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Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase . They are used for various purposes, such as enhancing , , , , and physical performance. Some stimulants occur naturally, while others are exclusively synthetic. Common stimulants include , , , , , and . Stimulants may be subject to varying forms of regulation, or outright prohibition, depending on jurisdiction.

Stimulants increase activity in the sympathetic nervous system, either directly or indirectly. Prototypical stimulants increase synaptic concentrations of , particularly and (e.g., methylphenidate). Other stimulants work by binding to the receptors of excitatory neurotransmitters (e.g., nicotine) or by blocking the activity of endogenous agents that promote sleep (e.g., caffeine). Stimulants can affect various functions, including , , the , , , and . Effects range from mild stimulation to , depending on the specific drug, dose, route of administration, and inter-individual characteristics.

Stimulants have a long history of use, both for medical and non-medical purposes. Archeological evidence from Peru shows that cocaine use dates back as far as 8000 B.C.E. Stimulants have been used to treat various conditions, such as , attention deficit hyperactivity disorder (ADHD), , depression, and . They have also been used as recreational drugs, performance-enhancing substances, and cognitive enhancers, by various groups of people, such as students, athletes, artists, and workers. They have also been used to promote aggression of combatants in wartime, both historically and in the present day.

Stimulants have potential risks and side effects, such as , , , , , , cardiovascular problems, and . The misuse and abuse of stimulants can lead to serious health and social consequences, such as , dependence, , and . Therefore, the use of stimulants is regulated by laws and policies in most countries, and requires medical supervision and prescription in some cases.


Definition
A stimulant is an overarching term that covers many including those that increase the activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Sympathomimetic effects are those effects that mimic or copy the actions of the sympathetic nervous system. The sympathetic nervous system is a part of the nervous system that prepares the body for action, such as increasing the heart rate, blood pressure, and breathing rate. Stimulants can activate the same receptors as the natural chemicals released by the sympathetic nervous system (namely and ) and cause similar effects.


Effects

Acute
Stimulants in therapeutic doses, such as those given to patients with attention deficit hyperactivity disorder (ADHD), increase 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 a decreased need for sleep.

Many, but not all, stimulants have effects; that is, they enhance physical performance. 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 , amphetamine and methylphenidate have been reported in healthy adolescents by some studies, and is a commonly cited reason among illicit drug users for use, particularly among college students in the context of studying. Still, results of these studies is inconclusive: assessing the potential overall neurocognitive benefits of stimulants among healthy youth is challenging due to the diversity within the population, the variability in cognitive task characteristics, and the absence of replication of studies. Research on the cognitive enhancement effects of modafinil in healthy non-sleep-deprived individuals has yielded mixed results, with some studies suggesting modest improvements in attention and executive functions while others show no significant benefits or even a decline in cognitive functions.

(2025). 9780198727392, Oxford University Press. .

In some cases, psychiatric phenomena may emerge such as stimulant psychosis, , and suicidal ideation. Acute toxicity has been reportedly associated with hyperhydrosis, panic attacks, severe anxiety, mydriasis, paranoia, aggressive behavior, excessive motor activity, psychosis, rhabdomyolysis, and . The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia. Most drugs classified as stimulants are sympathomimetic, meaning that they stimulate the sympathetic branch of the autonomic nervous system. This leads to effects such as (dilation of the pupils), increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called , , and , and may lead to , , , or . 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 . 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. However, a 2024 systematic review of the evidence found that stimulants overall improve ADHD symptoms and broadband behavioral measures in children and adolescents, though they carry risks of side effects like appetite suppression and other adverse events. 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, , and . Some effects are dependent upon the route of administration, with intravenous use associated with the transmission of many disease such as , HIV/AIDS and potential medical emergencies such as , or , while inhalation may be associated with increased lower respiratory tract infection, , 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.


Medical uses
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. In the US, the most frequently prescribed stimulants as of 2013 were (Vyvanse), (Ritalin), and (Adderall). It was estimated in 2015 that the percentage of the world population that had used during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including and ) the value was 0.7%, and for 0.4%.

Stimulants have been used in medicine for many conditions including , , , impulse control disorders, , and, in case of cocaine, as . Drugs used to treat obesity are called 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. are used in management of sleep disorders characterized by excessive daytime sleepiness, such as , and include stimulants such as and . Stimulants are used in impulse control disorders such as and in such as major depressive disorder to increase , focus and elevate mood. Stimulants such as , and orally have been used to treat asthma, but inhaled are now preferred due to less systemic side effects. 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.Bicopoulos D, editor. AusDI: Drug information for the healthcare professional, 2nd edition. Castle Hill: Pharmaceutical Care Information Services; 2002.


