Amphetamine

From PsychonautWiki
(Redirected from Evekeo)
Jump to: navigation, search
Summary sheet: Amphetamine
Amphetamine
Amphetamine.svg
Chemical Nomenclature
Common names Amphetamine, Speed, Adderall, Pep
Substitutive name α-Methylphenethylamine
Systematic name (RS)-1-Phenylpropan-2-amine
Class Membership
Psychoactive class Stimulant
Chemical class Phenethylamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 5 mg
Light 10 - 20 mg
Common 20 - 40 mg
Strong 40 - 70 mg
Heavy 70 mg +
Duration
Total 6 - 8 hours
Onset 15 - 30 minutes
Peak 2.5 - 4 hours
Offset 2 - 3 hours
After effects 5 - 10 hours



Insufflated
Dosage
Threshold 5 - 15 mg
Light 15 - 25 mg
Common 25 - 40 mg
Strong 40 - 75 mg
Heavy 75 mg +
Duration
Total 3 - 6 hours
Onset 1 - 5 minutes
Peak 1 - 2 hours






DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Amphetamine (also known as alpha-methylphenethylamine and speed) is a stimulant substance of the phenethylamine class. It is the parent compound of the substituted amphetamines, a group which includes a diverse range of substances like bupropion, phenmetrazine, MDMA, and DOx. Amphetamine acts primarily by enhancing the activity of the neurotransmitters dopamine and norepinephrine in the brain.[citation needed]

Amphetamine was first synthesized in 1887.[citation needed] In the 1930s, it began to be marketed and sold over-the-counter under the name Benzedrine. It was widely used to treat a wide range of ailments such as alcohol hangover, narcolepsy, depression, and weight reduction.[1] Today, amphetamine is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity.[2][3] Additionally, it sees widespread illicit use as a performance enhancing agent and recreational substance.

Amphetamine is viewed as one of the benchmark members of the stimulant class. Characteristic effects include stimulation, enhanced focus, increased libido, suppressed appetite, and euphoria. It is usually taken orally, but can also be insufflated, injected, or administered rectally. Lower doses are commonly reported to increase focus and productivity while higher doses tend to increase sociability, sexual desire, and euphoria.

Recreational use of amphetamine is associated with dependence and abuse. It is highly advised to use harm reduction practices if using this substance.

History and culture

Amphetamine was first synthesized in Germany in 1887 by the Romanian chemist Lazăr Edeleanu, who named it phenylisopropylamine.[4] However, its stimulant effects remained unknown until 1927, when it was independently re-synthesized by Gordon Alles and discovered to have sympathomimetic properties.[5]

In late 1933, Smith, Kline and French began selling amphetamine in the form of a decongestant inhaler under the name Benzedrine.[6] Benzedrine sulfate was introduced 3 years later and was used to treat a wide variety of medical conditions, including narcolepsy, obesity, low blood pressure, low libido, and chronic pain.[7]

During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects.[8][9] As its addictive properties became known, governments began to place strict controls on its sale.[10]

Amphetamine is still illegally synthesized and sold on the black market, primarily in European countries.[11] Among European Union (EU) member states, 1.2 million young adults used illicit amphetamine or methamphetamine in 2013. During 2012, approximately 5.9 metric tons of illicit amphetamine were seized within EU member states;[11] the "street price" of illicit amphetamine within the EU ranged from €6–38 per gram during the same period.[11] Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine and MDMA.[11]

Chemistry

Amphetamine, also known as alpha-methylphenethylamine, is a synthetic substance of the phenethylamine family. The chemical structure of amphetamine consists of phenethylamine, a phenyl ring bound to an amino (NH2) group through an ethyl chain, with an additional methyl substitution at Rα. It can be referred to as a methyl homolog of phenethylamine as it has the same general formula, differing only in the addition of one methyl group. The name 'amphetamine' is a contraction from αlphamethylphenethylamine

Amphetamine is a chiral compound. The racemic mixture can be divided into its optical antipodes: levo- and dextro-amphetamine. Today, dextroamphetamine sulfate is the predominant form used:[citation needed] it consists entirely of the d-isomer. Attention disorders are often treated using Adderall or a generic equivalent, a formulation of mixed amphetamine salts that contain both racemic-amphetamine and d-amphetamine in the sulfate and saccharate forms mixed to a final ratio of 3 parts d-amphetamine to 1 part l-amphetamine.[citation needed]

At room temperature, the pure free base of amphetamine is a mobile, colorless, and volatile liquid with a characteristically strong amine odor, and acrid, burning taste.[12]

Pharmacology

Amphetamine exerts its behavioral effects by increasing the signaling activity of neurotransmitters norepinephrine and dopamine in the reward and executive function pathways of the brain. The reinforcing and motivational effects of amphetamine are mostly due to enhanced dopaminergic activity in the mesolimbic pathway.[13] The euphoric and locomotor-stimulating effects of amphetamine are dependent upon the magnitude and speed by which it increases synaptic dopamine and norepinephrine concentrations in the striatum.[14]

Amphetamine is a potent full agonist of the trace amine-associated receptor 1 (TAAR1) and interacts with vesicular monoamine transporter 2 (VMAT2).[15][16][17] Combined action on TAAR1 and VMAT2 results in increased concentrations of dopamine and norepinephrine in the synapses, which stimulates neuronal activity.

Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.[18] Consequently, dextroamphetamine produces greater CNS stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects.[19][20]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
Child.svg

Visual effects
Eye.svg

Cognitive effects
User.svg

After effects
Aftereffects (3).svg

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Toxicity and harm potential

This radar plot shows therelative physical harm, social harm, and dependence of amphetamine.[21]

As of March 2014, there is no evidence that amphetamine is directly neurotoxic in humans.[22] However, high-dose amphetamine can cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.[23][24][25]

In rodents and primates, sufficiently high doses of amphetamine causes damage to dopamine neurons, characterized as reduced transporter and receptor function.[26] Animal models of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e., core body temperature ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity. [27]

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

The LD50 (the dosage required to kill 50% of the test subjects) of amphetamine in rats has been found to be between roughly 15mg and 180mg per kilogram depending on the study.[28] No formal studies in humans have been carried out and the exact toxic dosage is unknown.

Dependence and abuse potential

Amphetamine has a high abuse potential and can cause dependence with chronic use. When dependence has developed, cravings and withdrawal effects may occur if use is suddenly discontinued.[29][30] Withdrawal symptoms include paranoia, depression, dream potentiation, anxiety, itching, mood swings, irritability, fatigue, insomnia, an intense craving for more amphetamine or other stimulants. Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to arise from typical medical use.[31][32][33]

Tolerance to many of the effects of amphetamine develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. Upon single administration, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Amphetamine presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of amphetamine all stimulants will have a reduced effect.

Psychosis

Main article: Stimulant psychosis

Severe amphetamine overdose can result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia, hallucinations, delusions).[34] A review on treatment for amphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[34][35] The same review asserts that antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[34] Psychosis very rarely arises from therapeutic use.[36][37]

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The following lists some known dangerous combinations, but may not include all of them. A combination that appears to be safe in low doses can still increase the risk of injury or death. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume.

  • 25x-NBOMe & 25x-NBOH - Members of the 25x family are highly stimulating and physically straining. Combinations with stimulants should be avoided due to the risk of excessive stimulation. This can result in panic attacks, thought loops, seizures, increased blood pressure, vasoconstriction, and heart failure in extreme cases.
  • Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
  • DXM - Combinations with DXM should be strictly avoided due to DXM's effects on serotonin and dopamine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome.
  • MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.
  • Tramadol - Tramadol lowers the seizure threshold.[38] Combinations with stimulants may further increase this risk.
  • MDMA - The neurotoxic effects of MDMA may be increased when combined with amphetamines.
  • MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants.[39]
  • Tricyclic antidepressants - Amphetamine may increase the effects of tricyclic antidepressants to dangerous levels.[40]

Legal status

Internationally, amphetamine is a schedule II controlled substance under the United Nations 1971 Convention on Psychotropic Substances.[citation needed] It is therefore illegal to sell and possess without a prescription.

  • Austria: Amphetamine is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich).[citation needed]
  • Canada: Amphetamine is a Schedule I drug in Canada.[41]
  • Germany: Amphetamine is a controlled substance under Anlage 3 of the BtMG.[citation needed]
  • Japan: Amphetamine is prohibited even for medical use in Japan.[42]
  • South Korea: Amphetamine is prohibited even for medical use in South Korea.[citation needed]
  • Thailand: Amphetamine is classified as a category 1 narcotic under the Thai Narcotic Act of 2012.[43]
  • United Kingdom: Amphetamine is a Class B drug in the United Kingdom.[44]
  • United States: Amphetamine is a Schedule II controlled substance in the United States.[45]

See also

External links

Literature

  • Galli, A., Poulsen, N.W., Sulzer, D., & Sonders, M.S. (2005). Mechanisms of neurotransmitter release by amphetamines: a review. Progress in Neurobiology, 75 6, 406-33. https://doi.org/10.1016/j.pneurobio.2005.04.003
  • Berman, S. M., Kuczenski, R., McCracken, J. T., & London, E. D. (2009). Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123. https://doi.org/10.1038/mp.2008.90.
  • Baumann, M., Carroll, F.I., Dersch, C.M., Partilla, J.S., Rothman, R.B., Romero, D., & Rice, K. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse, 39 1, 32-41. doi: 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3

