Beta-blocker drug erases the emotion of fearful memories

By Ed Yong | February 16, 2009 7:45 am

Blogging on Peer-Reviewed ResearchThe wiping of unwanted memories is a common staple of science-fiction and if you believe this weekend’s headlines, you might think that the prospect has just become a reality. The Press Association said that a “drug helps erase fearful memories“, while the ever-hyperbolic Daily Mail talked about a “pill to erase bad memories“. The comparisons to The Eternal Sunshine of the Spotless Mind were inevitable, but the actual study, while fascinating and important, isn’t quite the mind-wiper these headlines might have you believe.

The drug in question is propranolol, commonly used to treat high blood pressure and prevent migraines in children. But Merel Kindt and colleagues from the University of Amsterdam have found that it can do much more. By giving it to people before they recalled a scary memory about a spider, they could erase the fearful response it triggered.

The critical thing about the study is that the entire memory hadn’t been erased in a typical sci-fi way. Kindt had trained the volunteers to be fearful of spidery images by pairing them with electric shocks. Even after they’d been given propranolol, they still expected to receive a shock when they saw a picture of a spider – they just weren’t afraid of the prospect. The drug hadn’t so much erased their memories, as dulled their emotional sting. It’s more like removing all the formatting from a Word document than deleting the entire file. Congatulations to Forbes and Science News who actually got it right.

Kindt’s work hinges on the fact that memories of past fears aren’t as fixed as previously thought. When they are brought back to mind, proteins at the synapses – the junctions between two nerve cells – are broken down and have to be created from scratch. This process is called “reconsolidation” and scientists believe that it helps to incorporate new information into existing memories. The upshot is that when we recall old memories, they have to be rebuilt on some level, which creates an opportunity for changing them.

A few years ago, two American scientists managed to use propranolol to banish fearful responses in rats. They injected the animals in their amygdalae, a part of their brains involved in processing emotional memories. The drug didn’t stop a fearful memory from forming in the first place, but it did impair the memory when the rats tried to retrieve it. Now, Kindt has shown that the chemical has the same effect in humans.

Propranolol.jpgHer team recruited 60 students and conditioned them to fear images of spiders, by pairing the pictures with uncomfortable electric shocks. A day later, they showed them the same pictures and measured how strongly they blinked in response to a loud noise. These responses are called “startle reflexes” and they reflect activity in the amygdala and whether a person is in a fearful state of mind. Sure enough, the students were more easily startled by the noise if it was accompanied by the electrifying spider pictures than images they hadn’t learned to fear.

On this second day, Kindt gave some of the recruits 40 milligrams of propranol about 90 minutes before they were tested again. The others were given a placebo, but both groups reacted in the same way. Both of them could remember the fearful nature of the spider visuals, showing that the drug didn’t affect their ability to recall their old memory.

Two days later, and things were very different. Now, Kindt found that the while the volunteers on the placebo still feared the spiders, those who had been given propranolol no longer did. In fact, they were as difficult to startle as volunteers who had been conditioned in the first place. The drug had completely eliminated their fear response.

Once erased by propranolol, the banished fears didn’t resurface either. Over the course of the second day of testing, even the placebo group became less easily startled but a quick electric shock on the third day soon brought the anxious associations back into their minds. But the propranolol group were totally unaffected – even new shocks failed to shock them, or to reinstate their forgotten fear.  

Propranolol does nothing on its own – it can’t exile fearful responses unless they are brought to the surface again. But once they are, the drug’s effects are quick and dramatic – just one reactivation under the influence of propranolol completely eliminated the response. However the volunteers still expected a shock when they saw the spidery images. They remembered that the pain of electricity would normally follow the sight of a spider – they just had no emotional reaction to that knowledge.

How this works isn’t entirely clear. For a start, the fear memory could be “erased” or simply inaccessible there’s no way of telling which at the moment. Nor do we really understand what propranolol does. It’s one of a group of drugs called beta-blockers that interferes with hormones like adrenaline, by preventing them from sticking to their receptors, particularly in the amygdala. It’s possible that when people bring old memories to the fore and “reconsolidate” them, these drugs block the production of new proteins. That’s an essential part of the process and without it, the temporarily malleable memory could fade away.

Kindt suggests that this intrusion happens in the amygdala, which is involved in emotions, but not the hippocampus, where facts and events are stored. This may explain why propranolol doesn’t erase memories so much as divorce them from their emotional content.

Even that limited effect could have important implications for people suffering from emotional disorders or post-traumatic stress syndrome. Could propranolol help them get on with their lives by dulling the emotional sting of their memories? And almost more importantly, should something like that even be attempted?

