Amphetamine, Energy Drinks and Associated Problems

Amphetamine is a psycho-stimulant drug which was first synthesized in 1887 by Lazăr Edeleanu, a Romanian chemist.

No pharmacological use was found for amphetamine until 1929, when psycho-pharmacologist Gordon Alles, in search of an allergy drug remedy, re-synthesized and tested it on himself. He noted a “feeling of well being,” “palpitation,” and eventually a “sleepless night” in which his “mind seemed to race from one subject to another.”(1)

A few years later a new drug dubbed “Benzedrine”, based on Alles re-synthesized amphetamine compound, was released on the market by the Philadelphia firm Smith, Kline and French as a decongestant inhaler.

The company then began to look for more commercial outlets for amphetamine in a wide range of medical specialties. The use that stirred interest among neuro-psychiatrists was for therapy of common, milder depressions. Amphetamine represented the first of the anti-depressant drugs and its use soon spread to general practice. (2)

However, the use of amphetamine soon spread outside general practice. By early 1937, abuse of the drug was reported among mid-western college students, and amphetamine tablets were taking on a new identity as “pep pills” or “pepper-uppers.” Students were mostly taking amphetamine while studying for, or actually taking, exams.(3)

After decades of reported abuse, the Food and Drug Administration (FDA) limited amphetamine to prescription use in 1965, but non-medical use remained common. In 1971, amphetamine became a schedule II drug, under the Controlled Substances Act.

A schedule II drug is classified as one that has a high potential for abuse, severe physiological and psychological dependence, and has a currently-accepted medical use, such as d-amphetamine used to treat attention deficit hyperactivity disorder (ADHD). (4)

More recently, many students have turned to a legal stimulant to aid their performance – the ‘energy drink’. Energy drinks are soft drinks advertised as boosting energy. These drinks usually contain a variety of stimulants, vitamins, and herbal supplements the manufacturer has combined.(5)

The central ingredient in most energy drinks is caffeine, the same stimulant found in coffee or tea, often in the form of guarana or yerba mate. Caffeine is found in varying quantities in the beans, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants.

“The caffeine content of energy drinks varies over a 10-fold range, with some containing the equivalent of 14 cans of Coca-Cola, yet the caffeine amounts are often unlabeled and few include warnings about the potential health risks of caffeine intoxication,” says Roland Griffiths, Ph.D., an author of an article that appears in the journal Drug and Alcohol Dependence.(6)

Caffeine Jitters

An acute overdose of caffeine usually in excess of about 300 milligrams, dependent on body weight and level of caffeine tolerance, can result in a state of central nervous system over-stimulation called caffeine intoxication or informally the “caffeine jitters”.

Caffeine intoxication is a recognized clinical syndrome included in the Diagnostic and Statistical Manual of Mental Disorders and the World Health Organisation’s International Classification of Diseases.

It is marked by;

  • nervousness
  • anxiety
  • restlessness
  • insomnia
  • gastrointestinal upset
  • tremors
  • rapid heartbeats (tachycardia) and;
  • psychomotor agitation (restlessness and pacing).

A major concern is that without adequate, prominent labeling, consumers most likely won’t realize whether they are getting a little or a lot of caffeine.

“It’s like drinking a serving of an alcoholic beverage and not knowing if its beer or scotch,” says Griffiths.

However, with energy drinks no warning labels are warranted. Because many energy drinks are marketed as “dietary supplements,” the limit that the FDA requires on the caffeine content of soft drinks (71 milligrams per 12-ounce can) does not apply. The caffeine content of energy drinks varies from 50 to more than 500 milligrams.

Griffiths also notes that most of the drinks advertise their products as performance enhancers and stimulants – a marketing strategy that may put young people at risk for abusing even stronger stimulants.

This view is substantiated by a 2008 study of 1,253 college students which found that energy drink and associated caffeine consumption significantly predicted subsequent non-medical prescription stimulant use, raising the concern that energy drinks might serve as “gateway” products to more serious abuse of drugs. (7)

Stimulants such as amphetamine and energy drinks alter behavioral effects in the brain by modulating several key neurotransmitters, including dopamine, serotonin, and melatonin which function to regulate appetite, sleep, memory, learning, temperature, and mood.

More specifically, if the melatonin signal – which forms part of the system that regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature – is inhibited, functional ability will be limited. Similarly, research into mood has speculated inhibition of serotonin levels have a role in depression.

