Callie Seaman was 16 years old when she started smoking cannabis to control her epilepsy. The attacks had begun two years earlier and were affecting her ability to lead a functional life; She used to be a wonderful student, but, since her diagnosis, her academic performance was suffering. The year was 1997, and then cannabis, even when used for therapeutic purposes, was still illegal throughout Europe. Anyone who wanted to purchase cannabis was forced to deal with dealers on the streets or entrust this task to a middleman.
“I never took it for the euphoric rush,” says Seaman, who lives near the English town of Sheffield. “I used it to be able to sleep at night – not getting enough sleep is one of the biggest triggers for episodes – and it worked,” adds Seaman, who continues to consume cannabis daily and, since 2018, can obtain the main compounds from the plant. of Cannabis sativa with medical prescription. She finds it reassuring to know that the medication now passes quality controls and contains predictable amounts of the active ingredient.
Laws regarding cannabis change from time to time. In almost all European countries, one of its active ingredients, cannabidiol, or CBD, is legal. But, in most cases, cannabis for personal consumption is not legal, although medical marijuana is increasingly widespread on the continent. “I haven’t had a crisis in two years. Epilepsy can be fatal, so it is very possible that cannabis saved my life,” says Seaman. However, it is not known with complete certainty how cannabis exerts its effect.
“Understanding how it works has never been more important than now, since this would allow us to find ways to use it in medicine and reduce the possible harmful effects of its consumption for recreational purposes,” explains Micah Allen, professor at the Center for Functional Integrative Neuroscience at the Aarhus University (Denmark).
Some cannabis compounds are believed to help relieve depression, anxiety, addiction, chronic pain, inflammatory diseases, and nausea associated with chemotherapy, among other problems. And while cannabis can be misused—some people, like teenagers or pregnant women, should probably avoid it altogether—European scientists are trying to find a way to take full advantage of the health-promoting properties of some of its ingredients. components.
Allen leads a research project that has received funding from the European Union to unravel the effects of some cannabis compounds, such as CBD, on human health. This five-year initiative, called CANNABODIES, will end in January 2027.
CBD and THC, the key compounds
Of the thousands of compounds produced by the cannabis plant, those of greatest medical interest are the group of cannabinoids, made up of more than a hundred of these compounds. Among them, CBD and tetrahydrocannabinol, or THC, are considered the most clinically important. Both CBD and THC trigger the release of chemical messengers in the brain that can influence pain sensation, mood, sleep, and memory. However, THC induces a state of intoxication that is not caused by CBD, which gives rise to the misuse of the former.
Cannabinoids do not cure any disease, but rather modify the way in which symptoms, physical or psychological, are perceived on a conscious level. By slightly altering the nervous system, these chemicals can modify a person’s perception of pain, for example. They can also change the emotional response to a stressful situation and, on the less positive side, decrease motivation.
Little is known about how exactly cannabinoids influence the human brain and body, since most studies have been carried out with animals. “This fact substantially limits our ability to design effective cannabinoid-based treatments,” says Allen.
The CANNABODIES project addresses the influence of THC and CBD on what is known as interoception, that is, the perception that people have of the internal state of their bodies and how this affects decisions. Concentrating the mind on hunger, heartbeat, or pain are examples of interoception. One might wonder, for example, whether a person who perceives less physical pain after consuming CBD is more likely to try harder when performing a task, or whether someone who is more focused on their heartbeat may feel more anxious after consuming THC.
Alteration of perception
According to Allen, the descriptions of their experiences by people who consume cannabinoids seem to indicate important changes at a sensory level, but no scientific study has addressed this question. “Many psychiatric disorders have to do with the alteration of healthy interoception. Therefore, if it is demonstrated that cannabinoids have therapeutic effects in this area, it would be very valuable information,” explains this researcher, who aims to lay the scientific foundations for this issue. “We want to find out what happens in the brain when a person consumes a cannabis product. What neural pathways are stimulated when CBD, THC or a placebo is ingested?”
For this research, participants must perform tasks while undergoing an MRI. Essentially, participants are instructed to squeeze a device in their hand or expel air into a tube in response to simple tests, which typically use images that appear on a screen, as if it were a video game. . They receive points for each correct choice and a financial reward of about one hundred Danish crowns (the equivalent of about €13) for completing a task.
The speed and accuracy of responses, participants’ willingness to try harder, and their perception of discomfort are some of the factors Allen will study. This neuroscientist aims to expand knowledge about the effects of cannabinoids on interoception to advance towards the goal of developing new treatments based on CBD or THC that are safe, effective and personalized.
Problems absorbing CBD
CBD is sold in oil form or incorporated into new foods and drinks, and is now widely sold as a powerful treatment for countless health problems; from anxiety or arthritis to intestinal disease and multiple sclerosis. But there is a big drawback with the products currently marketed: bioavailability, that is, the proportion of a drug or other substance that enters the bloodstream when it is introduced into the body.
Once the active ingredient of a CBD product purchased in a store has been ingested, only a small amount (just 6%) of it enters the bloodstream and is made available to the brain. Consequently, it is necessary to consume large amounts of CBD for it to take effect.
A team of researchers from the Universidade do Minho, in Braga (Portugal), has now reached the halfway point of a two-year project whose objective is to clarify the metabolic processes that determine the amount of CBD that the body can absorb after ingestion. . “There is some variability between people, but the reasons are not exactly known,” explained Dr. Renata Vardanega, Bioengineering expert and coordinator of the EU-funded project, CBDHIGHBIO, which will end in October 2024.
Vardanega and his team study the factors that determine the amount of the active ingredient that is absorbed after consuming CBD. Does it depend, for example, on what else the person has eaten or drunk? They also work to improve the absorption of CBD by pairing it with a long-chain fatty acid during administration. This method reroutes the absorption route to prevent CBD from being metabolized by the liver.
A third line of this research tries to find a way to enhance the absorption of CBD by combining it with piperine, a compound derived from black pepper. Piperine is an excellent bioenhancer, so it has the ability to increase the bioavailability of another substance, according to Professor Antonio Vicente, bioengineer of the project.
“We are looking for ways to take advantage of this property to increase the bioavailability of CBD once it enters the body,” he declared. The ultimate goal of the project is to create cannabinoid-based edibles, such as chocolate bars, drinks or butters, that are much more potent than any of the currently existing products, but contain as little CBD as possible. “What people consume today is expensive and not tremendously effective, plus many find it unpleasant to ingest,” Vicente commented. “We think we can do much better.”
The research referred to in this article has been funded through the European Research Council (ERC) and the Marie Skłodowska-Curie Actions (MSCA). The opinions of those interviewed do not necessarily reflect those of the European Commission.
Article originally published in Horizonthe European Union Research and Innovation Review.
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