Scientists identify a class of medications that may prevent alcohol use disorders in people with PTSD

Scientists identify a class of medications that may prevent alcohol use disorders in people with PTSD

Survivors of abuse and trauma are far more likely than other people to develop alcohol use disorder (AUD); By some estimates, up to three-quarters of people with post-traumatic stress disorder (PTSD) report problems with alcohol.

Now scientists at Scripps Research have identified a class of drugs that could break that connection. In animal models of PTSD, the drug reduced alcohol preference and consumption, as well as other behaviors associated with PTSD, including aggression, excessive anxiety, and hyperarousal. The results were published November 18, 2022 in Neuropsychopharmacology.

The overlap between PTSD and AUD is a big problem. We have shown that there is potential to alleviate both conditions by targeting common brain pathways.”

Marisa Roberto, PhD, co-senior author, Schimmel Family Chair in Molecular Medicine and Professor of Neuroscience at Scripps Research

According to the U.S. Department of Veterans Affairs' National Center for PTSD, approximately 12 million adults in the U.S. suffer from PTSD in a given year. Men and women who suffer from PTSD at some point in their lives are more than twice as likely as other people to have alcohol abuse or dependence. Additionally, people who suffer from both PTSD and AUD are at higher risk for suicidal thoughts and extreme aggression than people with either disorder alone.

Researchers know that FKBP5, a protein found in the brain, plays a role in both diseases. The FKBP5 gene is responsible for releasing the brakes on the brain's stress response pathways, and its genetic variants are associated with an increased risk of AUD and PTSD. In animals, higher levels of FKBP5 have been linked to both stress and alcohol.

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In the new study, co-first authors Bryan Cruz, PhD, and Valentina Vozella, PhD, and other colleagues examined rats with symptoms similar to comorbid human PTSD and AUD. Like people with the disorders, the animals drink above-average amounts of alcohol, are irritable and anxious, and exhibit anxiety and sleep disorders, the team showed. The researchers treated the animals with one of two drugs known to target FKBP5: benztropine (Cogentin®), which is FDA-approved for the treatment of Parkinson's disease and targets a range of molecules in the brain, or SAFit2, an experimental compound designed specifically to block FKBP5.

They found that benztropine reduced alcohol preference in stressed males and females, as well as aggressive behavior in females. SAFit2 reduced alcohol consumption in stressed men and reduced extreme anxiety in men and women. None of the medications affected sleep.

“The results may have been different between male and female animals due to reproductive hormones,” Cruz says. “There is emerging literature suggesting that the activity of these types of compounds varies in females during the estrous cycle.”

The team says the fact that benztropine is already approved by the FDA suggests the potential to reuse it in people with PTSD.

“We believe that FKBP5 inhibitors may be useful in preventing AUD after the onset of PTSD,” adds co-senior author Eric Zorrilla, PhD, associate professor in the Department of Molecular Medicine. “More work is needed to determine whether these compounds can also prevent the recurrent relapse that hinders recovery.”

Source:

Scripps Research Institute

Reference:

Cruz, B., et al. (2022) FKBP5 inhibitors modulate alcohol consumption and trauma-related behaviors in a model of comorbid posttraumatic stress and alcohol use disorder. Neuropsychopharmacology. doi.org/10.1038/s41386-022-01497-w.

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