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Methamphetamine

PubChem CID
10836
Structure
Methamphetamine_small.png
Methamphetamine_3D_Structure.png
Molecular Formula
Synonyms
  • METHAMPHETAMINE
  • Metamfetamine
  • d-Deoxyephedrine
  • d-Desoxyephedrine
  • d-Methamphetamine
Molecular Weight
149.23 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Methamphetamine is a member of the class of amphetamines in which the amino group of (S)-amphetamine carries a methyl substituent. It has a role as a neurotoxin, a psychotropic drug, a central nervous system stimulant, a xenobiotic and an environmental contaminant. It is a member of amphetamines and a secondary amine. It is functionally related to a (S)-amphetamine. It is a conjugate base of a methamphetamine(1+).
Metamfetamine (methamphetamine) is a psychostimulant and sympathomimetic drug, and a member of the amphetamine group of sympathomimetic amines. Methamphetamine can induce effects such as euphoria, increased alertness and energy, and enhanced self-esteem. It is a scheduled drug in most countries due to its high potential for addiction and abuse. The FDA withdrew its approval for the use of all parenteral drug products containing methamphetamine hydrochloride, a metamfetamine salt.
Methamphetamine is an Amphetamine Anorectic and Central Nervous System Stimulant. The physiologic effect of methamphetamine is by means of Appetite Suppression and Central Nervous System Stimulation and Increased Sympathetic Activity.
See also: Methamphetamine Hydrochloride (has salt form); Methamphetamine saccharate (is active moiety of).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Methamphetamine.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2S)-N-methyl-1-phenylpropan-2-amine
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

MYWUZJCMWCOHBA-VIFPVBQESA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@@H](CC1=CC=CC=C1)NC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C10H15N
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 Deprecated CAS

139-47-9, 14611-50-8, 1690-86-4, 45952-89-4
14611-50-8, 1690-86-4, 45952-89-4

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Deoxyephedrine
  • Desoxyephedrine
  • Desoxyn
  • Hydrochloride, Methamphetamine
  • Madrine
  • Metamfetamine
  • Methamphetamine
  • Methamphetamine Hydrochloride
  • Methylamphetamine
  • N Methylamphetamine
  • N-Methylamphetamine

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
149.23 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
2.1
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
149.120449483 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
149.120449483 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
12 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
11
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
95
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

Clear, colorless liquid
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 365
White crystalline powder
NIH; National Institute on Drug Abuse. Drug Facts. Methamphetamine. Rev Jan 2014. Washington, DC: Natl Inst Health. Available from, as of Oct 23, 2015: https://www.drugabuse.gov/publications/drugfacts/methamphetamine

3.2.3 Odor

Characteristic odor resembling geranium leaves
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 365
Odorless
NIH; National Institute on Drug Abuse. Drug Facts. Methamphetamine. Rev Jan 2014. Washington, DC: Natl Inst Health. Available from, as of Oct 23, 2015: https://www.drugabuse.gov/publications/drugfacts/methamphetamine

3.2.4 Taste

Bitter-tasting
NIH; National Institute on Drug Abuse. Drug Facts. Methamphetamine. Rev Jan 2014. Washington, DC: Natl Inst Health. Available from, as of Oct 23, 2015: https://www.drugabuse.gov/publications/drugfacts/methamphetamine

3.2.5 Boiling Point

212 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-344

3.2.6 Melting Point

170-2 °C
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 3: 185 (1978)

3.2.7 Flash Point

9.7 °C (49.5 °F) - closed cup
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

3.2.8 Solubility

In water, 0.5 g/mL
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 3: 185 (1978)
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 72
Miscible with chloroform
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 365
9.28e-01 g/L

3.2.9 LogP

2.07
HANSCH,C ET AL. (1995)
log Kow = 2.07
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 78
2.07
HANSCH,C ET AL. (1995)

3.2.10 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

3.2.11 Decomposition

When heated to decomposition it emits toxic vapors of Nitric oxides.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2926

3.2.12 pH

A saturated soln in water is alkaline to litmus
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 365

3.2.13 Dissociation Constants

Basic pKa
9.99
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
pKa
9.87 (at 25 °C)
PERRIN,DD (1965)
pKa = 9.87 (conjugate acid)
Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)

3.2.14 Collision Cross Section

133.5 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

3.2.15 Kovats Retention Index

Standard non-polar
1161
Semi-standard non-polar
1187 , 1188 , 1163.9
Standard polar
1562

3.2.16 Other Experimental Properties

Odorless; specific optical rotation: +16 to +19 deg /Methamphetamine hydrochloride/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 823
The drug occurs as white crystals or as a white, crystalline powder and is freely soluble in water (1:2) and in alcohol (1:3). /Methamphetamine hydrochloride/
American Hospital Formulary Service - Drug Information 89. Bethesda, MD: American Society of Hospital Pharmacists, 1989 (Plus Supplements)., p. 1172
Crystals. MP: 170-175 °C. Bitter taste. Specific optical rotation: +14 to +20 deg. Soluble in water, alcohol, chloroform. Practically insoluble in ether. A 1% aqueous solution is neutral or slightly acid to litmus. /Methamphetamine hydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1104
Methamphetamine /is/ the dextrorotatory isomer of phenylisopropylmethylamine.
American Hospital Formulary Service - Drug Information 89. Bethesda, MD: American Society of Hospital Pharmacists, 1989 (Plus Supplements)., p. 1172
Wt/mL: 0.921 to 0.922 g
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 365

3.3 SpringerMaterials Properties

3.4 Chemical Classes

3.4.1 Drugs

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds
S58 | PSYCHOCANNAB | Synthetic Cannabinoids and Psychoactive Compounds | DOI:10.5281/zenodo.3247723
Pharmaceuticals -> Illicit drugs
S56 | UOATARGPHARMA | Target Pharmaceutical/Drug List from University of Athens | DOI:10.5281/zenodo.3248837
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Street Drugs; Sympathomimetics; Dopamine Agents; Central Nervous System Stimulants; Adrenergic Agents; Wakefulness-Promoting Agents
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 2
Source of Spectrum
RCM-25-388-Methamphetamine
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
CAY-2023-1178-0
Catalog Number
<a href=https://www.caymanchem.com/product/13997>13997</a>
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

91.0543 100

150.1277 19.89

119.0855 16.04

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2 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

150.1279 100

91.0543 71.95

119.0855 28.24

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4.1.3 LC-MS

1 of 23
View All
Authors
Stravs M, Schymanski E, Singer H, Department of Environmental Chemistry, Eawag
Instrument
LTQ Orbitrap XL Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
35 % (nominal)
Fragmentation Mode
CID
Column Name
XBridge C18 3.5um, 2.1x50mm, Waters
Retention Time
3.7 min
Precursor m/z
150.1277
Precursor Adduct
[M+H]+
Top 5 Peaks

119.0857 999

150.1279 929

91.0543 478

104.0621 2

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License
CC BY
2 of 23
View All
Authors
Stravs M, Schymanski E, Singer H, Department of Environmental Chemistry, Eawag
Instrument
LTQ Orbitrap XL Thermo Scientific
Instrument Type
LC-ESI-ITFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
15 % (nominal)
Fragmentation Mode
HCD
Column Name
XBridge C18 3.5um, 2.1x50mm, Waters
Retention Time
3.7 min
Precursor m/z
150.1277
Precursor Adduct
[M+H]+
Top 5 Peaks

