Methamphetamine: Difference between revisions

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'''N-Methylamphetamine''' (also known as '''Methamphetamine''',<ref name="erowid">Erowid. (1992). Erowid Methamphetamine (Speed, Crank) Vault. Retrieved from https://erowid.org/chemicals/meth/meth.shtml</ref> '''Meth''',<ref name="erowid" /> '''Glass''',<ref name="erowid" /> '''Ice''',<ref name="erowid" /> '''Shard''',<ref name="erowid" /> '''Crank''',<ref name="erowid" /> '''Tina''',<ref name="erowid" /> '''Tweak''',<ref name="erowid" /> '''Yaba''',<ref name="erowid" /> and '''Crystal'''<ref name="erowid" />) is a ~~widely-used~~ [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class ~~known for~~ its ~~potent and long~~-~~lasting~~ effects.

'''N-Methylamphetamine''' (also known as '''Methamphetamine''',<ref name="erowid">Erowid. (1992). Erowid Methamphetamine (Speed, Crank) Vault. Retrieved from https://erowid.org/chemicals/meth/meth.shtml</ref> '''Meth''',<ref name="erowid" /> '''Glass''',<ref name="erowid" /> '''Ice''',<ref name="erowid" /> '''Shard''',<ref name="erowid" /> '''Crank''',<ref name="erowid" /> '''Tina''',<ref name="erowid" /> '''Tweak''',<ref name="erowid" /> '''Yaba''',<ref name="erowid" /> and '''Crystal'''<ref name="erowid" />) is a potent [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class. Along with [[heroin]] and [[cocaine]], it has a notorious reputation as a dangerous and highly addictive "street drug".{{citation needed}} It is structurally related to [[amphetamine]]; the addition of the methyl group is thought to increase its ability to cross the blood-brain barrier, significantly enhancing its potency.{{citation needed}} It produces its effects by increasing levels of the [[neurotransmitters]] [[serotonin]], [[dopamine]], and [[norepinephrine]] in the brain.

Methamphetamine ~~hydrochloride is approved by~~ the ~~United States Food and Drug Administration (USFDA) under the trade name "Desoxyn"~~.~~<ref>Desoxyn Label (FDA) | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf</ref>~~ However, it ~~is rarely prescribed due to its abuse potential~~, ~~typically being reserved for cases of severe obesity or ADHD~~ in which ~~all other treatment options have been exhausted~~.

Methamphetamine was discovered in Japan in 1893, shortly following the discovery of amphetamine. However, it was not widely used until World War II, in which both Allies and Axis forces utilized its stimulant effects.{{citation needed}} As the addictive properties became known, governments began to place strict controls on methamphetamine manufacture and distribution. Despite these efforts, methamphetamine abuse has become a major public health problem throughout the world.

[[Subjective effects]] include [[motivation enhancement]], [[stamina enhancement]], [[appetite suppression]], [[increased libido]], and [[euphoria]]. ~~At heavier doses, it~~ can induce states of [[anxiety]] & [[paranoia]], [[delusions]], [[thought disorganization]] ~~and~~ [[psychosis]]. It is associated with [[compulsive redosing]], especially when it is [[vaporized]] ("smoked") or [[injected]], due to the ~~initial~~ overwhelming [[euphoric]] rush it produces.

[[Subjective effects]] include [[motivation enhancement]], [[stamina enhancement]], [[appetite suppression]], [[increased libido]], and [[euphoria]]. Chronic high-dose use can induce states of [[anxiety]] & [[paranoia]], [[delusions]], [[thought disorganization]], [[psychosis]], and violent behavior. It is associated with [[compulsive redosing]], especially when it is [[vaporized]] ("smoked") or [[injected]], due to the overwhelming [[euphoric]] rush it produces in the user upon initial administration.

