Methamphetamine Washout Syndrome: More than Just Catecholamine Depletion?
Main Article Content
Abstract
Methamphetamine (MA) use continues to increase on a global scale. Patients using MA utilize emergency department and hospital resources at a higher rate than other patients due to serious associated medical conditions, including blunt and penetrating trauma, stroke, myocardial infarction, cardiomyopathy, and rhabdomyolysis. Mental health resources are also utilized at a high rate stemming from MA-associated agitation, aggression, psychosis, self-harm, and suicidal ideation. Patients presenting with MA toxicity frequently require a combined team effort of clinicians, nurses, psychiatric workers, and social services prior to final disposition. The phenomenon of “Methamphetamine Washout Syndrome” (MAWS) has been used to describe a period of MA-induced hypersomnolence greater than eight hours at our institution. During this period the patient cannot easily be awakened or interviewed, and they continue to occupy a hospital bed. The etiology of MAWS was initially thought to simply be a result of catecholamine depletion followed by a period of synthesis and restoration. In this report, we investigate this theory and other potential causes of MAWS such as MA neurotoxicity from microglial activation and cytokine release, mitochondrial dysfunction, energy supply disruption, and apoptosis. The effect of MA on sleep is also detailed, and potential treatment options to optimize patient outcome and decrease length of stay are discussed.
Article Details
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RICHARDS, John R..
Methamphetamine Washout Syndrome: More than Just Catecholamine Depletion?.
Medical Research Archives, [S.l.], v. 13, n. 4, apr. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6514>. Date accessed: 15 may 2025.
doi: https://doi.org/10.18103/mra.v13i4.6514.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Ciccarone D, Shoptaw S. Understanding Stimulant Use and Use Disorders in a New Era. Med Clin North Am. 2022;106(1):81-97. doi:10.1016/j.mcna.2021.08.010
4. Suto DJ, Xiao J, Bellinghausen AL, et al. Temporal Trends in Methamphetamine Use in Patients Admitted to the Hospital: A Retrospective Cohort Study. J Addict Med. 2024;18(3):339-341. doi:10.1097/ADM.0000 000000001294
5. Fulde GWO, Forster SL. The impact of amphetamine-type stimulants on emergency services. Curr Opin Psychiatry. 2015;28(4):275. doi:10.1097/YCO.0000000000000171
6. Jones CM, Compton WM, Mustaquim D. Patterns and characteristics of methamphetamine use among adults - United States, 2015-2018. MMWR Morb Mortal Wkly Rep. 2020;69(12):317-323. doi:10.15585/mmwr.mm6912a1
7. Gray SD, Fatovich DM, McCoubrie DL, Daly FF. Amphetamine-related presentations to an inner-city tertiary emergency department: a prospective evaluation. Med J Aust. 2007;186(7):336-339. doi:10.5694/j.1326-5377.2007.tb00932.x
8. Redona PT, Woods C, Jackson D, Usher K. Rates and Patterns of Australian Emergency Department Presentations of People Who Use Stimulants: A Systematic Literature Review. Cureus. 2022;14(10):e30429. doi:10.7759/cureus.30429
9. Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13. doi:10.1016/j.drugalcdep.2015.01.040
10. Gossop MR, Bradley BP, Brewis RK. Amphetamine withdrawal and sleep disturbance. Drug Alcohol Depend. 1982;10(2):177-183. doi:10.1016/0376-8716(82)90010-2
11. Richards JR, Derlet RW. Emergency Department Hallway Care From the Millennium to the Pandemic: A Clear and Present Danger. J Emerg Med. 2022;63(4):565-568. doi:10.1016/j.jemermed.2022.07.011
12. Van Der Linden MC, Van Loon M, Gaakeer MI, Richards JR, Derlet RW, Van Der Linden N. A different crowd, a different crowding level? The predefined thresholds of crowding scales may not be optimal for all emergency departments. Int Emerg Nurs. 2018;41:25-30. doi:10.1016/j.ienj.2018.05.004
