Pink is everywhere from your surroundings to your inside, life is just Pink. And now we know that deep under the layers of legal world lies in stealth from surveillance a drug called “The Pink Drug U47700”.

Apparently, it seems as if the color pink is getting its fair share of presence. If you even look at the media, we have “Pink Panther”- the clown- “Pink”-the singer-“Pink”-the song-“A Study in Pink”- the famous Sherlock story.

The synthetic drugs including opioid U4770 also known as the “Pink Drug” has been used for recreational purposes all around the world, usually as part of a cocktail of various drugs. Its acronym is pink heroine.

There is no official record of when the Pink Drug was first used recreationally. The first reported death, due to this drug in January 2016 was of a 27 year old man who was found dead at his home. Toxicological and forensic analysis of the drug powder found on his body and of his urine and blood samples revealed a mixture of known drugs (quetiapine, amphetamine, amitriptyline, mexedrone and ketamine).

However another, less easily identified, substance was also detected.  More detailed tests revealed the compound to be similar to AH-7921, another opioid that has been placed in schedule 1 of the Controlled Substances Act. Farther comparison of the unknown substance, with reference samples of the less common drug U4770, found the two to be identical.

Pink Drug

So it was that the drug U4770 increasingly began to become a part of the drug scene this year. Both AH-7921 and U4770 are on the NPS or New Psychoactive Substances list. This list is constantly being updated as information becomes available from around the world. The United Nations Office on Drug and Crime (UNODC) regularly publishes reports about these substances, global trends on their availability/production and recommendations for their control.

U4770 has come to attention recently because it has been implicated in the deaths of a number of people including celebrities such as Prince and most recently two 13 year old teenagers from Utah. According to the WHO critical report, 15 deaths due to U47700 have been reported in the US. NMS labs a private forensic and medicolegal laboratory reports 50 deaths

The Opioid Dependence Epidemic And It’s Consequences

The word opioid comes from Opium an extremely addictive substance extracted from the poppy plant.  Drugs such as heroin and other opioids derived from it have analgesic effects that make them desirable for use as pain killers.

However, this analgesic effect is accompanied by a host of other less desirable effects including sedation, anxiolysis, respiratory depression as well as its addictive potential. The challenge has always been to discover those opioids that can be safely used in a therapeutic setting for their analgesic effects while minimizing their potential to cause harm. The use of Laudanum in the 16th century gave way to Morphine, then Heroin, Methadone, fentanyl and a host of synthetic opioids.

Lethal and increasingly abused as the synthetic opioid U47700 is, it did not appear in a vacuum. There is a longstanding history of abuse of opioids worldwide as well as in the United States, reaching epidemic proportions. Out of 47,055 deaths due to accidental drug overdose in 2014, 18,893 were due to opioids.

This has occurred as a direct consequence of inappropriate opioid prescribing practices for the management of chronic pain. Doctors would prescribe narcotic medications for patients suffering from pain due to cancer and other chronic/terminal conditions.

However, patients would develop tolerance to the drugs requiring ever increasing doses to achieve the same level of analgesia. This would lead to some patients seeking other non-prescription opioids to relieve pain when their prescriptions stopped working. In addition some vulnerable patients were targeted by acquaintances that used them to obtain prescription opioids inappropriately.

Guidelines for the prescription of narcotic medications were published in 2009. These recommended strict policies for the selection and monitoring of patients receiving narcotics. Patients that showed increasing tolerance or inappropriate handling of their prescriptions would receive alternative medications in addition to opioids or would have opioids discontinued.

However, in spite of these guidelines the number of people addicted to opioids continued to increase. The American Society of Addiction Medicine noted four times as many prescription analgesic sales occurred in 2010 as in 1999.

Pink Drug u47700

According to a 2014 Senate Caucus presentation by Dr. Nora D. Volkow, on International Narcotics control, 467000 Americans were estimated to be addicted to Heroin in 2012.  A total of 2.1 million were suffering from substance abuse disorders secondary to the use of opioid analgesics prescribed by doctors in the United States. Up to 36 million people were estimated to abuse opioid related drugs all over the world.

