Keep reading for our in-depth guide on cannabis drug interactions.
Cannabis is a complex plant that, due to decades of prohibition, we still don’t completely understand. What we do know, however, is that cannabis’ unique chemical compounds can interact with other substances (both recreational and medical), and interrupt the way our bodies process different compounds.
If you’re thinking about mixing cannabis with other recreational substances or prescription medication, keep reading for a detailed overview of how cannabis interacts with other drugs.
Understanding Drug Interactions
A drug interaction is an interaction between a drug (prescription medicine or a recreational substance—legal or illicit) and any other drug, food, or drink. These interactions can alter the way one or more of the drugs taken together work, affecting their efficacy in turn.
When you take two or more substances together, a few different outcomes can occur:
- Additive effect: This means each substance produces the effect it is intended to produce independently. Thus, when combined, the effects of both substances are “added” to each other, rather than synergising.
- Synergistic effect: This is when substances combine to produce a greater effect than they would when taken separately.
- Antagonistic effect: This means one or more of the substances taken together become less effective than if they were taken on their own.
Drug interactions occur via numerous mechanisms, including:
- Increasing or decreasing drug absorption in the digestive tract
- Altering drug metabolism in the liver
- Increasing or decreasing the rate at which the body excretes drugs via the kidneys
- By triggering competing actions in the body
A few factors can affect how at-risk you are of experiencing a drug interaction:
- Being dehydrated
- Being very young or very old
- Being over- or underweight
- Having an underlying medical condition
- Taking multiple medications at a time
- Having poor nutrition
| Drug interactions with hepatic cytochrome 9450 enzymes | CBD | Amitriptyle | Celecoxib | |
|---|
| CYP2D6 |
X |
X |
|
| CYP2C19 |
X |
X |
|
| CYP3A4 |
| CYP1A2 |
X |
X |
X |
| CYP2C9 |
X |
X |
|
| CYP3A |
X |
|
X |
| Drug interactions with hepatic cytochrome 9450 enzymes | Citalopram | Etoricoxib | Fluoxetine | |
|---|
| CYP2D6 |
X |
|
X |
| CYP2C19 |
X |
|
|
| CYP3A4 |
| CYP1A2 |
X |
X |
|
| CYP2C9 |
|
|
X |
| CYP3A |
|
X |
|
| Drug interactions with hepatic cytochrome 9450 enzymes | Gabapentin | Hydrocortisone | Mirtazapine | |
|---|
| CYP2D6 |
X |
|
X |
| CYP2C19 |
X |
|
|
| CYP3A4 |
| CYP1A2 |
X |
|
X |
| CYP2C9 |
X |
|
X |
| CYP3A |
|
X |
|
| Drug interactions with hepatic cytochrome 9450 enzymes | Naproxen | Paroxetine | Prednisolone | |
|---|
| CYP2D6 |
|
X |
|
| CYP2C19 |
|
|
|
| CYP3A4 |
|
|
|
| CYP1A2 |
|
|
|
| CYP2C9 |
X |
|
|
| CYP3A |
|
|
X |
| Drug interactions with hepatic cytochrome 9450 enzymes | Pregabalin | Sertraline | Tofacitinib | |
|---|
| CYP2D6 |
X |
|
|
| CYP2C19 |
X |
|
X |
| CYP3A4 |
| CYP1A2 |
X |
X |
X |
| CYP2C9 |
X |
|
|
| CYP3A |
|
|
|
| Drug interactions with hepatic cytochrome 9450 enzymes | Tramadol | CARLA | CARLA | |
|---|
| CYP2D6 |
X |
| CYP2C19 |
|
| CYP3A4 |
| CYP1A2 |
|
| CYP2C9 |
|
| CYP3A |
|
|
Drug interactions with hepatic cytochrome 9450 enzymes |
|
CYP2D6 |
CYP2C19 |
CYP3A4 |
CYP1A2 |
CYP2C9 |
CYP3A |
| CBD |
X |
X |
X |
X |
X |
X |
| Amitriptyline |
X |
X |
X |
X |
X |
|
| Celecoxib |
|
|
X |
|
X |
|
| Etoricoxib |
|
|
X |
|
X |
|
| Fluoxetine |
X |
|
|
|
X |
|
| Gabapentin |
X |
X |
X |
X |
X |
|
| Hydrocortisone |
|
|
|
|
|
X |
| Mirtazapine |
X |
|
X |
X |
|
|
| Naproxen |
|
|
|
|
X |
|
| Paroxetine |
X |
|
|
|
|
|
| Prednisolone |
|
|
|
|
|
X |
| Pregabalin |
X |
X |
X |
X |
X |
|
| Sertraline |
|
|
X |
|
|
|
| Tofacitinib |
|
X |
X |
|
|
|
| Tramadol |
X |
|
|
|
|
|
| Citalopram |
X |
X |
X |
|
|
|
How Cannabis Is Broken Down by the Body
Cannabis contains over 100 different cannabinoid compounds, but the ones we know the most about are THC and CBD. Research shows that both compounds are metabolised by cytochrome p450, a group of enzymes responsible for metabolising a large number of compounds, particularly those found in prescription medications.
