Stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase the activity of the
.Stimulants work by affecting the levels of certain neurotransmitters, such as dopamine, norepinephrine, serotonin, histamine and acetylcholine, in the synapses between neurons. These neurotransmitters regulate various functions, such as arousal, the reward system, learning, memory, and emotion. By increasing their availability, stimulants can produce a range of effects, from mild stimulation to euphoria, depending on the dose, route of administration, and individual factors.
Stimulants have a long history of use, both for medical and non-medical purposes. They have been used to treat various conditions, such as
However, stimulants also have potential risks and side effects, such as
. Therefore, the use of stimulants is regulated by laws and policies in most countries, and requires medical supervision and prescription in some cases.Definition
A stimulant is an overarching term that covers many drugs including those that increase the activity of the central nervous system and the body,[1] drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects.[2] 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 and cause similar effects.[3]
Effects
Acute
Stimulants in therapeutic doses, such as those given to patients with
In some cases, psychiatric phenomena may emerge such as
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
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.[17] 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,[18] while inhalation may be associated with increased lower respiratory tract infection, lung cancer, and pathological restricting of lung tissue.[19] Cocaine may also increase risk for autoimmune disease[20][21][22] 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.[23][24][25][26]
Medical uses
Stimulants are widely used throughout the world as
Stimulants have been used in medicine for many conditions including
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.[40][41][42] However, they were largely abandoned for treatment of depression following the introduction of conventional antidepressants in the 1950s.[40][41] Subsequent to this, there has been a resurgence in interest in stimulants for depression in recent years.[43][44]
Stimulants produce a fast-acting and pronounced but transient and short-lived
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, a substituted amphetamine and consequently, a substituted phenethylamine.[citation needed]
When referring to stimulants, the parent drug (e.g., amphetamine) will always be expressed in the singular[according to whom?]; with the word "substituted" placed before the parent drug (substituted amphetamines).
Major stimulant classes include
Amphetamines (class)
Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat
Cocaine analogs
Hundreds of cocaine analogs have been created, all of them usually maintaining a benzyloxy connected to the 3 carbon of a
Mechanisms of action
Most stimulants exert their activating effects by enhancing
There are also more indirect mechanisms of action a drug can elicit activating effects. Caffeine is an adenosine receptor antagonist, and only indirectly increases catecholamine transmission in the brain.[72] Pitolisant is an histamine 3 (H3)-receptor inverse agonist. As histamine 3 (H3) receptors mainly act as autoreceptors, pitolisant decreases negative feedback to histaminergic neurons, enhancing histaminergic transmission.
The precise mechanism of action of some stimulants, such as modafinil, for treating symptoms of narcolepsy and other sleep disorders, remains unknown.[73][74][75][76][77]
Notable stimulants
Amphetamine
Amphetamine is a potent
The first pharmaceutical amphetamine was
Amphetamine is a
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.[93]
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.[94] 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.[95][96] 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.[95]
Caffeine is also included in some medications, usually for the purpose of enhancing the effect of the primary ingredient,[97] or reducing one of its side-effects (especially drowsiness).[98] Tablets containing standardized doses of caffeine are also widely available.[99]
Caffeine's mechanism of action differs from many stimulants, as it produces stimulant effects by inhibiting adenosine receptors.[100] Adenosine receptors are thought to be a large driver of drowsiness and sleep, and their action increases with extended wakefulness.[101] Caffeine has been found to increase striatal dopamine in animal models,[102] as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors,[103] 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.[104] 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.[105]
Coffee consumption is associated with a lower overall risk of
Ephedrine
Ephedrine is a
In chemical terms, it is an
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,
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".[122]
MDPV
Methylenedioxypyrovalerone (MDPV) is a
Incidents of psychological and physical harm have been attributed to MDPV use.[127][128]
Mephedrone
Mephedrone is a
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
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.[131][132][133]
Methamphetamine
Methamphetamine (contracted from
Methamphetamine may be sold illicitly, either as pure dextromethamphetamine or in an
In low doses, methamphetamine can cause an
Methylphenidate
Methylphenidate is a stimulant drug that is often used in the treatment of ADHD and narcolepsy and occasionally to treat obesity in combination with diet restraints and exercise. Its effects at therapeutic doses include increased focus, increased alertness, decreased appetite, decreased need for sleep and decreased impulsivity. Methylphenidate is not usually used recreationally, but when it is used, its effects are very similar to those of amphetamines.
