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Dextroamphetamine (Dexedrine) Side Effects & Natural Options

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Taking a pill
Dexedrine is a stimulant drug commonly used to treat ADHD and narcolepsy. Dexedrine is also among the most abused substances for focus and energy. Understand its side effects and learn about the best natural options.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.

What is Dextroamphetamine (Dexedrine)?

Dexedrine is the brand name for dextroamphetamine, a drug that stimulates the brain. Like all stimulants, it promotes wakefulness, enhances concentration, and increases energy.

Dexedrine is most commonly used to treat narcolepsy, attention-deficit/hyperactivity disorder (ADHD), and chronic fatigue syndrome [1, 2].

Night shift workers use the medication in order to stay awake during their job. Athletes take the drug to boost their athletic ability and combat fatigue. Students take it in hopes of improving studying ability. Others abuse Dexedrine recreationally, to get high [3].

But Dexedrine abuse can have harmful consequences. It can increase blood pressure and cause heart problems, headaches, drug dependence, panic attacks, and suicidal or aggressive behavior [4].

Mechanism of Action

As you can probably guess from its name, the main active ingredient of Dexedrine, dextroamphetamine, is a member of the amphetamine family of drugs.

Amphetamines increase certain neurotransmitters in your brain, such as dopamine, norepinephrine, and serotonin [5, 6].

Amphetamines also reduce levels of the enzyme monoamine oxidase, which results in an increase in neurotransmitters in the brain [1].

Amphetamines also increase the release of adrenaline, which can lead to increased blood pressure and heart rate [1].

While these drugs affect many different systems in the body, amphetamines’ effects on the neurotransmitters dopamine and norepinephrine are by far the strongest out of all of them and are the main causes of their stimulating and attention-enhancing effects [4, 7, 2, 8, 9].

However, amphetamines’ strong ability to boost dopamine levels can also cause feelings of reward and pleasure (euphoria), which gives these drugs high potential for abuse and can easily lead to addiction if not taken correctly [10].

By increasing serotonin, amphetamines can also alleviate symptoms of anxiety and depression, which commonly occur alongside conditions such as ADHD [11, 1].

Dexedrine vs. Other Stimulants

Dextroamphetamine is a member of the amphetamine family, making it similar to other common drugs such as Adderall and Vyvanse. However, these drugs work in slightly different ways.

Like your hands and ears, the forms of amphetamine are referred to by whether they are “left-handed” or “right-handed”. Levoamphetamine – also known as the “L-” form – is the “left-handed” version (levo = left), whereas dextroamphetamine – or the “D-” form – is the “right-handed” version (dextro = right) [12].

Even though both of these compounds are technically the “same” drug, their different orientations have different effects on the brain and body [12].

In general, dextroamphetamine is the form with the strongest effects on the brain and is the primary type used for treating medical conditions such as ADHD and narcolepsy. For example, its effect on dopamine release in the brain is up to 3 – 5 times stronger than that of the L- form [1].

However, scientists later discovered that pairing the D- form with a bit of the L- form can provide additional benefits, such as making the stimulation effects stronger and allowing amphetamine medications to last longer in the brain and body [1].

For these reasons, different stimulant medications often contain different mixtures of these two compounds. Dexedrine contains the “D-” form only, whereas other common ADHD drugs, such as Adderall, contain a mix of both D- and L- forms [13].

Other, newer medications, like Vyvanse, contain specially-designed prodrug forms of amphetamine that only become active when processed (metabolized) inside the body after ingestion [14].

Uses

1) ADHD

People with ADHD have difficulty focusing and staying still. Although it might seem counterintuitive, stimulants like Dexedrine can help people with ADHD regain focus and are the preferred medications for treating this disorder [15, 16, 7].

The way that stimulants improve the symptoms of ADHD is by increasing activity in the parts of the brain responsible for attention, focus, and motivation [17, 1, 18].

Dexedrine is commonly prescribed as a treatment of ADHD to both children and adults. Dexedrine helps increase attentional focus in ADHD, as well as reducing impulsiveness and hyperactivity [19].

