Long-term use of which substances can lead to serotonin depletion and depression?

Long-term use of which substances can lead to serotonin depletion and depression?

• A. Ecstasy and MDMA
• B. Ketamine
• C. LSD
• D. Psilocybin

Answer: (A)

Serotonergic neurotoxicity from repeated use is the key idea. Ecstasy/MDMA can cause a surge of serotonin release and uptake that, with repeated high-dose use, damages the serotonin system itself. This can lead to lasting reductions in serotonin signaling, which often show up as depressive symptoms between or after sessions. In other words, the drug’s effect on serotonin becomes counterproductive with chronic use, producing depletion and mood problems over time. Ketamine, LSD, and psilocybin operate through different mechanisms and aren’t classically linked to this kind of long-term serotonin depletion. Ketamine works mainly through NMDA receptors and is studied for rapid antidepressant effects; LSD and psilocybin are primarily 5-HT2A receptor agonists, with long-term mood disturbances not typically described as serotonin depletion in the same way.

Serotonergic neurotoxicity from repeated use is the key idea. Ecstasy/MDMA can cause a surge of serotonin release and uptake that, with repeated high-dose use, damages the serotonin system itself. This can lead to lasting reductions in serotonin signaling, which often show up as depressive symptoms between or after sessions. In other words, the drug’s effect on serotonin becomes counterproductive with chronic use, producing depletion and mood problems over time.

Ketamine, LSD, and psilocybin operate through different mechanisms and aren’t classically linked to this kind of long-term serotonin depletion. Ketamine works mainly through NMDA receptors and is studied for rapid antidepressant effects; LSD and psilocybin are primarily 5-HT2A receptor agonists, with long-term mood disturbances not typically described as serotonin depletion in the same way.