Ethics and Memory-Altering Drugs

In the last several years new research has come out that may indicate that our memories are not set in stone and may perhaps be erasable. In the article Give memory-altering drugs a chance, author Adam Kolber presents many ethical challenges facing research of memory altering drugs. Kolber writes that society is alarmed by the prospect of altering memories fearing a person’s sense of identity may be lost as well as the ability to lead a true and honorable life. However, this fear and excessive debate over the ethics of memory alteration is, at this point, extreme and could delay key research in therapies for people who are debilitated by their memories. I believe that the current research on memory modification is worth pursing and with proper regulations, like any intense therapy, can meet most ethical challenges.

Current research has shown that beta blockers, used to control hypertension like propranolol, can reduce the emotional association to a memory when taken after a distressing event. One such study found that patients who received two weeks of propranolol treatment showed a significant reduction in post-traumatic stress disorder (PTSD) symptom levels compared to the control group.¹ However, this line of research only suggests that emotional salience of these memories can be reduced, not the memories themselves. Ongoing studies in rodents have suggested that if impeding the process of memory consolidation, either during the initial consolidation or after memory retrieval, memories can be erased.² Many of these studies require direct drug infusions into the brain and are currently not applicable to humans.

Kolber writes that the use of pharmaceuticals to alter memories has led many bioethicists to argue that rather than seeking a pill bottle, we should do the rewarding emotional work to change a bad experience into a good one. I believe this argument is not at all persuasive. It is possible that some memories, war or natural disasters for example, have no positive aspects to them. Some people who experience these events are very negatively affected by their memories. These pharmaceuticals may be a key tool in aiding and accelerating counseling. Schiller et al recently published a study that propose noninvasive techniques, no pharmaceutical intervention, which are able to eliminate fearful memories in humans³. However, studies with similar paradigms to the Schiller et al study in rodents have produced opposite and varying results under what appear to be identical conditions^4-5. These studies seem to indicate that behavioral manipulation alone may not be an effective treatment for every patient, and that the aid of pharmaceuticals could be very beneficial to these patients. Kolber cites psychiatrist Peter Kramer who describes, in his book Listening to Prozac, that some patients even report feeling more like themselves after taking antidepressants.

Future research into these potential beneficial effects of memory altering pharmaceuticals should not be prohibited; however ethical concerns may reveal contexts under which these drugs would need to be regulated. Kolber writes that there is already a precedence to prevent egregious uses citing the use of alcohol to prevent a person testifying is an obstruction of justice. Researcher’s should be encouraged to pursue new therapies for people trying to cope with trauma rather than dissuaded by potential ethical concerns that with proper regulation, could be avoided.

--Katie MacPherson

Neuroscience Graduate Program

Sources

1. Vaiva G. et al Biol. Psychiatry 54, 947-949 (2002)

2. Nader K. et al Nat Rev Neurosic 1, 216-219 (2000)

3. Schiller D. et al Nature 463, 49-53 (2010)

4. Monfils M. et al Science 324, 951-955 (2010)

5. Chan W. et al Learn Mem 17, 512-521 (2010)

The Benefits of Memory-Altering Drugs

Pharmaceutical drugs that dampen memories and/or dissociate memories from physiological reactions have the potential to provide powerful benefits for society. There are widespread wars, natural disasters, and other traumatic events that cause people to suffer from their memories of these events, the most extreme manifestation being PTSD. Post-traumatic stress disorder has been notoriously difficult to treat with therapy alone and the addition of pharmaceutical drugs to the treatment regimen may speed the healing process and make it more complete. Propanolol, for example, has been shown to reduce physiological responses during mental imagery of a traumatic event (Brunet et al. 2007). In PTSD, strong physiological responses tag memories as important and increase the frequency with which the brain recalls the traumatic memory, thereby driving a positive feedback loop, which is difficult to disrupt. A drug like propanolol that decreases physiological responses associated with a traumatic memory may be a promising way to disrupt the positive feedback loop and pave the way towards a faster and more efficient healing process.

Drug addiction is another illness that could greatly benefit from the application of these memory-dampening pharmaceutical drugs. Drug addiction is driven in part by reward learning mechanisms in the brain, such that learned associations between cues and illicit drugs contribute strongly to the addiction. People who are recovering from drug addiction may fall into drug usage again if they walk by a particular street or see a certain person that they strongly associate with the rewards of using the illicit drug. One study found that a drug called ZIP causes cocaine-addicted rats to forget the locations where they had received cocaine (Li Y.-Q. et al. 2011). Drugs comparable to ZIP that are developed for humans could help drug addicts unlearn strong associations that drive them to relapse, thereby speeding the rehabilitation process.

