Opioids: What To Know

Written by Plinio Ferreira

Overview of Opioids

Q1: What are opioids? How are they produced?

Great question! Opioids are a class of drugs used to control pain therefore, analgesics. They act on the opioid receptors and have both brain and bodily effects.

Opioids can be natural, semi-synthetic and synthetic.

Natural opioids (known scientifically as opiates) are derived directly from the resin of the opium poppy plant. The three primary opiates are morphine, codeine, and thebaine.

Once natural opioids are extracted, they are taken to the lab and chemically-altered into what are known as semi-synthetic opioids. In addition to heroin, common synthetic opioids include oxycodone, hydrocodone, and hydromorphone.

Synthetic opioids are synthesised entirely in a lab, and designed to act on the same targets in the brain as natural opioids. Common synthetic opioids include nitazenes and fentanyls.

Opioids can be used by smoking, snorting or injecting. Injecting carries a higher risk of overdose than other routes of administration and increases the risk of blood-borne infections such as HIV and hepatitis B and C.

Q2: Why does opioid treatment require careful supervision by a health professional?

Tolerance and physical dependence can develop after regular use of opioids. When dependence is established, stopping opioid use abruptly can cause extremely unpleasant withdrawal symptoms, such as nausea, sweating, chills, difficulty sleeping, muscle and bone aches, diarrhoea, and irritability. It can take days or weeks for withdrawal symptoms to recede.

Opioids can also cause overdose and, subsequently, death. Most common signs and symptoms of overdose include: unconsciousness or awake but unable to talk, slow breathing, pinpoint pupils, cold/clammy skin, gurgling sounds (similar to a snore), and vomiting.

Naloxone is a life-saving drug that reverses the effects of an opioid overdose almost immediately by displacing the opioids from their receptors. It’s completely legal in the UK to carry naloxone. Contact your local drug and alcohol treatment service for a naloxone kit and brief training on how to use it.

Q3: How is opioid dependence treated?

Opioid substitution therapy (OST) is a medically-supervised treatment that replaces short-acting opioids, like heroin, with longer-acting prescription medicines. The medicines primarily used in OST in the UK are methadone and buprenorphine.

OST is proven to reduce harm to people who are dependent on opioids. Here’s why:

• Methadone and buprenorphine are prescribed in known doses and taken under medical supervision, making them much safer than using heroin or other illicit opioids of unknown strength or purity.

• Methadone is usually taken orally, while buprenorphine is usually taken as a tablet or film that dissolves under the tongue. In contrast, heroin is commonly injected or smoked. Injecting drugs increases the risk of blood-borne infections such as HIV and hepatitis B and C, particularly if needles or other injecting equipment are shared.

• Methadone and buprenorphine are long-acting medications that prevent withdrawal symptoms and reduce cravings for 24 hours or longer. This allows people to spend less time obtaining and using opioids, making it easier to work, study, care for family, and engage in everyday life.

Some people remain on OST for many years, while others choose to gradually reduce their dose under medical supervision. If someone decides to stop treatment, reducing the dose slowly can help minimise withdrawal symptoms and improve the chances of successfully coming off opioids.

Both methadone and buprenorphine act on the brain's μ-opioid (mu-opioid) receptors. Methadone is a full opioid agonist, meaning it fully activates these receptors. Buprenorphine is a partial opioid agonist, meaning it activates them to a lesser extent while binding very strongly. Because of this high binding affinity, buprenorphine can block or reduce the effects of other opioids taken at the same time, lowering the risk of overdose compared with methadone.

Q4: What contributed to the opioid crisis in the United States of America?

The World Health Organization (WHO) recommends 3 steps for pain management:

• 1^st option = non-opioid analgesics

• 2^nd option = weak opioids, such as codeine and tramadol

• 3^rd option = morphine or oxycodone

Defying these recommendations, intensified marketing of newly reformulated prescription opioid medications (e.g., oxycodone) and an influential and destructive pain advocacy campaign led to a rapid increase of prescription opioid medications from 1990 to 2010.  Research from the Centers for Disease Control and Prevention (CDC) shows that prescription opioid sales in the United States quadrupled from 1999 to 2010.

