Amphetamine Amphetamine is a potent psychostimulant 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. 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. 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. 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. A protective effect of caffeine against
Alzheimer's disease is possible, but the evidence is inconclusive. Moderate coffee consumption may decrease the risk of
cardiovascular disease, and it may somewhat reduce the risk of
type 2 diabetes. Drinking 1–3 cups of coffee per day does not affect the risk of
hypertension compared to drinking little or no coffee. However those who drink 2–4 cups per day may be at a slightly increased risk. Caffeine increases
intraocular pressure in those with
glaucoma but does not appear to affect normal individuals. It may protect people from
liver cirrhosis. There is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat
headaches. Caffeine may lessen the severity of
acute mountain sickness if taken a few hours prior to attaining a high altitude.
Ephedrine Ephedrine is a
sympathomimetic amine similar in molecular structure to the well-known drugs
phenylpropanolamine and
methamphetamine, as well as to the important
neurotransmitter epinephrine (adrenaline). Ephedrine is commonly used as a stimulant,
appetite suppressant, concentration aid, and
decongestant, and to treat
hypotension associated with anesthesia. In chemical terms, it is an
alkaloid with a
phenethylamine skeleton found in various plants in the genus
Ephedra (family
Ephedraceae). It works mainly by increasing the activity of
norepinephrine (noradrenaline) on
adrenergic receptors. It is most usually marketed as the
hydrochloride or
sulfate salt. The herb
má huáng (
Ephedra sinica), used in
traditional Chinese medicine (TCM), contains ephedrine and
pseudoephedrine as its principal active constituents. The same may be true of other herbal products containing extracts from other
Ephedra species.
MDMA 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly) is an
entactogen, euphoriant, and psychostimulant 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 similar psychostimulants like amphetamine.
MDPV Methylenedioxypyrovalerone (MDPV) is a
psychoactive drug with stimulant properties that acts as a
norepinephrine-dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a
designer drug. Products labeled as
bath salts containing MDPV were previously sold as recreational drugs in gas stations and convenience stores in the United States, similar to the marketing for
Spice and
K2 as incense. Incidents of psychological and physical harm have been attributed to MDPV use.
Mephedrone 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 Methamphetamine (contracted from ) is a potent psychostimulant of the
phenethylamine and
amphetamine classes that is used to treat
attention deficit hyperactivity disorder (ADHD) and
obesity. Methamphetamine exists as two
enantiomers,
dextrorotary and
levorotary. Dextromethamphetamine is a stronger CNS stimulant than
levomethamphetamine; Both dextromethamphetamine and racemic methamphetamine are
schedule II controlled substances in the United States. 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. Unlike
amphetamine and
cocaine, methamphetamine is
neurotoxic to humans, damaging both
dopamine and
serotonin neurons in the
central nervous system (CNS). 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 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.
Phenylpropanolamine Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the
stereoisomers norephedrine and norpseudoephedrine, is a
psychoactive drug of the
phenethylamine and
amphetamine chemical classes that is used as a stimulant,
decongestant, and
anorectic agent. It is commonly used in
prescription and
over-the-counter cough and cold preparations. In
veterinary medicine, it is used to control
urinary incontinence in dogs under
trade names Propalin and Proin. In the United States, PPA is no longer sold without a prescription due to a 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 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. or as a
wakefulness-promoting agent. The
salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many
over-the-counter preparations, either as a single ingredient or (more commonly) in combination with
antihistamines,
guaifenesin,
dextromethorphan, and/or
paracetamol (acetaminophen) or another
NSAID (such as
aspirin or
ibuprofen). It is also used as a precursor chemical in the illegal production of methamphetamine.
Catha edulis (Khat) Khat is a
flowering plant native to the
Horn of Africa and the
Arabian Peninsula. Khat contains a
monoamine alkaloid called
cathinone, a "keto-amphetamine". This alkaloid causes excitement,
loss of appetite, and
euphoria. In 1980, the
World Health Organization (WHO) classified it as a
drug of abuse that can produce mild to moderate
psychological dependence (less than tobacco or
alcohol), although the WHO does not consider khat to be seriously addictive.
Modafinil 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. 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 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. Pitolisant is also considered a medication of
eugeroic class, which means that it promotes wakefulness and alertness. Pitolisant is the first
wakefulness-promoting agent that acts by blocking the
H3 autoreceptor. 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.
Serotonin 5-HT2A receptor agonists Certain
serotonergic psychedelics and related non-
hallucinogenic drugs, acting as
serotonin 5-HT2A receptor agonists, have been reported to have mild stimulant and/or "
psychic energizing" (i.e., acute
antidepressant) effects, both in animals and humans. These effects are often present at low or sub-hallucinogenic doses. or cause
insomnia.
DON,
Ariadne (4C-DOM; BL-3912; Dimoxamine),
2C-B,
2C-D, and the
tryptamines
5-MeO-DiPT Conversely,
psilocybin does not seem to produce the same stimulant effects. Relatedly, serotonin 5-HT2A receptor agonists are known to produce stimulant-like effects in animals such as
hyperlocomotion (increased locomotor activity) and
pro-motivational effects. == Recreational use and issues of abuse ==