SIX

Methamphetamine—From Pervitin
to Desoxyn to Crystal Meth


Approved for the treatment of attention deficit hyperactivity disorder (ADHD) in children, the prescription drug methamphetamine is seldom prescribed because of the stigma attached to its illicit forms. In the treatment of ADHD, methamphetamine’s biochemical effects are very similar to those of amphetamine, which is understandable since the two drugs are chemical cousins. Methamphetamine’s chemical name is desoxyephedrine. It is widely known for its illicit manufacture. Clandestinely manufactured in kitchen laboratories or super-laboratories run by organized crime syndicates, methamphetamine is known by many names including crank, meth, glass, chalk, ice, shards, crystal, crystal meth, and zip.

This chapter describes the drug methamphetamine, including its use as a pharmaceutical therapy in ADHD, its history, development, medical uses, physiological and adverse effects, potential for causing drug dependency, effects on brain chemistry, and the circumstances that have contributed to its reputation as a nuisance to society. Unfortunately, this reputation may detract from methamphetamine’s legitimate medical uses when administered orally in low doses.


Methamphetamine in ADHD

As a pharmaceutical agent, methamphetamine hydrochloride is only available in the United States as the drug Desoxyn and as a generic drug made by Mylan Incorporated that became available in 5 mg tablets in late April 2010. Abbott pharmaceuticals initially developed Desoxyn but in 2002, Abbott sold their rights to Desoxyn to Ovation Pharma, which took over production and marketing. Another pharmaceutical company, Able Labs, also produced a generic formulation of methamphetamine hydrochloride at a lower price than brand name Desoxyn until the company went out of business several years ago.

Compared to other amphetamines and methylphenidate (Ritalin), Desoxyn is more closely related to drugs containing dextroamphetamine, and its dosing in ADHD is similar to that of Dexedrine. According to some reports Desoxyn is especially effective for the inattentive form of ADHD. Desoxyn is often used as a “second-line” medication when the “first-line” (i.e., most commonly prescribed) medications have been found ineffective or cause undesirable side effects. Desoxyn is approved as an integral part of a total treatment program that includes other remedial measures (psychological, educational, social) for the use of ADHD in children at least 6 years old. Desoxyn is also used off-label for adults with ADHD.

The information provided by the FDA, which accompanies every Desoxyn prescription includes the following information:

The following have been reported with use of methamphetamine hydrochloride and other stimulant medicines:

1. Heart-related problems:

• sudden death in patients who have heart problems or heart defects

• stroke and heart attack in adults

• increased blood pressure and heart rate

Tell your or your child’s doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.

Your or your child’s doctor should check you or your child carefully for heart problems before starting Desoxyn. Your or your child’s doctor should check you or your child’s blood pressure and heart rate regularly during treatment with Desoxyn.

Call your or your child’s doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking DESOXYN.

2. Mental (Psychiatric) problems:

All Patients

• new or worse behavior and thought problems

• new or worse bipolar illness

• new or worse aggressive behavior or hostility

Children and Teenagers

• new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms

Tell your or your child’s doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.

Call your or your child’s doctor right away if you or your child have any new or worsening mental symptoms or problems while taking Desoxyn, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious (http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088582.pdf, accessed May 1, 2010). See the FDA’s PDF file for complete information.

Dosing in ADHD

Desoxyn is available in an intermediate-acting tablet form that is usually taken twice each day. No long-acting forms of Desoxyn are available. For ADHD, Desoxyn is usually prescribed to be taken one-half hour before meals to maximize absorption, although it can be taken with or without meals. In children 6 years of age or older, an initial dose of 5 mg is administered once or twice daily. Daily dosage may be raised in increments of 5 mg at weekly intervals until an optimum clinical response is achieved. The usual effective dose is 20 to 25 mg daily. The total daily dose may be given in two divided increments.

Adverse Effects

The most common side effects of Desoxyn include restlessness, headache, insomnia, dry mouth, and elevated blood pressure. Healthcare providers should be notified if patients with ADHD also have hypertension, hyperthyroidism, heart disease, glaucoma, diabetes, Tourette’s syndrome or allergies to certain dyes. Patients should also let healthcare providers know if they are pregnant or breastfeeding before using this drug. Adverse effects, drug toxicity, and contraindications for methamphetamine are described in Chapter Eight.

