Amphetamine

Amphetamine (often abbreviated as Amp or Amph) is a stimulant of the phenethylamine class, commonly prescribed by doctors for treatment of ADHD and narcolepsy. Other common names for amphetamine are Addy/Addies, Adderall, Dexedrine, Vyvanse, and Speed. While it's properties make it ideal as a medical treatment, it is also often used recreationally as a study aid by students or as a party drug due to its euphoric properties.

Harm reduction

Amphetamine is most commonly taken in therapeutic dosages by people who use it as a medication or study aid. However, people who use it recreationally for its euphoric effects tend to take significantly higher and more dangerous doses.

The comedowns from moderate to high dosages of amphetamine or amphetamine-related substance (such as 2-FEA, 3-FEA, and methamphetamine) can be brutal. Often ranging from loss of energy, depression, anxiety and apathy to even insomnia, suicidal thoughts, and an overall disinterest in regular everyday life. Due to the severity of these comedowns, users often face the urge to redose just to avoid the comedown, though this eventually stops working due to side effects becoming stronger than the recreational effects.

Binging on amphetamine can cause the effects listed previously to become exponentially worse. The body eventually develops a tolerance to amphetamine, and even to its own neurotransmitters extremely quickly, causing it to need higher dosages for the same effects. Lack of sleep can also cause delirium, a state in which a user cannot differentiate reality from delusion. Coupled with high dosage redosing and lack of sleep, heavy-dosed amphetamines wrecks havoc on the brain, causing damage to the user's ability to feel pleasure over time.

To counteract this, sleep well before dosing and avoid pulling all-nighters. While amphetamine may seem to give you unlimited energy and endless euphoria, these effects will diminish quickly if one is sleep-deprived. Additionally, the "energy" provided after not sleeping for long periods of time (3 days+) can be extremely uncomfortable, risking stimulant psychosis.

Make sure to eat and stay hydrated. This is easier said than done, however, a lot of the negative side effects of amphetamine come from the body starving and being dehydrated, so no matter how hard it may seem, try to get important proteins in your body, even if a granola bar goes a long way in helping in the long run with amphetamine.

Injecting, snorting, or boofing (rectal) amphetamine may be more intense, but comes at the cost of a potentially harsher comedown, and shorter duration.

Avoid taking amphetamine with any heart problems. Extra strain added by amphetamine to the heart may result in a heart attack.

Avoid drinking or using depressants such as benzodiazepines or opioids with amphetamine. With amphetamine present, users often miscalculate and overdo it with depressants because they might not feel them as strongly compared to when they're sober. However, while they might not cognitively feel it, impairment can be equally present either sober or on amphetamine.

One of the main concerns when it comes to amphetamine-related neurotoxicity, and to extension amphetamine itself is overheating. Staying in a cold environment is the best thing one can do for their brain and body during amphetamine use.

Make sure to keep up with all normal hygiene practices. Feeling great doesn't mean that you look or smell great. Additionally, amphetamine can dry out your mouth, and correspondingly may increase tooth decay, so dental hygiene is of utmost importance.

Teeth grinding is a common side effect of amphetamine, so make sure to have some gum before carrying through the experience to negate this.

MOST IMPORTANTLY use the lowest dose possible, and don't use consistently for extended periods of time without indication from a doctor.

With that out of the way, there are a few things to do in order to to lower neurotoxicity and soften the comedown.

Supplements:

Magnesium: This essential mineral mitigates some amphetamine-induced neurotoxicity and slows down the development of drug tolerance. Amphetamine use can lower your body's magnesium quantity. Magnesium has been shown to positively modulate/enhance the activity of GABA receptors, so it's potentially helpful for anxiety caused by amphetamine. It's recommended to take it immediately before and after the experience. Magnesium is also an NMDA receptor antagonist, theoretically preventing tolerance buildup and giving it neuroprotective qualities. Make sure to get a type of magnesium that has high bioavailability, as not all magnesium formulations are equal. Some magnesium formulations can cause diarrhea.

