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Stimulant

Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription (either legally or illicitly) as performance-enhancing or recreational drugs. Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate (Ritalin), and amphetamine. It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including amphetamine and methamphetamine) the value was 0.7%, and for Ecstasy 0.4%.

Acute

Stimulants in therapeutic doses, such as those given to patients with ADHD, increases ability to focus, vigor, sociability, libido and may elevate mood. However, in higher doses stimulants may actually decrease the ability to focus, a principle of the Yerkes-Dodson Law. In higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects. Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while cocaine has the opposite effect. Neurocognitive enhancing effects of stimulants, specifically modafinil, amphetamine and methylphenidate have been documented in healthy adolescents, and is a commonly cited reason among illicit drug users for use, particularly among college students in the context of studying.

In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, and suicidal ideation. Acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia. Most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to effects such as mydriasis, increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, and may lead to rhabdomyolysis, stroke, cardiac arrest, or seizures. However, given the complexity of the mechanisms that underlie these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal.

Chronic

Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, but found a correlation between prescription stimulant use and ischemic heart attacks. A review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer-term studies. A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, and appears to be relatively safe.

Abuse of prescription stimulants (not following physician instruction) or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of cardiorespiratory disease, stroke, and sepsis. Some effects are dependent upon the route of administration, with intravenous use associated with the transmission of many disease such as Hepatitis C, HIV/AIDS and potential medical emergencies such as infection, thrombosis or pseudoaneurysm, while inhalation may be associated with increased lower respiratory tract infection, lung cancer, and pathological restricting of lung tissue. Cocaine may also increase risk for autoimmune disease and damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, resulting in an increased risk for Parkinson's disease.

Stimulants have been used in medicine for many conditions including obesity, sleep disorders, mood disorders, impulse control disorders, asthma, nasal congestion and, in case of cocaine, as local anesthetics. Drugs used to treat obesity are called anorectics and generally include drugs that follow the general definition of a stimulant, but other drugs such as cannabinoid receptor antagonists also belong to this group. Eugeroics are used in management of sleep disorders characterized by excessive daytime sleepiness, such as narcolepsy, and include stimulants such as modafinil. Stimulants are used in impulse control disorders such as ADHD and off-label in mood disorders such as major depressive disorder to increase energy, focus and elevate mood. Stimulants such as epinephrine, theophylline and salbutamol orally have been used to treat asthma, but inhaled adrenergic drugs are now preferred due to less systemic side effects. Pseudoephedrine is used to relieve nasal or sinus congestion caused by the common cold, sinusitis, hay fever and other respiratory allergies; it is also used to relieve ear congestion caused by ear inflammation or infection.

For details on stimulant classes, see Substituted phenethylamine and Substituted amphetamine.
A chart comparing the chemical structures of different amphetamine derivatives

Classifying stimulants is difficult, because of the large number of classes the drugs occupy, and the fact that they may belong to multiple classes; for example, ecstasy can be classified as a substituted methylenedioxyphenethylamine, a substituted amphetamine and consequently, a substituted phenethylamine.[citation needed]

When referring to stimulants, the parent drug (e.g., amphetamine) will always be expressed in the singular[according to whom?]; with the word "substituted" placed before the parent drug (substituted amphetamines).

Major stimulant classes include phenethylamines and their daughter class substituted amphetamines.[according to whom?]

Amphetamines (class)

Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, bupropion, methoxyphenamine, selegiline, amfepramone, pyrovalerone, MDMA (ecstasy), and DOM (STP). Many drugs in this class work primarily by activating trace amine-associated receptor 1 (TAAR1); in turn, this causes reuptake inhibition and effluxion, or release, of dopamine, norepinephrine, and serotonin. An additional mechanism of some substituted amphetamines is the release of vesicular stores of monoamine neurotransmitters through VMAT2, thereby increasing the concentration of these neurotransmitters in the cytosol, or intracellular fluid, of the presynaptic neuron.

Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat major depression, where subjects do not respond well to traditional SSRI medications,[citation needed] but evidence supporting this use is poor/mixed. Notably, two recent large phase III studies of lisdexamfetamine (a prodrug to amphetamine) as an adjunct to an SSRI or SNRI in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness. Numerous studies have demonstrated the effectiveness of drugs such as Adderall (a mixture of salts of amphetamine and dextroamphetamine) in controlling symptoms associated with ADHD. Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse.

Cocaine analogues

Hundreds of cocaine analogues have been created, all of them usually maintaining a benzyloxy connected to the 3 carbon of a tropane. Various modifications include substitutions on the benzene ring, as well as additions or substitutions in place of the normal carboxylate on the tropane 2 carbon. Various compound with similar structure activity relationships to cocaine that aren't technically analogues have been developed as well.

Most stimulants exert their activating effects by enhancing catecholamine neurotransmission. Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention, arousal, motivation, task salience and reward anticipation. Classical stimulants either block the reuptake or stimulate the efflux of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with empathogenic and hallucinogenic effects, also affect serotonergic transmission. Some stimulants, such as some amphetamine derivatives and, notably, yohimbine, can decrease negative feedback by antagonizing regulatory autoreceptors. Adrenergic agonists, such as, in part, ephedrine, act by directly binding to and activating adrenergic receptors, producing sympathomimetic effects.

There are also more indirect mechanisms a drug can elicit activating effects. Caffeine is an adenosine receptor antagonist, and only indirectly increases catecholamine transmission in the brain. Pitolisant is an H3-receptor inverse agonist. As H3 receptors mainly act as autoreceptors, pitolisant decreases negative feedback to histaminergic neurons, enhancing histaminergic transmission.

Amphetamine

Main article: Amphetamine

Amphetamine is a potent central nervous system (CNS) stimulant of the phenethylamine class that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Amphetamine is also used off-label as a performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. Although it is a prescription medication in many countries, unauthorized possession and distribution of amphetamine is often tightly controlled due to the significant health risks associated with uncontrolled or heavy use. As a consequence, amphetamine is illegally manufactured in clandestine labs to be trafficked and sold to users. Based upon drug and drug precursor seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.