These memory-dampening drugs have great promise in treating debilitating disorders and continued research should not be delayed or hampered by the unwarranted ethical arguments against them. Some bioethicists argue that the use of these drugs may weaken peoples’ sense of identity and cause them lead less genuine lives. Instead, these bioethicists argue, people suffering from trauma or addiction should go through the difficult work of therapy rather than resorting to pharmaceuticals. This argument is weak because oftentimes therapy and pharmaceutical drugs are working towards the same end—unlearning associations as well as decoupling memories from physiological reactions—but accomplish them through different means. For example, one study demonstrated that a non-pharmaceutical approach allowed subjects to forget a learned association between a visual cue and a shock (Schiller at al. 2010).

The bioethicists’ arguments are not so much about the end goals that therapy and pharmacological interventions are striving for—as this distinction is weak—but instead belie a bias against pharmaceutical intervention itself. If we could successfully treat drug addiction and PTSD with therapy alone, these bioethicists might have a leg to stand on. But as it stands, these disorders and illnesses are extremely difficult to treat and there is a high rate of relapse. If the application of pharmaceutical drugs could increase the speed and efficacy of recovery, it seems unethical to deny people this treatment option. If further research reveals the efficacy, side effects, and cost of pharmacological interventions to be less optimal than treatment with therapy alone, we can decide then to abandon it. However, because it shows promise at this point in time, we should pursue research into these pharmacological interventions or risk forgoing discovering a treatment option that could potentially heal trauma faster and more completely than therapy alone. Perhaps one day we will learn how to treat mental illnesses and disorders without any pharmacological interventions, but until that day arrives, it is unethical to deprive people of the possibility of a speedier and more complete recovery afforded by pharmaceutical drugs.

--Melanie Pincus

Neuroscience Graduate Program

Memory-Altering Drugs, Do We Really Have the Right?

The debate surrounding the use of memory-altering drugs is an important one – mainly because the social implications and the ethical questions raised are huge and varied, and also because there’s a compelling argument to be made for both sides.

The case for the use of such technology – specifically, memory dampening drugs for the treatment of victims of trauma – is fairly straightforward. A number of individuals who have suffered a traumatic experience go on to develop post-traumatic stress disorder (PTSD), and have to deal with a host of long-term psychological and physiological symptoms that severely affect their day-to-day life. Many of them believe that making that traumatic memory disappear would provide them with much-needed relief, allowing them to live happier lives. If this is truly the case then surely, every effort should be made to restore to these people the quality of life they deserve, unfettered by any emotional scarring caused by a traumatic incident. But of course, we don’t know that it IS true yet, which is where the problems arise. 

 

There are questions of biology; the biggest being that we don’t completely understand the neurobiology of a memory. Scientists working on drugs like propanolol, are careful to specify that they serve only to dampen memories, not to erase them entirely. The theory is that these beta-blockers target memories with high emotional arousal, disrupt the consolidation process of the memory, and somehow dissociate the negative emotional response from it[i]. In other words, we have another new drug (or a repackaged old one) that uses an extensive package insert to inform us that the “precise mechanism of action remains unknown.” True, that’s a risk we run with almost any drug, but is it one worth taking in this case? What if you end up losing not only the negative but also the positive memories? Also, assuming a specific targeting and elimination of the emotion associated with a memory is someday possible, the biological and biochemical substrates and consequences of a traumatic incident could still remain, and probably have equally significant effects.

Then, there are questions of self-identity. Bioethicists argue that “giving people too much power to alter their life stories could ultimately weaken their sense of identity and make their lives less genuine.[ii]” The counter argument to this, presented by Adam Kolber in his somewhat biased article is that the emotional baggage of a traumatic incident can sometimes dominate an individual’s life, thereby making them and their actions less true to themselves. The premise here is that our memories and experiences are what define us as individuals, like Oscar Wilde’s idea of a “diary that we all carry about with us.” It’s true that every experience shapes our life, but it is also true that we constantly go through a process of modification, enhancing and dampening of our own memories, a Darwinian natural selection of memories for our optimal functioning. Does this process diminish our self-identity, or does the choice we make to retain or forget further define our self-identity?