Multivitamins: Make sure that they are high in Vitamin C, Vitamin D, and all B Vitamins.. It's recommended to take one serving at some point after the amphetamine wears off. Intake before usage isn't recommended if the multivitamin contains Vitamin C, as it increases amphetamine's rate of clearance in the body.

L-Tyrosine: This amino acid is a necessary, albeit indirect, precursor for bodily dopamine and norepinephrine production. Both of these neurotransmitters are depleted by amphetamine usage, and depletion of L-Tyrosine & its precursor L-Phenylalanine stunts the release of dopamine by amphetamine(s).

L-Theanine: This amino acid can decrease anxiety & other negative effects.

L-Phenylalanine: This amino acid is a precursor to L-Tyrosine, and while it's an indirect precursor to dopamine and norepinephrine as well, certain rate-limiting factors make it less effective than L-Tyrosine.

N-Acetylcysteine: attenuates the damage caused by oxidative stress, and it's been demonstrated to specifically reduce damage induced by amphetamine and it's analogues. It's been recommended to take this supplement after the fact. Use with great caution, as some studies indicate possible cardiotoxicity, worsened anxiety, and symptoms of psychosis; although this effect has only been seen in animal studies.

Melatonin: has been shown to scavenge free radicals, and promotes enzymes which do the same, resulting in antioxidant effects. It's recommended to take this supplement close to the time which you plan to sleep, closest to 9pm is best as it mimics natural melatonin secretion.

Antacids: Antacids have been proven to aid in the absorption and extend the duration of amphetamine(s). It's recommended to take them 15 - 45 minutes before ingesting amphetamine, as absorption of amphetamine is somewhat pH-dependent. Acidic environments impede the speed and extent of absorption. Lower/acidic pH in the urinary tract will also speed up the excretion of amphetamine. Basic antacids have been proven to slightly raise the urinary pH, potentially extending the duration. Chewable antacids containing calcium carbonate (i.e. Tums) or similar are most effective. Baking soda is sometimes used, but comes at greater risk of harm than typical antacids due to heavy sodium intake.

Addiction potential

Amphetamine is considered to be a moderately-highly addictive substance, and has the potential to cause long term damage, mostly in the form of neurotoxicity/brain damage. It's dependence syndrome and accordingly withdrawal symptoms are mainly psychological, with physical withdrawals (such as those found with opioids and benzodiazepines) generally not being experienced whatsoever, or being mild in severity. The withdrawals generally last around a month on average, however the withdrawals have been reported to last multiple months in some extreme cases of abuse.

Lethargy

Flu-like body aches

Depression

Anxiety

Extreme appetite

Increased sleep

Parkinson-like shaking

Forgetfulness

Reduced motor ability

Apathy

Boredom

Urges to take amphetamine

Amphetamine is addictive in the short-term as well, with many users engaging in "binging" behaviors with this drug.

Effects

As a stimulant, amphetamine typically leaves users motivated, focused, hyper-aware of their environment, energetic, awake, and confident. Amphetamine also induces euphoria on recreational dosages for both people with ADHD and those without it.

Positive/neutral cognitive effects:

Feelings of motivation and confidence // A pinnacle effect of the amphetamine experience would be the increased drive for one to do things and confidence to go ahead and act on the things one wishes to do. This is an effect increasing in intensity as dosage increases. This usually encourages activity that a user would otherwise find menial or boring, and is the reason why it can be effectively used as a study or work drug.

Mental euphoria // This effect is particularly powerful at higher dosages, and can make even the most menial of tasks (i.e. cleaning your room) seem better than most things in sobriety. In lower dosages, particularly medical ones, one would actually get more of a feeling of emotional suppression instead of a feeling of euphoria, though this is set & setting dependent.

Perceived mental clarity // Alongside raising confidence, amphetamine allows a user to feel clear in their thinking, particularly at lower dosages. Sometimes during higher dosages, the speed of one's thoughts can decrease this perception of clarity.