The first pharmaceutical amphetamine was Benzedrine, a brand of inhalers used to treat a variety of conditions. Because the dextrorotary isomer has greater stimulant properties, Benzedrine was gradually discontinued in favor of formulations containing all or mostly dextroamphetamine. Presently, it is typically prescribed as mixed amphetamine salts, dextroamphetamine, and lisdexamfetamine.

Amphetamine is a norepinephrine-dopamine releasing agent (NDRA). It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2. At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved cognitive control. Likewise, it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength. In contrast, supratherapeutic doses of amphetamine are likely to impair cognitive function and induce rapid muscle breakdown. Very high doses can result in psychosis (e.g., delusions and paranoia), which very rarely occurs at therapeutic doses even during long-term use. As recreational doses are generally much larger than prescribed therapeutic doses, recreational use carries a far greater risk of serious side effects, such as dependence, which only rarely arises with therapeutic amphetamine use.

Caffeine

Main article: Caffeine
Roasted coffee beans, a common source of caffeine.

Caffeine is a stimulant compound belonging to the xanthine class of chemicals naturally found in coffee, tea, and (to a lesser degree) cocoa or chocolate. It is included in many soft drinks, as well as a larger amount in energy drinks. Caffeine is the world's most widely used psychoactive drug and by far the most common stimulant. In North America, 90% of adults consume caffeine daily. A few jurisdictions restrict its sale and use.[citation needed] Caffeine is also included in some medications, usually for the purpose of enhancing the effect of the primary ingredient, or reducing one of its side-effects (especially drowsiness). Tablets containing standardized doses of caffeine are also widely available.

Caffeine's mechanism of action differs from many stimulants, as it produces stimulant effects by inhibiting adenosine receptors. Adenosine receptors are thought to be a large driver of drowsiness and sleep, and their action increases with extended wakefulness. Caffeine has been found to increase striatal dopamine in animal models, as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors, however the implications for humans are unknown. Unlike most stimulants, caffeine has no addictive potential. Caffeine does not appear to be a reinforcing stimulus, and some degree of aversion may actually occur, which people preferring placebo over caffeine in a study on drug abuse liability published in an NIDA research monograph. In large telephone surveys only 11% reported dependence symptoms. However, when people were tested in labs, only half of those who claim dependence actually experienced it, casting doubt on caffeine's ability to produce dependence and putting societal pressures in the spotlight.

Coffee consumption is associated with a lower overall risk of cancer. This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer, but it may also have a modest effect on colorectal cancer. There does not appear to be a significant protective effect against other types of cancers, and heavy coffee consumption may increase the risk of bladder cancer. A protective effect of caffeine against Alzheimer's disease is possible, but the evidence is inconclusive. Moderate coffee consumption may decrease the risk of cardiovascular disease, and it may somewhat reduce the risk of type 2 diabetes. Drinking 1-3 cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee. However those who drink 2–4 cups per day may be at a slightly increased risk. Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals. It may protect people from liver cirrhosis. There is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat headaches. Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude.

Ephedrine

Main article: Ephedrine

Ephedrine is a sympathomimetic amine similar in molecular structure to the well-known drugs phenylpropanolamine and methamphetamine, as well as to the important neurotransmitter epinephrine (adrenaline). Ephedrine is commonly used as a stimulant, appetite suppressant, concentration aid, and decongestant, and to treat hypotension associated with anaesthesia.

In chemical terms, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae). It works mainly by increasing the activity of norepinephrine (noradrenaline) on adrenergic receptors. It is most usually marketed as the hydrochloride or sulfate salt.

The herb má huáng (Ephedra sinica), used in traditional Chinese medicine (TCM), contains ephedrine and pseudoephedrine as its principal active constituents. The same may be true of other herbal products containing extracts from other Ephedra species.

MDMA

Tablets containing MDMA
Main article: MDMA
See also: Its parent class and MDA

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly) is a euphoriant, empathogen, and stimulant of the amphetamine class. Briefly used by some psychotherapists as an adjunct to therapy, the drug became popular recreationally and the DEA listed MDMA as a Schedule I controlled substance, prohibiting most medical studies and applications. MDMA is known for its entactogenic properties. The stimulant effects of MDMA include hypertension, anorexia (appetite loss), euphoria, social disinhibition, insomnia (enhanced wakefulness/inability to sleep), improved energy, increased arousal, and increased perspiration, among others. Relative to catecholaminergic transmission, MDMA enhances serotonergic transmission significantly more, when compared to classical stimulants like amphetamine. MDMA does not appear to be significantly addictive or dependence forming.

Due to the relative safety of MDMA, some researchers such as David Nutt have criticized the scheduling level, writing a satirical article finding MDMA to be 28 times less dangerous than horseriding, a condition he termed "equasy" or "Equine Addiction Syndrome".

MDPV

Main article: MDPV

Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a designer drug. Products labeled as bath salts containing MDPV were previously sold as recreational drugs in gas stations and convenience stores in the United States, similar to the marketing for Spice and K2 as incense.

Incidents of psychological and physical harm have been attributed to MDPV use.

Mephedrone

Main article: Mephedrone

Mephedrone is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone and MCAT. It is reported to be manufactured in China and is chemically similar to the cathinone compounds found in the khat plant of eastern Africa. It comes in the form of tablets or a powder, which users can swallow, snort, or inject, producing similar effects to MDMA, amphetamines, and cocaine.

Mephedrone was first synthesized in 1929, but did not become widely known until it was rediscovered in 2003. By 2007, mephedrone was reported to be available for sale on the Internet; by 2008 law enforcement agencies had become aware of the compound; and, by 2010, it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom. Mephedrone was first made illegal in Israel in 2008, followed by Sweden later that year. In 2010, it was made illegal in many European countries, and, in December 2010, the EU ruled it illegal. In Australia, New Zealand, and the US, it is considered an analog of other illegal drugs and can be controlled by laws similar to the Federal Analog Act. In September 2011, the USA temporarily classified mephedrone as illegal, in effect from October 2011.

