Fentanyl primarily affects the central nervous system, which includes the brain and spinal cord. Fentanyl can cross the blood-brain barrier, a protective layer that separates the blood vessels in the brain from the rest of the body, and bind to opioid receptors in the brain. The effects of fentanyl on the brain can vary depending on the dose, the method of administration, and the individual’s biology and past drug use.

The following are some of the areas of the brain that are affected by fentanyl:

1. Ventral Tegmental Area (VTA) The ventral tegmental area (VTA) is a region in the midbrain that plays a critical role in the brain’s reward system. The VTA contains dopamine neurons, which release the neurotransmitter dopamine in response to rewarding stimuli, such as food, sex, and drugs. Fentanyl, like other opioids, can stimulate the release of dopamine in the VTA, leading to feelings of pleasure and reward.
2. Nucleus Accumbens (NAc) The nucleus accumbens (NAc) is a region in the basal forebrain that is connected to the VTA and plays a critical role in the brain’s reward system. The NAc contains dopamine receptors, which can bind to dopamine released from the VTA. Fentanyl can increase dopamine release in the NAc, leading to feelings of pleasure and reward.
3. Prefrontal Cortex (PFC) The prefrontal cortex (PFC) is a region in the frontal lobe of the brain that plays a critical role in decision-making, impulse control, and working memory. Fentanyl can impair PFC function, leading to poor decision-making, impulsivity, and memory impairment.
4. Hippocampus The hippocampus is a region in the medial temporal lobe of the brain that plays a critical role in learning and memory. Fentanyl can impair hippocampal function, leading to memory impairment and cognitive deficits.
5. Amygdala The amygdala is a region in the temporal lobe of the brain that plays a critical role in emotional processing, fear, and anxiety. Fentanyl can activate the amygdala, leading to increased feelings of pleasure and relaxation, but can also increase anxiety and fear.
6. Brainstem The brainstem is a region at the base of the brain that controls vital functions, such as breathing, heart rate, and blood pressure. Fentanyl can depress the respiratory center in the brainstem, leading to respiratory depression and potentially fatal respiratory arrest.

Fentanyl can have both short-term and long-term effects on the brain. Short-term effects include feelings of pleasure, relaxation, and pain relief, as well as side effects such as nausea, vomiting, dizziness, and confusion. Long-term effects of fentanyl can include addiction, tolerance, and dependence, which can lead to withdrawal symptoms when the drug is stopped.

Chronic fentanyl use can also lead to changes in the brain’s structure and function. Studies have shown that long-term opioid use can lead to a reduction in gray matter volume in the brain, particularly in regions involved in pain processing and reward, such as the amygdala, hippocampus, and prefrontal cortex. These changes can lead to cognitive deficits, memory impairment, and emotional dysregulation.