150.1278 999

119.0856 138

91.0542 83

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License
CC BY

4.1.4 Other MS

Other MS
MASS: 446 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63) /Methamphetamine hydrochloride/
Other MS
MASS: 21422 (NIST/EPA/MSDC Mass Spectral Database, 1990 version)

4.2 IR Spectra

4.2.1 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Film (MeCl2) (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
Free base of 01001
Lot Number
Free base of KS006
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3 Other Spectra

Intense mass spectral peaks: 58 m/z, 91 m/z, 134 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 172

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Street Drugs; Sympathomimetics; Dopamine Agents; Central Nervous System Stimulants; Adrenergic Agents; Wakefulness-Promoting Agents

7.3 Clinical Trials

7.3.1 ClinicalTrials.gov

7.3.2 NIPH Clinical Trials Search of Japan

7.4 DEA Drug and Chemical Information

Methamphetamine

(Trade Name:Desoxyn®; Street Names:Meth, Speed, Crystal, Glass, Ice, Crank, Yaba)

7.4.1 DEA Drug Facts

What is Methamphetamine?
Stimulant that speeds up body’s system that comes as pill or powder. Available in prescription as Desoxyn® to treat obesity and ADHD. Crystal meth resembles glass fragments and is an illegally altered version of the prescription drug that is cooked with over-the-counter drugs in meth labs.
Street Title
Batu, Bikers Coffee, Black Beauties, Chalk, Chicken Feed, Crank, Crystal, Glass, Go-Fast, Hiropon, Ice, Meth, Methlies Quick, Poor Man's Cocaine, Shabu, Shards, Speed, Stove Top, Tina, Trash, Tweak, Uppers, Ventana, Vidrio, Yaba, Yellow Barn
How is it used?
Powder, pill, smoked, snorted, injected to intensify the effects, users may take higher doses of the drug, take it more frequently, or change their method of intake
How does it affect the body?
Highly addictive, Agitation, increased heart rate and blood pressure, increased respiration and body temperature, Anxiety, paranoia, High doses can cause convulsions, cardiovascular collapse, stroke or death
What are its overdose effects?
High doses may result in death from stroke, heart attack, or multiple organ problems caused by overheating.
Fact sheet

7.5 Therapeutic Uses

Adrenergic Agents; Adrenergic Uptake Inhibitors; Appetite Depressants; Central Nervous System Stimulants; Dopamine Agents; Dopamine Uptake Inhibitors; Sympathomimetics
National Library of Medicine's Medical Subject Headings. Methamphetamine. Online file (MeSH, 2015). Available from, as of November 23, 2015: https://www.nlm.nih.gov/mesh/MBrowser.html
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Methamphetamine is included in the database.
NIH/NLM; ClinicalTrials.Gov. Available from, as of September 30, 2015: https://clinicaltrials.gov/search/intervention=Methamphetamine
Methamphetamine also is used as an adjunct to psychological, educational, social, and other remedial measures in the treatment of attention deficit hyperactivity disorder (ADHD).
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2537
Methamphetamine has been used as an adjunct to caloric restriction in the short-term (i.e., a few weeks) treatment of exogenous obesity. However, short-term or intermittent therapy with methamphetamine is unlikely to maintain a long-term benefit, and prolonged administration of methamphetamine for the treatment of obesity is not indicated.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2537
Vet: to stimulate central & sympathetic nervous systems to overcome depression, incr blood pressure by vasoconstriction, & as antidote to barbiturate overdosage. Resp stimulant. Reliability as post-anesthetic analeptic has been questioned. ... Orally, as anorexiant & as mood elevator in dogs. /Methamphetamine hydrochloride/
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 156

7.6 Drug Warnings

BOXED WARNING: Methamphetamine has a high potential for abuse. It should thus be tried only in weight reduction programs for patients in whom alternative therapy has been ineffective. Administration of methamphetamine for prolonged periods of time in obesity may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining methamphetamine for non-therapeutic use or distribution to others, and the drug should be prescribed or dispensed sparingly. Misuse of methamphetamine may cause sudden death and serious cardiovascular adverse events.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
Adults: Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
Tolerance to the anorectic effect usually develops within a few weeks. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
For more Drug Warnings (Complete) data for d-METHAMPHETAMINE (16 total), please visit the HSDB record page.

7.7 Reported Fatal Dose

The minimal lethal amphetamine dose varies with age & animal species. Children appear more susceptible than adults. ... In human, death has been reported with as little as 1.5 mg/kg methamphetamine, whereas survival occurred after an ingestion of 28 mg/kg amphetamine.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 343
Toxic methamphetamine blood concentration: 60-500 ug/dL; Lethal methamphetamine blood concentration: 1-4 mg/dL /From table/
Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 421

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.

8.2 MeSH Pharmacological Classification

Adrenergic Uptake Inhibitors
Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. (See all compounds classified as Adrenergic Uptake Inhibitors.)
Dopamine Agents
Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. (See all compounds classified as Dopamine Agents.)
Central Nervous System Stimulants
A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. (See all compounds classified as Central Nervous System Stimulants.)
Adrenergic Agents
Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. (See all compounds classified as Adrenergic Agents.)
Dopamine Uptake Inhibitors
Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake. (See all compounds classified as Dopamine Uptake Inhibitors.)
Sympathomimetics
Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. (See all compounds classified as Sympathomimetics.)

8.3 FDA Pharmacological Classification

FDA UNII
44RAL3456C
Active Moiety
METHAMPHETAMINE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Amphetamine Anorectic
Pharmacological Classes
Chemical Structure [CS] - Amphetamines
Pharmacological Classes
Physiologic Effects [PE] - Appetite Suppression
Pharmacological Classes
Established Pharmacologic Class [EPC] - Central Nervous System Stimulant
Pharmacological Classes
Physiologic Effects [PE] - Central Nervous System Stimulation
Pharmacological Classes
Physiologic Effects [PE] - Increased Sympathetic Activity
FDA Pharmacology Summary
Methamphetamine is an Amphetamine Anorectic and Central Nervous System Stimulant. The physiologic effect of methamphetamine is by means of Appetite Suppression and Central Nervous System Stimulation and Increased Sympathetic Activity.

8.4 ATC Code

N - Nervous system

N06 - Psychoanaleptics

N06B - Psychostimulants, agents used for adhd and nootropics

N06BA - Centrally acting sympathomimetics

N06BA03 - Metamfetamine

8.5 Absorption, Distribution and Excretion

Absorption
Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Moreover, when administered intranasally or as an inhalation, methamphetamine also demonstrates a high degree of absorption. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.
Route of Elimination
Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine.
Methamphetamine is readily absorbed from the GI tract and effects persist for 6-12 hours but may continue up to 24 hr after large doses. /Methamphetamine hydrochloride/
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2537
Single pharmacological doses of amphetamines (ie, 10-25 mg) given to human volunteers produce peak plasma levels within 1-2 hr & are rapidly absorbed from the GI tract. Amphetamine absorption usually is complete by 4-6 hr. The illicit use of amphetamines ... by insertion into the vagina (termed "balling") before intercourse suggests that these compounds are also absorbed through mucosal surfaces. ... Methamphetamine ... /has/ absorption characteristics similar to those of amphetamines. ... Sustained release prepn are avail as resin-bound rather than soluble salts. These compounds display reduced peak blood levels compared with std amphetamine prepn, but total bioavailability & time to peak levels remain similar. Pharmacokinetics in overdose are not well described.
Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 631
Methamphetamine is eliminated principally in urine. Urinary excretion of the drug is pH dependent, and excretion is enhanced in acidic urine. Following oral administration of methamphetamine hydrochloride, approximately 62% of the administered dose is excreted in urine within the first 24 hours, with metabolites and unchanged drug accounting for about two-thirds and one-third, respectively, of the recovered drug.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538
Methamphetamine hydrochloride has been measured in human sweat at a median range of 63.0 (low dose 16.8-175) and 307 (high dose 199-607) ng per patch(1). /Methamphetamine hydrochloride/
(1) Daughton CG, Ruhoy IS; Environ Toxicol Chem 28(12): 2495-521 (2009)
/MILK/ Amphetamines are distributed into milk. Therefore, nursing should be avoided during therapy with amphetamines.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538

