Avoid the consumption of grapefruit or grapefruit juice, which can significantly increase blood levels and undesired effects of the many different drugs, including some HIV medications and Ketamine.


What are Uppers?

Uppers work by sending the signal to speed up to your central nervous system (CNS) and brain, elevating your blood pressure. Adderall, meth, and cocaine are more well-known stimulants. Uppers are known to increase mood, alertness, sexual courage, and self confidence. However, this puts a massive amount of strain on your body, cardiovascular* and respiratory* systems to dangerous and sometimes fatal levels at the same time. When crashing, you may feel, weak, dizzy, or shaky.[VP1]

*Cardiovascular: What moves your blood (arteries, veins, etc.)

*Respiratory: The organs that help you breathe (blood vessels, airways, lungs etc.)

Mixing Uppers + Uppers (Overamping)

Stimulants, otherwise known as “uppers” are drugs that speed the body up. The most common forms of uppers are: cocaine, MDMA (ecstacy or molly), Ritalin, Adderall, and caffeine. Mixing multiple uppers at once puts strain on your heart, raising your blood pressure. It can also make you feel shaky and anxious, cause sweating, dehydration, high body temperature, and nausea.

It is important to try to pace your drugs out, and to start low, go slow. You may experience symptoms of overamping such as increased body temperature, extreme sweating, rapid heartbeat, and nausea. If you do feel any of these, the most important step is to regulate your body temperature and hydrate, these will help slow your heart rate, and prevent other organs from shutting down.

TIP: put ice-packs under your armpits, and drink electrolyte-rich beverages such as sports recovery drinks (not energy drinks-these dehydrate and contain caffeine, a stimulant).

Being a good Trip Buddy for someone who is experiencing overamping

When assisting someone who is experiencing a stimulant overdose (overamping), it is important to stay with them, and get them to a low-sensory area (away from noise and flashing lights). Hydration is vital to helping the substances pass through their system as quickly as possible, and also to help regulate their body temperature.

Self-regulation on Stimulants

Feelings of extreme pleasure, anger, or even sadness can come about when using stimulants. Feeling overwhelmed and overstimulated are also common reactions when using too much of a stimulant or multiple stimulants. Try some of the following:

  • Move yourself to a low-sensory area (away from the crowds, noise, lights, or overall party environment.
  • Try self-soothing/mindfulness activities: slow-deep breaths, talking to a friend over the phone, or naming something you can see, hear, and touch.
  • Stay hydrated and chew some gum so you don’t grind your teeth.


Mixing Downers + Downers (Opioid Poisonings)

Mixing different types of downers such as opioids, alcohol, or GHB/GBL, your nervous system slows down. This means you may not feel as aware of dangers such as slower heart-rate, low breathing rate; which causes people to pass out or overdose.

Alcohol and GHB/GBL

Alcohol and GHB can be a very dangerous combination. Both drugs slow down your central nervous system, heart rate, and breathing rate; and combining them intensifies these effects on your body. It is common to pass out, feel faint, and vomit when these drugs are combined. If someone is not breathing, it is important to call 911 straight away, and administer CPR. Naloxone will not reverse this type of overdose.

Prolonged use and combination of GHB and alcohol can lead to a risk of increased physical dependance. Being mindful of how often you use, and how much of your drugs that you are using can help prevent unwanted drug dependence.

Alcohol + Marijuana (weed)

Alcohol and weed can feel very differently for different people. For some it may intensify your high from weed, as alcohol metabolizes THC to higher levels. For others it can cause nausea, fatigue, and vomiting. It is important to try to pace these two substances out with food, to avoid passing out, as they can cause these negative experiences when used together.

Alcohol + Opioids

Alcohol and opioids intensify each others’ effects. Most commonly they both slow breathing, heart rate. When used together for long periods of time, they can lead to physical dependency. Side effects from mixing these drugs can include drowsiness, risk of opoid poisoning, becoming “blackout” drunk, impaired motor control, ,unusual behaviour, and intense mood swings.