13. Romann V, Illgen M, Derungs A, et al. Presentations with reported methamphetamine use to an urban emergency department in Switzerland. Swiss Med Wkly. 2021;151(5152):w30099-w30099. doi:10.4414/SMW.2021.w30099
14. Edmundson J, Skoblenick K, Rosychuk RJ. Flow Through the Emergency Department for Patients Presenting with Substance Use Disorder in Alberta, Canada. West J Emerg Med Integrating Emerg Care Popul Health. 2023;24(4). doi:10.5811/westjem.60350
15. Trabulsy ME. Cocaine washed out syndrome in a patient with acute myocardial infarction. Am J Emerg Med. 1995;13(5):538-539. doi:10.1016/0735-6757(95)90166-3
16. Sporer KA, Lesser SH. Cocaine washed-out syndrome. Ann Emerg Med. 1992;21(1):112. doi:10.1016/S0196-0644(05)82275-9
17. Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009;104(7):1085-1099. doi:10.1111/j.1360-0443.2009.02564.x
18. Baig AM. DARK Side of Amphetamine and Analogues: Pharmacology, Syndromic Manifestation, and Management of Amphetamine Addiction. ACS Chem Neurosci. 2018;9(10):2299-2303. doi:10.1021/acschemneuro.8b00137
19. Regmi S, Kedia SK, Schmidt M, Mahmood A, Lugemwa T, Dillon PJ. Methamphetamine-Induced Wakefulness and Sleep Management: A Qualitative Analysis of Online Narratives. J Psychoactive Drugs. 2024;56(4):595-602. doi:10.1080/02791072.2023.2246458
20. Rechtschaffen A, Maron L. The effect of amphetamine on the sleep cycle. Electroencephalogr Clin Neurophysiol. 1964;16(5):438-445. doi:10.1016/0013-4694(64)90086-0
21. Berro LF, Overton JS, Rowlett JK. Methamphetamine-Induced Sleep Impairments and Subsequent Slow-Wave and Rapid Eye Movement Sleep Rebound in Male Rhesus Monkeys. Front Neurosci. 2022;16. doi:10.3389/fnins.2022.866971
22. Borgatti DA, Rowlett JK, Berro LF. Effects of methamphetamine on actigraphy-based sleep parameters in female rhesus monkeys: Orexin receptor mechanisms. Drug Alcohol Depend. 2024;259:111285. doi:10.1016/j.drugalcdep.2024.111285
23. Samanta S, Bagchi D, Gold M, Badgaiyan R, Barh D, Blum K. A Complex Relationship Among the Circadian Rhythm, Reward Circuit and Substance Use Disorder (SUD). Psychol Res Behav Manag. 2024;Volume 17:3485-3501. doi:10.2147/PRBM.S473310
24. Boutrel B, Koob GF. What Keeps Us Awake: the Neuropharmacology of Stimulants and Wakefulness Promoting Medications. Sleep. 2004;27(6):1181-1194. doi:10.1093/sleep/27.6.1181
25. Krueger JM, Majde JA. Humoral Links between Sleep and the Immune System. Ann N Y Acad Sci. 2003;992(1):9-20. doi:10.1111/j.1749-6632.2003. tb03133.x
26. Vrajová M, Šlamberová R, Hoschl C, Ovsepian SV. Methamphetamine and sleep impairments: neurobehavioral correlates and molecular mechanisms. Sleep. 2021;44(6):zsab001. doi:10.1093/sleep/zsab001
27. Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2017;74(5):511-519. doi:10.1001/jamapsychiatry.2017.0135
28. Bousman CA, Glatt SJ, Everall IP, Tsuang MT. Genetic association studies of methamphetamine use disorders: A systematic review and synthesis. Am J Med Genet B Neuropsychiatr Genet. 2009;150B (8):1025-1049. doi:10.1002/ajmg.b.30936
29. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci Off J Soc Neurosci. 2001;21(5):1787-1794. doi:10.1523/JNEUROSCI.21-05-01787.2001
30. Rothballer AB. The effect of phenylephrine, methamphetamine, cocaine, and serotonin upon the adrenaline-sensitive component of the reticular activating system. Electroencephalogr Clin Neurophysiol. 1957;9(3):409-417. doi:10.1016/0013-4694(57)90030-5
31. Watson R, Hartmann E, Schildkraut JJ. Amphetamine withdrawal: affective state, sleep patterns, and MHPG excretion. Am J Psychiatry. 1972;129(3):263-269. doi:10.1176/ajp.129.3.263
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