smoking ketamine with weed

How Cannabis Interacts With Other Drugs and Medications

Cannabis is an extremely popular substance used for both recreational and therapeutic purposes around the globe. But before you go ahead and mix weed with other substances, read this review of cannabis drug interactions.

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
Drug interactions with hepatic cytochrome 9450 enzymes Citalopram Etoricoxib Fluoxetine
Drug interactions with hepatic cytochrome 9450 enzymes Gabapentin Hydrocortisone Mirtazapine
Drug interactions with hepatic cytochrome 9450 enzymes Naproxen Paroxetine Prednisolone
Drug interactions with hepatic cytochrome 9450 enzymes Pregabalin Sertraline Tofacitinib
Drug interactions with hepatic cytochrome 9450 enzymes Tramadol CARLA CARLA
Drug interactions with hepatic cytochrome 9450 enzymes
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.

Magic Mushrooms

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.

Salvia Divinorum

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 (NOS)

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.

Blood Sugar Medication

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.

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.

Blood Thinners

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.

Wondering how cannabis will affect your experience with other drugs or medications? Click here for a full review of how weed interacts with other substances.

Health Report

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The effect of cannabis and ketamine

By Dr Norman Swan on Health Report

Modern cannabis cultivation is changing the nature of the drug and making it more damaging. And the dangers of ketamine use.


Professor of Psychopharmacology,
University College London,


Norman Swan: Up there with alcohol and cigarettes which are screwing around with young people’s brains and bodies, not to mention many older ones, is cannabis. And fascinating research in London is suggesting that not all forms of marijuana are in fact the same when it comes to affecting the brain in particular. Val Curran is Professor of Psychopharmacology at University College London.

Val Curran: Cannabis is a really, really exciting plant.

Norman Swan: A lot of people think that.

Val Curran: We think it’s exciting because it contains about 70 unique ingredients all called cannabinoids and we’re only just beginning to tease apart the different effects these different cannabinoids might have.

Norman Swan: And are these just members of a similar chemical family?

Val Curran: They are a similar chemical family called cannabinoids but they have different properties from each other. Now the reason that most people smoke cannabis is to get the effects of just one of these ingredients which is called THC, tetrahydrocannabinol, and the other effects haven’t really been studied.

Now what’s happened not only in the UK but in many other parts of the world over the last 10 or 20 years is that people breeding cannabis have done so in a way by growing it hydroponically under intense lights with lots of nutrients.

Norman Swan: And out of the sight of police helicopters?

Val Curran: Maybe, maybe in Australia, and one effect of this has been to maximise the amount of THC in the crop to the expense of all the other 70 cannabinoids. Now we were particularly interested in one of these other cannabinoids called cannabidiol or CBD.

Norman Swan: And just before you go on and some people, particularly in London have suggested that the epidemic almost of psychosis and schizophrenia that you’re seeing in places like Brixton are due to this very strong form of cannabis as they say.

Val Curran: Well I think if you judge that evidence on balance it’s really only one study so I think as yet the jury is out on that one.

Norman Swan: So nonetheless what you’re saying is that there’s a lot of these different compounds, they interact with different receptors in the brain but they’ve been bred out by the dealers?

Val Curran: Well in particular cannabidiol because we have evidence that cannabidiol can offset some of the harmful effects of THC.

Norman Swan: Really?

Val Curran: Yes.

Norman Swan: What’s the evidence?

Val Curran: Well the evidence comes from different sources and it’s very new. It originally came from work by Professor Zuardi in Brazil who suggested that cannabidiol might have special properties that help people calm down and even help them reduce psychosis. He gave it to a few schizophrenic patients and found their psychotic symptoms decreased.

Norman Swan: He was actually using it therapeutically?

Val Curran: Yes as an experimental medicine. So that was very exciting and we decided to look at our own data because we’d done a lot of work with different drugs that induce psychosis like ketaminee and had a big data base. And we basically looked at people’s hair which I know sounds odd but hair’s a bit like the trunk of a tree, when you cut a tree across you can see how old it is, how many diseases it’s had.

Norman Swan: And what happened in 1826.

Val Curran: Absolutely and similarly with your hair, so your hair is about, what 3 cm long, so if we took a sample of your hair we could analyse to see what drugs you were taking over the past 12 weeks. It’s a very objective way of knowing, but not only which drugs, we could probably tell the type of cannabis you’ve been smoking yourself because we could look at the THC contents in your hair as well as the CBD.

So we looked at this in a huge sample of young drug users who have been doing research with us over the years. We compared people who had very high levels of THC in their hair with people who had no THC or any other cannabinoid, people who didn’t use cannabis and then with people, the third group, who had both THC and CBD.