Dexedrine may have higher rates of negative side-effects compared to other types of ADHD medications, such as modafinil and paroxetine [20].

2) Narcolepsy

Dextroamphetamine is one of the drugs that can be used to treat narcolepsy and other disorders involving excessive sleep [21, 22, 23].

As stimulants, Dexedrine and other amphetamines promote wakefulness and alertness by increasing levels of dopamine and norepinephrine in the brain [24, 22].

Dextroamphetamine was found to reduce feelings of sleepiness by 50% in a study of 169 narcoleptic patients. However, the treated narcoleptic patients still reported more sleepiness compared to healthy people [22].

Although Dexedrine can prevent sudden or excessive sleepiness, narcoleptic patients with other symptoms, such as cataplexy (the sudden loss of muscle control in response to strong emotions), may require additional medications to control their illness, such as antidepressants [24, 23].

3) Attention and Focus Issues

Dexedrine increases activity in the different parts of the brain that control attention and focus [17, 7].

Dexedrine can enhance performance on tests of attention, resulting in faster response speed and more accurate choices [25].

4) Wakefulness

One of the earliest uses of stimulants was to overcome the effects of sleep deprivation in military personnel, who often work extremely long hours in cognitively-demanding jobs with little or no sleep [26, 27].

These drugs’ ability to enhance wakefulness also make them useful in treating a variety of conditions involving excessive sleepiness [28].

Two studies of 18 total people found that dextroamphetamine can enhance alertness after a day of sleep deprivation. Although the drug affected how the subjects slept the following night, it did not negatively impact their mood or cognitive function the next day, and their sleep quality quickly returned to normal [29, 26].

However, although Dexedrine was able to help sleep-deprived people maintain focus and energy, the sleep that they got after this period was less restful. Therefore, while there might be short-term benefits to using Dexedrine to stay awake, it has possible long-term drawbacks [27].

5) Depression

Although depression is usually treated with serotonin-based drugs (like selective serotonin-reuptake inhibitors or SSRIs), a considerable number of depression patients do not respond fully to these drugs (a condition called treatment-resistant unipolar depression) [30].

In these patients, dopamine-targeting drugs – including dextroamphetamine – are sometimes added or given in place of these serotonin-based medications [31, 32].

Two case studies have reported that dextroamphetamine was able to help patients with treatment-resistant unipolar depression and postpartum depression who were not helped by other common antidepressants [30, 33].

6) Brain Injury

Strokes and traumatic brain injuries are serious conditions which can take several months to recover from and that often leave patients considerably impaired. Brain injury patients also often experience long-term difficulties with cognition and speech.

A few studies looked at the potential of drugs like Dexedrine to temporarily boost cognitive abilities in these patients, thereby aiding in brain injury recovery. A combination of dextroamphetamine and transcranial direct current stimulation (tDCS) treatment improved language and speech abilities in a study of 10 stroke patients [34].

However, in another clinical study, dextroamphetamine did not enhance brain injury recovery in 32 traumatic brain injury patients [35].

Dextroamphetamine (Dexedrine) Side Effects & Precautions

Dexedrine, like many amphetamines, can cause a variety of unwanted side-effects, even when the drug is used legally for legitimate medical purposes.

The potential side-effects vary according to dosage and length of treatment, and may include [36, 1, 37, 38, 39, 40]:

  • Anxiety [41]
  • Constipation or diarrhea
  • Dizziness
  • Dry mouth
  • Elevated blood pressure (hypertension)
  • Erectile dysfunction
  • Excessive sweating
  • High or low blood pressure
  • Increased heart rate (tachycardia)
  • Irregular heart rate
  • Insomnia
  • Loss of appetite/weight loss/anorexia
  • Muscle spasms/tics
  • Nausea
  • Psychotic symptoms (such as hallucinations and mania)
  • Stomach cramps/pain
  • Stunted growth in children (potentially) [42, 36]
  • Vomiting

Cardiovascular Effects

Although they are relatively rare in people without a pre-existing heart condition, cardiovascular side effects can occur and can be fatal for patients with existing heart problems or abnormalities. Tests and screening are recommended before starting Dexedrine or other stimulants [43, 44].