8.6 Metabolism / Metabolites

Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine.
Methamphetamine is metabolized in the liver by aromatic hydroxylation, N-dealkylation, and deamination; at least 7 metabolites have been identified in urine.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2537
A species difference was found in a study of the metabolism of methamphetamine, (+/-)-2-methylamino-1-phenylpropane. In man, 22% of an oral dose was excreted into urine unchanged, & 15% of the dose was excreted as 4-hydroxymethamphetamine. After ip admin to rat, 4-hydroxymethamphetamine was principal urinary metabolite (31% of dose), together with 4-hydroxynorephedrine (16%) & unchanged drug (11% of dose). In the guinea pig an ip dose was extensively metabolized to benzoic acid & its glycine & glucuronic acid conjugates.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 557
In vivo metab of N-alkylated amphetamines in rat produced 4-hydroxy- & 4-hydroxy-3-methoxy-metabolites. Relative quantities of phenolic metabolites formed were dependent upon the length of the N-alkyl substituent.
COUTTS RT ET AL; RES COMMUN CHEM PATHOL PHARMACOL 22 (3): 589-92 (1978)
Metamphetamine has known human metabolites that include 4-Hydroxymethamphetamine and Amphetamine.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. Route of Elimination: Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine. Half Life: The biological half-life has been reported in the range of 4 to 5 hours.

8.7 Biological Half-Life

The biological half-life has been reported in the range of 4 to 5 hours.
The biologic half-life of methamphetamine reportedly is 4-5 hours.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538

8.8 Mechanism of Action

Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.
Appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especialy norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. The toxic effects of methamphetamine on dopamine and serotonergic neurons have recently been linked to the endogenous formation of c-hydroxy dopamine and 5, 7 dihydrotryptamine, respectively. The ability of methamphetamine to both release dopamine and serotonin as well as to inhibit monoamine oxidase activity leads to the non-enzymatic oxidation of dopamine and serotonin. Methamphetamine induced neuronal damage is mediated by the production of free radicals. This drug causes a long lasting depletion of dopamine and serotonin in the striatum and that pre-treatment alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicate that oxygen free radicals have a role in methamphetamine induced neurotoxicity.
International Programme on Chemical Safety; Poisons Information Monograph: Methamphetamine (PIM 334) (1998) Available from, as of December 6, 2005: https://www.inchem.org/pages/pims.html

8.9 Human Metabolite Information

8.9.1 Tissue Locations

  • Kidney
  • Liver

8.9.2 Cellular Locations

  • Cytoplasm
  • Membrane

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
MEDICATION (VET)
MEDICATION
Methamphetamine, its salts, isomers, and salts of its isomers (DEA Code Number: 1105) are Schedule II controlled substances. /Methamphetamine, its salts, isomers, and salts of its isomers/
21 CFR 1308.12(d) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 7, 2015: https://www.ecfr.gov
Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.
US Department of Justice/Office of Diversion Control; Schedule of Controlled Substances. Available from, as of October 7, 2015: https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm
Adrenergic Agents; Adrenergic Uptake Inhibitors; Appetite Depressants; Central Nervous System Stimulants; Dopamine Agents; Dopamine Uptake Inhibitors; Sympathomimetics
National Library of Medicine's Medical Subject Headings. Methamphetamine. Online file (MeSH, 2015). Available from, as of November 23, 2015: https://www.nlm.nih.gov/mesh/MBrowser.html
For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Methods of Manufacturing

Can be prepared by reducing ephedrine or pseudoephedrine; ... Prepared by reducing the condensation product of benzyl methyl ketone and methylamine.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1104
Prepared from phenylacetone and methylamine or from (-)-ephedrine.
Houlihan WJ; Anti-Obesity Drugs. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2015). NY, NY: John Wiley & Sons. Online Posting Date: June 15, 2000

9.3 Impurities

Analysis of illicit preparations of methamphetamine ... revealed presence of significant quantities of zinc and minor amount of titantium.
Lomonte JN et al; J Forensic Sci 21 (3): 575-82 (1976)

9.4 Formulations / Preparations

Oral: tablets 5 mg, Desoxyn, C-II (Ovation)
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538
Ice is a very pure form of methamphetamine hydrochloride (98-100%) ... /"Ice"/
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 344
Common street names: Batu, Bikers Coffee, Black Beauties, Chalk, Chicken Feed, Crank, Crystal, Glass, Go-Fast, Hiropon, Ice, Meth, Methlies Quick, Poor Man's Cocaine, Shabu, Shards, Speed, Stove Top, Tina, Trash, Tweak, Uppers, Ventana, Vidrio, Yaba, and Yellow Bam.
USDOJ/DEA; Drugs of Abuse - A DEA Resource Guide p.50 (2015 edition). Available from, as of April 20, 2016: https://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=41

9.5 General Manufacturing Information

Methamphetamine (meth), a highly addictive drug, can be illegally manufactured using easily acquired chemicals; meth production can cause fires, explosions, injuries, and environmental contamination. To analyze injury incidence and trends, data on 1,325 meth-related chemical incidents reported to the Agency for Toxic Substances and Disease Registry's (ATSDR) Hazardous Substances Emergency Events Surveillance (HSEES) system and National Toxic Substance Incidents Program (NTSIP) by the five participating states (Louisiana, Oregon, Utah, New York, and Wisconsin) with complete information during 2001-2012 were examined. The findings suggested that meth-related chemical incidents increased with the drug's popularity (2001-2004), declined with legislation limiting access to precursor chemicals (2005-2007), and increased again as drug makers circumvented precursor restrictions (2008-2012). Seven percent of meth-related chemical incidents resulted in injuries to 162 persons, mostly members of the general public (97 persons, including 26 children) and law enforcement officials (42). Recent trends suggest a need for efforts to protect the general public, particularly children and law enforcement officials. Because individual state legislative actions can result in increased illegal meth production in neighboring states, a regional approach to prevention is recommended.
Melnikova N et al; MMWR Morb Mortal Wkly Rep 64 (33): 909-12 (2015)
Illicit methamphetamine may be synthesized by a method that involves the reaction of lead acetate and phenylacetic acid to form phenyl-2-propanone, a precursor methamphetamine in the amalgam process.
Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 348

