Ephedrine & Ephedra, and the Associated Alkaloids and Compounds :: Part 2

Ephedrine & Ephedra Part 1

Ephedra herbs
Ephedra herbs contain ephedrine and pseudoephedrine at varying levels. The main snag with herbal versions is that we don't know what compounds are contained in the rest of the herb and what effects these are having on our body. Noted on the labels of supplement preparations containing ephedra herbs will be something like the term 'standardised for ratios', 'standardised for ephedra alkaloids' or similar, followed by a percentage figure. This refers to the amount of active ephedrine there is in the herb contained in the product and you can equate this figure to ephedrine HCl for a suitable dose.

The main ephedra herbs are:

Má Háung
The most common herbal form of ephedrine is má háung (Ephedra Sinica) and it was the traditional Chinese form. The plant is standardised to varying degrees so the user must calculate exactly how much ephedrine is contained in the preparation. For example if you see on a label: má háung 335mg (standardised to 6% ephedra alkaloids) this is the equivalent of 20mg pure ephedrine.

Soma
Ephedra distachya (aka Ephedra vulgaris) contains a form of ephedrine called soma and had religious links in Hinduism.

Sida Cordifolia
Sida cordifolia is also known as bala and is from the family Malvaceae, and contains significant amounts of ephedrine and pseudoephedrine. It is used as a source of ephedrine in weight loss formulas because, mainly, its name is not so maligned and using herbal names is more fashionable. There are products available which contain it with forms of caffeine and aspirin, and these are essentially forms of the ECA stack (see below).

Citrus Aurantium aka Bitter Orange
Citrus aurantium or bitter orange extract is often referred to as a source of ephedra and is found in many supplementary weight loss aids. However, it doesn't strictly contain ephedra alkaloids, and is found in many ephedra-free formulas. Although native to Vietnam, citrus aurantium is a popular Chinese medicine. The active constituent is actually synephrine and so there are the same benefits and health risks as with plants containing ephedra alkaloids.

ECA aka the Ephedrine / Caffeine / Aspirin Stack
The ECA stack is a combination of the three compounds ephedrine, caffeine and aspirin and is very popular because it's been shown that the three compounds ephedrine, caffeine and aspirin are synergistic, i.e. the effect of them being used together is far greater than them being used independently. Some people make their own ECA stack from the three ingredients, but there are also many commercially produced ECA formulas available legally.

Caffeine is a commonly consumed stimulant found in tea and coffee amongst other products. More information can be found in our Caffeine article. It is available on it's own as caffeine in formulas like ProPlus, or from herbal supplements like guarana or kola nut which are sources of caffeine. Indeed, some legally sold ECA stacks may be labelled as containing guarana or kola nut as they make the product sound more 'healthy' as the word caffeine is often maligned.

Aspirin is a non-steroidal anti-inflammatory (NSAID) drug used commonly as a pain killer, available off-the-shelf from shops. A natural source of aspirin is white willow bark.

• Guarana extract is 22% caffeine, therefore 910mg of guarana is equivalent to 200mg caffeine
• Kola nut contains 20% caffeine
• White willow bark contains 15% salicin, the equivalent of aspirin

Formulas are not always sold as the ECA stack raw compounds and ingredients may be labelled as má háung for ephedrine, guarana for caffeine and white willow bark for aspirin. Although laws are tightening up for this supplement in some countries, there are many formulas which remain very popular. Often commercial ECA products contain an additional forth compound, e.g. cayenne pepper, yohimbine or narnigin.

Standard ECA dosages are typically:

• Ephedrine 20-30mg
• Caffeine 200mg (equivalent to approx 2.5 cups of coffee)
• Aspirin 75mg

The theoretical ratio is E:C:A = 1:10:3. A certain ratio of ephedrine / caffeine / aspirin is known to be most effective and this is patented and only found in approved supplements.