And when we looked at how psychotic those three groups were we found the people with only THC in their hair scored much higher on all psychotic measures than either of the other two groups. If you have CBD as well as THC in your hair you were just like people who had never smoked cannabis.

Norman Swan: That’s amazing. And was there anything about those groups — for example it may be that your source of cannabis means that you live in a certain suburb which has more organic kinds of cannabis rather than hydroponic. I mean is there any of those differences in between the groups and that could mean that could make the difference?

Val Curran: Yes, that’s a really good question. That’s why we had to then go on and look at the cannabis people were actually smoking, so rather than just rely on samples of hair we then wanted to look at the effects of each person’s chosen cannabis. As you say they could buy it in a particular area where it’s more likely to be skunk or something similar than a more natural form, and to look at how their chosen cannabis affects them psychologically; and compare them on cannabis with them when they were sober. And to do this the government thankfully gave us permission to take a sample of the cannabis actually smoked from each person.

Norman Swan: So you were allowed to be in possession as they say?

Val Curran: I know, my children were absolutely delighted, their mother was suddenly able you know to lawfully deal in cannabis. But all we did was take samples from them and deliver it to the forensic science services who analysed the cannabinoid content in the cannabis.

Norman Swan: And have you got any results from that study yet?

Val Curran: This study showed, it’s our first results really, that if you had cannabidiol in your chosen cannabis, you would like pictures of cannabis-related stimuli less when you were stoned and also.

Norman Swan: What does that mean?

Val Curran: Well we know that when people have problems with drugs, controlling their drug taking, things to do with the drug itself such as papers they roll up in or pipes or whatever, the sight of cannabis grabs their attention, whereas it wouldn’t grab someone’s attention who doesn’t use the drug.

Norman Swan: So they are hooked on the visual stimulus as well, it’s part of the whole deal?

Val Curran: Yes, the visual stimulus, the social environment, the smell, all those factors become to be rewarding in themselves and we can measure this by using computer tasks. And what we found is that if your cannabis contained predominately THC without any of the other compounds you were much more likely to have your attention completely grabbed by cannabis related stimuli and also to rate those stimuli much higher in terms of personal liking than other related stimuli — food or neutral stimuli. So the cannabis was taking over all attention compared to anything else and we found that if you had THC only in your cannabis sample that was much more likely to be the case. If you had the CBD it protected against that.

So we’re quite excited now that this is another case in which CBD seems to offset the toxic effects of THC.

Norman Swan: Is there any evidence that certain types of personality or people with depression and anxiety might go hunting for a THC type cannabis and reject the other one without knowing what they’re doing? In other words they are getting stuff from certain types of cannabis that they’re not getting from others and that there’s a self selection process going on here?

Val Curran: That could well be the case, I don’t think we have any evidence as yet but people rarely can or do choose, the problem is at the moment in the UK 83% of all cannabis sold is this high THC variety.

Norman Swan: So you don’t have much choice?

Val Curran: You don’t have much choice and what’s scary is that kids who are starting to use say between 12 and 14 they are trying their first joint, it’s probable that they are experiencing this high THC variety rather than the older fashioned herbal resin varieties.

Norman Swan: And of course it does fixate you more on cannabis the earlier you use the more often you use the higher the risk of things like psychosis?

Val Curran: Oh I think it’s not just psychosis, there’s still a debate about psychosis.

Norman Swan: Oh, you’re not a believer yet?

Val Curran: I’m part of the discussion, let’s say that. But there’s also an issue to do with cannabis dependence. Across the whole of Europe there’s a monitoring centre to look at drug dependence and cannabis dependence which wasn’t an issue years ago when I was a student, we didn’t know people getting hooked on cannabis, but over the last 8 to 10 years cannabis dependence has suddenly gone up and in fact the European Monitoring Service released figures over the last two years consistently showing that the new referrals to substance treatment clinics cannabis is now second only to heroin.

Norman Swan: Really?

Val Curran: Yes, it might be to do also with changing the law whereby if you’re caught with cannabis you’re more likely to be given a drug treatment order.

Norman Swan: These are the diversion programs?

Val Curran: Yes, it could partly have to do with that but we think it’s more likely to be due to the high THC strains of cannabis that young people are now buying.

Norman Swan: And of course this cannabis dependence has been a strong area of research interest in Australia.

Val Curran: Yes, Australia has done lots of very interesting work, people are doing very important work on cannabis.

Norman Swan: Tell me about this work on ketamine, first of all what is ketamine, you hear of ambulance officers using it to relieve pain?

Val Curran: Well ketamine is a very interesting drug that was kind of discovered in the early 60s and used as an anaesthetic in a medical context. It was a good anaesthetic, it’s very good at pain relief, it’s very good at knocking you out. But what started to emerge through the 60s was that when people came round from their anaesthetic they were often having delusions, or hallucinations, in a sense psychotic-like experiences which soon meant it was withdrawn for general anaesthesia use. It’s still used in emergency situations, for example in the war.

