Stimulant

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]



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Overview

Stimulants are drugs that temporarily increase alertness and awareness. They usually have increased side-effects with increased effectiveness, and the more powerful variants are therefore often prescription medicines or illegal drugs.

Function

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Stimulants increase the activity of either the sympathetic nervous system, the central nervous system (CNS) or both. Some stimulants produce a sense of euphoria, in particular the stimulants which exert influence on the CNS. Stimulants are used therapeutically to increase or maintain alertness, to counteract fatigue in situations where sleep is not practical (e.g. while operating vehicles), to counteract abnormal states that diminish alertness consciousness, (such as in narcolepsy), to promote weight loss (phentermine) as well as to enhance the ability to concentrate in people diagnosed with attentional disruptions (especially ADHD). Occasionally, they are also used to treat depression. Stimulants are sometimes used to boost endurance and productivity as well as to suppress appetite. The euphoria produced by some stimulants leads to their recreational use, although this is illegal in the majority of jurisdictions.

Caffeine, found in beverages such as[coffee and soft drinks, as well as nicotine, which is found in tobacco, are among some of the world's most commonly used stimulants.

Examples of other well known stimulants include ephedrine, amphetamines, cocaine, methylphenidate, MDMA, and modafinil. Stimulants are commonly referred in slang as "uppers".

Stimulants with significant abuse potential are very carefully controlled substances in America and most other jurisdictions. Some may be legally available only by prescription (e.g. methamphetamine, brand name Desoxyn, mixed amphetamine salts, brand name Adderall, dexamphetamine, brand name Dexedrine) or not at all (e.g. methcathinone).

Phenethylamines

Phenethylamine is an alkaloid and monoamine and believed to be a neuromodulator or neurotransmitter. Furthermore it is the basic chemical structure behind most stimulants, especially sympathomimetic amines. Common phenethylamines include:

Amphetamines

Amphetamines (prescribed as either racemic amphetamine or dextroamphetamine) increase the heart and respiration rates, increase blood pressure and in some users, dilate the pupils of the eyes and decrease appetite. Like NDRIs, amphetamine increases the levels of norepinephrine and dopamine in the brain via reuptake inhibition; however, the more important mechanism by which amphetamines cause stimulation is through the direct release of these catecholamines from storage vesicles in cells. Amphetamines are known to cause elevated mood and euphoria as well as rebound depression and anxiety. Other possible effects include blurred vision, insomnia, and dizziness.

Amphetamines are sometimes prescribed therapeutically by physicians and their availability makes them prime candidates for misuse [2]. Used properly, amphetamines increase alertness, concentration and physical endurance. They are often prescribed to counter the effects of narcolepsy, a disorder marked by episodes of uncontrollable sleep, and to help patients with learning disabilities such as ADD and ADHD. Dextrorotary methamphetamine is occasionally used in the treatment of AD(H)D that does not respond sufficiently to traditional amphetamines. On occasion, major depression is treated with amphetamines as well. Amphetamines can be used as an add-on to antidepressant therapy as well, with some success in certain populations.

Methylenedioxymethamphetamine

Methylenedioxymethamphetamine (MDMA) is a drug that comes either in tablet or capsule form (known as ecstasy, zoom, scrap), as a powder or crystal. Stimulant effects of MDMA include increased blood pressure and heart rate, loss of appetite, rapid sweating, and a dry mouth and throat. Ecstasy pills often contain amounts of other drugs which may include any of a wide range of substances such as MDA, MDEA, MBDB, PCP, DXM, Ketamine, Caffeine, Amphetamine, Methamphetamine, Ephedrine, Pseudoephedrine, Aspirin, Paracetamol, and, in a small number of cases, PMA [3], Cocaine [4], Fentanyl [5], mCPP, BZP+TFMPP, DOB [6], and 2C-B [7]. In some cases the substance sold as ecstasy may not contain MDMA at all.

MDMA was historically used in a therapeutic setting by a small number of psychiatrists for marriage counseling, before it was outlawed by the DEA because of its widespread recreational use. As of 2001, it is being considered by the FDA in the treatment of Post-traumatic stress disorder. It is also being evaluated for possible usages in palliative care [8].

Norepinephrine and Dopamine Reuptake Inhibitors (NDRIs)

These compounds inhibit the uptake of the monoamines dopamine and norepinephrine into storage vesicles, effectively increasing their amounts in the brain and causing a stimulating effect. Many of these compounds are effective ADHD medications and antidepressants. The most popular and well-known dopamine and norepinephrine reuptake inhibitor antidepressant is bupropion (Wellbutrin). Other examples of NDRIs include MDPV, ciclazindol, pyrovalerone, mazindol, pipradrol, and amfonelic acid. Although these medicines have similar methods of action to stimulants, they are less popular for abuse (thus not scheduled) and have an extended release mechanism or a very long half life. Many NDRIs are also phenethylamines.

Cocaine

Cocaine is made from the leaves of the coca shrub, which grows in the mountain regions of South American countries such as Bolivia, Colombia, and Peru. In Europe and North America, the most common form of cocaine is a white crystalline powder. Cocaine is a stimulant but is not normally prescribed therapeutically for its stimulant properties, although it sees clinical use as a local anesthetic, particularly in ophthalmology. Most cocaine use is recreational and its abuse potential is high, and so its sale and possession are strictly controlled in most jurisdictions.

Caffeine

Caffeine is a drug that is found naturally in coffee, tea, and to a small extent cocoa. It is also found in many soft drinks particularly energy drin]s. Caffeine stimulates the body, increasing heart rate and blood pressure, and alertness, making some people feel better and able to concentrate. Caffeine is also a diuretic. The vast majority (over 80%) of people in the United States consume caffeine on a daily basis. As a result, few jurisdictions restrict its sale and use.

Caffeine is also sold in some countries as an isolated drug (as opposed to its natural occurrence in many foods). It serves as a mild stimulant to ward off sleepiness and sees wide use among people who must remain alert in their work (e.g., truck drivers). Some medications contain caffeine as one of their minor active ingredients, often for the purpose of enhancing the effect of the main ingredient or reducing one of its side effects.

Nicotine

Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae), predominantly in tobacco, and in lower quantities in tomato, potato, eggplant (aubergine), and green pepper. Nicotine alkaloids are also found in the leaves of the coca plant. Nicotine constitutes 0.3 to 5% of the tobacco plant by dry weight, with biosynthesis taking place in the roots, and accumulates in the leaves. It is a potent nerve poison and is included in many insecticides. The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with its risks to health.

In very low concentrations, nicotine acts as a stimulant, and it is one of the main factors responsible for the dependence-forming properties of tobacco smoking. Although pure nicotine is noncarcinogenic, its presence may inhibit the body's ability to cull aberrant cells [9].

Ampakines

Recently, there have been improvements in the area of stimulant pharmacology, producing a class of chemicals known as Ampakines, or eugeroics, (good arousal). These stimulants tend to increase alertness without the peripheral (body) effects or addiction/tolerance/abuse potential of the traditional stimulants. They have minimal effect on sleep structure, and do not cause rebound hypersomnolence or "come down" effects. Currently, there are two stimulants in this class being used: modafinil and adrafinil, marketed as Provigil and Olmifon, respectively.

In Russia, Carphedon is sold as a general stimulant under the brand name Phenotropil.

See also

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