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Like Mixing Cannabis With Other Substances? Here Are the Pitfalls of Polysubstance Use

Lemetria Whitehurst

by Lemetria Whitehurst

February 6, 2023 08:00 am ET Estimated Read Time: 8 Minutes
Like Mixing Cannabis With Other Substances? Here Are the Pitfalls of Polysubstance Use

Mixing cannabis with recreational drugs, medications, or alcohol can be a rollercoaster ride for your mind and body. While it may seem like an exciting idea to indulge in some extra fun, the pursuit of pleasure could come with undesired risks down the line. 

With a unique mix of over 550 chemical compounds and 100 cannabinoids, cannabis is truly a medicinal powerhouse. Depending on what you’re mixing, the results could go from being relatively mild to downright dangerous. 

In this article, we’ll explore the fascinating world of cannabis and its interactions with the four major drug classes: 

And, of course, no discussion would be complete without addressing something more unconventional—exploring what happens when marijuana meets psychedelics like
psilocybin or ketamine. Here’s what science has to say about how cannabis interacts with other drugs.

A Brief Review of Combining Cannabis With Other Substances

When it comes to cannabis, our endocannabinoid system (ECS) ensures that we are uniquely responsive and open to the effects of this incredible plant—so much so that its interactions with a vast range of substances can be far-reaching. 

According to research published in Therapeutic Advances In Psychopharmacology, cannabis presents a unique dilemma due to its rich chemical diversity. Unlike LSD, MDMA, or psilocybin, which are single compounds, cannabis contains a variety of lesser-known cannabinoids that are not fully understood. 

Do Stimulants Interact With Cannabis?

Stimulants offer a brief escape from reality, often providing users with an intense rush of energy and positive feelings. Stimulants work on neurotransmitters in the brain to increase focus and wakefulness. However, while they may have short-term positive effects, stimulants can ultimately harm our central nervous system by increasing neurotransmitter activity, leading to elevated heart rate and blood pressure levels, which can cause paranoia and anxiety.

The most common stimulants are:

  • Cocaine
  • Methamphetamine
  • Caffeine
  • Nicotine
  • Ritalin 
  • Adderall 
  • Concerta

Since everyone reacts differently to different drugs, it is hard to predict the general effects of combining stimulants and cannabis. While these drugs tend to help boost alertness and concentration, these same qualities can potentially intensify when mixed with cannabis. 

Ultimately, the outcome of mixing cannabis and stimulants depends heavily on the amount of each substance taken and how an individual responds to them. The ECS interacts with both substances, so it shouldn’t be surprising that they have similar effects, with too much of either leading to increased heart rate and racing thoughts. 

Interestingly, many people with ADHD report successfully self-treating their condition exclusively with cannabis, while others find more success by combining multiple medications, lifestyle changes, and cannabis. 

Despite potential therapeutic benefits, combining THC with stimulants can lead to dangerous side effects. A 2015 study presented by the Journal Of Substance Abuse Treatment revealed that THC and methylphenidate place undue strain on the cardiovascular system. Whatever the case, you should always consult your doctor or pharmacist before combining cannabis and stimulants. 

Combining Cannabis With Depressants

Depressants deliver a tranquil respite from everyday stress, though high doses can quickly turn this relaxation into disorientation and drowsiness. But embarking too far down this path can lead you astray, negatively affecting coordination or concentration.

There are several common depressants, which include:

  • Valium (diazepam)
  • Xanax (alprazolam)
  • Halcion (triazolam)
  • Klonopin (clonazepam)
  • Alcohol
  • Kava

Our brain is like a finely-tuned vehicle, with neurotransmitters acting as the fuel that powers us.
The gamma-aminobutyric acid (GABA) system is an essential piece of the neurological puzzle. It’s like having a brake pedal in the brain that brings it all to a slow, steady and relaxed state when deployed—which depressants frequently do at higher doses. THC acts in much the same way at larger doses causing users an extreme case of sedation if consumed with another depressant.

In contrast, combining CBD with depressants appears to have another interaction. An alarming 2019 article documented that, when taken together with the class of depressants called benzodiazepines, CBD can lead to a heightened risk of adverse effects such as drowsiness and confusion.

Due to its pharmacokinetic ability to prevent the effective breakdown of the drug in the liver, depressants remain elevated in the blood, posing potential health risks. 

Additionally, combining THC with alcohol can create an unpredictable experience. With just a single cocktail or beer accompanying your cannabis experience, the effects are more powerful than either substance on their own—significantly heightening psychoactivity. 

Why You Should Get Your Medical Marijuana Card

Veriheal has satisfied millions of patients nationwide by giving them access to these benefits

  • Larger purchase limits
  • Peace of mind
  • Enhanced legal protection
  • Access to higher potency strains
  • Save up to 25% on cannabis purchases
  • Skip the line at the dispensary

While this combination may be enticingly enjoyable in moderation, research shows mixing these two substances often lead to traffic accidents at higher rates than if consumed separately.

In addition, it is also pertinent to be aware that high blood concentrations of depressants will also cause respiratory depression, or ineffectively slow breathing, therefore, use caution if adding CBD to the mix. In contrast, consuming CBD with alcohol does not appear to be associated with decreased respiration.

Could Cannabis Be a Viable Alternative to Opioids?

