Should You Mix Drugs? An Overview Of Polydrug Use
4 min

Should You Mix Drugs? An Overview Of Polydrug Use

4 min

Find out what you must know about mixing drugs. What is drug synergy, what are the risks involved, and which combinations are relatively safe versus dangerous?

If you are considering polydrug use on your next ride, this article is for you. Let’s see whether mixing drugs is a good idea, what the potential risks are, a few relatively safe combinations, and some others that should be avoided at all times.

Is Mixing Drugs A Good Idea?


If you listen to the most conservative voices around, taking drugs, in general, is never a good idea. Imagine mixing two or more. But let’s set aside paternalistic and narrow-minded positions and face reality. People experiment with different drugs every day, everywhere. As the availability and variety of recreational drugs increases, together with individual experiences, some of you may be in the mood to combine different substances to see what happens.

At the same time, there are a lot of variables that may inspire different judgments on whether mixing drugs is a good idea or not. Among these are: which drugs you are mixing, the dose, your physical and mental state, and the objective purity of the drugs you are taking.

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What Is Drug Synergy?

In many cases of polydrug use, one substance acts as the base (or primary drug), with additional drugs to lighten, boost, or compensate for its effects, making the experience more enjoyable and capitalising on the potential for synergy.

Positive synergy is basically what you’re after. From here, there are different types of outcomes you may be searching for. The most common are:

  • Substances acting on the same cellular system, generating a more potent, complementary high;
  • Preventing or delaying the degradation of the other drug, extending the experience of the primary drug;
  • Substance counterbalancing the undesired side effects of another.

What Are The Risks Of Mixing Drugs?


Again, it all depends on what are you mixing, and what your subjective conditions (both mental and physical) are when using two or more psychoactive drugs in combination. Each substance comes with its own chemistry and effects—and combining two or more drugs means getting an outcome that won’t simply be the sum of two parts.

Keeping this in mind, the risk of combining the wrong substances and generating an undesired or dangerous outcome is a serious one. Some combos simply require caution and informed dosing, others are downright deadly.

Let’s have a look at 5 drug combinations that work in positive synergy, versus 5 other combinations you should avoid at all times.

5 Relatively Safe Drug Combinations


There are literally hundreds of drug combinations out there. Keeping in mind everything we just said concerning the risk and subjectivity of any drug experience, here are some relatively safe combinations that are known to produce a nice synergy.

  • Dmt & Mushrooms

DMT is a powerful psychedelic, typically taken in one of two ways: either vaporized for a short "breakthrough" experience, or taken in combination with an MAO inhibitor for a long, intense trip (this is what happens with ayahuasca or its synthetic version, pharmahuasca). The combination of DMT with magic mushrooms also allows for a longer journey, with more intense and deeper feelings, more extraordinary visuals, and an overall boost in positive energy. The two work well together, with relatively low risks.

  • Mushrooms & Mescaline

Mescaline is a psychedelic found in certain cacti, including peyote and San Pedro, among others. Experienced psychonauts affirm that it is better to start with mescaline (the trip has a longer onset and duration) before taking shrooms. When you start to feel a good trip coming on, dose the mushrooms. After 30 minutes, you will feel a strong double-trip, with the distinct plus of being able to recognise the unique attributes of each substance.

  • Mushrooms & Mdma

Known as "hippy flip", "flower flip", or "ethno flip", it is a popular mix among experienced drug users. The idea is that MDMA ensures a quite reliably good high, while shrooms are more unpredictable. Hence, the former acts as a stabiliser of the latter in terms of vibes. The outcome is intense as hell, with strong visuals paired with a euphoric state. You will be walking on clouds, tearing rainbows from your eyes.

  • Cannabis & Mdma

Called the "stoner flip", it is also a popular and well-established combination. The two substances lead to opposite side effects. MDMA increases body temperature and oxidative stress on the brain, especially when taken in warm temperatures. THC, on the other hand, slightly reduces body temperature and exerts anti-inflammatory and antioxidant effects. When combined, this is a case of compensating synergy, in which each substance counterbalances the other (with proper dosing and hydration).

  • Cannabis & Ketamine

These two drugs aren't likely to cause an adverse or undesirable reaction when used carefully. Most users agree that weed is perfect for rounding off the effects of ketamine. It adds another layer to the psychedelic effects, deepening the headspace, enhancing body euphoria and dissociation, and making the whole experience more organic.

5 Combinations To Avoid At All Times


Some drugs just aren’t worth mixing. Unlike the above combinations, you’ll notice fewer natural substances like cannabis and mushrooms, and more substances like pharmaceutical drugs and alcohol. Here too, there are literally hundreds of additional dangerous combinations that we’ve left out.

  • Alcohol & Ketamine

Both substances cause ataxia (dysfunction in areas of the nervous system that control and coordinate movement) and bring about a very high risk of vomiting and unconsciousness. If you fall unconscious while on this mix, there is a severe risk of vomit aspiration if you are not placed in a recovery position by your sitter.

  • Amphetamine & Tramadol

Tramadol is a potent opioid pain medication that, taken alone, causes common side effects such as constipation and nausea, but also more severe ones like seizures and serotonin syndrome. Both tramadol and stimulants like amphetamines increase the risk of seizures.

  • Opioids & Cocaine

An example of this dangerous combo is known as "speedball" or “snowball”, which consists of heroin combined with cocaine. Cocaine increases respiration rate, allowing for higher doses of the opioid. If the stimulant wears off first, the opioid may overcome it and cause respiratory arrest.

  • Maoi & Mdma

These two substances are very dangerous when mixed, potentially leading to a fatal condition called serotonin syndrome. In particular, MAO-B inhibitors can increase the potency and duration of MDMA to an unpredictable degree; MAO-A inhibitors will lead to hypertensive crisis.

  • Ssri & Maoi

SSRIs and MAOIs are both antidepressants, with the latter being more potent. The combination of the two can be extremely harmful to your body, leading to fatal serotonin syndrome in worst-case scenarios. Today, individuals with depression are most often prescribed SSRIs, as they have fewer risky interactions with other drugs than MAOIs.

Combining Drugs Is Inherently Risky

This was only a brief overview of the complex topic that is polydrug use. Some combos may synergise well, providing an even more pleasant experience, whilst others are simply dangerous and should be avoided at all times.

Even when it comes to the relatively safe ones, there are two takeaways we’d like you to consider. First, always start slow; do careful research and experimentation before taking higher doses of any substance, alone or in combination. And second, keep in mind that, due to increased risk of side effects and synergies (sometimes positive, sometimes negative), there will always be a general degree of risk when combining drugs. Proceed with caution.


Written by: Chiara
Cannabis and psychedelics connoisseur, always on the go. In her previous lives, she was a witch and botanist; nowadays, she mixes reminiscences of the past in a life full of plants and magic. She is very Italian, with enough energy to move mountains, and a smile that could melt an iceberg.

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