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 clinical and scientific literature. Please discuss your medications with your doctor.
What is Ephedrine?
Ephedrine is derived from the plant Ephedra, which has long been used by the Chinese for medicinal purposes. After its initial discovery in 1885, ephedrine became a popular and effective treatment for asthma .
It is now used as a recreational drug or nutritional supplement. Ephedrine is banned in many countries including the United States, as it is a major source of the drug methamphetamine (crystal meth) [3, 4].
Ephedrine exists in 4 different molecular arrangements or isomers. The 4 isomers are classified as true ephedrine or pseudoephedrine, depending on the way their chemical structures are rotated around their centers .
Pseudoephedrine is a diastereomer of ephedrine. This means that while they are made of the same elements, the 2 molecules differ in the arrangement at 2 molecular centers .
The 2 types of ephedrine are called (+)-ephedrine or L-ephedrine, and (-)-ephedrine or D-ephedrine, depending on if the molecule is rotated clockwise or counterclockwise around their centers, respectively .
Ephedrine Mechanism of Action
Ephedrine mainly functions by increasing the release and activity of adrenaline on its receptors. This action increases heart rate, narrows the blood vessels, opens the airways to the lungs, and stimulates the brain .
Ephedrine stimulates 3 main types of adrenaline receptors: alpha, beta-1, and beta-2. It specifically targets the beta-type adrenaline receptors and increases the production of the messenger molecule, cyclic AMP (cAMP). Ephedrine acts on alpha receptors by decreasing the production of cAMP. Decreasing cAMP decreases glycogen, sugar, and fat production [3, 4, 11].
It can also increase or decrease blood pressure based on the type of beta receptors it targets. By stimulating the beta-1 receptors in the heart, ephedrine can cause high blood pressure. On the other hand, ephedrine can lower blood pressure by activating beta-2 receptors, leading to fainting and flushing .
Ephedrine also acts as a mild brain stimulant. Because of its unique structure, it can easily dissolve through fats and act directly on the brain. This increases the activity of sections of the brain that control emotion (limbic system) .
Ephedrine may also act by:
- Directly stimulating adrenaline receptors .
- Blocking adrenaline transporters, which increases the activity of adrenaline by allowing it to remain active longer in the brain. This increases heart rate and blood pressure [4, 12].
- Partially inhibiting monoamine oxidase (MAO), an enzyme that breaks down adrenaline. This causes adrenaline to stay active longer, resulting in irregular heartbeat and headaches .
- Increasing the release and blocking the uptake of dopamine, which enhances physical activity [13, 14].
- Increasing the release of acetylcholine at adrenaline nerves .
- Increasing serotonin release, which promotes weight loss by suppressing appetite .
Uses of Ephedrine
1) Increases Blood Pressure
In a study (double-blind randomized controlled trial) of 204 pregnant female patients under spinal anesthesia for urgent delivery via C-section, ephedrine was more effective in treating low blood pressure than phenylephrine .
In a randomized study of 51 vein-surgery patients under long-term treatment for high blood pressure, ephedrine effectively increased blood pressure when it went below normal levels .
Ephedrine administered through the veins increased the rate at which the heart contracted in dogs, which can cause a rise in blood pressure .
In male rats, the (-)-ephedrine isomer form of ephedrine (a single isomer form of ephedrine), reduced vein width more than a racemic mixture of ephedrine, which can result in higher blood pressure .
Ephedrine has a greater capacity to constrict veins than arteries. This means it is more effective in increasing blood flow through the veins than the arteries, which increases blood pressure .
Ephedrine is commonly used to treat low blood pressure during pregnancy. However, in a review of 7 studies (randomized controlled trials) of a total of 292 pregnant women undergoing spinal anesthesia during delivery, there was no difference in blood pressure increase between ephedrine and phenylephrine. In fact, phenylephrine was more likely to increase heart rate than ephedrine .
In one study (double-blind randomized controlled trial) of 32 adolescents, ephedrine did not significantly increase blood pressure and heart rate .
2) May Improve Asthma Symptoms
Ephedrine treats shortness of breath and airway spasms. In a study of 25 asthma patients, ⅔ of the group experienced relief from their symptoms .