Methylphenidate acts as a norepinephrine-dopamine reuptake inhibitor, by blocking the norepinephrine transporter (NET) and the dopamine transporter (DAT). Methylphenidate has a higher affinity for the dopamine transporter than for the norepinephrine transporter, and so its effects are mainly due to elevated dopamine levels caused by the inhibited reuptake of dopamine, however increased norepinephrine levels also contribute to various of the effects caused by the drug.
Methylphenidate is sold under a number of brand names including Ritalin. Other versions include the long lasting tablet Concerta and the long lasting transdermal patch Daytrana.
Cocaine
Cocaine is an
Nicotine
Phenylpropanolamine
Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the
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.[153] In India, human use of PPA and its formulations were banned on 10 February 2011.[154]
Lisdexamfetamine
Lisdexamfetamine (Vyvanse, etc.) is an amphetamine-type medication, sold for use in treating ADHD.[155] Its effects typically last around 14 hours.[156] Lisdexamfetamine is inactive on its own and is metabolized into dextroamphetamine in the body.[56] Consequently, it has a lower abuse potential.[56]
Pseudoephedrine
Pseudoephedrine is a
The
). 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.[159][160]
Khat contains a
Modafinil
Pitolisant
Pitolisant is an inverse agonist (antagonist) of the histamine 3 (H3) autoreceptor. As such, pitolisant is an antihistamine medication that also belongs to the class of CNS stimulants.[171][172][173][174] Pitolisant is also considered a medication of eugeroic class, which means that it promotes wakefulness and alertness. Pitolisant is the first eugeroic drug that acts by blocking the H3 autoreceptor.[175][176][177]
Pitolisant has been shown to be effective and well-tolerated for the treatment of narcolepsy with or without cataplexy.[177][176][175]
Pitolisant is the only non-controlled anti-narcoleptic drug in the US.[175] It has shown minimal abuse risk in studies.[175][178]
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.[179] 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.[180]
Recreational use and issues of abuse
Stimulants enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, awareness, wakefulness, endurance, productivity, and motivation, arousal, locomotion, heart rate, and blood pressure, and a diminished desire for food and sleep. Use of stimulants may cause the body to reduce significantly its production of natural body chemicals that fulfill similar functions. Until the body reestablishes its normal state, once the effect of the ingested stimulant has worn off the user may feel depressed, lethargic, confused, and miserable. This is referred to as a "crash", and may provoke reuse of the stimulant.
Dependence potentials of common stimulants[161] | ||||
---|---|---|---|---|
Drug | Mean | Pleasure | Psychological dependence | Physical dependence |
Cocaine | 2.39 | 3.0 | 2.8 | 1.3 |
Tobacco | 2.21 | 2.3 | 2.6 | 1.8 |
Amphetamine | 1.67 | 2.0 | 1.9 | 1.1 |
Ecstasy |
1.13 | 1.5 | 1.2 | 0.7 |
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.[184]
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.[185]
See also
- Antidepressants
- Depressants
- Hallucinogens
- Nootropics
- Psychoanaleptics
Notes
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There is compelling evidence that the negative neuropsychiatric consequences of METH abuse are due, at least in part, to drug-induced neuropathological changes in the brains of these METH-exposed individuals ...
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External links
- "Long Island Council on Alcohol & Drug Dependence – About Drugs – Stimulants". Archived from the original on 5 June 2008. Retrieved 4 August 2007.
{{cite web}}
: CS1 maint: unfit URL (link) - "Online – Publications – Drugs of Abuse – Stimulants". Archived from the original on 22 September 2006. Retrieved 11 January 2008.
{{cite web}}
: CS1 maint: unfit URL (link) - Asia & Pacific Amphetamine-Type Stimulants Information Centre (APAIC)