~~Unlike~~ [[amphetamine]] at therapeutic doses, methamphetamine at moderate to heavy [[recreational drug use|recreational doses]] is considered to be directly neurotoxic to humans, damaging both [[dopamine]] and [[serotonin]] [[neurons]] within the central nervous system ~~that are essential in maintaining the proper processing and integration of sensory information, its integration and controlling motor and behavioral output~~.{{citation needed}} ~~Additionally~~, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.{{citation needed}}

Methamphetamine has been shown to have extremely high abuse and addiction potential; it is widely considered to be one of the most addictive substances due to the intense euphoria it produces.{{citation needed}} Additionally, unlike [[amphetamine]] at therapeutic doses, methamphetamine at moderate to heavy [[recreational drug use|recreational doses]] is considered to be directly neurotoxic to humans, damaging both [[dopamine]] and [[serotonin]] [[neurons]] within the central nervous system.{{citation needed}} It also displays cardiotoxicity, including [[increased blood pressure]] and elevated risk of stroke. It is highly advised to use [[responsible drug use|harm reduction practices]] if using this substance.

~~Due to its potent psychostimulant effects, established toxicity profile, and ability to cause mental and physical~~ [[~~dependence~~]] and ~~[[addiction]] when misused, it~~ is highly advised to use [[responsible drug use|harm reduction practices]] if using this substance.

[[File:Crystal Meth.jpg|250px|thumbnail|right|Pure "shards" of Methamphetamine Hydrochloride, commonly known as "crystal meth".]]

==History and culture==

Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.<ref>Lazăr Edeleano: Über einige Derivate der Phenylmethacrylsäure und der Phenylisobuttersäure. In: Berichte der Deutschen chemischen Gesellschaft zu Berlin; 20. Jg. (1887), Band 3, S. 616–622. https://doi.org/10.1002/cber.188702001142</ref> Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.<ref>Grobler, Sias R.; Chikte, Usuf; Westraat, Jaco (2011). "The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town". ISRN Dentistry. 2011: 1–4. PMC 3189445 Freely accessible. PMID 21991491. https://doi.org/10.5402/2011/974768</ref> Neither drug had a pharmacological use until 1934, when Smith, Kline and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant.<ref>Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039. SKF first packaged it as an inhaler so as to exploit the base's volatility and, after sponsoring some trials by East Coast otolaryngological specialists, began to advertise the Benzedrine Inhaler as a decongestant in late 1933.</ref>

Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.<ref>Lazăr Edeleano: Über einige Derivate der Phenylmethacrylsäure und der Phenylisobuttersäure. In: Berichte der Deutschen chemischen Gesellschaft zu Berlin; 20. Jg. (1887), Band 3, S. 616–622. https://doi.org/10.1002/cber.188702001142</ref> Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.<ref>Grobler, Sias R.; Chikte, Usuf; Westraat, Jaco (2011). "The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town". ISRN Dentistry. 2011: 1–4. PMC 3189445 Freely accessible. PMID 21991491. https://doi.org/10.5402/2011/974768</ref> Neither drug had a pharmacological use until 1934, when Smith, Kline, and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant.<ref>Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039. SKF first packaged it as an inhaler so as to exploit the base's volatility and, after sponsoring some trials by East Coast otolaryngological specialists, began to advertise the Benzedrine Inhaler as a decongestant in late 1933.</ref>

During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects.<ref>Rasmussen N (2011). "Medical science and the military: the Allies' use of amphetamine during World War II". J. Interdiscip. Hist. 42 (2): 205–233. PMID 22073434. https://doi.org/10.1162/JINH_a_00212</ref><ref>Defalque RJ, Wright AJ (April 2011). "Methamphetamine for Hitler's Germany: 1937 to 1945". Bull. Anesth. Hist. 29 (2): 21–4, 32. PMID 22849208. https://doi.org/10.1016/s1522-8649(11)50016-2.</ref> Eventually, as the addictive properties of the drugs became known, governments began to place strict controls on the sale of the drugs.<ref>"Historical overview of methamphetamine". Vermont Department of Health. Government of Vermont. Retrieved 29 January 2012.</ref> For example, during the early 1970s in the United States, amphetamine became a schedule II controlled substance under the Controlled Substances Act.<ref>"Controlled Substances Act". United States Food and Drug Administration. 11 June 2009. Retrieved 4 November 2013.</ref>

