Regular, repeated use of opioids over several weeks can lead to a so-called "tolerance" to the analgesic, euphoric and sedative effects. The dose must be increased in order to achieve the desired states again. How quickly opioids lead to psychological and physical dependence depends on individual factors, social circumstances, dose, frequency, etc. Those affected perceive the negative effects more and more clearly, but the craving for the calming and euphoric effects of the substance is unbroken.

If the substance is promptly discontinued after a longer period of use, the body - which has become accustomed to the intake of foreign substances - reacts with very unpleasant physical withdrawal symptoms (painful cramps, sweating, yawning, increased pulse and breathing rate, sweating, tearing and sniffling, abdominal cramps, diarrhoea, nausea, vomiting, dilated pupils, sleep disorders, restlessness, irritability, anxiety, depressive states) in addition to the massive craving for the substance.

Regardless of the duration of use - i.e. even the first time - the use of previously used syringes and syringe equipment (such as spoons and filters) can lead to the transmission of chronic infectious diseases such as hepatitis or HIV.

As with all opioids, serious interactions can be caused by joint consumption with cocaine (exposure due to opposite effects → cardiovascular failure) and downers such as heroin, alcohol, GHB/GBL or benzodiazepines. However, the combination of opioids with benzodiazepines is relatively common. There is evidence that this combination leads to increased euphoria at moderate doses. However, the risk of an opioid overdose and associated respiratory depression is greatly increased.

Depending on the type of application, the active ingredient enters the body via the blood or the mucous membranes (or the skin in the case of pain patches). The onset of action occurs after approx. 10 seconds with intravenous consumption and after approx. 2-5 minutes with nasal consumption. When applied to the skin as a plaster, the effect only occurs after several hours, but remains relatively constant for over 72 hours.

The best-known opioid receptors are the G-protein-coupled μ-, κ- and δ- Opioid receptors. According to the current state of research, most synthetic opioids act as µ-opioid receptor agonists (e.g. fentanyl and its derivatives, U-47,700). In higher doses, the opioid AH-7921 also acts as an agonist at the κ-opioid receptor, MT-45 stimulates, among other things, the δ- and κ-opioid receptors. The activation of the opioid receptors results in a pain-relieving effect (analgesia). Certain receptor types are responsible for other possible effects. Activation of the μ-Opioid receptor causes euphoria, respiratory depression, sedation (severe drowsiness) and nausea. The κ-Receptor binding, on the other hand, can lead to dysphoria (emotional moodiness) and sedation. Activation of the δ- opioid receptor is associated with a feeling of reward and anxiety relief. Therefore, the effects elicited are highly dependent on the receptor binding profile of the opioid in question. Fentanyls are generally strong μ-Opioid receptor agonists. Many nitazenes are also strong and selective μ-Opioid receptor agonists. New studies also suggest that they are even more strongly linked to the μ-Opioid receptor than fentanyl (binding affinity).

A highly potent nitazene is isotonitazene, which is converted in the body into N-desethylisotonitazene is degraded. Since N-Since desethylisotonitazene itself is also a highly potent opioid, the duration of action is extended, among other things. Studies show that isotonitazene can cause significant and long-lasting respiratory depression.

To prevent the fatal consequences of overdosing Naloxone used as an "antidote" (intravenously or as a nasal spray), which has an competitive antagonist at the µ-opioid receptor. This means that it displaces the opioids from the receptor, resulting in a rapid cancellation of the opioid effect and triggering an opioid withdrawal syndrome.

The effect of the opioid is generally longer lasting than the naloxone effect. Respiratory depression and thus a life-threatening situation can occur again within 15 minutes. Depending on the previous opioid dose, this process can be repeated over a period of hours, which means that continuous monitoring by medical staff is always required.

Whenever naloxone is administered, the emergency services must be called at the same time.

• Diseases of the lungs (e.g. asthma), as synthetic opioids depress the respiratory centre.
• Liver or kidney diseases
• Epilepsy
• Pregnancy and breastfeeding
• Participation in road traffic

Due to the high potency and the increased risk of overdose, we advise against consumption. If you decide to use synthetic opioids despite the high risk, please note the following:

• If you have a synthetic opioid: Be sure to use a drug checking service to make sure which substance it is.
• If you don't have the opportunity for drug checking, test a small amount carefully.
• Do not consume substances alone and not at the exact same time as the rest of the group, so that one of you can call for help in an emergency.
• Use gloves and a mask when handling, as well as a pad that you can clean or dispose of afterwards.
• Only use pharmaceutical products (e.g. fentanyl patches) in accordance with the information in the package leaflet or doctor's instructions and as prescribed by your doctor.
• Avoid mixed use: The combination (before, at the same time and after) of two or more "downers" such as opioids, sleeping pills and tranquillisers, GHB and alcohol increases the risk of nausea, vomiting, unconsciousness, choking on vomit and respiratory paralysis. There is a particularly high risk of overdose with substances with a long duration of action, such as certain benzodiazepines or synthetic opioids.
• The risk of overdosing is particularly high after long periods of non-consumption.

Risks exist not only for potential consumers, but also for people involved in transport and production. For example, the highly potent synthetic substances can pose health risks to postal workers and law enforcement officers.

Many synthetic opioids are subject to the Narcotic Drugs Act. For example, fentanyl and its derivatives, some nitazenes (isotonitazene, protonitazene, etacene, etonitazepyne), U-47,700, AH-7921 and 2-methyl-AP-237. In particular, the acquisition, production, import and export, transfer to and procurement for others (transfer, sale, etc.) is punishable by law and can result in fines and imprisonment.

Other substances are subject to the New Psychoactive Substances Act (NPSG). Any person who intentionally produces, imports, exports or transfers or procures new psychoactive substances to be used by the other person or a third party to achieve a psychoactive effect in the human body is liable to prosecution.