10 Identification

10.1 Analytic Laboratory Methods

There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. METHOD: The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. RESULTS: Rapid (~10min), sensitive detection (~ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. CONCLUSIONS: This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace.
Christodoulides N et al; Drug Alcohol Depend 153: 306-13 (2015)
The concentrations of 17 drugs of abuse, including cocaine, several amphetamines, opioid drugs, and 2 metabolites-benzoylecgonine, a metabolite of cocaine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine, a metabolite of methadone-were investigated in an urban watershed that is heavily impacted by discharges of municipal wastewater. The artificial sweetener sucralose was also monitored as a persistent tracer of contamination from municipal wastewater. Monitoring was conducted in a municipal wastewater treatment plant (WWTP) and at sites upstream and downstream of the WWTP discharge, as well as in a drinking water treatment plant (DWTP) located 19 km downstream of the WWTP discharge that withdraws raw water from the river. Drug concentrations were monitored with polar organic chemical integrative samplers deployed for 2 wk in the river and in the WWTP and DWTP. Several of the investigated compounds exhibited a decrease in concentration with distance downstream from the wastewater discharge into the river, but there was little attenuation of sucralose, cocaine, benzoylecgonine, morphine, acetylmorphine, acetylcodeine, and oxycodone. Heroin and methadone were not detected at any sample locations. Amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine were not detected in the samples collected at the drinking water intake. Many of the drugs of abuse were not removed effectively in the DWTP, including cocaine, benzoylecgonine, methylenedioxyamphetamine, ephedrine, and several prescription opioids, most probably because the DWTP was operating at or above its rated treatment capacity. These data indicate that there can be transport of drugs of abuse from wastewater sources into drinking water in urban watersheds.
Rodayan A et al; Environ Toxicol Chem. 2015 Jul 18. doi: 10.1002/etc.3085. (Epub ahead of print)
BACKGROUND: Wastewater analysis is a new approach developed to estimate drug (of abuse) consumption in large communities, such as cities or even whole countries. AIMS: This paper presents data on the loads of amphetamine and methamphetamine measured in ten wastewater treatment plants in different parts of a German federal state. It provides an estimation of the intensity of the consumption and a comparison to other regions in Germany and Europe. METHODS: Consumption of amphetamine and methamphetamine was estimated by analysis of drug residues in composite 24 hr samples of wastewater after mechanical treatment over one week by liquid chromatography-high resolution tandem mass spectrometry. Samples were collected from the inlet of ten wastewater treatment plants (WWTP) in the federal state of Saarland, representing bigger cities (>200,000 inhabitants), medium sized cities (>50,000 inhabitants), small cities (>25,000 inhabitants), and villages (<25,000 inhabitants). In each WWTP, samples were taken daily for seven consecutive days in July 2014. RESULTS: We observed differences of amphetamine versus methamphetamine loads (expressed as mg/day/1000 inhabitants): Amphetamine loads were much higher in all tested WWTPs indicating a low prevalence of methamphetamine abuse in the federal state of Saarland at the tested period. These findings are in line with previous reports about the distribution of amphetamine and methamphetamine in Germany and Europe. CONCLUSIONS: The approach confirms that wastewater analysis can provide valuable data about the abuse pattern of drugs of abuse in cities and larger areas. It can be useful for planning interventions aimed at specific areas and substances.
Meyer MR et al; Drug Alcohol Depend 156: 311-4 (2015)
A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games.
Gul W et al; J Anal Toxicol. 2015 Nov 4. pii: bkv124. (Epub ahead of print)
For more Analytic Laboratory Methods (Complete) data for d-METHAMPHETAMINE (10 total), please visit the HSDB record page.

10.2 Clinical Laboratory Methods

To assess whether analysis of oral fluid can be used to identify individual drivers with drug concentrations in blood above 25ng/mL for amphetamine and methamphetamine, 10ng/mL for cocaine and 1.0ng/mL for tetrahydrocannabinol (THC), which are the cut-off concentrations used in the European DRUID Project, by calculating the diagnostic accuracies when using the analytical cut-off concentrations in oral fluid as well as for the optimal cut-off concentrations. METHODS: Paired samples of whole blood and oral fluid collected with the Statsure SalivaSampler were obtained from 4080 drivers in four European countries and analysed for amphetamine, methamphetamine, cocaine and THC using GC-MS or LC-MS. The vast majority (89%) were random drivers not suspected of drug-impaired driving. Receiver-Operating Characteristic analysis was used to evaluate the analytical results. RESULTS: The prevalence of drug findings above the cut-off concentrations in blood was 1.3% for amphetamine, 1.0% for methamphetamine, 0.6% for cocaine and 1.3% for THC. The cut-off concentrations in oral fluid that gave the highest diagnostic accuracy were for amphetamine 130ng/mL (accuracy 99.8%), methamphetamine 280ng/mL (accuracy 99.9%), cocaine 570ng/mL (accuracy 99.6%), and THC 38ng/mL (accuracy 98.3%). The proportion of false positives were 0.2%, 0.1%, 0.1% and 0.9%; and the proportion of false negatives were 0.1%, 0.0%, 0.3% and 0.8%, respectively, when using those cut-offs. The positive predictive values were 87.9%, 92.9%, 84.6% and 35.7% for amphetamine, methamphetamine, cocaine and THC, respectively. CONCLUSIONS: Analysis of concentrations of illicit drugs in oral fluid could not be used to accurately identify drivers with drugs concentrations above the selected cut-offs in blood in a cohort of drivers with low prevalence of drugs.
Gjerde H et al; Forensic Sci Int 256: 42-5 (2015)
A rapid & simple hemaglutination inhibition test is described for the mass screening of urine samples containing methamphetamine. The antiserum prepared was specific for methamphetaine.
NIWAGUCHI T ET AL; J FORENSIC SCI 24 (2): 319-22 (1979)
The reverse phase high performance liquid chromatographic was used in the forensic identification of methamphetamine in urine & feces. Calibration curves revealed a linear relation over 0.05 to 1.00 mg/mL. Ephedrine did not interfere with the measurement. The method was rapid & simple compared to the gas chromatography method.
YAMAMOTO Y ET AL; NIPPON HOIGAKU ZASSHI 33 (2): 105-10 (1979)
A radioimmunoassay method is described for the detection of methamphetamine in urinary specimens.
ALEXANDER GJ ET AL; NEUROTOXICOL 1: 93-102 (1977)
For more Clinical Laboratory Methods (Complete) data for d-METHAMPHETAMINE (10 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

1 of 2
View All
Pictogram(s)
Acute Toxic
Signal
Danger
GHS Hazard Statements
H301 (97.6%): Toxic if swallowed [Danger Acute toxicity, oral]
Precautionary Statement Codes

P264, P270, P301+P316, P321, P330, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 42 reports by companies from 3 notifications to the ECHA C&L Inventory.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 3 (97.6%)

11.2 Fire Fighting

11.2.1 Fire Fighting Procedures

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.3 Accidental Release Measures

11.3.1 Cleanup Methods

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

11.3.3 Preventive Measures

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion-proof equipment.Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.4 Handling and Storage

11.4.1 Storage Conditions

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 °C
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.5 Exposure Control and Personal Protection

11.5.1 Personal Protective Equipment (PPE)

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html
Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.6 Stability and Reactivity

11.6.1 Hazardous Reactivities and Incompatibilities

Incompatible materials: Acids, Oxidizing agents, Alkali metals, Strong oxidizing agents, Strong acids, Acid chlorides, Acid anhydrides, Reducing agents, Strong reducing agents, Phosphorus halides
Sigma-Aldrich; Material Safety Data Sheet for S(+)-Methamphetamine solution, Product Number: M-020, Version 5.3 (Revision Date 08/15/2014). Available from, as of November 24, 2015: https://www.sigmaaldrich.com/safety-center.html

