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What You Need to Know About Drug Combinations

Combining Substances

Combining two or more substances may not seem risky, especially if you are experienced with taking those drugs individually. However, drug interactions aren't simple, and the effects they produce aren’t always an equal mix of the individual effects of each drug.

Psychoactive drugs don’t just have unique interactions with other psychoactive drugs; it's important to consider any other drugs you take, such as antidepressants, seizure medications, blood thinners, and so on.

Many drug combinations may cause the effects of the other to be amplified, essentially creating a new drug.


Defined as an interaction between two or more substances that causes the total effects experienced to be greater than the sum of the individual effects of those drugs. The effects are essentially being multiplied, creating a novel experience - not just an equal mix of each drug's effect. 

Additive Effect

1 + 1 = 2 The effects are added together

Synergistic Effect

1 + 1 > 2

The effects are more than the addition than the two

A visual representation of the comparison between additive and synergistic effects.

Drug Combination Categories

Drug combos may be categorized based on effect. TripSit organizes them into 5 categories:

Low Risk & Synergy

The combined effect is greater than the sum of the individual drug effects, however they are unlikely to cause a negative/adverse reaction when used carefully.

Low Risk & No Synergy

Effects are additive & are unlikely to cause a negative effect (beyond what may be expected from these substances).


Not usually physically harmful, however they may cause discomfort or overstimulation - the synergistic effects aren’t always predictable. Proceed with caution.


Should be avoided because of the risk of physical harm.


Should always be avoided because they are extremely harmful. Reactions are unpredictable and have a potential to cause death.

Examples of Dangerous Combinations

Ketamine & Alcohol or GHB/GBL or Tramadol or Opioids

Alcohol & MXE or Ketamine or DXM or GHB/GBL or Opioids or Tramadol or Benzodiazepine

GHB/GBL & Ketamine or MDMA or MXE or DXM or Alcohol or Opioids or Tramadol or Benzodiazepine

MDMA & DXM or Tramadol or MAOIs

Check Your Combo

TripSit is an excellent harm reduction resource that offers support and education. Their site offers a deep dive into each substance, as well as their combined effects, and other information about risk minimization.

You can look up drug combinations very easily and get information about what to expect, what precautions you should take, or learn about potentially fatal combinations, avoiding a dangerous situation!

ALWAYS look up drug combinations before trying them!


TripSit Wiki. (2021, February 10). Drug Combinations: Categorizations.

Clinical Info HIV.Gov. (n.d.). HIV/AIDS Glossary: Drug Synergism.


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