From recent advances in underlying neurocircuitry of fear and anxiety to promising pharmacotherapies for PTSD: The saga of heart, sex and the developing brain

Summary & key facts

This paper reviews what we know about how the brain makes fear and anxiety and what that means for medicines for PTSD and anxiety. Current drugs work only partly well, and no new anxiety drug has been approved in about 40 years. The review points to several promising directions, such as using low doses of serotonin psychedelics together with psychotherapy, ketamine, drugs that act on the stress hormone system right after a trauma, and new targets like cannabinoid and GABA systems. The authors also highlight big gaps in research, especially the lack of studies in females, how stress during development changes fear circuits, and the need to understand healthy versus harmful fear to make better, more tailored treatments.

Key facts:

• Existing medicines for PTSD mostly rely on two antidepressants, sertraline and paroxetine, and they help some people but often do not fully fix symptoms.
• No new drug specifically for anxiety has been approved since the 1980s, so drug development for anxiety has stalled for about four decades.
• Researchers are testing several new or renewed approaches, including low-dose serotonergic psychedelics (like psilocybin, LSD, and ayahuasca), MDMA, ketamine, cannabinoid-related drugs, and new GABA-targeting compounds.
• One idea is to give glucocorticoid drugs (stress hormones) soon after a traumatic event to try to change how the fearful memory is stored; this might help people who show a weak stress-hormone response after trauma, but the evidence is still uncertain.
• The paper warns that most preclinical studies use male animals, even though women have a higher chance of anxiety and PTSD; female hormones like estrogen seem to change how well fear extinction (the ability to reduce fear) works.
• Scientists are also studying deep brain circuits that control fear, such as the amygdala, hippocampus, prefrontal cortex, and brain stem areas, because better maps of these circuits could point to more precise treatments.
• The authors note a link between internal bodily signals (like heart and cardiovascular activity) and emotion regulation, and they suggest these body signals might be another route to treat PTSD, which often includes heart or autonomic problems.

Topics

Cancer, Stress, Anesthesia, and Immune Response Memory and Neural Mechanisms Stress Responses and Cortisol

Categories

Behavioral Neuroscience Life Sciences Neuroscience

Tags

Anxiety Anxiety disorder Anxiolytic Clinical psychology Exposure therapy Neuroscience Psychiatry Psychological intervention Psychology Psychotherapist Specific phobia

Substances

Ayahuasca Cannabis Ketamine LSD MDMA Psilocybin

Conditions & symptoms

Anxiety PTSD Anxiety or worry Panic Poor sleep