From an evolutionary perspective, it is incredibly important that living things remember the important events in their lives – even traumatic or fearful ones could stop them from making costly or lethal mistakes later on. But the indelible nature of strongly emotional memories can be a double-edged sword. Most of the time, they provide valuable information but in some cases, they can be harmful as in the case of post-traumatic stress disorder.

But remember, that propranolol didn’t erase memories wholesale, just their emotional side. The usually excellent Science Media Centre released a couple of comments from scientists interested in medical ethics, neither of which really reflected this subtlety. For example, one John Harris said:

“An interesting complexity is the possibility that victims ,say of violence, might wish to erase the painful memory and with it their ability to give evidence against assailants.”

I fail to see how this is relevant. There’s no indication from Kindt’s work that victims of crime who used propranolol would lose the ability to recall details from previous incidents – they would just be less worried about future ones. You could argue that they risk putting themselves in similar situations again, but it certainly wouldn’t hamper their ability to testify in court.[Update: This criticism isn't valid based on previous research not discussed in the paper; see Vaughan's informative comment below]

Best of all, the Daily Mail predictably went into overdrive with talk of an “ethical furore” over drugs that “threaten human identity“. Presumably, someone missed the heavy, heavy irony of writing a fear-mongering headline about a drug designed to mitigate a fearful response. Perhaps Mail readers would benefit from a shot of propranolol before they delve into their daily dose of vitriolic terror?

Reference: Merel Kindt, Marieke Soeter, Bram Vervliet (2009). Beyond extinction: erasing human fear responses and preventing the return of fear Nature Neuroscience DOI: 10.1038/nn.2271

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Comments (20)

  1. Gil

    Propanolol is already used to treat social phobia and panic disorders because it reduces the physical symptoms associated with anxiety e.g. palpitations, sweating and shaking which often act as a precipitant to a full panic attack.
    There is a theory that we experience physical reactions first, and then interpret those to create an emotional response (there is also an opposite theory suggesting emotions lead to physical responses). Maybe that’s part of propanolol’s effect here.

  2. I would think it would make them more able to testify… without the intense emotion, they might be able to recall details they “block out” or face their attacker when they would otherwise have been to scared to.

  3. One little discussed aspect of past propranolol studies is that they typically report a reduction in the total episodic recall for emotional but not neutral stimuli in the propranolol condition.
    This doesn’t apply to Kindt’s study as there is no measure of episodic memory – it entirely relies on conditioning (implicit memory).
    However, there is a serious concern that propranolol-treated victims may not be able to fully recall all the relevant details of their experience which clearly has implications for the legal system.
    There’s a good review of the relevant studies and exactly this issue in:
    Henry R, Fishman JR, Youngner SJ (2007) Propranolol and the prevention of post-traumatic stress disorder: Is it wrong to erase the “sting” of bad memories? The American Journal of Bioethics 7: 12–20.
    http://dx.doi.org/10.1080/15265160701518474

  4. Ed Yong

    Thanks for the clarification Vaughan. I’ve struck out that criticism in the post.

  5. Glad someone on SB covered this, been worried about it since I caught the story on the BBC news site. I was taking propanolol for anxiety attacks during the period of my break-up with my wife. My friends have been surprised at how well I handled everything – so have I, given how badly it affected me at the time – and now I can’t help but wonder if the propanolol has had anything to do with it.
    It seems to be a positive thing in terms of effects but I don’t know, something about it makes my skin crawl. Is it really helpfuul to have these emotional memories blocked out rather than dealing with them properly? Wish I understood the science a bit better…

  6. Merel Kindt

    The media has blown our study out of proportion. Thank you for your detailed explanation of both the study and the confusion. We indeed tested also the declarative memory (CS-US contingency) , which was completely intact after propranolol intake. Thus, there was no memory erasure, just elimination of the fearful response.

  7. It makes my skin crawl too. I know too many people on SSRI’s who no longer (if ever) derive any benefit but continue to take them because the side effects of withdrawal were so difficult. That makes me leery of the industrial applications of brain research that on its own is interesting. Conditioning with electric shock and spiders (which makes my skin crawl too…not the spiders, just the whole notion) is very simple. It doesn’t have the full context of violent experiences, especially when repeated and in a situation of helplessness such as ptsd due to war or even more so due to child abuse when the brain is still developing. I have great concern with the way pharmaceuticals run with research and how drugs get over-prescribed. Our society is too eager to get people happier and calmer with drugs. But our society, despite the vast number of mood altering prescriptions issued, is not happy and calm, and less so than countries that are more circumscribed with pills.

  8. Ed Yong

    Lilian, your point is well-taken, specifically on the difference between the spider-shocks and the full context of violent experiences. This is why it’s really important to not sensationalise studies like this.
    And let’s apply the same calm to our reactions – the only applications discussed in the paper were for specific conditions like PTSD and anxiety disorder, rather than more casual use.
    Cannonball – I think the question is what “dealing with them properly” actually means? Gil, care to chime in on this?

