Ephedrine

Top 13 Positive and Negative Ephedrine Effects [Weight Loss Review]

Ephedrine EffectsWhat are the positive and negative effects of ephedrine and is this stimulant worth it for weight loss?

Ephedrine is well-known for having the ability to modestly increase fat loss results while boosting energy.

How does this drug actually work and is it too dangerous to take as a diet pill? Research shows that ephedrine increases metabolism, alertness, mental focus, suppresses the appetite and may enhance athletic performance

It also increases heart rate, blood pressure, causes lungs and nasal passages to dilate and promotes heat generation in the body. Ephedrine has a number of medicinally-recognized benefits and is used in asthma drugs and nasal decongestants.

However, not all of the effects of this drug are positive. Ephedrine and the herb from which it is derived – ephedra – are banned from certain products in the USA due to harmful side effects. Click here to buy ephedra supplements online legally without a prescription.


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Ephedrine and Ephedra Effects

Before discussing the mental and physical effects of ephedrine, it is important to understand the difference between this chemical and ephedra. They are often confused for one another, but they are in fact two different things.

Ephedrine refers to a specific alkaloid or nitrogen-based compound that was initially derived from the ephedra plant. It has a ‎molecular formula of C10H15NO.

Ephedra, on the other hand, refers to a plant that grows in specific regions around the world, from Asia to middle Europe, to the southwestern and western coastal areas of the US, Mexico and South America.

Over sixty species of ephedra have been identified, and not all of them are created equal. Different species of this plant contain different active chemicals. Some species like the E. Sinica plant from China has a high concentration of ephedrine alkaloids while other species like E. Viridis contains almost none of this alkaloid.

Other popular species of the plant include but are not limited to:

  • Ephedra intermedia
  • Ephedra major
  • Ephedra equisetina
  • Ephedra geridiana
  • Ephedra nevadensis

The most widely used of these plants is E. Sinica, also known as Ma Huang or Chinese ephedra. It has been used in traditional medicine for over 2000 years to treat lung and breathing conditions.

In the early 1900’s, ephedrine was first extracted and isolated from this plant. It was initially marketed as an anti-asthma drug throughout North American and Europe.

This plant also contains other alkaloids, some of which have been studied for their effects and mechanisms of action. Constituents include:

  • Pseudoephedrine
  • Norephedrine
  • Norpseudoephedrine
  • Methylephedrine
  • Methylpseudoephedrine

Of these, pseudoephedrine is the best-known for its medicinal effects. This compound is the active ingredient in the drug Sudafed. The plant also contains flavonoids, tannins, proanthocyanins and volatile oils.

In traditional Chinese medicine (TCM) and traditional Ayurveda medicine (TAM), ephedra has been used to bronchial asthma, the common cold, fever, narcolepsy, and rheumatism. [1] It is also used in the treatment of lung conditions such as wheezing and chest tightness and in some cases for relief of symptoms of COPD or emphysema.


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Ephedrine Mechanism of Action

The effects of ephedra are largely attributed to the mechanism of action for ephedrine, although some effects are linked to other components of the plant.

Ephedrine is an alkaloid, which is a type of plant compound that has a physiological or psychological effect on humans. Alkaloids are naturally occurring nitrogenous chemicals and they are found in many prescription drugs today.

Ephedrine has sympathomimetic properties and is sometimes referred to as an adrenergic drug. It behaves as a stimulant that triggers a reaction in the sympathetic nervous system (SNS).

The SNS is part of the autonomic nervous system. It is responsible for our “fight or flight” response, mainly associated with periods of fear or intense stress.

When we perceive danger or a threat to our survival, the body responds by releasing the hormone adrenaline (epinephrine). This hormone promotes several changes in the body that better enable us to respond to in the face of external stressors.

Some effects of adrenaline include increasing our breath rate, dilating our pupils so that we can see better in the darkness, increasing blood pressure, and pumping blood to vital areas of the body.

Ephedrine mimics this response by binding to the same receptor sites on nerves in the body that are associated with adrenaline. In addition to directly stimulating adrenergic receptors, it can also indirectly increase norepinephrine activity.

It causes artificial activation of the SNS, increasing mental alertness and physical readiness to react to danger. This reaction causes our cells to begin breaking down and metabolizing more energy.