Methamphetamine

Main article: Methamphetamine

Methamphetamine (contracted fromN-methyl-alpha-methylphenethylamine) is a potent psychostimulant of the phenethylamine and amphetamine classes that is used to treat attention deficit hyperactivity disorder (ADHD) and obesity. Methamphetamine exists as two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine; however, both are addictive and produce the same toxicity symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name Desoxyn. Recreationally, methamphetamine is used to increase sexual desire, lift the mood, and increase energy, allowing some users to engage in sexual activity continuously for several days straight.

Methamphetamine may be sold illicitly, either as pure dextromethamphetamine or in an equal parts mixture of the right- and left-handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in the United States. Also, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In contrast, levomethamphetamine is an over-the-counter drug in the United States.

In low doses, methamphetamine can cause an elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis, rhabdomyolysis, and cerebral hemorrhage. Methamphetamine is known to have a high potential for abuse and addiction. Recreational use of methamphetamine may result in psychosis or lead to post-withdrawal syndrome, a withdrawal syndrome that can persist for months beyond the typical withdrawal period. Unlike amphetamine and cocaine, methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the central nervous system (CNS). Unlike the long-term use of amphetamine in prescription doses, which may improve certain brain regions in individuals with ADHD, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity. However, recreational amphetamine doses may also be neurotoxic.

Methylphenidate

Main article: Methylphenidate

Methylphenidate is a stimulant drug that is often used in the treatment of ADHD and narcolepsy and occasionally to treat obesity in combination with diet restraints and exercise. Its effects at therapeutic doses include increased focus, increased alertness, decreased appetite, decreased need for sleep and decreased impulsivity. Methylphenidate is not usually used recreationally, but when it is used, its effects are very similar to those of amphetamines.

Methylphenidate acts as a norepinephrine-dopamine reuptake inhibitor, by blocking the norepinephrine transporter (NET) and the dopamine transporter (DAT). Methylphenidate has a higher affinity for the dopamine transporter than for the norepinephrine transporter, and so its effects are mainly due to elevated dopamine levels caused by the inhibited reuptake of dopamine, however increased norepinephrine levels also contribute to various of the effects caused by the drug.

Methylphenidate is sold under a number of brand names including Ritalin. Other versions include the long lasting tablet Concerta and the long lasting transdermal patch Daytrana.

Cocaine

Lines of illicit cocaine, used as a recreational stimulant
Main article: Cocaine

Cocaine is an SNDRI. 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, regions in which it was cultivated and used for centuries mainly by the Aymara people. In Europe, North America, and some parts of Asia, 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, in particular in ophthalmology. Most cocaine use is recreational and its abuse potential is high (higher than amphetamine), and so its sale and possession are strictly controlled in most jurisdictions. Other tropane derivative drugs related to cocaine are also known such as troparil and lometopane but have not been widely sold or used recreationally.

Nicotine

Main article: Nicotine

Nicotine is the active chemical constituent in tobacco, which is available in many forms, including cigarettes, cigars, chewing tobacco, and smoking cessation aids such as nicotine patches, nicotine gum, and electronic cigarettes. Nicotine is used widely throughout the world for its stimulating and relaxing effects. Nicotine exerts its effects through the agonism of nicotinic acetylcholine receptor, resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain reward system, and acetaldehyde one of the tobacco constituent decreased the expression of monoamine oxidase in the brain. Nicotine is addictive and dependence forming. Tobacco, the most common source of nicotine, has an overall harm to user and self score 3 percent below cocaine, and 13 percent above amphetamines, ranking 6th most harmful of the 20 drugs assessed, as determined by a multi-criteria decision analysis.

Phenylpropanolamine

Main article: Phenylpropanolamine

Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes that is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs under trade names Propalin and Proin.

In the United States, PPA is no longer sold without a prescription due to a proposed increased risk of stroke in younger women. In a few countries in Europe, however, it is still available either by prescription or sometimes over-the-counter. In Canada, it was withdrawn from the market on 31 May 2001. In India, human use of PPA and its formulations were banned on 10 February 2011.

Propylhexedrine

Main article: Propylhexedrine

Propylhexedrine (Hexahydromethamphetamine, Obesin) is a stimulant medication, sold over-the-counter in the United States as the cold medication Benzedrex. The drug has also been used as an appetite suppressant in Europe. Propylhexedrine is not an amphetamine, though it is structurally similar; it is instead a cycloalkylamine, and thus has stimulant effects that are less potent than similarly structured amphetamines, such as methamphetamine.

The abuse potential of propylhexedrine is fairly limited, due its limited routes of administration: in the United States, Benzedrex is only available as an inhalant, mixed with lavender oil and menthol. These ingredients cause unpleasant tastes, and abusers of the drug have reported unpleasant "menthol burps". Injection of the drug has been found to cause transient diplopia and brain stem dysfunction.

Pseudoephedrine

Main article: Pseudoephedrine

Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent.

The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations, either as a single ingredient or (more commonly) in combination with antihistamines, guaifenesin, dextromethorphan, and/or paracetamol (acetaminophen) or another NSAID (such as aspirin or ibuprofen). It is also used as a precursor chemical in the illegal production of methamphetamine.

Catha edulis (Khat)

Main article: Khat
Catha edulis

Khat is a flowering plant native to the Horn of Africa and the Arabian Peninsula.

Khat contains a monoamine alkaloid called cathinone, a "keto-amphetamine", that is said to cause excitement, loss of appetite, and euphoria. In 1980, the World Health Organization (WHO) classified it as a drug of abuse that can produce mild to moderate psychological dependence (less than tobacco or alcohol), although the WHO does not consider khat to be seriously addictive. It is banned in some countries, such as the United States, Canada, and Germany, while its production, sale, and consumption are legal in other nations, including Djibouti, Ethiopia, Somalia, and Yemen.