Opioids are potent substances capable of altering the body’s perception and experience of acute pain. They work by manipulating the body’s natural opioid receptors to increase its threshold of discomfort and desensitize nerve endings. In essence, these highly effective painkillers work by tricking the brain into feeling less distress. 

There are several common opioids, including:

  • Vicodin (hydrocodone)
  • Oxycontin (oxycodone)
  • Morphine
  • Ultram (tramadol)
  • Methadone
  • Codeine

With the opioid epidemic continuing to ravage our nation, scientists are inspired by cannabis research that shows it as a
potential alternative pain management solution. The ECS and opioid pathways work in harmony as if part of one extended relief network within everyone. 

With cannabis and opioids, users should exercise caution as with any other medication. Nevertheless, don’t be too alarmed, as a 2019 rhesus monkey study published in Behavioural Pharmacology concluded that THC and opioids don’t impair memory or decision-making. 

As a result, there is hope that cannabis will play an increasingly important role in today’s healthcare landscape, with evidence that this natural remedy can reduce overdose and addiction dangers associated with prescription medications.

Cannabis May Enhance Psychedelic Experiences

Hallucinogens are an intriguing class of psychedelic substances that induce surreal transformations in how we perceive, feel, and think. These compounds produce an array of mind-altering effects through a single pathway, activating serotonin (5-HT2A) receptors. Although the effects of cannabis on most major drug classes are widely understood, adding hallucinogens into the equation remains a mystery—a fascinating unknown yet to be fully explored.

Psychedelics include the following:

  • Psilocybin (the active ingredient in magic mushrooms)
  • MDMA
  • DMT
  • LSD
  • Mescaline 
  • Ketamine
  • Salvia
  • Dextromethorphan (present in cough medications like Dimetapp and Mucinex)

Psychedelics activate the serotonin system, which connects directly to the ECS. In some cases, the combination enhances psychoactivity, but it can also mellow out the tripping experience in others. Nevertheless, it is possible to become overwhelmed by the use of either substance if you use too much.

High doses of THC can mimic the effects of hallucinogens, as experts point out that cannabis and psychedelics have many parallels. But it’s ultimately as varied an experience as those who consume them, with dose and individual tolerance determining how these two altered states intertwine.

Although data on mixing hallucinogens and cannabis is scarce, years of anecdotal experience have shown no apparent adverse effects. In fact, recent research indicates that pairing psychedelics with low doses of cannabis can dramatically heighten mystical experiences associated with the psychedelic journey. On the other hand, higher doses might increase undesirable sensations like fear or what was referred to as “insanity” in the study. 

Do Prescription Medications Interact With Cannabis?

Simply put, yes! Cannabis can also interact with other medications and compounds besides the substances listed above.

THC does not significantly affect prescription medications. In contrast, CBD has a unique interaction with certain medications, blocking the metabolic pathway used by drugs such as:

  • Blood thinners like warfarin and clopidogrel
  • Heart medicines like amiodarone
  • Transplant immunosuppressants like Tacrolimus
  • Antihistamines like Claritin and Benadryl

Similar to how components of grapefruit or St. John’s Wort tend to react with pharmaceuticals, CBD could inhibit the breakdown of these medications, resulting in them circulating longer than usual. To ensure your safety and well-being, always consult your doctor before using cannabis or CBD with other medicines.

A Few Tips For Avoiding Cannabis Drug Interactions

When combining psychoactive substances, it’s essential to exercise caution and proceed with a controlled approach. A great way of doing this is by taking small steps by microdosing. For example, take no more than two puffs every 15 minutes when combining cannabis with other substances. This way, you can enjoy the experience while remaining in control of your responses afterward.

Additionally, potent cannabis edibles can make for an intense experience. Therefore, it’s a great idea to be mindful of dosage. Delays in digestion mean the effects may take a while before they truly hit—and when the euphoria does knock on your door, you won’t be able to reverse the high until it wears off. Keep a watchful eye if you want to avoid being overwhelmed by marijuana’s potent power, and above all, consult your doctor or pharmacist before mixing things up.

Note: The content on this page is for informational purposes only and is not intended to be professional medical advice. Do not attempt to self-diagnose or prescribe treatment based on the information provided. Always consult a physician before making any decision on the treatment of a medical condition.

Post Your Comments

M.F. Laboo says:

February 7, 2023 at 9:40 am

Thank you for a very informative summary. One small point. Near the beginning of the article it lists psilocybin, MDMA and LSD as examples of single compounds as compared to cannabis with its spectrum of ingredients. In fact, pure extracted or synthesized psilocybin is rarely seen in the wild — and the raw mushrooms contain a mixture of indoles, etc., just as cannabis has various cannabinoids and terpenes. Later in the article, psilocybin is accurately described as the “active ingredient” in magic mushrooms. We could also flip the script and say that highly refined cannabis extracts are, for all practical purposes, single compounds. I personally avoid mixing cannabis with other street or prescription drugs, but agree with the author’s statement that prudent use of cannabis in conjunction with psychedelics (after the peak) can enhance the experience.

Michael Zimmerman says:

February 8, 2023 at 11:44 am

I have Parkinson’s Frozen Gate!! Is there anything that I can do or get information that I can take for this I currently am A pot smoker any help be much appreciated?? I’m thinking smoking weed would affect all of my neurotransmitters in the brain?? Thanks


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