Methylphenidate

Methylphenidate
Chemical Nomenclature
Common names	Methylphenidate, Concerta, Methylin, Ritalin, Equasym XL
Substitutive name	Methylphenidate
Systematic name	Methyl 2-phenyl-2-piperidin-2-ylacetate
Class Membership
Psychoactive class	Stimulant
Chemical class	Phenidate
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 Bioavailability 11-52%[1] Threshold 5 mg Light 10 - 20 mg Common 20 - 40 mg Strong 40 - 60 mg Heavy 60 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 mg Light 10 - 15 mg Common 15 - 30 mg Strong 30 - 60 mg Heavy 60 mg + Duration Total 2 - 4 hours Onset 5 - 20 minutes Come up 15 - 40 minutes Peak 30 - 45 minutes Offset 2 - 4 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.
Interactions
Alcohol
DXM
MXE
MDMA
Stimulants
25x-NBOMe
25x-NBOH
Tramadol
MAOIs

Methylphenidate (also known as MPH, MPD, and its brand names Ritalin, Concerta, and Methylin, among others) is stimulant substance of the phenidate class. Methylphenidate is the parent compound of the substituted phenidates, a family of compounds that includes ethylphenidate, isopropylphenidate, and others. It acts primarily by enhancing the activity of the neurotransmitters dopamine and norepinephrine in the brain.

Methylphenidate was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating what was then known as "hyperactivity." Although it was prescribed to patients as early as 1960, it only became heavily prescribed in the 1990s when the diagnosis of ADHD itself became more widely accepted.^[2][3]

Methylphenidate is 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.

Chemistry

Methylphenidate is a synthetic molecule of the substituted phenethylamine and substituted phenidate classes. 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 R_α which is incorporated into a piperidine ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains a methyl acetate bound to R_β or its structure.

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.

Dexmethylphenidate in skeletal formula

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.^[4] Methylphenidate binds to and blocks dopamine transporters and norepinephrine transporters.^[5]

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.^[6][7][8][9]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses are more likely to induce the full spectrum of effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

• Experience:Methylphenidate (45mg, Insufflated) - Phenomenal Focus Aid

Additional experience reports can be found here:

• Erowid Experience Vaults: Methylphenidate

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of methylphenidate^[13]

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.^[14] 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.^[15] 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.^[16]

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.^[17] 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.^[18] The abuse and addiction potential of methylphenidate is therefore significantly lower than other dopaminergic stimulants.^[19][20]

The abuse potential is increased when methylphenidate is crushed and insufflated (snorted) or injected.^[21]. 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.^[22]

Psychosis

Chronic abuse of methylphenidate can potentially lead to psychosis.^[23][24] 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.^[25] 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.

Alcohol & Methylphenidate

Methylphenidate (when taken orally) has a low bioavailability around 30%. If taken with alcohol (ethanol), blood plasma levels of dexmethylphenidate are increased by up to 40%.^[26] A metabolite called ethylphenidate is also formed.^[27]

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

• 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 handled with extreme care due to DXM's effects on serotonin and norepinephrine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome with stimulants that increase levels of serotonin (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
• MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants. There is also a risk of excessive heart strain.
• MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.
• Stimulants - Methylphenidate can be potentially dangerous in combination with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
• Tramadol - Tramadol lowers the seizure threshold.^[28] 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, and some antidepressants.^[29]

Legal status

Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.^[30]

• 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.^[31]
• 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).^[32] It 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.
• Germany: Methylphenidate is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.^[33]
• 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.^{[citation needed]}
• 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.^[34]
• Switzerland: Methylphenidate is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.^[35]
• Turkey: Methylphenidate is a 'red prescription' only substance^[36] and illegal when sold or possessed without a prescription.^{[citation needed]}
• 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.^[37]
• 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.^{[citation needed]}

It is a widespread myth that methylphenidate could lead to false-positives for amphetamin in drug screenings. However, there was found no immunoassay cross reactivity in laboratory study.^[38]

See also

• Responsible use
• Stimulants
• Amphetamine

External links

• Methylphenidate (Wikipedia)
• Methylphenidate (Erowid Vault)
• Methylphenidate (Isomer Design)

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