Depression
Stimulants were one of the first classes of drugs to be used in the treatment of depression, beginning after the introduction of the amphetamines in the 1930s.
(2016). 9780230589445, Springer. .
However, they were largely abandoned for treatment of depression following the introduction of conventional in the 1950s. Subsequent to this, there has been a resurgence in interest in stimulants for depression in recent years.

Stimulants produce a fast-acting and pronounced but transient and short-lived . In relation to this, they are minimally effective in the treatment of depression when administered continuously. In addition, tolerance to the mood-lifting effects of amphetamine has led to dose escalation and . Although the efficacy for depression with continuous administration is modest, it may still reach statistical significance over and provide benefits similar in magnitude to those of conventional antidepressants. The reasons for the short-term mood-improving effects of stimulants are unclear, but may relate to rapid . Tolerance to the effects of stimulants has been studied and characterized both in animals and humans. Stimulant is remarkably similar in its symptoms to those of major depressive disorder.

(2025). 9783642030000
(2025). 9780123668660


Chemistry
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, can be classified as a substituted methylenedioxyphenethylamine, a substituted amphetamine and consequently, a substituted phenethylamine.

Major stimulant classes include phenethylamines and their daughter class substituted amphetamines.


Amphetamines (class)
Substituted amphetamines are a based upon the structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more in the amphetamine core structure with .
(2025). 9781609133450, Wolters Kluwer Health/Lippincott Williams & Wilkins.
Examples of substituted amphetamines are amphetamine (itself), , , , , , , , , , , (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 , , and . An additional mechanism of some substituted amphetamines is the release of of monoamine neurotransmitters through VMAT2, thereby increasing the concentration of these neurotransmitters in the , or intracellular fluid, of the presynaptic neuron.

Amphetamine-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat major depressive disorder, where subjects do not respond well to traditional selective serotonin reuptake inhibitor (SSRI) medications, but evidence supporting this use is mixed. Two large phase III studies of (a to amphetamine) as an adjunct to an SSRI or serotonin–norepinephrine reuptake inhibitor (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 like (a mixture of salts of amphetamine and dextroamphetamine) in controlling symptoms associated with . Non-stimulants such as have also found to be effective. Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse. Efforts of the National Institute on Drug Abuse to Prevent and Treat Prescription Drug Abuse , Testimony Before the Subcommittee on Criminal Justice, Drug Policy, and Human Resources Committee on Government Reform, United States House of Representatives, 26 July 2006


Cocaine analogs
Hundreds of cocaine analogs have been created, all of them usually maintaining a benzyloxy connected to the 3 carbon of a . Various modifications include substitutions on the , 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 analogs have been developed as well.


Mechanisms of action
Most stimulants exert their activating effects by enhancing 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 and effects, also affect transmission. Some stimulants, such as some amphetamine derivatives and, notably, , can decrease negative feedback by antagonizing regulatory . Adrenergic agonists, such as, in part, , act by directly binding to and activating adrenergic receptors, producing sympathomimetic effects.

There are also more indirect mechanisms of action by which a drug can elicit activating effects. Caffeine is an adenosine receptor antagonist, and only indirectly increases catecholamine transmission in the brain. is an histamine 3 (H3)-receptor inverse agonist. As histamine 3 (H3) receptors mainly act as , pitolisant decreases negative feedback to neurons, enhancing histaminergic transmission.

The precise mechanism of action of some stimulants, such as modafinil, for treating symptoms of narcolepsy and other sleep disorders, remains unknown.

(2017). 9781108228749, Cambridge University Press.
(2025). 9783030112707


Notable stimulants

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 . Amphetamine is also used off-label as a performance and , and recreationally as an and .
(2025). 9780071481274, McGraw-Hill Medical.
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 seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of .

The first pharmaceutical amphetamine was , 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 , dextroamphetamine, and .

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 .

(2025). 9780071624428, McGraw-Hill.
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
Caffeine is a stimulant compound belonging to the class of chemicals naturally found in , , and (to a lesser degree) or . It is included in many , as well as a larger amount in . Caffeine is the world's most widely used psychoactive drug and by far the most common stimulant. In , 90% of adults consume caffeine daily.