Mixing multiple Opioids

When mixing multiple opioids, such as fentanyl, oxycontin, morphine, Tylenol 3’s, or hydromorphone, it increases your risk of experiencing an opioid poisoning. It is best to start with a low dose of an opioid, and use slowly, as opposed to all at once.

An opioid poisoning (sometimes referred to as an overdose) occurs when opioids are (sometimes unknowingly) mixed into non-opioid drugs, or when the potency of opioids being used are too strong for a person’s body to handle. This can cause someone to stop breathing, as the opioid receptors in the brain tell the body to relax, and not perform these functions. Naloxone is a drug that can reverse an opioid overdose. If you want to check your drugs for extremely potent opiates such as Fentanyl, you can also test your drugs using Fentanyl test strips, or by bringing your drugs into a local Supervised Injection Site for laboratory testing. Naloxone and Fentanyl test strips are available for FREE at ACT.

Mixing Uppers and Downers

Mixing uppers and downers is more common and dangerous than we think. However, it is equally important that we remember, dangerous drug interactions can also occur accidentally while taking prescription drugs as well.

Unwanted interactions are common for those who take medications for ADHD, anxiety, depression, and pain management, specifically when mixed with alcohol. Whether intentional or not, dangerous drug interactions can lead to central nervous system (CNS) depression or a slowing of your body’s heart-rate and breathing.

A common myth about mixing uppers and downers is that they cancel each others effects out, when instead, the effect of each substance can be amplified. Uppers can hide our body’s warning signs for the beginning of a drug poisoning, while downers may mask an extremely accelerated heart rate. Combining various drugs, forces the body to process more toxins that are in competition with each other, creating a push-pull effect.

Possible long-term effects of mixing uppers and downers:

  • Strokes
  • Heart and respiratory failure
  • Aneurysms.

Combined immediate effects include:

  • A minimization of symptoms which can cause us to underestimate our level of intoxication and continue to party.

    Amplified adverse effects 

  • “Push-pull” leads to a strain on breathing and blood flow.
  • Severe dehydration, which can be made worse with consumption of alcohol.

 Specifically dangerous upper + downer combinations:

  • Cocaine and Alcohol: As the two drugs interact with each other in the body it creates an interestingly fatal chemical called “cocaethylene”. Which is potentially more poisonous than alcohol or cocaine alone.
  • Potent Opioids (Fentanyl,heroin) and Cocaine/Crack/Methamphetamine (Tina,T,Speed) AKA: “speedball or dynamite”: Potent opioids slow down our body, and cocaine speeds it up, disorienting and confusing the body and limiting its ability to take in enough oxygen to balance out the effects of the cocaine. The high of potent opioids are much longer than the highs of stimulants , this may encourage us to take more than we need.


LSD, peyote, ketamine (k, special k), and mushrooms (psilocybin) are all examples of hallucinogens. However, weed (cannabis) and molly/MDMA (ecstasy) can also display hallucinogenic traits.

Hallucinogenic drugs, like K or shrooms distort our perceptions of reality and provide an exaggerated perception of our senses (hearing, sight, touch, taste, and smell).

Effects will vary from person to person, but there are some common short lasting, undesired effects. These can include; vomiting, dizziness, confusion, increased heart- rate, and emotional peaks and crashes.

Long-term use of hallucinogens can reveal and sometimes lead to various physical and mental health concerns (keeping in mind that many mental health conditions are hereditary). Try keeping a trip journal to document things like; last dose, funny memories, important phone numbers, ideas, affirmations, or even things to help re-ground you on a bad trip.

Uppers and hallucinogens

We don’t know how each drug may interact with us and our friends or partners. Because we are all different, it’s important for us to know the possible undesired effects and how they may appear. Hallucinogens like LSD have similar effects on our bodies as uppers do, one possible undesired effect of mixing the two would be overamping.