The synergistic effects of the compounds are weight-loss, increased 'energy' and enhanced athletic performance. The importance of the aspirin is debatable in the grand scheme of things, but it is included in the hope that it acts as a prostaglandin inhibitor and an enhancer of lipolytic activity (fat breakdown). However, as many people are intolerant to aspirin, they can still get the benefits by using a compound which doesn't include it.

People commencing ECA should refer to the section above discussing the doses of ephedrine. Typically users start by using just one dose per day, either 30 minutes before breakfast or 30 minutes prior to exercise. Many find that this will provide them with plenty of stimulation and will negate the necessity to increase the frequency of doses for maybe a week or more. In time, if the user becomes more tolerant of the effects, they may increase to two doses per day, often split. It is considered that three doses per day is the absolute maximum, with the last dose taken no later than early evening to avoid sleep problems.

Ephedrine and Clenbuterol
You can find detailed information in about clenbuterol in our clenbuterol article. It is generally not recommended that you use ephedrine and clenbuterol concurrently in a cycle as they are both beta-agonists, and if you do you get the unpleasant side effects of both and sub-optimal benefits. Ephedrine is thought to increase the conversion of thyroid hormone thyroxine (T4) to triiodothyronin (T3) through the activation of deiodinase enzymes responsible for this process, whereas clenbuterol is known to slow the rate of T4 to T3 conversion.

Clenbuterol is a notably better metabolism stimulant then ephedrine. However, its effects as an appetite suppressant are less apparent. Plus, clenbuterol is less effective in providing 'energy' than ephedrine. So, taking all things into consideration, ephedrine is probably the better weight loss aid.

Quite often people cycle ephedrine or ECA 2 weeks on, 2 weeks off, and use clenbuterol in the opposite 2 weeks on, 2 weeks off.

Ephedrine and Theophylline (aka dimethylxanthine)
Theophylline is a methylxanthine drug used in therapy for respiratory diseases under a variety of brand names. Due to the numerous side-effects, theophylline drugs are now rarely administered for clinical use. Caffeine is another methylxanthine and has a structural and pharmacological resemblance to theophylline. Theophylline is found naturally in trace amounts in tea. Side effects of theophylline use include nausea, diarrhoea, raised heart rate, arrhythmias, headaches, insomnia, irritability, dizziness and light-headedness.

Theophylline is often found alongside ephedrine or pseudoephedrine in medicines used to treat respiratory problems, e.g. ChestEze, and if these products are used for performance enhancing reasons, extra caution must be taken in view of the theophylline.

Other Compounds used Alongside ECA
In addition to the caffeine, aspirin and naturally occurring herbal forms of them found in ECA products, there are a few other weight loss or stimulant supplement aids which are frequently found in conjunction with ephedrine or ephedra herbs. These include:

Naringin aka Grapefruit Extract
Naringin is the major flavonoid glycoside in grapefruit and gives grapefruit juice its bitter taste. It has a number of effects including acting as an antioxidant, lowering blood lipids and inhibition of selected drug-metabolizing cytochrome P450 enzymes, including CYP3A4 and CYP1A2, meaning that certain drugs which are metabolised by these enzyme systems may have their effects potentiated.

Capsaicin aka Cayenne Pepper Extract
The cayenne (Capsicum annuum) is a red hot chilli pepper and it is used to flavour dishes and for medicinal purposes. The powdered spice of the cayenne contains capsaicin which is its active ingredient and Plantenga et al (2006) demonstrated it having a metabolic stimulant effect. In fact, capsaicin acts through the beta-androgenic pathway in a similar way to that of ephedrine, with an effect of 23% increase directly after administration having been reported.

In addition to the metabolic stimulatory effects, cayenne pepper can also blunt appetite leading to a reduced intake of food.