11.7 Regulatory Information

REACH Registered Substance

11.7.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including methamphetamine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methamphetamine hydrochloride/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of September 30, 2015: https://www.fda.gov/cder/ob/
Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... (d) Stimulants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system: Methamphetamine, its salts, isomers, and salts of its isomers (DEA Code Number: 1105) is included on this list. /Methamphetamine, its salts, isomers, and salts of its isomers/
21 CFR 1308.12(d) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 7, 2015: https://www.ecfr.gov

11.8 Other Safety Information

11.8.1 Special Reports

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332
DHHS/NIDA; Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330
DHHS/NIDA; Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335
DHHS/NIDA; Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400
For more Special Reports (Complete) data for d-METHAMPHETAMINE (8 total), please visit the HSDB record page.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION AND USE: Methamphetamine is a white solid odorless crystals. Indications: Narcolepsy and hyperkinetic states in children (as an adjunct to psychological, educational and social measures). Its misuse includes performance enhancement and relief of fatigue. It is a Schedule II Controlled Substance. HUMAN EXPOSURE AND TOXICITY: Main risks include: acute central nervous system (CNS) stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning. Myocardial ischemia, infarction and ventricular dysfunction are described. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects include: increased bladder sphincter tone which may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. The ability of methamphetamine to both release dopamine and serotonin as well as to inhibit monoamine oxidase activity leads to the non-enzymatic oxidation of dopamine and serotonin. Methamphetamine induced neuronal damage is mediated by the production of free radicals. This drug causes a long lasting depletion of dopamine and serotonin in the striatum and that pre-treatment alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicate that oxygen free radicals have a role in methamphetamine- induced neurotoxicity. In fatal cases of poisoning in human patients, the panic state is followed by convulsions, coma and death from intracranial hemorrhages or cardiac arrhythmias. The use of amphetamine and its congeners for medical indications do not pose a significant risk to the fetus for congenital anomalies. They generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. These poor outcomes are probably multifactorial in origin, involving multiple drug use, life-styles and poor maternal health. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. Sixty-five children were followed whose mothers were addicted during pregnancy, at least during the first trimester. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: The administration of high dose of methamphetamine causes long lasting damage to central dopaminergic and serotonergic neurons through a mechanism known to involve presynaptic, cytoplasmic stores of those transmitters dependent upon a free radical reaction in experimental animals. Confinement and aggregation markedly increased lethality of methamphetamine in mice. Pregnant sheep given methamphetamine appeared anxious, with quick side to side movements of the head and feet.
Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

12.1.2 Drug Induced Liver Injury

Compound
methamphetamine
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.3 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

12.1.4 Health Effects

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

12.1.5 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Because there is no published experience with methamphetamine as a therapeutic agent during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. One expert recommends that amphetamines not be used therapeutically in nursing mothers.

Methamphetamine should not be used as a recreational drug by nursing mothers because it may impair their judgment and childcare abilities. Methamphetamine and its metabolite, amphetamine, are detectable in breastmilk and infant's serum after abuse of methamphetamine by nursing mothers. However, these data are from random collections rather than controlled studies because of ethical considerations in administering recreational methamphetamine to nursing mothers. Other factors to consider are the possibility of positive urine tests in breastfed infants which might have legal implications, and the possibility of other harmful contaminants in street drugs. Breastfeeding is generally discouraged in mothers who are actively abusing amphetamines. In mothers who abuse methamphetamine while nursing, withholding breastfeeding for 48 to 100 hours after the maternal use been recommended, although in many mothers methamphetamine is undetectable in breastmilk after an average of 72 hours from the last use. It has been suggested that breastfeeding can be reinstated 24 hours after a negative maternal urine screen for amphetamines.

◉ Effects in Breastfed Infants

A 2-month-old infant whose mother used illicit street methamphetamine recreationally by nasal inhalation was found dead 8 hours after a small amount of breastfeeding and ingestion of 120 to 180 mL of formula. The infant's serum methamphetamine concentration on autopsy was 39 mcg/L. Although the infant's mother was convicted of child endangerment for the use of methamphetamine during breastfeeding, the role that methamphetamine played in the infant's death has been questioned because of the low infant serum methamphetamine concentration and the mother's alleged minimal breastfeeding.

South Australian government pathologists reported the death of a breastfed infant who was co-sleeping with its mother. Methamphetamine was found in a “significant” concentration in the infant on autopsy and the drug in breastmilk was thought to be potentially contributory to the death. These authors also reported that in prior deaths of infants under 12 months of age, detectable methamphetamine and its metabolite, amphetamine, may have been partially obtained via breastmilk. Pathologists from the New Zealand government confirmed similar findings in their country.

◉ Effects on Lactation and Breastmilk

A single oral dose of 0.2 mg/kg to a maximum of 17.5 mg of d-methamphetamine was given to 6 subjects (4 male and 2 female). Serum prolactin concentrations were unchanged over a period of 300 minutes after the dose.

In 2 papers by the same authors, 20 women with normal physiologic hyperprolactinemia were studied on days 2 or 3 postpartum. Eight received dextroamphetamine 7.5 mg intravenously, 6 received 15 mg intravenously and 6 who served as controls received intravenous saline. The 7.5 mg dose reduced serum prolactin by 25 to 32% compared to control, but the difference was not statistically significant. The 15 mg dose significantly decreased serum prolactin by 30 to 37% at times after the infusion. No assessment of milk production was presented. The authors also quoted data from another study showing that a 20 mg oral dose of dextroamphetamine produced a sustained suppression of serum prolactin by 40% in postpartum women.

A study compared 31 methamphetamine-dependent subject to 23 non-dependent subjects. The serum prolactin concentrations in the methamphetamine-dependent subjects were elevated at days 2 and 30 of abstinence. The elevation was greater in women than in men. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

In a retrospective Australian study, mothers who used intravenous amphetamines during pregnancy were less likely to be breastfeeding their newborn infants at discharge than mothers who abused other drugs (27% vs 42%). The cause of this difference was not determined.

A prospective, multicenter study followed mothers who used methamphetamine prenatally (n = 204) to those who did not (n = 208). Infants exposed to methamphetamine exhibited poor suck, excessive suck and more jitteriness compared to nonexposed infants. Mothers who used methamphetamine were less likely to breastfeed their infants (38%) at hospital discharge than those who did not use methamphetamine (76%).

◈ What is methamphetamine?

Methamphetamine is also known as metamfetamine, methylamphetamine, and desoxyephedrine. Other names for methamphetamine include “meth,” “crystal meth,” “crank,” “speed” or “ice.” Methamphetamine has been smoked, snorted, swallowed, injected, inhaled, taken rectally, or dissolved under the tongue.Methamphetamine has been used illegally without medical supervision. It has also been prescribed by a healthcare provider for attention deficit hyperactivity disorder (ADHD). This sheet will focus on the use of methamphetamine without medical supervision.

◈ I take methamphetamine. Can it make it harder for me to get pregnant?

Methamphetamine has not been studied to see if using it could make it harder to get pregnant.

◈ I just found out that I am pregnant, should I stop taking methamphetamine?

If you are using methamphetamine without medical supervision (sometimes called recreational use), treatment is available to help you stop. Talk to your healthcare provider as soon as possible so that you can start treatment. If you do not have a healthcare provider, call the national number for drug treatment referral at 800-662-4357. When you call, let them know that you are pregnant so that you can get connected to the best facility to meet your needs.

