The drug, acetazolamide (ACD), has long been prescribed for glaucoma, seizure disorders, and altitude sickness. Scientists now believe it could influence brain processes involved in returning to opioid use.
How Medications Affect Opioid Addiction in the Brain
The investigation was led by psychiatrist Dr. John Wemmie from the University of Iowa Carver College of Medicine. The team examined how the medication affects an enzyme in the brain called carbonic anhydrase 4 (CA4).
Their work focused on whether altering this enzyme could reduce biological changes that drive renewed drug seeking. Most medications used to treat opioid addiction interact with the mu-opioid receptor.
Examples include methadone and buprenorphine, which reduce withdrawal symptoms and limit cravings. However, these treatments do not fully address sustained changes in neural circuits connected to reward and motivation.
Because these changes remain after drug use stops, people can still be activated by stress or remainders associated with past use.
How Brain Changes Trigger Opioid Relapse
The Iowa group concentrated on the nucleus accumbens core, a region that’s strongly tied to reinforcement learning and motivation. Persistent shifts in neural connections within this structure are thought to contribute to relapse behavior.
Earlier experiments from the same laboratory showed that suppressing CA4 reduced harmful synaptic remodeling caused by cocaine exposure in animals.
How ACD May Prevent Opioid Relapse
In the new research, blocking CA4 increased activity of acid sensing ion channels, often called ASICs. These channels respond to small shifts in acidity during normal signaling between neurons.
When ASIC function is reduced, nerve cells react more strongly to drug-related stimuli. Increasing their activity appears to stabilize communication between cells and limit pathways linked to relapse.
Experiments reported in Neuropsychopharmacology found that either disrupting CA4 genetically or giving one dose of acetazolamide reversed opioid related synaptic alterations in mice.Â
The treatment also lowered oxycodone seeking during withdrawal. Because acetazolamide already has regulatory approval for other conditions, researchers believe it could move faster toward clinical testing as a potential treatment for opioid addiction.
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