Xylazine, a non-opioid sedative substance, complicates the overdose crisis not only in North America but in Estonia as well. A report with pragmatic recommendations to people who use drugs by Mart Kalvet from LUNEST.
In mid-January, the Estonian drug users’ association LUNEST received a signal that in addition to synthetic opioids, xylazine (a veterinary drug with strong sedative, muscle-relaxing, pain-relieving, hypnotic, and anaesthetic effects) was found in the bodies of two people who died due to drug overdose at the end of December.
The news is alarming because it suggests that the dangerous habit of tempering with xylazine in order to enhance and prolong the effect of street opioids, such as fentanyls or nitazenes, has reached Estonia from North America, with all its potentially fatal consequences.
The origins of xylazine
Aljona Kurbatova, head of the Center for Drug Addiction and Infectious Disease Prevention at the Estonian National Health Development Institute, said that a few years ago, the efforts of the police and the prosecutor’s office bore fruit, and fentanyl practically disappeared from the Estonian drug market. “This time, an alternative was found in the USA, where by then substances belonging to the group of nitazenes and fentanyl mixed with e.g. xylazine, which is a particularly dangerous combination, were already spreading. Maybe wars and geopolitics also affect the drug market,” she said.
At the beginning of the 2000s, the practice of mixing heroin with “horse anaesthetic” (Anestesia de Caballo) began to spread on the streets of Puerto Rico. In the past few years, xylazine has been increasingly seen in the US opioid market, where it is mixed with fentanyls or nitazenes. In some parts of North America (e.g. Philadelphia) it is already difficult to find opioids that are not “enhanced” with xylazine.
According to experts in the US, xylazine is added to opioids with a fast half-life such as fentanyl and nitazene, in order to make the interaction of the substances more similar to the longer-lasting effects of heroin. Unfortunately, the unintended consequences of using opioids mixed with xylazine are extremely unpleasant. Regular use is accompanied by, among other things, painful skin lesions (because xylazine inhibits the skin’s oxygen metabolism), loss of consciousness (from which the opioid-blocking antidote naloxone does not wake the victim), and withdrawal symptoms, which are not alleviated by substitution drugs such as methadone or buprenorphine.
“The withdrawal symptoms of opioids are still relieved by methadone,” commented one Tallinn user, who suspects that he has used a new “cocktail” in recent months. “But severe anxiety and insomnia remain,” he added. In the US, doctors treat xylazine withdrawal symptoms mainly with blood pressure-lowering, pain-relieving, and anti-anxiety medications.
According to a recent report in the New York Times, one of the most diabolical consequences of combining a short-acting opioid with a longer-acting xylazine is that by the time the user recovers from the hypnotic effects of the xylazine, the opioid has long since worn off and withdrawal symptoms have set in, prompting them to immediately seek out and administer another dose.
Drug overdose deaths in Estonia soared in 2022
In 2022, the number of drug overdose deaths in Estonia skyrocketed compared to previous years. While there were 31 such deaths in 2020 and 39 in 2021, a total of 80 overdose deaths have been registered in the whole country based on toxicological analyses in 2022.
Of the confirmed 80 drug overdose deaths, 38 percent are related to synthetic opioids, specifically the nitazene group of substances. Most of them (22) are related to the use of protonitazene, seven to metonitazene, and six to isotonitazene. Some overdose deaths involved several different combinations of nitazenes. There has also been a noticeable increase in carfentanil deaths (7 in total), which decreased in the previous couple of years. According to data so far, 15 percent of deaths in 2022 were related to cocaine use and 29 percent to amphetamine use. Most overdose deaths are caused by a combination of several different narcotic and psychotropic substances. In addition to so-called street drugs, various antidepressants, benzodiazepines, and other drugs have been found in post-mortem toxicology.
The average age of people who lost their lives due to an overdose is 38 (among people aged between 17 and 68 years). 62 of those who died were male and 17 were female. If we look at the deaths related to substances belonging to the nitazene group separately, the average age is 41 (among people aged between 32 and 51 years), 28 for men and 2 for women. There have been a total of eight overdose deaths in the 17−20 age group as of the beginning of December, which is very worrying. Methylphenidate was found in four people belonging to this age group. Methylphenidate is a central nervous system stimulant with a similar but milder effect to cocaine. The substance is also legally used as medicine.
Wounds of xylazine users heal poorly and slowly and become infected easily. Pus with a specific smell is released from the wounds, and in more severe cases the infected body part must be amputated. The results of typing “xylazine wound” into the Google image search are blindingly terrible, reminding us of the “krokodil” panic a decade ago (which fortunately turned out to be unfounded in Estonia). If desomorphine produced at home had toxic production residues as the reason for its decomposing effect on the body, causing limbs to fall off, xylazine also causes lesions when pure.
The xylazine content of the mixed substance or substances distributed in Estonia is unknown. The fatally toxic dose of pure xylazine is between 40 and 2400 mg. Neither a safe nor a lethal dose of xylazine has been well defined, as there is a large overlap in body concentrations of xylazine in non-fatal and fatal administration cases. So far, there is no specific antidote for xylazine, and overdoses are treated symptomatically.
