Methamphetamine addiction leads to depleted neurotransmitter levels, causing movement problems, depression, reduced sexual function, insomnia, and even schizophrenia

Methamphetamine Addiction and Neurotransmitter Balance

Posted Ramona Richard, MS, NC Blog

Methamphetamine is a synthetic recreational drug with highly addictive properties. It creates a euphoric feeling—the “high” that meth users become neurochemically dependent on to feel good. In 2012, the National Survey on Drug Use and Health stated that there are 1.2 million people worldwide who used meth that year.[1] Methamphetamine is the second most common drug in the world[2], making treatment of meth abuse the target of many research efforts. While methamphetamine itself has a highly specific mode of action, prolonged use of the drug can cause a cascade of neuroendocrine imbalances and result in long-term brain and neuron damage.

Methamphetamine and Neurotransmitters

Methamphetamine can enter the body in several ways. Many users inject it directly into their bloodstream, but the drug can also be smoked or taken orally.[3] Upon entering the body, methamphetamine is absorbed into the plasma where it has a twelve-hour half-life.[4] Once it reaches the brain, methamphetamine amplifies dopaminergic transmission. Dopamine is the neurotransmitter that allows us to feel pleasure and euphoria, to control motor function, and to direct memory and focus.[5] When methamphetamine binds to dopamine transporter (DAT), reuptake of dopamine is blocked[6], leaving more dopamine available at the synapse (space between two neurons). Methamphetamine also upregulates the activity of tyrosine hydroxylase, an essential enzyme in the formation of dopamine, norepinephrine, and epinephrine[7]. These are all excitatory neurotransmitters necessary for various bodily processes and responses to stimuli. The transporters of norepinephrine and serotonin (a neurotransmitter responsible for mood, sleep, and neuroendocrine regulation) are also acted on by methamphetamine.[8] Meth causes 5-HTT transporter loss[9], which prevents serotonin reuptake by neurons. Depleted norepinephrine and serotonin levels have been shown to return to normal after cessation of methamphetamine use[10], while depleted dopamine may have more detrimental long-lasting effects.

Increasing available dopamine in the brain is initially extremely pleasurable for the user, and it is typical for meth users to be addicted to the drug. Repeated use of methamphetamine will result in dopamine depletion and destruction of DAT[11]. Dopamine lingering around the synapse is actually toxic to dopamine receptors at high levels, leading to desensitization. Ongoing methamphetamine use will eventually reduce the activity of tyrosine hydroxylase, in turn depleting dopamine, norepinephrine, and epinephrine levels.[12] This decrease in dopamine and desensitization of receptors can cause violent behavior and paranoid psychosis.[13] Prolonged meth use will also cause brain inflammation which reduces essential brain grey matter.[14] Other studies have found that meth abuse can cause hypoglycemia in the human brain by limiting glucose (the main source of cellular energy for brain cells) uptake.[15] Those suffering from methamphetamine addiction have depleted neurotransmitter levels, causing movement problems, depression, reduced sexual function, insomnia, and even schizophrenia.[16]

The neuroendocrine system is maintained through feedback loops, checks and balances, and intricate homeostatic mechanisms. There are many lifestyle, genetic, and nutritional factors that can alter the HPA-Axis, but addictive drugs have some of the most powerful and long-lasting impacts on this delicate balance. The human body is extraordinary in its ability to correct for excesses or insufficiencies, but it can only take so much abuse to its receptors and enzymatic pathways. Partial restoration of dopaminergic transmission is possible with prolonged cessation of methamphetamine use.[17] Despite neurotransmitter malfunction and depletion, the body’s resilience will allow formerly addicted individuals to feel euphoric effects of dopamine upon eating a good meal, falling in love, or laughing with friends.



[1] Methamphetamine Abuse and Addiction. (n.d.). Retrieved April 3, 2017, from

[2] Muneer, P. M., Alikunju, S., Szlachetka, A. M., & Haorah, J. (2011). Methamphetamine Inhibits the Glucose Uptake by Human Neurons and Astrocytes: Stabilization by Acetyl-L-Carnitine. PLoS ONE, 6(4). doi:10.1371/journal.pone.0019258

[3] Methamphetamine Abuse and Addiction. (n.d.). Retrieved April 3, 2017, from

[4] Julien, R. M., & Julien, R. M. (2005). Cocaine and the Amphetamines. In A primer of drug action: a comprehensive guide to the actions, uses, and side effects of psychoactive drugs. New York, NY: Worth .

[5] Methamphetamine Abuse and Addiction. (n.d.). Retrieved April 3, 2017, from

[6] Nakagawa, T., Suzuki, Y., Nagayasu, K., Kitaichi, M., Shirakawa, H., & Kaneko, S. (2011). Repeated Exposure to Methamphetamine, Cocaine or Morphine Induces Augmentation of Dopamine Release in Rat Mesocorticolimbic Slice Co-Cultures. PLoS ONE, 6(9). doi:10.1371/journal.pone.0024865

[7] Graham, D., Noailles, P., & Cadet, J. (2008). Differential neurochemical consequences of an escalating dose-binge regimen followed by single-day multiple-dose methamphetamine challenges. Neurotoxicology and Teratology, 30(3), 258. doi:10.1016/

[8] Thanos, P. K., Kim, R., Delis, F., Cachati, G., Ananth, M., Rocco, M. J., . . . Volkow, N. D. (2017). Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS ONE, 12(2).

[9] Graham, op. cit.

[10] Krasnova, I. N., Jusintova, Z., Ladenheim, B., Jayanthi, S., McCoy, M. T., Barnes, C., . . . Cadet, J. L. (2010). Methamphetamine Self-Administration Is Associated with Persistent Biochemical Alterations in Striatal and Cortical Dopaminergic Terminals in the Rat. PLoS One, 5(1).

[11] Thanos op. cit.

[12] Graham, op. cit.

[13] Julien, op. cit.

[14] Thanos, op. cit.

[15] Muneer, op. cit.

[16] Methamphetamine Abuse and Addiction. (n.d.). Retrieved April 3, 2017, from

[17] Krasnova, op. cit.


Clinical Contributor

Sophie Thompson

Sophie Thompson

Clinical Support Specialist at Sanesco Health
Sophie recently obtained her degree in Biology from UNCA in Asheville. Born and raised in Asheville, her hobbies include painting, writing and spending quality time with her dog and her family.
Sophie Thompson

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    Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.