The sympathetic nervous system can also constrict blood vessels, increase pulse, cause airways in the lungs to dilate and decreases non-essential body functions such as digestion. It pumps blood to the muscles in anticipation of action needed for safety or survival.

Essentially this system readies the body for a sudden burst of mental or physical activity. [2] Because of its mechanism of action, ephedrine is often likened to amphetamine.

Ephedrine Health Benefits

When used properly, ephedrine has a number of recognized medicinal benefits. It is an approved drug in many countries for use in the treatment of lung and breathing problems as well as hypotension or low blood pressure.

Millions of patients internationally have been prescribed this medicine for its bronchodilator and vasopressor effects. Because of its behavior as an alpha and beta-adrenergic agonist, it has been used to treat depression, heart failure, rhinitis, and asthma in the past. [3]

However, it is no longer widely used as a pharmaceutical agent because it carries a high risk of side effects. Due to the development of newer drugs that are more selective in their mechanism of action, ephedrine is not found in medicines as commonly today.

At present, the drug is most widely used among athletes and bodybuilders. It demonstrates a positive effect on weight loss, energy, physical power output and exercise intensity. While not a steroid, it is commonly used in bodybuilding cutting cycles.

Research shows that this stimulant can promote short-term increases in fat loss. It works by:

  1. Increasing basal metabolic rate between 5-10%
  2. Enhancing physical energy and mental wakefulness
  3. Boosting the release and breakdown of stored fats in the body
  4. Causing more fat to be used for energy instead of carbohydrates
  5. Promoting thermogenesis (conversion of stored calories into body heat)
  6. Inhibiting hunger signals in the hypothalamus

In research trials, it has been found to promote an increase in weight loss of 0.9 kg per month loss more than someone using a placebo. [5] It is reliably more effective when combined with caffeine.

Dosages of 20-30 mg ephedrine HCl have been combined with 200 mg caffeine in an EC stack. This stack can support weight loss goals when taken up to four to six months, however no studies have looked at the effects of the drug beyond six months in duration.

Positive effects are independent of changes in exercise or calorie restricted diets. However, increasing activity and eating a healthy diet will be necessary to maintain results over the long term. [4]

This drug is also purported to have benefits for athletic performance enhancement and physical stamina. It is used in pre-workout stacks by bodybuilders because it is a stimulant.

There is less research available to evaluate its efficacy for boosting athletic performance. Most of the information available comes from anecdotal user reviews which claim benefits for workout intensity.

In one study, it was determined that there was not a significant influence on power output from taking this drug. Other studies have found that this compound may improve physical endurance and reduce perception of exertion during workouts.

Another study found that ephedrine may moderately decrease the rate of skeletal muscle breakdown (atrophy) over a calorie restricted diet of 6 weeks. In the study, participants experienced a drop in metabolic rate from consuming a low-calorie diet. However, use of ephedrine restored normal metabolism.

The half-life of this drug can last between one and six hours, depending on individual metabolism and whether other substances are used. Caffeine and aspirin are sometimes added to this stack because they are purported to increase the half-life of the drug. [7]

Because many people are sensitive to aspirin, this ingredient is often left out of the stack or substituted with White Willow Bark – a natural source of salicin.

Long-term use of this drug has not been studied due to potential health risks. Taking this drug can contribute to negative cardiovascular reactions. [6]

Ephedrine might indeed prove beneficial for weight loss, but optimal results will only be achieved in conjunction with appropriate diet, caloric restriction, and exercise.


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Banning of Ephedra Supplements

Between the 1990’s and early 2000’s, ephedra was one of the most popular dietary supplements sold internationally. According to one report, 12 million Americans had used the supplement by 1999.

Many men and women swore by ephedrine benefits for weight loss, greater energy and appetite control. Research showed that it did have benefits for fat loss, but the potential side effects often outweighed the positive effects.

Excess use of any stimulant can put too much strain on the heart and cardiovascular system as well as lead to cerebrovascular side effects. In patients with certain risk factors, the elevated heart rate caused by ephedrine could result in dangerous outcomes.

According to a RAND corporation study, “Sentinel events with prior ephedra consumption included 2 deaths, 3 myocardial infarctions, 9 cerebrovascular/stroke events, 3 seizures, and 5 psychiatric cases.”

In 2004, the FDA determined that ephedrine was unsafe to use in dietary supplements. According to the FDA, this plant alkaloid posed an unreasonable risk of adverse effects.