◈ Does taking methamphetamine increase the chance of miscarriage?

Miscarriage is common and can occur in any pregnancy for many different reasons. Based on the studies reviewed, methamphetamine use might increase the chance for miscarriage.

◈ Does taking methamphetamine increase the chance of birth defects?

Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Based on the studies reviewed, it is not known if methamphetamine increases the chance for birth defects above the background risk. Information on whether methamphetamine increases the chance of birth defects is mixed. This makes it hard to know the actual risks for each person who uses methamphetamine.

◈ What can I do to find out if the baby has a birth defect or other problems?

It is important to talk with your healthcare provider about any exposures you have had during your pregnancy. They can help you find treatment or support and can go over any screening options that are available. A detailed ultrasound can screen for some birth defects. There is no test in pregnancy that can look for learning problems. Once your baby is born, you should also tell your child’s healthcare provider so your baby can get the care that is best for them.

◈ Does taking methamphetamine in pregnancy increase the chance of other pregnancy-related problems?

Methamphetamine use has been linked to a higher chance for preterm delivery (delivery before 37 weeks of pregnancy), poor growth (babies born too small and/or with a small head size), and low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). Some studies have suggested that methamphetamine use in pregnancy can increase the chance for high blood pressure, placental abruption (the placenta pulls away from the uterus) and for fetal death or infant death. Some studies also show an association between methamphetamine misuse and a higher chance of postpartum mood disorders. Pregnancy complications are more likely to happen when methamphetamine is used throughout the whole pregnancy or when taken at high doses.

◈ Will my baby have withdrawal if I continue to take methamphetamine?

When people who are pregnant use methamphetamines near the end of their pregnancy, babies could show signs of withdrawal after they are born. Symptoms can include trouble eating, sleeping too little or too much, having floppy (poor) muscle control or tight muscles, being jittery, and / or having a hard time breathing. Withdrawal symptoms usually go away within a few weeks but can last for a few months. The baby might need to be admitted to the special care nursery (NICU). It is important that your healthcare providers know you are taking methamphetamine so that if symptoms occur your baby can get the care that is best for them.

◈ Does taking methamphetamine in pregnancy affect future behavior or learning for the child?

Studies have suggested that children who were exposed to methamphetamine during pregnancy could have a higher chance for changes in their brain development, as well as learning and behavior problems later in life.

◈ Breastfeeding while taking methamphetamine:

Methamphetamine can pass into breast milk. Methamphetamine should not be used without medical supervision while breastfeeding. If methamphetamine is used, it has been suggested to express and discard breastmilk for 48-100 hours. Be sure to talk to your healthcare provider about all of your breastfeeding questions.

◈ If a male takes methamphetamine, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?

Methamphetamine misuse might affect the sperm, making it harder to get someone pregnant. Studies have not been done to see if methamphetamine could increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/,

12.1.6 Exposure Routes

Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.

12.1.7 Symptoms

Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

12.1.8 Acute Effects

12.1.9 Treatment

Management of acute methamphetamine intoxication is largely symptomatic and includes gastric evacuation, administration of activated charcoal, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard. Acidification of urine increases methamphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates methamphetamine overdosage. Usually a gradual drop in blood pressure will result when sufficient sedation has been achieved. Chlorpromazine has been reported to be useful in decreasing CNS stimulation and sympathomimetic effects. (L1712)
L1712: RxList: The Internet Drug Index (2009). http://www.rxlist.com/

12.1.10 Interactions

BACKGROUND: Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. METHODS: Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/hr), methylphenidate (0.032-0.32mg/kg/hr), or cocaine (0.1-0.32mg/kg/hr). RESULTS: During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/hr d-amphetamine did eliminate methamphetamine choice in two monkeys. CONCLUSIONS: The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice.
Schwienteck KL, Banks ML; Drug Alcohol Depend 155: 16-23 (2015)
College age subjects learned & recalled a series of word lists prior to being injected with 0.2 or 0.3 mg/kg methamphetamine, 8 mg/kg scopolamine, or a placebo. Following injection, subjects were tested for their free recall & recognition of the words & they completed a short term digit recall task. Subjects who had previously received scopolamine were next injected with either 0.2 mg/kg or 0.3 mg/kg methamphetamine, physostigmine, or placebo, while other subjects received a placebo injection. The memory procedure was then repeated with a 2ND series of word lists. ... Scopolamine & methamphetamine did not affect recall of information learned prior to injection. Scopolamine did, however, impair performance in both the digit recall task & in the second series of memory tests. Physostigmine & methamphetamine alleviated most of the memory deficits & sedation produced by scopolamine. Methamphetamine impaired performance in both the digit recall task & in the 2ND series of memory tests. When given alone, it also produced subjective arousal & small improvement in recall of words learned after injection & large incr in incorrect responding.
MEWALDT SP, GHONELM MM; PHARMACOL, BIOCHEM BEHAV 10 (2): 205-10 (1979)
Neurologic and circulatory reactions have been reported in patients who have received parenteral methamphetamine concomitantly with monoamine oxidase inhibitor drugs, and fatalities have occurred. Methamphetamine is therefore contraindicated during or within 14 days of administration of monoamine oxidase inhibitors.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538
Patients receiving concomitant therapy with tricyclic antidepressants and indirect-acting sympathomimetic amines (e.g., amphetamines) should be closely monitored, and dosage carefully adjusted.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2538
For more Interactions (Complete) data for d-METHAMPHETAMINE (9 total), please visit the HSDB record page.

12.1.11 Antidote and Emergency Treatment

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat agitation, seizures, coma, and hyperthermia if they occur. 3. Continuously monitor the temperature, other vital signs, and the ECG for a minimum of 6 hours. /Amphetamines/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79
Specific drugs and antidotes. There is no specific antidote. 1. Agitation. Benzodiazepines are usually satisfactory, although antipsychotic agents may be added as needed. 2. Hypertension is best treated with sedation and, if this is not effective, a parenteral vasodilator such as phentolamine or nitroprusside. 3. Treat tachyarrhythmias with propranolol or esmolol. NOTE: Paradoxical hypertension can occur owing to unopposed alpha-adrenergic effects when beta2-mediated vasodilation is blocked; be prepared to give a vasodilator if needed. 4. Treat arterial vasospasm ... . /Amphetamines/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79
Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Consider whole-bowl irrigation and repeated doses of charcoal after ingestion of drug-filled packets (body stuffers). /Amphetamines/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79
Enhanced elimination. Dialysis and hemoperfusion are not effective. repeat-dose charcoal has not been studied. Renal elimination of dextroamphetamine may be enhanced by acidification of the urine, but this is not recommended because of the risk for aggravating the nephrotoxicity of myoglobinuria. /Amphetamines/
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 79
For more Antidote and Emergency Treatment (Complete) data for d-METHAMPHETAMINE (7 total), please visit the HSDB record page.

12.1.12 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ In fatal cases of poisoning in human patients, the panic state is followed by convulsions, coma and death from intracranial hemorrhages or cardiac arrythmias.
International Programme on Chemical Safety; Poisons Information Monograph: Methamphetamine (PIM 334) (1998) Available from, as of December 6, 2005: https://www.inchem.org/pages/pims.html
/SIGNS AND SYMPTOMS/ Injected intravenously, it induces intense euphoria (a "rush"). Overdoses may produce confusion, hallucinations, convulsions, mania, and acts of self-destruction. Its psychic and motor effects resemble those of cocaine but last longer.
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-372
/SIGNS AND SYMPTOMS/ Intravenous or smoked methamphetamine produces an abuse/dependence syndrome similar to that of cocaine.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 571
/SIGNS AND SYMPTOMS/ Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
For more Human Toxicity Excerpts (Complete) data for d-METHAMPHETAMINE (13 total), please visit the HSDB record page.

