CNS Stimulant
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Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
s including those that increase activity of the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
and the body, drugs that are pleasurable and invigorating, or drugs that have
sympathomimetic Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...
effects. Stimulants are widely used throughout the world as
prescription medicine A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s as well as without a prescription (either legally or illicitly) as performance-enhancing or
recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or pleasure ...
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 Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eating ...
(Vyvanse),
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...
(Ritalin), and
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
(Adderall). It was estimated in 2015 that the percentage of the world population that had used
cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
and
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
) the value was 0.7%, and for
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
0.4%.


Effects


Acute

Stimulants in therapeutic doses, such as those given to patients with
ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
, 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 Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where ba ...
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 Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...
, 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 phenomena may emerge such as
stimulant psychosis Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or ...
,
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concer ...
, and
suicidal ideation Suicidal ideation, or suicidal thoughts, means having thoughts, ideas, or ruminations about the possibility of ending one's own life.World Health Organization, ''ICD-11 for Mortality and Morbidity Statistics'', ver. 09/2020MB26.A Suicidal ideatio ...
. Acute toxicity has been reportedly associated with homicide, paranoia, aggressive behavior, motor dysfunction, and
punding Punding is compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting household objects. The term was originally coined to describe complex prolonged, purposeless, and stereotyped behaviou ...
. 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 Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, as ...
, increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
,
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, and
hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...
, and may lead to
rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...
,
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
,
cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
, or
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
. 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 Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
s. 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 Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, and
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. Some effects are dependent upon the route of administration, with intravenous use associated with the transmission of many disease such as
Hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
,
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
and potential medical emergencies such as
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
,
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
or
pseudoaneurysm A pseudoaneurysm, also known as a false aneurysm, is a locally contained hematoma outside an artery or heart due to damage to the vessel wall. The injury goes through all the three layers of the arterial wall causing a leak, which is contained b ...
, while inhalation may be associated with increased
lower respiratory tract infection Lower respiratory tract infection (LRTI) is a term often used as a synonym for pneumonia but can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, cough ...
,
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
, 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 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
.


Medical uses

Stimulants have been used in medicine for many conditions including
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
,
sleep disorders A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are tests ...
,
mood disorders A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
,
impulse control disorders Impulse-control disorder (ICD) is a class of mental disorder, psychiatric disorders characterized by impulsivity – failure to resist a temptation, an urge, or an impulse; or having the inability to not speak on a thought. Many psychiatric disor ...
,
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...
,
nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathing. ...
and, in case of cocaine, as
local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general an ...
s. Drugs used to treat obesity are called
anorectic An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ...
s and generally include drugs that follow the general definition of a stimulant, but other drugs such as
cannabinoid receptor antagonist A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They includ ...
s also belong to this group.
Eugeroic Eugeroics (originally "eugrégorique" or "eugregoric"), also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of ce ...
s are used in management of sleep disorders characterized by
excessive daytime sleepiness Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompass ...
, such as
narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
, and include stimulants such as
modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...
. Stimulants are used in impulse control disorders such as
ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
and
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
in
mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
s such as
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
to increase
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of heat a ...
, focus and elevate mood. Stimulants such as
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
,
theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
and
salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...
orally have been used to treat asthma, but inhaled adrenergic drugs are now preferred due to less systemic side effects.
Pseudoephedrine Pseudoephedrine (PSE) 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 in higher doses. It was first characteri ...
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. However, they were largely abandoned for treatment of depression following the introduction of conventional
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s 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 mood lift. 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 dependence. Although the efficacy for depression with continuous administration is modest, it may still reach
statistical significance In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the p ...
over
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
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. Tolerance to the effects of stimulants has been studied and characterized both in animals and humans. Stimulant
withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * ''Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from a ban ...
is remarkably similar in its symptoms to those of major depressive disorder.


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, ecstasy can be classified as a
substituted methylenedioxyphenethylamine Substitution reaction, Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivative (chemistry), derivatives of the phenethylamines, which includes many psychoactive drugs that act as entactogens, psychedelic drug, ...
, a
substituted amphetamine 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 sub ...
and consequently, a
substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by ...
. When referring to stimulants, the parent drug (e.g., ''amphetamine'') will always be expressed in the singular; with the word "substituted" placed before the parent drug ( ''substituted amphetamines''). Major stimulant classes include
phenethylamines Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by ...
and their daughter class
substituted amphetamines 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 sub ...
.


