FTLOScience
FTLOScience

How Methamphetamine Fueled Blitzkrieg and Beyond

By Published On: May 3, 2020Last Updated: November 23, 2022

The initial success of Nazi Germany in World War II is largely attributed to the strategy of Blitzkrieg: quick, surprise maneuvers through enemy territory that gives opponents little time to react. This, however, placed a tremendous physical and mental strain on the invading soldiers. To counter this, German chemists prescribed them methamphetamine, under the brand name Pervitin. After the war, the huge stockpiles of leftover methamphetamine found their way to civilians worldwide, where recreational use of ‘meth’ persists to this day.

Blitzkrieg

The German Invasion of Europe

The First World War was a war of attrition, with trenches being dug on both sides of no man’s land and battles lasting months, or even years. In contrast, the Nazi strategy of World War II—dubbed ‘Blitzkrieg’ or ‘lightning war’—embraced fast, penetrative attacks deep behind enemy lines, cutting off troops and supply lines before they even knew what hit them.

In 1940, war broke out over Western Europe following the German invasion of France. It was initially predicted that the capture of the first major French city, Sedan, would take two weeks. The German army managed it in just three days. For 72 hours straight, German troops rampaged through the countryside without rest, all while maintaining high alertness and the willingness to fight.

In the air, the Luftwaffe bombers continuously flew bombing raids over key cities and infrastructures. Their incessant bombing of the port of Rotterdam led directly to the surrender of the Dutch after only four days of fighting.

France and its allies, caught off guard, were completely overwhelmed by the speed and aggression of the German army. Little did they know that tiny pills of methamphetamine were the powerhouse behind this literally superhuman effort1.



Pervitin

First manufactured by the Berlin-based pharmaceutical company Temmler in 1938, the active ingredient of Pervitin was methamphetamine, also known today as ‘meth’ or ‘crystal meth’. Pervitin quickly became popular with the German public. The little pill increased productivity and improved wakefulness, all while being as accessible as candy. With its use already widespread when war broke out, the German army was quick to pounce on Pervitin’s potential to fuel the war effort.

It was also found that methamphetamine suppressed hunger, making it perfect for sustained assaults on enemy positions over several days. However, there were severe side effects following its prolonged use. Reports surfaced of methamphetamine-induced violence towards fellow soldiers and even civilians. Some soldiers died of heart failure, while others committed suicide under methamphetamine-induced psychotic episodes.

Back in the 1930s, especially with the shadow of war on the horizon, there was little to no regulation surrounding the sales, marketing and use of pharmaceutical products. Safety was a mere afterthought in drug discovery and development; clinical trials were practically unheard of.

pervitin capsules methamphetamine
Pervitin tablets came in various forms of colorful and whimsical packaging

Mechanism of Action

Methamphetamine is classified as a potent central nervous system (CNS) stimulant. Once methamphetamine enters the bloodstream, it can pass through the blood-brain barrier into the brain. It binds to and activates the trace amine-associated receptor 1 (TAAR1), a G-protein coupled receptor (GPCR). This induces neurotransmitters such as dopamine, noradrenaline and serotonin to be released. These neurotransmitters in the brain trigger an improvement in mood (euphoria), increased concentration and reduction of fatigue.

In addition to inducing the release of neurotransmitters, methamphetamine binding to TAAR1 also inhibits their reuptake, allowing their effects to persist much longer than they are supposed to. Methamphetamine itself is also able to directly activate various other receptors in the brain, facilitating a range of stimulant and neurotoxic effects.

Methamphetamine can persist for days in the bloodstream before it is metabolized and broken down by CYP2D6, an enzyme in the liver that is part of the cytochrome p450 family. Its long half-life of 5-30 hours coupled with high bioavailability allow it to sustain its potent effects over an extended period2.

chemical structure of methamphetamine
Methamphetamine has a simple chemical structure; its small size and high lipophilicity make it an ideal molecule for bypassing the blood-brain barrier quickly

Post-War Methamphetamine Use

Obetrol

After the war, German methamphetamine stocks seized by the Allied forces were marketed in the United States as a weight-loss pill under the brand name Obetrol. Throughout the 1950s and 1960s, its hunger-suppressing effects made it a popular diet pill. However, its widespread availability quickly led to recreational users abusing the drug. As is the case with many drugs that work on the brain, the body rapidly develops tolerance. This means that with each hit, a higher dose is required to produce the same effect in an individual. Combined with methamphetamine’s addictiveness and severe withdrawal effects, made the drug dangerous for long-term users.

