On which part of the body does long-term use of stimulants (e. g., nicotine, cocaine, and methamphetamine) have the most significant impact?

Stimulants are substances that all result in the increase of levels of dopamine in the brain, which is a neurotransmitter that affects attention and pleasure. What this means is that stimulants affect our brain and the way it works by changing the ways that nerve cells communicate.

Neurons (nerve cells) are the cells that have a role in transmitting messages from the brain to other parts of our body, and vice-versa, which is important for pain response, alertness, energy etc.

With long-term use, the use of stimulants would affect the central nervous system (speeding it up), the brain, and the functions necessary to live, like respiration, heart rate, blood pressure, body temperature. Levels of neurotransmitters like dopamine, serotonin, and GABA, which are responsible for the regulation of different processes,  are also impacted, which creates a chemical disbalance ultimately resulting in behavioral changes, mood swings, altered attention, movement and energy, stress etc.

So the part of the body that is affected the most with the long-term use of stimulants like cocaine, nicotine, methamphetamine is the brain of course, which is where these substances have the most impact, but the impact on the central nervous system, autonomous nervous system, and neurotransmitter levels is significant.