When the term was coined in the 1980s, a wide range of narcotics were being sold as heroin on the black market. Many were based on fentanyl or meperidine. One, MPPP, was found in some cases to contain an impurity called MPTP, which caused brain damage that could result in a syndrome identical to full-blown Parkinson's disease, from only a single dose. Other problems were highly potent fentanyl analogues, which were sold as China White, that caused many accidental overdoses. Because the government was powerless to prosecute people for these drugs until after they had been marketed successfully, laws were passed to give the DEA power to emergency schedule chemicals for a year, with an optional 6-month extension, while gathering evidence to justify permanent scheduling, as well as the analogue laws mentioned previously.
Emergency-scheduling power was used for the first time for MDMA. In this case, the DEA scheduled MDMA as a Schedule I drug and retained this classification after review, even though their own judge ruled that MDMA should be classified Schedule III on the basis of its demonstrated uses in medicine. The emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, and BZP. In 2004, a piperazine drug, TFMPP, became the first drug that had been emergency-scheduled to be denied permanent scheduling and revert to legal status.
In the late 1990s and early 2000s, there was a huge explosion in designer drugs being sold over the internet. The term and concept of "research chemicals" was coined by some marketers of designer drugs (particularly of psychedelic drugs in the tryptamine and phenethylamine family). The idea was that by selling the chemicals as for research rather than human consumption, the intent clause of the U.S. analogue drug laws would be avoided. This was later shown to be faulty logic when the DEA raided multiple suppliers, first JLF Primary Materials, and then multiple vendors several years later in Operation Web Tryp. This process was accelerated greatly when vendors began advertising via search engines like Google by linking their sites to searches on key words such as chemical names and terms like psychedelic or hallucinogen. Widespread discussion of consumptive use and the sources for the chemicals in public forums also drew the attention of the media and authorities.
Many substances that were sold as "research chemicals" in this period of time are hallucinogens and bear a chemical resemblance to well-known drugs, such as psilocybin and mescaline. As with other hallucinogens, these substances are often taken for the purposes of facilitating spiritual processes (see entheogen), mental reflection (see psychedelic) or recreation. Some research chemicals on the market were not psychoactive, but can be used as Precursors in the synthesis of other potentially psychoactive substances, for example, 2C-H which could be used to make 2C-B and 2C-I among others. Extensive surveys of structural variations have been conducted by pharmaceutical corporations, universities and independent researchers over the last century, from which some of the presently available research chemicals derive. One particularly notable researcher is Dr. Alexander Shulgin, who presented syntheses and pharmacological explorations of hundreds of substances in the books TiHKAL and PiHKAL (co-authored with Ann Shulgin), and has served as an expert witness for the defense in several court cases against manufacturers of psychoactive drugs.
Most chemical suppliers sold research chemicals in bulk form as powder, not as pills, as selling in pill form would invalidate the claims that they were being sold for non-consumptive research. Active dosages vary widely from substance to substance, ranging from sub-microgram levels to hundreds of milligrams, but while it is critical for the end user to weigh doses with a precision scale, instead of guessing ("eyeballing"), many users did not do this and this led to many emergency room visits and several deaths, which were a prominent factor leading to the emergency scheduling of several substances and eventually Operation Web Tryp. When a chemical increases in popularity, it will often be sold in pill form to reach a wider market. Some of the most popular chemicals are also given street names (like "Foxy" or "Foxy Methoxy" for 5-Meo-DiPT). Once a chemical reaches this kind of popularity, it is usually just a matter of time before it is added to the list of scheduled (i.e. illegal) drugs.
While most designer drugs to date have been either opioids, hallucinogens or anabolic steroids, the range of possible compounds is limited only by the scientific literature, and recently designer drug stimulants such as MDPV and desoxypipradrol, and designer sedatives such as methylmethaqualone have also appeared on the market. Most recently of all, designer analogues of sildenafil (Viagra) have been reported as active compounds in supposedly "herbal" aphrodisiac products.
In 2004, the US Drug Enforcement Administration raided and shut down several internet based research chemical vendors in an operation called Web Tryp. With help from the authorities in India and China, two chemical manufacturers were also closed. Many other internet based vendors promptly stopped doing business, even though their products are still not scheduled.