Misuse and Abuse

Because Dexedrine is an amphetamine, the increase in dopamine levels caused by taking it can produce positive feelings or euphoria, in many people, meaning it has a high potential for abuse. Thus, all amphetamines are considered class II drugs and are only legally available via prescription [1, 45].

In some cases, people who abuse amphetamines will snort or inject them. These methods are dangerous and are strongly advised against [1, 19].

Some people misuse amphetamines for other purposes, such as to suppress their appetite and aid in weight loss, to boost their athletic performance, or to help them study or work for longer hours. Those who misused prescribed stimulants were also more likely to be abusing other drugs [15, 5].

Nonetheless, in general, abuse is generally rare among people who take prescription amphetamine for medical purposes – most abusers are recreational drug users who obtain the drug illegally [46, 1].

Between 2005 and 2010, visits to the emergency room due to stimulant use have more than doubled. Recreational users also often combine Dexedrine with alcohol and other drugs, which can lead to serious side effects and can potentially be fatal [15, 47].

Physical signs of stimulant abuse include [48]:

  • Difficulty sleeping
  • Drug cravings
  • Irregular sweating
  • Increased heartbeat
  • Nausea or vomiting
  • Severe weight loss
  • Tics

Emotional or mental signs include [48]:

  • Anxiety
  • Feelings of invincibility
  • Mood swings
  • Loss of interest in activities
  • Restlessness
  • Depression

Addiction Potential

Because amphetamines cause the release of dopamine – the main neurotransmitter involved in the brain’s reward system – these drugs can be highly “reinforcing,” meaning that using them can easily lead to addiction [1].

Prolonged abuse can cause the brain to become unable to function normally without the drug. This causes dependence, resulting in a cycle of increasing abuse [49].

Tolerance

Long-term use of amphetamines can also cause tolerance, which is when the brain adapts to the presence of the drug and becomes less sensitive to it over time. This causes the user to require higher and higher doses of the drug to achieve the same effect [49, 6].

It is important to note that tolerance can occur both through abuse as well as regular medical use. Nonetheless, it is more common as a result of abuse, where drug dosage is less controlled [6].

Tolerance can also increase the likelihood of overdosing [6].

Overdose

Overdosing on Dexedrine can be very dangerous and can result in a number of symptoms including [19, 4]:

  • Aggression
  • Agitation
  • Anxiety
  • Coma
  • Confusion
  • Death
  • Feverishness
  • Hallucinations
  • Paranoia
  • Rapid breathing
  • Seizures
  • Tremors
  • Twitchiness
  • Uncontrollable or exaggerated reflexes (hyperreflexia)

In a hospital setting, overdoses can be treated with benzodiazepines or antipsychotics, which can counteract the negative effects long enough to stabilize the patient. Because of this, overdoses are rarely fatal if the person seeks immediate medical care [4].

Withdrawal

Withdrawal occurs when there is a quick decrease or halt in the amount of the drug in the body after continued long-term use. This can occur when stopping prescribed use, abuse, or even after frequent recreational use [50].

Withdrawal from amphetamines often involves intense withdrawal symptoms. In fact, this process is so unpleasant that avoiding the withdrawal process is one of the primary reasons people who abuse these drugs continue to stay addicted [51].

The symptoms and severity of withdrawal can depend on the dosage a person is used to and may include [51, 52]:

  • Apathy/lack of pleasure (anhedonia)
  • Anxiety
  • Depression
  • Drug cravings
  • Fatigue

Going through withdrawal can also make certain people prone to aggressive and violent behaviors. This can be especially difficult to prevent when a person attempts to detox from the drug without medical supervision [50, 50].