Drug Metabolism of Desoxyn

In humans using oral doses of Desoxyn, methamphetamine is rapidly absorbed from the gastrointestinal tract, with effects occurring within 15–20 minutes of oral dosing. The biological half-life (time when half of the dose has been metabolized) of methamphetamine has been reported in the range of 4 to 5 hours. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation, and deamination. At least seven metabolites of methamphetamine have been identified in the urine. Excretion occurs primarily in the urine and is dependent on the urine pH. Alkaline urine will significantly increase the drug half-life. Approximately 62 percent of an oral dose is eliminated in the urine within the first 24 hours with about one-third as intact drug and the remainder as metabolites.


The Discovery of Methamphetamine

Methamphetamine was first synthesized from ephedrine in 1898 by the Japanese chemist Nagayoshi Nagai. Early on, methamphetamine was celebrated for its “feel good” effect, although commercial production was limited due to the complexity of its synthesis. Because of this complexity methamphetamine was not investigated thoroughly for its medical effects. In 1919, another Japanese chemist, Akira Ogata, discovered a much simpler chemical process in which methamphetamine could be synthesized from red phosphorus, the active ingredient on the striker plate of a matchbook, iodine, and ephedrine. This basic process for making methamphetamine is still used today, although slight variations have been made when the basic ingredients have been difficult to procure. From a historical perspective, Akira’s simple chemical processing method led to the mass production of methamphetamine and to its widespread use. As a pharmaceutical compound, methamphetamine made its first worldwide impact when it became widely used by the German military at the onset of World War II.

Differences Between Amphetamine
and Methamphetamine

One mere atom separates methamphetamine from amphetamine, but this one atom is enough to evoke some major differences. Methamphetamine is composed of an amphetamine molecule with an additional methyl molecule attached to its nitrogen (amine) group. Although this structural change is slight, it makes methamphetamine a slightly more potent central nervous system stimulant than amphetamine. However, methamphetamine has slightly less cardiovascular activity. Methamphetamine’s reduced cardiac effects have a biochemical basis. Methamphetamine isn’t as effective as amphetamine in inhibiting the norepinephrine transporter in sympathetic nerves. As a result, methamphetamine doesn’t cause the increase levels of norepinephrine (a stimulating neurotransmitter) associated with amphetamine. Consequently, methamphetamine users can take higher drug doses without noticing disturbing cardiac effects. This presumably adds to its abuse potential, since higher doses can be tolerated without the user noticing a racing heart or palpitations.

Pharmacokinetics of Methamphetamine

The added methyl group attached to its basic amphetamine structure also gives methamphetamine the property of increased fat solubility. This property allows methamphetamine to cross the blood-brain barrier and penetrate the brain more readily than amphetamine. Therefore, its stimulating effects on the central nervous system are faster and more intense. In addition, the added methyl group makes methamphetamine resistant to degradation by the body’s monoamine oxidase enzymes. This property increases the drug’s stability. Compared to amphetamine, methamphetamine is also easier to synthesize by novice chemists using simple, although hazardous, ingredients. Methamphetamine’s chemical structure also increases its tolerance for heat, and higher temperatures fail to degrade it. This property makes it easy to dissolve, crystallize and smoke or inject methamphetamine.

Methamphetamine Stereoisomers

Like amphetamine, methamphetamine can exist in the form of two isomers, the levorotary (L) and dextrorotary (D) forms. The levorotary form of the drug, levomethamphetamine (L-methamphetamine) has virtually no central nervous system effects and is primarily used in over-the-counter inhalers as a nasal decongestant. Because levomethamphetamine doesn’t cause any significant psychostimulant effects, it has no addictive properties. Most drugs made from methamphetamine contain the dextromethamphetamine (D-methamphetamine) isomer. Alternately, methamphetamine products may contain racemic forms of the drug. Racemic forms contain a mixture of both D and L-methamphetamine isomers.

The pharmacological actions of methamphetamine are so similar to those of amphetamine that the drugs are considered interchangeable when used in small doses. However, when larger doses of the drugs are used, there’s a significant difference. Larger doses of methamphetamine produce a well-sustained rise in blood pressure due to both cardiac stimulation and peripheral vasoconstriction (narrowing of blood vessels). Unfortunately (for medical uses), the cardiovascular actions of the drug can only be obtained at the price of increased central nervous system stimulation (Goodman and Gilman 1955). With higher doses of methamphetamine, cardiac output is increased, although the heart rate may be lowered as a reflex action of the drug. The venous constriction characteristic of methamphetamine causes the peripheral venous pressure to increase. This is the ultimate cause of the increased cardiac output, which, in turn, can increase the pulmonary arterial pressure, contributing to pulmonary hypertension (Westfall and Westfall 2006).


