Methylphenidate

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Summary sheet: Methylphenidate
Methylphenidate
Methylphenidate.svg
Chemical Nomenclature
Common names Methylphenidate, Concerta, Methylin, Ritalin, Equasym XL
Substitutive name Methylphenidate
Systematic name Methyl phenyl(piperidin-2-yl)acetate
Class Membership
Psychoactive class Stimulant
Chemical class Phenidate / Piperidine
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 - 10 mg
Light 10 - 20 mg
Common 20 - 50 mg
Strong 50 - 80 mg
Heavy 80 mg+
Duration
Total 4 - 6 hours
Onset 20 - 60 minutes
Come up 20 - 60 minutes
Peak 1.5 - 2.5 hours
Offset 1 - 2 hours
After effects 2 - 6 hours



Insufflated
Dosage
Threshold 5 - 10 mg
Light 10 - 15 mg
Common 15 - 30 mg
Strong 30 - 60 mg
Heavy 60 mg +
Duration
Total 2 - 4 hours
Onset 15 - 40 minutes
Come up 15 - 40 hours
Peak 1 - 2 hours
Offset 1 - 2 hours
After effects 1 - 4 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.

Methylphenidate (trade names Concerta, Methylin, Ritalin, Medikinet and Equasym XL) is a stimulant drug and substituted phenethylamine approved for treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It is often used by students with or without ADHD to enhance their mental abilities, improve their concentration, and help them study.

This pharmaceutical was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating ADHD, or what was then known as "hyperactivity." Although it was prescribed to patients as early as 1960, the drug only became heavily prescribed in the 1990s when the diagnosis of ADHD itself became more widely accepted.[1][2]

Chemistry

Methylphenidate is a synthetic molecule of the substituted phenethylamine class. It contains a phenethylamine core featuring a phenyl ring bound to an amino (-NH2) group through an ethyl chain. It is structurally similar to amphetamine, featuring a substitution at Rα which is incorporated into a piperidine ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl acetate bound to R2 or its structure. Methylphenidate is structurally different to ethylphenidate by the length of the carbon chain on their acetate group. Methyl- regards the side chain of one carbon atom, phen- indicates the phenyl ring, id- is contracted from a piperidine ring, and -ate indicates the acetate group containing the oxygens. Methylphenidate is a chiral compound, presumably produced as a racemic mixture. It has an enantiopure also sold as a pharmaceutical; the dextrorotary enantiopure is known as "dexmethylphenidate" and is commonly sold as Focalin and Focalin XR.

Pharmacology

Methylphenidate primarily acts as a dopamine-norepinephrine reuptake inhibitor. It is most active at modulating levels of dopamine and, to a lesser extent, norepinephrine.[3] Methylphenidate binds to and blocks dopamine transporters and norepinephrine transporters.[4]

While both amphetamine and methylphenidate are dopaminergic, it should be noted that their methods of action are somewhat distinct. Specifically, methylphenidate is a dopamine reuptake inhibitor while amphetamine is both a releasing agent and reuptake inhibitor of dopamine and norepinephrine. Each of these drugs have a corresponding effect on norepinephrine which are weaker than their effects on dopamine. Methylphenidate's mechanism of action at dopamine-norepinephrine release is still debated, but is fundamentally different from most other phenethylamine derivatives as methylphenidate is thought to increase general firing rate, whereas amphetamine reduces firing rate and reverses the flow of the monoamines via TAAR1 activation.[5][6][7][8]

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

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

Radar plot showing relative physical harm, social harm, and dependence of methylphenidate[12]

Toxicity

A toxic dose of methylphenidate is considered to be more than 2 mg/kg or 60 mg of an immediate-release formulation, or more than 4 mg/kg or 120 mg of an intact extended-release formulation.[13] In the majority of cases in one study, methylphenidate overdose was asymptomatic or characterized by minor symptoms even in children under age 6. However, a significant amount of patients (31%) in the study developed symptoms typical of stimulant overdose, most commonly tachycardia, agitation, and paradoxically lethargy.[14] In the 2012 National Poison Data System report, methylphenidate exposure was reported 9,787 times, with 1,609 reporting no adverse effects, 1,009 reporting mild effects, 662 reporting moderate effects, 33 reporting major symptoms, and no cases resulting in death.[15]

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

Tolerance and addiction potential

In terms of its tolerance, methylphenidate can be used multiple days in a row for extended periods of time and is often prescribed to be used in this way. Tolerance to many of the effects of methyphenidate develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects.[16] In the case of acute (i.e. one-off) exposure, it generally 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).[citation needed] Methylphenidate presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of methyphenidate all stimulants will have a reduced effect."[citation needed]

As with other stimulants, the chronic use of methylphenidate can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage. Methylphenidate has some potential for abuse due to its action on dopamine transporters. Methylphenidate, like other stimulants, increases dopamine levels in the brain. However, at therapeutic doses this increase is slow and thus euphoria only rarely occurs even when it is administered intravenously.[17] The abuse and addiction potential of methylphenidate is therefore significantly lower than other dopaminergic stimulants.[18][19]

The abuse potential is increased when methylphenidate is crushed and insufflated (snorted) or injected.[20]. It should be noted that due to the fillers in the pill, however, that this can be harmful to the nasal cavities. The primary source of methylphenidate for abuse is the diversion from legitimate prescriptions rather than illicit synthesis. Those who use methylphenidate medicinally generally take it orally as instructed while intranasal and intravenous are the preferred means for recreational use.[21]