There is currently no FDA-approved medication for treating stimulant dependence, although some drugs are being studied for this purpose. Several of these include non-amphetamine drugs with either stimulant-like effects (such as modafinil) or which target the dopamine system (such as bupropion, a dopamine-based antidepressant). Temporarily using these drugs could allow users to feel relatively normal while detoxing, thereby improving their chances of making it through the withdrawal phase without relapsing into using amphetamines again [53].

Contraindications

Dexedrine should not be used in people with [19, 54]:

  • Agitation
  • Allergies to stimulant medication
  • Glaucoma
  • Heart disease
  • History of drug abuse or addiction
  • Moderate to severe high blood pressure
  • Overactive thyroid (hyperthyroidism)
  • Severe anxiety
  • Taking antidepressant medication such as monoamine oxidase inhibitors
  • Tics (though rare, it can worsen tics)

During Pregnancy and Breastfeeding

It is unknown whether taking amphetamines during pregnancy can potentially harm a developing child. Although a few animal studies have reported decreased birth weight and premature births, a lack of human trials makes it difficult to come to any conclusions about its safety during pregnancy [55].

When taken by nursing mothers, Dexedrine does not appear to have negative effects on breastfeeding children. However, some studies have suggested that Dexedrine may interfere with the ability to produce breast milk, especially at high dosages [56].

Drug Interactions

Acids

Acids, such as certain foods or fruit juices and medications such as methenamine, reduce the efficacy of amphetamines [57].

Bases

These drugs can increase absorption and thus, the effect, of amphetamines. Drugs of this category include acetazolamide, certain thiazides, and common items like sodium bicarbonate (baking soda) [57].

Alcohol and Other Sedatives

About 20% of emergency room visits for amphetamine abuse also involved mixing stimulant medications with alcohol. Alcohol in combination with Dexedrine is dangerous for the heart, blood vessels, and mental state. It can cause side effects such as [15, 58, 19]:

  • Chest pains
  • Headaches
  • Increased heart rate
  • Increased blood pressure

Antidepressants

Several types of antidepressant medication including monoamine oxidase inhibitors should not be combined with Dexedrine, as that can result in very high blood pressure, internal bleeding, stroke [19, 59].

Antihistamines

Amphetamines can counteract antihistamines’ sedative effects [57].

Antipsychotics

Chlorpromazine and haloperidol work by blocking dopamine and norepinephrine reuptake and therefore can inhibit amphetamines [57].

Anti-Seizure Medications

Amphetamines can delay absorption of ethosuximide and phenytoin, anti-seizure medications as well as phenobarbital, a medication for epilepsy [57].

Blood-Pressure Medication

Adrenergic blockers, also known as beta blockers, are inhibited by amphetamines. Veratrum alkaloids are also inhibited by amphetamines. However, norepinephrine’s effect may be enhanced by amphetamines [57].

Bipolar Medication

Lithium carbonate, a type of bipolar medication, treats and prevents manic episodes and can inhibit amphetamines [57].

Caffeine

Combining caffeine with Dexedrine may additionally trigger or worsen heart problems [58].

Pain Medication

Certain pain medications, such as meperidine, can have a synergistic effect with amphetamines. Propoxyphene and amphetamines used together can be fatal [57].

Sympathomimetics (Stimulants)

Sympathomimetics are drugs that mimic the activation of the heart and increase heart rate. The combination of Dexedrine and other amphetamines, such as this, can lead to overdose [19, 60].

Dexedrine Dosage

The effects of dextroamphetamine reach their maximum strength at about 45 minutes. The dosage depends on the issue being treated and starts at the lowest recommended dosage and is increased gradually until achieving the desired response [1, 19].

For narcolepsy:

  • 5 mg/day for children aged 6 – 12
  • 10 mg/day for children aged 12 – 18
  • 5 – 60 mg/day for adults

For ADHD:

  • 2.5 mg/day for children aged 3 – 5
  • 5 mg/day for children aged 6 – 18
  • 5 – 40 mg/day for adults

Limitations and Caveats

Although Dexedrine has mostly been found to be safe, there is a general lack of studies on the potential long-term effects of amphetamines. The few studies that have been done have reported mixed findings, making it had to draw any conclusions about the long-term safety of amphetamines [61].