Modafinil

Modafinil, sold under the brand name Provigil among others, is a CNS stimulant used to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea. While it has seen off-label use as a purported cognitive enhancer, the research on its effectiveness for this use is not conclusive.

See also: Substance abuse

Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep. Use of stimulants may cause the body to reduce significantly its production of natural body chemicals that fulfill similar functions. Until the body reestablishes its normal state, once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and miserable. This is referred to as a "crash", and may provoke reuse of the stimulant.

Abuse of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to medical, psychiatric, and psychosocial deterioration. Drug tolerance, dependence, and sensitization as well as a withdrawal syndrome can occur. Stimulants may be screened for in animal discrimination and self-administration models which have high sensitivity albeit low specificity. Research on a progressive ratio Self-administration protocol has found amphetamine, methylphenidate, modafinil, cocaine, and nicotine to all have a higher break point than placebo that scales with dose indicating reinforcing effects.

Drug Mean Pleasure Psychological dependence Physical dependence.
Methamphetamine 5.53 6.0 7.0 3.0
Cocaine 2.39 3.0 2.8 1.3
Tobacco 2.21 2.3 2.6 1.8
Amphetamine 1.67 2.0 1.9 1.1
Ecstasy 1.13 1.5 1.2 0.7

Psychosocial treatments, such as contingency management, have demonstrated improved effectiveness when added to treatment as usual consisting of counselling and/or case-management. This is demonstrated with a decrease in dropout rates and a lengthening of periods of abstinence.

The presence of stimulants in the body may be tested by a variety of procedures. Serum and urine are the common sources of testing material although saliva is sometimes used. Commonly used tests include chromatography, immunologic assay, and mass spectrometry.

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Look up stimulant or upper in Wiktionary, the free dictionary.