A few jurisdictions restrict the sale and use of caffeine. In the United States, the FDA has banned the sale of pure and highly concentrated caffeine products for personal consumption, due to the risk of overdose and death. The Australian Government has announced a ban on the sale of pure and highly concentrated caffeine food products for personal consumption, following the death of a young man from acute caffeine toxicity. In Canada, Health Canada has proposed to limit the amount of caffeine in energy drinks to 180 mg per serving, and to require warning labels and other safety measures on these products.

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, per a study on drug abuse liability published in an NIDA research monograph that described a group preferring placebo over caffeine. 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 . 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 . 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 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 but does not appear to affect normal individuals. It may protect people from . There is no evidence that coffee stunts a child's growth.

(2025). 9780805083125, Times Books. .
Caffeine may increase the effectiveness of some medications including ones used to treat . Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude.


Ephedrine
Ephedrine is a similar in molecular structure to the well-known drugs phenylpropanolamine and , as well as to the important (adrenaline). Ephedrine is commonly used as a stimulant, appetite suppressant, concentration aid, and , and to treat associated with anesthesia.

In chemical terms, it is an with a skeleton found in various plants in the genus Ephedra (family ). It works mainly by increasing the activity of (noradrenaline) on adrenergic receptors. Merck Manuals EPHEDrine Last full review/revision January 2010 It is most usually marketed as the hydrochloride or sulfate salt.

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


MDMA
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly) is an , euphoriant, 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 properties. The stimulant effects of MDMA include , anorexia (appetite loss), , social disinhibition, (enhanced wakefulness/inability to sleep), improved , increased arousal, and increased , 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 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
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.US Patent 3478050 – 1-(3,4-methylenedioxy-phenyl)-2-pyrrolidino-alkanones MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a . 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
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 plant of . It comes in the form of tablets or a powder, which users can swallow, snort, or inject, producing similar effects to , , and .

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.

Mephedrone is neurotoxic and has abuse potential, predominantly exerted on 5-hydroxytryptamine (5-HT) terminals, mimicking that of MDMA with which it shares the same subjective sensations on abusers.


Methamphetamine
Methamphetamine (contracted from ) is a potent psychostimulant of the and amphetamine classes that is used to treat attention deficit hyperactivity disorder (ADHD) and .
(2025). 9780071481274, McGraw-Hill Medical.
Methamphetamine exists as two , and . 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 , , and increase , 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 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.

(2025). 9789211482232, United Nations. .
In contrast, levomethamphetamine is an over-the-counter drug in the United States.

In low doses, methamphetamine can cause an and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis, , and cerebral hemorrhage. Methamphetamine is known to have a high potential for 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 and , methamphetamine is to humans, damaging both and 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 volume in several brain regions and adverse changes in markers of metabolic integrity. However, recreational amphetamine doses may also be neurotoxic.


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 (NDRI), 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
Cocaine is an . Cocaine is made from the leaves of the shrub, which grows in the mountain regions of South American countries such as , , and , regions in which it was cultivated and used for centuries mainly by the . 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 . 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 derivative drugs related to cocaine are also known such as and but have not been widely sold or used recreationally.


Nicotine
is the active chemical constituent in , which is available in many forms, including , , , and smoking cessation aids such as , , 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 receptors, resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain , 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
Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the norephedrine and norpseudoephedrine, is a psychoactive drug of the and that is used as a stimulant, , and 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 Propalin and Proin.

In the United States, PPA is no longer sold without a prescription due to a possible increased risk of 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.


Lisdexamfetamine
Lisdexamfetamine (Vyvanse, etc.) is an amphetamine-type medication, sold for use in treating ADHD. Its effects typically last around 14 hours. Lisdexamfetamine is inactive on its own and is metabolized into dextroamphetamine in the body. Consequently, it has a lower abuse potential.


Pseudoephedrine
Pseudoephedrine is a of the phenethylamine and amphetamine . It may be used as a , as a stimulant, or as a wakefulness-promoting agent.

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


Catha edulis (Khat)
Khat is a native to the Horn of Africa and the Arabian Peninsula.

Khat contains a called , a "keto-amphetamine". This alkaloid causes excitement, , 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 countries, including , , , Kenya and .Haight-Ashbury Free Medical Clinic, Journal of psychoactive drugs, Volume 41, (Haight-Ashbury Publications: 2009), p.3.


