Study: How Ketamine Changes Chronic PTSD Patient’s Brain Neurochemistry
Ketamine, which has long been used as an anesthetic and recreational drug, receives more attention nowadays for its therapeutic applications. Ketamine-assisted therapy (ketamine sessions combined with psychotherapy) seems especially useful in the treatment of depression. This includes the types that are treatment-resistant or which feature suicidality.
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Ketamine For PTSD
Like classic psychedelics, ketamine also seems to benefit people with various forms of emotional distress. These include:
- Bipolar disorder
- Anxiety
- Obsessive-compulsive disorder (OCD)
- Drug and alcohol addiction
- Post-traumatic stress disorder (PTSD)
A new brain imaging study, published in the journal Neuropsychopharmacology, suggests how ketamine may help those living with chronic PTSD.
PTSD is a type of anxiety disorder, affecting about 12 million adults in the U.S. during a given year. Six percent of the population will have PTSD at some point in their lives. In some individuals, though, that condition can be severe, chronic, and treatment-resistant. In these cases, the symptoms can be highly distressing and interfere with work, relationships, and everyday activities. These symptoms include intrusive memories related to the trauma and negative changes to thinking, mood, and emotional reactions.
When conventional treatments (psychiatric medication and psychotherapy) fail, ketamine can sometimes help. However, how the drug actually benefits people has not been clear. The experience itself may play a significant role, which seems to apply in the case of classic psychedelics.
Researchers believe that the way ketamine alters the brain — in terms of neurochemistry and brain region activity — matters, too. Ketamine may restore brain regions (and connections between them) affected by depression to a normal level of activity. And the same could apply in the case of PTSD and other conditions as well.
How Ketamine Alters The Brain In People With Chronic PTSD
This new study published in Neuropsychopharmacology, led by Adriana Feder, M.D., suggests improvements in PTSD following ketamine are related to specific changes in connectivity between several brain regions.
Feder and a team of researchers analyzed detailed brain imaging data of individuals with chronic PTSD. Each patient had been treated with ketamine in a randomized clinical trial. The trial was small, involving 30 chronic PTSD patients with moderate to severe symptoms.
Half of the participants received six ketamine infusions over a period of two weeks. The other half received infusions of the psychoactive placebo control drug midazolam. Both of these drugs act as anesthetics. However, in the trial, they were both given at sub-anesthetic doses.
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The trial was fully blind, so neither the participants nor the researchers knew which drug participants were randomly given.
Feder and colleagues had published previous research showing that repeated ketamine infusions over a two-week period significantly reduced PTSD symptoms in many participants while also reducing depression symptoms that often accompany PTSD.
The control drug from the study (which has anti-anxiety effects) also alleviated PTSD symptoms in some patients, but not to the same degree as ketamine.
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How The Study Was Conducted
In this new paper, the team analyzed brain imaging data from 21 of the 30 trial participants, drawing upon data from two scanning sessions: One carried out before the trial began, the other after most or all of the infusions were administered. This data allowed the team to identify “neural correlates” — changes in brain activity following the infusion of ketamine or the control drug.
The brain imaging sessions included scans made while participants were asked to respond to a computer monitor displaying faces depicting various emotions. The researchers also conducted a scan while participants were “at rest” — when they weren’t performing any task.
Irrespective of the drug given, improvements in PTSD symptom severity were related to connectivity changes between brain regions found to show abnormal activity in people with PTSD. These included two cortical areas: the ventromedial prefrontal cortex (vmPFC) and the dorsal/rostral anterior cingulate cortex (d/rACC), as well as emotion-processing areas including the amygdala and the anterior section of the insula.
The changes in connectivity in these areas were seen mainly when participants responded to “emotional faces” during the scanning sessions. More specifically, faces that were ambiguous or neutral, and those that displayed negative emotions, such as fear.
Results From The Ketamine For PTSD Study
The team suggests that there is a drug-specific mechanism that leads to changes in connectivity between the vmPFC and amygdala. Improvements in symptoms with both drugs were correlated with decreased excitation of circuitry from the amygdala to the vmPFC when participants viewed the emotional faces.
The vmPFC helps us make decisions based on information gathered from connections to the amygdala. It often involves controlling and regulating emotional experiences. Normally, it keeps the amygdala in check, allowing us to regulate stress, anxiety, and anger. This helps us to avoid feeling overwhelmed by our emotions.
In conditions like PTSD and depression, regions of the prefrontal cortex are underactive, while the amygdala is overactive.
By altering the connections between the vmPFC and the amygdala, ketamine can reduce PTSD symptoms like hypervigilance and hyperarousal. The ability of the vmPFC to restrain emotional responses can return, in other words.
Indeed, in Feder’s study, this connectivity change was only seen in participants with a decrease in symptoms following ketamine treatments. Ketamine increased “top-down” inhibition of the amygdala, exerted by the vmPFC.
Therefore, the team proposes that a reduction in the intensity of the threat response and/or an enhancement of learning to extinguish memory-based fear responses may be driving these decreases in PTSD symptom severity following ketamine treatment. Ketamine led to a greater response rate as well as a longer time — on average — to relapse. This might be due to ketamine’s ability to increase neural plasticity in brain regions linked to chronic symptoms.
The Benefits Of Using Ketamine Alongside Psychotherapy
If less intense threat and fear responses contribute to ketamine-related improvements in PTSD symptoms, Feder suggests combining ketamine treatment with psychotherapy might be especially beneficial. This is because many forms of psychotherapy help people with fear extinction learning (the lessening of conditioned fear responses following exposure to material that is normally distressing).
According to the team, ketamine-assisted psychotherapy could “‘open a window’ for the relearning of ingrained cognitive biases or maladaptive fear memories” associated with persistent PTSD symptoms.