Early Uses of Methamphetamine

In 1939 Europe, methamphetamine was first manufactured and marketed as a central nervous system stimulant called Pervitin. Like its chemical cousin Benzedrine in the United States, Pervitin was recommended for narcolepsy, depression, and alcohol abuse, and it was widely studied for its effects on military performance, particularly its ability to reduce symptoms of fatigue.

In 1943, Abbott Laboratories in the United States also began manufacturing methamphetamine and requested FDA approval for its use as a treatment for narcolepsy, depression, postencephalitis Parkinsonism, chronic alcoholism, cerebral arteriosclerosis and hay fever. Methamphetamine was approved for all of these indications, including its use in over the counter inhalers. However, its approval for many of these uses was later withdrawn. Years after the introduction of Desoxyn, a sustained-release formulation in the form of a plastic-matrix tablet, “Desoxyn Gradumet,” was also distributed. Abruptly, however, Abbott discontinued production of the Gradumet form of Desoxyn in late 1999, citing manufacturing difficulties as the reason.

In 1947, the FDA first approved methamphetamine (in the drugs Hydrin and Desoxyn) as an anorectic (weight loss) agent. By 1955 commercial forms of methamphetamine included: Amphedroxy, generic desoxyephedrine, Desoxyn, Dexoval, Doxyfed, Efroxine, Norodin, Semoxydrine, Syndrox, Methedrine, and Pervitin (Goodman and Gilman 1955). Injectable amphetamines, manufactured by Burroughs-Wellcome as Methedrine, were also available and often used to help bring surgical patients out of anesthesia despite their potential for causing dangerous side effects. Widely abused as an injectable drug, Methedrine is the original drug from which the nickname meth is derived.

Despite the abundance of different amphetamine-like drugs that were being developed in the late 1940s, the only real competition for SKF’s hugely popular Benzedrine was Abbot Labs’ methamphetamine tablets known as Desoxyn. In the 1960s, Abbot combined Desoxyn with the short-acting barbiturate drug pentobarbital to produce the prescription drug Desbutal. Today, only Desoxyn remains in use as a pharmaceutical methamphetamine product, and it is approved solely for the use of obesity and attention deficit hyperactivity disorder (ADHD).


Effects of Methamphetamine

Like its cousins amphetamine and ephedrine, methamphetamine (taken orally in small doses) causes a number of short-term central nervous system and cardiovascular effects, including increased activity, attention, activity, wakefulness and talkativeness; increased libido; decreased appetite; decreased fatigue; euphoria and a rush; increased respiration; rapid and sometimes irregular heartbeat; hyperthermia (increased body temperature) and a general improved sense of well-being. In addition, similar to amphetamine, methamphetamine has a calming effect on most individuals with ADHD.

However, when used at doses comparable to amphetamine, higher levels of methamphetamine make their way into the brain. This results in methamphetamine’s causing more potent and longer lasting psychostimulant effects. For this reason, a 5 mg dose of dextromethamphetamine is considered comparable to a 10 mg dose of dextroamphetamine.

Chronic use of methamphetamine is associated with a number of potential side effects. Long-term effects of methamphetamine, which are also described in Chapter Eight, include addiction, psychosis (including paranoia, hallucinations, repetitive motor activity), changes in brain structure and function, memory loss, aggressive or violent behavior, mood disturbances, weight loss, and severe dental problems. Although amphetamines may increase libido, long-term methamphetamine abuse may be associated with decreased sexual functioning in men (National Institute on Drug Abuse 2006).

Effects on Neurotransmitters

Methamphetamine causes the dopamine, norepinephrine, and serotonin transporters to reverse their direction of flow. This inversion allows for increased neurotransmitter (dopamine, norepinephrine, and serotonin) release from the synaptic vesicles to the neuron’s cytoplasm, and from the neuron’s cytoplasm to the synapse (extracellular circulation). This, in turn, stimulates post-synaptic receptors, indirectly increasing levels of all three neurotransmitters. Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft longer, extending the duration of the drug’s effects. Simply stated, when high doses of methamphetamine are ingested, there’s a longer “high.”

In studies, both amphetamine and methamphetamine have been shown to cause very significant increases in dopamine release in the nucleus accumbens region of the brain (10-fold over baseline). However, in the prefrontal cortex, amphetamine has been shown to be much more effective than methamphetamine in stimulating dopamine release. This could account for the different behavioral changes and dependency elicited by the two drugs. Dopamine release in the nucleus accumbens is a known major mediator of drug reinforcement (Melega 2001). With methamphetamine primarily causing dopamine increases in the nucleus accumbens, its abuse potential is higher.

