A finger adjusting the slider of the Rehaler, and a pair of lungs.
Asger Hee Stjernholm, MSc

How Does Rehaler Work?

Below you can see how the Rehaler looks when it is unpacked and ready for use:
Picture of the Rehaler when it is folded and unfolded.

When you feel that a migraine attack is coming, you unpack the Rehaler and start breathing through the mouth piece. The Rehaler works by increasing the content of CO2 in the air you breathe, while making sure that you get enough oxygen. The Rehaler doesn’t use gas flasks to provide this mixture of gases, but instead uses part of the CO2 your body produces and carefully balances it with fresh air, by a principle called partial rebreathing. 

When you breathe out through the Rehaler, part of your expired air is captured in the cube while a smaller part flows out of the valve. This expired air has a high content of CO2 (about 4-6% depending on the person), compared to normal air where the CO2 content is almost zero. When you afterwards breathe in, part of the air is CO2-rich air from the cube and part of it is fresh air flowing in through the valve from outside the cube.

A flow chart showing the development of the different gas compositions through the use of Rehaler.

The end result is an increase in the CO2 content of the air you breathe, while ensuring an adequate supply of oxygen. As will be explained below scientific studies have shown that this combination of CO2 and oxygen levels is effective in stopping migraine attacks.

What happens in the body when you use Rehaler?

When you breathe air with a high CO2 content, the CO2 level in the body increases as well. With the Rehaler in its normal setting, the increase in the body’s CO2 level is close to 25%, but this can be adjusted up or down to suit different needs. The increase in CO2 has several effects in the body: 

  1. Within less than ten seconds, the blood vessels that supply your brain dilate, which increases the delivery of oxygen and blood sugar to the brain’s cells. This is an especially important effect in migraine because these blood vessels are very often contracted before and during attacks, which starves the brain of energy and makes it more vulnerable to the triggering and chain reaction happening during attacks. This problem is effectively and quickly reversed by the Rehaler. When CO2 is used for increasing the blood flow to the brain it is very important that the oxygen content of the blood is still normal, otherwise the brain might still be starved of oxygen. This is why the Rehaler’s design is exactly balanced to ensure a high CO2 content and a normal oxygen content at the same time. 
  2. The nerve cells in the body become less excitable, because a high CO2 level makes it less easy to make a nerve cell “fire”. This is an important effect in migraine, because attacks are more likely to be triggered and worsen when nerve cells are very excitable.

Why use CO2 to treat migraine?

It has been known since 1950 that CO2 is an effective migraine treatment. This was shown in experiments done by the doctor and scientist Harold Wolff who is by many regarded as the father of modern headache science. In these experiments, migraine patients were able to stop attacks by breathing gas from gas flasks with a high CO2 content.

Unfortunately, gas flasks were never a practical solution for migraine patients, most importantly because they are heavy and bulky. High contents of CO2 stimulate the breathing, often to more than three times the normal number of liters per minute, meaning that CO2 gas flasks will quickly run out unless they are very large, in which case they are also very heavy (15 kg or more) and hard to carry around. Gas flasks also need to be refilled or exchanged with regular intervals, which would add a lot of cost and practical problems for the migraine patient. For those reasons, CO2 gas never came into use for migraine treatment. 

Inspired by Harold Wolff’s results, other experiments with CO2 treatment of migraine were carried out in the 1980’ies, but using plastic bags for rebreathing. In those experiments, patients breathed into a closed plastic bag during the pre-headache and/or headache phase of migraine attacks. Unfortunately, this method is very risky – and potentially life-threatening – because the oxygen in the bag will quickly run out. Because of that, the patients in the experiment had to be very concentrated on taking breaths of fresh air with regular intervals, in order not to suffocate. This was obviously not an ideal solution and likely caused a lot of worry to the patients in the experiments! Even with this problematic way of giving CO2, the treatment effect on migraine was very positive – especially when the gas treatment was done early in attacks. 

Because of the practical problems and risks involved, neither of these ways of providing CO2 were satisfactory, even though the effect on migraine was very strong.

The advantages of Rehaler

The Rehaler is the first device offering a practically usable and safe way of treating migraine with CO2. Because it uses the body’s own CO2, it does not – like gas flasks – run out of gas or need refilling, and it can be carried around easily in a pocket or purse because of its small size and very light weight. Because it supplements the inspired air with a controlled, stable amount of fresh air, the user does not – like with closed rebreathing bags – run out of oxygen or need to worry about when to pause the treatment, since use of the Rehaler can be continued for as long as needed.

Overall, the Rehaler delivers the exact levels of oxygen and CO2 when and where you need it to control and stop your migraine attacks.

The Rehaler’s effect was from 2016 to 2017 tested in a first clinical study at Aarhus University Hospital’s Headache Clinic. The study included eleven migraine patients and was a so-called crossover study, meaning that there were two devices used in the study: the real Rehaler and a placebo device that looked like the Rehaler but did not increase CO2 in the inspired air. Each patient started by treating two attacks with one of the devices, followed by two attacks with the other device, but did not know which was the real Rehaler (using a placebo is very important in making sure that the results of clinical studies can be trusted).