Cases of methamphetamine overdose quickly became a common occurrence in emergency rooms. Other long-term health effects include neural damage and impairment of brain function, as well as cardiovascular disease and stroke3. The drug is also associated with risky sexual activities, which increase the risk of sexually transmitted infections such as HIV4. In 1973, under new regulations, the FDA finally ordered Obetrol to be withdrawn from the market; its medical usefulness could not be justified as both safe and effective.

Soon after its recall, Obetrol underwent a change in formulation, with amphetamine salts replacing methamphetamine as the active ingredient. This new concoction was sold on the market as Adderall for treating attention-deficit/hyperactivity disorder (ADHD) and is still a common prescription drug today.

obetrol promotional poster weight loss
Obetrol was heavily marketed and sales were not regulated – this promotional leaflet included a cutout for samples of the drug


Amphetamine

Very similar in chemical structure to methamphetamine, amphetamine or ‘speed’ was also prevalent in World War II, used by both the Axis and Allied powers. As its name suggests, amphetamine differs from methamphetamine by just a single methyl (-CH3) group, with similar effects in the body such as euphoria and increased alertness. However, it was designed to be less toxic and with shorter-lasting effects. In place of methamphetamine, amphetamine has been heavily studied and tested for its effectiveness as a CNS stimulant.

chemical structure of amphetamine
With an identical backbone, amphetamine’s structure contains the parent compound of methamphetamine with the terminal methyl group removed

Furthermore, long-term use of amphetamine at therapeutic doses has been shown to be both safe and effective for the treatment of ADHD and related illnesses5. Coupled with the lower risk of addiction and fewer severe adverse effects when compared to methamphetamine, amphetamine has been used by military forces in combat situations even till the Gulf War in the early 1990s. 58-61% of individuals taking amphetamine before operations reported benefits or usefulness, but several high-profile accidents linked to taking the drug have seen a halt to its military use in recent years6.

Methamphetamines Today

At the time of writing, most countries require a prescription for methamphetamine, which is marketed as Desoxyn in the United States. The drug is approved for the treatment of ADHD and obesity, despite its limited therapeutic benefit when compared to the high risks involved. The L-enantiomer, known as levomethamphetamine, can also be purchased over the counter for use as an effective nasal decongestant in many countries. Unlike the D-enantiomer, dextromethamphetamine, this form of methamphetamine does not affect dopamine release and hence has little potential for inducing euphoria and addiction.

Tablets of Desoxyn, manufactured by Abbott Laboratories

Although methamphetamines are no longer used as stimulants by military forces today, it remains a popular recreational drug and is reported to be the second most widely misused substance worldwide3. One of the main reasons is its ease of synthesis (à la Breaking Bad), with precursors and equipment that are fairly easily obtainable. This, in turn, ensures a cheap and steady supply, making methamphetamine abuse one of the more pressing public health issues today.

Reference

  1. Defalque, R. J., & Wright, A. J. (2011). Methamphetamine for Hitler’s Germany: 1937 to 1945. Bulletin of anesthesia history29(2), 21-4.
  2. Schep, L. J., Slaughter, R. J., & Beasley, D. M. G. (2010). The clinical toxicology of metamfetamine. Clinical Toxicology48(7), 675-694.
  3. Krasnova, I. N., & Cadet, J. L. (2009). Methamphetamine toxicity and messengers of death. Brain research reviews60(2), 379-407.
  4. Halkitis, P. N., Parsons, J. T., & Stirratt, M. J. (2001). A double epidemic: crystal methamphetamine drug use in relation to HIV transmission. Journal of homosexuality41(2), 17-35.
  5. Huang, Y. S., & Tsai, M. H. (2011). Long-term outcomes with medications for attention-deficit hyperactivity disorder. Cns Drugs25(7), 539-554.
  6. Emonson, D. L., & Vanderbeek, R. D. (1995). The use of amphetamines in US Air Force tactical operations during Desert Shield and Storm. Aviation, space, and environmental medicine.

About the Author

sean author
Sean Lim

Sean is a consultant for clients in the pharmaceutical industry and is an associate lecturer at La Trobe University, where unfortunate undergrads are subject to his ramblings on chemistry and pharmacology.

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