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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Friday, May 18, 2012

Narcotics: A Modern Timeline


1800's: 

Morphine is first isolated from opium. (04)

1820's:

English writer Thomas DeQuincey portrays the use of opium and morphine preparations in a romantic fashion, in his memoir, "Diaries of an English Opium Eater". (21) This as well as similar writings of this era create a dramatic/sensationalized perception of narcotic use, which is, unfortunately, still prevalent in popular culture.

Morphine is marketed by Merck (pharmaceutical company). (27)

1830's:

Nearly 3 decades after the discovery of pure morphine, codeine is the second opiate alkaloid to be isolated from opium, by a French chemist in 1832.

1840's:

The hypodermic needle is invented. It revolutionizes medicine and changes the way drugs are administered. Opiate users discover that morphine can be made more effective, and its effects felt more rapidly, when the drug is injected into the bloodstream. A Doctor in Edinburgh was the first to administer morphine systemically. It was not known until the syringe was developed just how addictive morphine could be. (42)

1860's:

The American Civil War begins. IV morphine is given to wounded and dying soldiers on the battlefield. All military medics carry single use morphine syrettes in their medical bags. (61)

Following the Civil War, many soldiers return home with morphine habits. Many would carry around purse-like bags which contained morphine tablets.

1870's: 

Heroin is synthesized when morphine is heated on a stovetop with acetic anhydride (74)

The Chinese practice of opium smoking is banned in San Francisco (75)

1880's:

The molecular functional groups of morphine are identified (81)

1890's: 

Heroin is resynthesized by Felix Hoffman in Germany at what is now the Bayer company. (97)

Heroin is launched as a painkiller, cough suppressant, and as a cure for morphine addiction. It would later become apparent that heroin was just as addictive as morphine, and twice as potent. It was discovered that heroin was simply a prodrug for morphine. (98)

Tabloids owned by drug warrior William Randolph Hearst print stories of white women being lured into opium dens and seduced by Chinamen, contributing to the current national fear of 'Yellow Peril'. (1890)

1900's:

A religious organization in the US sends free heroin samples through the mail to morphine addicts, touting the drug as a cure for morphine dependence. (00)

Dihydromorphine is developed in Germany. (1900)

The addictive properties of heroin are documented in multiple medical journals. Some physicians question the merits of using heroin as a treatment for morphine addiction. (02)

Rates of heroin addiction in the US reach alarming levels. (03)

The Pure Food and Drug Act of 1906 is passed by congress, establishing the US Food & Drug Administration (FDA) and placing labeling regulations on the patent medicine industry. Patent medicines containing opiates or cocaine must now list their ingredients and their quantities. (06)

Dihydrocodeine is first developed in Germany. (08)

US Government bans the practice of smoking opium - this applies only to the smoking of opium, and does not affect medicinal opium preparations or patent medicines. (09)

By the end of the first decade of the 1900's, the addictive properties of heroin had become apparent. This becomes a concern.

1910's:

Dihydrocodeine is introduced as a cough suppressant and analgesic. (11)

Bayer removes heroin from the market. (13)

With the end of the heroin legacy, there becomes a high demand for alternatives to morphine for cough and pain.

Oxymorphone is first developed in Germany. (14)

The Harrison Narcotics Tax Act is enacted by US Congress to regulate the sale and prescription of opiates and cocaine. (14)

Oxycodone is first synthesized in Germany. (16)

US Supreme Court Rules that supplying narcotics to users simply to maintain them does not constitute legitimate medical practice. (19)

1920's:

Hydrocodone is first developed in Germany (20)

The Bureau of Narcotics becomes a branch of the US Treasury, devoted to enforcing narcotic laws. Nonmedical narcotic users begin buying from illegal street dealers. (23)

US Supreme Court Rules that the federal government has the power to regulate the prescribing practices of physicians. Doctors fall into place. (23)

Congress bans the manufacture, sale, importation (and medical use) of heroin in the US. (24)

Hydromorphone is first developed in Germany (24)

An illicit market for opium emerges in NYC's Chinatown. (25)

Heroin is banned internationally by the League of Nations. (25)

The molecular structure of morphine is correctly identified. (25)

Hydromorphone is introduced to the US market by Knoll Corporation, by the brand name Dilaudid, for oral and parenteral use. (26)

Analogues of heroin begin to appear on the illicit market, and are widely used as alternatives to heroin until 1930 when the compounds are banned by the League of Nations.

