A Blog by Virginia Hughes

Want to Erase Fear Memories? Choose Weed, Not Booze.

Tomorrow marks the 11th anniversary of the terrorist attacks on the World Trade Center, which killed nearly 3,000 people and traumatized hundreds of thousands of others. One out of four witnesses to that awful scene — fires, blood, flying glass and metal and stone and people — developed post-traumatic stress disorder (PTSD), characterized by fearful memories that just won’t recede.

It’s no wonder that many people with PTSD — about 14 percent — try to self-medicate with alcohol. Booze helps us forget, right? The idea lurks in idioms — I might get “trashed” or “wasted,” or “drown my sorrows” — and in Proverbs 31:7, and in the gospel of Dave Matthews: Excuse me please / one more drink / Could you make it strong / ‘Cause I don’t need to think… One drink to remember / Then another to forget…

So I was fascinated by a new study showing the opposite. Alcohol, it seems, helps cement painful memories into neural circuits.

In the study, a team led by Andrew Holmes of the National Institute on Alcohol Abuse and Alcoholism first made murine alcoholics, exposing mice to 16 hours of vaporized ethanol followed by 8 hours of withdrawal for four days in a row. They did that whole thing four more times, with 80 hours of withdrawal between each cycle. Each dose of alcohol was equivalent to double the legal driving limit in humans.

After that, the researchers taught alcoholic and non-alcoholic mice to be afraid of a sound by repeatedly pairing it with an electric shock to the feet. This is a common technique. Once the animals learn the association (sound = pain), they will freeze to the sound alone, Pavlov style. But this fear response doesn’t last forever. After a few dozen trials of a sound with no shock, mice eventually forget the bad memory and don’t freeze when they hear the sound. For the alcoholic mice, though, this so-called ‘fear extinction’ happened much more slowly than it did in controls.

The brains of the alcoholic mice were different, too. In part of the prefrontal cortex, neurons in alcoholic mice lacked a key protein of the NMDA receptor. Chemical signaling at this receptor underpins the learning process, but without the protein, the receptor can’t work properly. Fittingly, the researchers also found that the alcoholic mice showed less signaling at NMDA receptors than controls.

The whole thing makes sense, the researchers say, because alcohol is a known blocker of NMDA receptors. So the mechanism is something like this: Lots of alcohol –> Blocks function of NMDA receptors –> over time –> the receptors break down significantly –> the alcoholic mice can’t un-learn a fear memory.

The study is unusual because the alcohol exposure happened before the scary event, rather than after. That certainly has real-world relevance, as excessive drinkers have an increased risk of trauma, such as a car accident or life-threatening fight. But Holmes told me he’d predict the same extinction patterns if the mice were first traumatized and then inebriated, because presumably alcohol would be wreaking the same havoc at those NMDA receptors. So that’s pretty bad news for the thousands of people who have both PTSD and alcoholism.

On the upside, there’s pot.

The next PTSD treatment?
The competition between cats and dogs often takes amusing turns. Last year, cats seemed to edge ahead in the ‘drinking’ event. Until recently, people thought that both pets drink by using their tongues as simple ladles to lap up liquids. But Pedro Reis and Roman Stocker from MIT found that cats do something very different. Using high-speed video recordings, they showed cats drink by using their tongues to draw columns of water into their open jaws. While dogs supposedly drink by scooping up water in a mundane way, cats were portrayed as masters of physics that “defeat gravity” whenever they drink. Now, A. W. Crompton and Catherine Musinsky from Harvard University have stepped up to even the score for dogs. Through their own high-speed videos – including X-ray films of drinking dogs – they have found that dogs use the same technique the cats do. It’s a draw.

