Substance abuse methylphenidate

Slow-onset, long duration dopamine reuptake inhibitors with reduced potential for substance abuse have been suggested as therapies for psychostimulant addiction [33-35]. A series of slow-onset, long duration N-alkyl analogues of methylphenidate were recently reported to have enhanced selectivity for the dopamine transporter [34]. A representative compound is 13, an RR/SS diastereomer (DAT K, = 16nM, SERT K = 5900 nM, NET K-, = 840 nM). In a locomotor activity assay in mice, 13 has a slow onset of activity (20-30 min) with peak activity occurring between 90 and 120 min. In contrast, both methylphenidate and cocaine are active within 10 min and reach peak activity within 30 min. 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

Medications play an important part in the treatment of ADD. Stimulants are the mainstay of the treatment of ADD methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert). These differ in their half-lives, with Ritalin having the shortest and Cylert the longest. A warning has recently been issued about Cylert because of reports of sometimes fatal liver toxicity. Thus, it is recommended that it be used only if methylphenidate and dextroamphetamine are ineffective. There is individual variability in resporise, so that a person who does not respond to one may respond well to another. Other medications can also be effective in the treatment of ADD and may be useful, especially in residual ADD, where substance abuse may be an issue. These include tricyclic antidepressants (especially desipramine and imi-pramine) SSRIs, bupropion, venlafaxine, and clonidine. There are reports of antipsy-chotics and lithium being helpful in selected cases, as well. 

Methylphenidate and amphetamines have been used for ADHD management for many years but due to abuse potentials, these drugs are controlled substances." " Lisdexamfetamine itself is inactive and acts as a prodrug to dextroamphetamine upon cleavage of the lysine portion of the molecule. It was developed for the intention of creating a longer-lasting and more-difficult-to-abuse version of dextroamphetamine, as the requirement... 

The adverse effects associated with methylphenidate are generally mild and short-lived, with the most common effects being insomnia, decreased appetite, stomach ache, headache, and jitteriness. Although methylphenidate has been abused, the problem of abuse is generally seen in adults who use multiple substances or in adolescents experimenting with medications (28). Sweden withdrew methylphenidate from its market in 1968 because some adults dissolved tablets and injected the solution, leading to serious cases of talc granulomatosis (38). However, most cases of methylphenidate abuse apparently have led to less serious consequences (28). 

One of the most controversial CNS-acting drugs in contemporary society is methylphenidate (Ritalin ). This drug is structurally related to amphetamine and is a mild stimulant that has abuse potential similar to amphetamine. Methylphenidate is classified as a Schedule II controlled substance. It is effective in the treatment of narcolepsy and attention-deficit hyperactivity disorder (ADHD). Its use in ADHD has caused the greatest controversy. 

The treatment of narcolepsy with psychostimulants such as amphetamine 2 (Adderall), and methylphenidate 3 (Ritalin) has been reported.3 However, these are schedule 2 DEA-controlled substances and have a potential risk of abuse, overdose, and dependence, which present substantial barriers to widespread use.4 As a result, there has been a significant effort to identify novel therapeutic agents for the... 

Tablets of medication intended for oral use contain inert filler materials such as talc (magnesium silicate), corn starch, cotton fibers, and other refractile and nonrefractile substances. Long-term drug abusers are known to prepare a suspension of medication for injection by dissolving the crushed tablet of cocaine, heroin, methylphenidate, or other narcotic in water. They then boil the solution and filter it through a crude cigarette or cotton filter before injecting the solution intravenously, subcutaneously, or intramuscularly. The talc particles eventually embolize to the retinal circulation and produce a characteristic form of retinopathy.

Methylphenidate shares the pharmacological properties and the abuse potential of the amphetamines. When given intravenously, it activates psychotic symptoms in schizophrenic patients if administered during the active phase of their illness, but not after remission. It failed to produce a psychotic reaction in most manic or depressed patients or in healthy subjects (27). Adults with childhood-onset ADHD had an earlier onset of psychoactive substance use disorders, independent of any psychiatric co-morbidity (33). However, bipolar disorders conferred a significantly increased risk for early onset psychoactive substance use disorders independent of ADHD. The question arises as to the contribution of stimulant treatment to psychoactive substance use disorders. There were no differences in medicated versus unmedicated adolescents with ADHD in a review of eight outcome studies comprising 580 adolescents briefly treated with stimulants for six months to five years (34). 

Atomoxetine, a selective norepinephrine reuptake inhibitor, is the first nonstrmulant approved by the Food and Drug Administration (FDA) for the treatment of ADHD. In contrast to the stimulants, it has no apparent abuse potential and is not a controlled substance. Placebo-controlled, short-term trials (6 to 12 weeks) have shown that atomoxetine is effective in reducing ADHD symptoms in children, teens, and adults. It is not clear whether it is as effective as the stimulants, although one preliminary open study suggested comparable efficacy with methylphenidate. ... 

Methylphenidate also shares the abuse potential of the amphetamines and is listed as a schedule II controlled substance in the United States. Methylphenidate is effective in the treatment of narcolepsy and ADHD. 

In the United States, methylphenidate is classified as a controlled substance, with medical value but also a high potential for abuse. People abuse MPH by crushing the tablets and snorting them to produce the high. Ritalin has the same problem as cocaine or amphetamine in leading to possible addiction. As the number of children taking Ritalin has increased, it is at times over-prescribed to sedate problem schoolchildren to stop their disrupting class. 

The amphetamines with a primarily psychoanaleptic effect are mainly subject to the narcotics laws or are no longer on the market. Medicaments such as fenetyllin (the substance most abused by young people in the mid-1980s), amfetaminil and methylphenidate are no longer used in significant quantities. Prolintane, marketed as an antihypotonic until 1994, is still occasionally used. However, the likelihood of encountering any of these today is fairly remote. 

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