1930's: 

Meperidine is the first synthetic narcotic to be developed and is marketed by the brand name Demerol. It becomes a popular alternative to morphine for acute pain. (32)

The US Government opens the Federal Medical Center in Lexington Kentucky, originally under the name 'US Narcotic Farm' - it is a prison, farm, and treatment/research center and will become a site of major research into narcotics and narcotic addiction. (35)

Methadone is developed in Germany at the start of World War II, shortly after meperidine. Germans anticipate a shortage of opium and its derivatives. (37)

Oxycodone is introduced in the US as an analgesic (39)

World War II is under way by 1939.

1940's: 

Hydrocodone is introduced in the US as a cough suppressant and analgesic. (43)

World War II comes to an end. Allied forces collect German patents and many are handed over to the US.
Methadone is patented by an American company and introduced as a painkiller in the US by the brand name Dolophine. (47)

Levorphanol (i.e. Levo-Dromoran) is developed in Germany with a minor molecular addition to the recently synthesized morphine-backbone N-methylmorphinan.

1950's:

In the early 1950's, the efficacy of the newly introduced drug methadone in suppressing morphine and heroin withdrawal is noted. 

Percodan (oxycodone/aspirin) is introduced to the US market as a painkiller. (50)

Pentazocine is developed in the United States in 1958.

Oxymorphone is introduced to the US market under the brand name Numorphan, for oral and parenteral use. (59)

1960's: 

In the early 1960's, the US would escalate its involvement in the Vietnam conflict. America's role in Vietnam marked the first undeclared war involvement by the US Government, and for this reason would be widely condemned, abroad and at home, as the conflict continued senselessly over the next 15 years.

Fentanyl is discovered and introduced as an anaesthetic. (60)

The opioid antagonist naloxone is developed by Sankyo (early 60's), while another antagonist (naltrexone) is developed by Endo (63).

Pentazocine is FDA approved as a painkiller. (67)

A novel series of over 200 semi synthetic opiate compounds are synthesized from thebaine by Kenneth Bentley and his colleageus. Some of these drugs were found to be thousands of times more potent than morphine. The series, known presently as the orvinols or Bentley compounds, included etorphine and buprenorphine.

Richard Nixon - who will end up declaring the "war on drugs" - becomes the US President. (69)

1970's: 

By 1970, oxymorphone had become a popular drug on the street. Numorphan tablets were used illicitly and referred to as "blues", in reference to their light blue color. 

US involvement in Vietnam continues under President Nixon, while major protesting ensues. US troops in Vietnam have access to a large amount of opium, morphine, and heroin. Addiction among the troops is known to be prevalent in the early 70's. Meanwhile, back in the States, heroin and the opioids are considered public enemy number one.

The Controlled Substances Act of 1970 abolishes the "taxing" disguise of earlier drug laws and becomes the first federal criminal drug law. It creates the enforcement branch which is eventually to become known as the DEA and places prescription and recreational drugs into a regulatory system of 5 classifications, and designates penalties for violations involving each drug class. (70)

The "methadone clinic" is born, in New York City, after a highly publicized study. Methadone is used clinically as a long term substitute for heroin and morphine in addicted individuals. Methadone Maintenance Treatment (MMT) is born. (Early 70's Nixon Era)

While the Nixon Administration pursues its plans to destroy the poppy crops of other countries around the world, US Government bio-engineers develop an alternative poppy which produces thebaine only, for pharmaceutical manufacturing purposes. Its botanical name is the papaver braceatum. At a time in which opiate based cough medicines are becoming scarce, it is hoped this poppy will replace the traditional opium poppy in meeting the needs of coughing Americans. (early 70's Nixon Era)

