It’s important to have at least a basic understanding of the different parts and processes of the brain that are involved with the reward pathway because they are fundamental to addiction. There are neuropeptides that activate the various chemical receptors and act on the reward pathway. Neurotransmitters are chemicals that relay, amplify, and modulate signals within the brain, transmitting information between neurons (nerve cells). Neurons consist of several parts, including dendrites, a cell body (called a soma), an axon, and terminal branches. Neurons are separated by gaps or spaces known as synapses. As the brain’s chemical messengers, neurotransmitters must find receptors on other neurons in order to transmit the messages they contain.
How do drugs affect neurotransmitters?
It is helpful for addiction counselors to be familiar with the neurotransmitters affected by drugs. This information is also important in understanding how psychiatric medications are thought to work. There are many neurotransmitters in the brain, but we will focus on the ones that are involved with the reward pathway. Different drugs have differential effects on neurotransmitters. Marijuana and opiates/opioids can activate neurons because their chemical structure emulates that of a natural neurotransmitter. Cocaine and crystal meth, on the other hand, can cause the nerve cells to release much larger than normal amounts of natural neurotransmitters or prevent the usual reabsorption of these brain chemicals. Serotonin is a neurotransmitter that affects mood, memory processing, and cognition. Psychiatric medications frequently “target” serotonin in order to modify the levels of this neurotransmitter in the brain. Selective Serotonin Reuptake Inhibitors (SSRIs) are a class of antidepressant medications that includes Prozac and Paxil. SSRIs are believed to modulate serotonin in the brain as their primary mechanism of action, and are often prescribed to treat depression and anxiety. Dopamine is the primary neurotransmitter and the final activation chemical in the reward pathway. Dopamine is linked to motivation, pleasure, and motor functioning. Dopamine activates the dopamine receptors and is responsible for reinforcing behavior. Most mind—and mood—altering drugs generate high levels of pleasure in the reward center by increasing dopamine levels. If the nervous system can be considered a highway that transports people mentally and emotionally, dopamine functions as the car that travels the highway of the nervous system. If you’re driving and press the gas pedal to the floor, you’re going to go really fast. But if you keep your foot on the accelerator, not only are you at great risk of getting into an accident, but you will eventually run out of gas—and that’s what happens with the repetitive use of substances that takes place in addiction. Almost all drugs of abuse exert an effect on dopamine levels, causing a release of and/or preventing reuptake of this neurotransmitter. Interestingly, in addiction treatment we don’t see too many people come in because they’re addicted to LSD and other hallucinogens because these drugs affect serotonin though not dopamine levels. Stimulants such as cocaine and crystal meth cause the biggest increase in dopamine levels, effectively flooding the brain with it. Not only does cocaine stimulate the release of extraordinary amounts of dopamine, but it also inhibits the reuptake of that dopamine, effectively blocking it from entering the next neuron. As a result the dopamine remains in the synaptic space much longer. This is what creates the incredibly intense high users describe. However, the massive release of dopamine also means that the brain’s supply of it is rapidly depleted, precipitating an equally intense crash as the car runs out of gas. Cannabinoids are neurotransmitters linked to pain modulation. Cannabinoid receptors share some properties with opiate receptors in that they are involved with nociception, the ability to feel pain. So the cannabinoid receptors are anti-pain receptors and their activation can also cause sedation. Cannabinoid receptors are activated by cannabinoids, generated naturally inside the body (endocannabinoids) or introduced into the body externally as cannabis or a related synthetic compound. when people smoke marijuana, they experience sedation. The GABA system is where the depressants or “downers” come into play. GABA is the chief inhibitory neurotransmitter, so it is involved with alcohol and tranquilizer use. Use of alcohol, xanax, and Valium makes the individual feel calmer, sleepier, and less anxious via activation of the GABA receptor system. And GABA binds to the sub-receptors and activates secondary messengers, which have an effect on dopamine as well. Glutamate is the principal excitatory neurotransmitter, but it is also involved in the regulation of learning and memory. It binds to the NMDA receptor and is implicated in many of the excitatory chemical reactions. Neurotransmitters can be viewed as the electrical plugs and receptors as the electrical outlets that neurotransmitters fit into. Every cell in our body has many types of receptors on it. Receptors allow substances, such as dopamine, to enter cells. Without receptors a substance can have no effect because it cannot enter the cell. An agonist is a substance that binds to a specific receptor and triggers a response in the cell. Agonists can be drugs, medications, or naturally occurring chemicals that interact with nerve cell receptors to stimulate drug actions or effects. For example, if you sprain your ankle, your body is going to release natural cannabinoids and natural opioids (known as endorphins) that bind to their specific receptors and decrease pain. All neurotransmitters—serotonin, dopamine, glutamate, endorphins, cannabinoids, etc.—have specific receptors in the brain that they plug into. For example, opioid pain medications bind to endorphin receptors in the brain and their effects are limited by the number of receptors present. The neurotransmitter receptors that are involved in addiction are:
- the dopamine receptor
- the opioid receptor
- the glutamate (NMDA) receptor
- the GABA receptor
- the cannabinoid receptor
- the adrenergic receptors
There are three major opioid receptors. The mu receptor is the key to opiate addiction. Some of the other receptors have more to do with pain, but the mu receptor, when it’s ignited, triggers the most dramatic psychoactive response. When opioids attach to the mu receptors, dopamine is released, causing pleasurable feelings to be produced. As opioids leave the receptors, pleasurable feelings fade and withdrawal symptoms (and possibly cravings) begin. This blog post is an excerpt from The Therapist’s Guide to Addiction Medicine – A Handbook for Addiction Counselors and Therapists – by Barry Solof, MD, FASAM; Published by Central Recovery Press (CRP).