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Due to the large underground market for these drugs, they are frequently illegally synthesized by clandestine chemists, trafficked, and sold on the black market.<ref>Chawla S, Le Pichon T (2006). "World Drug Report 2006" (PDF). United Nations Office on Drugs and Crime. pp. 128–135. Retrieved 2 November 2013.</ref> Based upon drug and drug precursor seizures, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.{{citation needed}}

Methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name "Desoxyn".<ref>Desoxyn Label (FDA) | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf</ref> However, it is rarely prescribed due to its abuse potential, typically being reserved for cases of severe obesity or ADHD in which all other treatment options have been exhausted.

==Chemistry==

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==Toxicity and harm potential==

===Neurotoxicity===

There is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.{{citation needed}}

Unlike [[amphetamine]], methamphetamine is directly neurotoxic to [[dopamine]] neurons.<ref>Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 978-0-07-148127-4. "Unlike [[cocaine]] and [[amphetamine]], methamphetamine is directly toxic to midbrain dopamine neurons."</ref> Moreover, methamphetamine abuse is associated with an increased risk of Parkinson's disease due to excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity.<ref>A review of the clinical pharmacology of methamphetamine (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19426289</ref><ref>Methamphetamine-induced neurotoxicity: the road to Parkinson’s disease | http://www.if-pan.krakow.pl/pjp/pdf/2009/6_966.pdf</ref><ref>Intraneuronal dopamine-quinone synthesis: a review (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12835101</ref><ref>Dopaminergic neuron-specific oxidative stress caused by dopamine itself (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18596830</ref> Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to [[serotonin]] [[neurons]].<ref>Methamphetamine toxicity and messengers of death (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19328213</ref> It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.<ref>Relationship between temperature, dopaminergic neurotoxicity, and plasma drug concentrations in methamphetamine-treated squirrel monkeys (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16293712</ref> As a result of methamphetamine-induced neurotoxicity to dopamine neurons, chronic use may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year.<ref>A review of the clinical pharmacology of methamphetamine (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19426289</ref>