Levorphanol is used in the research which first discovers the presence of opioid binding sites in the human nervous system. Soon after, it is discovered that there are various subtypes of opioid receptor. (early 70's)

Buprenorphine is first administered in humans. Three chemists involved in its development (Lewis, Cowan, Crocker) are given IV doses of 50, 100, and 200 micrograms. (71)

Percocet (oxycodone/APAP) is introduced in the US by Endo. (71)

Endo Pharmaceuticals removes the original Numorphan oral preparation from the market due to widespread illicit use. (72)

The Bureau of Narcotics & Dangerous Drugs becomes the Drug Enforcement Administration (DEA). The office of diversion control becomes a DEA branch focusing on prescription drugs. (73)

Sufentanil is developed by Janssen and colleagues. (74)

Buprenorphine is sent to the Federal Medical Center at Lexington for testing in the human prisoner population. (74)

American troops return home from Vietnam. During an era of heavy heroin use in the US, not to mention widespread narcotic use among US troops in Vietnam, soldiers are forced to pass drug tests or complete detox treatment before boarding their flight back to the States, out of government fear that the troops may "infect" the American public with what was at the time considered a "plague of the walking dead". (75)

At the Federal Medical Center in Lexington, concerns over the ethics of testing new drugs in prisoners are delaying the testing of buprenorphine. The research team allays these concerns by suggesting that buprenorphine could be of use in the treatment of narcotic addiction; an indication which could be of particular benefit for the prisoner population at Lexington, most of whom are former opiate addicts. In 1975, the investigation into buprenorphine as a treatment for addiction begins.

In 1978, buprenorphine is first introduced in the UK as a painkiller. Meanwhile, at about the same time, butorphanol and nalbuphine are introduced in the United States. (78)

Tramadol is first launched as an analgesic (late 70's)

1980's: 

Buprenorphine is introduced by the British firm Reckitt & Colman (now Reckitt Benckiser) in the United States as a painkiller, under the brand name Buprenex. (84)

Naltrexone is approved by the FDA as a treatment for opioid addiction. (84)

MS Contin is the first modified release narcotic formulation for oral use to be introduced in the US. The novel extended release matrix (i.e. "Contin") used for MS Contin had been designed in 1972. (84-87)

MS Contin marks the start of the modern "chronic pain management" movement; physicians begin to more casually prescribe long term opioid therapies for chronic noncancer pain. (late 80's)

The American Society of Addiction Medicine (ASAM) officially joins the ranks of the American Medical Association (AMA). (88)

1990's: 

"Addiction Medicine" is officially designated by the AMA as a medical sub-specialty. (90)

Levacetylmethadol (LAAM) is introduced in the US by the brand name ORLAAM, indicated solely as an alternative to methadone for maintenance treatment of narcotic addiction. (94)

By the mid 90's, the use of strong opioids to treat chronic noncancer pain had become standard practice. Opioids become more available and accessible to patients and casual or habitual drug users.

A long acting transdermal fentanyl patch is introduced for treating chronic pain, by the brand name Duragesic. (mid 90's)

A long acting oxycodone tablet is introduced by the brand name OxyContin, for treatment of chronic pain. It marketed by Purdue Pharma, and is based on their novel modified release system originally applied to MS Contin. (96)

2000's:

By the year 2000, the public has begun taking notice of the prevalence of illicit prescription narcotic use and addiction.