It was banned from sale in diet pills or weight loss formulations. Dozens of products had to be recalled from store shelves, including Lipodrene, Xenadrine RFA-1, Metabolife 356, and the original Hydroxycut with ephedra.

While ephedrine was made illegal in dietary supplements, it was allowed to remain on the market as an ingredient in nasal decongestants like Bronkaid and Primatene.

The FDA ban also only applied to products containing ephedrine alkaloids, and not to the whole ephedra herb. As a result, many companies have re-launched supplements that contain forms of ephedra extract without the alkaloids. These supplements are legal to buy online without a prescription.

Dosage Recommendations

The recommended dosage of ephedrine will depend on your health status, reasons for taking the compound, sensitivity to stimulants and whether other supplements are being used at the same time.

While this drug has been used with acceptable tolerability by many, it is not safe for everyone. Consult with a doctor before taking this stimulant to determine whether it is appropriate for you.

Research studies have used ephedrine at a dosage of 20-25mg, taking three times per day. This provides for a total daily dose of 60-75 mg. It is typically stacked with caffeine at a dose of 100-200 mg per serving.

In isolation, ephedrine HCL has been administered at higher dosages of 30-50mg, up to 150mg per day. This dose may be too stimulatory for many users and can result in side effects such as headaches or restlessness.

If using ephedra, dosages should be standardized to the content of ephedrine alkaloids. Different species can contain different amounts of this alkaloid, so a safe dose to use with E. Viridis may not be safe with E. Sinica.

It is recommended for beginners to start their cycle with a low dose to to gauge how the body reacts to it. 8mg and 12.5mg tablets are ideal for cycling because they allow for better flexibility with dosages.

If you are using a product that provides 25 mg of ephedrine HCL per tablet, it is recommended to split the pill in half when first using. Do not increase the dosage if you experience negative effects.

The half-life is between three to six hours, depending on the age, weight, metabolism and body composition of the person using it. [8] Users will typically repeat doses every 4 to 6 hours.

Most of the serious side effects linked to ephedrine usage come from misuse and abuse of the drug. Taking this compound in high doses or combining it with other stimulants like caffeine can increase the risk of negative effects.

Some people are more sensitive to the effects of stimulants than others. Even at a low dose of 10 mg to 25 mg, adverse reactions are possible. Consuming this product with food can help prevent certain side effects.

It is not recommended to use this drug for long periods of time. Health Canada advises people not to take it for longer than 7 days, although it has been used safely in some studies for 4- 6 months. Long-term use has the potential to lead to ephedrine tolerance and addiction.

Bodybuilders generally recommend cycling ephedrine or ephedra for 4-6 weeks, followed by an off-cycle of 4 weeks before using it again. This may reduce the potential for adverse reactions and for building up a tolerance to the drug.

Negative Side Effects

Users of ephedrine should be aware of its potential to cause negative side effects and serious adverse reactions. Ephedrine supplements were banned by the FDA in 2004 due to increasing reports of harmful effects. [9]

Many of the side effects are similar to those one would experience when consuming high amounts of caffeine. Following safe dosage guidelines can minimize potential adverse effects. Some of the commonly reported negative effects include but are not limited to:

  • Headaches
  • Nausea, sometimes with vomiting
  • High blood pressure
  • Heart palpitations
  • Difficulty sleeping (insomnia)
  • Increased sweating
  • Increased urination
  • Restlessness or hyperactivity
  • Jitters, muscle tremors
  • Nervousness or a sense of unease

A small number of more dangerous side effects have been reported in medical journals and case studies. Users should be aware of the potential for life-threatening reactions if this drug is misused. Some of the more serious adverse events include:

  • Brain seizures
  • Strokes
  • Temporary Psychosis
  • Heart attack

Ephedrine overdose can lead to cardiotoxicity. In an animal study published in 2000, administering an excessively high dosage of this compound to rodents (rats) resulted in the following symptoms [10]:

  • Excessive hyperactivity
  • Ataxia (lack of muscle control)
  • Lethargy
  • Ultimate failure to stimulus responses

In another rat model study, a combination of high doses of ephedrine and caffeine resulted in acute hemorrhagic myocardial necrosis. [11]

Even when used responsibly, ephedrine and caffeine can contribute to unexpected and unpleasant side effects. While many people will experience no adverse reactions, for some it can be dangerous.

