|Summary sheet: Methylphenidate|
|Common names||Methylphenidate, Concerta, Methylin, Ritalin, Equasym XL|
|Systematic name||Methyl 2-phenyl-2-piperidin-2-ylacetate|
|Routes of Administration|
Methylphenidate (also known as MPH, MPD, and the trade names Ritalin, Concerta, and Methylin, among others) is a classical stimulant substance of the phenidate class. It is the parent compound of the substituted phenidates, a family of stimulants that includes ethylphenidate, isopropylphenidate, and others. The mechanism of action involves increasing concentrations of the neurotransmitters dopamine and norepinephrine.
It was first synthesized in 1944 and was approved for medical use in the United States in 1955. It was originally sold by Swiss company CIBA (now Novartis). It is approved for treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It is often used by students with or without ADHD as a cognitive enhancer and study aid.
Subjective effects include stimulation, focus enhancement, motivation enhancement, increased libido, appetite suppression, and euphoria. It is usually taken orally, but can also be insufflated or administered rectally. The effects are comparable to those of amphetamine; however, it is reported to produce less euphoria and generally have less recreational value. Some users also report it produces a stronger comedown relative to amphetamine.
It has moderate abuse potential. Chronic use (i.e. high dose, repeat administration) is associated with compulsive redosing, escalating tolerance, and psychological dependence. It is highly advised to use harm reduction practices if using this substance.
History and culture
This History and culture section is a stub.
As a result, it may contain incomplete or wrong information. You can help by expanding it.
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.
It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012. In 2019, it was the 51st most commonly prescribed medication in the United States, with more than 14 million prescriptions. It is available as a generic medication.
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 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 Rβ of 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.
Four isomers of methylphenidate are possible, since the molecule has two chiral centers. One pair of threo isomers and one pair of erythro are distinguished, from which primarily d-threo-methylphenidate exhibits the pharmacologically desired effects.
The erythro diastereomers are pressor amines, a property not shared with the threo diastereomers. When the drug was first introduced it was sold as a 4:1 mixture of erythro:threo diastereomers, but it was later reformulated to contain only the threo diastereomers. "TMP" refers to a threo product that does not contain any erythro diastereomers, i.e. (±)-threo-methylphenidate. Since the threo isomers are energetically favored, it is easy to epimerize out any of the undesired erythro isomers.
The drug that contains only dextrorotatory methylphenidate is sometimes called d-TMP, although this name is only rarely used and it is much more commonly referred to as dexmethylphenidate, d-MPH, or d-threo-methylphenidate. A review on the synthesis of enantiomerically pure (2R,2'R)-(+)-threo-methylphenidate hydrochloride has been published.
Methylphenidate primarily acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It is most active at modulating levels of dopamine and, to a lesser extent, norepinephrine. Methylphenidate binds to and blocks dopamine transporters and norepinephrine transporters.
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.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Stimulation - Methylphenidate is usually reported to be energetic and stimulating in a fashion that is distinct but much weaker than that of amphetamine or methamphetamine and stronger than that of modafinil and caffeine. At lower to moderate doses, it encourages general productivity but at higher dosages it can encourage physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which methylphenidate presents can be described as forced. This means that at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general lack of motor control.
- Increased heart rate
- Abnormal heartbeat
- Frequent urination
- Dry mouth
- Appetite suppression
- Increased perspiration
- Nausea - May occur at higher doses, although tends to fade after a short period.
- Dizziness - May occur at higher doses, although tends to fade after a short period.
- Teeth grinding - Teeth grinding is present, but typically at higher doses and not to the same extent as other stimulants like amphetamine, or more severely, MDMA.
- Increased libido - Higher doses of methylphenidate can increase sexual desire, although this enhancement is reported to be less intense and reliable than amphetamines and cocaine.
- Pupil dilation
- Anxiety - Anxiety is reported with slightly more frequency than other common stimulants like amphetamine or cocaine.
- Cognitive euphoria - Compared to other stimulants such as amphetamine, this effect is mild but occasionally occurs at higher or non-orally administered doses .
- Ego inflation
- Emotion suppression - This is typically most intense at light and common doses, and is more commonly reported from medical usage rather than recreational.
- Derealisation - This effect is usually reaported at moderate/high doses.
- Focus enhancement - This component is most effective at low to moderate dosages as anything higher will usually impair concentration.
- Memory enhancement - Therapeutic doses of methylphenidate improve performance on working memory tests both in normal functioning individuals and those with ADHD.
- Time distortion - This can be described as the experience of time speeding up and passing much quicker than it usually would when sober.
- Thought acceleration
- Thought organization
- Analysis enhancement
- Motivation enhancement
- Suggestibility suppression
- Increased music appreciation - In comparison to other common stimulants such as amphetamine or cocaine, this effect is reported to be relatively mild or present only at higher doses.
- Compulsive redosing - Compulsive redosing is reported but with less frequency than other common stimulants such as amphetamine or cocaine, and typically at high or non-orally administered doses.
The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
- Cognitive fatigue
- Motivation suppression
- Increased heart rate
- Thought deceleration
Anecdotal reports which describe the effects of this compound within our experience index include:
- Experience: Ritalin 110mg (oral)
- Experience:Methylphenidate (45mg, Insufflated) - Phenomenal Focus Aid
- Experience:Methylphenidate (Insufflated) - Clear Headed Stimulation
- Experience:Pregabalin (450mg, oral) + Methylphenidate (20mg, oral) - Gaba Flipping
Additional experience reports can be found here:
Toxicity and harm potential
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
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. 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. 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.
It is strongly advised to use harm reduction practices if using this substance.
Dependence and abuse 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.
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). Methylphenidate presents cross-tolerance with all dopaminergic stimulants, meaning that after the consumption of methyphenidate all stimulants will have a reduced effect."
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. The abuse and addiction potential of methylphenidate is therefore significantly lower than other dopaminergic stimulants.
The abuse potential is increased when methylphenidate is crushed and insufflated (snorted) or injected.. It should be noted that due to the fillers in the pill, however, that this can be harmful to the nasal cavities, and intravenous use can cause emphysema (a lower respiratory tract disease, aka ritalin lung when caused by Ritalin tablets). The intravenous use of methylphenidate, commonly marketed as Ritalin and widely used as a stimulant drug in the treatment of attention deficit hyperactivity disorder, can lead to emphysematous changes known as Ritalin lung.
. 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.
Chronic use (i.e. high dose, repeat dosing) may increase the risk of psychosis. 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.
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.
Combination with alcohol
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%. A metabolite called ethylphenidate is also formed.
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with Methylphenidate should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
- Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
- MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
- MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
- Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
- Stimulants - Methylphenidate may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
- Tramadol - Tramadol is known to lower the seizure threshold and combinations with stimulants may further increase this risk.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.
Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.
- 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).
- Canada: Methylphenidate is listed in Schedule III of the Controlled Drugs and Substances Act (along with LSD, psychedelic mushrooms, and mescaline). 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.
- 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.
- Switzerland: Methylphenidate is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
- Turkey: Methylphenidate is a 'red prescription' only substance and illegal when sold or possessed without a prescription.
- 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.
- 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.
It is a widespread myth that methylphenidate could lead to false-positives for amphetamine in drug screenings. However, there was found no immunoassay cross reactivity in laboratory study.
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