Management of pain with opioids becomes its own subspecialty in some areas, with walk in 'Pain Clinics' in Florida, many of which dispense opioids on site. Massive demand, coupled with restricted supply incentivize unscrupulous Doctors to grab their piece of the market. The "pain management" industry has evolved to resemble the medical marijuana industry in some respects. The media sensationalizes the crisis. Federal Drug Enforcement expands to target the medical profession as opposed to only street dealers, launching a domestic paramilitary assault on doctors and patients, and leading a new phase in the war on drugs that is even more repressive and over-reaching than before (2000 to present day)

The internet is increasingly convenient sales front for the illicit prescription drug trade; web based businesses offer RX narcotics and controlled substances without prescriptions required, though many are actually scams. The DEA launches assaults on internet drug suppliers. (early 2000's)

A modified release form of hydromorphone is introduced in the US by Purdue Pharma, under the brand name Palladone. (early 2000's)

OxyContin has become a popular drug of misuse. A series of local news pieces out of rural appaliacia catalyze a media cycle of sensational stories about the drug. OxyContin is dubbed by the press as "Hillbilly Heroin" - the name has stuck ever since. (early 2000's)

The Drug Addiction Treatment Act is passed, allowing regular family doctors to treat narcotic addiction from their offices using specially approved opioids - the rule applies only to drugs with a schedule III through schedule V DEA control classification. The DATA reverses the 1919 Supreme Court ruling which prohibited doctors from prescribing narcotics to treat addiction. (2000)

ORLAAM is removed from the market due to reports of serious cardiovascular side effects. (01)

Portugal decriminalizes all personal drug use. (01)

High dose sublingual buprenorphine preparations are approved for use in the treatment of opioid dependence (under the drug addiction treatment act of 2000), by the brand names Subutex and Suboxone, the latter of which contains both buprenorphine and the opioid antagonist naloxone to deter intravenous use of the tablet. (02)

OxyContin acquires a black box warning label (02)

The UK plans to offer legal heroin to addicts through the National Health Service. (02)

Nora Volkow becomes head of the National Institute on Drug Abuse (NIDA). (03)

The DEA unexpectedly withdraws their list of guidelines for pain specialists, which had previously served to reassure physicians that they would not be prosecuted if they followed certain practices. The legal line between legitimate medical practice and drug trafficking is no longer clear, allowing the DEA to arbitrarily prosecute any prescribing physician they see fit. (04)

FDA approves the use of Palladone, a long acting hydromorphone product made by Purdue Pharma, in the US for chronic pain. (04)

FDA threatens a ban on Palladone (a recently introduced long acting hydromorphone product) due to inadvertent overdoses when mixed with alcohol. It is concluded that due to the widespread casual use of alcohol, there is a significant danger of unintentional overdose, and this danger can not be effectively addressed through warning labels alone. Shortly after its release, Palladone is removed from the US market voluntarily. (05)

A modified release (12 hour) form of oxymorphone is introduced in the US under the brand name Opana ER. A new immediate release form similar to the traditional Numorphan product is introduced under the name Opana. Both products are marketed by Endo pharmaceuticals. (mid 2000's)

Mexican government passes a bill which would legalize the personal use of all drugs - Mexican president vows to sign it, but buckles under pressure from the drug warriors of the US government, who continue to impose their will on the rest of the world. (06)

Executives of Purdue Pharma are convicted in criminal court of felony misbranding, due to their role in the aggressive promotion of OxyContin (07)

Generic alternatives to Subutex become available (09)

Tapentadol is introduced in the US by the brand name Nucynta, indicated for acute pain. (09)

A few years after the removal of Palladone from the US market, a new formulation of hydromorphone is introduced by the brand name Exalgo. The tablet lasts 24 hours and is intended for chronic pain. (09)

2010's:

Purdue Pharma releases a new formulation of OxyContin which is less effective but more difficult to break down for injection (10)

By 2010, with the help of media outlets, prescription drug addiction is perceived as public enemy number one. 

A modified release transdermal buprenorphine product is released for chronic pain under the trade name BuTrans - a seven day patch which is worn on the skin surface. It is the first modified release buprenorphine product available in the US, and is developed and marketed by Purdue Pharma. (11)

A series of media articles are published revealing the ties between pain management advocacy groups and the manufacturers of big name narcotic drugs (OxyContin, etc). (12)

The American Pain Foundation - a major pain advocacy organization - dissolves, following a period of financial struggles and negative press. (12)

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