When THC and CBD are present in our bodies, they compete for oxidation by cytochrome p450, which often slows down the metabolism of other compounds found in recreational drugs (like LSD, amphetamines, and alcohol, among others) and prescription medications. Make sure to keep that in mind whenever you’re thinking of combining cannabis with other substances.
What Makes Cannabis Unique to Other Drugs?
Cannabis is unique to many other drugs (both recreational substances and prescription medications) in numerous ways:
- Chemical composition: Cannabis doesn’t contain just one single active ingredient. While THC is by far the most recognised component in cannabis, the plant contains over 400 different compounds of note, including other cannabinoids, terpenes, and more.
- Variety: Cannabis strains vary dramatically. Even strains of the same name can have very different chemical profiles and potencies, and therefore produce very different effects.
- Personal experience: Cannabis affects different people in different ways, and some people may be more tolerant of its effects than others.
- Effects: Cannabis doesn’t fit neatly into the categories we use to classify other substances. While it can definitely be a “downer” (or depressant), it can also produce uplifting effects similar to those produced by stimulants or “uppers”. At the same time, cannabis can produce some of the effects typically associated with hallucinogens (such as a warped perception of time).
Understanding the unique nature of cannabis and, more importantly, the way it affects us personally, can be very useful in helping us decide when, where, and how to use the herb. If you find cannabis often has a relaxing, sedative-like effect on you, make sure to keep that in mind when mixing it with other substances that have the same or opposite effect.
How Does Cannabis Interact With Other Recreational Drugs?
Cannabis is one of the most commonly used recreational drugs on the planet, even in areas where it remains criminalised. Here’s how it reacts with other recreational drugs.
Alcohol is arguably the most popular recreational drug on the planet. And, while you can legally buy almost unlimited amounts of alcohol almost anywhere in the world, it's far from safe, especially when you compare it to other substances.
There’s limited scientific research on the effects of mixing alcohol and cannabis. One study[1] suggests that drinking alcohol prior to consuming cannabis can increase absorption of THC in the body. Elevated levels of THC in the body will not lead to fatality, but it can cause sweating, dizziness, nausea, and vomiting.
Cannabis is often used in conjunction with amphetamines and derivatives like MDMA. Anecdotal evidence suggests cannabis may attenuate some of the negative symptoms of the amphetamine comedown.
Few scientific studies have actually looked at the interaction between cannabis and amphetamines. However, animal studies[2] suggest that the endocannabinoid system may play a role in addiction, and therefore affect the addictive properties of amphetamines. However, it’s also important to remember that amphetamines are stimulant drugs, and cannabis can produce depressant, stimulant, and even hallucinogenic effects, complicating the interaction between the two drugs.
Cocaine is a potent stimulant, and the way it interacts with cannabis can be difficult to pin down. When it acts as a depressant, cannabis might offset the cocaine high, and possibly offset some of the cravings and negative side effects of a cocaine comedown. However, mixing the stimulative effects of cocaine with the depressant effects of cannabis may exacerbate some of the negative side effects of either drug.
Cannabis can also block[3] cocaine-induced blood vessel constriction, which increases absorption of cocaine in the body, resulting in a faster onset, longer-lasting cocaine rush, and an increased risk of side effects and overdose. When it acts as a stimulant, cannabis might exacerbate some of the effects of cocaine. Because both drugs are capable of inducing anxiety and paranoia on their own, combining the two can increase the possibility of those effects taking hold.
Codeine is an opioid drug that depresses the central nervous system. When combined with cannabis, the two substances can produce a very sedative and euphoric buzz. And while cannabis isn’t technically classified as a depressant, it can act like one, and therefore have a synergistic effect on codeine and other depressants. Studies[4] have also shown that using codeine with cannabis can cause anxiety and depression.
DMT is a psychedelic drug that’s typically smoked, or consumed with monoamine oxidase inhibitors to create the ayahuasca brew. There are no formal studies showing how cannabis interacts with DMT, but users often find the two to have a synergistic effect.