@@ Line 2: / Line 2: @@
 {{SubstanceBox/Methamphetamine}}
-'''N-Methylamphetamine''' (also known as '''Methamphetamine''',<ref name="erowid">Erowid. (1992). Erowid Methamphetamine (Speed, Crank) Vault. Retrieved from https://erowid.org/chemicals/meth/meth.shtml</ref> '''Meth''',<ref name="erowid" /> '''Glass''',<ref name="erowid" /> '''Ice''',<ref name="erowid" /> '''Shard''',<ref name="erowid" /> '''Crank''',<ref name="erowid" /> '''Tina''',<ref name="erowid" /> '''Tweak''',<ref name="erowid" /> '''Yaba''',<ref name="erowid" /> and '''Crystal'''<ref name="erowid" />) is a widely-used [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class known for its potent and long-lasting effects.
+'''N-Methylamphetamine''' (also known as '''Methamphetamine''',<ref name="erowid">Erowid. (1992). Erowid Methamphetamine (Speed, Crank) Vault. Retrieved from https://erowid.org/chemicals/meth/meth.shtml</ref> '''Meth''',<ref name="erowid" /> '''Glass''',<ref name="erowid" /> '''Ice''',<ref name="erowid" /> '''Shard''',<ref name="erowid" /> '''Crank''',<ref name="erowid" /> '''Tina''',<ref name="erowid" /> '''Tweak''',<ref name="erowid" /> '''Yaba''',<ref name="erowid" /> and '''Crystal'''<ref name="erowid" />) is a potent [[psychoactive class::stimulant]] substance of the [[chemical class::amphetamine]] class. Along with [[heroin]] and [[cocaine]], it has a notorious reputation as a dangerous and highly addictive "street drug".{{citation needed}} It is structurally related to [[amphetamine]]; the addition of the methyl group is thought to increase its ability to cross the blood-brain barrier, significantly enhancing its potency.{{citation needed}} It produces its effects by increasing levels of the [[neurotransmitters]] [[serotonin]], [[dopamine]], and [[norepinephrine]] in the brain.
-Methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name "Desoxyn".<ref>Desoxyn Label (FDA) | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf</ref> However, it is rarely prescribed due to its abuse potential, typically being reserved for cases of severe obesity or ADHD in which all other treatment options have been exhausted.
+Methamphetamine was discovered in Japan in 1893, shortly following the discovery of amphetamine. However, it was not widely used until World War II, in which both Allies and Axis forces utilized its stimulant effects.{{citation needed}} As the addictive properties became known, governments began to place strict controls on methamphetamine manufacture and distribution. Despite these efforts, methamphetamine abuse has become a major public health problem throughout the world.
-[[Subjective effects]] include [[motivation enhancement]], [[stamina enhancement]], [[appetite suppression]], [[increased libido]], and [[euphoria]]. At heavier doses, it can induce states of [[anxiety]] & [[paranoia]], [[delusions]], [[thought disorganization]] and [[psychosis]]. It is associated with [[compulsive redosing]], especially when it is [[vaporized]] ("smoked") or [[injected]], due to the initial overwhelming [[euphoric]] rush it produces.
+[[Subjective effects]] include [[motivation enhancement]], [[stamina enhancement]], [[appetite suppression]], [[increased libido]], and [[euphoria]]. Chronic high-dose use can induce states of [[anxiety]] & [[paranoia]], [[delusions]], [[thought disorganization]], [[psychosis]], and violent behavior. It is associated with [[compulsive redosing]], especially when it is [[vaporized]] ("smoked") or [[injected]], due to the overwhelming [[euphoric]] rush it produces in the user upon initial administration.
-Unlike [[amphetamine]] at therapeutic doses, methamphetamine at moderate to heavy [[recreational drug use|recreational doses]] is considered to be directly neurotoxic to humans, damaging both [[dopamine]] and [[serotonin]] [[neurons]] within the central nervous system that are essential in maintaining the proper processing and integration of sensory information, its integration and controlling motor and behavioral output.{{citation needed}} Additionally, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.{{citation needed}}
+Methamphetamine has been shown to have extremely high abuse and addiction potential; it is widely considered to be one of the most addictive substances due to the intense euphoria it produces.{{citation needed}} Additionally, unlike [[amphetamine]] at therapeutic doses, methamphetamine at moderate to heavy [[recreational drug use|recreational doses]] is considered to be directly neurotoxic to humans, damaging both [[dopamine]] and [[serotonin]] [[neurons]] within the central nervous system.{{citation needed}} It also displays cardiotoxicity, including [[increased blood pressure]] and elevated risk of stroke. It is highly advised to use [[responsible drug use|harm reduction practices]] if using this substance.
-Due to its potent psychostimulant effects, established toxicity profile, and ability to cause mental and physical [[dependence]] and [[addiction]] when misused, it is highly advised to use [[responsible drug use|harm reduction practices]] if using this substance.
 [[File:Crystal Meth.jpg|250px|thumbnail|right|Pure "shards" of Methamphetamine Hydrochloride, commonly known as "crystal meth".]]
 ==History and culture==
-Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.<ref>Lazăr Edeleano: Über einige Derivate der Phenylmethacrylsäure und der Phenylisobuttersäure. In: Berichte der Deutschen chemischen Gesellschaft zu Berlin; 20. Jg. (1887), Band 3, S. 616–622. https://doi.org/10.1002/cber.188702001142</ref> Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.<ref>Grobler, Sias R.; Chikte, Usuf; Westraat, Jaco (2011). "The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town". ISRN Dentistry. 2011: 1–4. PMC 3189445 Freely accessible. PMID 21991491. https://doi.org/10.5402/2011/974768</ref> Neither drug had a pharmacological use until 1934, when Smith, Kline and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant.<ref>Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039. SKF first packaged it as an inhaler so as to exploit the base's volatility and, after sponsoring some trials by East Coast otolaryngological specialists, began to advertise the Benzedrine Inhaler as a decongestant in late 1933.</ref>
+Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.<ref>Lazăr Edeleano: Über einige Derivate der Phenylmethacrylsäure und der Phenylisobuttersäure. In: Berichte der Deutschen chemischen Gesellschaft zu Berlin; 20. Jg. (1887), Band 3, S. 616–622. https://doi.org/10.1002/cber.188702001142</ref> Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.<ref>Grobler, Sias R.; Chikte, Usuf; Westraat, Jaco (2011). "The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town". ISRN Dentistry. 2011: 1–4. PMC 3189445 Freely accessible. PMID 21991491. https://doi.org/10.5402/2011/974768</ref> Neither drug had a pharmacological use until 1934, when Smith, Kline, and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant.<ref>Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039. SKF first packaged it as an inhaler so as to exploit the base's volatility and, after sponsoring some trials by East Coast otolaryngological specialists, began to advertise the Benzedrine Inhaler as a decongestant in late 1933.</ref>
 During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects.<ref>Rasmussen N (2011). "Medical science and the military: the Allies' use of amphetamine during World War II". J. Interdiscip. Hist. 42 (2): 205–233. PMID 22073434. https://doi.org/10.1162/JINH_a_00212</ref><ref>Defalque RJ, Wright AJ (April 2011). "Methamphetamine for Hitler's Germany: 1937 to 1945". Bull. Anesth. Hist. 29 (2): 21–4, 32. PMID 22849208. https://doi.org/10.1016/s1522-8649(11)50016-2.</ref> Eventually, as the addictive properties of the drugs became known, governments began to place strict controls on the sale of the drugs.<ref>"Historical overview of methamphetamine". Vermont Department of Health. Government of Vermont. Retrieved 29 January 2012.</ref> For example, during the early 1970s in the United States, amphetamine became a schedule II controlled substance under the Controlled Substances Act.<ref>"Controlled Substances Act". United States Food and Drug Administration. 11 June 2009. Retrieved 4 November 2013.</ref>
@@ Line 22: / Line 20: @@
 Due to the large underground market for these drugs, they are frequently illegally synthesized by clandestine chemists, trafficked, and sold on the black market.<ref>Chawla S, Le Pichon T (2006). "World Drug Report 2006" (PDF). United Nations Office on Drugs and Crime. pp. 128–135. Retrieved 2 November 2013.</ref> Based upon drug and drug precursor seizures, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.{{citation needed}}
+Methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name "Desoxyn".<ref>Desoxyn Label (FDA) | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/005378s028lbl.pdf</ref> However, it is rarely prescribed due to its abuse potential, typically being reserved for cases of severe obesity or ADHD in which all other treatment options have been exhausted.
 ==Chemistry==
@@ Line 132: / Line 132: @@
 ==Toxicity and harm potential==
 ===Neurotoxicity===
+There is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.{{citation needed}}
 Unlike [[amphetamine]], methamphetamine is directly neurotoxic to [[dopamine]] neurons.<ref>Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 978-0-07-148127-4. "Unlike [[cocaine]] and [[amphetamine]], methamphetamine is directly toxic to midbrain dopamine neurons."</ref> Moreover, methamphetamine abuse is associated with an increased risk of Parkinson's disease due to excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity.<ref>A review of the clinical pharmacology of methamphetamine (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19426289</ref><ref>Methamphetamine-induced neurotoxicity: the road to Parkinson’s disease | http://www.if-pan.krakow.pl/pjp/pdf/2009/6_966.pdf</ref><ref>Intraneuronal dopamine-quinone synthesis: a review (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12835101</ref><ref>Dopaminergic neuron-specific oxidative stress caused by dopamine itself (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18596830</ref> Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to [[serotonin]] [[neurons]].<ref>Methamphetamine toxicity and messengers of death (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19328213</ref> It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.<ref>Relationship between temperature, dopaminergic neurotoxicity, and plasma drug concentrations in methamphetamine-treated squirrel monkeys (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16293712</ref> As a result of methamphetamine-induced neurotoxicity to dopamine neurons, chronic use may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year.<ref>A review of the clinical pharmacology of methamphetamine (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19426289</ref>