However, in the prefrontal cortex, dopamine release (which is primarily related to amphetamine) may be related to inhibition of reward (Iversen 2008). In addition, while amphetamine causes an increase in glutamate release in the nucleus accumbens, methamphetamine does not. Consequently, by activating dopamine release in both the nucleus accumbens and in the prefrontal cortex, amphetamine may invoke changes that tend to counteract the rewarding effects of the drug, making it less likely to cause dependence when compared to methamphetamine.


America’s Early Love Affair with Methamphetamine

By 1933 when early reports of its benefits began to emerge in European studies, methamphetamine was heralded in the United States as a drug with benefits equivalent to those of penicillin. American pharmaceutical companies were eager to develop their own products. Several individuals interviewed for this book who reported using low doses of Desoxyn for depression or for cognitive enhancement in the past report that very low doses caused increased alertness, and improved well-being. In addition, a very low dose of the drug (2–5 mg) made them feel more energetic and focused without causing jitteriness. None of the individuals interviewed considered using higher than therapeutic or recommended doses during the time that they used the drug. All of these individuals said they would use the drug again if it was more easily available and they lamented the fact that restrictions on amphetamine compounds prohibited its availability.


Use in World War II

In his book On Speed, Nicolas Rasmussen writes, “The German Blitzkrieg was powered by amphetamines as much as it was powered by machine,” (Rasmussen 2008a, 54). (In this quote, Rasmussen is using amphetamines as a collective term to include methamphetamine, a common usage when speaking of amphetamines as a class of drugs.) Awareness of what was considered Germany’s powerful wartime advantage led to studies by military leaders in the United States, the U.K. and Japan. These studies, which showed some conflicting results and some benefits of amphetamine that were quite similar and not necessarily superior to those of caffeine, led to the subsequent use of amphetamines by these military forces in World War II.

Pervitin

In the 1930s, the Temmler pharmaceutical company introduced methamphetamine to the European market in a product called Pervitin. Because Japanese pharmacologists had earlier studied methamphetamine without patenting it, methamphetamine could no longer be patented. Pervitin was advertised as a psychiatric drug in much the same way as Benzedrine was marketed in the United States. The two drugs were essentially identical for medical and recreational use. Sales of methamphetamine roughly imitated those of amphetamine.

PERVITIN STUDIES • The Academy of Military Medicine in Berlin began studying methamphetamine in early 1938. Realizing that many soldiers were already using Pervitin, they decided to evaluate its use in combat situations. In 1938, Professor Ranke, the head of the physiological institute of the newly founded Military Doctors’ Academy in Berlin, started testing Pervitin with the help of his students. During the combat in Poland, a number of military doctors received large amounts of Pervitin to test under fighting conditions. They suggested that pilots and drivers of trucks and tanks, in particular, should use the drugs. This was followed by widespread use of Pervitin by German troops to eliminate fatigue and increase physical endurance (Iversen 2008, 72).

The evaluations and field reports suggested that Pervitin caused marginal improvement on mathematical and other mental tasks along with several unpleasant mental disturbances and physical reactions in some subjects. Nevertheless, military officials listed 3 mg Pervitin tablets among the medicines available for use by military units. During the first few months of the Blitzkrieg, German troops widely used Pervitin. The German military consumed 35 million Pervitin tablets from April through June 1940 (Rasmussen 2008a, 54).

PERVITIN CRITICS • Among the higher-ranking military officials, Pervitin was causing many doubts. During the 1939 clinical trials, researchers observed that many of the subjects were regular abusers of methamphetamine. Officials were concerned that the time needed to recuperate after using high doses of methamphetamine could easily interfere with the soldiers’ performance. The German air force, the Luftwaffe, also expressed concern that one’s performance wasn’t as good objectively as the pilot seemed to think. They felt this overconfidence among pilots could lead to accidents.

Field reports suggested that troops under the influence of methamphetamine made poor decisions and were prone to act erratically. In mid–1941, Germany placed methamphetamine, along with amphetamine, under strict narcotics regulation, making these drugs only available by special prescriptions. In addition, German’s military leaders declared that methamphetamine and amphetamine depleted the users’ energy stores and were dangerously habit-forming. Consequently, by 1942 the German military’s use of methamphetamine had significantly declined and German medicine officially recognized amphetamine compounds as addictive (Rasmussen 2008a, 55).