Some say, for example, that smoking cannabis before using DMT helps them relax both into and out of the trip. These accounts are similar to those from users of other psychedelics, such as LSD and magic mushrooms. Some "psychonauts" find cannabis to help reduce the nausea associated with hallucinogens, while others say it catalyses an upset stomach.
Ketamine is a medical-grade anesthetic that can be swallowed, snorted, injected, or smoked, often together with cannabis or tobacco. Again, there are no studies into how ketamine and cannabis interact, but users tend to report that cannabis increases the ketamine high and can, in some instances, exacerbate effects like drowsiness and dizziness.
Mixing LSD and cannabis tends to produce a synergistic effect. Many people find that cannabis enhances the visual hallucinations of an acid trip, or even re-triggers them. In fact, it's common to smoke a joint towards the end of an acid trip in hopes of "bringing back" some of the visuals. LSD users often smoke cannabis on the come-up as well, in part to reduce the jitters and nausea associated with the early stages of a trip.
Like with LSD, cannabis tends to have a synergistic relationship with psilocybin mushrooms. Experienced psychedelics users find that combining weed and magic mushrooms has positive effects; cannabis can help people relax into their trip, reduce some of the nausea associated with taking mushrooms, and enhance some of their psychedelic hallucinations. Keep in mind that the synergistic effects of mixing these two substances can be overwhelming for those new to mushrooms.
Like the other psychedelics mentioned above, cannabis and salvia tend to be synergistic. If you’re looking to intensify some aspects of your salvia trip, adding cannabis to the mix might help you get there. If you’re new to salvia, however, you may find the experience a bit overwhelming. On its own, salvia can be described as extremely intense (depending on intake method), causing extreme acute dissociation in some cases.
Laughing gas, or nitrous oxide, is used as a sedative to provide pain relief and produce a calm, giggly euphoria. Cannabis tends to increase the effects of laughing gas, and some people find taking the two can produce profound sedative effects (especially when taking high doses of the latter), similar to those produced by ketamine.
How Does Cannabis Interact With Prescription Drugs?
As mentioned, studies show that THC and CBD are metabolised[5] by cytochrome p450 enzymes. A subset of these enzymes, known as the CYP3A family, is responsible for metabolising up to 60% of all drugs in use[6]. If you’re taking medication, keep reading to see how cannabis might interact.
One of the most common blood sugar medications on the market today is metformin, which is prescribed to diabetes patients. THC is thought to decrease the effectiveness of this medication, yet cannabinoids are also believed to have potential benefits[7] related to diabetes treatment, including stabilising blood sugar levels.
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Blood Pressure Medication
Both THC and CBD have been studied[8] to some extent for their impact on blood pressure. Healthy individuals tend to experience increased heart rate and lowered blood pressure when taking THC. However, many people also experience postural hypotension (a sudden, unpleasant drop in blood pressure when standing up that can cause vertigo, fainting, and nausea) under the influence of THC. CBD-rich cannabis products have also been shown to reduce blood pressure, but in a more steady (and potentially desirable) way.
Research suggests that cannabinoids have a synergistic relationship with blood thinners. This may be because cannabis inhibits the metabolism of these drugs, but more research is needed to properly understand how the two interact.
Cannabis and opioids don’t seem to interact in a direct fashion, potentially because the compounds within are processed via different systems (the endocannabinoid system and the opioid system, respectively). However, some of the compounds in cannabis have analgesic effects that may complement the effects of opioids used for pain relief. Intriguingly, there is growing clinical evidence[9] to support the use of cannabis as a novel strategy to prevent opioid abuse and fatalities.
Studies suggest that cannabis has an antagonistic interaction with sedative medications. While everyone experiences cannabis differently, some strains definitely have sedative effects, which may make patients more tolerant of sedative medications. Research[10] from The Journal of the American Osteopathic Association shows that patients who regularly used cannabis needed significantly higher sedative doses prior to an endoscopy than patients who didn’t use cannabis.
There are many different antidepressants on the market, each of which have different effects. In terms of how cannabis interacts with different antidepressants, some people find the herb to produce mood-boosting effects, while others experience exacerbated depression and anxiety symptoms.
Mixing Cannabis With Other Drugs — The Bottom Line
Unfortunately, there’s still a whole lot we don’t know about cannabis and the way it affects our bodies—even when taken alone. Hence, we always recommend enjoying it by itself rather than mixing it with other drugs. Hopefully, as more time and energy goes into understanding cannabis, we’ll have a lot more clarity about how to best use this amazing plant.
Disclaimer:
This content is for educational purposes only. The information provided is derived from research gathered from external sources.