12.1.13 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Neurotoxicity/ The effect of long term repeated iv admin of methamphetamine in increasing doses to rhesus monkeys was evaluated. Monkeys treated 8 times/day for 3 to 6 MO showed tolerance to the disruptive effects of the drug on behavior. Monkeys treated for a prolonged period & killed 3 to 6 MO after cessation of treatment showed 70% loss of caudate dopamine & 33 & 52% loss of norepinephrine in midbrain & frontal cortex, respectively.
SEIDEN LS ET AL; ADV BEHAV BIOL 21, ISS COCAINE OTHER STIMUL 179-85 (1977)
/LABORATORY ANIMALS: Neurotoxicity/ Methamphetamine (2-6 mg/kg) given to cats repeatedly incr reactivity of autonomic nervous system, & reactivity lasted 3 MO after cessation of admin.
SATO M; SEISHIN SHINKEIGAKU ZASSHI 81 (1): 21-32 (1979)
/LABORATORY ANIMALS: Neurotoxicity/ Chronic use of high doses of amphetamines has been reported to produce microvascular damage, neuronal chromatolysis (primarily in brain areas rich in adrenergic neurons), and profound and long-lasting (or permanent) depletion of dopamine in the caudate nucleus. Admin of large doses of methamphetamine to rats causes the appearance in the CNS of detectable concn of 6-hydroxydopamine, a substance that destroys adrenergic neurons.
Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 554
/BEHAVIORAL STUDIES/ Behavioral Toxicity: Methamphetamine impairs pigeon's performance in visual discrimination tasks.
Dews PB; J Pharmacol Exp Ther 115: 380-9 (1955) as cited in DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability p.67 (1984) DHHS Pub No. (ADM)87-1332
For more Non-Human Toxicity Excerpts (Complete) data for d-METHAMPHETAMINE (9 total), please visit the HSDB record page.

12.1.14 Human Toxicity Values

Therapeutic or normal methamphetamine blood concentration: 20-60 ug/dL; Toxic methamphetamine blood concentration: 60-500 ug/dL; Lethal methamphetamine blood concentration: 1-4 mg/dL /From table/
Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 421

12.1.15 Non-Human Toxicity Values

LD50 Mouse intraperitoneal 70 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1104

12.1.16 Populations at Special Risk

Adults: Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712
Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
NIH; DailyMed. Current Medication Information for METHAMPHETAMINE HYDROCHLORIDE- methamphetamine hydrochloride tablet (Revised: May 2015). Available from, as of November 23, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f31f580f-1f08-4a0f-b078-0b9e3308f712

12.2 Ecological Information

12.2.1 Environmental Fate / Exposure Summary

d-Methamphetamine's production and administration as a human and veterinary medication and illicit drug may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 5.4X10-3 mm Hg at 25 °C indicates d-methamphetamine will exist solely as a vapor in the atmosphere. Vapor-phase d-methamphetamine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 1 hour. d-Methamphetamine does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, d-methamphetamine is expected to have low mobility based upon an estimated Koc of 900. The pKa of d-methamphetamine is 9.87, indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. d-Methamphetamine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation half-lives of 131 days in sandy loam and 502 days in loam soil suggest that biodegradation in soil is dependent upon soil conditions. If released into water, d-methamphetamine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. d-Methamphetamine present at 1090 ng/L, decreased in concentration to 675 and 529 ng/L in duplicate test runs over 15 days using river microcosm bioreactors, suggesting that biodegradation may be an important environmental fate process in water. The pKa indicates d-methamphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 11 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to d-methamphetamine may occur through inhalation and dermal contact with this compound at workplaces where d-methamphetamine is produced or used. Monitoring data indicate that the general population may be exposed to d-methamphetamine via ingestion of contaminated water. Exposure to d-methamphetamine among the general population will be by direct medical treatment and also occurs among those abusing this drug. (SRC)

12.2.2 Artificial Pollution Sources

d-Methamphetamine's production and administration as a human and veterinary medication and illicit drug(1) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 1104 (2013)

12.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that d-methamphetamine is expected to have low mobility in soil(SRC). The pKa of d-methamphetamine is 9.87(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. d-Methamphetamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation half-lives of 131 days in sandy loam and 502 days in loam(5) suggest that biodegradation in soil is dependent upon soil conditions(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Pal R et al; Chemosphere 85: 1009-9 (2011). Available from, as of Oct 23, 2015: https://www.ncbi.nlm.nih.gov/pubmed/?term=21777940
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that d-methamphetamine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.87(3) indicates d-methamphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 11(SRC), from its log Kow of 2.07(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). d-Methamphetamine present at 1090 ng/L, decreased in concentration to 675 and 529 ng/L in duplicate test runs over 15 days using river microcosm bioreactors(6), suggesting that biodegradation may be an important environmental fate process in water(SRC). However d-methamphetamine is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(7).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 78 (1995)
(6) Bagnall J et al; Water Res 47: 5708-18 (2013)
(7) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), d-methamphetamine, which has an estimated vapor pressure of 5.41X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase d-methamphetamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1 hour(SRC), calculated from its rate constant of 9.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). d-Methamphetamine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

12.2.4 Environmental Biodegradation

AEROBIC: Half-lives of 131 and 502 days have been reported in Sturt Gorge (sandy loam: pH 5.98, 2.88% organic carbon, 60.0% sand, 25.0% silt, 15.0% clay) and Waite Campus (loam: pH 5.64, 2.26% organic carbon, 42.5% sand, 42.5% silt, 15.0% clay) soils from Maawson Lakes, South Australia(1). d-Methamphetamine present at 650 ng/L, decreased in concentration to 500 and 400 ng/L over 15 days using river microcosm bioreactors with and without sediment, respectively, maintained under dark conditions at pH 8.3, 29.5 °C and 7.1 mg/L dissolved oxygen. River water was from the River Avon at Saltford (West of Bath UK), collected during September 2011(2).
(1) Pal R et al; Chemosphere 85: 1009-9 (2011). Available from, as of Oct 23, 2015: https://www.ncbi.nlm.nih.gov/pubmed/?term=21777940
(2) Bagnall J et al; Water Res 47: 5708-18 (2013)

12.2.5 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of d-methamphetamine with photochemically-produced hydroxyl radicals has been estimated as 9.3X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about one hour at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). d-Methamphetamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). d-Methamphetamine, present at 650 ng/L, showed no decrease in concentration over 15 days using river microcosm abiotic reactors with and without sediment, respectively, maintained under light conditions at pH 9.3, 29.7 °C and 8.2 mg/L dissolved oxygen. River water was from the River Avon at Saltford (West of Bath UK), collected during September 2011(3). d-Methamphetamine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)
(3) Bagnall J et al; Water Res 47: 5708-18 (2013)

12.2.6 Environmental Bioconcentration

An estimated BCF of 11 was calculated in fish for d-methamphetamine(SRC), using a log Kow of 2.07(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 78 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