Opioid addiction has wreaked havoc all over the world and the reasons behind this raging epidemic have been

  1. The increasing numbers of prescriptions for such drugs
  2. The fact that the use of opioids and narcotics, for different purposes, is increasingly becoming more socially acceptable.
  3. Pharmaceutical companies have a vested interest in ensuring their products are aggressively marketed and achieve targeted sales and profits.
  4. The drug seeking behavior of patients suffering from chronic pain and dependent on various opioids.
  5. The booming opium trade in war torn Afghanistan where regulatory measures are difficult or impossible to achieve.
  6. The ability of myriad unregulated laboratories in countries such as China to experiment on and synthesize new opioid derivatives that are then sold online without any need for describing the drug characteristics, potencies and fitness for human consumption.

Where Did Pink Drug (U47700) Come From And Why Is It A Problem Now?

In the late 1970s, two scientists Philip F. Vonvoigltander and Jacob Szmuszkovicz (employees of the pharmaceutical company Upjohn) were working on the development of drugs for use as anticonvulsants. Their aim was to develop benzamide compounds that had little analgesic effects and more potent antiseizure activity in laboratory animals and later on in humans.

They applied for and were granted a patent for these compounds, one of which was trans-3, 4-dichloro-N-(2-(dimethyl amino) cyclohexyl)-N-methylbenzamide or U47700. This patent was filed in 1987 and published in January 1989.

It described the concerned drugs as having phenytoin like anticonvulsant properties but very little or no analgesic effects. It described in detail the procedure by which these compounds were synthesized. The patent expired on April 15th 1997 due to failure to pay maintenance fees.

Various companies have since been involved in the manufacture and sale of the drug U47700. One such company Cayman chemicals, describes U47700 as analytical reference material and specifies that it is only meant for sale in bulk to qualified institutions for research purposes. However there are other websites that sell the drug to whoever wants to buy it.

 In March 2015, China banned the export of 116 synthetic opioids. These opioids contained fentanyl and other related compounds. As reported by the Drug Enforcement Agency (DEA), by December 2015 at least one Chinese manufacturer had offered to bypass this ban by supplying new altered versions of the opioid fentanyl to American consumers. In the same intelligence report the DEA describes how 500 tablets of what appeared to be Oxycodone were appropriated in March 2016 Ohio. However, they were contaminated with the drug U47700.

China continues to be a major source of fentanyl and related opioids. The very same companies that legally produce synthetic opioids for research purposes can also act as sources of the drugs for illegal purposes, as reported by the DEA.

Regulatory Measures To Control Or Ban The Sale Of Pink Drug U47700 In USA

A notice of intent to place the drug U47700 in schedule 1 of the Controlled Substance Act, has been issued by the Drug Enforcement Administration of the US Department of Justice, in September 2016. The Controlled Substance Act is meant to regulate the manufacture, distribution, use, possession and storage of drugs that may be abused. It became a part of US law in 1970 when President Richard Nixon approved it.

Drugs that are classified as schedule 1 under the Controlled Substances Act are considered to be at high risk for abuse and do not have any acceptable medical indication.

However no final order has yet been filed based on this notice of intent. As such the drug is still freely available for use online.

Regulations On Availability Of U47700 In Other Countries

In the UK, the Psycho-active substances act of 2016, has been implemented to regulate the availability of U47700 and similar drugs.

In Belgium it is as yet unregulated according to a June 2016 fact sheet issued by the Belgian Early warning Drug System.

In Finland, a government decree was passed in September 2015, to control the availability of 65 psychoactive drugs, including U47700.

In Sweden U4770 along with all other narcotics is controlled by various laws.

China has a Narcotics Control Law in place since 2008. This controls the availability of narcotics such as u47700 and fentanyl related opioids in China but fails to control the export of drugs to countries where they have not yet been banned.

What Is Pink Drug? Understand How Pink Drug Effetcts On Body  Differently Than Heroine

To understand the pink drug, one has to understand the proximity between pink drug and opioids. The mechanism of action of pink drug is much potent to heroin, and the reason behind is the inherent difference and similarity, it carries among other opioids and morphine.

Chemical Name And Structure Of Morphine, Heroin And Pink Drug

The opioids are alkaloids derived from Opium. Morphine, a narcotic analgesic, is one of these natural alkaloids:

Its chemical name is (5 alpha, 6 alpha)-17-Methyl-7,8-didehydro-4,5-epoxymorphinan-3,6-diol

Heroin one of these alkaloids, also known as diamorphine is basically formed by the acetylation of the above molecule. So Heroine is (5 alpha, 6 alpha)-17-Methyl-7, 8-didehydro-4, 5-epoxymorphinan-3, 6-diol acetate. It is 2 to 3 times more potent than morphine.

