An organism is any living thing that functions as an individual.
Such a definition raises more problems than it solves, not least
because the concept of an individual is also difficult. Many criteria,
few of them widely accepted, have been proposed to define what an
organism is. Among the most common is that an organism has autonomous reproduction, growth, and metabolism. This would exclude viruses, despite the fact that they evolve like organisms. Other problematic cases include colonial organisms; a colony of eusocial insects is organised adaptively, and has germ-soma specialisation, with some insects reproducing, others not, like cells in an animal's body. The body of a siphonophore, a jelly-like marine animal, is composed of organism-like zooids, but the whole structure looks and functions much like an animal such as a jellyfish, the parts collaborating to provide the functions of the colonial organism.
The evolutionary biologists David Queller and Joan Strassmann
state that "organismality", the qualities or attributes that define an
entity as an organism, has evolved socially as groups of simpler units
(from cells upwards) came to cooperate without conflicts. They propose
that cooperation should be used as the "defining trait" of an organism.
This would treat many types of collaboration, including the fungus/alga partnership of different species in a lichen, or the permanent sexual partnership of an anglerfish, as an organism.
Etymology
The term "organism" (from the Ancient Greekὀργανισμός, derived from órganon, meaning 'instrument, implement, tool', 'organ of sense', or 'apprehension') first appeared in the English language in the 1660s with the now-obsolete meaning of an organic structure or organization. It is related to the verb "organize". In his 1790 Critique of Judgment, Immanuel Kant defined an organism as "both an organized and a self-organizing being".
Whether criteria exist, or are needed
One criterion proposes that an organism cannot be divided without losing functionality. This basil plant cutting is however developing new adventitious roots from a small bit of stem, forming a new plant.
Among the criteria that have been proposed for being an organism are:
noncompartmentability – structure cannot be divided without losing functionality. Richard Dawkins stated this as "the quality of being sufficiently heterogeneous in form to be rendered non-functional if cut in half". However, many organisms can be cut into pieces which then grow into whole organisms.
individuality – the entity has simultaneous holdings of genetic uniqueness, genetic homogeneity and autonomy
"anti-entropy", the ability to maintain order, a concept first proposed by Erwin Schrödinger; or in another form, that Claude Shannon's information theory can be used to identify organisms as capable of self-maintaining their information content
Other scientists think that the concept of the organism is inadequate in biology;
that the concept of individuality is problematic;
and from a philosophical point of view, question whether such a definition is necessary.
Problematic cases include colonial organisms: for instance, a colony of eusocial insects fulfills criteria such as adaptive organisation and germ-soma specialisation. If so, the same argument, or a criterion of high co-operation and low conflict, would include some mutualistic (e.g. lichens) and sexual partnerships (e.g. anglerfish) as organisms. If group selection occurs, then a group could be viewed as a superorganism, optimized by group adaptation.
Another view is that attributes like autonomy, genetic
homogeneity and genetic uniqueness should be examined separately rather
than demanding that an organism should have all of them; if so, there
are multiple dimensions to biological individuality, resulting in
several types of organism.
Organisms at differing levels of biological organisation
A lichen consists of a body formed mainly by fungi, with unicellular algae or cyanobacteria (green) interspersed within the structure, and a bacterial microbiome. The species are mutually interdependent, like cells within a multicellular organism.
Differing levels of biological organisation give rise to potentially different understandings of the nature of organisms. A unicellular organism is a microorganism such as a protist, bacterium, or archaean, composed of a single cell, which may contain functional structures called organelles. A multicellular organism such as an animal, plant, fungus, or alga is composed of many cells, often specialised. A colonial organism such as a siphonophore is a being which functions as an individual but is composed of communicating individuals. A superorganism is a colony, such as of ants, consisting of many individuals working together as a single functional or social unit. A mutualism is a partnership of two or more species which each provide some of the needs of the other. A lichen consists of fungi and algae or cyanobacteria, with a bacterial microbiome;
together, they are able to flourish as a kind of organism, the
components having different functions, in habitats such as dry rocks
where neither could grow alone. The evolutionary biologists David Queller and Joan Strassmann
state that "organismality" has evolved socially, as groups of simpler
units (from cells upwards) came to cooperate without conflicts. They
propose that cooperation should be used as the "defining trait" of an
organism.
Queller and Strassmann's view of organisms as cooperating entities at differing levels of biological organisation
Free-living unicellular amoebae for most of lifetime; swarm and
aggregate to a multicellular slug, cells specialising to form a dead
stalk and a fruiting body
Samuel Díaz‐Muñoz and colleagues (2016) accept Queller and
Strassmann's view that organismality can be measured wholly by degrees
of cooperation and of conflict. They state that this situates organisms
in evolutionary time, so that organismality is context dependent. They
suggest that highly integrated life forms, which are not context
dependent, may evolve through context-dependent stages towards complete
unification.