The Biochemistry of xylazine
Biochemically, xylazine is an alpha2-adrenoceptor agonist. It directly stimulates both central alpha2-receptors and peripheral alpha-adrenoreceptors in several tissues, inhibiting the synaptic transmission of norepinephrine and dopamine in the central nervous system. By binding to the presynaptic surfaces of autoreceptors, xylazine mimics the effect of norepinephrine, which in turn causes inhibition of norepinephrine secretion.
The effect occurs within about 15 to 30 minutes of administration and the sedative effect can last from one to four hours. More frequent acute side effects are a short-term increase in blood pressure, followed by a decrease in blood pressure, heart arrhythmia and respiratory depression (sparse and weak breathing and, in more severe cases, respiratory arrest).
If overdose symptoms appear after taking a mixture of opioid and xylazine, the victim should be given naloxone, emergency services should be notified immediately and details of the incident should be exactly described to them. In Estonia, both substitution treatment centres and harm reduction service providers, including a mobile unit, issue naloxone to anyone who wants it.
Xylazine is only allowed to be used in the treatment of animals, which is why the substance’s mechanisms of action in humans have not been thoroughly studied to date. In Estonia, xylazine is not included in the lists of narcotic and psychotropic substances; so far it has only been regulated by the Ministry of Rural Affairs, which prohibits veterinarians from issuing it to livestock keepers. Only a veterinarian can inject xylazine into an animal.
Taking into account the described dangers, the non-profit Estonian Association of People who Use Psychotropic Substances (LUNEST) recommends avoiding the use of black market opioids altogether. Express tests to detect xylazine from mixtures are not available either here or in the USA. It is possible to test pure xylazine with reagents, but so far we do not know what the answer is when testing xylazine mixed with nitazenes and ballasts, or whether it is possible to rule out the presence of xylazine in the substance. We encourage citizens suffering from opioid addiction disorder to join the opioid substitution treatment service, which has been expanded in Estonia in 2023.
Recommendations to People Who Use Drugs
If it is not possible to check the purity of the substance and it is not possible to avoid using it, the NGO LUNEST recommends to follow these principles when using street opioids of unknown composition:
• Start with a low dose and administer slowly (especially if you have also taken central nervous system depressants such as alcohol, benzodiazepines, or opioids);
• Some high blood pressure medicines that contain similar active ingredients, such as clonidine, may increase the effect of xylazine. If you are using any of these drugs, reduce the amount of either the narcotic substance or the medicinal drug and use in the presence of a friend who can make sure that your breathing does not stop and, if necessary, administer naloxone and perform artificial respiration;
• If you think a person has overdosed on a substance containing xylazine, give them naloxone – this can stop respiratory arrest caused by the opioid. The most important thing is that the victim’s body receives enough oxygen. If breathing does not resume after administration of naloxone, begin CPR until help arrives;
• Heat the drugs in a heating cooker before injection – this helps to get rid of impure additives that can promote the formation of skin lesions;
• Xylazine can cause skin lesions all over the body, not just near the injection site. If you notice sores on your body, see a doctor as soon as possible.
Take care of yourself and your loved ones. If possible, make sure the substances you use are clean, get a naloxone kit and carry it with you at all times. Never use alone and don’t be afraid to seek help when things get overwhelming! By following these recommendations, we will be able to survive this drug disaster as well.
Policy responses to xylazine
In a darkly ironic way, the drug arrived on the Estonian drug market at the same time that, at the global level, the ice of the drug policy-glacier has begun to move after three decades of stagnation: in December of 2022, the UN General Assembly adopted a general resolution that broke the so-called Vienna consensus, which had inhibited the humanisation and rationalisation of drug policy for a long time. If until now there was an agreement that all drug policy resolutions and declarations of the UN Commission on Narcotic Drugs must be 100 percent consensual, this time it was decided to adopt the document by vote. Estonia, together with 116 more progressive countries, voted in favour of the resolution, which has lost the backward rhetoric of a “drug-free world” and instead focuses on human rights. Russia and eight other supporters of continuing the brutal drug war voted against it.
In light of such developments, there is hope that global drug policies will become evidence and science-based in our lifetime. The question is how long we will have to endure the prohibition regime in its current form.
Aljona Kurbatova explained in writing that there is a lack of relevant legislation, financial resources, and specialists: “Both the service of checking drugs before use and the service of centres for safer use (both mentioned in our new drug policy) require changes to the laws in force today, which would allow a person in a public space to possess a small amount of drugs for personal use. We also need to have enough financial and also human resources (trained people with the right attitude) to implement these interventions in a way that is really beneficial.”
“In a situation of lack of resources, we must be ready to make choices. For example, substitution treatment based on pharmacological heroin is tens of times more expensive (due to the high price of the drug), and for the same budget it would be possible to increase the volume of opioid addiction treatment with other drugs, as well as, for example, the naloxone program. Facilitating the availability of naloxone is a priority in the current situation. This year, we plan to contribute primarily to the development of a warning system and increase the volume of the naloxone program, and buprenorphine/naloxone will be added as the drug of choice in the provision of the state-funded opioid addiction service”, explained Kurbatova.
The text is based on an article published in Estonian in Ypsilon.