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Harm reduction when mixing substances
Peder Olai Skjeflo Holman, resident physician in clinical pharmacology at the Section for Forensic Toxicological Interpretation at Oslo University Hospital.
Images: Einar Hyndøy.
Combining substances
Compared with taking just one substance, combining two or more drugs can produce more unpredictable effects and pose greater risks to the user. How big the risk is, what can go wrong, and what can be done to prevent negative consequences depend, among other things, on which substances and doses are taken, the order and timing, the user’s physical and mental condition and predispositions, and the situation the user is in. There is a lot to learn if you want to stay safe. One should have good theoretical knowledge of drugs and medicines, as well as a healthy dose of self-insight, before even considering combining substances. Be careful, be smart, don’t play guessing games, don’t harm yourself — and don’t die.
Compared with taking just one substance, combining two or more drugs can produce more unpredictable effects and pose greater risks to the user. How big the risk is, what can go wrong, and what can be done to prevent negative consequences depend, among other things, on which substances and doses are taken, the order and timing, the user’s physical and mental condition and predispositions, and the situation the user is in. There is a lot to learn if you want to stay safe. One should have good theoretical knowledge of drugs and medicines, as well as a healthy dose of self-insight, before even considering combining substances. Be careful, be smart, don’t play guessing games, don’t harm yourself — and don’t die.
10 main points
1. Taking more substances or higher doses makes the effects and side effects harder to predict.
2. It is often riskier to take two or more substances than just one, but there are exceptions.
3. Calling a substance a ‘drug’ or a ‘medicine’ in everyday language makes little difference to its risk. It doesn’t magically become safer just because it has medicinal status.
1. Taking more substances or higher doses makes the effects and side effects harder to predict.
2. It is often riskier to take two or more substances than just one, but there are exceptions.
3. Calling a substance a ‘drug’ or a ‘medicine’ in everyday language makes little difference to its risk. It doesn’t magically become safer just because it has medicinal status.
4. Most drug deaths happen when people have several substances in their body.
5. The most risky combination with respect to the risk of death is combining two or more respiratory-depressant substances (alcohol, tranquilizers/sedatives, sleeping pills, strong analgesics/strong painkillers, and GHB), or high doses of two or more substances that increase levels of serotonin, noradrenaline and dopamine in the brain and body (for example MDMA, (meth)amphetamine, cocaine, mephedrone, tramadol, antidepressants and MAO inhibitors).
6. One should be careful when combining substances that can increase the risk of drug-induced psychosis, such as stimulants, hallucinogens, and cannabis.
7. If you combine substances that can make you dizzy, unsteady, or cause a drop in blood pressure, you risk falling and injuring yourself. This applies, for example, to alcohol and other mentioned respiratory depressants, cannabis, ketamine, nitrous oxide, poppers, potency drugs such as Viagra, blood pressure–lowering medications, and many medicines used in the treatment of mental disorders.
8. If you do not have solid theoretical knowledge about drugs and medicines, you should definitely not try to guess what might happen if you combine them.
9. If you combine substances, you may need to adjust the dosage very differently (often lower) than you would if taking each substance separately.
10. The timing and order in which you take the substances you combine can have a huge impact.
5. The most risky combination with respect to the risk of death is combining two or more respiratory-depressant substances (alcohol, tranquilizers/sedatives, sleeping pills, strong analgesics/strong painkillers, and GHB), or high doses of two or more substances that increase levels of serotonin, noradrenaline and dopamine in the brain and body (for example MDMA, (meth)amphetamine, cocaine, mephedrone, tramadol, antidepressants and MAO inhibitors).
6. One should be careful when combining substances that can increase the risk of drug-induced psychosis, such as stimulants, hallucinogens, and cannabis.
7. If you combine substances that can make you dizzy, unsteady, or cause a drop in blood pressure, you risk falling and injuring yourself. This applies, for example, to alcohol and other mentioned respiratory depressants, cannabis, ketamine, nitrous oxide, poppers, potency drugs such as Viagra, blood pressure–lowering medications, and many medicines used in the treatment of mental disorders.
8. If you do not have solid theoretical knowledge about drugs and medicines, you should definitely not try to guess what might happen if you combine them.
9. If you combine substances, you may need to adjust the dosage very differently (often lower) than you would if taking each substance separately.
10. The timing and order in which you take the substances you combine can have a huge impact.
Be smart
Do thorough research and make informed choices. Never try a new drug combination without first making sure you understand the effects you can expect and what could potentially go wrong. |
Where can I find information?
