Fake pot

Experiments with placebo cannabis

Bart Braun

Smoking pot leads to more mistakes – and a reduced ability to recognise them, as psychologist Mikael Kowal discovered with the aid of pot placebo produced in Leiden.

Studying cannabis is more complicated than you might expect. Some patients use cannabis as medication, but that doesn’t mean that the substance is actually registered as a medicine. Despite the large number of patients and recreational users, hashish and pot are still illegal substances in the Netherlands. As a result, a test using cannabis is far more difficult to arrange than research into the effects of Ritalin, for example. A scientist needs permission from the Ministry of Public Health as well as from the medical-research ethics committee. The Ministry may grant dispensation from the Opium Act, but it will take time. "It was two years before we could actually get to work on the study", recalls psychologist Mikael Kowal. "Which sucks, if you’re doing a doctorate and your time is limited."

Once you get started, there’s a methodological problem you have to deal with: if you want to study the results of anything, you need a control group. That group’s test subjects must not know that they are only taking part for the sake of comparison. That’s easy enough if you are doing research on pills: you set up two groups and give one the pills that work and the other the pills that don’t work. Of course, if you are researching cannabis and you give one half of your test subjects a joint and the other half a Marlboro light, all the smokers are going to know whether they’re part of the control group or not.

So, in short, you need a better placebo: fake pot.

Which exists. Bedrocan, the company that grows medicinal pot for chemists and Kowal’s current employer, also produces placebo cannabis. They make it at Proxy Labs in Leiden’s Bioscience Park.

"We have a method that extracts all THC-related substances and we extract the terpenoids too, which produce pot’s specific taste and smell. Then we put the terpenoids back again. We need two kilograms of active cannabis for one kilogram of the placebo, but the final product is indistinguishable from the real thing. It tastes and smells like cannabis, in fact, like the specific pot variety we used."

Kowal and his colleagues conducted two psychological studies: one of control and one of creativeness.

The first centers on a phenomenon that psychologists call "error monitoring". Your brain keeps an eye on everything you are conscious of doing. If something goes wrong, your brain will report it so that you can - hopefully - correct it. If you stick electrodes on the heads of your test subjects, you can measure error monitoring with two signals of electrical activity in the brain.

One signal, called "error positivity", makes people aware that they have made a mistake. It is likely that error positivity has much to do with the "Oops" feeling you get when your car grazes the curb or when Super Mario falls into a hole, but it’s not quite the same. It’s like a fire alarm, while a much larger part of your brain decides whether there really is a fire or not.

The other signal is called "error-related negativity". "You notice that sooner and it is something you’re not at all conscious of. It’s a fundamental process running in your brain", Kowal explains.

Kowal and his colleagues put up notices in cannabis cafés etc. and gathered together 61 test subjects who regularly used cannabis. That group was split into three sub-groups: one took a high dosage of THC, one took a low dosage and one was given the special pot placebo. The test subjects inhaled it with a medicinal marijuana vapour inhaler.

The first conclusion is that the placebo proved adequate at fooling people. Kowal says: "These people had been smoking pot at least twice a week for at least two years, and most of them had been smoking it much longer and more frequently. You would expect them to be experts, but all of them except two thought they had simply been given the lower dosage.

The stoners were given a test to see how fast they reacted to information on the screen. On average, the placebo group made slightly fewer mistakes, but that’s not what the psychologists wanted to know; the maximum reaction time had been fixed so that it was so short no one could avoid making mistakes. It’s more interesting to know how the brains of the test subjects responded to those mistakes. The signal for error-related negativity functioned more poorly in the group who were given a high dosage of THC. Both the high and low dosages had an impact on the signal for error positivity.

In other words: smoking pot leads to more mistakes and reduces the ability to recognise them, even if you are an experienced pot smoker to whom the effects of cannabis should not come as complete and utter surprise. Kowal knew, from other research, that reduced error positivity had already been identified in chronic users, even if they hadn’t used cannabis just before the test. "As a reduced ability to learn from mistakes is related to poor prognoses for treating drug addiction, it seems important that we learn more about the effects of cannabis on that ability", Kowal reports in his dissertation.What do the results mean for non-addicts? "In situations that require quick adjustments to changing circumstances, such as driving a car, you won’t manage as well as otherwise if you are under the influence of cannabis. Because cannabis also slows down users’ reactions, in real life, it won’t always be possible to determine the actual consequences of reduced error control.

In another test, Kowal studied the effects of cannabis on certain thinking tasks. The test subjects were given a brain-storming assignment. "They were asked to come up with, say, as many ways of combining a pen with a shoe as possible," explains Kowal. A high dosage of THC produced bad scores while a lower dosage did not produce any measureable effect.

A remarkable discovery, because there is a wide-spread belief that smoking pot makes you more creative. Kowal says: "That’s what you’d expect: if a substance reduces your inhibitions, you expect to be better at this kind of thinking assignment. Perhaps the results would be different if you gave people a creative assignment that suited their interests: ask musicians to write music and artists to draw. But, you know, how could you test whether it works?"

Hottest topic in cannabis research

The last chapter of Kowal’s dissertation is a literature retrospective on the effects of cannabidiol, a compound that is chemically related to THC but that has completely different effects on your brain; for instance, it does not make you high. That is precisely why it is easier to study: in many countries, you may grow hemp as long as it contains very low quantities of THC. “It’s the hottest topic in cannabis research”, says Kowal. “It seems to reduce the detrimental effects of THC, such as anxiety, etc.” You can even buy the substance in its pure form, more or less. Who buys it, then? Mainly people suffering from epilepsy and parents of children with epilepsy. Around thirty per cent of epileptics who take prescribed medicine still suffer attacks, so it’s not surprising that they’re on the lookout for something else. While there is plenty of anecdotal evidence that it works, there is very little scientific evidence. “It’s too early to draw any conclusions from it”, states a retrospective published earlier this year in the New England Journal of Medicine. Kowal, in his own retrospective, limits his comments to the question of whether cannabidiol also has an effect on how users deal with emotions or cognition. Very little is known about that matter either, but he speculates, on the basis of the research available, that cannabidiol also reduces people’s awareness of the mistakes they make.

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Fake pot

Smoking pot leads to more mistakes – and a reduced ability to recognise them, as …