Amphetamines (class)

Substituted amphetamines 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 sub ...
are a class of compounds based upon the
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
structure; it includes all
derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...
compounds which are formed by replacing, or substituting, one or more
hydrogen atom A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively charged proton and a single negatively charged electron bound to the nucleus by the Coulomb force. Atomic hydrogen consti ...
s in the amphetamine core structure with
substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
s. Examples of substituted amphetamines are amphetamine (itself),
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
,
ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
,
cathinone Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub '' Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the m ...
,
phentermine Phentermine ( phenyl- tertiary-butyl amine), with several brand names including Ionamin and Sentis, is a medication used together with diet and exercise to treat obesity. It is taken by mouth for up to a few weeks at a time, after which the ben ...
,
mephentermine Mephentermine is a cardiac stimulant. It has been used as a treatment for low blood pressure. Mephentermine belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of heart failure. Me ...
,
bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the case ...
,
methoxyphenamine Methoxyphenamine (trade names ASMI, Euspirol, Orthoxine, Ortodrinex, Proasma), also known as 2-methoxy-''N''- methyl amphetamine (OMMA), is a β-adrenergic receptor agonist of the amphetamine class used as a bronchodilator. It acts as an anti ...
, selegiline, amfepramone,
pyrovalerone (Centroton, 4-Methyl-β-keto-prolintane, Thymergix, O-2371) is a psychoactive drug with stimulant effects via acting as a norepinephrine-dopamine reuptake inhibitor (NDRI), and is used for the clinical treatment of chronic fatigue or letharg ...
,
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
(ecstasy), and
DOM Dom or DOM may refer to: People and fictional characters * Dom (given name), including fictional characters * Dom (surname) * Dom La Nena (born 1989), stage name of Brazilian-born cellist, singer and songwriter Dominique Pinto * Dom people, an et ...
(STP). Many drugs in this class work primarily by activating
trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
(TAAR1); in turn, this causes
reuptake inhibition Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of trans ...
and effluxion, or release, of
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, and
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
. An additional mechanism of some substituted amphetamines is the release of vesicular stores of
monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromaticity, aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All mo ...
s through
VMAT2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
, thereby increasing the concentration of these neurotransmitters in the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, or intracellular fluid, of the
presynaptic neuron Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous sys ...
. Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat
major depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
, where subjects do not respond well to traditional
SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
medications, but evidence supporting this use is poor/mixed. Notably, two recent large phase III studies of
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eating ...
(a
prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...
to amphetamine) as an adjunct to an SSRI or SNRI in the treatment of
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
showed no further benefit relative to
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
in effectiveness. Numerous studies have demonstrated the effectiveness of drugs such as
Adderall Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio bet ...
(a mixture of
salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively cha ...
of
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
and
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
) in controlling symptoms associated with
ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
. 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.


Mechanisms of action

Most stimulants exert their activating effects by enhancing
catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a subst ...
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
hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...
ic effects, also affect
serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
transmission. Some stimulants, such as some amphetamine derivatives and, notably,
yohimbine Yohimbine (), also known as quebrachine, is an indole alkaloid derived from the bark of the African tree ''Pausinystalia johimbe''; also from the bark of the unrelated South American tree ''Aspidosperma quebracho-blanco''. Yohimbine is an α2- ...
, can decrease
negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
by antagonizing regulatory autoreceptors.
Adrenergic agonist An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between ...
s, such as, in part,
ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...
, act by directly binding to and activating
adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
s, producing sympathomimetic effects. There are also more indirect mechanisms a drug can elicit activating effects. Caffeine is an
adenosine receptor antagonist An adenosine receptor antagonist is a drug which acts as an antagonist of one or more of the adenosine receptors. The best known are xanthines and their derivatives (natural: caffeine, theophylline, and theobromine; and synthetic: PSB-1901), but ...
, and only indirectly increases catecholamine transmission in the brain.
Pitolisant Pitolisant, sold under the brand name Wakix among others, is a medication for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist. It represents the first commercia ...
is an H3-receptor inverse agonist. As H3 receptors mainly act as autoreceptors, pitolisant decreases negative feedback to
histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
rgic neurons, enhancing histaminergic transmission.


Notable stimulants


Amphetamine

Amphetamine is a potent
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS) stimulant of the phenethylamine class that is approved for the treatment of
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD) and
narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
. Amphetamine is also used off-label as a
performance A performance is an act of staging or presenting a play, concert, or other form of entertainment. It is also defined as the action or process of carrying out or accomplishing an action, task, or function. Management science In the work place ...
and cognitive enhancer, and recreationally as an
aphrodisiac An aphrodisiac is a substance that increases sexual desire, sexual attraction, sexual pleasure, or sexual behavior. Substances range from a variety of plants, spices, foods, and synthetic chemicals. Natural aphrodisiacs like cannabis or cocain ...
and
euphoriant Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
. 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 Drug precursors, also referred to as precursor chemicals or simply precursors, are substances which are known to be used in the illegal manufacture of illicit drugs. Most precursors also have legitimate commercial uses and are legally used in a wid ...
seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
. The first pharmaceutical amphetamine was
Benzedrine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used a ...
, 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 Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
, and
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eating ...
. Amphetamine is a norepinephrine-dopamine releasing agent (NDRA). It enters neurons through
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
and
norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...
s and facilitates neurotransmitter efflux by activating
TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
and inhibiting
VMAT2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
. At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved
cognitive control In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and succe ...
. 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 Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
(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
xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base (genetics), base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, incl ...
class of chemicals naturally found in
coffee Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulant, stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world. S ...
,
tea Tea is an aromatic beverage prepared by pouring hot or boiling water over cured or fresh leaves of ''Camellia sinensis'', an evergreen shrub native to East Asia which probably originated in the borderlands of southwestern China and north ...
, and (to a lesser degree)
cocoa Cocoa may refer to: Chocolate * Chocolate * ''Theobroma cacao'', the cocoa tree * Cocoa bean, seed of ''Theobroma cacao'' * Chocolate liquor, or cocoa liquor, pure, liquid chocolate extracted from the cocoa bean, including both cocoa butter and ...
or
chocolate Chocolate is a food made from roasted and ground cacao seed kernels that is available as a liquid, solid, or paste, either on its own or as a flavoring agent in other foods. Cacao has been consumed in some form since at least the Olmec civ ...
. It is included in many
soft drink A soft drink (see § Terminology for other names) is a drink that usually contains water (often carbonated), a sweetener, and a natural and/or artificial flavoring. The sweetener may be a sugar, high-fructose corn syrup, fruit juice, a su ...
s, 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. 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. This is primarily due to a decrease in the risks of hepatocellular and
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
, 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 Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
. 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 Diabetes mellitus type 2, type 2 diabetes. Drinking 1-3 cups of coffee per day does not affect the risk of
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
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