There are not always good scientific sources of information about combinations of psychoactive substances. This is because there are infinitely many possible ways to combine drugs, making it impossible to research them all. It is usually possible to find experiences and advice from users online, but it is very important to be critical of your sources.
Who is the sender, and where did they get their information? There is a big difference between anecdotes from random individuals and scientific meta-analyses of randomized, placebo-controlled, double-blind crossover studies.
Check out Chemfriendly and the Association for Safer Drug Policy’s online seminar on mixing substances.
Some drugs can reduce the unwanted effects of other substances while preserving some of the desired ones. However, there will always be certain negative effects that cannot be compensated for.
There are not always good scientific sources of information about combinations of psychoactive substances. This is because there are infinitely many possible ways to combine drugs, making it impossible to research them all. It is usually possible to find experiences and advice from users online, but it is very important to be critical of your sources.
Who is the sender, and where did they get their information? There is a big difference between anecdotes from random individuals and scientific meta-analyses of randomized, placebo-controlled, double-blind crossover studies.
Check out Chemfriendly and the Association for Safer Drug Policy’s online seminar on mixing substances.
Some drugs can reduce the unwanted effects of other substances while preserving some of the desired ones. However, there will always be certain negative effects that cannot be compensated for.
Check out Chemfriendly and the Association for Safer Drug Policy’s online seminar on mixing substances.
Some drugs can reduce the unwanted effects of other substances while preserving some of the desired ones. However, there will always be certain negative effects that cannot be compensated for.
More substances = more variability
There is already great variation in how individual substances affect different people. The variation can become even greater when multiple substances are combined, and the effects can be harder to predict.
More substances = more dangerous?
Most people who die from drug use have multiple substances in their system. Even though there are exceptions, it is often wise to assume that taking several substances is more dangerous than taking just one.
More substances = better?
Some substances can reduce the unwanted effects of others, while some of the desired effects may be preserved, enhanced, or altered in a way that feels positive. This is probably the main reason why people combine drugs. However, there will always be certain negative effects that cannot be “compensated for” by taking more substances, and some side effects will almost always worsen (for example, impaired impulse control and reduced ability to assess risk).
There is already great variation in how individual substances affect different people. The variation can become even greater when multiple substances are combined, and the effects can be harder to predict.
More substances = more dangerous?
Most people who die from drug use have multiple substances in their system. Even though there are exceptions, it is often wise to assume that taking several substances is more dangerous than taking just one.
More substances = better?
Some substances can reduce the unwanted effects of others, while some of the desired effects may be preserved, enhanced, or altered in a way that feels positive. This is probably the main reason why people combine drugs. However, there will always be certain negative effects that cannot be “compensated for” by taking more substances, and some side effects will almost always worsen (for example, impaired impulse control and reduced ability to assess risk).
Fun + fun = double fun?
Unfortunately, it’s not that simple. And it's by no means guaranteed that “quite safe + quite safe = still quite safe.” Substances that are not necessarily life-threatening and that usually produce pleasant effects when taken individually can sometimes cause unpleasant or harmful side effects when combined. “Fun + fun = overheating and diarrhea,” and “quite safe + quite safe = respiratory arrest” are situations you’d definitely want to avoid.
Don’t play the guessing game
Even if you have experience with individual substances, you should not try to guess what will happen when combining them. Mixing drugs requires a much higher level of knowledge about substances compared to taking them separately — if your goal is to avoid health damage, death, and other negative consequences.
Unfortunately, it’s not that simple. And it's by no means guaranteed that “quite safe + quite safe = still quite safe.” Substances that are not necessarily life-threatening and that usually produce pleasant effects when taken individually can sometimes cause unpleasant or harmful side effects when combined. “Fun + fun = overheating and diarrhea,” and “quite safe + quite safe = respiratory arrest” are situations you’d definitely want to avoid.
Don’t play the guessing game
Even if you have experience with individual substances, you should not try to guess what will happen when combining them. Mixing drugs requires a much higher level of knowledge about substances compared to taking them separately — if your goal is to avoid health damage, death, and other negative consequences.
Photo: Ole Magnus Kinappel / PION – Sex Workers’ Interest Organization
Timing is super important!
Different substances can have completely different durations of effect. Their effects and side effects change in both intensity and quality depending on how long it has been since the substance was taken. Therefore, the order in which substances are taken — and the time between each one — matters a great deal.