A number of psychologists argue that the counseling and therapy used to turn negative experiences into positive ones is more rewarding and healing than any pharmaceutical interventions, and that learning from these experiences can be a positive thing. They also believe that a crucial aspect of the healing process is to acknowledge the traumatic incident and work through the negative emotions, as opposed to blocking them out altogether; but while we’ve all heard that what does not kill us makes us stronger, it is important to note that some people are just more equipped to handle a traumatic incident than others. So while these people may not need a stronger intervention than counseling to deal with their problems, others may. And if an alternative of “therapeutic forgetting[iii]” exists, it should probably be made available to anyone who chooses it. After all, don’t we have a right to pursue the highest possible level of happiness and comfort?

With which, I can segue into the panoply of questions of social implications and responsibility: Do we really have that right? When our personal comfort conflicts with the benefit of society as a whole, are we morally obligated to take one for the team? If you choose to erase the memory of a traumatic incident where you were a victim, this could prevent you from providing important information that could apprehend the criminal. Alternatively, should you choose to reduce the emotional effect of a traumatic incident, and are required to testify in court against the perpetrator, ethicists argue that the emotional blunting could affect your judgment of their actions as right or wrong. So, are your memories always entirely your own to do away with, even when they have socially valuable information?

Finally there are a host of legal implications including the potential overuse, over-prescription, and misuse of such powerful drugs. The most obvious threat is the use of these agents by terrorists and offenders, either to escape punishment or to obtain exculpation. There is also the crucial question of assessing the degree of a trauma and determining whether or not it merits the use of such a therapy. One of the main issues with propanolol treatment is that it is most effective within 6 hours of the trauma[iv], and victims of trauma may not be able to make an objective decision regarding whether or not they would like to retain the memory so soon after the incident.

As Kolber rightly points out, it is important to encourage adequate research into the efficacy of both pharmaceutical and non-pharmaceutical therapeutics to ensure that this treatment option could be available. At the same time, we must ensure that the use of such drugs is highly regulated. If not, we may be headed for that highly hedonistic, yet dystopic future described in so many sci-fi stories, and we all know how those end...

--Nisha Raj

Neuroscience Graduate Program

Sources

[i] Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR (2003). Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biological Psychiatry, 54(9):947-9

[ii] Kolber A. (2011) Neuroethics: Give memory-altering drugs a chance. Nature, 476(7360), 275-276.

[iii] Adam J. Kolber (2006). Therapeutic Forgetting: The Legal and Ethical Implications of Memory Dampening. Vanderbilt Law Review 59 (5),1561-1626

[iv] Elise Donovan. (2010). Propranolol use in the prevention and treatment of posttraumatic stress disorder in military veterans: Forgetting therapy revisited. Perspectives in Biology and Medicine 53(1), 61-74

Give Mind-Altering Drugs a Chance

Recent studies in posttraumatic stress disorder (PTSD) research have identified several pharmacological treatments that promise to lessen the emotional pain associated with memories of traumatic events. These recent advances have sparked early debates surrounding the ethics of pharmaceutically “dampening” memories, fears of unwanted memory manipulations, and misconceptions of full-blown memory erasing in the future. In a recent Nature article, Adam Kobler, a Professor of Law at Brooklyn Law School, and the editor of the Neuroethics and Law Blog, argues that these fears surrounding pharmaceutical memory manipulation are “overblown” and instead hinder important research that is needed to help individuals cope with and recover from emotionally distressing memories¹.



Several drugs are undergoing research for their potential applications in PTSD, such as Propranolol, which is a non-selective beta-adrenergic blocker used to treat hypertension³. Preliminary research has shown that when taken even a few hours following a traumatic event, propranolol may prevent the development of PTSD symptoms. 

Kolber cites the US President’s Council on Bioethics as an early challenger to the use of memory altering drugs like Propranolol. The Council’s 2003 report claimed that such drugs aimed to manipulate memories could pose serious threats to an individuals “sense of identity” and “ability to lead true and honorable lives,” by discouraging individuals from taking the time to transform negative memories into positive ones². To these concerns, Kobler counters with stories of depressed patients who often feel “like themselves for the first time” after taking antidepressants, and patients whose use of drugs could “speed up the healing process” allowing them the unburdened clarity to truly live their lives¹. Considering these arguments, we might want to consider whether it is ethical to not provide such pharmaceutical treatments to individuals coping with the effects extreme trauma.

The ethical implications of pharmaceutical memory manipulation are heavily debated, even as many of these drugs remain in preliminary studies for their use in PTSD treatment. However, the ethical implications of non-pharmaceutical approaches to memory manipulation, such as cognitive behavioral treatment, are largely left un-debated. For example, exposure therapy is commonly used in treating PTSD and has well-documented clinical efficacy in modifying painful memories of traumatic events³. If cognitive behavioral therapies have similar effects in modulating how individuals experience difficult and emotionally charged memories, is it simply the fact that propranolol is a pharmaceutical intervention, that causes members of the public to leap to possibilities of manipulating and changing our core identities? 