Research shows that depression and other mental disorders, or a substance-abuse disorder (often in combination with other mental disorders) are risk factors for suicide. More than 90 percent of people who die by suicide have these risk factors. (Facts about suicide)

It also shows:

  • A person dies by suicide about every 18 minutes in the U.S.  An attempt is estimated to be made once every minute.
  • Suicide is the second leading cause of death among college students and the third leading cause of death among all youth 15–24 years old.
  • Seventy percent of youth who make a suicide attempt are frequent users of alcohol and/or other drugs.
  • The rates of depression in younger people have steadily grown to outnumber rates of depression in the older populations.(8)

So what’s behind the rising rates of depression among young people?

A statistical modeling study suggests that problems with alcohol abuse may lead to an increased risk of depression, as opposed to the reverse model in which individuals with depression self-medicate with alcohol, according to a report in the March (2009) issue of Archives of General Psychiatry.(9)

However, some researchers think loss of healthy bacteria may have an effect. Emory neuro-scientist Charles Raison, MD, and colleagues say there is mounting evidence that disruptions in ancient relationships with microorganisms in soil, food and the gut may contribute to the increasing rates of depression. (10) (see… A benefit of flu: protection from asthma?)

According to the authors, the modern world has become so clean, we are deprived of the bacteria our immune systems came to rely upon over long ages to keep inflammation at bay.

“We have known for a long time that people with depression, even those who are not sick, have higher levels of inflammation,” explains Raison.

Inflammation is the body’s immune response to irritation, injury, or trauma. The immune system is complex – different types of immune cells and proteins do different jobs.

cytokines and inflammatory response

Cytokines are among those proteins which are released by cells into the circulation or directly into tissue.  The release triggers, or stimulates, specific responses by the target cells.(11)

Overproduction or inappropriate production of certain cytokines by the body can result in disease. Furthermore severe depressive illness is accompanied by signs of immune activation and by elevations of cytokine production or levels.(12)

Raison says:  “Since ancient times benign microorganisms, some times referred to as ‘old friends,’ have taught the immune system how to tolerate other harmless microorganisms, and in the process, reduce inflammatory responses that have been linked to the development of most modern illnesses, from cancer to depression.”

In the December 15 , 2010 issue of Cancer Research, scientists say they can now definitively show that an inflammatory process within the breast itself promotes growth of breast cancer stem cells responsible for tumor development.(13)

Researchers, led by Richard G. Pestell, M.D., Ph.D, found that if they selectively blocked inflammation just in the breast, tumors would not develop.

So, is a clean environment, as Raison suggests, the main culprit for the onset of inflammation and modern disease? Or do other factors play a part, such as the stimulants amphetamine and caffeine?

Let’s turn our attention to caffeine, the main ingredient in most energy drinks.


Caffeine enters the bloodstream through the stomach and small intestine and can have its effects as soon as 15 minutes after it is consumed. Once in the body, caffeine will stay around for hours: it takes about 6 hours for one half of the caffeine to be eliminated. (14)

One of the negative effects of caffeine is its ability to disrupt sleep cycles, causing less deep sleep, particularly when you have caffeinated beverages within a few hours of bedtime.

Night-shift workers especially should avoid drinking coffee if they wish to improve their sleep, according to new research. A study led by Julie Carrier, a University of Montreal psychology professor has found the main byproduct of coffee, caffeine, interferes with sleep and this side-effect worsens as people age. (15)

Circadian Rhythm

Scientists suspect that overnight work, and subsequent altered sleep patterns, is dangerous because it disrupts the circadian rhythm, the body’s biological clock. This disruption can result in inhibition of the hormone melatonin, which can suppress tumor development, and is normally produced at night. Disruption of circadian rhythms has been classified as a probable cause of human cancer by the International Agency for Research on Cancer.

