects throughout the body like increased energy, constricted blood vessels, dilated
pupils, increased body temperature, increased heart rate, and increased blood pressure. And finally, higer levels of serotonin are
associated with greater confidence. Now, cocaine can get into the blood and to
the brain a few ways. One way is by ingesting it, but the drug is
often inactivated by stomach acid unless it’s mixed with something alkaline. It’s also metabolized by the liver, and
cocaine causes capillaries in the mouth and esophagus to constrict, making it harder for
it get absorbed. A more direct route is insufflation – or snorting
it – because the drug is rapidly absorbed through the mucous membranes of the nasal
passages, or smoking it so the drug can be absorbed through the lungs. The fastest route, though, is direct injection
into the blood. Typically, the faster cocaine reaches the
brain, the stronger the relationship between the behavior and the reward, which ultimately
leads to addiction. And this addiction can cause many individuals
keep coming back to use cocaine. Now, your brain is constantly striving for
balance, and if you use cocaine regularly, your brain starts to notice that it is constantly
flooded with dopamine. As a result, it down-regulates dopamine receptors,
which means that the receptor is no longer active and the dopamine can’t give its message
to the postsynaptic neuron. This decreases the effect that a particular
amount of dopamine can have in your brain, so it you want to continue to feel euphoric
when taking cocaine, you have to take more and more to make up for the down-regulated
receptors – at this point, you’ve developed a physiological tolerance to cocaine’s effects. More cocaine use – means more down-regulation,
but if the cocaine use stops, then the receptors slowly up-regulate once more. Alright, so now let’s say that you’re
at rest, there aren’t any drugs or anything stimulating your reward pathway. In this situation, your brain keeps your heart
rate, your 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 message, your brain brings things back down to this baseline. With repeated cocaine use, a few things start
to happen. Let’s say you take cocaine at a specific
time and setting, like 3pm in the bedroom, and, because it’s a stimulant, it makes
everything speed up, including heart rate, blood pressure, and wakefulness. Your brain being the smart brain that it is,
though, will pick up on the pattern. Now, next time, at 3pm in the bedroom, the
brain preemptively decreases each one, since it knows that when you take cocaine, everything’s
going to increase again. Now, let’s say 3pm in the bedroom rolls
around again, but there’s no cocaine… In that situation, the brain still decreases
everything..but the changes aren’t countered with the effects of the drug, and so the person
can feel awful, and these are called withdrawal symptoms. These symptoms can persist to the point where
a person may need drugs just to feel normal, and if that’s the case, they are considered
to be dependent on that drug. Now, on the flip side, let’s say that you
use the drug in an unfamiliar setting, like at 11pm at a party. Well in that situation, your body’s not
ready for the drug and there’s no physiologic “counterbalance” to help offset the effect
of the drug. When that’s the case, it can lead to overdose,
even on a dose that the person’s been normally taking, and that’s often times what happens. Mild symptoms of cocaine withdrawal are mostly
psychological: and include things like depression, anxiety, fatigue, reduced concentration, cravings,
tiredness, increased appetite, excessive sleeping, and vivid dreaming due to increased time in
REM sleep. The worst cocaine withdrawal symptoms begin
after a long period of habitual use: this period is called a “crash”, with long-time
users experiencing suicidal ideation, and physical symptoms like nausea, vomiting, and
in severe cases, the sensation of insects crawling over the skin. These symptoms are really awful, and often
drive people to use cocaine again; a process called negative reinforcement, since stopping
the drug results in negative consequences, and that reinforces more drug use. There is also positive reinforcement from
the dopamine-induced euphoria, again leading to more drug use. Together this positive and negative reinforcement
leads to cocaine addiction also known as stimulant use disorder. The DSM-5 or Diagnostic and Statistical Manual,
the 5th edition, defines stimulant use disorder as causing at least two of the following behavior
patterns within a year: 1. Using more stimulants or using them for longer
than intended. 2. Being unable to cut down on the use of stimulants. 3. Having stimulant use take up a significant
amount of time 4. Having cravings to use stimulants. 5. Having stimulant use affect responsibilities
at work, school, or home. 6. Using stimulants even if they cause recurrent
interpersonal problems 7. Giving up important activities in order to
use stimulants. 8. Using stimulants in physically dangerous situations. 9. Using stimulants even if its worsening a physical
or psychological problem 10. Becoming tolerant to the stimulants. And finally 11. Feeling withdrawal symptoms from stimulants. Having 2 or 3 of these symptoms is considered
mild, having 4 or 5 is considered moderate, and having 6 or more is considered severe. Now, cocaine dependence often leads to an
overdose, which kills thousands of people each year. A cocaine overdose can cause hyperthermia,
where the body temperature gets really high, as well as seizures, and a very high blood
pressure, to the point where a person may have a stroke, a brain hemorrhage, or even
a heart attack. In those situations, the most important thing
is to keep a person physically safe, protect their airway, make sure that blood is circulating,
and to give a sedative like diazepam or lorazepam to relax the muscles and to cool the body
using a cool compress or fan. Generally speaking, higher doses of cocaine
carry the greatest risk of addiction and death. Taken by itself, cocaine has a short half-life
and is almost completely metabolized by the liver in about an hour. Cocaine, though, is frequently consumed alongside
alcohol, which produces a new substance in the body called cocaethylene. Cocaethylene has similar actions to cocaine,
but its half-life is longer, and it has an greater-than-additive effect, enhancing the
body’s responses to both alcohol and cocaine. In other words, taking cocaine with alcohol
is worse than simply adding up the effects of each of them alone. There are limited options for medical treatment
of cocaine addiction – Modafinil, a drug used to treat narcolepsy, has been researched,
and another medication – Ibogaine – has been used in some countries around the world. As a result, the focus has largely centered
on psychotherapy techniques and support groups done in both inpatient rehabilitation settings
and outpatient settings. All right, as a quick recap, cocaine use inhibits
the reuptake of dopamine, norepinephrine and serotonin neurotransmitters in the brain,
which produces feelings of euphoria. 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 cocaine to feel normal and avoid withdrawal. Treatment is focused primarily on therapy
— with a lot of love and support from family and friends.


  1. It would have been a bit nicer if you went more into the pharmacodynamics and the specific mechanism of action. but good video anyways!

  2. This video brought to you by Merc and Co. Cocaine tm, "She don't lie, she don't lie.. Cocaine"

    Physiologic counterbalance, best taken with alcohol.

  3. You forgot to mention one of its main feature
    As opioid agonist
    Which is why it’s been used in medical practice for years as an opioid agonist like morphine )

  4. great video!, i wonder if you have temperature related injury like frostbite, hypothermia and heat stroke….those are complicated af…..

  5. I totally love your channel!!! I am a third year medical student and your videos are extremely interesting and helpful! Keep up the wonderful work!

  6. Just a minor mistake – the structure you marked as nucleus accumbens is actually the thalamic adhesion 🙂

  7. I remember this one class with my social studies teacher….
    Teacher: And so, I'm on the RUN, cause I got my COCAINEEEEE in the back seat of my car, but DO NOT let the cops find out! Ohhhhh boy!

    She's so energetic, I honestly think she does use some drugs….XD

  8. 4 months clean now. I didn't use it a lot but worked in bars here it became a almost everyday thing. Unfortunately it is rampant in that environment but if you ever feel like you are having a hard time just educate yourself and find something to do

  9. why am i watching this blasted out of my mind on blow, it's 1:33am and i just came out of a party why am i watching this

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