Stimulant
Stimulant Language Watch Edit Stimulants also often referred to as psychostimulants or colloquially as uppers is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body 1 drugs that are pleasurable and invigorating or drugs that have sympathomimetic effects 2 Stimulants are widely used throughout the world as prescription medicines as well as without a prescription either legally or illicitly as performance enhancing or recreational drugs Among narcotics stimulants produce a noticeable crash or comedown at the end of their effects The most frequently prescribed stimulants as of 2013 were lisdexamfetamine methylphenidate Ritalin and amphetamine 3 It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0 4 For the category amphetamines and prescription stimulants with amphetamines including amphetamine and methamphetamine the value was 0 7 and for Ecstasy 0 4 4 Ritalin 20 mg sustained release SR tablets Contents 1 Effects 1 1 Acute 1 2 Chronic 2 Medical uses 3 Chemistry 3 1 Amphetamines class 3 2 Cocaine analogues 4 Mechanisms of action 5 Notable stimulants 5 1 Amphetamine 5 2 Caffeine 5 3 Ephedrine 5 4 MDMA 5 5 MDPV 5 6 Mephedrone 5 7 Methamphetamine 5 8 Methylphenidate 5 9 Cocaine 5 10 Nicotine 5 11 Phenylpropanolamine 5 12 Propylhexedrine 5 13 Pseudoephedrine 5 14 Catha edulis Khat 5 15 Modafinil 6 Recreational use and issues of abuse 7 Treatment for misuse 8 Testing 9 See also 10 Notes 11 References 12 External linksEffects EditAcute Edit Stimulants in therapeutic doses such as those given to patients with ADHD increases ability to focus vigor sociability libido and may elevate mood However in higher doses stimulants may actually decrease the ability to focus a principle of the Yerkes Dodson Law In higher doses stimulants may also produce euphoria vigor and decrease need for sleep Many but not all stimulants have ergogenic effects Drugs such as ephedrine pseudoephedrine amphetamine and methylphenidate have well documented ergogenic effects while cocaine has the opposite effect 5 Neurocognitive enhancing effects of stimulants specifically modafinil amphetamine and methylphenidate have been documented in healthy adolescents and is a commonly cited reason among illicit drug users for use particularly among college students in the context of studying 6 In some cases psychiatric phenomenon may emerge such as stimulant psychosis paranoia and suicidal ideation Acute toxicity has been reportedly associated with a homicide paranoia aggressive behavior motor dysfunction and punding The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia 7 Most drugs classified as stimulants are sympathomimetics that is they stimulate the sympathetic branch of the autonomic nervous system This leads to effects such as mydriasis increased heart rate blood pressure respiratory rate and body temperature 8 When these changes become pathological they are called arrhythmia hypertension and hyperthermia and may lead to rhabdomyolysis stroke cardiac arrest or seizures However given the complexity of the mechanisms that underlie these potentially fatal outcomes of acute stimulant toxicity it is impossible to determine what dose may be lethal 9 Chronic Edit Assessment of the effects of stimulants is relevant given the large population currently taking stimulants A systematic review of cardiovascular effects of prescription stimulants found no association in children but found a correlation between prescription stimulant use and ischemic heart attacks 10 A review over a four year period found that there were few negative effects of stimulant treatment but stressed the need for longer term studies 11 A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only 12 Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning and appears to be relatively safe 13 Abuse of prescription stimulants not following physician instruction or of illicit stimulants carries many negative health risks Abuse of cocaine depending upon route of administration increases risk of cardiorespiratory disease stroke and sepsis 14 Some effects are dependent upon the route of administration with intravenous use associated with the transmission of many disease such as Hepatitis C HIV AIDS and potential medical emergencies such as infection thrombosis or pseudoaneurysm 15 while inhalation may be associated with increased lower respiratory tract infection lung cancer and pathological restricting of lung tissue 16 Cocaine may also increase risk for autoimmune disease 17 18 19 and damage nasal cartilage Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons resulting in an increased risk for Parkinson s disease 20 21 22 23 Medical uses EditStimulants have been used in medicine for many conditions including obesity sleep disorders mood disorders impulse control disorders asthma nasal congestion and in case of cocaine as local anesthetics 24 Drugs used to treat obesity are called anorectics and generally include drugs that follow the general definition of a stimulant but other drugs such as cannabinoid receptor antagonists also belong to this group 25 26 Eugeroics are used in management of sleep disorders characterized by excessive daytime sleepiness such as narcolepsy and include stimulants such as modafinil 27 28 Stimulants are used in impulse control disorders such as ADHD 29 and off label in mood disorders such as major depressive disorder to increase energy focus and elevate mood 30 Stimulants such as epinephrine 31 theophylline and salbutamol 32 orally have been used to treat asthma but inhaled adrenergic drugs are now preferred due to less systemic side effects Pseudoephedrine is used to relieve nasal or sinus congestion caused by the common cold sinusitis hay fever and other respiratory allergies it is also used to relieve ear congestion caused by ear inflammation or infection 33 34 Chemistry EditFor details on stimulant classes see Substituted phenethylamine and Substituted amphetamine A chart comparing the chemical structures of different amphetamine derivatives Classifying stimulants is difficult because of the large number of classes the drugs occupy and the fact that they may belong to multiple classes for example ecstasy can be classified as a substituted methylenedioxyphenethylamine a substituted amphetamine and consequently a substituted phenethylamine citation needed When referring to stimulants the parent drug e g amphetamine will always be expressed in the singular according to whom with the word substituted placed before the parent drug substituted amphetamines Major stimulant classes include phenethylamines and their daughter class substituted amphetamines according to whom Amphetamines class Edit Main article Substituted amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure 35 it includes all derivative compounds which are formed by replacing or substituting one or more hydrogen atoms in the amphetamine core structure with substituents 35 36 37 Examples of substituted amphetamines are amphetamine itself 35 36 methamphetamine 35 ephedrine 35 cathinone 35 phentermine 35 mephentermine 35 bupropion 35 methoxyphenamine 35 selegiline 35 amfepramone 35 pyrovalerone 35 MDMA ecstasy and DOM STP Many drugs in this class work primarily by activating trace amine associated receptor 1 TAAR1 38 in turn this causes reuptake inhibition and effluxion or release of dopamine norepinephrine and serotonin 38 An additional mechanism of some substituted amphetamines is the release of vesicular stores of monoamine neurotransmitters through VMAT2 thereby increasing the concentration of these neurotransmitters in the cytosol or intracellular fluid of the presynaptic neuron 39 Amphetamines type stimulants are often used for their therapeutic effects Physicians sometimes prescribe amphetamine to treat major depression where subjects do not respond well to traditional SSRI medications citation needed but evidence supporting this use is poor mixed 40 Notably two recent large phase III studies of lisdexamfetamine a prodrug to amphetamine as an adjunct to an SSRI or SNRI in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness 41 Numerous studies have demonstrated the effectiveness of drugs such as Adderall a mixture of salts of amphetamine and dextroamphetamine in controlling symptoms associated with