Natural Options

There are a variety of natural ways to improve cognition and focus, such as using caffeine and fish oil.

These substances don’t work in exactly the same way as amphetamine drugs, although some of their mechanisms may overlap (such as blocking MAO-A or affecting certain neurotransmitters).

On the other hand, most of the listed natural options offer interesting added benefits: increasing key antioxidants (such as glutathione and SOD). Once shunned as not-so-relevant, antioxidants are now emerging as key players in brain health. Their levels and activity can affect cognition, focus, memory, and many ADHD symptoms that amphetamine drugs are typically used for [62, 63, 64].

Let’s not jump ahead of ourselves, though. Studies have yet to confirm their effectiveness and long-term safety.

You should always consult your doctor before changing or stopping your medications.

It’s also important to let your doctor know of all the supplements you are currently taking, in case of potential interactions.

1) Synephrine

Synephrine (or p-synephrine) is an organic compound naturally found in plants and animals, most notably in bitter orange.

Synephrine works via several pathways. One activates TAAR1, a protein that controls neurotransmitter transport; amphetamine medications also activate it. This ultimately increases dopamine and norepinephrine [65, 66].

One review of over 20 studies including 360 people found that synephrine increases metabolism, resulting in modest weight loss [67].

In a small study of 25 people, synephrine increased energy use while at rest. Participants also reported increased optimism about exercise performance and improved cognitive function [68].

There is some concern that synephrine may negatively impact the heart. It is known to activate receptors that increase heart rate and blood pressure (alpha-1 and alpha-2) [69].

According to the most recent research, synephrine has minimal to no effect on heart rate and blood pressure. In a large review of 30 human studies, it didn’t have any negative effects on the heart [69, 67, 70, 71].

But be careful when buying synephrine supplements. There are multiple forms available and they do not all have the same effect. Check out our synephrine article for a full breakdown.

2) Tyrosine

Your body uses tyrosine (an amino acid) to make different compounds, including neurotransmitters. In the brain, it is a building block for dopamine and norepinephrine [72].

Tyrosine is also naturally converted into a compound called tyramine. Similar to dextroamphetamine, tyramine can activate TAAR1, which boosts dopamine and norepinephrine release [73].

According to a review of 15 studies, tyrosine supplementation improves working memory and information processing, but only in stressful situations [74].

Other humans studies suggest that tyrosine may improve deep thinking, self-control, and cognitive flexibility as well [75, 76, 77].

As far as ADHD goes, it’s less clear how useful tyrosine is.

In an older study of 12 adults, tyrosine improved ADHD symptoms in 8 of the participants. However, all of the patients developed a tolerance after 6 weeks and no longer saw improvements [78].

In another small study of 7 children diagnosed with ADHD, tyrosine had no effect [79].

3) Ginkgo Biloba

Ginkgo biloba is an ancient plant that has long been used as a traditional medicine. It may also have interesting effects on cognition [80].

In two reviews of 16 studies in total, ginkgo biloba extract improved cognition in patients with dementia. [81, 82].

In an analysis of 21 trials with 2608 people, ginkgo biloba improved cognitive function and daily living activities in those with Alzheimer’s disease [83].

A few small, preliminary studies suggest that ginkgo biloba may improve ADHD symptoms as well [84, 85].

These cognitive effects are likely due to increases in dopamine and norepinephrine in the brain. Similar to dextroamphetamine, ginkgo biloba may affect the expression of neurotransmitter transporters, such as VMAT2, DAT, and NET [86, 87, 88].

4) Asian Ginseng

Asian ginseng (Panax ginseng), also known as red or Korean ginseng, contains chemicals that may boost cognitive function. More specifically, compounds called ginsenosides have been shown to increase dopamine and norepinephrine levels in the brain [89, 90].

A small study of 18 children with ADHD found improvements to attention and focus after 2 months of ginseng supplements [91].

According to a review of 5 clinical trials, ginseng may improve some aspects of cognitive function, behavior, and quality of life. However, the researchers concluded that the existing evidence is weak and that more studies are needed [92].