Yohimbine aka Yohimbe Extract
Although marketed as a supplement, yohimbine is a psychoactive drug with stimulant and aphrodisiac effects. It is an alkaloid and is found naturally in yohimbe (Pausinystalia yohimbe or Corynanthe yohimbe) where it is known as yohimbe extract. It is also found naturally in Indian Snakeroot (Rauwolfia serpentina), along with several other active alkaloids. Yohimbe extract is available in OTC supplements and as yohimbine HCl in prescription medicine for the treatment of sexual dysfunction.

Supplementation with yohimbine has been shown to improve fat loss in athletes (Ostogic 2006) and from this study its use in weight loss formulas has risen dramatically. However, it's not without its side effects, many of which are similar to the ones experiences with ephedrine; so caution should be heeded when both compounds are used in conjunction. Interestingly, the ECY stack (ephedrine / caffeine / yohimbine) is being used more and more, and there are also some commercial ECYA formulas available.

Catechin aka Green Tea Extract
Green tea extract is known as catechin, or, more precisely, epigallocatechin gallate (EGCG). EGCG is a powerful polyphenolic anti-oxidant with the asscoaited benefits, but, more importantly, it's been shown to be lipolytic independent of caffeine (Dulloo et al 1999). Green tea extract is often found in weight loss preparations with ephedrine or synephrine.

Legality of Ephedrine and Pseudoephedrine
In the UK ephedrine is regulated as a prescription only medicine (POM), i.e. it may only be lawfully supplied within a registered pharmacy and while a responsible pharmacist is present. The maximum amount of ephedrine legally available without prescription in one sale is 180mg.

One product commonly sold within these restrictions is ChestEze (aka Do Do ChestEze) tablets which consist of nine pills of 18.31mg ephedrine HCl, 30mg caffeine and 100mg anhydrous theophylline. ChestEze is sold as a nasal decongestant but is commonly abused by bodybuilders and those looking to lose weight, and there are issues here with people reacting badly to theophylline. Higher strengths of pure ephedrine are available as POMs but are not currently Controlled Drugs under the Misuse of Drugs Act.

Like ephedrine, pseudoephedrine is available on prescription or over the counter under the supervision of a qualified pharmacist. As of 2009 UK pharmacies sell Sudafed (pseudoephedrine HCl) in 12 tablet pack size containing 60mg per pill.

In 2004, the US FDA imposed a ban on ephedrine alkaloids that are marketed for reasons other than asthma, colds, allergies, other disease or traditional Asian use. This means that all ephedra compounds are not allowed, though currently this doesn't extend to synephrine. The legality of ephedrine and ephedra compounds in the USA is ever changing, and there are many politicians wishing to be viewed as proactive over the use of drugs in sports. Ephedrine is still legal in many clinical areas, like in respiratory medicines, but purchasing is currently limited and monitored, with specifics varying from state to state.

In the USA the law changed in 2006 concerning the sale of pseudoephedrine-containing products. The Federal statute included a number of strict requirements for merchants who sell pseudoephedrine including keeping a record of customers, limits on daily and monthly amounts sold.

WADA Position on Ephedrine and Pseudoephedrine
The World Anti-Doping Agency (WADA) 2009 and 2010 Prohibited Lists both include ephedrine under the sub-section 'Specified Stimulants' with the reference:

Each of ephedrine and methylephedrine is prohibited when its concentration in urine is greater than 10 micrograms per millilitre'. And pseudoephedrine is prohibited when its concentration in urine is greater than 150 micrograms per millilitre.

Although the half life of ephedrine is 3-6 hours, it's said that to be sure that it is undetectable, there should be 72 hours from last administration. Random drug testing would mean that ephedrine may be detected.

