Methylphenidate

Methylphenidate
The skeletal formula of methylphenidate
Chemical Nomenclature
Common names	Concerta, Methylin, Ritalin, and Equasym XL
Substitutive name	Methylphenidate
Systematic name	methyl phenyl(piperidin-2-yl)acetate <-- Class Membership -->
Class Membership
Psychoactive class	Stimulant
Chemical class	Amphetamine
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. DISCLAIMER: PW's dosage information is a summary of data gathered from users and resources. It is NOT a recommendation and should be verified with other sources for accuracy. Threshold 5 - 10 mg Light 10 - 20 mg Common 20 - 30 mg Strong 30 - 40 mg Heavy 40+ mg Duration Total 4 - 6 hours Onset 15 - 30 minutes Peak 3 - 4 hours Afterglow 2 hours

Summary sheet: Methylphenidate

Methylphenidate (trade names Concerta, Methylin, Ritalin, Medikinet and Equasym XL) is a central stimulant drug and substituted phenethylamine approved for treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It is often used by students to enhance their mental abilities, improve their concentration, and help them study.

This substance 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, the drug only became heavily prescribed in the 1990s when the diagnosis of ADHD itself became more widely accepted.

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 R_α which is incorporated into a piperdine ring ending at the terminal amine of the phenethylamine chain. Additionally, it contains an methyl acetate bound to R₂ or its structure. Methylphenidate is structurally differed 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.

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. 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 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 has a corresponding effect on norepinephrine which is weaker than its effect 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.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of methylphenidate can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:

• Stimulation - In terms of its effects on the physical energy levels of the user, methylphenidate is usually considered 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 encourages 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
• Dehydration
• Appetite suppression
• Increased perspiration

Cognitive effects

The cognitive effects of methylphenidate can be broken down into several components which progressively intensify proportional to dosage. The general head space of methylphenidate is described by many as one of extreme mental stimulation, increased focus, and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.

The most prominent of these cognitive effects generally include:

• Euphoria - In comparison to other stimulants such as amphetamine, this effect is very mild and rare but occasionally occurs at higher dosages.
• Focus enhancement - This component is most effective at low to moderate dosages as anything higher will usually impair concentration.
• Wakefulness
• Memory enhancement - Therapeutic doses of methylphenidate improve performance on working memory tests both in normal functioning individuals and those with ADHD.
• Thought acceleration
• Analysis enhancement
• Motivation enhancement
• Anxiety
• Depression

Toxicity and harm potential

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

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. 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.

Tolerance and addiction potential

In terms of its tolerance, methyphenidate can be used multiple days in a row for extended periods of time and is often prescribed to be used in exactly this way. Acute tolerance does exist but builds up gradually over repeated extended use requiring an increase in dosage.

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. The primary source of methylphenidate for abuse is diversion from legitimate prescriptions rather than illicit synthesis. Those who use methylphenidate medicinally generally take it orally while intranasal and intravenous are the preferred means for recreational use.

Psychosis

Main article: Stimulant psychosis

Chronic abuse of methylphenidate can potentially lead to 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, grandiosity, paranoid delusions, confusion, increased aggression, and irritability.

Dangerous interactions

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

• 25x-NBOMe - Both the NBOMe series and methylphenidate induce powerful stimulation. Side effects such as thought loops, seizures, increased blood pressure, vasoconstriction, increased heart rate, and heart failure (in extreme cases) may occur.
• Alcohol - It is dangerous to combine alcohol, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of alcohol which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of alcohol will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
• DXM - This combination may cause increased heart rate and panic attacks (in extreme cases).
• MXE - Increased heart rate and blood pressure may occur.
• Tramadol - This combination can increase the risk of seizures.
• 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.
• Cocaine - This combination will increase strain on the heart.

Legal issues

• International: Methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.
• 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.
• 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.
• 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.
• 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.
• 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.

See also

• Responsible use
• Stimulants
• Amphetamine
• Methylphenidate (Wikipedia)
• Methylphenidate (Erowid)