Adolf Hitler

Numerous reports portray Adolf Hitler as a frequent injector of methamphetamine prescribed to him by his personal physician, Theodor Morell. Several theories blame Hitler’s erratic behavior on his methamphetamine addiction. The neurologist and psychiatrist Fritz Redlich, professor emeritus of psychiatry at both Yale University and the University of California at Los Angeles, has studied the medical records and personal notes of Adolf Hitler extensively and interviewed surviving sources to assess his mental status. Redlich’s goal in writing Hitler: Diagnosis of a Destructive Prophet (Oxford University Press, 1998) was to ascertain if Hitler suffered from a genuine psychiatric illness or if he was, as has often been suggested, manipulated by Theodor Morell.

According to Redlich, Hitler’s list of medical complaints was extensive, including severe abdominal spasms, indigestion, bloating and constipation. In the early 1930s Hitler complained of tinnitus, and he was afflicted with hypertension, headaches and heart trouble. In addition, following a mustard gas injury in World War I, he suffered vision problems, including two episodes of temporary blindness. Near the end of life Hitler also suffered from symptoms of Parkinson’s syndrome.

After his review, Dr. Redlich concluded that Hitler also had spina bifida occulta, a hereditary condition that can cause difficulties in urination and susceptibility to bladder infections, and a condition of hypospadia, which refers to an abnormally positioned urethra. In addition, Redlich suspects that Hitler suffered from the autoimmune vascular disease temporal or giant cell arteritis, a condition that causes headaches, vision problems and cardiac disturbances. As for methamphetamine, Dr. Redlich believes that, while Hitler used methamphetamines extensively for several years, which was a popular practice at the time, he quit using them when he realized they were harmful. Redlich concludes that Hitler’s crimes were not caused by illness or drug abuse (Goode 1998). The contributions of methamphetamine to his actions, however, are still a matter of wide debate.


Japan’s Early Embrace of Methamphetamine

After World War II, a large supply of methamphetamine stockpiled by the Japanese military became available in Japan under the street name shabu (also Philopon). This led to a post-war epidemic that illustrates how easily the drug can take over the lives of millions of people when it is freely available without any health warnings. From 1942 onwards the Japanese armed forces used Pervitin to enhance wakefulness and performance. The government also encouraged its use, sometimes by coercion, by civilian workers involved in materials needed for the war effort (Iversen 2008, 107).

After the war, people in Japan experienced unprecedented social confusion, poverty, unemployment and a shortage of food. At the same time, pharmaceutical companies had large supplies of methamphetamine, which were available over the counter under the trade names Hiropon and Sedorin. To encourage sales, the pharmaceutical companies advertised these drugs as a remedy for sleepiness and depression. Around this time leftover supplies of methamphetamine purchased by the military were dumped onto the illegal market. Because of its wide availability, people from all walks of life—including former military personnel who had become acquainted with it during the war years—quickly embraced methamphetamine.

By 1946 physicians were seeing chronic methamphetamine addicts. The Drug Control Law of 1948 made it harder to get methamphetamine, but it was still readily available and its use continued to spread. By 1948, physicians estimated that 5 percent of Japanese citizens between 16 and 25 years of age were using methamphetamine and some people were injecting it.

During the peak of Japan’s methamphetamine epidemic in 1954, about half a million people in Japan were reported to be abusing methamphetamine, mainly by intravenous injection. Between 1945 and 1954, two million people in Japan reported having used methamphetamine (Iversen 2008, 108). The incidence of methamphetamine-induced psychosis and schizophrenia soared, and many of these individuals were confined to psychiatric hospitals. Due to widespread abuse, the Japanese Ministry of Health banned its use in 1951, but the epidemic continued. A series of new laws with very harsh penalties finally proved effective, with more than 50,000 arrests made in 1954, and the use of methamphetamine soon subsided. A rash of methamphetamine-related crimes and violence also caught the attention of the public and contributed to its falling out of favor. In the Kyoto incident, a methamphetamine addict murdered a 10 year-old-girl, which brought the effects of methamphetamine abuse into a very clear light.

Since then (as in the United States) methamphetamine is primarily produced by criminal organizations, such as the Yazuka organization, a major criminal element in Japan. Today methamphetamine is still associated with the Japanese underworld and the lower classes. Its use is discouraged by strong social taboos.