  9. I agree with gil, I don’t believe we’ll find the effect of this drug is actually directly on the brain but rather it interrupts a feedback cycle between negative emotions or fear and the sympathetic input that makes those experiences so much worse – the racing heart, the shaking hands, the feeling like your stomach just collided with your testicles. And once you start feeling those things the experience becomes even more frightening because you feel like you’re losing control, you’re shaking in front of other people and generally evincing the objective symptoms of fear. It’s much more real a feeling and makes sense it would generate a negative memory than rationally considering one’s fears without such physical inputs.
    Hence you give people just the tiniest dose of the drug and it works wonders for performance anxiety. It’s the secret of many musicians, comedians and other public performers. And they are really quite safe. B-blockers are really benign in terms of neural effects, but may cause some depression. Some people with heart conditions or potential for arrhythmia might be at some risk. But for the most part the drug is working on the sympathetic nervous system, not the central nervous system and rarely has any effect on mood or personality. Certainly with sporadic usage like with performers or after potentially PTSD-inducing events the effect can only be beneficial in situations in which there is just nothing to offer sufferers.
    And Lillian, your fear of drugs is irrational and quite harmful. There is no highly effective treatment for PTSD and this would offer enormous hope to a great number of people who are affected by an incredibly disabling disorder. There are few things more benign in the medical armentarium than a 5mg dose of propanolol and we have to stop representing that people that seek help for mental illness are weak, defective, or somehow more harmed by its receipt than by its absence.

  10. Valhar2000

    There are few things more benign in the medical armentarium than a 5mg dose of propanolol and we have to stop representing that people that seek help for mental illness are weak, defective, or somehow more harmed by its receipt than by its absence.

    But drugs are not natural!!!1! Their damgerous!!1!!! REMEMBER HEATH LEDGER!!!11!1!!!!eleventy!!!1!

  11. Valhar2000

    Has anyone checked if this drug affects other emotional responses besides fear? For example, if you recall the best date you ever had while under the effects of this drug, would you thereafter not feel anything while remembering said date?
    And, a crazy idea: what if you gave this drug to a born again christian, and then asked them to describe the moment when they accepted Jesus as their Lord and Saviour (if that is the correct terminology)? Would they no longer give as much importance to their conversion?
    Also, if anyone tried that, they should ask an atheist to remember their deconversion while under the influence and see what changes.

  12. More on the media coverage of this story here

  13. Jeremy

    Don’t you spell it propranolol, not propanolol? Or can it be either?

  14. Ed Yong

    Oh dear, that’s embarrassing. FAIL. Now corrected.

  15. Michael

    Personally I spell it proprano… lol!

  16. Flymises

    Valhar,
    “Has anyone checked if this drug affects other emotional responses besides fear? For example, if you recall the best date you ever had while under the effects of this drug, would you thereafter not feel anything while remembering said date?”
    That’s an excellent point and certainly needs considering.
    Also, by experimenting with this, some more insight into the mechanism might be revealed.
    i.e. if a person does NOT lose their positive emotional connection with a memory while under the influence of Propranolol, it would suggest a behavioural mechanism where it’s the association of the relaxation induced from the drug paired with the stimulus that’s removing the memory.
    If positive emotions are erased, however, causation is more difficult because it could be an association with the neutrality of the drug and/or the prevention of the new ‘consolidation’ protein production.
    Additionally, of course, if positive emotions are erased, a whole new can of ethics is cracked wide open. People can’t really prevent themselves from recalling desirably emotive memories while under the influence of the drug! Eek!
    Or perhaps the can would be closed and the drug ditched for nothing more than experimentation…

  17. Flymises

    Ahem, Correction:
    “i.e. if a person does NOT lose … induced from the drug paired with the stimulus that’s removing the memory*.”
    *EMOTION/EMOTIONAL RESPONSE

  18. Flymises

    Ahem – correction:
    “i.e. if a person does NOT lose … induced from the drug paired with the stimulus that’s removing the memory*.”
    *EMOTION/EMOTIONAL RESPONSE

  19. I was on beta-blockers to treat familiar tremors from 1978 -1986. During that time, it seemed that I was a different person -practically fearless. Almost every memory prior to taking Inderal is gone –my childhood, my marriages, and raising my children.
    Sadly, it seems that it not only wiped out the bad memories, but all the good ones as well. It is as though there was never any bonding with my parents or my children. I think I would rather have my memories than to have lost all the good ones.
    They are addictive and when doctors switched dosage to long acting I have severe –almost psychotic side effects to the point I had to be hospitalized and weaned off them.

  20. Ed Yong

    Recommendation: for a beautiful and fascinating account of a year on propranolol, head on over to Stephanie Zvan’s blog Almost Diamonds.

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