Pink drug U47700 has the chemical name trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide). It is an atypical opioid from the benzamide group of compounds. It has been described as being 7.5 times more potent than morphine. Other sources have claimed that is actually 2.5 times more potent.

It must be remembered that as U47700 was never meant for human consumption, detailed studies on its potency in humans have not been carried out and these are subjective estimates given by users.

Receptors Responsible For The Physical Effects Of Morphine, Heroin And Pink Drug:

Morphine and other opioids have an effect on the human body because their receptors are already present in the central nervous system. These receptors are meant for endogenous opioids (such as enkephalins and endorphins) that are released from neurons in response to pain. Four main types of receptors have been identified.

mReceptor

kReceptor

dReceptor

Opioid receptor like-1(ORL-1)

These are all large 7 subunit, trans-membrane G protein linked receptors. They are inhibitory in nature and through the G-protein mediated activation of cAMP they alter the function of calcium ion channels. They have been shown to reduce intracellular calcium ion concentrations.

dReceptors in particular also inhibit the movement of sodium ions into the cell and potassium ions out of the cell under hypoxic/ischemic conditions and are therefore thought to protect neurons from hypoxic insults.

The opioid receptor coupled alteration in function of various ion channels as well as transcription of different cellular proteins is thought to be responsible for their inhibitory effect on pain fibers and the consequent analgesic effects.

These receptors have a wide variety of effects in addition to analgesia. This is because they are found in the gastrointestinal tract, heart, liver and lungs in addition to the central nervous system.

m (Mu) receptors have analgesic effects when stimulated but also cause euphoria through the release of dopamine. This is why they have been described as a “gateway to drug addiction”.

k (kappa) receptors have been shown to induce dysphoria and depression in mice, in addition to analgesia.

dReceptors are thought to be expressed in greater amounts in response to inflammatory conditions and may be more effective in reducing sharp pain associated with injuries. They are also linked to anxiolytic and antidepressant effects, thought to be mediated through their effect on dopamine, serotonin and adrenergic systems.

They also affect the cardiovascular, respiratory and gastrointestinal systems in various ways, the most well-known effects being respiratory depression, constipation and cough inhibition.

Effects Of Various Opioid Agonists On Opioid Receptors:

Morphine is primarily a m receptor agonist which is why it has potent analgesic effects as well as euphoric and addictive effects. Tolerance develops rapidly to morphine requiring ever increasing doses of the drug to achieve the same level of analgesia. This development of tolerance was thought to be due to the down regulation of m receptors in response to their stimulation.

However, it has been discovered that the actual mechanism of tolerance is more complex than that and involves the alteration in transcription of various cellular proteins in response to receptor stimulation.

Heroin is also a m receptor agonist and is more potent than Morphine causing greater analgesia and euphoria at lower doses and also greater respiratory depression.

Other opioids such as Fentanyl and Methadone are µ receptor agonists too.

Physical Effects Of Pink Drug

According to a WHO critical report, it has potent effects on the m opioid receptor, binds less strongly to the k receptor and has minimal effects on the d receptor. It has 7.5 times more potent pain killer effects than morphine, according to results from testing on mice. It causes respiratory depression, cyanosis, meiosis and reduced consciousness. Naloxone has been shown to reverse the negative opioid like effects of this drug.

It has been described as causing intense euphoria and less of the negative effects of depression and dysphoria (thought to be mediated by ĸ receptors). It is also thought to be less highly addictive and tolerance inducing than Heroin.

However, it has a number of very unpleasant side effects such as irritation of mucosal membranes at sites of administration (nasal and rectal mucosa) as well as bleeding from these sites. It may also be responsible for respiratory depression leading to death either alone or in combination with the other opioids that it is often mixed with for recreational purposes. Again the specific effects of U47700, on its own, in human beings have not been studied as it was never intended for human consumption.

As long as the opium trade flourishes in Afghanistan and similar war torn regions of the world, where drug enforcement measures are difficult or impossible to implement, opioid dependence will continue to plague the human race.

As long as pharmaceutical companies continue to aggressively market narcotics and doctors continue prescribing/providing opioids, people will continue developing tolerance and dependence to the drugs. As a result the demand for synthetic opioids will increase.

Any long term measures designed to control the manufacture of synthetic opioids such as Pink drug, U477O0 must take into account all these factors.