Hyperfocus // Amphetamine's hyperfocus can be particularly intense, though you can at times also get a feeling of restless energy from being overly stimulated. Focus enhancement is more common to occur at lower & common dosages, but it occurs in all dosages. The higher the dosage, the more intense it is, although with higher dosages there is a higher chance of being overly stimulated and being in an overstimulated mental state making focusing more difficult. At higher dosages this can also manifest in a more scattered way, like hyperfocusing on something while also having a restless desire to complete other tasks at the same time. This is why higher dosages tend to work less well for treating ADHD, since beyond a certain point it would make you hyper even if you're a more focused & alert sort of hyper than you would be sober.

Wakefulness // This is proportionate to dosage taken, with low doses allowing for less wakeful states or sleep to be feasible, but higher dosages make you stay awake and unable to sleep. This can linger for awhile after proportionate to dosage. With amphetamines in particular, it is very strong, and that is why it allows people who continue to redose it to be awake for multiple days with minimal fatigue and continue staying awake. Wakefulness doesn't necessarily entail alertness & cognition however, as cognition is still impaired while awake for multiple days with or without stimulants to aid in the process.

Mental stimulation // In essence, this stimulates your internal monologue and makes thoughts run faster. It can make you feel as though you need to be thinking about something or immersed in something at all times. In lower doses, this is typically more focus inducing, although higher dosages can encourage a more scatterbrained mental stimulation.

Enhanced sex drive // With amphetamine-type stimulants in particular, this effect is particularly intense, although the vasoconstriction can make it difficult to achieve erection & climax. The climax also significantly increases in intensity.

Inaccurate time perception // Time may seem to fly by way more quickly on amphetamines than it would sober. This can at times be amplified by the hyperfocus, causing one to lose track of time.

Music enhancement // The listener of music under the influence of amphetamine may consider the experience more pleasurable and/or meaningful than it would sober.

Increased seriousness // Generally occurs in a large subset of people and is one reason it's used for ADHD, it encourages more serious & productive behaviors as opposed to nonsensical and humorous ones. This scales proportionate to dosage, and does not always occur, but is a common associated mindset. One can still laugh and have fun on amphetamines, though usually amphetamines make one more apt to make a serious & well thought out joke as opposed to something thoughtless. This is why it can encourage people who otherwise don't care about school and more intellectual pursuits to have a shift in personality under the influence.

Increased socialization & talkativeness // This does not occur with everyone, but amphetamine can have the effect on people of making you want to talk more & even feel more connected to others. This can sometimes lead to being overly open about things, and is proportional to dosage. Some users do not get this effect & may even desire to isolate themselves, but others get it so much they compare the feeling to other empathogenic stimulants. Users undergoing this effect should try to remember not to do things they would regret sober, like telling someone you barely know your entire life story. Coupled with the aforementioned increased seriousness, this can also lead to one sometimes being less pleasant to talk to under the influence since they could more focused on intellectual things as opposed to unserious & fun things. This can also lead to users being more picky of whom they wish to talk to under the influence, and sometimes one can get in a state wherein they really yearn for conversation but are unusually picky of who they talk to. The opposite can occur however, especially on the peak, and socialization can universally be encouraged. Ultimately, it is extremely set and setting dependent.

Positive/neutral physiological effects:

Physical stimulation and energy // Makes the user want to move, and couples with the mental motivation to make people want to do things. It can actually encourage you to sit still more on lower dosages, although in higher amounts the effect becomes more and more forced, occasionally resulting in subtle twitches or shakes. Sometimes this can interact with music enhancement to encourage a user to dance, or with hyperfocus to encourage movement to continue with the task. Regardless of what it is, amphetamine will increase your desire to move.

Physical euphoria // Dosage dependent, typically being noticable at more intense dosages. This can persist into the comedown as well to a degree, and generally consists of a nice feeling throughout the body.

Appetite suppression // Becomes more intense as dosage increases, can discourage eating ample quantities of food. At higher dosages, food may literally feel more difficult to consume, and you may chew excessively. Can be good in some cases, but especially with binges, can quickly become unhealthy.

