Cocaine use disorder

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Introduction0:00–0:45

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.

Physiological effects0:45–2:30

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.

Pharmacokinetics2:30–3:22

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.

Tolerance3:22–4:45

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.

Chronic use and withdrawal4:45–7:13

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.

Cocaine use disorder7:13–9:33

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.

Treatment9:33–9:58

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.

Review9:58–11:14

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.