Amphetamine and methamphetamine-type substances belong to a broader class of compounds known as phenethylamines. These synthetic stimulants are widely known for their psychoactive effects, and they play a dual role in society — as valuable medications and as substances of abuse. Understanding their chemistry, pharmacology, medical applications, and abuse potential is essential in the context of public health, clinical practice, and law enforcement.

1. What Are Phenethylamines?

Phenethylamines are a class of organic compounds that include many naturally occurring and synthetic substances. They are structurally based on the phenethylamine molecule, which consists of a phenyl ring and an ethylamine chain.

Major Subclasses Include:

• Amphetamines (e.g., amphetamine, methamphetamine, dextroamphetamine)

• Substituted Amphetamines (e.g., MDMA, MDA, DOM)

• Cathinones (e.g., mephedrone, methylone)

• Other designer drugs (often referred to as “bath salts” or “research chemicals”)

2. Chemistry and Structure

Amphetamine (C9H13N):

• Molecular structure: A phenyl group attached to a carbon chain with a terminal amine.

• Chiral center: Exists as two enantiomers — dextroamphetamine (d-amphetamine) and levoamphetamine (l-amphetamine). The d-form is more potent in terms of central nervous system (CNS) stimulation.

Methamphetamine (C10H15N):

• Similar to amphetamine but with a methyl group attached to the nitrogen atom.

• This modification increases lipid solubility, enabling it to cross the blood-brain barrier more efficiently, making it more potent.

3. Mechanism of Action

Amphetamine-type stimulants primarily exert their effects by increasing the concentration of monoamines — dopamine, norepinephrine, and serotonin — in the synaptic cleft.

Key Mechanisms:

• Inhibition of monoamine reuptake transporters (DAT, NET, SERT)

• Reversal of transporter flow, pushing neurotransmitters out of the neuron

• Inhibition of monoamine oxidase (MAO), reducing breakdown

• Displacement of neurotransmitters from synaptic vesicles

This results in increased neurotransmission, leading to the stimulant effects associated with these substances.

4. Medical Uses

Amphetamines:

• ADHD (Attention Deficit Hyperactivity Disorder) – e.g., Adderall (mixed amphetamine salts)

• Narcolepsy – helps reduce excessive daytime sleepiness

• Obesity – in rare cases, as appetite suppressants

Methamphetamine:

• Marketed under the brand name Desoxyn (rare use)

• Prescribed in very limited scenarios for ADHD and obesity

Despite legitimate medical applications, methamphetamine is rarely used clinically due to its high abuse potential.

5. Effects and Risks

Short-Term Effects:

• Increased alertness, focus, energy

• Euphoria, enhanced confidence

• Suppressed appetite

• Increased heart rate, blood pressure

Long-Term Effects:

• Neurotoxicity (especially with methamphetamine)

• Addiction and dependence

• Cognitive deficits

• Psychiatric symptoms (e.g., anxiety, paranoia, hallucinations)

• Physical deterioration – “meth mouth,” skin sores, weight loss

6. Recreational Use and Abuse

Amphetamine-type stimulants are commonly abused for their euphoric and performance-enhancing effects. Methamphetamine, in particular, is associated with high rates of dependency and addiction due to its intense and long-lasting high.

Forms of Use:

• Oral ingestion (tablets, capsules)

• Nasal insufflation (snorting)

• Smoking (crystal meth)

• Intravenous injection

Street Names:

• Amphetamine: Speed, uppers, pep pills

• Methamphetamine: Crystal, meth, ice, crank

7. Global and Legal Context

Amphetamines are classified under different schedules depending on the country, reflecting their medical use and potential for abuse.

Examples:

• United States: Schedule II (under the Controlled Substances Act)

• United Nations (INCB): Controlled under Schedule II of the Convention on Psychotropic Substances (1971)

The UNODC and WHO monitor and report on global trends in production, trafficking, and abuse, particularly in Southeast Asia and North America, where methamphetamine abuse is high.

8. Emerging Trends: Designer Phenethylamines

In recent years, novel psychoactive substances (NPS) have emerged — synthetic derivatives of phenethylamines designed to mimic the effects of amphetamines while evading legal control.

Examples:

• 2C family (e.g., 2C-B, 2C-E)

• NBOMe series (e.g., 25I-NBOMe)

• Substituted cathinones (e.g., alpha-PVP, known as “flakka”)

These pose significant risks due to unknown potency, toxicity, and limited research.

Amphetamine and methamphetamine-type phenethylamines occupy a complex space in modern society — simultaneously serving as essential medications and dangerous drugs of abuse. As synthetic chemistry advances and the drug landscape evolves, continued research, harm reduction strategies, and international cooperation are vital to address both the medical benefits and public health challenges associated with these potent substances.