While I do agree with Kobler that fears surrounding pharmaceutical memory manipulation are “overblown” (perhaps because they are uninformed), I can understand the caution of the public in leaping from non-pharmaceutical to pharmaceutical treatments for intervening with memories. Pharmaceutical interventions represent more of an invasive threat to our bodies and minds than behavioral therapies. This is where misinformation from the media (I imagine headlines of “new drugs to erase all your painful memories!”) causes an ill-informed public to associate advances in important research with scary invasions into their minds and most precious memories. Members of the scientific community play an essential role in being the first to inform members of the public of the mechanisms and effects of such drugs, and also of the immense benefit such drugs promise for individuals suffering from trauma. 

--Filomene Morrison

Neuroscience Graduate Program 

Sources and Additional Reading

¹Kolber, A. Give memory-altering drugs a chance. Nature. 476, 275-276 (2011).

²President’s Council on Bioethics. Beyond Therapy: Biotechnology and the Pursuit of Human Happiness Ch. 5, 205-273 (2003).

³Cukor, J., Spitalnick, J., Difede, J. Rizzo, A. & Rothbaum, B.O. Clin. Psychol. Rev. 29, 715-726 (2009).

Ethics of Memory-Altering Drugs

Disturbances in memory represent some of the most frightening aspects of several psychiatric and neurological diseases. It gets right to our sense of self as in many ways our memories shape our view of the world and are critical for our ability to function normally in it. We are often surprised, though, to find just how fallible our memories can be, especially for highly stimulating or traumatic events. Kubie took a particularly cynical view of the matter in a 1959 comment suggesting that humans have trouble telling the truth even when they try.[i]

There is little doubt that our memories are inherently subjective and are affected by myriad factors. Why, then, are so many worried about the potential implications of memory altering drugs? Is it because we recognize how susceptible our memories are to producing errors and do not want to push it further from reality, or, is it rather that we hold our memories as real records of truth and thus something that should not be manipulated even if we could? Most likely it is the latter. Unfortunately, exposure to trauma can lead to consolidation of painful memories with intense emotional attachments which can be effectively paralyzing. These types of memories serve no productive purpose.

This is a serious matter, as post-traumatic stress disorder (PTSD) is increasingly recognized as a major public health burden. Evidence suggests that up to 35% of witnesses to a traumatic event will develop PTSD at some point.[ii]^,[iii] So what is happening in the other 65% who experienced the same thing? This may be a good example of how memory is truly subjective and the emotional aspect – which may be most important in pathological memory problems such as in PTSD – can be dependent on the individual. In fact, recent studies using propranolol (a β-adrenergic receptor antagonist currently approved for hypertension) have shown that the emotional aspects can be dissociated from traumatic memories.[iv] A small cohort studied in 2003 suggested that propranolol may be able to prevent PTSD if given immediately after a traumatic event.[v] These results, while far from conclusive, suggest that it may be possible to dampen the painful, emotional part of memories without impairing an individual’s recollection of an event. In a way, that may lead to a more dependable account of an event without the subjective emotional coloring.

Immediate treatment after trauma to prevent painful memories is not an ideal way to fend off PTSD; especially since the majority of witnesses will probably not develop the condition. Hopefully, further research will lead to more targeted strategies that can treat PTSD at the first sign, perhaps in combination with talk therapy. In the mean time, propranolol and other drugs like it should be further studied and used as warranted if it becomes clear that they significantly reduce incidence of PTSD. For some, altering memory represents crossing a line that could set a precedent for more devious drug uses. In this case, that is not an immediate concern. Our memories have already been shown to be quite fallible and prone to errors. In some cases those errors can take a real psychological toll and if it is in our power to prevent them then we should do so.

--Ryan Purcell

Neuroscience Graduate Program 

References  

[i] Kubie, Lawrence S. Implications for Legal Procedure of the Fallibility of Human Memory, 108 U. Pa. L. Rev. 59 (1959-1960)

[ii] Yehuda, Rachel. Post-traumatic stress disorder, New England Journal of Medicine, 2002; 346: 108-114

[iii] Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry 1995; 52: 1048-60

[iv] Kindt M, Soeter M, Vervliet B. Beyond Extinction: erasing human fear responses and preventing the return of fear. Nature Neuroscience 2008; 12: 256-8

[v] Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propanolol decreases posttraumatic stress disorder two months after trauma. Biological Psychiatry, 2003; 54(9):947-9