Substance use disorders (SUDs) are ‘treatable, chronic diseases characterized by a problematic pattern of use of a substance or substances leading to impairments in health, social function, and control over substance use’ ¹. Drugs of abuse exhibit their effect on the body through the body’s natural messengers, neurotransmitters. To get a basic understanding of neurotransmitters, please see this article here. Different drugs affect various neurotransmitters in different ways. Further understanding of drugs of abuse and their affected neurotransmitters can lead to a more complete understanding of the effects experienced by the user. This article will cover a few common neurotransmitters and how some drugs affect them.  

Common Neurotransmitters 

Norepinephrine is a neurotransmitter that plays a key role in attention, arousal, cognitive function and stress reactions². It can also act as a hormone and contributes to the ‘fight or flight’ response in the sympathetic nervous system. High levels of norepinephrine are associated with increased concentration, increased alertness and arousal, enhanced retrieval of memory, and increased heart rate. Low levels of norepinephrine are associated with lack of energy and motivation, and decreased mood. 

Dopamine is another neurotransmitter which is most known for playing a key role in the ‘reward’ center of the brain³. It is involved in memory, movement, mood, attention, and pleasurable reward and motivation. Dopamine can also affect blood pressure through manipulation of blood vessels. High levels of dopamine are linked to feelings of happiness, motivation, focus, and alertness while low levels of dopamine can cause fatigue, mood swings, memory loss, concentration problems and a low sex drive.  

Serotonin is a neurotransmitter which plays a key role in sleep, mood, sexual drive, learning, memory, and happiness⁴. It also helps regulate body temperature and your hunger. Low levels of serotonin are thought to play a role in many mental health disorders such as anxiety, depression, schizophrenia, obsessive-compulsive disorder, and mania. High levels of serotonin can cause confusion, high blood pressure and muscle twitches, but can also have severe effects such as fever and seizures.  

Drug Classes 

Amphetamine, cocaine, and hallucinogens all affect the levels of norepinephrine, dopamine and serotonin in the body.

Cocaine causes an elevated amount of norepinephrine, dopamine, and serotonin in the body by preventing the reuptake of those neurotransmitters⁵. In other words, those neurotransmitters get ‘trapped’ next to the receptors, so the receptors continuously send out signals

 Cocaine has a stronger effect on norepinephrine and dopamine than it does on serotonin.  

Amphetamine also causes an increased amount of norepinephrine, dopamine, and serotonin in the body, but does so through various mechanisms of action6. Like cocaine, amphetamine prevents reuptake, but amphetamine also has been reported to inhibit the neurotransmitter metabolism, allowing the neurotransmitter to have more time to bind to receptors and release signals⁶

Amphetamines, like cocaine, have a stronger effect on norepinephrine and dopamine than it does on serotonin. 

Hallucinogens act differently than amphetamines and cocaine in the fact that hallucinogens act as serotonin and dopamine agonists⁷. In other words, these hallucinogens act like serotonin, binding to the serotonin receptors and activating them, even when serotonin is not available.

Also, unlike amphetamine and cocaine, hallucinogens have the strongest effect on serotonin. 

Even though amphetamine, cocaine, and hallucinogens all affect the same neurotransmitters, the overall effects experienced by the user for each drug class are vastly different. This is because each drug class has different mechanisms of action, and they affect each neurotransmitter to different degrees. Understanding neurotransmitters and how the drug classes affect them can help us to understand the effects experienced by different illicit substances. 

References:

1. CDC. “Disease of the Week – Substance Use Disorders (SUDs).” Centers for Disease Control and Prevention, 5 Oct. 2022, https://www.cdc.gov/dotw/substance-use-disorders/index.html#:~:text=Substance%20Use%20Disorders%20(SUDs)%20are,and%20con 

2. Hussain, Laila S., et al. “Physiology, Noradrenergic Synapse.” PubMed, StatPearls Publishing, 2022, https://www.ncbi.nlm.nih.gov/books/NBK540977/#:~:text=First%20identified%20in%20the%201940s,cognitive%20function%2C%20and%20stress%20reactions.

3. Cleveland Clinic. “Dopamine.” Cleveland Clinic, Cleveland Clinic, 23 Mar. 2022, https://my.clevelandclinic.org/health/articles/22581-dopamine 

4. Cleveland Clinic. “Serotonin.” Cleveland Clinic, Cleveland Clinic, 18 Mar. 2022, https://my.clevelandclinic.org/health/articles/22572-serotonin 

5. Sora, I., et al. “Molecular Mechanisms of Cocaine Reward: Combined Dopamine and Serotonin Transporter Knockouts Eliminate Cocaine Place Preference.” Proceedings of the National Academy of Sciences, vol. 98, no. 9, 24 Apr. 2001, pp. 5300–5305, https://www.pnas.org/doi/10.1073/pnas.091039298 

6. Martin, Dustin, and Jacqueline K. Le. “Amphetamine.” PubMed, StatPearls Publishing, 2021, https://www.ncbi.nlm.nih.gov/books/NBK556103/#:~:text=Go%20to%3A-,Mechanism%20of%20Action,through%20a%20variety%20of%20mechanisms. 

7. “Brain Mechanisms of Hallucinogens and Entactogens.” New Perspectives in Chronic Psychoses, vol. 3, no. 4, Dec. 2001, pp. 265–279, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181663/#:~:text=Recent%20electrophysiological%20studies%20have%20produced,receptors%20in%20the%20frontal%20cortex