ADHD Due to their availability and fast acting effects substituted amphetamines are prime candidates for abuse 42 Cocaine analogues Edit Main article List of cocaine analogues Hundreds of cocaine analogues have been created all of them usually maintaining a benzyloxy connected to the 3 carbon of a tropane Various modifications include substitutions on the benzene ring as well as additions or substitutions in place of the normal carboxylate on the tropane 2 carbon Various compound with similar structure activity relationships to cocaine that aren t technically analogues have been developed as well Mechanisms of action EditMost stimulants exert their activating effects by enhancing catecholamine neurotransmission Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention arousal motivation task salience and reward anticipation Classical stimulants either block the reuptake or stimulate the efflux of these catecholamines resulting in increased activity of their circuits Some stimulants specifically those with empathogenic and hallucinogenic effects also affect serotonergic transmission Some stimulants such as some amphetamine derivatives and notably yohimbine can decrease negative feedback by antagonizing regulatory autoreceptors 43 Adrenergic agonists such as in part ephedrine act by directly binding to and activating adrenergic receptors producing sympathomimetic effects There are also more indirect mechanisms a drug can elicit activating effects Caffeine is an adenosine receptor antagonist and only indirectly increases catecholamine transmission in the brain 44 Pitolisant is an H3 receptor inverse agonist As H3 receptors mainly act as autoreceptors pitolisant decreases negative feedback to histaminergic neurons enhancing histaminergic transmission Notable stimulants EditAmphetamine Edit Main article Amphetamine Amphetamine is a potent central nervous system CNS stimulant of the phenethylamine class that is approved for the treatment of attention deficit hyperactivity disorder ADHD and narcolepsy 45 Amphetamine is also used off label as a performance and cognitive enhancer and recreationally as an aphrodisiac and euphoriant 46 47 48 49 Although it is a prescription medication in many countries unauthorized possession and distribution of amphetamine is often tightly controlled due to the significant health risks associated with uncontrolled or heavy use 50 51 As a consequence amphetamine is illegally manufactured in clandestine labs to be trafficked and sold to users 52 Based upon drug and drug precursor seizures worldwide illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine 52 The first pharmaceutical amphetamine was Benzedrine a brand of inhalers used to treat a variety of conditions 53 54 Because the dextrorotary isomer has greater stimulant properties Benzedrine was gradually discontinued in favor of formulations containing all or mostly dextroamphetamine Presently it is typically prescribed as mixed amphetamine salts dextroamphetamine and lisdexamfetamine 53 55 Amphetamine is a norepinephrine dopamine releasing agent NDRA It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2 38 At therapeutic doses this causes emotional and cognitive effects such as euphoria change in libido increased arousal and improved cognitive control 47 48 56 Likewise it induces physical effects such as decreased reaction time fatigue resistance and increased muscle strength 46 In contrast supratherapeutic doses of amphetamine are likely to impair cognitive function and induce rapid muscle breakdown 45 47 57 Very high doses can result in psychosis e g delusions and paranoia which very rarely occurs at therapeutic doses even during long term use 58 59 As recreational doses are generally much larger than prescribed therapeutic doses recreational use carries a far greater risk of serious side effects such as dependence which only rarely arises with therapeutic amphetamine use 45 57 58 Caffeine Edit Main article Caffeine Roasted coffee beans a common source of caffeine Caffeine is a stimulant compound belonging to the xanthine class of chemicals naturally found in coffee tea and to a lesser degree cocoa or chocolate It is included in many soft drinks as well as a larger amount in energy drinks Caffeine is the world s most widely used psychoactive drug and by far the most common stimulant In North America 90 of adults consume caffeine daily 60 A few jurisdictions restrict its sale and use citation needed Caffeine is also included in some medications usually for the purpose of enhancing the effect of the primary ingredient or reducing one of its side effects especially drowsiness Tablets containing standardized doses of caffeine are also widely available Caffeine s mechanism of action differs from many stimulants as it produces stimulant effects by inhibiting adenosine receptors 61 Adenosine receptors are thought to be a large driver of drowsiness and sleep and their action increases with extended wakefulness 62 Caffeine has been found to increase striatal dopamine in animal models 63 as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors 64 however the implications for humans are unknown Unlike most stimulants caffeine has no addictive potential Caffeine does not appear to be a reinforcing stimulus and some degree of aversion may actually occur which people preferring placebo over caffeine in a study on drug abuse liability published in an NIDA research monograph 65 In large telephone surveys only 11 reported dependence symptoms However when people were tested in labs only half of those who claim dependence actually experienced it casting doubt on caffeine s ability to produce dependence and putting societal pressures in the spotlight 66 Coffee consumption is associated with a lower overall risk of cancer 67 This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer but it may also have a modest effect on colorectal cancer 68 There does not appear to be a significant protective effect against other types of cancers and heavy coffee consumption may increase the risk of bladder cancer 68 A protective effect of caffeine against Alzheimer s disease is possible but the evidence is inconclusive 69 70 71 Moderate coffee consumption may decrease the risk of cardiovascular disease 72 and it may somewhat reduce the risk of type 2 diabetes 73 Drinking 1 3 cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee However those who drink 2 4 cups per day may be at a slightly increased risk 74 Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals 75 It may protect people from liver cirrhosis 76 There is no evidence that coffee stunts a child s growth 77 Caffeine may increase the effectiveness of some medications including ones used to treat headaches 78 Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude 79 Ephedrine Edit Main article Ephedrine Ephedrine is a sympathomimetic amine similar in molecular structure to the well known drugs phenylpropanolamine and methamphetamine as well as to the important neurotransmitter epinephrine adrenaline Ephedrine is commonly used as a stimulant appetite suppressant concentration aid and decongestant and to treat hypotension associated with anaesthesia In chemical terms it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra family Ephedraceae It works mainly by increasing the activity of norepinephrine noradrenaline on adrenergic receptors 80 It is most usually marketed as the hydrochloride or sulfate salt The herb ma huang Ephedra sinica used in traditional Chinese medicine TCM contains ephedrine and pseudoephedrine as its principal active constituents The same may be true of other herbal products containing extracts from other Ephedra species MDMA Edit Tablets containing MDMA Main article MDMA See also Its parent class and MDA 3 4 Methylenedioxymethamphetamine MDMA ecstasy or molly is a euphoriant empathogen and stimulant of the amphetamine class 81 Briefly used by some psychotherapists as an adjunct to therapy the drug became popular recreationally and the DEA listed MDMA as a Schedule I controlled substance prohibiting most medical studies and applications MDMA is known for its entactogenic properties The stimulant effects of MDMA include hypertension anorexia appetite loss euphoria social disinhibition insomnia enhanced