Faced with a growing tolerance and dependence, people began turning to illegal markets for opioids to maintain their tolerance. The rate of opioid-involved overdose deaths doubled from 2.9 to 6.8 deaths per 100,000 people. This initial rise in opioid-related deaths is often referred to as the "first wave" of the opioid crisis.

Around that time, retail prices for heroin (an illegal opioid) began to decline. Coupled with an increase in availability, heroin-related overdose deaths increased from 1 to 4.9 per 100,000 people between 2010 and 2016. In 2015, heroin surpassed prescription medications as the leading opioid involved in overdose deaths. The rise in heroin-involved deaths has been referred to as the "second wave" of the opioid crisis in the United States. In 2016, synthetic opioids, led by fentanyls, surpassed heroin and prescription drugs as the leading type of opioids involved in overdose deaths.

In comparison, prescription opioids in the UK have been better controlled. Heroin has always been the most common opioid in the black market but, due to production shortages in recent years, synthetic opioids are on the rise.

Synthetic Opioids: A Spotlight on Fentanyls and Nitazenes

Q1: What are fentanyls?

Fentanyls are a class of synthetic opioids commonly administered intravenously by an anaesthetist in surgical settings. They are used to block pain, stabilise vital signs, and prevent coughing when a breathing tube is inserted. Fentanyl takes effect in 1 to 2 minutes and typically lasts 30 to 60 minutes, making it highly effective for rapid-turnover procedures.

Fentanyl has become highly successful on the illegal market due to its cheap production, high potency, and ability to be trafficked more easily than heroin. Because fentanyl is around 50 times more potent than heroin, much smaller quantities are needed to produce similar effects.

Compared to heroin, fentanyl is much more potent, carries a much higher risk of overdose, and is a lot harder to stop using.

Q2: What are nitazenes, and why is everyone talking about them?

Nitazenes are a class of strong synthetic opioids developed in the 1950s by the Swiss pharmaceutical company CIBA. Due to their strong potency and potential overdose risk, they have never been commercialised. Isotonitazene in particular is 5 to 9 times more potent than fentanyl, meaning a dose as small as the size of a pencil tip can cause death.

As opioids, nitazenes have opioid-like effects: initial euphoria and relief from physical pain, drowsiness, relaxation, shallow breathing, pinpoint pupils, reduced heart rate and low blood pressure. They have high potential for tolerance and dependence.

After their discovery, they appeared sporadically in illicit markets around Europe and did not draw too much attention. In 1998, a cluster of 10 deaths linked to nitazenes was reported in Moscow. However, in recent years, their popularity in the illegal market has grown exponentially. The class of nitazenes expanded from a single notified nitazene analogue in 2019 to 34 distinct variants flagged globally.

Q4: Why are overdoses so common with nitazenes and fentanyls?

When added to an illegal drug batch unevenly mixed, the strength of nitazenes and fentanyl can vary between bags in the same batch. For someone with no tolerance to opioids, as much as 2 mg of fentanyl can kill a person. Etonitazenes can be 10x stronger than fentanyl, and can be lethal with as little as 0.2 mg - roughly the weight of a grain of sand.  

Even experienced heroin users are increasingly concerned about heroin purchased on the illegal market because it may contain fentanyls or nitazenes. People are refraining from injecting and switching to smoking instead, since it has a lower risk of overdose.

Q5: How can I test for nitazenes and fentanyls?

Test strips are generally reliable and are distributed freely in most drug and alcohol services in the UK. They can also be purchased legally online in the UK. As a general principle, only a small amount of drug is needed to be tested against these contaminants, and the sample can’t be used afterwards. 

Q6: Does naloxone work on nitazenes and fentanyls, and how much is needed?

People often ask this because overdoses can be hard to reverse. Naloxone can reverse opioid overdoses, including those involving nitazenes, but more than one dose may be needed. Naloxone won’t reverse non-opioid depressants ("downers") like alcohol/benzos, but it can still save someone’s life by reversing the opioid part. If you come across someone having an overdose, in addition to administering naloxone, it’s important to also call 999.

Q7: What makes nitazenes and fentanyls especially risky to mix with other substances?

The overdose risk goes up a lot when opioids are combined with other “downers” like alcohol, benzodiazepines (e.g. Valium [diazepam]) and Xanax [alprazolam]), GHB, ketamine, or other opioids.