America’s First Methamphetamine Epidemic

Historians report that the first methamphetamine epidemic in the United States occurred in the Haight-Ashbury district of San Francisco in 1967. At the time, both methamphetamine and the street drug ecstasy, including both methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA), became the drugs of choice in the Bay area. The term “speed freak” came into use at this time to describe the stereotyped psychotic behavior exhibited by methamphetamine users, particularly those who injected the drug and cycled between binges lasting for days on end and the inevitable crashes. In contrast to the “love drug” effects of ecstasy, methamphetamine users were prone to poor judgment, anger and violence. Methamphetamine was readily available due to its illegal production by the Hells Angels motorcycle club.

The physician David E. Smith, who opened the first free clinic in the area to deal with the problems related to methamphetamine drug overdoses, binges and crashes, testified before Congress in 1971 in a Hearing on Diet Pills (Amphetamines) Traffic, Abuse, and Regulation, warning that after a major speed epidemic runs its cycle a downer or depressant phase occurs. Smith also reported that his medical clinic initiated the “Speed Kills” campaign because of the increased violence seen by individuals using methamphetamine. An expert on methamphetamine abuse, Smith wrote his 1965 thesis on the effects of caged mice subjected to methamphetamine. He reported that a mouse on meth interpreted grooming as a violent attack, often instigating a fatal fight (Warth 2007).

The inevitable downer phase Smith referred to occurred is America’s late-1970s heroin epidemic (Rasmussen 2008a, 255). In the next major speed cycle in the late 1980s, California was back in the news with San Diego reported to be the methamphetamine capital of the United States (Warth 2007). Methamphetamine has moved its away across the country and can be found in most every city on the map, especially small rural areas in the Midwest. The downer phase emerging as a result of this most recent speed epidemic appears to revolve around the increased use of opiates such as Vicodin and OxyContin.


Abuse Potential of Methamphetamine
in the United States

Despite occasional press releases saying methamphetamine use has been curtailed, the abuse of methamphetamine continues to be a very serious problem in the United States. Meth babies are a regular addition to hospital nurseries, and meth lab busts are commonplace even in upper middle class neighborhoods. Although widespread abuse of methamphetamine was initially limited to Hawaii and the western United States, today the problem is widespread. The addictive potential is especially high because methamphetamine is widely available and it can be smoked, snorted or injected, causing higher levels of the active drug to enter the brain.

According to the 2005 National Survey on Drug Use and Health, an estimated 10.4 million people age 12 or older (4.3 percent of the population) have used methamphetamine at least once. Approximately 1.3 million individuals reported using methamphetamine in the past year, and 512,000 reported current use (National Institute on Drug Abuse 2006).

The Community Epidemiology Work Group (CEWG) of the National Institute of Drug Abuse is an early warning network of researchers that studies the nature and pattern of drug abuse in 21 major areas of the U.S. In January 2006, CEWG reported that methamphetamine continues to be a problem in the West, with indicators persisting at high levels in Honolulu, San Diego, Seattle, San Francisco, and Los Angeles; in addition, the problem continues to spread to other areas of the country, including both rural and urban sections of the South and Midwest. In 2006, methamphetamine was reported to be the fastest growing problem in metropolitan Atlanta (National Institute on Drug Abuse 2006).

The Drug Abuse Warning Network (DAWN), which collects data on drug-related emergency room visits throughout the nation, has reported a greater than 50 percent increase in the number of visits involving methamphetamine abuse between 1995 and 2002.

Smoking, Sniffing and Shooting Crystal Meth

About 50 percent of methamphetamine users in the United States today are reported to smoke the drug. This number varies in different geographical regions, with higher numbers of methamphetamine smokers reported in California and higher numbers of methamphetamine injectors in Texas. In the Minneapolis–St. Paul area sniffing is reported to be the favored route of ingestion (http://www.drug-rehabs.com/methamphetamines-rehab.htm).

In the 1980s, “ice,” which is a smokable form of methamphetamine, was first introduced in Hawaii. Ice is a large, usually clear crystal of high purity that is smoked in a glass pipe similar to the pipes used for crack cocaine. Impurities in the production process can affect the color of ice. The smoke produced by ice is odorless, leaves a residue that can be reused, and produces effects that may persist for more than 12 hours. Ice can be easily produced because methamphetamine hydrochloride can be volatilized at high temperatures without being physically degraded. Amphetamine, on the other hand, requires higher temperatures for it to volatize, and at these high temperatures amphetamine is degraded or rendered inert.