wakefulness inability to sleep improved energy increased arousal and increased perspiration among others Relative to catecholaminergic transmission MDMA enhances serotonergic transmission significantly more when compared to classical stimulants like amphetamine MDMA does not appear to be significantly addictive or dependence forming 82 Due to the relative safety of MDMA some researchers such as David Nutt have criticized the scheduling level writing a satirical article finding MDMA to be 28 times less dangerous than horseriding a condition he termed equasy or Equine Addiction Syndrome 83 MDPV Edit Main article MDPV Methylenedioxypyrovalerone MDPV is a psychoactive drug with stimulant properties that acts as a norepinephrine dopamine reuptake inhibitor NDRI 84 It was first developed in the 1960s by a team at Boehringer Ingelheim 85 MDPV remained an obscure stimulant until around 2004 when it was reported to be sold as a designer drug Products labeled as bath salts containing MDPV were previously sold as recreational drugs in gas stations and convenience stores in the United States similar to the marketing for Spice and K2 as incense 86 87 Incidents of psychological and physical harm have been attributed to MDPV use 88 89 Mephedrone Edit Main article Mephedrone Mephedrone is a synthetic stimulant drug of the amphetamine and cathinone classes Slang names include drone 90 and MCAT 91 It is reported to be manufactured in China and is chemically similar to the cathinone compounds found in the khat plant of eastern Africa It comes in the form of tablets or a powder which users can swallow snort or inject producing similar effects to MDMA amphetamines and cocaine Mephedrone was first synthesized in 1929 but did not become widely known until it was rediscovered in 2003 By 2007 mephedrone was reported to be available for sale on the Internet by 2008 law enforcement agencies had become aware of the compound and by 2010 it had been reported in most of Europe becoming particularly prevalent in the United Kingdom Mephedrone was first made illegal in Israel in 2008 followed by Sweden later that year In 2010 it was made illegal in many European countries and in December 2010 the EU ruled it illegal In Australia New Zealand and the US it is considered an analog of other illegal drugs and can be controlled by laws similar to the Federal Analog Act In September 2011 the USA temporarily classified mephedrone as illegal in effect from October 2011 Methamphetamine Edit Main article Methamphetamine Methamphetamine contracted from N methyl alpha methylphenethylamine is a potent psychostimulant of the phenethylamine and amphetamine classes that is used to treat attention deficit hyperactivity disorder ADHD and obesity 92 93 94 Methamphetamine exists as two enantiomers dextrorotary and levorotary 95 96 Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine 57 95 96 however both are addictive and produce the same toxicity symptoms at high doses 96 Although rarely prescribed due to the potential risks methamphetamine hydrochloride is approved by the United States Food and Drug Administration USFDA under the trade name Desoxyn 93 Recreationally methamphetamine is used to increase sexual desire lift the mood and increase energy allowing some users to engage in sexual activity continuously for several days straight 93 97 Methamphetamine may be sold illicitly either as pure dextromethamphetamine or in an equal parts mixture of the right and left handed molecules i e 50 levomethamphetamine and 50 dextromethamphetamine 97 Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in the United States 93 Also the production distribution sale and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty 98 99 In contrast levomethamphetamine is an over the counter drug in the United States note 1 In low doses methamphetamine can cause an elevated mood and increase alertness concentration and energy in fatigued individuals 57 93 At higher doses it can induce psychosis rhabdomyolysis and cerebral hemorrhage 57 93 Methamphetamine is known to have a high potential for abuse and addiction 57 93 Recreational use of methamphetamine may result in psychosis or lead to post withdrawal syndrome a withdrawal syndrome that can persist for months beyond the typical withdrawal period 102 Unlike amphetamine and cocaine methamphetamine is neurotoxic to humans damaging both dopamine and serotonin neurons in the central nervous system CNS 92 94 Unlike the long term use of amphetamine in prescription doses which may improve certain brain regions in individuals with ADHD there is evidence that methamphetamine causes brain damage from long term use in humans 92 94 this damage includes adverse changes in brain structure and function such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity 103 104 94 However recreational amphetamine doses may also be neurotoxic 105 Methylphenidate Edit Main article Methylphenidate Methylphenidate is a stimulant drug that is often used in the treatment of ADHD and narcolepsy and occasionally to treat obesity in combination with diet restraints and exercise Its effects at therapeutic doses include increased focus increased alertness decreased appetite decreased need for sleep and decreased impulsivity Methylphenidate is not usually used recreationally but when it is used its effects are very similar to those of amphetamines Methylphenidate acts as a norepinephrine dopamine reuptake inhibitor by blocking the norepinephrine transporter NET and the dopamine transporter DAT Methylphenidate has a higher affinity for the dopamine transporter than for the norepinephrine transporter and so its effects are mainly due to elevated dopamine levels caused by the inhibited reuptake of dopamine however increased norepinephrine levels also contribute to various of the effects caused by the drug Methylphenidate is sold under a number of brand names including Ritalin Other versions include the long lasting tablet Concerta and the long lasting transdermal patch Daytrana Cocaine Edit Lines of illicit cocaine used as a recreational stimulant Main article Cocaine Cocaine is an SNDRI 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 regions in which it was cultivated and used for centuries mainly by the Aymara people In Europe North America and some parts of Asia 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 in particular in ophthalmology 106 Most cocaine use is recreational and its abuse potential is high higher than amphetamine and so its sale and possession are strictly controlled in most jurisdictions Other tropane derivative drugs related to cocaine are also known such as troparil and lometopane but have not been widely sold or used recreationally 107 Nicotine Edit Main article Nicotine Nicotine is the active chemical constituent in tobacco which is available in many forms including cigarettes cigars chewing tobacco and smoking cessation aids such as nicotine patches nicotine gum and electronic cigarettes Nicotine is used widely throughout the world for its stimulating and relaxing effects Nicotine exerts its effects through the agonism of nicotinic acetylcholine receptor resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain reward system and acetaldehyde one of the tobacco constituent decreased the expression of monoamine oxidase in the brain 108 Nicotine is addictive and dependence forming Tobacco the most common source of nicotine has an overall harm to user and self score 3 percent below cocaine and 13 percent above amphetamines ranking 6th most harmful of the 20 drugs assessed as determined by a multi criteria decision analysis 109 Phenylpropanolamine Edit Main article Phenylpropanolamine Phenylpropanolamine PPA Accutrim b hydroxyamphetamine also known as the stereoisomers norephedrine and norpseudoephedrine is a psychoactive drug of the phenethylamine and amphetamine chemical classes that is used as a stimulant decongestant and anorectic agent 110 It is commonly used in prescription and over the counter cough and cold preparations In veterinary medicine it is used to control urinary incontinence in dogs under trade names Propalin and Proin In the United States PPA is no longer sold without a prescription due to a proposed increased risk of stroke in younger