Among the first to spot the night shift-cancer connection was Richard Stevens, a cancer epidemiologist and professor at the University of Connecticut Health Center. In 1987, Stevens published a paper suggesting a link between light at night and breast cancer. He was trying to figure out why breast cancer incidence suddenly shot up starting in the 1930s in industrialized societies, where night-time work was considered a hallmark of progress. (16)

Animals that have their light-dark schedules switched develop more cancerous tumors and die earlier. In humans, sleep deprivation and the ensuing melatonin suppression lead to immunodeficiency. For example, sleep deprivation suppresses natural killer-cell activity and alters cytokine balance, reducing cellular immune defense.(17)

Recent research with animal models (animals with a disease that is similar to or the same as a disease in humans) suggests that the body’s neuro-endocrine response (release of hormones into the blood in response to stimulation of the nervous system) can directly alter important processes in cells that help protect against the formation of cancer, such as DNA repair and the regulation of cell growth.(18)

Akio Ohta et al reason if caffeine activates bio-chemical targets, it is important to test whether the consumption of caffeine during an acute inflammation episode would lead to the exacerbation of immune-mediated tissue damage. They examined treatment with caffeine for its effects on acute liver inflammation. It was shown that caffeine at lower doses (10 and 20 mg/kg) strongly exacerbated acute liver damage and increased levels of pro-inflammatory cytokines.(19)

One of the main reasons for liver damage is chronic alcohol consumption. As the liver heals from alcohol metabolism, it begins to scar (cirrhosis of the liver) from continual regeneration. The damage interferes with regulatory processes like metabolism of proteins, and carbohydrates, causing malnutrition and toxicity in the blood.(20)

People who have poor general health resulting from liver disease and large amounts of alcohol consumption run the risk of developing serious and persistent changes in the brain.(21)

In a study with human postmortem brains Crews et al found, neuro-inflammation and levels of pro-inflammatory cytokine were significantly higher in the brains of alcoholics than the brains of control, moderate-drinking individuals.  Crews’ findings suggest that excessive alcohol consumption sets off a spreading cytokine process.(22)

University of Illinois animal sciences professor Rodney Johnson believes excessive cytokine production in the brain causes associated problems. He states:

“We think this contributes to cognitive aging and is a predisposing factor for the development of neuro-degenerative diseases.” (23)

A number of proposed mechanisms for depression appear to be similar to those implicated in neuro-degenerative diseases.  For example, neuro-inflammation observed in depression are found to be associated with the development of Alzheimers disease .(24)

It would appear the over production of cytokines causing major inflammatory problems, initiated by excessive alcohol consumption and exacerbated by both caffeine intake and sleep deprivation, are associated with major health problems such as depression and cancer.

A drug commonly used to treat depression is the prescribed anti-depressant duloxetine, or cymbalta which has recently been reported to be effective at reducing joint and muscle pain associated with breast cancer treatment. It is believed to decrease pain through its actions in the central nervous system.(25)

However, the FDA requires all anti-depressants, including duloxetine, to carry a black box warning stating that anti-depressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyzes conducted by FDA experts that found a 2-fold increase of suicidal behavior in children and adolescents, and 1.5-fold increase of suicide in the 18–24 age group.(26)

In addition, interview data from the U.S.A.’s Third National Cancer Survey, suggested along with alcohol ingestion, several common drugs acting in a similar manner could be cancer promoters. The drugs, including d-amphetamine and tricyclic anti-depressants, were associated with a higher occurrence of cancers of the breast, thyroid, and malignant melanoma. Over 20,000 (25%) of all new breast-cancer cases each year in the U.S.A. could be preventable if this hypothesis is correct.(27)

Anti-depressants don’t appear to be a healthy option for young people.


luteolin rich foods

What about luteolin, a compound found in many plants, including carrots, peppers, celery, olive oil, peppermint, rosemary and chamomile.

Should this be added to energy drinks?


Rodney Johnson, who has spent nearly a decade studying the anti-inflammatory properties of nutrients and various bio-active plant compounds, suggests that luteolin improves cognitive health by acting directly on microglial cells to reduce their production of inflammatory cytokines in the brain.(28)

The researchers showed microglial cells that were exposed to a bacterial toxin produced inflammatory cytokines that could kill neurons. When the microglia were exposed to luteolin before they encountered the toxin, however, the neurons lived.

“The neurons survived because the luteolin inhibited the production of neuro-toxic inflammatory mediators,” Johnson said.

Exposing only the neurons to luteolin before the experiment had no effect on their survival, the researchers found.

“This demonstrated that luteolin isn’t protecting the neurons directly,” he said. “It’s doing it by affecting the microglial cells.

“These data suggest that consuming a healthy diet has the potential to reduce age-associated inflammation in the brain, which can result in better cognitive health,” he adds.

Better cognitive health resulting in reduced depression and suicide rates.  Now that helps me sleep better at night.


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