Pseudoephedrine was on the banned substances International Olympic Committee (IOC) list until 2004. The gymnast Andrea Răducan was stripped of her gold medal at the 2000 Sydney Olympics after testing positive for pseudoephedrine. She took two pills given to her by the team coach for a cold. Although she was stripped of the overall gold medal, she kept her other medals, and, unlike in most other doping cases, was not banned from competing again. Pseudoephedrine has a longer half life than ephedrine (9-16 hours), but the levels allowed by the WADA mean that restricted use of nasal decongestants can be used. However, caution is recommended and alternative medication is advisable. The use of pseudoephedrine in competitions is being monitored by the WADA during 2010 who may review their ruling. WADA (2009) noted the following about pseudoephedrine:

• Until 2003, the stimulant pseudoephedrine had been prohibited in sports with a threshold of 25µg/mL. Pseudoephedrine has been included in the Monitoring Program since 2004. Results from the Monitoring Program over the past 5 years have shown a sustained increase in urinary concentrations of pseudoephedrine. In addition, there is clear evidence of abuse in some sports and some regions which show clusters of samples with high pseudoephedrine concentrations many times in excess of concentrations normally found. Furthermore, the available literature demonstrates scientific proof of its performance enhancing effects at certain doses. Therefore, the List Committee has reintroduced pseudoephedrine as a specified stimulant in the 2010 Prohibited List at a urinary threshold of 150µg/ml based on the results from controlled excretion studies as well as the literature. Given the wide availability of pseudoephedrine-containing medicines, WADA recommends that the reintroduction of pseudoephedrine is supported by active information/education campaign by all stakeholders.
• Although pseudoephedrine is now prohibited, it will remain in the Monitoring Program for urinary concentrations below 150µg/ml.

Popularity of Ephedrine and Related Compounds as 'Supplements'
There is no doubt that the popularity of ephedrine, ephedra herbs and related compounds is rife in many sports, bodybuilding and the general weight loss community. This is primarily because the products 'work' and the 'buzz' they produce is deemed favourable. The adverse reactions are scarce, but they do exist so anyone considering using ephedrine or related herbs needs to be cautious. Also the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK are clamping down on supplements sold legally containing ephedrine and related ingredients. Many health stores have been visited and had their stocks confiscated. However, the products or specific ingredients which are being regulated is unclear, and it appears that synephrine is ok for now, at least. As a consequence of this, people are tending to source their ephedrine through the black market.

A Final Note of 'Fat Burning' Supplements
Ephedrine and other thermogenic 'fat burning' supplements are merely there to supplement or compliment a suitable diet and exercise regimen. They must not be seen as short cuts, and they are by no means a substitute for a healthy lifestyle. The minute someone feels they are relying on such products, is the minute they should reconsider using them.
References:

• Bouchard et al (2005). Ischemic Stroke Associated With Use of an Ephedra-Free Dietary Supplement Containing Synephrine. Mayo Clin Proc. 80(4):541-545
• Dulloo et al (1999). Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 70: 1040-1045
• Greenway et al (1999). Double-blind, randomized, placebo-controlled clinical trials with non-prescription medications for the treatment of obesity. Obes Res 7(4):370-8
• Ostogic (2006). Yohimbine: the effects on body composition and exercise performance in soccer players. Res Sports Med 14(4):289-99
• Plantenga et al (2006). Metabolic Effects of Spices, Teas and Caffeine. Physiol and Behav 89: 85-91
• Wellman & Marman (1985). Comparison of brown adipose tissue thermogenesis induced by congeners and isomers of phenylpropanolamine. Life Sci 37(11):1023-8
• The World Anti-Doping Agency (2008). The World Anti-Doping Code: The 2009 Prohibited List - International Standard
• The World Anti-Doping Agency (2009). The World Anti-Doping Code: The 2010 Prohibited List - International Standard
• The World Anti-Doping Agency (2009). 2010 Prohibited List: Summary of Major Modifications

If you are considering using ephedrine, synephrine or any herbal compound mentioned in this article, then you must always consult your doctor.

Warning! Articles related to the use of illegal performance enhancing drugs are for information purposes only and are the sole expressions of the individual authors opinion. We do not promote the use of these substances and the information contained within this publication is not intended to persuade or encourage the use or possession of illegal substances. These substances should be used only under the advice and supervision of a qualified, licensed physician.