“If one oversteps the bounds of moderation, the greatest pleasures cease to please.” – Epictetus
One of the first posts that I placed on this blog was titled “Part II – The Dopamine Response, Addiction Stole My Brain”. In that post, I addressed my understanding of the reason that the dopamine system exists in our brain and how it is hijacked by addictive behaviors or substances. In that discussion, I stated that the brain starts shutting down dopamine receptors in response to the flood of dopamine and that is the cause of drug tolerance. This is true although it is not the only cause of drug tolerance and I want to address that now.
Drug Tolerance Due to Turning Off Receptors
I think that nearly everyone is familiar with drug tolerance that occurs when someone abuses drugs. In short, the more often and the more heavily you misuse a substance, the less your brain responds to it and the more that you require. This is the reason that someone with a substance use disorder (SUD) requires more and more of their drug of choice as their active addiction continues.
In an earlier post, I stated that your brain responds to the massive flood of dopamine caused by drug use by progressively turning off dopamine receptors. Since the “high” that comes from drug use is the result of a huge release of this feel good chemical, dopamine, hitting dopamine receptors in your brain, the brain attempts to protect itself by progressively shutting down receptors. With fewer and fewer receptors, the individual needs more drugs to prompt the release of more dopamine. However, this person will never reach that first “good” high that they got when all their receptors were active. I presented this explanation because I believe that it is true but there are other things going on that also contribute to drug tolerance.
Drug Tolerance – Less Dopamine
I believe that the brain of someone with a SUD cannot stop the flood of dopamine caused by misuse and that is why the brain resorts to shutting down receptors. It is apparent, however, that there is a decrease in the amount of dopamine released. It was explained to me that this decrease in dopamine release is the result of fatigue. In other words, the individual’s brain is unable to keep up with the demand for dopamine created by the drug. This does not completely explain our observations because it does not explain how increasing the amount of drug used would increase the response of a fatigued system. It would, however, explain the observed, lower baseline dopamine levels in individuals suffering from addiction.
Adaptation
Tolerance can also be viewed as adaptation. Adaptation implies that there is something more that results from ongoing misuse than just a change in the dopamine system. That is, as misuse continues, your brain adapts more and more to the effects of the substances that you are misusing. Therefore, your brain fulfills less and less of the role that the drug is providing and you require more and more of that substance.
This is the primary problem with prescribing opiates to control chronic pain. As the brain adapts to the dose of opiates, the body requires more opiates to alleviate the pain. If a doctor responds to continued pain with increased dose (as they were taught in the 1990s and 2000s), the patient is put on the fast track to addiction.
Adaptation is also very apparent when a person with a SUD experiences withdrawal. It is my understanding that withdrawal is horrendous, and that heroin withdrawal is almost unbearable. Since the brain has adapted to having the drug of choice, it ceases to provide the effects that the drug was providing. When the drug of choice is no longer used, the brain is not immediately equipped to replace the effects that the drug provided. For example:
- Opiates provide pain relief and sedative/relaxation effects. When someone who has been abusing opiates goes into withdrawal, they experience tremendous pain throughout their entire body, they cannot sleep, they cannot relax, and they experience panic-attacks.
- Crystal meth and other methamphetamines hype you up. They may keep you up and active for a few days without sleep. Withdrawal causes individuals that misused these substances to sleep for long periods during the first few weeks that they are experiencing withdrawal.
- Benzodiazepines, such as Xanax, Klonopin, Ativan, and Valium, are prescribed for anxiety, depression and as antiseizure medicines. Withdrawal may cause insomnia, anxiety, panic attacks, and seizures.
- Cocaine is a stimulant that causes euphoria. Withdrawal from cocaine use may cause anxiety, depression, and fatigue.
Summary
There appear to be three different factors associated with drug tolerance while misusing drugs. These include:
- Dopamine receptors are turned off by the brain in an effort to protect itself from the excessively high dopamine levels caused by the use of addictive substances. It is believed that the brain cannot control the dopamine release, so shutting down receptors is the only option.
- The brain’s dopamine system may experience fatigue, meaning that the brain can no longer produce enough dopamine to satisfy the demand placed on it by the drug misuse. This response does not explain all the effects of tolerance but it does fit the observed reduction in dopamine levels in the brain of a person suffering from SUD.
- Adaptation causes tolerance by the brain adapting to the presence of the drug. This becomes apparent during withdrawal.
Do you have ideas or experiences to share? Please comment, let’s work together and help each other to understand this problem.