women In a few countries in Europe however it is still available either by prescription or sometimes over the counter In Canada it was withdrawn from the market on 31 May 2001 111 In India human use of PPA and its formulations were banned on 10 February 2011 112 Propylhexedrine Edit Main article Propylhexedrine Propylhexedrine Hexahydromethamphetamine Obesin is a stimulant medication sold over the counter in the United States as the cold medication Benzedrex 113 The drug has also been used as an appetite suppressant in Europe Propylhexedrine is not an amphetamine though it is structurally similar it is instead a cycloalkylamine and thus has stimulant effects that are less potent than similarly structured amphetamines such as methamphetamine The abuse potential of propylhexedrine is fairly limited due its limited routes of administration in the United States Benzedrex is only available as an inhalant mixed with lavender oil and menthol These ingredients cause unpleasant tastes and abusers of the drug have reported unpleasant menthol burps Injection of the drug has been found to cause transient diplopia and brain stem dysfunction 114 115 116 Pseudoephedrine Edit Main article Pseudoephedrine Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes It may be used as a nasal sinus decongestant as a stimulant 117 or as a wakefulness promoting agent 118 The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over the counter preparations either as a single ingredient or more commonly in combination with antihistamines guaifenesin dextromethorphan and or paracetamol acetaminophen or another NSAID such as aspirin or ibuprofen It is also used as a precursor chemical in the illegal production of methamphetamine Catha edulis Khat Edit Main article Khat Catha edulis Khat is a flowering plant native to the Horn of Africa and the Arabian Peninsula 119 120 Khat contains a monoamine alkaloid called cathinone a keto amphetamine that is said to cause excitement loss of appetite and euphoria In 1980 the World Health Organization WHO classified it as a drug of abuse that can produce mild to moderate psychological dependence less than tobacco or alcohol 121 although the WHO does not consider khat to be seriously addictive 120 It is banned in some countries such as the United States Canada and Germany while its production sale and consumption are legal in other nations including Djibouti Ethiopia Somalia and Yemen 122 Modafinil Edit Modafinil sold under the brand name Provigil among others is a CNS stimulant used to treat sleepiness due to narcolepsy shift work sleep disorder or obstructive sleep apnea While it has seen off label use as a purported cognitive enhancer the research on its effectiveness for this use is not conclusive Recreational use and issues of abuse EditMain article Recreational drug use Stimulants See also Substance abuse Stimulants enhance the activity of the central and peripheral nervous systems Common effects may include increased alertness awareness wakefulness endurance productivity and motivation arousal locomotion heart rate and blood pressure and a diminished desire for food and sleep Use of stimulants may cause the body to reduce significantly its production of natural body chemicals that fulfill similar functions Until the body reestablishes its normal state once the effect of the ingested stimulant has worn off the user may feel depressed lethargic confused and miserable This is referred to as a crash and may provoke reuse of the stimulant Abuse of central nervous system CNS stimulants is common Addiction to some CNS stimulants can quickly lead to medical psychiatric and psychosocial deterioration Drug tolerance dependence and sensitization as well as a withdrawal syndrome can occur 123 Stimulants may be screened for in animal discrimination and self administration models which have high sensitivity albeit low specificity 124 Research on a progressive ratio Self administration protocol has found amphetamine methylphenidate modafinil cocaine and nicotine to all have a higher break point than placebo that scales with dose indicating reinforcing effects 125 Drug Mean Pleasure Psychological dependence Physical dependence 126 Methamphetamine 5 53 6 0 7 0 3 0Cocaine 2 39 3 0 2 8 1 3Tobacco 2 21 2 3 2 6 1 8Amphetamine 1 67 2 0 1 9 1 1Ecstasy 1 13 1 5 1 2 0 7Treatment for misuse EditPsychosocial treatments such as contingency management have demonstrated improved effectiveness when added to treatment as usual consisting of counselling and or case management This is demonstrated with a decrease in dropout rates and a lengthening of periods of abstinence 127 Testing EditThe presence of stimulants in the body may be tested by a variety of procedures Serum and urine are the common sources of testing material although saliva is sometimes used Commonly used tests include chromatography immunologic assay and mass spectrometry 128 See also EditAntidepressants Depressants Hallucinogens Nootropics PsychoanalepticsNotes Edit The active ingredient in some OTC inhalers in the United States is listed as levmetamfetamine the INN and USAN of levomethamphetamine 100 101 References Edit stimulant definition of stimulant in English Oxford Dictionaries Oxford Dictionaries English Archived from the original on 26 February 2017 Treatment Center for Substance Abuse 1999 Chapter 2 How Stimulants Affect the Brain and Behavior Substance Abuse and Mental Health Services Administration US Archived from the 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amphetamine or dextroamphetamine displays five times greater psychostimulant activity compared with its R isomer 78 Most such molecules are produced exclusively through chemical syntheses and many are prescribed widely in modern medicine For example S amphetamine Figure 4b a key ingredient in Adderall and Dexedrine is used to treat attention deficit hyperactivity disorder ADHD 79 Figure 4 b Examples of synthetic pharmaceutically important substituted amphetamines a b Glennon RA 2013 Phenylisopropylamine stimulants amphetamine related agents In Lemke TL Williams DA Roche VF Zito W eds Foye s principles of medicinal chemistry 7th ed Philadelphia USA Wolters Kluwer Health Lippincott Williams amp Wilkins pp 646 648 ISBN 9781609133450 The simplest unsubstituted phenylisopropylamine 1 phenyl 2 aminopropane or amphetamine serves as a common structural template for hallucinogens and psychostimulants Amphetamine produces central stimulant anorectic and sympathomimetic actions and it is the 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Liddle DG Connor DJ June 2013 Nutritional supplements and ergogenic AIDS Prim Care 40 2 487 505 doi 10 1016 j pop 2013 02 009 PMID 23668655 Amphetamines and caffeine are stimulants that increase alertness improve focus decrease reaction time and delay fatigue allowing for an increased intensity and duration of training Physiologic and performance effects Amphetamines increase dopamine norepinephrine release and inhibit their reuptake leading to central nervous system CNS stimulation Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40 Improved reaction time Increased muscle strength and delayed muscle fatigue Increased acceleration Increased alertness and attention to task a b c Malenka RC Nestler EJ Hyman SE 2009 Chapter 13 Higher Cognitive Function and Behavioral Control In Sydor A Brown RY eds Molecular Neuropharmacology A Foundation for Clinical Neuroscience 2nd ed New York McGraw Hill Medical p 318 ISBN 978 0 07 148127 4 Therapeutic relatively low doses 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1999 pp 203 208External links EditLook up stimulant or upper in Wiktionary the free dictionary Media related to Stimulants at Wikimedia Commons Long Island Council on Alcohol amp Drug Dependence About Drugs Stimulants Archived from the original on 5 June 2008 Retrieved 4 August 2007 CS1 maint unfit URL link Online Publications Drugs of Abuse Stimulants Archived from the original on 22 September 2006 Retrieved 11 January 2008 CS1 maint unfit URL link Asia amp Pacific Amphetamine Type Stimulants Information Centre APAIC Retrieved from https en wikipedia org w index php title Stimulant amp oldid 1048187942, wikipedia, wiki, book,

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