Overamping is when our bodies don’t quite feel right, this could be mentally, physically, or both. Overamping is a little trickier than overdosing as it can happen regardless of the amount that we take, or how long we’ve been taking it. Overamping can cause overheating, heart attacks, seizures, and strokes.

Say we were to mix K and coke, the interaction of the two may make us feel as though the coke isn’t working, making us think we can take more. We might link symptoms like; our increased heart rate, or nausea to the K when we may be experiencing signs of overamping. Uppers like coke are known to enhance effects of other drugs in your body, mixing it with hallucinogens may elongate or increase the severity of undesired, and possibly desired effects.

Some common, physical effects of overamping include elevated blood pressure, insomnia, tremors, convulsions, tight chest/ pain, stroke. While overamping, we might also feel; extreme anxiety, panic, hyperaware, suspicious, irritable, we may hallucinate.

Downers and hallucinogens 

Much like uppers, we may get two identical undesired effects when combined, once coming from the downer and the other from the hallucinogen, simultaneously. For example, Xanax or benzos and K, or alcohol, all increase the risk of CNS depression. Centra Nervous System depression can cause us to fall unconscious, for extended and sometimes extended periods of time, these can lead to coma and sometimes death.

Downers tend to blur judgment, impair thinking and motor control.

There is recent evidence-based research surrounding hallucinogens like mushrooms (psylocibin) being used to treat mental health concerns, in micro doses when monitored by a practitioner but there is still a lot of research to be done on the benefits and effects.


Weed is a tricky drug because it can be placed into many different classes. Cannabis’ effects are unique to each of us, making it difficult to tell how it will interact in our bodies, particularly when mixed with other drugs. Weed is a stimulant, depressant, and hallucinogen, some effects may include greening out (overamping), alternatively weed can be used to balance the negative effects of prescription drugs like Adderall. Depending on how our bodies metabolize the THC, will dictate how it interacts with the chemicals in our prescription drugs. This may cause our tolerance, or threshold to become much lower than if we were not taking these prescription medications.

Alcohol and weed can feel very differently for different people. For some it may intensify your high from weed, as alcohol metabolizes THC to higher levels. For others it can cause nausea, fatigue, and vomiting. It is important to try to pace these two substances out with food, to avoid passing out, as they can cause these negative experiences when used together.


Poppers come in various chemical types, but most often are still nitrates. Both nitrates and erectile drugs will cause low blood pressure. Therefore poppers and erectile drugs should NEVER be combined, as this can cause heart failure, which could be fatal. If you have any heart conditions or take any medications for heart or blood-related conditions, the risk of death is heightened.

Poppers + Stimulants

Poppers and uppers such as meth are very common, especially when taken to enhance and prolong sexual pleasure. Poppers and stimulants will typically make your heart and breathing rate go faster, and make you possibly feel even more light-headed than with just poppers alone. This combination is relatively not harmful as long as you do not have pre-existing heart conditions.

HIV treatment, PrEP + Recreational Drugs

There are many different types of treatments for HIV, which helps people living with HIV live long, happy, healthy lives. Some HIV treatments however, are more reactive to other prescription or recreational drugs. Older medications such as protease inhibitors, can cause a person living with HIV who uses recreational drugs to feel a more intense and quicker high or drunkness, even when they have not used as much as they had before. It is important to consult with a medical professional such as a community pharmacist before mixing multiple substances with your treatment.

As with PrEP, there are a plethora of different methods. Most forms of PrEP are not very reactive to substances. Truvada has had some reports of mild reactivity to certain substances such as alcohol, such as making a person feel drunk or high quicker than normal. It is important to consult with a medical professional such as your PrEP provider or community pharmacist before mixing multiple substances with your treatment.

Mental Health treatment +Recreational Drugs

If you are taking medications for depression, anxiety, and other mental health conditions such as SSRI’s, consuming weed at the same time may make your tolerance lower than usual.