5) Pycnogenol

Pycnogenol is the trademarked name for an extract made from the French maritime pine bark [93].

The extract has antioxidant and anti-inflammatory activity, which may explain its cognitive enhancing effects [93].

For instance, a study of 60 healthy adults found that Pycnogenol improves cognitive function, attention, and memory. Similar results have been found in research looking at students [94, 95].

A different study of 78 people with mild cognitive impairment found that Pycnogenol improves cognition test scores by 18% [96].

Research is also examining Pycnogenol’s usefulness in ADHD, a condition that is linked to oxidative damage [97].

According to a clinical trial of 57 children with ADHD, Pycnogenol reduces dopamine and norepinephrine, two compounds that can worsen oxidative stress. This led to fewer hyperactivity symptoms after one month of treatment [98].

Another trial, this time with 61 ADHD children, also found improvements to hyperactivity, attention, and coordination. However, symptoms returned a month after stopping Pycnogenol, implying that the extract must be used continuously to see benefits [99].

6) Bacopa

Bacopa (Bacopa monnieri) is a medicinal herb that is traditionally used in Ayurvedic medicine [100].

This herb may have benefits on cognition, thanks in part to its antioxidant and anti-inflammatory effects in the brain. Cell studies also show that bacopa is an MAO-A blocker, much like dextroamphetamine [100, 101].

A number of scientific reviews have supported bacopa’s cognitive benefits.

One review of 9 studies including 518 people found that bacopa improves cognition, attention, and memory [102].

Other reviews have found similar results, plus improvements to hyperactivity and other ADHD symptoms [103, 104].

Bacopa has also demonstrated protective effects against Alzheimer’s, Parkinson’s, and schizophrenia, but only in research using rats [105, 106, 107].

7) Gotu Kola

The herb known as gotu kola (Centella asiatica) has long been used as a traditional medicine throughout Asia [108].

It’s not entirely clear how gotu kola works and multiple mechanisms are likely involved. Some studies suggest antioxidants (like glutathione) and anti-inflammatory compounds play a role [109].

Animal and cell studies show that gotu kola helps with depression, anxiety, and cell injury caused by Alzheimer’s [110, 111, 112].

But the health benefits in humans are a bit more ambiguous.

A review of 11 clinical trials found no improvements to cognitive function compared to placebo. However, they did find that gotu kola improves alertness and reduces feelings of anger [113].

8) Celastrus

Celastrus paniculatus is another possibly nootropic medicinal plant [114].

Research in rats shows that celastrus may reduce stress and improve memory. The seed oil from the plant may also improve mental performance and spatial memory [115, 116].

These cognitive improvements may be due to the acetylcholinesterase blocking ability of celastrus [117].

Based on other animal studies, celastrus may protect brain cells from oxidative damage, thanks to its antioxidant properties [114, 118].

But be careful, no clinical trials have been performed with celastrus. Its safety and effectiveness in humans is unclear.

9) Sunlight Exposure

Improving mood and brain health may be as simple as getting more sunlight.

A number of studies have revealed sunlight’s important role in mood, behavior, and cognition [119].

One large observational study looked at the effect of sunlight on 16.8k people. They found a strong association between low sunlight exposure and increased cognitive impairments [120].

According to another study of 109 office workers, sunlight reduces depression and improves sleep quality [121].

And it doesn’t take much. Just 5 minutes of daytime light exposure can increase activity in the brain, according to one study [122].

Why does sunlight help?

Sunlight’s role in vitamin D production is well known. The vitamin has a variety of biological effects and low levels are linked to poor cognition [123, 124].

But other mechanisms may be at play as well. Research indicates that sunlight increases glutamate release. It also regulates the circadian rhythm, which has important effects on mood disorders (especially for bipolar disorder) [119, 125, 126].

Want More Targeted Ways to Enhance Brain Function?

If you’re interested in improving your cognitive function, we recommend checking out SelfDecode’s Limitless Mind DNA Protocol. It gives genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

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About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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