It’s not unusual to hear of people who smoke, inject, sniff or snort methamphetamine to develop symptoms of paranoia and psychosis. Higher levels of the drug reach the brain, and there’s also a tendency for methamphetamine abusers to use the drug excessively in binges. In his book Methland, Nick Reding describes the way in which methamphetamine can devastate small towns already torn by a downtrodden economy. Reding spent several years in Oelwein, Iowa, a city of 6,126 inhabitants with a depressed local economy and a horrendous methamphetamine problem. In Oelwein, Lori Arnold (comedian Tom Arnold’s sister) runs a clandestine methamphetamine superlab, grew rich, went to jail, got out and started right back up where she left only to return to jail again.


Crystal methamphetamine (U.S. government at Erowid).

Roland Jarvis earned a certain fame in that his cautionary tale has been shared in Reding’s book and in a television documentary.

Jarvis, a former employee of Iowa Ham, used to make eighteen dollars an hour with full union benefits back in 1990. Jarvis often worked double shifts and socked money away toward his future marriage to his girlfriend. He soon found that working back-to-back shifts was easier while high on crank. Through the 1970s and 1980s, prescriptions for Methedrine were easy to come by with the help of a since retired general practitioner and phenyl-2-propane (P2P), a type of clandestine methamphetamine.

For 16 hours, Jarvis could stay focused at work without needing to sleep or eat. Many call methamphetamine America’s drug because of the fierce dedication to their work that marked America’s early settlers and continues to drive Americans today. Jarvis is often referred to as methamphetamine’s poster boy, his productivity at work unrivalled. When the drug was hard to get, Jarvis would even trade sex with men to get more meth.

In 1992, the Gilette Corporation bought out Iowa Ham and Jarvis found his wage reduced to $6.20 an hour. Figuring out his expenses, including the money spent on the meth required for him to put in long hours, Jarvis decided to start making and selling his own meth. In May 2005, 35-year-old Roland Jarvis blew up his mother’s house and himself. On fire, with his nose gone, Jarvis begged someone to kill him to relieve the pain. Today, gripping a meth pipe in his rotted teeth, Jarvis continues to use meth and freely talked to Reding about losing everything of any value he once had (Reding 2009, 54–57).

Consequences of Methamphetamine Abuse

Methamphetamine abuse leads to devastating medical, psychological and social consequences, including criminal behavior. Adverse health effects include malnutrition, severe dental problems, anemia, anorexia, cachexia (wasting syndrome), hypertension, pulmonary edema, cardiac irregularities, ischemic bowel disease, nasal septum defects, chronic obstructive lung disease, impotence, infertility, rhabdomyolysis (potentially fatal condition of muscle breakdown), sinus problems, and immune system dysfunction.

Mental problems related to methamphetamine abuse include psychosis, paranoia, schizophrenia, memory loss, aggression, and changes to brain chemistry. Intravenous methamphetamine abuse contributes to the spread of transmissible blood diseases, including human immunodeficiency virus (HIV) and viral hepatitis.

Brain Changes

With the advent of sophisticated imaging techniques, brain images can be used to show the changes caused by methamphetamine. Methamphetamine abusers have depleted stores of dopamine and have a significant loss of dopamine transporters. Sustained high-dose administration of amphetamines (especially methamphetamine) to animals in experiments produces a persistent depletion of dopamine transporters, which is associated with terminal degeneration as well as neuronal chromatolysis (destruction of cell DNA) in the brain stem, cortex and striatum. These changes, which are not seen with the use of cocaine, are associated with reduced motor speed and impaired verbal learning (Iversen 2008, 137).

In postmortem studies of the brains of 12 methamphetamine abusers who died within 24 hours of their last dose (death from overdoses in 8 subjects, two from heart attacks and two from gunshot wounds), large reductions of dopamine were seen in the basal ganglia and nucleus accumbens with no reductions of norepinephrine or serotonin. Dopamine transporter levels were also markedly reduced in the basal ganglia and nucleus accumbens. Levels of the enzyme tyrosine hydroxylase needed to produce dopamine was only decreased in the nucleus accumbens (Iversen 2008a, 137–8).

Areas of the brain associated with emotions and memory show severe structural and functional changes in recent studies of methamphetamine abusers. These changes may explain why chronic abusers tend to have many emotional and cognitive problems.

NEUROTOXICITY • Neurotoxicity refers to any adverse effect on the structure or function of the central or peripheral nervous system by a biological, chemical or physical agent. Neurotoxic effects may be permanent or reversible, produced by pharmacological or neurodegenerative properties of a toxic agent, or the result of direct or indirect actions on the nervous system (Melega 2001).

