Finally solved: how the body's own marijuana spreads through the brain
Since its discovery thirty years ago, it remained a mystery: how does the body’s own marijuana move between nerve cells in the brain? Mario van der Stelt and his research group have now uncovered the answer. This insight could aid the development of new treatments for pain and neurological disorders.
Marijuana produced by your own body—how does it travel through the brain? It turns out that the body’s own marijuana is transported in fatty vesicles. This surprising discovery contrasts with how traditional messenger molecules move. Dopamine and serotonin, for instance, travel as free-floating molecules between nerve cells. ‘This is possibly a new form of communication between nerve cells in the brain,’ says chemist Mario van der Stelt.
Van der Stelt suspects that other fatty messenger molecules might move through the brain in the same way. This insight could lead to new treatments. ‘The body’s own marijuana plays a role in pain and other neurological conditions. Now that we know how it moves, we can look for ways to influence its function,’ he explains.
Did you know?
Our brains produce substances that resemble the active compounds in cannabis. These naturally occurring substances, called endocannabinoids, play an important role in various processes, such as memory, anxiety, and pain. They act as messenger molecules between nerve cells. There are two types: anandamide and 2-AG. Van der Stelt and his team focused on 2-AG.
Why did it take so long for scientists to uncover how one type of the body’s own marijuana, 2-AG, is transported? The problem with 2-AG was that it could not be tracked directly. ‘Because it is a fatty substance, you can’t simply see it under a microscope,’ Van der Stelt says. Standard measurement methods were ineffective because they destroyed the cells, making it impossible to track the substance over time.
On average, each vesicle contained about two thousand 2-AG molecules.
Glowing cells as the key
The breakthrough came when Chinese researchers developed a smart sensor. This sensor uses cells that light up when they detect 2-AG from a neighbouring nerve cell. For the first time, this made it possible to observe 2-AG’s movement in real time. This discovery laid the foundation for four years of research, culminating in the latest publication in the scientific journal PNAS, which marks the final piece of Verena Straub’s PhD research.
Thanks to this sensor, Straub discovered that 2-AG is transported in vesicles. She tested this by isolating and analysing the vesicles. She found that when she blocked 2-AG production, vesicles still formed but no longer contained 2-AG. Conversely, when she prevented vesicle formation, the amount of 2-AG decreased. On average, each vesicle contained about two thousand 2-AG molecules.
Testing the new model from all angles
To confirm the accuracy of their model, the researchers tested their findings in brain tissue in collaboration with a US-based group. They found indications that the same process occurs in intact brain tissue. Additionally, together with Coen van Hasselt’s team, they developed a mathematical model that could only explain the observed signals if 2-AG was indeed transported via vesicles. ‘That provided extra evidence for our model.’