Pharma & Psychedelic Interventions for Trauma
Prof Merel Kindt has been researching the potential of pharmaceuticals used in conjunction with exposure therapy to undo emotional learning and fear memory.
Kindt’s work explores using propranolol for people with post-traumatic stress disorder (PTSD) when recalling memories, even many years after a traumatic event has occurred. Her work has demonstrated that administering propranolol can bring about a reduction of fear associated with trauma leading to a reduction in avoidant behaviour, intrusive memories and other symptoms relating to PTSD.
Propranolol, known as ‘beta blockers’, is commonly used to treat a number of health conditions – high blood pressure, irregular heart rate, performance anxiety, thyroid problems, tremors, migraines, to prevent further heart problems in those with angina or previous heart attacks – to name a few. In addition to these, used in the appropriate way, propranolol could be a breakthrough treatment for symptoms of PTSD. Propranolol blocks the effects of norepinephrine – a hormone similar to adrenaline involved in the fight or flight response – in the brain. Used in conjunction with recalling traumatic events it has the potential to neutralise fear associated with the traumatic memory by disrupting the way a memory is put back into storage after being retrieved in process called ‘reconsolidation’.
Prof Kindt initially conducted research among healthy participants using Pavlovian-style fear conditioning using images and an electric current. Later she treated people with phobias, especially arachnophobes (people with a fear of spiders). In a controlled study Kindt exposed arachnophobes to spiders for two minutes and then gave them propranolol. Results saw participants being able to touch a tarantula within days and, by three months, many felt comfortable holding the spider with their bare hands. Their fear did not return even at the end of one year. The following quote from an article by Freidman (2016) best describes how it works:
Arachnophobes have an emotional memory that involves an association between spiders and a dreaded outcome, like a spider bite. This “fear memory” is the source of their phobia — even if (as is often the case) it never actually happened. The basic idea is that when Dr. Kindt briefly exposed the subjects to the spider, she reactivated their fear, which made the fear memory susceptible to the influence of propranolol. Reconsolidation is a bit like pulling up a file on your computer, rewriting the same material in a bigger, bolder font and saving it again. Disrupting reconsolidation with propranolol or another drug is akin to retrieving this document, erasing some or all of the text and then writing something new in its place.
In the 1960s, scientists knew that pharmaceutical drugs could affect memory recall but because it was difficult to isolate one part of the brain such research was discarded. In 2000 Karmin Nader and Dr Glen Shafe published research that heavily influenced Kindt. They injected rats with a drug in their amygdala that blocks protein synthesis shortly after fear conditioning. Consequently, the rats did not acquire long term fear memory. From these experiments they asserted that memory is unstable; not fixed but reinforced by neurological processes of re-remembering. This discovery also explained that memories are open to suggestion, why people have false memories, and why two people will remember the same
event very differently, especially over a long duration of time from that event. Sandra Blakeslee (2000) explains:
It seems that every time an old memory is pulled into consciousness, the brain takes it apart, updates it and then makes new proteins in the process of putting the memory back into long-term storage. The fact that new proteins are made means that the memory has been transformed permanently to reflect each person’s life experiences — not the memory itself.
Nader et al.’s research proved the treatment to be time dependent – if the drug was administered 6 hours after the event then the brain had already made new proteins to consolidate and store the memory. They wanted to find a way to make memories “liable” again after they have been consolidated. Nader et al. theorized that old memories were made “labile” whenever they were recalled, and required further protein synthesis in order to be of use in future situations. Their research suggested that there seemed to be a brief window in between the retrieval of an old memory and the creation of a new memory in which the old memory is vulnerable to manipulation.
In 2003 Prof Kindt got her post at the University of Amsterdam to research reconsolidation, and four years later won a grant to study the theory in humans. For people with PTSD, compared to those who have phobias, memory is much more complex as it is more difficult to pinpoint external stimuli (such as a tarantula) that will trigger their fear. Nevertheless, Kindt’s work treating anxiety disorders has been very successful, with propranolol assisted therapy working 70 percent of the time with panic disorder and with ten of the twelve PTSD cases she has accepted.
Her work also builds on the work of Roger Pitman et al. (2002) who published a ground-breaking, albeit controversial, study that proved his hypothesis that by administering propranolol after a traumatic incident – in this case car accidents – the incidences of PTSD occurring in victims would be significantly reduced.
PTSD can be described as a disorder of the memory whereby the effects of traumatic event/s invade the sufferer’s everyday life in intrusive ways. By blocking the effect of norepinephrine and disrupting memory reconsolidation, Kindt’s research may offer people a way out of uncontrollable fearful memories being relived in the present. Her 2015 paper on the subject concluded that ‘[a] new wave of treatments that pharmacologically target the synaptic plasticity underlying learning and memory seems to be within reach.’
A tenant of this research which I personally find fascinating is the aspect of bioethics. Does such a breakthrough in traumatic memory processing create a world whereby we have a pill that soothes victim and perpetrator alike, allowing soldiers to enact violence guilt-free, where dystopian style dehumanised armies could kill without conscience? Her research is often cited alongside the fictional film Eternal Sunshine of the Spotless Mind in which two ex-lovers hire a company to have their memories of each other erased, only to repeat their mistakes when they meet by chance and, unaware of their past, start a romantic relationship again. Memories are an important part of the human psyche; they contribute towards the creation of personality and self, and serve important evolutionary functions that protect us from harm’s way based upon past experience. Kindt is aware of the ethical considerations has co-authored a research paper with James Elsey (2016) on ethical debates related to memory modification.
References
Blakeslee S. (2000) Brain-Updating Machinery May Explain False Memories in The New York Times Online.
Elsey, J & Kindt, M. (2016) ‘Manipulating Human Memory Through Reconsolidation: Ethical Implications of a New Therapeutic Approach’ in AJOB Neuroscience, 7:4, 225-236, DOI: 10.1080/21507740.2016.1218377
Nader K., Schafe G.E., LeDoux J.E. (2000) ‘Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval’ in Nature; 406: 722-726
Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP. (2002) ‘Pilot study of secondary prevention of posttraumatic stress disorder with propranolol.’ Biological Psychiatry. Jan 15;51(2):189-92. doi: 10.1016/s0006-3223(01)01279-3. PMID: 11822998.
Soeter, M and Kindt, M (2015) ‘An Abrupt Transformation of Phobic Behavior After a Post-Retrieval Amnesic Agent’ in Biological Psychiatry. Volume 78, Issue 12, P880-886.
