In an experimental study published in Translational Psychiatry, taking a single dose of hydrocortisone immediately after watching a stressful movie was found to reduce intrusive memories related to the movie compared to the placebo group in the following days. Voluntary memory was unaffected. The effect was observed in both men and women.
Persistent, distressing involuntary memories are a feature of many psychological disorders. In posttraumatic stress disorder or PTSD, they are one of the most prominent features. PTSD develops in the aftermath of experiences of psychological trauma and is found in trauma survivors worldwide. In contrast to its wide spread, capacities for treating it are lacking.
Researchers have been studying ways to prevent the development of PTSD and one of the promising approaches focuses on prevention of the consolidation of traumatic memory. Conceptually, if a disorder is primarily characterized by intrusive memories, preventing such memories from being formed could potentially prevent the disorder as a whole. But can the formation of these memories be prevented using ingestible drugs?
“Uniquely among psychiatric disorders, there is a known cause for PTSD,” explained study author Sunjeev Kamboj, a professor of translational clinical psychology at University College London. “The cause is usually a traumatic (often life-threatening) event, which sets off a cascade of biological events in the brain that eventually lead to symptoms of PTSD, including the so-called ‘re-experiencing’ cluster of symptoms that includes distressing involuntary memories, and in extreme cases, true flashbacks.”
“These arise because the biochemical processes involved in ordinary memory formation are ‘hijacked’ by the traumatic event, resulting in abnormally strong memories. This abnormal strengthening occurs in the hours or days after the event, and as a result, we have a window of opportunity after a traumatic event to interfere with the formation of traumatic memories.”
“For example, it might be possible to use drugs to interrupt the biochemical processes involved in the formation of hyper-strong trauma memories,” Kamboj explained. “Various lines of experimental and clinical evidence suggest that raised levels of the ‘stress hormone’ cortisol might be associated with reduced occurrence of PTSD. My lab is particularly interested in developing treatments that affect memory formation, so we wanted to know whether giving participants cortisol (in the form of the oral medication, ‘hydrocortisone’) immediately after a mild simulated traumatic event in the lab, would affect the occurrence of subsequent traumatic memories.”
“We’ve also been very interested in the role of sex and sex hormones in PTSD, so we also looked at whether the effects of hydrocortisone would be affected by the background levels of estrogen and progesterone. Incidentally, it’s important to remember that women and men have these ‘female’ sex hormones in their systems!”
To test this, Kamboj and his colleagues conducted an experimental study on 120 healthy young adult volunteers, 18-35 years of age, recruited via online advertisements. Participants were randomly divided into two groups – an experimental and a placebo group.
All participants had their blood pressure and heart rate measured and saliva samples taken before and after the experiment. They completed a set of psychological assessments of mental health and general psychological characteristics that included depression (Beck Depression Inventory), anxiety (Spielberger Trait Anxiety Inventory), dissociation (Dissociative Experiences Scale-II), sleep quality and others.
Before and after the experimental treatment, researchers assessed subjective affect (Positive and Negative Affect Schedule, PABAS) and a range of subjective cognitive and physical sensations (The Bodily Symptoms Scale).
The experiment was conducted over 8 days. On the first day, after completing the described psychological and medical assessments, all participants viewed a stressful movie, intended as a proxy for traumatic experience. When the movie was finished, experimenters administered capsules containing 30 mg of hydrocortisone to the experimental group and identical looking capsules without active agents (placebo) to the control group.
The experiment followed a double-blind procedure, meaning that neither the experimenters, people who were giving capsules and running the experiment, nor the study participants knew whether they were in the experimental or the control group i.e., whether they are taking a hydrocortisone or a placebo capsule.
A 2-hour period followed to allow for drug absorption and participants were tasked to press a button on a wrist-worn device issued to them whenever they had a movie-related intrusive memory. For the next 6 days, participants were to complete a memory diary in which they would record intrusive memories related to the movie.
As expected, with days passing, intrusive memories related to the movie became less frequent, but this reduction in frequency was faster in the group that ingested hydrocortisone capsules. While the occurrences of intrusive memories were the same on average on the first day in both groups, on the second day already, and all subsequent days, intrusive memories about the movie were rarer in the group that received hydrocortisone than in the placebo group.
However, the difference became large enough to be confirmed with statistical tests, only from the fourth day onward. Further analyses confirmed the expectation that the frequency of intrusive memories was declining faster with time in the hydrocortisone group.
“Although the findings need to be properly tested in larger scale clinical trials with recently traumatized individuals, it seems that hydrocortisone might help people to more quickly ‘forget’ traumatic events if it is given very soon after a traumatic event,” Kamboj told PsyPost. “This is going to be difficult to test in clinical settings because traumatized individuals are usually treated in busy, chaotic emergency departments, and often their physical needs understandably take precedence over mental health. ”
“Nonetheless, a team in New York is doing this challenging work in a large-scale clinical trial using a very high dose of hydrocortisone (6 times higher than the dose we used in our study). The researchers expect to have preliminary results in spring or summer 2023.”
Effects of hydrocortisone were the same for people of both sexes, but appeared to depend on levels of female sex hormones – estradiol and progesterone. “Hydrocortisone-treated men showed fewer intrusions as estradiol levels increased, whereas women showed the opposite pattern”, the authors conclude, noting that a similar effect of progesterone was also present, but less pronounced.
“Although hydrocortisone, on average, sped up the rate at which people forgot about the traumatic event, the total number of involuntary memories they had after hydrocortisone treatment seemed to depend on their levels of circulating estrogen and progesterone,” Kamboj said.
“And the way in which these two hormones interacted with hydrocortisone seemed to differ in men and women. Overall, our findings suggested that whether hydrocortisone was helpful (or even potentially harmful) depended on biological sex, and the levels of estrogen and progesterone in saliva. For example, men with high levels of estrogen had the fewest involuntary trauma memories following hydrocortisone.”
“Interestingly, women seemed to show the opposite pattern – high levels of estrogen in women were associated with more intrusive memories following treatment with hydrocortisone,” the researcher continued. “Of course, these preliminary findings need to be replicated, but they suggest that hydrocortisone might not be a universally beneficial treatment for the prevention of PTSD and we need to do more work on determining which factors are responsible for making hydrocortisone an effective preventative treatment and whether there are conditions that potentially make it a harmful treatment in some individuals.”
The study provides an important contribution to finding new ways of preventing adverse psychological consequences of trauma. However, the authors note that the study design in which a movie is used to elicit intrusions might not adequately “mirror the phenomenon seen following real-life traumas.”
“As noted above, the key question is whether hydrocortisone is effective in trauma victims,” Kamboj explained. “There is unlikely to a simple answer to this question. For example, the clinical trial I mentioned is testing one (very high) dose of hydrocortisone but we know from a lot of previous experimental work that the effects of hydrocortisone strongly depend on its dose and that the relationship between dose and response is not linear.”
“I hope those researchers have selected ‘the right’ dose to test, but if they do not find an effect of hydrocortisone on PTSD prevention, we won’t know whether it was because the dose wasn’t quite right.”
The study, “Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone”, was authored by Vanessa E. Hennessy, Luzia Troebinger, Georges Iskandar, Ravi K. Das, and Sunjeev K. Kamboj.