A virus such as tobacco mosaic virus is not a cell; it contains only its genetic material, and a protein coat.
Viruses are not typically considered to be organisms, because they are incapable of autonomous reproduction, growth, metabolism, or homeostasis. Although viruses have a few enzymes
and molecules like those in living organisms, they have no metabolism
of their own; they cannot synthesize the organic compounds from which
they are formed. In this sense, they are similar to inanimate matter. Viruses have their own genes, and they evolve.
Thus, an argument that viruses should be classed as living organisms is
their ability to undergo evolution and replicate through self-assembly.
However, some scientists argue that viruses neither evolve nor
self-reproduce. Instead, viruses are evolved by their host cells,
meaning that there was co-evolution of viruses and host cells. If host
cells did not exist, viral evolution would be impossible. As for
reproduction, viruses rely on hosts' machinery to replicate. The
discovery of viruses with genes coding for energy metabolism and protein
synthesis fuelled the debate about whether viruses are living
organisms, but the genes have a cellular origin. Most likely, they were
acquired through horizontal gene transfer from viral hosts.
There is an argument for viewing viruses as cellular organisms. Some
researchers perceive viruses not as virions alone, which they believe
are just spores of an organism, but as a virocell - an ontologically mature viral organism that has cellular structure. Such virus is a result of infection of a cell and shows all major physiological properties of other organisms: metabolism, growth, and reproduction, therefore, life in its effective presence.
The philosopher Jack A. Wilson examines some boundary cases to demonstrate that the concept of organism is not sharply defined. In his view, sponges, lichens, siphonophores, slime moulds, and eusocial colonies such as those of ants or naked molerats, all lie in the boundary zone between being definite colonies and definite organisms (or superorganisms).
Jack A. Wilson's analysis of the similar organism-like nature of siphonophores and jellyfish
Scientists and bio-engineers are experimenting with different types of synthetic organism, from chimaeras composed of cells from two or more species, cyborgs including electromechanical limbs, hybrots
containing both electronic and biological elements, and other
combinations of systems that have variously evolved and been designed.
An evolved organism takes its form by the partially understood mechanisms of evolutionary developmental biology, in which the genome
directs an elaborated series of interactions to produce successively
more elaborate structures. The existence of chimaeras and hybrids
demonstrates that these mechanisms are "intelligently" robust in the
face of radically altered circumstances at all levels from molecular to
organismal.
Synthetic organisms already take diverse forms, and their diversity will increase. What they all have in common is a teleonomic
or goal-seeking behaviour that enables them to correct errors of many
kinds so as to achieve whatever result they are designed for. Such
behaviour is reminiscent of intelligent action by organisms;
intelligence is seen as an embodied form of cognition.
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, mood, and physical performance. Some stimulants are naturally-occuring while others only occur synthetic. Some of the most common stimulants are caffeine, nicotine, amphetamines, cocaine, methylphenidate, and modafinil. 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 excitatory neurotransmitters, particularly norepinephrine and dopamine (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 arousal, attention, the reward system, learning, memory, and emotion. Effects range from mild stimulation to euphoria, 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 narcolepsy, attention deficit hyperactivity disorder (ADHD), obesity, depression, and fatigue. 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.
A stimulant is an overarching term that covers many drugs 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 epinephrine and norepinephrine) 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 ergogenic
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 modafinil, 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.
In some cases, psychiatric phenomena may emerge such as stimulant psychosis, paranoia, 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 punding. 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 mydriasis (dilation of the pupils), increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, and may lead to rhabdomyolysis, stroke, cardiac arrest, or seizures.
However, given the complexity of the mechanisms that underlie these
potentially fatal outcomes of acute stimulant toxicity, it is impossible
to determine what dose may be lethal.
Chronic
Assessment
of the effects of stimulants is relevant given the large population
currently taking stimulants. A systematic review of cardiovascular
effects of prescription stimulants found no association in children, but
found a correlation between prescription stimulant use and ischemicheart attacks.
A review over a four-year period found that there were few negative
effects of stimulant treatment, but stressed the need for longer-term
studies. A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only.
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, stroke, and sepsis.
Some effects are dependent upon the route of administration, with
intravenous use associated with the transmission of many disease such as
Hepatitis C, HIV/AIDS and potential medical emergencies such as infection, thrombosis or pseudoaneurysm, while inhalation may be associated with increased lower respiratory tract infection, lung cancer, and pathological restricting of lung tissue. Cocaine may also increase risk for autoimmune disease
and damage nasal cartilage. Abuse of methamphetamine produces similar
effects as well as marked degeneration of dopaminergic neurons,
resulting in an increased risk for Parkinson's disease.