Psychosis

Main article: Stimulant psychosis

Chronic abuse of methylphenidate can potentially lead to psychosis.[22][23] The safety profile of short-term methylphenidate therapy has been well-established, with short-term clinical trials revealing a very low incidence (0.1%) of methylphenidate-induced psychosis at therapeutic dose levels.[24] Psychotic symptoms from methylphenidate can include hearing voices, visual hallucinations, urges to harm oneself, severe anxiety, mania, disinhibition, paranoid and grandiose delusions, confusion, emotional suppression, increased aggression, and irritability.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

  • 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.[25] Combinations with stimulants may further increase this risk.
  • MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.
  • 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.[26]
  • Cocaine - This combination may increase strain on the heart.

Legal status

Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.[27]

  • Australia: Methylphenidate is a 'Schedule 8' controlled substance. Such drugs must be kept in a lockable safe before being handed out and possession without prescription carries hefty fines and even imprisonment.
  • Austria: Methylphenidate is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).[citation needed]
  • Canada: Methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline) and is illegal to possess without a prescription pursuant to Part G (section G.01.002) of the Food and Drug Regulations under the Food and Drugs Act.
  • New Zealand: Methylphenidate is a 'Class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and the distribution of it is punishable by a 14-year sentence.
  • Sweden: Methylphenidate is a List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison.[28]
  • United Kingdom: Methylphenidate is a controlled 'Class B' substance. Possession without prescription carries with a sentence up to 5 years and/or an unlimited fine and supplying it is 14 years and/or an unlimited fine.[29]
  • United States: Methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high potential for abuse.

See also

External links

Literature

  • Leonard, B. E., McCartan, D., White, J., & King, D. J. (2004). Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects. Human Psychopharmacology: Clinical and Experimental, 19(3), 151-180. https://doi.org/10.1002/hup.579

References

  1. Diller, Lawrence (1999). Running on Ritalin. ISBN 978-0553379068.
  2. The history of attention deficit hyperactivity disorder (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000907/
  3. Methylphenidate and its Isomers | http://link.springer.com/article/10.2165%2F00023210-200620090-00002
  4. Neurotransmitter transporters and their impact on the development of psychopharmacology (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760736/
  5. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9766762
  6. Neurotransmitter transporters and their impact on the development of psychopharmacology (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760736/
  7. Focalin XR review | http://www.pharma.us.novartis.com/product/pi/pdf/focalinXR.pdf
  8. Concerta Xl slow release | http://www.medicines.org.uk/emc/medicine/8382/SPC/Concerta#PHARMACOLOGICAL_PROPSSPC
  9. 9.0 9.1 Montastruc, F., Montastruc, G., Montastruc, J. L., & Revet, A. (2016). Cardiovascular safety of methylphenidate should also be considered in adults. BMJ: British Medical Journal (Online), 353.
  10. 10.0 10.1 10.2 10.3 10.4 Leonard, B. E., McCartan, D., White, J., & King, D. J. (2004). Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects. Human Psychopharmacology: Clinical and Experimental, 19(3), 151-180. https://doi.org/10.1002/hup.579
  11. 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: McGraw-Hill Medical. p. 318. ISBN 9780071481274.
  12. Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  13. Methylphenidate poisoning: An evidence-based consensus guideline for out-of-hospital management (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18058301
  14. Characterization of Methylphenidate Exposures Reported to a Regional Poison Control Center | http://archpedi.jamanetwork.com/article.aspx?articleid=352627
  15. 2012 Annual Report of the American Association of Poison Control Centers ’ National Poison Data System (NPDS): 28th Annual Report | https://aapcc.s3.amazonaws.com/pdfs/annual_reports/2012_NPDS_Annual_Report.pdf
  16. Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/10511066
  17. Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high" (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9862747
  18. Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high" (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9862747
  19. Variables That Affect the Clinical Use and Abuse of Methylphenidate in the Treatment of ADHD | http://ajp.psychiatryonline.org/article.aspx?articleID=176483
  20. Methylphenidate Abuse and Psychiatric Side Effects (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC181133/
  21. Abuse and toxicity of methylphenidate | http://journals.lww.com/co-pediatrics/pages/articleviewer.aspx?year=2002&issue=04000&article=00013&type=abstract
  22. Methylphenidate Abuse and Psychiatric Side Effects | http://www.psychiatrist.com/PCC/article/Pages/2000/v02n05/v02n0502.aspx
  23. http://www.nejm.org/doi/full/10.1056/NEJM197204202861607
  24. Ritalin & Ritalin-SR Prescribing Information | http://www.pharma.us.novartis.com/product/pi/pdf/ritalin_ritalin-sr.pdf
  25. 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
  26. 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
  27. "Green List: Annex to the annual statistical report on psychotropic substances (form P)" (PDF). Archived from the original (PDF) on 31 August 2012. (1.63 MB) 23rd edition. August 2003. International Narcotics Board, Vienna International Centre. Retrieved 2 March 2006.
  28. Narkotikastrafflag (1968:64) | https://lagen.nu/1968:64
  29. Misuse of Drugs Act 1971 | http://www.legislation.gov.uk/ukpga/1971/38/schedule/2