Why does the addict have to take more and more of the substance to get the same high as before?
A quick review. Tolerance happens when the neurons start down-regulating the amount of receptors they have that would normally respond to a drug or dopamine itself.
There is a second way Tolerance can develop. In the center of the brain, right behind your nasal sinuses is an area called the Nucleus Accumbens (NA). This is the part of the brain mainly responsible for the euphoria associated with drug use. More specifically the LIKING of using a drug. MRI scans have shown high activity in this area when rats taste sweet juice, when mothers see pictures of smiling babies or men see pictures of attractive women.
When a drug is present causing euphoria the NA can get overstimulated. It happens to have a built in process to decrease its own stimulation. It would be like if you get overworked and you have a level you can pull to decrease your workload instantly. The NA does just this. In biology it is called a homeostatic feedback inhibition loop. In layman terms it’s a process to slow down it’s function to go back to an acceptable equilibrium.
For my nerdy friends and other doctors it happens via Kreb, a genetic transcription factor which is produced by the NA and leads to the transcription of Dynorphin, a natural endogenous opioid. The dynorphin will then inhibit the NA.
When this happens, even everyday pleasures get numbed, things like seeing a friend, eating ice cream or seeing your sports team win.
Luckily this can go back to normal once the drug use is halted.
Another change that happens in the brain in response to repetative substance use is called Sensitization. The Dopamine circuit gets stronger meaning the associated cues get more and more reinforced which ultimately leads to more and more craving for the drug. For example, with tobacco use, research has shown in a 1-2 pack per day smoker there is almost a thousand triggers associated with craving a cigarette. Things like seeing a gas station, smelling smoke, getting in the car, waking up, a cup of coffee, a meal, after sex, seeing smoking on TV, the colors of your favorite cigarette, stress, a lunch break and so on.
There is a process called Stacking which refers to the events leading up to an unexpected reward. Similar to chess players who come across a surprize tactic that results in a win, they tend to remember all the moves that led up to that win. Similarly the brain starts remembering the actions taken that leads up to using a drug. This can be stopping by the ATM to get cash, then calling the dealer at the right time, then driving to a certain place for lunch in close proximity to the drug deal, then stopping at the park to use before getting home and so on.
The third major change in the brain is an actual physical change. The prefrontal cortex (PFC) is the advanced human brain that many animals lack. It’s the biggest in humans and it’s responsible for executive function, like the CEO of the brain. The PFC helps you get to work on time, prevent you from swearing in front of your children or running naked down a busy road. MRI scans have shown shrinkage in this area over time as people continue to engage in substance abuse.
An easy way to test the PFC is via the Stroop Experiment, check it out here.
It is very difficult for chronic drug or alcohol users to rapidly read these words correctly.
It is also noted, that the more the PFC loses control to the primitive brain, the part responsible for pleasure seeking, the more likely it will lose future battles.
This is where coping mechanisms play a huge role in addiction recovery, check back next time for some coping skills.
Information obtained from The Great Courses: The Addictive Brain.