Norman Swan: And in Australia it’s used by ambulance officers for major trauma for pain relief.

Val Curran: Yes absolutely, because it’s a very safe drug, it doesn’t suppress your respiration so it’s used in emergency situations. It’s also still used with children who have respiratory problems and it’s very widely used with animals in veterinary medicine.

Norman Swan: So why is it a drug of abuse?

Val Curran: For precisely the same reasons that it was withdrawn from clinical practice as an anaesthetic.

Norman Swan: So it’s used as a hallucinogen?

Val Curran: It’s used as a mood altering drug which does have properties, delusional properties, it makes you feel very, very strange, it has all sorts of effects that young people enjoy and it’s only recently that its use has really increased hugely across Europe.

Norman Swan: And how is it taken, is it injected?

Val Curran: It’s mostly snorted like cocaine, the odd person injects it but by far the greatest way of taking it is through the nose and it’s mostly taken at parties and clubs and most people who take it only take it maybe once a month, or twice a month.

Norman Swan: So it’s literally a party drug. But you’ve been looking at heavier users.

Val Curran: Yes, there’s a small subset of people — and I must emphasise a small subset — who basically have been using daily for years. The typical pattern is they get up about 2 o’clock in the afternoon, they start snorting ketamine, they’ll go on until their supplies are finished and they crash out, do the same the next day. And these people are having severe problems. We’ve worked with people like that for over ten years now and have found that ketamine does affect the brain. There are changes in the brain that we can relate to ketamine use, heavy use.

Norman Swan: This is when you take magnetic resonance images of the brain?

Val Curran: Yes, you put people in a scanner and look at their brains while they are trying to think about things. Then we did find an area of the brain called the dorsolateral prefrontal cortex which was affected in heavy ketamine users. We think that relates also to another fact we found, that these people have very poor working memory functions. So it really impacts especially on students and younger people taking this drug. But for all the various psychological effects of heavy use of ketamine there’s something that’s even more worrying to me, is that in heavy users this drug causes terrible bladder problems. In fact they’ve isolated a phenomenon called ketamine-induced ulcerative cystitis where if you look at scans of people’s bladders they appear cut and very bloody and some neurologists say they look very much like cancerous bladders. And certainly here at UCH and other hospitals around here.

Norman Swan: University College Hospital.

Val Curran: People are having bladders removed because of the damage done to their bladders by ketamine.

Norman Swan: Really, because it’s permanent?

Val Curran: Well there seem to be three types of people that get these terrible bladder problems. About a third of people manage to stop taking ketamine and the bladder problems gradually improve. About a third stop and have continuing cystitis and there’s been no real treatment for that. The other third opt to have bladders removed and they can be cured but it horrifies me to say that a few of the patients who have gone through here and had their bladders removed have then gone on to start ketamine use again.

Norman Swan: A dreadful drug.

Val Curran: Well I think if used in very small doses occasionally as an experimental thing, people don’t seem to be suffering that much but it’s clearly an addictive drug and it clearly has major problems in terms of the bladder and probably the kidneys as well.

Norman Swan: And those cerebral effects, those brain effects you’re talking about, some of them sound quite similar to ice.

Val Curran: To methamphetamine?

Norman Swan: Yes, in terms of memory and so on and brain changes.

Val Curran: I think there probably are similarities, I think with other drugs people have found more changes in areas of the brain like the striatum although probably several areas are affected with methamphetamine.

Norman Swan: And just finally, have you done any work that’s going to an issue that certainly has a lot of interest in Australia and in New York they’ve done a lot of work on this, which is early brain changes from early drug use generically. In other words the notion that when you drink, smoke, use cannabis or what have you in your adolescence, your formative years, you actually change your brain in a semi-permanent way.

Val Curran: Yes, this is a really important question. What we’re doing at the moment with the ketamine data looking at the brains of those ketamine users is we’re trying to relate the changes in the brain to the age at which people started taking ketamine. Because within our sample of people some started as young as 11, you hear that among that age group it’s called kiddy smack, heroin for young people, so we’re just going to see — because that’s the greatest worry clearly, your brain goes on developing to your early 20s so if you are starting the use of a drug, alcohol, ketamine or whatever when you’re 11 or 12 then it could have a much more profound effect on you than starting in your 20s.

Norman Swan: Val Curran is Professor of Psychopharmacology at University College London.

Muetzelfeldt L et al. Journey through the K-hole: phenomenological aspects of ketamine use. Drug and Alcohol Dependence 2008;95(3):219-229

Modern cannabis cultivation is changing the nature of the drug and making it more damaging. And the dangers of ketamine use.