Drugs and The Brain

20.02.2021 |

Episode #2 of the course Introduction to drugs and behavior by Dr. Daniel McGrath

 

Welcome back! In the last lecture, we discussed the definition of psychoactive drugs and the most common routes of administration. In this lecture, we are going to focus on how drugs are absorbed into the bloodstream, distributed to the brain, and how they reach their site of action.

In order for drugs to have any psychoactive effect, the drug molecules must first reach the brain. In most cases, molecules are delivered to the brain through the circulatory system. However, this first involves the absorption of drug molecules through tissues. This is actually a very complex process, but what it essentially means is that the drug will pass through lung tissue (for inhalation), the lining of the intestinal tract (for oral administration), or the mucus membranes (for sublingual and intranasal). In the case of intravenous administration, drugs are injected directly into the bloodstream.

Once drug molecules reach the blood, a process called distribution takes place. The circulatory system carries the molecules throughout the body, including the brain. However, several sophisticated pharmacokinetic processes reduce the number of drug molecules available or can slow their distribution. In addition, the body begins to break down drug molecules quite quickly.

The liver and kidneys are responsible for metabolism, whereby drug molecules are modified via enzymes created by the liver, making it easier for the body to eliminate them in the urine. For drugs taken orally, like alcohol, drug molecules go to the liver first, which results in many of these particles being broken down and exited from the body soon after. The result is that far fewer alcohol molecules actually make it to their site of action in the brain. This process is called the first-pass metabolism, and it plays an important role in helping the body break down drugs and to avoid toxic doses.

Once drug molecules enter the blood, they are soon distributed throughout the body and to the brain. In order to enter the brain, a drug must be able to move through the blood-brain barrier (BBB). The BBB is a network of specialized cells that are tightly linked together and are designed to keep toxins away from brain cells. As it turns out, though, the most common psychoactive drugs that people use are able to pass through the BBB quite easily.

When drug molecules reach the brain, they influence how neurons (brain cells) communicate with each other. Neurotransmitters are chemical messengers that are chiefly responsible for communication between billions of brain cells. The key neurotransmitters, when it comes to most psychoactive drugs, are dopamine, acetylcholine, glutamate, γ-aminobutyric acid (GABA), norepinephrine, and serotonin. Depending on the drug and the exact neurotransmitter implicated, the degree of influence that the drug will have on behavior will be different. The relationship between neurotransmitters and individual drugs will be described further in later lectures.

With a few exceptions, most psychoactive drugs are known to increase the amount of dopamine released in the brain. Dopamine is a neurotransmitter involved in many vital functions, including memory, movement, learning, and reward. Most psychoactive drugs increase the amount of dopamine available in the reward circuitry of the brain. The reward system is comprised of the ventral tegmental area (VTA) and the nucleus accumbens, with axons also extending to the cerebral cortex and the amygdala.

The reward system has evolved over time and is critical to ensuring our individual survival. It plays a direct role in motivation, emotion, and learning. Imagine you are hiking on a trail, and you come across raspberry bushes. You stop and enjoy some delicious berries, which also provide your body with nutrition. Meanwhile, your reward system releases dopamine. This neurochemical process will help to reinforce your memory for that event. The next time you are on the trail, there is a good chance that you will remember that exact spot. Hopefully, more raspberries will have grown since last time. This provides a general idea of how the reward system and dopamine contribute to survival.

Now, dopamine has often been called the pleasure chemical; however, this is not really correct. Today, dopamine is better understood as being the chemical that motivates us to seek out natural rewards, such as food. This is often beneficial for us, but not always. Many psychoactive drugs, especially those that are highly addictive, are said to “hijack” this reward system, leading to compulsive use and addiction.

In tomorrow’s lesson, we are going to discuss tolerance and withdrawal, two processes that are also critical for understanding substance use and ultimately addiction.

See you tomorrow!

 

Recommended book

Memoirs of an Addicted Brain by Marc Lewis

 

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