Which statement about chronic opioid use is true?

• A. It has no effect on tolerance
• B. It only causes dependence
• C. It only causes tolerance
• D. It causes both tolerance and dependence

Answer: (D)

Chronic opioid exposure drives adaptive changes in the nervous system that produce both tolerance and physical dependence. Tolerance means you need higher doses to achieve the same effect because repeated stimulation of mu receptors leads to desensitization and receptor downregulation, plus compensatory changes in downstream signaling. Physical dependence means the body comes to rely on the drug to function normally, so stopping the drug or giving an antagonist triggers withdrawal symptoms such as yawning, lacrimation, sweating, muscle aches, diarrhea, and irritability. Because both processes commonly arise with long-term opioid use, the statement that it causes both tolerance and dependence is the true one. The other options miss one of these aspects or claim no effect on tolerance, which isn’t accurate.