Modafinil
is an medication, which means that it promotes wakefulness and alertness. Modafinil is sold under the brand name Provigil among others. Modafinil is used to treat excessive daytime sleepiness due to , 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. Despite being a CNS stimulant, the addiction and liabilities of modafinil are considered very low. Although modafinil shares biochemical mechanisms with stimulant drugs, it is less likely to have . The similarities in effects with are not clearly established. Unlike other stimulants, modafinil does not induce a subjective , which is commonly associated with , an intense feeling of well-being. Euphoria is a potential indicator of , which is the compulsive and excessive use of a substance despite adverse consequences. In clinical trials, modafinil has shown no evidence of abuse potential, that is why modafinil is considered to have a low risk of addiction and dependence, however, caution is advised.


Pitolisant
Pitolisant is an (antagonist) of the histamine 3 (H3) autoreceptor. As such, pitolisant is an that also belongs to the class of CNS stimulants. Pitolisant is also considered a medication of class, which means that it promotes wakefulness and alertness. Pitolisant is the first wakefulness-promoting agent that acts by blocking the H3 autoreceptor.

Pitolisant has been shown to be effective and well-tolerated for the treatment of with or without cataplexy.

Pitolisant is the only non-controlled anti-narcoleptic drug in the . It has shown minimal abuse risk in studies.

Blocking the histamine 3 (H3) autoreceptor increases the activity of histamine in the brain. The H3 autoreceptors regulate in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting biosynthesis and release upon binding to endogenous histamine. By preventing the binding of endogenous histamine at the H3, as well as producing a response opposite to that of endogenous histamine at the receptor (inverse agonism), pitolisant enhances histaminergic activity in the brain.


5-HT2A receptor agonists
Certain serotonergic psychedelics and related non- drugs, acting as 5-HT2A receptor , have been reported to have mild stimulant and/or "psychic energizing" (i.e., acute ) effects, both in animals and humans.
(1991). 9780963009609, Transform Press.
These effects are often present at low or sub-hallucinogenic doses. Psychedelics are also known to promote wakefulness or cause .

Psychedelic and related drugs that have been reported to produce stimulant effects include the phenethylamines 2,5-DMA (DOH), DOM, DOET, DOPR, MTFEM,

(2025). 9783037887004, Nachtschatten-Verlag. .
Ariadne (4C-DOM), and ASR-2001 (2CB-5PrO), among others. The lysergamide has also been reported to have mild stimulant effects.
(2025). 9783031619915, Springer Nature Switzerland.
Conversely, does not seem to produce the same stimulant effects. The non-hallucinogenic Ariadne was under development as a potential pharmaceutical drug to take advantage of such effects in the treatment of conditions like depression in the 1970s, and reached phase 3 , but was shelved for strategic economic reasons.
(2025). 9780963009630, Transform Press.
ASR-2001, which is likewise non-hallucinogenic, is under development for use as a stimulant-like medication for treatment of psychiatric disorders.

Serotonin 5-HT2A receptor agonists have been found to increase levels in brain areas like the , , and nucleus accumbens in . Relatedly, serotonin 5-HT2A receptor agonists are known to produce stimulant-like effects in animals such as (increased locomotor activity)

(2025). 9783662558782
and pro-motivational effects. The serotonin 5-HT2C receptor, which most psychedelics additionally activate to varying degrees, is known to have opposing effects on dopamine release and stimulant-related behavior, which may contribute to inverted U-shaped dose–response relationships as well as divergent stimulant-like effects between different psychedelics.


Recreational use and issues of abuse
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased , , , , , and , , locomotion, , and , and a diminished desire for and . 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.

of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to , , and deterioration. , , and sensitization as well as a 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. A progressive ratio self-administration protocol is a way of testing how much an animal or a human wants a drug by making them do a certain action (like pressing a lever or poking a nose device) to get the drug. The number of actions needed to get the drug increases every time, so it becomes harder and harder to get the drug. The highest number of actions that the animal or human is willing to do to get the drug is called the break point. The higher the break point, the more the animal or human wants the drug. In contrast to the classical stimulants such as amphetamine, the effects of modafinil depend on what the animals or humans have to do after getting the drug. If they have to do a performance task, like solving a puzzle or remembering something, modafinil makes them work harder for it than placebo, and the subjects wanted to self-administer modafinil. But if they had to do a relaxation task, like listening to music or watching a video, the subjects did not want to self-administer modafinil. This suggests that modafinil is more rewarding when it helps the animals or humans do something better or faster, especially considering that modafinil is not commonly abused or depended on by people, unlike other stimulants.

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0.7


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


Testing
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.AJ Giannini. Drug Abuse. Los Angeles, Health Information Press, 1999, pp.203–208


See also


Notes

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