Here’s what I wrote about Reis and Stocker’s cat study last year (the full post, featuring an Oscar-winning film and YouTube, is worth a read too):
Drinking is more of a challenge for cats than for us. They have to drink from flat, horizontal bodies of water. Even with our hands tied, we could do that just by putting out mouth at the surface and sucking, but then we have large cheeks that can form a proper seal. Pigs, sheep and horses have the same ability, but cats and dogs do not. Their cheeks don’t extend far enough forward so they have to use a different technique: lapping. Cat owners have watched their pets lap at water for thousands of years but when Stocker did so, his curiosity was piqued. “Three years ago, when I was watching my cat Cutta Cutta lap during breakfast, I realized there was an interesting biomechanics problem behind this simple action,” he says. The lapping motion is so fast that to fully appreciate it, you need a high-speed camera. Slow-motion films of Cutta Cutta revealed that a cat doesn’t actually scoop up its drink with its tongue in the way that a dog does. Its technique is more subtle. For a start, it drinks only using the very tip of its tongue. As it extends its tongue, it curls the tip upwards so that the bottom side rests on the surface of the liquid, without actually breaking it.  The cat lifts its tongue, drawing a column of liquid with it. Just before the column collapses, the cat closes its mouth, captures the elevated liquid, and takes a refreshing drink. This sequence depends on a battle between two forces. The first is inertia, the tendency for the water column to keep moving in the same way until another force acts upon it. That force is gravity, which constantly threatens to pull the water column back into the bowl. With its rising tongue, a cat uses inertia to “defeat gravity” long enough to close its mouth on the almost-collapsing tower of liquid.
Crompton was “originally skeptical” about Reis and Stocker’s conclusion because he had studied lapping in the American opossum and found a completely different method. But he was particularly intrigued by the assertion that dogs also drink differently. They supposedly drink by curling their tongues towards their chin, and using the bottom surface as a spoon to scoop up liquid. But once the water is inside their mouths, how do they swallow? With their heads pointing downwards, they would need to move the water to the top of their tongues and push it back into their mouths against the pull of gravity – a difficult job for an animal without cheeks. Then there’s the fact that dogs and cats have fairly similar skulls and mouths – why should they drink in fundamentally different ways? To address their concerns, the duo shot a high-speed video of a drinking dog, at far greater resolution than the grainier video that Reis and Stocker had seen. The video showed that the dog did indeed scoop some water with the bottom of their tongues, but most of this falls off as the tongue retracts. If it’s acting as a spoon, it’s not a very good one. Thankfully, the tip of the tongue also draws up a column of water, and before this collapses, the dog closes its mouth around it. That’s exactly what cats do. Crompton and Musinsky also filmed the dog with an X-ray camera to show what happens to the water inside the animal’s mouth. The tongue presses the water against the roof of the mouth, and keeps it there even as the tip of the tongue sticks out for another lap. As the tip draws up another column, the trapped water from the previous cycle is shoved backwards, and eventually swallowed. By filming cats, Crompton and Musinsky showed that they do the same thing. The tongues of both species do several things at the same time – they draw up a fresh lot of water, while pushing back older ones up into their throat.

So cats and dogs drink in the same way. If anything, the difference is that cats are more elegant, and dogs messier. Drinking dogs stick their tongues more deeply into liquids than cats do, and when they retract, they spray more liquid about. Cats are tidier about it, so their technique is easier to see. Stocker says, “I'm delighted to see this research, not only because it adds a new element to the story of how animals drink, but also because it exemplifies how science progresses - by interactions and debate between different groups, even between MIT and Harvard. Masterfully done and bringing all pets on a par!” Reference: Crompton & Musinsky. 2011. How dogs lap: ingestion and intraoral transport in Canis familiaris. Biology Letters http://dx.doi.org/10.1098/rsbl.2011.0336

In the past year, Holmes and others have shown that cannabinoids — a family of chemicals that includes THC, the active ingredient in pot — can curb stress responses in rodents. For example, a study in January showed that giving a THC-like compound to rats within one day of severe stress reduced their anxious behaviors. In June, Holmes’s team showed in mice that boosting anandamide, a cannabinoid produced naturally by the body, helps the animals extinguish fear memories.

And in July, scientists demonstrated this effect in humans for the first time. Researchers recruited 29 healthy adults and studied them over three days. On the first day, participants sat in front of a computer screen and learned a fear association: blue squares and yellow squares were paired with an unpleasant “white noise burst” on their headphones. On day two, half of the participants received a low dose of dronabinol, a form of synthetic THC that’s sometimes prescribed to stop chemo-related nausea, and the other half a placebo. Two hours later, they went through an extinction trial, in which blue squares were no longer paired with that hideous noise. Finally, on day three, participants came back and saw a series of blue and yellow squares. During all sessions, the researchers measured the electrical conductance of participants’ skin — a direct measure of sweat and indirect measure of stress.

For participants who got a placebo, the fear extinction procedure didn’t take: On day 3 they showed no difference in their stress response to blue and yellow squares, despite having seen the previous day that blue squares can appear without a noise. In contrast, participants who had received dronabinol showed a lower stress response to blue squares than to yellow ones. Bottom line: synthetic pot helped them un-learn a fear memory.

One caveat here is that while low doses of pot can lessen anxiety, high doses may bring on paranoia. Still, the drug has fairly minor side effects (less than or comparable to those of antidepressants). In states that have legalized medical marijuana, doctors are already prescribing it for PTSD. In New Mexico, apparently, one-quarter of medical marijuana patients are being treated for PTSD.

Anecdotal reports say that it helps. But what we really need is a rigorous clinical trial of pot’s effects on a large group of people with PTSD. Pulling that off will be politically tricky because the bodies that fund this kind of research, namely the Department of Veterans Affairs and the National Institutes of Health, are part of the same federal government that is fighting a futile war on drugs. But I think it’s an important debate to have — especially on this 9/11 anniversary, when we’re all reminded of the people who are still living, and re-living, the nightmare.

Photos from Wikimedia and Alexodus

Read Maia Szalavitz’s excellent explanation of the rat THC study here.

This post was originally published on The Last Word on Nothing