References

  1. Angrist, B., & Sudilovsky, A. (1978). Central nervous system stimulants: historical aspects and clinical effects. In Stimulants (pp. 99-165). Springer, Boston, MA.
  2. The pharmacology and clinical outcomes of amphetamines to treat ADHD: does composition matter? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/22329564
  3. Narcolepsy: current treatment options and future approaches |http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526380/
  4. Lazăr Edeleano: Über einige Derivate der Phenylmethacrylsäure und der Phenylisobuttersäure. In: Berichte der Deutschen chemischen Gesellschaft zu Berlin; 20. Jg. (1887), Band 3, S. 616–622. https://doi.org/10.1002/cber.188702001142
  5. Sulzer D, Sonders MS, Poulsen NW, Galli A (April 2005). "Mechanisms of neurotransmitter release by amphetamines: a review". Prog. Neurobiol. 75 (6): 406–433. doi:10.1016/j.pneurobio.2005.04.003. PMID 15955613.
  6. Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039.
  7. Bett WR (August 1946). "Benzedrine sulphate in clinical medicine; a survey of the literature". Postgrad. Med. J. 22 (250): 205–218. doi:10.1136/pgmj.22.250.205. PMC 2478360  Freely accessible. PMID 20997404.
  8. Rasmussen N (2011). "Medical science and the military: the Allies' use of amphetamine during World War II". J. Interdiscip. Hist. 42 (2): 205–233. PMID 22073434. https://doi.org/10.1162/JINH_a_00212
  9. Defalque RJ, Wright AJ (April 2011). "Methamphetamine for Hitler's Germany: 1937 to 1945". Bull. Anesth. Hist. 29 (2): 21–4, 32. PMID 22849208. https://doi.org/10.1016/s1522-8649(11)50016-2.
  10. "Historical overview of methamphetamine". Vermont Department of Health. Government of Vermont. Archived from the original on 5 October 2012. Retrieved 29 January 2012.
  11. 11.0 11.1 11.2 11.3 Mohan J, ed. (June 2014). "World Drug Report 2014" (PDF). United Nations Office on Drugs and Crime. p. 3. Retrieved 18 August 2014.
  12. "Chemical and Physical Properties". Amphetamine. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 13 October 2013.
  13. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York, USA: McGraw-Hill Medical. pp. 318, 321. ISBN 9780071481274.
  14. Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC 3666194 Freely accessible. PMID 23539642.
  15. The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/
  16. Drug banks amphetamine targets | http://www.drugbank.ca/drugs/DB00182#targets
  17. TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364
  18. Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorg. Med. Chem. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098 Freely accessible. PMID 22037049.
  19. Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill. ISBN 9780071624428.
  20. Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMC 4183197 Freely accessible. PMID 21272013.
  21. Development of a rational scale to assess the harm of d rugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  22. Human health effects - Amphetamine | http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+300-62-9
  23. Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 9780071481274. "Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons."
  24. Toxicity of amphetamines: an update | http://link.springer.com/article/10.1007%2Fs00204-012-0815-5
  25. Dopaminergic neuron-specific oxidative stress caused by dopamine itself. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18596830
  26. Update on Amphetamine Neurotoxicity and Its Relevance to the Treatment of ADHD | http://jad.sagepub.com/content/11/1/8
  27. Bowyer JF, Hanig JP (November 2014). "Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity". Temperature (Austin). 1 (3): 172–182. "Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. ... The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. ... In animal models that evaluate the neurotoxicity of AMPH and METH, it is quite clear that hyperthermia is one of the essential components necessary for the production of histological signs of dopamine terminal damage and neurodegeneration in cortex, striatum, thalamus and hippocampus." | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008711/
  28. Amphetamine - human health effects | http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+3287
  29. "Amphetamines: Drug Use and Abuse" | http://web.archive.org/web/20070217053619/http://www.merck.com/mmhe/sec07/ch108/ch108g.html
  30. Pérez‐Mañá, C., Castells, X., Torrens, M., Capellà, D., & Farre, M. (2013). Efficacy of psychostimulant drugs for amphetamine abuse or dependence. Cochrane Database of Systematic Reviews, (9). DOI: 10.1002/14651858.CD009695.pub2
  31. "Adderall XR Prescribing Information" | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
  32. Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin; London: Springer. p. 78. ISBN 9783540686989.
  33. "Miscellaneous Sympathomimetic Agonists" | http://accessmedicine.mhmedical.com/content.aspx?bookid=374&sectionid=41266218&jumpsectionID=41268855
  34. 34.0 34.1 34.2 Shoptaw, S. J., Kao, U., & Ling, W. (2009). Treatment for amphetamine psychosis. The Cochrane database of systematic reviews, (1), CD003026-CD003026.
  35. Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.
  36. Stimulant Misuse: Strategies to Manage a Growing Problem | http://www.acha.org/prof_dev/ADHD_docs/ADHD_PDprogram_Article2.pdf
  37. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
  38. Talaie, H., Panahandeh, R., Fayaznouri, M. R., Asadi, Z., & Abdollahi, M. (2009). Dose-independent occurrence of seizure with tramadol. Journal of Medical Toxicology, 5(2), 63-67. https://doi.org/10.1007/BF03161089
  39. Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
  40. Adderall Prescription info | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf
  41. Controlled Drugs and Substances Act | http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-24.html#h-28
  42. The problem of the abuse of amphetamines in Japan | https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1957-01-01_3_page003.html
  43. Thai Narcotic Act of 2012 | http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf
  44. Misuse of Drugs Act of 1971 | http://www.legislation.gov.uk/ukpga/1971/38/schedule/2
  45. Controlled Drugs and Substances Act | http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm