Since the first preparation was reported in 1887, numerous synthetic routes to amphetamine have been developed. The class includes amphetamine itself, stimulants like methamphetamine, serotonergic empathogens like MDMA, and decongestants like ephedrine, among other subgroups. In organic chemistry, amphetamine is an excellent chiral ligand for the stereoselective synthesis of 1,1′-bi-2-naphthol.
Notes
In contrast to human studies, adult female rats exhibit markedly greater dopamine release in the nucleus accumbens and more pronounced behavioral effects from amphetamine administration relative to males, effects that may be modulated by fluctuating estradiol levels across the estrous cycle or more broadly by adult gonadal hormones. Moreover, neuroimaging studies have reported significant sex differences in the neural response to amphetamine in humans, including differences in dopamine release within the striatum and other brain regions. Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in a dose-dependent release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2. The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine because of its effects on monoamine transporters. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.
Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptorsnote 14 in the nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysine residue 9 dimethylation (H3K9me2) and blocks the induction of ΔFosB-mediated neural and behavioral plasticity by chronic drug use,sources 12 which occurs via H3K9me2-mediated repression of transcription factors for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5). Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness;sources 9 these effects depend on the user’s personality and current mental state. However, amphetamine pharmaceuticals are contraindicated in individuals with preexisting cardiovascular disease.sources 8
- Chronic overuse of dextroamphetamine can lead to severe drug dependence, resulting in withdrawal symptoms when drug use stops.
- Amphetamines are a type of stimulant drug that makes your nervous system more active.
- Reviews of human studies have also noted that men typically report stronger positive subjective responses to amphetamine compared to women tested during the luteal phase, whereas these sex differences are absent when women are tested during the follicular phase;sources 18 subjective responses to amphetamine appear to correlate positively with plasma or salivary estrogen concentrations.
- According to a 2025 review, the discontinuation of amphetamine at therapeutic doses does not typically result in withdrawal symptoms.
- Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these.
The reinforcing and motivational salience-promoting effects of amphetamine are due mostly to enhanced dopaminergic activity in the mesolimbic pathway. A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. An amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia. Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose.
Missed Dose
This medication also may cause sudden death, heart attack or stroke in adults, especially adults who have heart defects or serious heart problems. Do not take a double dose to make up for a missed one. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Take the missed dose as soon as you remember it. Talk to your doctor about drinking fruit juice while taking this medicine.
Amphetamines
Recreational use of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes. As amphetamines affect the way the brain processes dopamine naturally, cessation can cause uncomfortable withdrawal symptoms. Here we look at the types of amphetamines, their effects, potential for addiction, and treatment options.
Amphetamine
‡IP₃ binds to its receptors on the endoplasmic reticulum to release intracellular Ca²⁺ stores, and together with diacylglycerol activates conventional PKC isoforms. TAAR1 has been identified as a biomolecular target of amphetamine that initiates some of amphetamine’s kinase-dependent signaling cascades. Phosphorylation of DAT by either kinase induces transporter internalization (non-competitive reuptake inhibition), but PKC-mediated phosphorylation alone induces the reversal of dopamine transport through DAT (i.e., dopamine efflux). In parallel, amphetamine also increases intracellular cAMPTooltip cyclic adenosine monophosphate, which activates protein kinase A (PKA) and protein kinase C (PKC), whilst elevated intracellular Ca²⁺ activates PKC alone. As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. In humans, the only post-synaptic receptor at which amphetamine is known to bind is the 5-HT1A receptor, where it acts as an agonist with low micromolar affinity.
Amphetamine (oral route)
You might be hesitant to use one because the word “amphetamine” can carry negative connotations. Your healthcare provider can tell you more about how long you should wait after taking your medication before it’s OK to drink alcohol. You shouldn’t drink alcohol too soon after taking an amphetamine. Make sure your healthcare provider knows about every medication, herbal remedy or supplement you take. They can also tell you which side effects need immediate care and which can wait for an appointment. Your healthcare provider or pharmacist can tell you more about possible or likely side effects.
Treatment for amphetamine abuse
Dextroamphetamine also activates TAAR1 in peripheral organs along the gastrointestinal tract that are involved in the regulation of food intake and body weight. The pathophysiology of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the cortico-striatal-thalamic-cortical loop. Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.
Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. This includes noradrenergic neurons in the locus coeruleus, dopaminergic neurons in the ventral tegmental area, histaminergic neurons in the tuberomammillary nucleus, and serotonergic neurons in the dorsal raphe nucleus. Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing monoamine neurotransmitter activity in the ARAS. Lateral hypothalamic orexin neurons innervate every component of the ascending reticular activating system (ARAS), which includes noradrenergic, dopaminergic, histaminergic, and serotonergic nuclei that promote wakefulness. Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms.
You may take this medicine with or without food or liquid. It is best to take this medicine when you wake up in the morning. This medicine should come with a Medication Guide. If too much of this medicine is taken, it may become habit-forming (causing mental or physical dependence). Take this medicine exactly as directed by your doctor. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
- Hence, in contrast to dextroamphetamine, parenteral use does not enhance the subjective effects of lisdexamfetamine.
- Amphetamine also interacts with MAOIs, particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); therefore, concurrent use of both is dangerous.
- Dextroamphetamine is a subtype of amphetamine.
However, a typical dose of amphetamine is generally between 5mg and 40mg per day, split into one to three doses. Amphetamines are a form of central nervous system (CNS) stimulant drugs that come as either prescription medication or illegal narcotics, such as speed. These side effects may go away during treatment as your body adjusts to the medicine.
Symptoms of overdose
Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams. One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system. In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D2 (DRD2) density in the striatum. A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in randomized controlled trials (RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain.
Dextroamphetamine, marketed under the brand names Dexedrine and Zenzedi, is the only Amphetamine Drug Profile enantiopure amphetamine product currently available. Of those, Evekeo (including Evekeo ODT) is the only product containing only racemic amphetamine (as amphetamine sulfate), and is therefore the only one whose active moiety can be accurately referred to simply as “amphetamine”. Several currently marketed amphetamine formulations contain both enantiomers, including those marketed under the brand names Adderall, Adderall XR, Mydayis,note 1 Adzenys ER, Adzenys XR-ODT, Dyanavel XR, Evekeo, and Evekeo ODT. As a result of the United Nations 1971 Convention on Psychotropic Substances, amphetamine became a schedule II controlled substance, as defined in the treaty, in all 183 state parties. Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine and MDMA. During 2012, approximately 5.9 metric tons of illicit amphetamine were seized within EU member states; the “street price” of illicit amphetamine within the EU ranged from €6–38 per gram during the same period.
Do not take other medicines unless they have been discussed with your doctor. The results of some tests may be affected by this medicine. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body. These may be symptoms of a serious condition called serotonin syndrome. This medicine may cause Raynaud’s phenomenon, which is a problem with blood circulation in the fingers or toes. Do not drive or do anything else that could be dangerous until you or your child know how this medicine affects you.
Amphetamine, specifically the more dopaminergic dextrorotatory enantiomer (dextroamphetamine), is also used recreationally as a euphoriant and aphrodisiac, and like other amphetamines; is used as a club drug for its energetic and euphoric high. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects.sources 3 Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness, and improved cognitive control.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding.
An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. Exercise therapy improves clinical treatment outcomes and may be used as an adjunct therapy with behavioral therapies for addiction.sources 10
Leave a Reply