The study found a number of statistically and clinically significant results:

  • CO2 levels in the body increased by an average of 24% when using the Rehaler, while average oxygen saturation stayed above 97%.
  • Patients were markedly more satisfied with the Rehaler compared to the placebo device
  • The Rehaler provided higher pain relief than the placebo device (60% vs. 29%).
  • The Rehaler’s effect increased with each use of the device: from the first attack treated with the Rehaler to the second attack treated, the precentage of attacks with pain relief increased from 45% to 78%.

Follow-up studies with Rehaler are planned that will include a higher number of patients, and different types of migraine.

Why does Rehaler work on migraine attacks?

The Rehaler treats migraine by stabilizing the brain, decreasing its excitability and defending its supply of oxygen and energy. This allows many migraine attacks to be stopped or reduced. In order to visualize the effect of the Rehaler on migraine, we can use the image of the Jenga tower. Imagine that the Jenga tower sits on a table next to a row of domino pieces representing the nerve cells in the brain:
A Jenga tower standing at the start of a long row of standing domino pieces.
Each blue domino piece has a “pain side” that is red. When the piece falls, it shows its red side – representing that it is causing pain.
A domino piece falling over, with the red side facing upwards.
When the migraine threshold is crossed and an attack is triggered, the Jenga tower falls and knocks over the first domino, leading to a chain reaction that eventually ends up knocking over all the domino pieces:
A tumbling Jenga tower knocking over a row of domino pieces which land with the red side facing upwards.

At this point all the dominos are showing their red pain side, representing how the nerve cells have lost their balance and started to cause migraine symptoms. In this example, the more red you see on the table at the end, the worse the migraine attack will be. This represents the fact that the more nerve cells are caught up in the chain reaction, the worse the migraine symptoms will be and the longer the attack will be.

When you use the Rehaler, you increase the stability of your nerve cells because you boost their supply of energy and oxygen, and at the same time make them less excitable. In this example, this is the same as putting a little bit of glue on each of the Jenga blocks and the domino pieces. That means that if you use the Rehaler just when an attack is about to be triggered, you are more likely to avoid it from happening and keeping the Jenga tower from falling.

However, often the attack has already been triggered when you notice that something is wrong – in other words the Jenga tower has already collapsed and the first domino pieces have started falling, as shown in the figure below where the third domino piece is just about to fall and push over the next in the row:

A Jenga tower that has crashed and in the process knocked over several domino pieces which are now lying with the red side upwards.
Because the row of domino pieces represents millions of nerve cells, it may take as much as an hour for the entire row of domino pieces to fall. In the time when domino pieces are still falling, it is still possible to minimize how much of the table ends up being “red” in the end. As an example, think of the time point in the figure above, where piece A has just fallen down. If you immediately afterwards glue domino piece B to the table with super glue, it will not fall down, and the table will end up looking like this instead:
A Jenga tower that has crashed and in the process knocked over half of a long row of domino pieces which now lie facing with the red side upwards.
Because domino piece B was glued down it did not fall, and by staying up it protected all the dominos behind it from falling over as well. The result is that there is less red color showing when the domino effect stops: in the real world, this represents that the attack did not become as bad and long-lasting as it otherwise would have. What would happen if you were quick and glued piece C to the table before it fell? The board would then end up looking like this:
A Jenga tower that has crashed and in the process knocked over several domino pieces which now lie with the red side facing updwards.

In this case, the glued-down “C” domino has stopped the chain reaction short so that only a few pieces have fallen and very little red is visible, corresponding to a mild and short-lasting attack.

The domino example is a way to show why you may often get a better effect by treating migraine attacks early, before they have developed fully. This is the case for the common migraine drug type triptans, and for the Rehaler as well.

One of the advantages of the Rehaler is that, unlike drugs, there is no upper limit on how often you can use it. That means that if you suspect that you are getting a migraine attack you can use the Rehaler immediately and for as long as needed, and not (like is often the case with triptans) wait until you are absolutely sure that you are getting an attack before starting the treatment. That means that you may often be able to treat attacks earlier in their development and thereby increase the chance of getting a good effect.

Does Rehaler have side effects?

The Rehaler has been designed in such a way that the increase in CO2 will be suitable for almost everyone, and so that you will not run out of oxygen, not matter how long you use it. For people that wish a higher or lower CO2 level, the valve can be adjusted by the use of the slider.

Many people who use the Rehaler (especially when it is for the first time) will experience that their breathing becomes deeper. Some users (about 20%) may also feel a warm sensation in the body, and some users (about 10%) may feel sweaty. These effects are perfectly natural and harmless reactions to an increased CO2 level, and disappear within a few minutes when you stop using the Rehaler.

About one in ten people have a very strong reaction to CO2, meaning that they can feel dizzy, restless, breathless, get a mild headache or otherwise feel uncomfortable when using the Rehaler at the normal CO2 setting. For these people, the CO2 level provided by the Rehaler can easily be reduced. For the 10% of people that experience one of these side effects, the effects will in general disappear or milden with each use of the Rehaler, so at a later point they may be able to tolerate the standard CO2 level of the Rehaler without any problems.

Contact us

We use cookies to deliver content, for statistics and to improve your experience on the site. By using rehaler.com you accept the terms for the use of cookies.

Login to your Rehaler account