Ephedrine is a sympathomimetic amine similar in molecular structure to the well-known drugs phenylpropanolamine and
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
, as well as to the important neurotransmitter
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
(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 (genus), Ephedra'' (family Ephedraceae). It works mainly by increasing the activity of
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
(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'' (''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

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 Drug Enforcement Administration, DEA listed MDMA as a Controlled substances act#Schedule I controlled substances, Schedule I controlled substance, prohibiting most medical studies and applications. MDMA is known for its entactogenic properties. The stimulant effects of MDMA include
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, anorexia (symptom), anorexia (appetite loss), euphoria, social disinhibition, insomnia (enhanced wakefulness/inability to sleep), improved
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of heat a ...
, 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

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 (drug), 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 (drug), Spice and K2 (drug), K2 as incense. Incidents of psychological and physical harm have been attributed to MDPV use.


Mephedrone

Mephedrone is a Organic compound#Synthetic compounds, synthetic stimulant drug of the substituted amphetamine, amphetamine and substituted cathinone, 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 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
,
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
s, and
cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
. 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 structural analog, 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

Methamphetamine (contracted from ) is a potent psychostimulant of the phenethylamine and substituted amphetamine, amphetamine chemical classification, classes that is used to treat
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD) and
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
. 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 aphrodisiac, increase sexual desire, euphoriant, lift the mood, and increase
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of heat a ...
, 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 racemate, 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 Substance, 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 Convention on Psychotropic Substances, 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 euphoria, elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce methamphetamine psychosis, psychosis,
rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...
, and cerebral hemorrhage. Methamphetamine is known to have a high potential for substance abuse, abuse and substance dependence, 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 Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
and
cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
, methamphetamine is neurotoxic to humans, damaging both
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
and
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
neurons in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(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

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 The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...
(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 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

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

Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the stereoisomerism, stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
chemical classes that is used as a stimulant, decongestant, and
anorectic An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ...
agent. It is commonly used in prescription drug, prescription and over-the-counter drug, 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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
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

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 anorectic, 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 diplopia, transient diplopia and brain stem dysfunction.


Pseudoephedrine

Pseudoephedrine is a sympathomimetic
drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
of the substituted phenethylamine, phenethylamine and substituted amphetamine, amphetamine chemical classes. It may be used as a decongestant, nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent. The Salt (chemistry), salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter drug, over-the-counter dosage form, preparations, either as a single ingredient or (more commonly) in combination with antihistamines, guaifenesin, dextromethorphan, and/or paracetamol (acetaminophen) or another non-steroidal anti-inflammatory drug, NSAID (such as aspirin or ibuprofen). It is also used as a precursor chemical in the illegal production of methamphetamine.


''Catha edulis'' (Khat)

Khat is a flowering plant native to the Horn of Africa and the Arabian Peninsula. Khat contains a monoamine alkaloid called
cathinone Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub '' Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the m ...
, a "keto-amphetamine", that is said to cause excitement, Anorectic, loss of appetite, and euphoria (emotion), euphoria. In 1980, the World Health Organization (WHO) classified it as a drug of abuse that can produce mild to moderate Substance dependence, 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, Kenya and Yemen.Haight-Ashbury Free Medical Clinic, ''Journal of psychoactive drugs'', Volume 41, (Haight-Ashbury Publications: 2009), p.3.


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.


Recreational use and issues of abuse

Stimulants enhance the activity of the central nervous system, central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, animal locomotion, 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 "Comedown (drugs), crash", and may provoke reuse of the stimulant. Drug abuse, Abuse of
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS) stimulants is common. Substance use disorder, Addiction to some CNS stimulants can quickly lead to medical, psychiatric, and psychosocial deterioration. Drug tolerance, dependence, and Drug sensitization, sensitization as well as a Drug withdrawal, 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.


Treatment for misuse

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.


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

* Antidepressants * Depressants * Hallucinogens * Nootropics * Psychoanaleptics


Notes


References


External links

* * *
Asia & Pacific Amphetamine-Type Stimulants Information Centre (APAIC)
{{Authority control Stimulants, Psychopharmacology