In 12 patients with inflamed and spasming airways, gaseous ephedrine was effective in reducing 6 of the 12 patients’ symptoms. Oral ephedrine, however, was not effective on any of the 12 patients .
In a 2-week study of 8 asthma patients, ephedrine prevented lung function decline. However, after being treated with ephedrine 3 times per day in this 2-week period, a single dose of ephedrine had no additional effect in opening up the patients’ airways .
In a double-blind crossover study of 20 asthma patients comparing the immediate effects of terbutaline (a bronchodilator) and ephedrine on the heart and bronchial tubes, ephedrine significantly widened the airways, but not as much as terbutaline .
In one adult, ephedrine was ineffective in treating the symptoms of asthma alone, but when given in combination with 1 grain of natural thyroid, it prevented the return of the patient’s attacks for months .
While ephedrine is generally effective in treating asthma, there are some instances where it does not work. This may be because the dosage was too small to have any effect on the airway spasms .
3) Relieves Nasal Congestion
In one study (double-blind randomized controlled trial) of 54 patients experiencing the common cold, a single 60 mg dose of pseudoephedrine improved the symptoms of congestion .
Another 3-day trial (double-blind randomized controlled trial) of 238 patients with illness-caused nasal congestion found that pseudoephedrine reduced symptoms with a single 60 mg dose. Multiple doses were also effective .
One study (double-blind randomized controlled trial) of 58 adult patients with congestion due to allergies also found that oral pseudoephedrine effectively increased nasal airflow .
Additionally, in combination with antihistamines, pseudoephedrine was more effective in reducing nasal congestion than pseudoephedrine alone in a 15-day, randomized trial of 1,018 patients .
4) May Promote Weight Loss
Three patients with obesity who had been steadily gaining weight lost an average of 13.9% of their body weight, and 2 of them maintained weight loss for a period of years when taking ephedrine with caffeine .
A randomized trial conducted on 43 obese patients (41 being women) found that the patients lost an average of 12.6 kg after taking a combination of ephedrine and caffeine 3 times a day, and 8 weeks of a low-energy diet .
Another 16-week study (randomized controlled trials) of 57 patients found that a combination of ephedrine and caffeine reduced body fat by 6%, and triglycerides by 15.2 mg/dL. When combined with a drug used to treat type 2 diabetes, ephedrine reduced triglyceride levels by 41 mg/mL .
In a 6-month study (double-blind randomized controlled trial) of 167 patients, herbal ephedra and caffeine decreased body weight and body fat by nearly double the amount of that of placebo .
In an 8-week randomized, double-blind placebo-controlled (double-blind randomized controlled trial) study of 67 subjects, an herbal mixture of Ma Huang (ephedrine plant) and Guarana (caffeine plant) promoted short-term weight and fat loss .
Average body weight was significantly reduced after 4 and 12 weeks of treatment in a study of 5 overweight women .
In a study (double-blind randomized controlled trial) with a 1-year follow-up period of 225 heavy smokers, weight gain was significantly reduced when ephedrine and caffeine were taken during the first 12 weeks of the study .
Additionally, another trial (double-blind randomized controlled trial) of adolescents found that a caffeine and ephedrine combination reduced body weight, BMI, and body fat .
In naturally obese mice, ephedrine reduced weight and suppressed appetite .
5) Lowers Cholesterol Levels
Ephedrine increases the activity of a protein (hepatic lipase) that breaks down a type of LDL cholesterol that blocks arteries. When combined with caffeine, it increases HDL cholesterol. This protects against artery blockage, which may prevent cholesterol-related heart disease .
In a 6-month trial (double-blind randomized controlled trial) of 167 subjects, herbal ephedra and caffeine decreased LDL cholesterol and increased HDL cholesterol levels .
In a study (randomized controlled trial) of 32 obese women, a combination of 20 mg ephedrine and 200 mg caffeine maintained HDL cholesterol levels by week 4 of the trial .
In a 16-week double-blind randomized controlled trial of 57 patients, a combination of ephedrine, caffeine, and a type 2 diabetes-treating drug increased HDL cholesterol by 7.8 mg/dL .
In obese mice, ephedrine reduced cholesterol levels in the blood .
6) May Protect the Brain
In a 2-week double-blind randomized controlled trial, ephedrine had some effect in improving attention .