Neurons are the primary cells of the central nervous system. Neurotoxicity, particularly when it develops at an early age, may predispose amphetamine abusers to premature onset of movement disorders such as Parkinson’s disease and other involuntary movement disorders. Amphetamine and methamphetamine can also lead to the production of autoantibodies to SB100 brain protein and glutamate that may destroy brain cells and cause autoimmune neurospsychiatric disorders. Methamphetamine abuse increases the risk of stroke and cerebral bleeding, disorders that can irreversibly damage the brain (National Institute on Drug Abuse 2006).

Magnetic resonance spectroscopy studies show significantly reduced concentrations of the neuronal marker N-acetylaspartate in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter correlated inversely with the logarithm of the lifetime cumulative methamphetamine use. This finding provides evidence of long-term neuronal damage even in abstinent methamphetamine users (Ernst, Chang, Leonido-Yee, and Speck 2000). Animal studies show that methamphetamine exposure results in long-term decreases in striational dopamine uptake binding sites associated with the dopamine transporter, in dopamine concentrations, and of dopamine system-related proteins, tyrosine hydroxylase, and the vesicular monoamine transporter. In addition, after high doses of methamphetamine, and also MDMA, alterations in the diameter and density of neuronal fibers and evidence of nerve fiber degeneration have been seen (Melega 2001).

Methamphetamine abuse can also lead to longstanding drug dependence and its consequences. Methamphetamine dependence is considered to be a chronic, relapsing disease characterized by changes in the brain’s neural circuitry that cause a persistent craving for the abused drug (see also Chapter Eight). Currently there are no therapies available to treat methamphetamine dependence (Hanson 2008, 258).

RECOVERY • Imaging studies of the brain show that some of the effects of chronic methamphetamine abuse appear to be partially reversible. A restoration of dopamine transporters was seen in some areas of the brain after two years of methamphetamine abstinence. At shorter intervals, significant changes were not observed. However, function in other brain regions showed no signs of recovery even after two years of abstinence. This indicates that some methamphetamine-induced changes are very long lasting (NIDA 2006).


Methamphetamine Production

Most of the methamphetamine used in the United States comes from foreign or domestic superlabs, with the greatest part produced in Mexico. Clandestine laboratories scattered throughout the country also produce methamphetamine with inexpensive over-the-counter toxic ingredients. Restrictions by the drug enforcement agency (DEA) on selling ephedrine in the 1990s curbed methamphetamine production somewhat, but, with resistance from lobbyists, pseudoephedrine wasn’t regulated. The illicit drug manufacturers substituted pseudoephedrine for ephedrine in their recipes and ended up making an even more potent form of methamphetamine than the old P2P.

Because of the failed DEA legislation, by 1999 superlabs were producing up to a hundred pounds of crystal methamphetamine daily, a huge increase compared to the 10–25 pounds produced every other day in days past. This new product made methamphetamine both more available and more affordable, adding fuel to the fire of an already burgeoning epidemic. Changes in immigration laws helped to make Mexico the top supplier of methamphetamine in the United States.

Hells Angels

The Hells Angels organization is rooted in the World War II Hells Angels B-17 Bombers group, one of the toughest squadrons in the military. The name Hells Angels was adapted from the 1927 World War I fictional fighter squadron movie produced by Howard Hughes. As trained paratroopers, the Hells Angels were part of the U.S. Army’s 11th Airborne Division. The Hells Angels motorcycle gang’s organizational structure even mimics that of the U.S. Army. However, drug trafficking has traditionally been its primary source of illicit income.

In 2003 more than 7000 illicit methamphetamine laboratories were seized, mainly in the United States and mainly in California. The Hells Angels ran the majority of these laboratories and for many years they controlled the methamphetamine market by manufacturing the drug and intimidating rivals through violence. With the advent of superlabs and Mexican drug trafficking organizations, the Hells Angels are no longer the major illegal methamphetamine suppliers in the United States.

New Restrictions

Restrictions on the availability of precursor chemicals such as ephedrine have led to a sharp decline in methamphetamine lab seizures in recent years. In 2003 the main source countries of methamphetamine manufacture were Mexico, Myanmar, China, the Philippines and North Korea. Chemists can also bypass the use of ephedrine and pseudoephedrine and produce methamphetamine from toxic starter chemicals such as phenylacetone, methylamine, and formic acid. Most of the illicitly manufactured amphetamines are of poor quality with numerous chemical contaminants and as little as 10 percent purity. Illicit methamphetamine labs frequently suffer from poisoning or laboratory accidents and fires (Iversen 2008, 120).