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 lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including amphetamine and methamphetamine) the value was 0.7%, and for MDMA 0.4%.
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 antidepressants 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 over placebo 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 is remarkably similar in its symptoms to those of major depressive disorder.
Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat major depression, where subjects do not respond well to traditional SSRI medications, but evidence supporting this use is poor/mixed. Notably, two recent large phase III studies of lisdexamfetamine (a prodrug to amphetamine) as an adjunct to an SSRI or SNRI in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness. Numerous studies have demonstrated the effectiveness of drugs such as Adderall (a mixture of salts of amphetamine and dextroamphetamine) in controlling symptoms associated with ADHD. Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse.
Hundreds of cocaine analogs 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
analogs have been developed as well.
Mechanisms of action
Most stimulants exert their activating effects by enhancing catecholamine
neurotransmission. Catecholamine neurotransmitters are employed in
regulatory pathways implicated in attention, arousal, motivation, task
salience and reward anticipation. Classical stimulants either block the reuptake or stimulate the efflux of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with empathogenic and hallucinogenic effects, also affect serotonergic transmission. Some stimulants, such as some amphetamine derivatives and, notably, yohimbine, can decrease negative feedback by antagonizing regulatory autoreceptors. Adrenergic agonists, such as, in part, ephedrine, act by directly binding to and activating adrenergic receptors, producing sympathomimetic effects.
Amphetamine is a potent central nervous system (CNS) stimulant of the phenethylamine class that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Amphetamine is also used off-label as a performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant.
Although it is a prescription medication in many countries,
unauthorized possession and distribution of amphetamine is often tightly
controlled due to the significant health risks associated with
uncontrolled or heavy use. As a consequence, amphetamine is illegally manufactured in clandestine labs to be trafficked and sold to users. Based upon drug and drug precursor seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.
The first pharmaceutical amphetamine was Benzedrine, a brand of inhalers used to treat a variety of conditions.
Because the dextrorotary isomer has greater stimulant properties,
Benzedrine was gradually discontinued in favor of formulations
containing all or mostly dextroamphetamine. Presently, it is typically
prescribed as mixed amphetamine salts, dextroamphetamine, and lisdexamfetamine.
Amphetamine is a norepinephrine-dopamine releasing agent (NDRA). It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2.
At therapeutic doses, this causes emotional and cognitive effects such
as euphoria, change in libido, increased arousal, and improved cognitive control. Likewise, it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength. In contrast, supratherapeutic doses of amphetamine are likely to impair cognitive function and induce rapid muscle breakdown. Very high doses can result in psychosis (e.g., delusions and paranoia), which very rarely occurs at therapeutic doses even during long-term use.
As recreational doses are generally much larger than prescribed
therapeutic doses, recreational use carries a far greater risk of
serious side effects, such as dependence, which only rarely arises with
therapeutic amphetamine use.
Roasted coffee beans, a common source of caffeine.
Caffeine is a stimulant compound belonging to the xanthine class of chemicals naturally found in coffee, tea, and (to a lesser degree) cocoa or chocolate. It is included in many soft drinks, as well as a larger amount in energy drinks. Caffeine is the world's most widely used psychoactive drug and by far the most common stimulant. In North America, 90% of adults consume caffeine daily.
A few jurisdictions restrict 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 cancer. This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer, but it may also have a modest effect on colorectal cancer.
There does not appear to be a significant protective effect against
other types of cancers, and heavy coffee consumption may increase the
risk of bladder cancer. A protective effect of caffeine against Alzheimer's disease is possible, but the evidence is inconclusive.Moderate coffee consumption may decrease the risk of cardiovascular disease, and it may somewhat reduce the risk of type 2 diabetes. Drinking 1-3 cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee. However those who drink 2–4 cups per day may be at a slightly increased risk. Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals. It may protect people from liver cirrhosis. There is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat headaches. Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude.
In chemical terms, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae). It works mainly by increasing the activity of norepinephrine (noradrenaline) on adrenergic receptors. It is most usually marketed as the hydrochloride or sulfate salt.
The herb má huáng (Ephedra sinica), used in traditional Chinese medicine (TCM), contains ephedrine and pseudoephedrine as its principal active constituents. The same may be true of other herbal products containing extracts from other Ephedra species.