In rats, Ephedra plant extract treated blood-brain barrier breakage and an abnormal buildup of fluid in the brain after spinal cord and brain injury. This may be a protective factor against early brain injury caused by bleeding in the brain .
7) May Improve Narcolepsy-Related Symptoms
The most popular treatment of narcolepsy with ephedrine was conducted by Doyle and Daniels in the 1930s, successfully curing 5 out of 6 patients of their narcoleptic seizures. In another trial conducted on 46 patients, 20 were completely relieved of their symptoms, and all but 2 had some form of improvement .
Narcolepsy was also successfully treated with ephedrine in children. A 13-year-old male and two 9-year-old females were all cured of their sudden sleeping spells when taking ephedrine .
8) May Improve Athletic Performance
While the mechanisms are unclear, pseudoephedrine can improve athletic performance.
In a double-blind randomized controlled crossover trial of 22 healthy male athletes, a 180 mg dose of pseudoephedrine increased maximum rotation, power, and knee function during cycling exercise, as well as lung function .
In another study, pseudoephedrine improved the running time of athletes in a 1,500-meter time trial by 2.1% .
While pseudoephedrine can improve athletic performance, its mechanisms are not very understood and it may not always work. In a trial (randomized controlled trial), pseudoephedrine failed to increase cycling time and time to fatigue, and also failed to improve knee function in both athletes and healthy individuals .
In a trial (randomized controlled trial) of non-professional cyclists, pseudoephedrine failed to increase cycling performance and had little to no effect on increasing blood pressure and oxygen uptake .
Doses of 40 mg and 60 mg of ephedrine did not significantly improve oxygen uptake, breathing efficiency, or blood pressure, which are all key factors used to determine physical performance .
9) May Alleviate Neuromuscular Disease
Ephedrine has been used to treat Myasthenia gravis, a disease that causes rapid weakness and fatigue of the muscles.
Four patients in a series of placebo-controlled, double-blind, and randomized, multiple crossover (double-blind randomized controlled study) studies took ephedrine as an add-on to their main treatment. This resulted in a small but consistent reduction of their symptoms and weakness .
In a separate follow-up study, 10 out of 12 patients experienced greater strength and mobility after 6 to 8 months of ephedrine treatment .
10) May Treat Adams-Stokes disease
Ephedrine may treat Adams-Stokes disease, defined as a sudden lapse into unconsciousness caused by irregular heart rhythms .
A 65-year-old white male no longer experienced fainting spells after being treated with 30 mg/day of ephedrine .
Another patient with Adams-Stokes disease no longer experienced seizures after taking 50 mg of ephedrine .
11) May Reduce Inflammation
In a case study of a 65-year-old woman with relapsing polychondritis (a rare, inflammatory chronic disorder of the cartilage), ephedrine (in gaseous form) immediately reduced the inflammation of the woman’s larynx after it was inhaled .
12) May Alleviate Amytal Poisoning Symptoms
A 3-year-old girl with Amytal (amobarbital) poisoning was treated with ephedrine to boost her lung function, in combination with picrotoxin. The next day, she fully recovered from the poisoning .
13) May Alleviate Bladder Problems
In a study of 37 patients with loss of bladder control (urinary incontinence), ephedrine improved control in those with mild wetting problems, regardless of cause .
Side Effects, Interactions, Natural Sources, Forms and Dosage of Ephedrine
Normally, ephedrine is known to have a variety of side effects, including:
- Nausea and vomiting 
- Anxiety 
- Mood change 
- Increased heart rate 
- Painful urination 
- Increased blood pressure 
- Insomnia 
- A headache 
- Irregular heartbeat 
- Dry mouth 
- Loss of vision 
The more serious possible side effects include:
- Heart attacks [62, 67, 68, 69]
- Seizures 
- Stroke 
- Schizophrenia (only after prolonged exposure) 
- Mania and psychosis [71, 72]
- Coma 
- Death [62, 74, 75, 76]
There is also a high risk of abuse of ephedrine, especially by those who have been prescribed the drug to treat asthma.
While ephedrine has been given to young children in trials in the U.S. in the past, French medical societies strongly advise against giving ephedrine to children under the age of 15. The age limit for the safe use of ephedrine remains unclear .
