Recent work published by researchers in Barcelona has just uncovered more details about the neurochemical pathway that leads to marijuana’s psychoactive effects, specifically its effects on memory. Not only did they make a breakthrough in the neurochemistry of cannabis, they also designed a compound that was able to block THC’s effects on memory in mice.
Since the discovery of the cannabinoid receptor by Raphael Mechoulam and colleagues, medical scientists have continued to investigate this newly found receptor and have found that it has a presence all over the body, not just in the brain. In fact, two cannabinoid receptors exist: CB1 and CB2. While the CB2 receptor stills retains some of its mystery, scientists have know for a while that the CB1 receptor is the one responsible for the “high” in cannabis.
More recently however, neuroscientists have found links between the certain serotonin receptors and the cannabinoid system. Not only do these receptors share a region in the brain, but also activation of the 5HT2A receptor causes a release of endocannabinoids, the body’s natural “darts” for the cannabinoid receptor’s “dartboard” (in a similar way that your body produces serotonin to act as a signal carrier in your serotonin system).
Going along this line of thought, researchers in Barcelona decided to look deeper into the serotonin receptor – cannabinoid receptor connection, and they found that the two receptors are literally connected to each other. The two receptors associate with each other to form what’s called a heteromer. Receptors are located on the cell wall of neurons in the brain, but the heteromer receptor was only found in certain areas.
By performing experiments on mice they found that THC’s effect on short-term memory is not the cannabinoid receptor’s “fault,” in a manner of speaking. The attached serotonin receptor seems like the culprit for certain psychoactive effects, while the pain relief and other medical benefits of THC stem from the cannabinoid receptor.
There you can see a schematic of what’s going on in the neurons of some really high mice. Normally the cannabinoid receptor (CB1R) and the serotonin receptor (5HT2AR) form the heteromer, attached halfway in and out of the cell wall of a neuron. When THC binds to CB1R on the outside of the cell, it makes a signal on the inside that affects the neuron’s behavior. Recent findings show that when THC hits CB1R, it also makes 5HT2AR produce a signal. This same serotonin receptor is also involved the hallucinogenic and psychedelic effects of famous substances like LSD and psilocybin, the active component of magic mushrooms.
When normal mice were given a special drug (the “interference peptide” from the drawing) that blocked the association between the two receptors, they didn’t get short-term memory loss when given THC but it still had its pain-relieving effects. Genetically modified mice without a 5HT2A receptor, but with an intact CB1 receptor, didn’t suffer short-term memory loss when given even high doses of THC, but they still got the pain-relieving effects.
The results of their work are highly important for the development of new medicines. Cannabis has great medical potential, but the effects on memory and anxiety are clearly not for everybody, even as a matter of taste. Hopefully this discovery will one day lead to a safer alternative to dangerous opiate pain relievers and habit-forming sleep aids.
