In our previous article we examined the genetic and environmental correlates of addiction, focussing on how drugs create dependence. In this article, I’d like to take some time to examine the neurobiology behind tolerance and withdrawal.
Tolerance refers to our capacity to endure the effects of a drug. When we ingest a neuroactive substance, we flood our brains with a range of neurochemicals. Over time, we build a tolerance to the drug, meaning that we have to take more and more of it to get the same effect. So why does this happen? Well, our bodies are designed to maintain homeostatic balance (Pietrzykowski & Treistman, 2008). When we flood our nervous system with excess neurotransmitters, our neurons adapt to return activation levels to baseline, leading us to take more and more of the substance to overcome our own adaptation (Turton & Lingford-Hughes, 2016).
Withdrawal is very closely related to tolerance. Essentially, the opposing adaptations our nervous systems make to maintain homeostasis are unmasked when the substance is taken away (Substance Abuse and Mental Health Services Administration | US & Office of the Surgeon General, 2016). In fact, many individuals who have used substances for extended periods of time, note that much of their usage is done to avoid withdrawals (Hyman & Malenka, 2001). Let’s think about alcohol as an example. Alcohol is a depressant and chronic use of it will lead to a chronically under activated nervous system. In order to counteract this underactivation, your nervous system will naturally remodel itself to produce more glutamate, a neurotransmitter that excites the nervous system. When alcohol is removed, all that remains is a hyperexcitable nervous system (until enough time goes by and it is remodeled again to reach homeostasis). This is why it can be dangerous for an alcoholic to stop drinking cold turkey. The hyper excitability can cause seizures and psychotic symptoms (Newman et al., 2021).
Today, we have detoxification clinics to assist individuals in achieving sobriety without severe withdrawals. Drugs such as Naltrexone, methadone, and Suboxone are used to dramatically reduce the withdrawal symptoms one might experience. If you or a loved one is looking to kick your addiction, speak with a healthcare professional about safe and comfortable ways to enter sobriety.