Additionally, ephedrine has caused brain damage in rats .
Drug Interactions of Ephedrine
Combining ephedrine with other drugs can be beneficial, but also cause problematic side effects.
However, taking ephedrine with aspirin is not advised. When combined with potassium permanganate (a chemical used to clean wounds) and aspirin, ephedrine caused nerve and movement disorders in teenagers .
Ephedrine should not be taken with drugs that prevent the reabsorption of adrenaline because it can cause severe high blood pressure, such as antidepressants, monoamine oxidase inhibitors (MAOIs), and cocaine [83, 84].
Combining ephedrine with monoamine oxidase inhibitors can cause irregular heartbeats and headaches .
Taking ephedrine with painkillers like acetaminophen (Tylenol) is ill-advised, as this combination caused a heart attack in a healthy 46-year-old male .
In dogs, ephedrine decreased the effectiveness of procaine hydrochloride, a local anesthetic .
On the other hand, when combined with the local anesthetics bupivacaine and lidocaine, ephedrine enhanced the ability of these drugs to block movement. This means that it has the potential to reduce the amount of local anesthetic needed to cause an effect .
A pretreatment of ephedrine made it easier to insert a tube in patients’ throats (to provide an air supply during surgery) when they were under the anesthetics propofol and rocuronium .
Combining nicotine and ephedrine should be avoided prior to a medical imaging exam. In rats, a mixture of nicotine and ephedrine increased the uptake of F-FDG, a chemical used in medical imaging .
When combined with theophylline, ephedrine caused insomnia, nervousness, and stomach issues during a trial conducted on 23 children with chronic asthma .
Ephedrine and propranolol cancel out the negative effects of each other. Propranolol prevented an increase in heart rate caused by ephedrine, while ephedrine prevented the widening of arteries normally caused by propranolol .
In anesthetized dogs with low blood pressure, ephedrine and dopamine improved heart output and oxygen delivery .
Reserpine reversed the effects of ephedrine and caused a spontaneous beating of muscles taken from cats .
Ephedrine can overpower the effects of some drugs that lower blood pressure. In rats, ephedrine not only reversed the suppressive effects of guanethidine on the nervous system but also reduced the uptake of it by adrenaline receptors. This caused an increase in blood pressure .
Natural Sources of Ephedrine
Ephedrine is derived naturally from the plant type Ephedra. Different species of this plant can be found in many regions around the world, but the first known extraction was an ephedrine alkaloid (an organic, nitrogen-containing compound) obtained from the Chinese herb, Ma Huang .
Ephedrine is also naturally found in Indian species of the ephedra plant .
There are many other species of this plant that ephedrine can be extracted from, such as ephedra sinica. Extracts from ephedra sinica are used in weight loss supplements .
Forms and Dosage of Ephedrine
In clinical trials, this drug is commonly taken in 32 to 65 mg doses. The adult human body can tolerate up to 4 grams of ephedrine without experiencing any negative effects. Prolonged ingestion of 0.2 to 0.225 grams produced no ill effects .
Children normally receive small amounts of ephedrine, about 0.1 to 0.2 mg per dose .
Ephedrine can become very dangerous if taken in excess amounts and outside of medical supervision. Ephedrine poisoning and death have occurred in many cases from excessive consumption of this drug [76, 105, 75].
If the effects of ephedrine seem to decrease over prolonged use, do not increase the dose unless you talk to your doctor first.
Limitations and Caveats
There are few studies currently available that examine the long-term use of ephedrine. More trials that determine which drug combinations with ephedrine improve safety and efficiency are needed. More long-term trials also need to be conducted on male groups .
Some users report that ephedrine increased their energy levels and suppressed appetite.
Other users experienced negative effects when combining caffeine and ephedrine. They felt more tired, could not think, and experienced compulsive urges such as nose-blowing or cleaning their nose with their nails, to the point where they drew blood. After stopping the drug combination, their compulsions ceased.
One user experienced prostate complications and bleeding from his genitals after prolonged consumption of a caffeine and ephedrine combination.
Many other users suggest drinking water when taking ephedrine, as it can cause bad breath and upset stomach.
A few users experienced increased acne, mild abnormal heartbeats, chest tingling, numbness, dizziness, and sweating (in the heat) after taking ephedrine.
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