Bronchodilation and decongestion // Amphetamines and similar compounds are present in some inhalers and OTC decongestants. This can lead to a feeling of increased stamina, however, it is not recommended to exercise or undergo physical exertion on amphetamines, unless it's mild and/or your dosage is low, as it can be extremely dangerous.

Negative cognitive effects:

Psychosis // Typically occurs with heavy doses or alongside sleep deprivation, this leads to a disconnect from reality comparable to what deliriant drugs offer, with effects such as hallucinations not distinguishable from reality, nonsensical thinking, delusions, and more.

Irritability // It typically scales to dosage and is much more prevalent during the comedown. It can be apparent during the peak, although the peak can actually make one more patient & pleasant about things as opposed to irritable. Due to its focus enhancing effects & stimulating effects, being interrupted from a task is a common culprit. This can sometimes lead to angry outbursts in certain situations with certain individuals.

Impulsivity // Can cause one to act impulsively due to its euphoric effects making things seem much nicer coupled with the motivation & confidence enhancement making your choice seem more obvious and correct.

Extreme fixations on small details // A side effect of hyperfocus most typically exacerbated on the comedown is the hyperfocus on small things. For instance, being particularly bothered by a slight asymmetry in something, or being excessively picky about word choice.

Anxiety and paranoia // This can occur on the peak, although is typically much more intense on the comedown. Amphetamines can amplify fears that would not normally bother one as much sober, and this can lead to negative mental states.

Negative physiological effects:

Increased heart-rate and blood pressure // Heart rate and blood pressure can significantly increase, which can cause paranoia in some users & can lead to more serious issues. In general, one is advised to avoid physical activity, and dose carefully.

Nausea // Occasionally, typically in heavier doses, amphetamine can cause nausea. This can also occur while trying to eat on amphetamines sometimes.

Dizziness // Occasionally, typically in heavier dosages, amphetamine can cause a feeling of dizziness.

Vasoconstriction // Blood pressure increases under the influence proportional to dosage. This can be uncomfortable at times, but it can also lead to a body high.

Grinding of teeth // Increases proportional to dosage, it is encouraged to chew gum during the experience for this reason.

Increase in tempurature // Amphetamine can increase bodily temperature.

Sweatiness and body odor // Due to increased release of norepinephrine, amphetamine can cause you to sweat more and therefore smell worse.

Dehydration and dry mouth // Amphetamine can cause one's mouth to dry up & it can be uncomfortable in some people.

A common myth states users with ADHD cannot derive recreational effects from amphetamine, or that they always experience sedation instead of stimulation. This is untrue, and stimulant addiction and abuse can still occur in those with ADHD.

Basic Pharmacology

Amphetamine is a central nervous stimulant that increases concentrations of the monoamine neurotransmitters norepinephrine, dopamine (and serotonin, to a lesser extent) in the brain by eliciting their release. Norepinephrine is a chemical related to adrenaline (epinephrine) that stimulates the sympathetic nervous system, which is responsible for the body's "fight or flight" response. Dopamine is a chemical used for many neurological processes, mainly in the brain's "reward system". The former involvement is responsible for much of the effects on attention, motivation, etc. that amphetamine possesses. Amphetamine's neurological effects can be seen in contrast to reuptake inhibitors, such as methylphenidate (brand name Ritalin) and cocaine, which purely block the removal of the aforementioned neurotransmitters which were released naturally. Amphetamine, on the other hand, causes your neurons to release these chemicals an abnormal, elevated amount compared to normal, in addition to preventing their removal/reuptake.

