Less than a week to go until I’m drinking coffee again. I miss it so much! I’ve noticed some upsides of not drinking coffee: I’m less panicky, and sweat less – both probably related to caffeine’s effect on adrenaline release. But I’m also slower – I can’t do multiple things at once as well as with coffee – and I had those weird migraines I wrote about last week. I also really miss having easy access to a drink that switches my brain on in the mornings.

Some of the benefits of caffeine are not even obvious immediately. Just over a decade ago, I was writing a literature summary as part of my masters requirement in pharmacology. I picked a topic that sounded interesting, and spent a few weeks digging through papers to write a review. The topic I chose was “New drug treatments for Parkinson’s disease”.

The thing with discoveries in science is that you need to be in the right place at the right time, and a lot of that is luck. I was never lucky in research, but this one time, writing the Parkinson’s literature report, my timing was perfect. While I was doing lit research, a new study came out that suggested that caffeine was able to prevent the onset of Parkinson’s disease. Caffeine! Of all the drug treatments I was researching, this newest one was definitely the coolest. It was not in any of our course material yet, and my oral presentation on the paper was the first time several of the professors in the department heard about it. I won an award for this literature review at the time, thanks in a large part to this lucky timing, but now, a decade later, the effect of caffeine on Parkinson’s is well-known.

The paper I read during my masters was “Neuroprotection by Caffeine and A2A Adenosine Receptor Inactivation in a Model of Parkinson’s Disease“  In this study, mice were given a small amount of caffeine, which by body weight ratio would amount to about a cup per day for a human. This was enough to slow down the hallmarks of Parkinson’s disease: the loss of dopamine in the striatal part of the brain.

This experiment on mice didn’t come out of the blue. Before then, people had already noticed that Parkinson’s was less common in people who drank coffee regularly. The mouse study was just a way to figure out how it worked. Caffeine blocks the A(2A) adenosine receptor, and according to this study, that’s the mechanism by which it helps prevent Parkinson’s.

Since this study, lots more evidence has been found that shows that caffeine protects against Parkinson’s disease. Recently, one study even suggested that coffee can work as a treatment as well. At three cups of coffee per day, Parkinson’s patients were relieved of some of their symptoms.

So for all the jitters it causes in healthy people, caffeine seems to have the opposite effect on Parkinson’s patients. And if you drink coffee regularly, in moderation, your chances of even getting Parkinson’s are significantly reduced.

And this is just one of the reasons why I could never quit coffee for good.
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The coffee experiment is getting more interesting. When I was sick, I started having weird flashing lights in my field of vision. I thought it was related to being sick, but it happened again after I was otherwise completely better. Googling a vague description of what it looked like, I found this. The animation on that page is exactly what it looked like. Argh. So apparently I have migraines now. I hope this is related to coffee, which I suppose I’ll find out when I start drinking coffee again. (Meanwhile, I don’t get headaches, just the weird vision thing, so it’s fine until then.)

I tried to find some papers about coffee and migraines, but there doesn’t seem to be much consistent information. Apparently caffeine and the first few days of caffeine withdrawal are both a trigger for migraines, but caffeine is also a treatment. It’s complicated, and depends on the amounts of caffeine and types of migraines.

Today is day 24 without coffee. I miss it so much. It’s actually worse again now, after finally recovering form my cold. Or maybe it’s because I now work in the middle of London, and pass about ten coffee places in the few minutes walk between the tube stop and the office. So much coffee, so close… I have two coffee chains’ loyalty cards in my wallet begging me to come back and get a discounted coffee. But I’m past the half-way point of my self-imposed coffee-less period, and I’m sure I’ll be able to hold on another three weeks.

Meanwhile, my plan to blog caffeine science in this period was made extra easy by caffeine be prominently in the news this week. A study in Science described how caffeine from nectar of coffee and citrus plants helps bees to remember the plants, and encourages them to visit more flowers of the same type of plant.

In mammals, caffeine improves mental activity by blocking adenosine receptors. When activated, adenosine receptors pass on signals that say “relax”. Caffeine undoes that. In the hippocampus area of the brain, caffeine uses this mechanism to improve memory formation. Bees don’t have a hippocampus, but they have an equivalent area in their brains called Kenyon cells. The researchers showed that caffeine activates Kenyon cells in bees in the same way as it activates the hippocampus in mammals. In other words: it’s biologically possible for caffeine to help memory formation in bees. But does it?

