ECA stack

The ECA stack is a drug combination used as a stimulant and in weight loss. ECA is an acronym for ephedrine, caffeine, and aspirin.

Mechanism of effect in weight loss
The effects of the ECA stack in weight loss are primarily due to the ephedrine component. Ephedrine acts both as a beta agonist and stimulates the release of norepinephrine. Increased circulating norepinephrine in the body then acts on white adipose tissue by increasing cAMP levels. This causes a thermogenic effect, raising body temperature and increasing the user's metabolism in conjunction with the rest of the stack.

However, the body's negative feedback system then activates to normalize the metabolism. This is done via the production of phosphodiesterase inside the cells, and prostaglandins outside the cell, which both lower cAMP levels within the cell.

Caffeine inhibits the production of phosphodiesterase inside the cell and therefore slows cAMP breakdown. It also binds with and competitively inhibits adenosine receptors in the brain, triggering the release of epinephrine and increasing cAMP levels further.

Aspirin inhibits prostaglandin production outside of the cells, which, in conjunction with caffeine, greatly prolongs the thermogenic effects and increased metabolism by substaining elevated cAMP levels.

Ephedrine also has an anorectic, or appetite-suppressing, effect. However, these effects only last for about two weeks if the stack is not cycled, as the body becomes tolerant to ephedrine to some degree. It is estimated that 60% – 75% of the weight loss from using the ECA stack comes from the anorectic effect, and the remainder from thermogenesis.

The final component in weight loss of the ECA stack is that of a simple stimulant; the higher epinephrine and norepinephrine levels result in increased aerobic exercise performance and less fatigue.

Mechanisms of effect in energy gain
Ephedrine acts to increase energy by its actions as a sympathomimetic amine. It directly acts in the brain to increase the release of norepinephrine into the synaptic cleft, and also partially serves as a norepinephrine reuptake inhibitor, thereby also partially functioning as a dopamine reuptake inhibitor due to the shared action between the two terminals. Caffeine blocks adenosine receptors which lessens feelings of tiredness, and also increases dopamine levels, resulting in greater concentration, focus, and memory. The effects of caffeine on dopamine levels are usually short lived, but ephedrine's partial action as a dopamine reuptake inhibitor lengthens the duration.

Dosage
Typically the ECA stack is consumed two or three times per day in a 1:10:10 or 1:10:15 ratio of ephedrine:caffeine:aspirin. These ratios vary across studies and across users but despite variance they all seem to be effective. Usually, no more than 25 mg of ephedrine, 200 mg of caffeine and 325 mg of aspirin is consumed in a single dose. It is not recommended that the stack be taken past late afternoon as this may contribute to insomnia.

Addiction
While aspirin is not physically addictive, caffeine is, and users develop a tolerance to lowered adenosine levels, leading to withdrawal symptoms from adenosine sensitivity if caffeine use is discontinued too quickly. Psychological addiction to ephedrine and caffeine are also possible.

Risks
The primary risk of the ECA stack is in the effect of ephedrine on the heart. Ephedrine has been linked to deaths in people with valve damage, heart problems and heart disease, but also in previously healthy young adults when taken in high doses. It is not recommended that stimulants be taken in users with a pre-existing heart condition. Additionally, there is some evidence that the long term use of amphetamines can lead to heart damage, but this has not been shown for ephedrine use.

Caffeine and ephedrine also act to raise blood pressure by approximately 4 – 7 mmHg on average, so users with existing hypertension must be careful that the stack does not increase their blood pressure to dangerous levels &mdash; especially during exercise (for example, by lifting exceptionally heavy weights).

Other risks include insomnia, dry mouth, irritability, stress, euphoria, headache, anxiety, dizziness, nausea, irregular heartbeat, interaction with MAO inhibitors, trembling hands, increased need for water and potassium, and psychosis resulting from the long-term use of ephedrine.

Controversy and legality
Due to deaths linked to ephedrine and its potential use as a precursor in illegal methamphetamine manufacture, many countries have taken steps to regulate ephedrine. If ephedrine cannot be obtained, pseudoephedrine, ephedrine's optical isomer, can be substituted, but many countries are restricting sales of over the counter pseudoephedrine as well, because it is likewise used as a precursor in methamphetamine manufacture. Contrary to popular belief studies have shown pseudoephedrine to have a thermogenic effect; approximately three times less than L-ephedrine.

Many people have felt that ephedrine is not worth the risks, and have tried "ephedrine free" stack formulas. However, there is no proof that any of these formulations are actually effective, whereas a great deal of evidence exists to support the effectiveness of the ECA stack, albeit with apparent risks.

Currently in the United States, ephedrine is legal, but the FDA bars marketing any supplements containing ephedrine as weightloss or bodybuilding supplements. To be legal, ephedrine must be marketed for medical conditions such as asthma. In addition, the FDA recently barred the sale of herbal supplements containing ephedra (a herb which contains both ephedrine and pseudoephedrine) under any circumstances. Ephedrine is still commonly available as a bronchodilator in several over the counter asthma medications from companies such as Biotek and Vasopro as well as in Primatine tablets.

As of 4/14/2005, U.S. District Judge Tena Campbell struck down the FDA's ban of weight loss supplements containing ephedrine alkaloids in the US, which may pave the way for its reintroduction as a weight loss supplement in the US. The ban on marketing ephedrine as a weightloss supplement at the moment is being challenged by several companies. A judge in Utah has ruled in favor of a pharmaceutical company that challenged the FDA's ban and the company may once again release products containing ephedrine back into the market.