A drug that increases levels of a key endocannabinoid in the brain may be useful for helping patients with post-traumatic stress disorder (PTSD) unlearn fear, suggests an early-stage study published online in Biological Psychiatry.
“We have used a medication that blocks the way the body breaks down its own cannabis-like substances, or ‘endocannabinoids,’” said lead investigator Leah Mayo, PhD, of the center for social and affective neuroscience at Linköping University in Sweden. “Our study shows that this class of medications, called [fatty acid amide hydrolase] inhibitors, may offer a new way to treat PTSD and perhaps also other stress-related psychiatric conditions.”
Originally developed as a painkiller that subsequently failed to demonstrate adequate effectiveness in clinical trials, the medication increases levels of the endocannabinoid anandamide in regions of the brain that control anxiety and fear, researchers explained.
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In this experimental, double-blind study involving 45 healthy volunteers, investigators tested the drug’s effect on fear-extinction learning. Over 10 days, 16 participants received the fatty acid amide hydrolase (FAAH) inhibitor and 29 received placebo. Participants then underwent a slate of psychologic and physiologic tests. In one, they learned to associate the sound of fingernails across a blackboard with an image of a lamp. Afterward, they were coached to unlearn the fear memory through repeated exposure to the image without the unpleasant sound.
The next day, researchers gauged how well participants remembered that the lamp was no longer a threat.
“We saw that participants who had received the FAAH inhibitor remembered the fear-extinction memory much better,” Dr. Mayo said. “This is very exciting.”
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Dr. Mayo and colleagues are hopeful the drug can boost fear-extinction learning in patients with PTSD who undergo prolonged exposure therapy.
“Numerous promising treatments coming out of basic research on psychiatric disorders have failed when tested in humans. This has created quite a disappointment in the field,” said coauthor Markus Heilig, MD, PhD, a professor at Linköping University. “This is the first mechanism in a long time where promising results from animal experiments seem to hold up when put to test in people.
“The next step, of course, is to see whether the treatment works in people with PTSD.”
Mayo LM, Asratian A, Lindé J, et al. Elevated anandamide, enhanced recall of fear extinction, and attenuated stress responses following inhibition of fatty acid amide hydrolase (FAAH): a randomized, controlled experimental medicine trial. Biological Psychiatry. 2019 August 13;[Epub ahead of print].