One Drug to Remember, One Drug to Forget?

By Matt Walker | 4.30.07

Back in 3rd grade or so, I got involved in a game of kick Matt in the shins so hard that he falls over and continue to kick him in the shins when he gets up. It was a fun game that pushed me directly away from sports into the world of music and punk rock. Could I have avoided all the bad rock shows, black T-shirts, and stupid haircuts with the aid of a simple pill originally designed to combat high blood pressure?

In the last few years, research has been done on the use of propranolol and its effectiveness in erasing certain memories. (Please do not confuse propranolol with propanol, a basic alcohol, which has its own effects on memory erasing, i.e. death.) Propranolol was the first successful beta blocker, a drug that blocks the adrenergic receptors involved in the “fight-or-flight” response. The drug gave its discoverer, James W. Black, a Nobel Prize, and has accumulated numerous clinical applications, mostly relating to the heart, but also for treating migraines and brain tumors, and most recently as a memory eraser.

The potential for this latter therapy is based on modern neurobiological theories about the vulnerability of memory. When memories are formed, they are first held in short-term memory, the place where you can hold a seven-dight phone number long enough to dial, but not so long that you can remember it the next day. To make the jump into permanence, memories need to be “consolidated,” or transferred from short-term memory into long-term storage. Furthermore, when these memories are retrieved, they must be “reconsolidated,” or filed back among the brain’s memory library; before this re-shelving process occurs, the memories are theorized to be in a labile state, vulnerable to alteration or deletion. Previous research suggests that fearful and traumatic experiences are more readily and firmly put into long term storage due to the simultaneous presence of stress factors and adrenaline that are thought to enhance the reconsolidation process. This is why I can still remember getting beat up at Boy Scouts, but cannot remember what happened the following week in 3rd grade.

The idea behind the therapeutic use of propranolol is that the drug can inhibit the activity of these stress factors and inhibit unpleasant memories from forming. Propranolol has been used experimentally as a drug for the treatment of post-traumatic stress disorder (PTSD), despite some reports that its efficacy is limited to a short time period directly after the traumatic event in question. Nevertheless, some psychiatrists claim that in PTSD patients, the use of propranolol and therapy can aid in the erasing of memories even if they were from many years ago. Patients have both praised and razed the technique for either providing them with a normal life or giving them false hope. The traditional method of dealing with PTSD is therapy alone, and there is little evidence to show that the increased effectiveness of propranolol and therapy was due to the drug itself or merely a placebo effect. While this has limited the effectiveness of propanolol for psychiatric purposes, a recent study showed that another drug could be more effective in its ability to erase memories.

In this paper by Valerie Doyere and colleagues, an inhibitor of an intracellular protein called MAP kinase, U0126, was shown to have an effect on memory in rats. Drug inhibitors like U0126 are chemicals that interact with specific proteins to stop their function. This class of drugs is becoming more common in the treatment of disease, as they can block specific cellular activators. The paper shows that 2 different musical tones can be associated with an electrical shock. When these tones are replayed, the rats are afraid of being shocked. The Doyere group went on to show that they can eliminate the fear response by playing one of the musical tones while the rats are in a limited amnesia state caused by the U0126. Subsequently, the rats showed no fear response to the musical tone that was heard while under U0126, but still had a response to the other musical tone. In addition, the treated rats were seen to have a decrease in the brain activity associated with the fear response, implying that the memory was indeed erased. If this holds true in humans, this could mean that certain memories can be “erased” by bringing them back up while the patient is in the limited amnesia state induced by U0126.

If the relatively modest effects of propranolol treatment caused a moral uproar, imagine what a more effective drug that puts the patient in a state of limited amnesia will do. While the drug shows promise, it is still not approved for use in humans and is used mostly as a tool for cell biologists. If the drug does get approved, it is likely that Leon Kass of the President’s Council on Bioethics will have something to say about it. When the first studies using propranolol in the treatment of PTSD were being done, Kass wrote that, “Falsifying our perception and understanding of the world risks making shameful acts seem less shameful, or terrible acts less terrible, than they really are.” While it’s not surprising that the notoriously conservative council held this opinion, it was a bit hypocritical in light of the fact that the US Army has been testing propranolol in PTSD treatment of their soldiers. In recent years, the armed forces have garnered much criticism for their psychiatric care of veterans. A drug like U0126 would be a valuable tool in the treatment of PTSD caused by war situations, as PTSD can be a crippling disorder that can ruin people’s lives if it goes untreated and/or uncontrolled.

Overall, it is interesting to see how effective these treatments will actually be. The propranolol treatments have been shown to have widely varying degrees of effect and U0126 is still awaiting FDA approval for its primary use, reducing the injury caused by strokes. In the end, it may be the ethics of the treatment that end up hindering its passage through the FDA for the treatment of PTSD. Kass and other conservatives are apprehensive about the use of “memory erasers” and the arguments could escalate if U0126 shows increased efficacy over propranolol.

Furthermore, it should be considered that the ability of U0126 to erase memories could also be highly lucrative for supervillains, say someone diabolical like, I don’t know, OJ Simpson. Poisoning the water with U0126 could leave the general population vulnerable to a critical memory erasing period that could be exploited by a carefully-timed Super Bowl commercial. OJ could film a television ad making people forget about his heinous crimes and revert back to thinking of him as the affable personality he used to be, and he could then resurrect his role from The Naked Gun into a new primetime series on ABC. For the 1% of the population who do not watch the Super Bowl, they will suddenly be the crazy ones spouting nonsense about Nicole Brown-Simpson, only to have their “fake” memories erased at OJ Simpson’s new memory institute financed by the millions of dollars he made selling his show into syndication. Meanwhile, oil companies could erase the bad press of oil spills, celebrities racist slips will be forgotten with ease, and politicians could make voters forget all about egregious foreign policy mistakes. On second thought, maybe the FDA shouldn’t approve the drug after all.

References

Alvarez M. 2007. Dr. Manny: memory-erasing drugs. Fox News. March 21, 2007.

Doyere V, Debiec J, Monfils MH, Schafe GE, Ledoux JE. 2007. Synapase-specific reconsolidation of distinct fear memories in lateral amygdala Nat Neurosci. 10(4): 414-6.

Kass LR. 2003. The pursuit of biohappiness. Washington Post. October 16, 2003.

LaFee S. 2004. Blanks for the memories: someday you may be able to take a pill to forget painful recollections. San Diego Union Tribune. February 11, 2004.