Dosage is super important!
You may need to dose very differently when combining substances than when taking them separately. This will depend greatly on timing and which substances are involved. Please make sure to find this out beforehand, so you don’t end up in the hospital or die!
Have a plan
If you’ve decided to try a combination that could be risky, you should have a strategy to prevent negative consequences. You should also have a plan for what to do if things start to go wrong. The best strategy — and what your plan should include — depends entirely on which substances are being combined.
Different substances can have completely different durations of effect. Their effects and side effects change in both intensity and quality depending on how long it has been since the substance was taken. Therefore, the order in which substances are taken — and the time between each one — matters a great deal.
Dosage is super important!
You may need to dose very differently when combining substances than when taking them separately. This will depend greatly on timing and which substances are involved. Please make sure to find this out beforehand, so you don’t end up in the hospital or die!
Have a plan
If you’ve decided to try a combination that could be risky, you should have a strategy to prevent negative consequences. You should also have a plan for what to do if things start to go wrong. The best strategy — and what your plan should include — depends entirely on which substances are being combined.
Which combinations should be avoided?
There are infinitely many possible drug combinations, and unfortunately, it is impossible to create a short and simple list of recommendations that can prevent all potential negative consequences. However, here are some combinations that should generally be avoided.
1. Two or more substances that suppress breathing (for example, alcohol, benzodiazepines, opioids, and GHB). Combining such substances is significantly more dangerous than taking them individually and can be fatal.
There are infinitely many possible drug combinations, and unfortunately, it is impossible to create a short and simple list of recommendations that can prevent all potential negative consequences. However, here are some combinations that should generally be avoided.
1. Two or more substances that suppress breathing (for example, alcohol, benzodiazepines, opioids, and GHB). Combining such substances is significantly more dangerous than taking them individually and can be fatal.
Photo: Ole Magnus Kinappel / PION – Sex Workers’ Interest Organization
2. Two or more substances that increase the levels of the neurotransmitters: serotonin, noradrenaline, and/or dopamine in the brain and body (for example MDMA, cocaine, amphetamine, methamphetamine, mephedrone, methylphenidate (Ritalin), tramadol, and antidepressants). This can lead to potentially fatal side effects such as overheating, seizures, cardiac arrest, and stroke. Avoid at all costs combining such substances with so-called MAO inhibitors (found, among other things, in ayahuasca and the medication moclobemide/Aurorix)..
3. Various combinations of stimulants, hallucinogens, and/or cannabis. This can cause confusion, agitation, and a higher risk of drug-induced psychosis.
3. Various combinations of stimulants, hallucinogens, and/or cannabis. This can cause confusion, agitation, and a higher risk of drug-induced psychosis.
What else should I keep in mind?
Be careful when combining substances that can cause unsteadiness, dizziness, poor coordination, and/or a drop in blood pressure — for example alcohol and other respiratory depressants mentioned above, cannabis, ketamine, nitrous oxide, poppers, potency drugs such as Viagra, blood pressure–lowering medications, and many drugs used to treat mental disorders (especially antipsychotics). Falling is not only embarrassing — it can also be dangerous.
It’s wise to remember that all psychoactive substances, to a greater or lesser degree, impair mental functions such as impulse control, short-term memory, and the ability to assess risk. This impairment can be intensified when taking multiple substances.
All psychoactive substances make you perceive and relate to things differently than when sober. This effect can become more variable and unpredictable when using multiple substances, and it may become harder to know whether the decisions you make are good ones.
Be careful when combining substances that can cause unsteadiness, dizziness, poor coordination, and/or a drop in blood pressure — for example alcohol and other respiratory depressants mentioned above, cannabis, ketamine, nitrous oxide, poppers, potency drugs such as Viagra, blood pressure–lowering medications, and many drugs used to treat mental disorders (especially antipsychotics). Falling is not only embarrassing — it can also be dangerous.
It’s wise to remember that all psychoactive substances, to a greater or lesser degree, impair mental functions such as impulse control, short-term memory, and the ability to assess risk. This impairment can be intensified when taking multiple substances.
All psychoactive substances make you perceive and relate to things differently than when sober. This effect can become more variable and unpredictable when using multiple substances, and it may become harder to know whether the decisions you make are good ones.
This text was written for publication by Chemfriendly Norway and on rusopplysningen.no.
Published 14.04.2026