Understanding the Effects of Substituted Amphetamines

Substituted amphetamines are a group of chemically related substances that possess a strong chemical resemblance to the manmade stimulant drug amphetamine. Some of these substances-including ephedrine, pseudoephedrine, and cathinone-come from plant sources and predate synthetic amphetamine by thousands of years or more. Others-including methamphetamine and MDMA (Ecstasy)-are synthetic and have only existed for anywhere from decades up to slightly more than a century. Almost all substituted amphetamines produce pleasure and stimulant effects in the central nervous system; to varying degrees, they may also produce hallucinations and increased feelings of connectedness toward others. Side effects common to most of these substances include potentially deadly toxic reactions (overdoses) and long-term risks for drug addiction.

The Basics

The naturally occurring substituted amphetamines ephedrine and pseudoephedrine come from the plant species Ephedra sinica, as well as from several other related species in the Ephedra genus. Naturally occurring cathinone comes from Catha edulis, a plant known commonly as khat, which grows in the regions of eastern Africa and the Arabian Peninsula that border on the Red Sea. In traditional Chinese medicine, Ephedra sinica is known as ma huang; therapeutic uses of the plant-which stem from its ephedrine and pseudoephedrine content-include narrowing of the blood vessels (vasoconstriction) and widening of the airways inside the lungs (bronchodilation). Traditional uses of cathinone-rich khat include mental stimulation, appetite suppression and easing of social interactions.

Technically speaking, chemists consider manmade amphetamine itself a form of substituted amphetamine. This means that, apart from its main amphetamine core, each molecule of the drug contains other, secondary chemical structures that alter its shape and bodily effects. In addition to methamphetamine and MDMA, other relatively common manmade substituted amphetamines include synthetic ephedrine, synthetic pseudoephedrine, a methamphetamine-cathinone combination called methcathinone, a close relative of MDMA called MDA, and MDMA substitutes know by the chemical abbreviations PMA and PMMA. Some of these substances-including methamphetamine, MDMA and MDA-can be made from naturally occurring amphetamines or other ingredients found in different plant materials. Others come entirely from the manipulation of manmade chemicals in a laboratory setting.

Basic Drug Effects

As a group, substituted amphetamines achieve their primary stimulating effects by blocking the normal recycling of two essential substances in the central nervous system called dopamine and norepinephrine. Among its many roles in the body, dopamine carries the chemical signals that activate the brain’s pleasure centers. Norepinephrine’s main role is activation of the involuntary nerves that control the body’s natural physical reactions to danger and stress. By blocking dopamine and norepinephrine recycling, substituted amphetamines cause those chemicals to build up in brain tissue; in turn, this accumulation triggers dopamine-related euphoria and a host of norepinephrine-related changes that include increased alertness, reduced hunger, accelerated heart and breathing rates, heightened blood pressure and increased blood flow to the body’s major muscles.

Substituted amphetamines with strong hallucinogenic properties include MDMA, MDA, PMA and PMMA. These substances produce their hallucinogenic effects by artificially mimicking the actions of serotonin, a natural chemical in the body that plays a role in the normal processing of the perceptual information that comes in through the five senses. MDMA, MDA and several lesser-known types of substituted amphetamine also act as empathogens (also known as entactogens). Chemicals with this property produce an increased sensitivity to touch, as well as feelings of expansiveness and good will toward others. The stimulant, hallucinogenic, and empathogenic properties of the various substituted amphetamines can interact in a wide variety of ways. As a rule, the specific effects of any given drug in the class depend on its particular mixture of these properties. For example, methamphetamine produces a particularly intense form of euphoria by simultaneously blocking dopamine recycling and increasing new dopamine production.

Overdose

Overdose related to the use of substituted amphetamines occurs when the effects of these substances overwhelm normal function in the central nervous system, as well as normal function in a related network of involuntary nerves called the sympathetic nervous system, which extends throughout the body. Potential psychological effects of overdose include extreme anxiety and a mental state called psychosis, which produces strong hallucinations and irrational, delusional thinking. Potential physical effects include a dangerous increase in body temperature, extreme blood pressure elevations, an accelerated heartbeat and an irregular heartbeat. At their worst, these physical effects can produce fatal outcomes.

Addiction

Certain substituted amphetamines-including amphetamine and methamphetamine-eventually produce reductions in the brain’s dopamine production when used for extended periods of time. These dopamine reductions start the cycle of addiction by encouraging an offsetting increase in drug use; the end result of this process is addiction, which occurs when a physical reliance on a given drug produces prominent drug cravings and leads the user to focus his or her lifestyle on continuing cycles of drug acquisition and use. Some substituted amphetamines-including MDMA and MDA-produce inconsistent results when assessed for their potential to trigger addiction. A few relatively unknown drugs in the class are primarily hallucinogenic and produce little or no long-term risks for addiction.