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly) is a euphoriant, empathogen, and stimulant of the amphetamine class. Briefly used by some psychotherapists as an adjunct to therapy, the drug became popular recreationally and the DEA listed MDMA as a Schedule I controlled substance, prohibiting most medical studies and applications. MDMA is known for its entactogenic properties. The stimulant effects of MDMA include hypertension, anorexia (appetite loss), euphoria, social disinhibition, insomnia (enhanced wakefulness/inability to sleep), improved energy, increased arousal, and increased perspiration,
among others. Relative to catecholaminergic transmission, MDMA enhances
serotonergic transmission significantly more, when compared to
classical stimulants like amphetamine. MDMA does not appear to be
significantly addictive or dependence forming.
Due to the relative safety of MDMA, some researchers such as David Nutt
have criticized the scheduling level, writing a satirical article
finding MDMA to be 28 times less dangerous than horseriding, a condition
he termed "equasy" or "Equine Addiction Syndrome".
Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a designer drug. Products labeled as bath salts
containing MDPV were previously sold as recreational drugs in gas
stations and convenience stores in the United States, similar to the
marketing for Spice and K2 as incense.
Incidents of psychological and physical harm have been attributed to MDPV use.
Mephedrone is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone and MCAT. It is reported to be manufactured in China and is chemically similar to the cathinone compounds found in the khat plant of eastern Africa. It comes in the form of tablets or a powder, which users can swallow, snort, or inject, producing similar effects to MDMA, amphetamines, and cocaine.
Mephedrone was first synthesized in 1929, but did not become
widely known until it was rediscovered in 2003. By 2007, mephedrone was
reported to be available for sale on the Internet; by 2008 law
enforcement agencies had become aware of the compound; and, by 2010, it
had been reported in most of Europe, becoming particularly prevalent in
the United Kingdom. Mephedrone was first made illegal in Israel in 2008,
followed by Sweden later that year. In 2010, it was made illegal in
many European countries, and, in December 2010, the EU ruled it illegal.
In Australia, New Zealand, and the US, it is considered an analog of other illegal drugs and can be controlled by laws similar to the Federal Analog Act. In September 2011, the USA temporarily classified mephedrone as illegal, in effect from October 2011.
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 may be sold illicitly, either as pure dextromethamphetamine or in an equal parts mixture of the right- and left-handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in the United States.
Also, the production, distribution, sale, and possession of
methamphetamine is restricted or illegal in many other countries due to
its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In contrast, levomethamphetamine is an over-the-counter drug in the United States.
In low doses, methamphetamine can cause an elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis, rhabdomyolysis, and cerebral hemorrhage. Methamphetamine is known to have a high potential for abuse and addiction.Recreational use of methamphetamine may result in psychosis or lead to post-withdrawal syndrome, a withdrawal syndrome that can persist for months beyond the typical withdrawal period. Unlike amphetamine and cocaine, methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the central nervous system (CNS).
Unlike the long-term use of amphetamine in prescription doses, which
may improve certain brain regions in individuals with ADHD, there is
evidence that methamphetamine causes brain damage from long-term use in
humans;this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity. However, recreational amphetamine doses may also be neurotoxic.
Methylphenidate 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 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 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 receptors, 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.
In the United States, PPA is no longer sold without a prescription due to a possible increased risk of stroke
in younger women. In a few countries in Europe, however, it is still
available either by prescription or sometimes over-the-counter. In
Canada, it was withdrawn from the market on 31 May 2001. In India, human use of PPA and its formulations were banned on 10 February 2011.
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.
Modafinil is an eugeroic
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 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. Despite being a CNS stimulant, the addiction and dependence liabilities of modafinil are considered very low. Although modafinil shares biochemical mechanisms with stimulant drugs, it is less likely to have mood-elevating properties. The similarities in effects with caffeine are not clearly established. Unlike other stimulants, modafinil does not induce a subjective feeling of pleasure or reward, which is commonly associated with euphoria, an intense feeling of well-being. Euphoria is a potential indicator of drug abuse,
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 has been shown to be effective and well-tolerated for the treatment of narcolepsy with or without cataplexy.
Pitolisant is the only non-controlled anti-narcoleptic drug in the US. It has shown minimal abuse risk in studies.
Blocking the histamine 3 (H3) autoreceptor increases the activity of histamine neurons in the brain. The H3 autoreceptors regulate histaminergic activity in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting histamine 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.
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep.
Use of stimulants may cause the body to reduce significantly its
production of natural body chemicals that fulfill similar functions.
Until the body reestablishes its normal state, once the effect of the
ingested stimulant has worn off the user may feel depressed, lethargic,
confused, and miserable. This is referred to as a "crash", and may provoke reuse of the stimulant.
Abuse of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to medical, psychiatric, and psychosocial deterioration. Drug tolerance, dependence, and sensitization as well as a withdrawal syndrome can occur.
Stimulants may be screened for in animal discrimination and
self-administration models which have high sensitivity albeit low
specificity.[186] 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.
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.
