Marijuana in the Brain

In order to understand how marijuana/THC affects the senses and behavior, you need a basic understanding of how the brain’s internal communications function.

Neurons (brain cells) process information. Neurotransmitters and receptors govern their functions. Neurotransmitters are the "messenger" chemicals in the brain. They are released into the gap between the neurons, the synapse, and then travel to the receptors on neighboring neurons. Receptors are "binding sites" for chemicals in the brain. They instruct neurons to regulate various brain and body functions. Their actions are triggered by neurotransmitters if there is a precise fit, or a "bind," between the transmitter and the receptor. If the transmitter molecules don’t fit exactly into a receptor, then nothing happens.

Neurons can have thousands of receptors for different neurotransmitters, so any neurotransmitter can have diverse effects in the brain. However, various neurotransmitters are believed to regulate specific processes. For example, serotonin is believed to regulate mood, sleep, and learning. Norepinephrine and epinephrine regulate the body’s reactions to stress. Dopamine regulates the "reward system" in the brain.

Naturally occurring neurotransmitters, such as serotonin, norepinephrine, epinephrine, and dopamine, are also called endogenous ligands. Various drugs can mimic endogenous ligands. It is by mimicking endogenous ligands that many drugs of abuse produce their effects.

After many years of study, a cannabinoid receptor site in the brain was discovered in 1988. This implied that the brain has endogenous ligands that are substantially similar to the cannabinoids in marijuana (THC and others.) It is now considered likely that the neurotransmitter that naturally triggers cannabinoid receptors is one known as anandamide. Anandamide is a recently discovered neurotransmitter that plays a role in pain, depression, appetite, memory, and fertility. Its name comes from ananda, the Sanskrit word for "bliss." This suggests that THC produces its pleasurable effects by mimicking anandamide.

The cannabinoid binding sites are largely concentrated in the basal ganglia, cerebellum, and limbic system of the brain. The basal ganglia control unconscious muscle movements, and the substantia nigra section of the basal ganglia has the highest level of cannabinoid binding sites. The cerebellum also affects movement and coordination. The limbic system seems to integrate memories and strong emotions such as love, fear, and anger. The limbic system includes the hippocampus, where short-term memory is processed into long term memory; the amygdala, the region most responsible for strong emotions; and the hypothalmus, a gland which releases endocrine hormones. Because the cannabinoid receptors are found in the brain regions that control movement and emotions, it follows that cannabinoids affect an individual’s control of those functions. THC causes lack of physical coordination. It can also make it difficult for a user to integrate emotions and actions, meaning that his actions may be inappropriate for his emotions.

Cannabinoids, naturally-occurring and drug-related, affect memory and sleep because memory and sleep are regulated in the hippocampus. One way these effects have been studied is by finding the cannabinoids’ receptor antagonist. A receptor antagonist prevents a neurotransmitter from binding to the receptor. When scientists can find the chemical that prevents a neurotransmitter’s actions, they can verify that those are the actions of that neurotransmitter. The receptor antagonist for THC and anandamide is called SR141716. It functions like an antidote to THC and anandamide. What does SR141716 do? It enhances the same memory functions that anandamide inhibits in the brain. This means that our brains naturally make a chemical – anandamide – that prevents us from forming some short-term memories! Scientists next had to determine why the brain would have a process for preventing the formation of memories.

The answer lies in the sleep cycle. Rats given SR141716 during sleep had their normal sleep cycles disturbed. They experienced a lack of short-wave and REM sleep. Without adequate amounts of these kinds of sleep, neither rats nor humans can function at peak levels. It seems, then, that the intended role of anandamide is to ensure that the individual makes the most of his sleep time rather than forming short-term memories.

There is a key difference between anandamide and other cannabinoids, such as THC, however. Although they have substantially similar structures, the fact that one is naturally occurring and the other is introduced from outside the brain makes all the difference. While anandamide is carefully measured out by the brain to regulate certain processes and make them run more smoothly, THC and other marijuana-related cannabinoids interfere with the brain’s chemical balance. Where anandamide might smooth the coordination of emotions and movement, for example, THC might get in the way of that coordination. Where anandamide inhibits, or limits, the formation of short-term memories during the sleep cycle, THC blocks the formation of short-term memories while the user is awake!

Clearly, being structurally similar on a molecular level does not make the two substances identical. The brain is deeply complex, mysterious, and delicately balanced. Any chemical added to its mix disrupts its normal functions.