To put the bees to the test, the team trained individual bees to associate the scent of flowers with a mixture of sugar and caffeine. The sugar level was the same for all mixtures, but the caffeine concentration varied. Three days later, bees that were given low doses of caffeine were able to remember the flower far more often than bees that only received sugar.

Coffee and citrus plants use caffeine as a sort of customer loyalty card for bees. Just like the coffee cards that I carry with me, it serves as a reminder to return to the same chain – or type of plant, in this case.

This research is surprising, because until now it was believed that the main reason that plants produce caffeine is to repel insects, and caffeine is toxic to bees – and other insects – at high concentrations. Of course bees are the kind of insect that a flowering plant would rather attract than repel. Plants don’t decide how much caffeine they produce, but in this case, caffeine levels are low enough that they don’t repel the bees, and happen to reward them in the process!

Wright G.A., Baker D.D., Palmer M.J., Stabler D., Mustard J.A., Power E.F., Borland A.M. & Stevenson P.C. (2013). Caffeine in Floral Nectar Enhances a Pollinator’s Memory of Reward, Science, 339 (6124) 1202-1204. DOI: 10.1126/science.1228806

In 1948, P.N. Witt tried to change the time of day during which spiders build webs, from crazy early in the morning to a more observable hour. He gave them a range of psychoactive drugs, from LSD to caffeine, but the spiders still built webs well before the crack of dawn. The drugs didn’t change the spiders’ internal web building clock, but it did have an effect on the structure of the webs itself.

Spiders on low doses of caffeine made small, but relatively normal, webs. On higher doses, the webs became erratic and messy.

The spiders on drugs experiment was repeated by NASA in 1995, and they found similar results.

NASA systematically measured the shape of the webs to generate a sort of toxicity scale. They proposed using spiders for toxicity measurements. How this correlates to toxicity in humans is a bit unclear to me from the very brief publication, but then again, LD50 in rats (the default toxicity scale) is not exactly the same as toxicity in humans either, so maybe the spiders could serve as another unit of toxicity levels. What is pretty clear, though, is that in spiders, caffeine has an enormous effect of web building.

At equivalent doses, marihuana does much less to a spider’s web building skills. Of course, aside from this being a different organism than humans, the dosage of various drugs doesn’t mean much unless you consider what a regular “consumer” dose is. Spiders don’t use marihuana or caffeine, but when humans do, they tend to consume the two in entirely different methods and levels. So the drugged spider webs don’t mean much for human drug use, but it’s pretty striking to see what caffeine does to spiders.

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Meanwhile, I’m doing relatively okay without coffee. I’ve been drinking tea, which I drank in between coffee previously as well, so I’m getting much less caffeine. However, I’ve had a cold for a week, and now a sinus infection, and I’m not used to illnesses lasting so long. Normally I’m completely back to full health in three days or so. But I can’t say whether lack of caffeine played a role in my prolonged misery, or whether it’s more the fact that I had my last week at work and moved house. Like I said at the start of the caffeine experiment, I need a control me…

The American Psychiatric Association publishes the Diagnostic and Statistical Manual of Mental Disorders – or DSM for short – which standardizes mental disorders, at least in the US. It gets updated every few years, and for each new edition psychiatrists will argue which disorders need to be included, or which need to go. For example, the most high-profile update in the next edition concerns the removal of Asperger’s Syndrome. What was previously Asperger’s is now a subtype of autism.

I was surprised to discover that the DSM also contains caffeine-related mental disorders. Caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified are all included in the current edition.

Caffeine dependence is not on the list, but in the run-up to the fourth, and more recently the fifth, edition of the DSM, several researchers have made the case to also include caffeine withdrawal as a distinct recognized disorder in the manual.

To qualify for DSM inclusion, a mental disorder has to affect quality of life, among other things, and caffeine withdrawal does that. But it also has a very simple diagnosis and treatment (caffeine!) which makes it almost laughable as inclusion.

It’s not yet clear whether caffeine withdrawal will be included in the new edition, which comes out in May. If it is, it doesn’t change much for people going through withdrawal, other than that it will be an official thing. My headaches and exhaustion felt pretty official, too, but they weren’t yet – that’s the difference.