Advanced Pharmacology

Amphetamine, in addition to basic reuptake inhibition as with drugs such as cocaine, methylphenidate, and most cathinones, is a releaser of monoamines, with significant bias towards norepinephrine and dopamine over serotonin. It's mechanism, as a result, is considerably more complex. First, amphetamine enters the cell via one of two mechanisms: simple diffusion through the neuron's membrane, or transport via one of the monoamine transporters. It's theorized it's mainly the former, as amphetamine's binding affinity for monoamine transporters is relatively low in comparison to most reuptake inhibitors. Once in the cell, it either agonizes TAAR1 (trace amine-associated receptor 1) or inhibits VMAT2 (vesicular monoamine transporter 2). Both of these are equally important in it's action, and VMAT2 inhibition alone actually reduces monoamine release and activity. Firstly, via VMAT2 inhibition, it causes a release of held monoamines into the cytosol via collapsing the pH gradient, allowing the monoamines to leave freely. Normally, this would prevent their release, as they'd be stuck in the cytosol and unable to be transported to the synapse. However, it's concurrent agonism of TAAR1 causes these monoamines to be released. TAAR1 agonism causes activation of both protein kinase a, and protein kinase c. While both of these kinases cause non-competitive reuptake inhibition via transporter internalization, the latter also causes phosphorylation of transporters entering the cell. Phosphorylation induces the transporters direction to reverse, transporting the monoamines released by VMAT2 inhibition into the synapse. This combo of effects is responsible for all the releasing properties of amphetamine(s), however amphetamine has additional, albeit less significant, targets as well. An excitatory amino acid transporter, EAAT3, is inhibited, along with a non-neuronal monoamine transporter, EMT, and a carnitine transporter, SLC22A5. The latter two are thought to be irrelevant, however the first, EAAT3 inhibition, is possibly associated with neurotoxicity, as it's partially responsible for maintaining non-neurotoxic levels of glutamate. It's last target is the postsynaptic 5-HT1A receptor, where it binds as an agonist. This is different from presynaptic 5-HT1A, which functions as an autoreceptor and lowers serotonergic activity.

History

Amphetamine was synthesized in 1887 by Romanian chemist Lazăr Edeleanu, but the effects were largely unknown until 1927 when chemist Gordon Alles discovered amphetamine's stimulant properties while researching the relation between the chemical constitution and physiological actions of compounds acting as stimulants or inhibitors of the central or peripheral nervous systems .

Amphetamine and its cousin methamphetamine were widely used during World War II by soldiers for its stimulant and performance-enhancing abilities. It has also been believed that Adolf Hitler was a user of methamphetamine.

Overdose

In the case of an overdose, one may experience abnormally increased heart rate (decreased is possible, but unlikely), blood pressure, temperature, and sweating. Symptoms resulting of overstimulation of the sympathetic nervous system aside from those listed such as muscle twitching and tightness, increased urination, dilated pupils, restlessness, and generalized anxiety are also likely. All of these can result from normal amphetamine usage, but are more likely to occur and of greater intensity in overdose. The user may fall into a state of state not unlike typical psychosis. This can manifest as delusions, hallucinations, general paranoia, irrational thinking, and can make the user act in a violent and atypical manner. However, unlike most cases of psychosis, stimulant psychosis generally resolves on it's own after sleeping and/or cessation of usage. Stimulant psychosis, while being a symptom of overdose, is also possible with normal doses, especially when coupled with sleep deprivation. The LD50 of Amphetamine is 96.8 mg/kg orally in rats, or ~14.2mg/kg orally in humans. This is 854mg for a 60kg (130lbs) person person, meaning there's a 50 percent chance of death at that dose and weight.

If you or someone you know believes they're overdosing on amphetamine, it's highly advised to request medical help. Deaths from amphetamine(s) alone are rare, but tens of thousands still succumb to it every year. Symptoms indicating increased risk of lethality include pain in the chest, left arm, left shoulder, or jaw, the feeling of intense pressure or tightness in/on the chest, convulsions, extreme lightheadedness, unconciousness, seizure, and delirium/confusion.

Legality

Amphetamine is a heavily controlled or banned substance in most countries. Possession without a prescription, distribution, or manufacture license is generally punishable by jail time and/or significant fines. Possession carries heavier punishment in some countries.