12.2.7 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of d-methamphetamine can be estimated to be 900(SRC). According to a classification scheme(2), this estimated Koc value suggests that d-methamphetamine is expected to have low mobility in soil. The pKa of d-methamphetamine is 9.87(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

12.2.8 Volatilization from Water / Soil

A pKa of 9.87(1) indicates d-methamphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). d-Methamphetamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-3 mm Hg(SRC), determined from a fragment constant method(2).
(1) Perrin DD; Dissociation constants of organic bases in aqueous solution. IUPAC Chem Data Ser, Buttersworth, London (1965)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Oct 23, 2015: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

12.2.9 Environmental Water Concentrations

DRINKING WATER: d-Methamphetamine was present at a 4% frequency (mean concentration was below the limit of quantitation of 0.8 ng/L) with a maximum concentration of 1.4 ng/L in tap water from 43 cities in Spain, sampled from fall 2008 to summer 2009. A maximum concentration of 0.6 ng/L (4% frequency) was reported for 26 samples collected from Europe, Japan and Latin America(1). d-Methamphetamine was not detected in finished drinking water from a treatment plant on the Llobregat River in northeast Spain, monitored from January 2007 to June 2007(2).
(1) Rosa Boleda M et al; Chemosphere 84: 1601-7 (2011)
(2) Huerta-Fontela M et al; Environ Sci Technol 42(48): 6809-16 (2008)
SURFACE WATER: d-Methamphetamine was detected at a range of 2-40 and 0.8-1 ng/L in unspecified UK waste water treatment plant influent and effluent samples, respectively(1). The compound was not detected in river water samples from the Llobregat River in northeast Spain and two tributaries, Cardener River and Anoia River sampled in January, March and May 2007. An estimated load of 8 g/day during January was calculated for the Rubi Creek(2). d-Methamphetamine estimated loadings of <0.04, 0.2, 0.1, 0.4 and <0.04 g/day were calculated for spring 2006, summer, 2006, fall 2006, winter 2006/2007 and spring 2007, respectively, in samples from the Llobregat River collected near a drinking water plant intake(2). The compound was detected at a mean concentration of 0.4 ng/L (range 0.3-0.7 ng/L; 14% of 28 samples positive) in surface water samples from the Ebro River Basin, Spain, sampled in October 2007 and July 2008(3). d-Methamphetamine levels in the Jarama and Manzanares Rivers of the Madrid Region, Spain ranged from 1.4 to 10.3 ng/L, sampled in February and March, 2012(4).
(1) Petrie B et al; Water Res 72: 3-27 (2015)
(2) Huerta-Fontela M et al; Environ Sci Technol 42(48): 6809-16 (2008)
(3) Postigo C et al; Environ Int 36(1): 75-84 (2010)
(4) Mendoza A et al; Chemosphere 95: 247-55 (2014)

12.2.10 Effluent Concentrations

d-Methamphetamine was present at an average loading rate of 806 and <18 g/day in influent and effluent, respectively, collected from a wastewater treatment plant in conjunction with a US major sporting event (National Football League's Super Bowl). Non-event loadings were 930 and <10 g/day(1). The compound was detected at a range of <0.1-0.3 ng/L, maximum concentration of 0.3 ng/L also reported, in unspecified UK surface water samples(2). The compound was detected at a mean concentration of 4.6 ng/L (range 0.8-8.4 ng/L; 14% samples positive) in influent sewage samples from the Ebro River Basin, Spain, sampled in October 2007 and July 2008. A median concentration of 1.3 ng/L (range 0.5-7.6 ng/L; 43% samples positive) was reported for effluent samples(3).
(1) Gerrity D et al: Water Res 45: 5399-11 (2011)
(2) Petrie B et al; Water Res 72: 3-27 (2015)
(3) Postigo C et al; Environ Int 36(1): 75-84 (2010)

12.2.11 Probable Routes of Human Exposure

Occupational exposure to d-methamphetamine may occur through inhalation and dermal contact with this compound at workplaces where d-methamphetamine is produced or used. Monitoring data indicate that the general population may be exposed to d-methamphetamine via ingestion of contaminated water. Exposure to d-methamphetamine among the general population will be by direct medical treatment and also occurs among those abusing this drug. (SRC)

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Chemical Co-Occurrences in Literature

14.7 Chemical-Gene Co-Occurrences in Literature

14.8 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: ATC

19.5 KEGG: Target-based Classification of Drugs

19.6 KEGG: Drug Groups

19.7 WHO ATC Classification System

19.8 FDA Pharm Classes

19.9 ChemIDplus

19.10 ChEMBL Target Tree

19.11 UN GHS Classification

19.12 EPA CPDat Classification

19.13 Drug Enforcement Administration (DEA) Classification

19.14 NORMAN Suspect List Exchange Classification

19.15 CCSBase Classification

19.16 EPA DSSTox Classification

19.17 LOTUS Tree

19.18 EPA Substance Registry Services Tree

19.19 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
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    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
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  5. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  6. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
  7. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. Hazardous Substances Data Bank (HSDB)
  9. Human Metabolome Database (HMDB)
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    http://www.hmdb.ca/citing
  10. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  11. ChEBI
  12. FDA Pharm Classes
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    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  14. NCI Thesaurus (NCIt)
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  15. Open Targets
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    https://platform-docs.opentargets.org/licence
  16. Toxin and Toxin Target Database (T3DB)
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    http://www.t3db.ca/downloads
  17. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  18. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  19. Comparative Toxicogenomics Database (CTD)
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    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  20. Drug Gene Interaction database (DGIdb)
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    http://www.dgidb.org/downloads
  21. Therapeutic Target Database (TTD)
  22. Drug Enforcement Administration (DEA)
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    https://www.justice.gov/legalpolicies
    DEA drug and chemical classification
    https://www.dea.gov/drug-information/drug-scheduling
  23. Drug Induced Liver Injury Rank (DILIrank) Dataset
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  24. NORMAN Suspect List Exchange
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    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Methamphetamine
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  25. Drugs and Lactation Database (LactMed)
  26. Mother To Baby Fact Sheets
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    Copyright by OTIS. This work is available under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported license (CC BY-NC-ND 3.0).
    https://www.ncbi.nlm.nih.gov/books/about/copyright/
  27. EPA Chemical and Products Database (CPDat)
  28. Japan Chemical Substance Dictionary (Nikkaji)
  29. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  30. MassBank Europe
  31. MassBank of North America (MoNA)
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
  32. Metabolomics Workbench
  33. NIPH Clinical Trials Search of Japan
  34. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
  35. NLM RxNorm Terminology
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  36. PharmGKB
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    https://www.pharmgkb.org/page/policies
  37. Pharos
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    https://pharos.nih.gov/about
  38. Protein Data Bank in Europe (PDBe)
  39. RCSB Protein Data Bank (RCSB PDB)
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    https://www.rcsb.org/pages/policies
  40. SpectraBase
  41. Springer Nature
  42. SpringerMaterials
  43. Thieme Chemistry
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  44. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  45. Wikidata
  46. Wikipedia
  47. Wiley
  48. Medical Subject Headings (MeSH)
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    Adrenergic Uptake Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68018759
    Central Nervous System Stimulants
    https://www.ncbi.nlm.nih.gov/mesh/68000697
  49. PubChem
  50. GHS Classification (UNECE)
  51. EPA Substance Registry Services
  52. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  53. PATENTSCOPE (WIPO)
  54. NCBI
CONTENTS