Contraindications

There are certain individuals who should not use ephedra or ephedrine. Multiple contraindications are listed on medical databases.

If you have been diagnosed with a medical condition, discuss use of this product with a physician. Do not take if you are being treated with a disease that affects the metabolic or cardiovascular system.

Use extreme caution if you have been diagnosed with closed angle glaucoma, diabetes, thyroid problems, pheochromocytoma, asymmetric septal hypertrophy, a mental health condition such as anxiety or depression, urinary problems or patients with hypersensitivity to the drug.

Avoid taking ephedrine with prescription drugs, over-the-counter products or herbal supplements due to the risk of interactions. Consult with a doctor if you are currently using medication to treat a health condition.

Women who are pregnant, planning to become pregnant or women who are breast-feeding should not use this drug. It should not be given to children under the age of 18.

Use is contraindicated in patients who are taking monoamine oxidase inhibitors (MAO inhibitors). Do not take this drug within 14 days of using MAOIs. These drugs may prolong and amplify the effects of ephedrine HCL.

Substitutes for Ephedrine

A number of supplements are marketed as substitutes for this banned stimulant. In the USA, ephedra is legal to use in supplements so long as it has the ephedrine alkaloids removed.

This is akin to drinking decaffeinated coffee. Without the caffeine, much of the stimulatory effects of coffee are eliminated.

To compensate for the removal of these alkaloids, legal herbal stimulants will be stacked with the ephedra extract. These products usually contain high doses of caffeine, green tea extract, guarana, kola nut extract, yohimbine and yerba mate.

One of the most common alternatives to ephedrine is Citrus aurantium, otherwise known as Bitter Orange fruit extract. This orange contains p-synephrine, which is an adrenergic amine that has a similar effect on metabolism and fat loss.

Synephrine is viewed as safer than ephedrine because it has less of a vasopressor effect. It does not increase blood pressure as much and is better tolerated by most users.

However, overuse of this extract can lead to adverse effects. Rodent studies have examined the effects of p-synephrine in dosages of 300 mg, 350 mg, and 400 mg per kilogram of bodyweight. This is many times higher than the standard dosage used in dietary supplements.

At these extremely high doses, reported effects included [12]:

  • Excessive salivation
  • Agitation
  • Seizures
  • Death caused by cardiopulmonary hemorrhage

Whether using ephedrine, ephedra or a substitute, it is important to understand both the positive and negative effects. Overuse of these compounds can lead to dangerous side effects that could put your health at risk.


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References
  1. Obtandon.files. Ephedra.
  2. PubMed Health. Sympathetic Nervous System
  3. Drugbank. Ephedrine
  4. FDA.gov. Evidence Report/Technology Assessment Number 76. Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects.
  5. Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ, Rhodes SL, Jungviq L, Gagné J. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA. 2003 Mar 26;289(12):1537-45. Epub 2003 Mar 10.
  6. Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose supplement use. Clin Pharmacol Ther. 2002 Jun;71(6):421-32.
  7. Haller CA, Jacob P 3rd, Benowitz NL. Enhanced stimulant and metabolic effects of combined ephedrine and caffeine. Clin Pharmacol Ther. 2004 Apr;75(4):259-73.
  8. Obtandon.files. Ephedra.
  9. Harvard Health Publishing. Harvard medical School. Why the FDA banned ephedra
  10. J.K. Dunnick, G. Kissling, D.K. Gerken, M.A. Vallant, A. Nyska. Cardiotoxicity of Ma Huang/Caffeine or Ephedrine/Caffeine in a Rodent Model System. Toxicol Pathol. 2007: 35(5): 657-664. Doi: 10.1080/01926230701459978
  11. Nyska A, Murphy E, Foley JF, Collins BJ, Petranka J, Howden R, Hanlon P, Dunnick JK. Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. Toxicol Sci. 2005 Feb;83(2):388-96. Epub 2004 Nov 10.
  12. Schmitt GC, Arbo MD, Lorensi AL, Maciel ES, Krahn CL, Mariotti KC, Dallegrave E, Leal MB, Limberger RP. Toxicological effects of a mixture used in weight loss products: p-synephrine associated with ephedrine, salicin, and caffeine. Int J Toxicol. 2012 Mar;31(2):184-91. doi: 10.1177/1091581811435708. Epub 2012 Mar 9.
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