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Cannabis vs. OTC Medications: Acetaminophen, AKA Tylenol

Cannabis vs Medication

Many Americans use painkillers to manage chronic pain. While prescription medications can be very useful, their addictive qualities can lead to problems. Some users try to self-medicate with alcohol and other painkillers, but there is another alternative with a generally well-established safety profile.

Cannabis can be an effective painkiller and may be used to reduce dependency on addictive, opioid-based painkillers, but what about some everyday medications like acetaminophen (aka Tylenol)?

The media often discusses cannabis’s potential to replace the need for long-term painkiller use and many other prescription medications, like benzodiazepines (e.g., Valium, Xanax, Ativan, Klonopin) and barbiturates (e.g., Amytal, Butisol, Nembutal). There’s also the possibility that, for some people, it may replace or reduce the ingestion of alcohol and other recreational substances.

However, few people have discussed cannabis’s potential to replace even the more benign, over-the-counter (OTC) drugs like ibuprofen and acetaminophen. So, could getting an MMJ card help you reduce your intake of OTC drugs?

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What is Acetaminophen, aka Tylenol, Used For?

Tylenol, in which the active ingredient is acetaminophen, is perhaps one of the most commonly used drugs in the world. Acetaminophen is usually used to reduce fever and relieve mild-to-moderate pain arising from osteoarthritis, back pain, headaches, postoperative pain, dental pain, and many other kinds of acute or chronic pain.

How It Works

Tylenol may work for some kinds of mild-to-moderate pain because it inhibits the enzyme that breaks down anandamide (our bodies’ “bliss” molecule), meaning that there is more of this pain-relieving bliss molecule in our blood. This means that Tylenol works on cannabinoid receptors, and this could be one of how it alleviates pain.

Compared to THC, Tylenol is not as psychoactive. Tylenol is thought to relieve inflammatory pain through CB1 receptors. It may also prevent the release of inflammatory lipids (called prostaglandins), which reduces pain and body temperature.

Beyond this, scientists and doctors do not know the precise mechanism of how Tylenol works, although this relatively recent discovery of interaction with cannabinoid receptors gives us one big clue!


The efficacy of Tylenol is very much up for debate. The US National Library of Medicine from the National Institutes of Health found:

“Paracetamol [Tylenol] is ineffective in the treatment of low back pain and provides minimal short term benefit for people with osteoarthritis. These results support the reconsideration of recommendations to use paracetamol for patients with low back pain and osteoarthritis of the hip or knee in clinical practice guidelines.”

These findings are verified by studies conducted around the globe. A review by Cochrane UK also comes to a similar conclusion:

“We found high-quality evidence that paracetamol (4 g per day) is no better than placebo for relieving acute LBP [lower back pain] in either the short or longer term. It also worked no better than placebo on the other aspects studied, such as quality of life and sleep quality. About one in five people reported side effects, though few were serious, and there was no difference between intervention and control groups.”

There are times when Tylenol can be useful, such as for fevers and different kinds of pain, such as migraines and tension headaches. So, it seems that acetaminophen is useful for some health problems and injuries, but not all of them. Some of its benefits could come from the placebo effect.

Side Effects and Risks

So, how dangerous is acetaminophen overall, and how many does it kill every year? First, it must be remembered that being ineffective and being dangerous and two very different things. However, adding a medication that is not necessarily needed can complicate matters and change the safety profile of a drug. Two pieces from ProPublica, “Only Use as Directed” and “Behind the Numbers,” also paint an interesting picture, as they draw their conclusions from several major studies from different organizations.

“Data obtained from the U.S. Centers for Disease Control and Prevention show that more than 300 people die annually as a result of acetaminophen poisoning…Beginning in 2006, according to the CDC, the number of people who died after accidentally taking too much acetaminophen surpassed the number who died from intentionally overdosing to commit suicide.

…The American Association of Poison Control Centers (AAPCC), a nonprofit that receives federal funds, shows about 113 people dying each year as a result of overdosing on medicines with acetaminophen. Since 2006, acetaminophen has accounted for more fatalities than all other over-the-counter pain relievers combined, according to AAPCC data.”

Acetaminophen is not necessarily dangerous in small doses. However, in large doses or taken consistently over longer periods, it can cause fatal liver damage and, in some cases, kidney damage. Skin reactions like Stevens-Johnson syndrome are rare, but still possible. There are also some potential links between asthma and paracetamol use. Many experts claim that doses of up to 4,000 mg of acetaminophen a day are relatively safe for most people.

As for how many people die per year due to Tylenol (acetaminophen) poisoning, the number is around 113, but some numbers show around 300. Acetaminophen is often combined with opioid-based drugs for its synergistic effects (i.e. adding acetaminophen to opioids makes the opioids stronger), so some of the numbers may crossover into deaths associated with other drugs.

Mixing Acetaminophen with Other Medications

There are wide discrepancies between the numbers because the FDA doesn’t necessarily demonstrate a causal relationship between a person’s death and a particular drug, just an association. The other problem is that paracetamol is such a commonly-used drug that is often used in combination with other medications to strengthen their effects (e.g., ibuprofen and acetaminophen, Vicodin [acetaminophen and hydrocodone] and Co-Codamol [codeine and paracetamol]).

Mixing Tylenol with Alcohol

Acetaminophen can be quite dangerous when taken in combination with alcohol, which can increase the chances of liver failure. This means that if acetaminophen was the cause of death (or at least a contributor), it is often “hidden” by other factors. Therefore, the number of deaths via acetaminophen could be higher than expected.

So, is the relatively benign acetaminophen/paracetamol/Tylenol dangerous? Not extremely, but it’s not completely safe, either, especially when it’s taken with other drugs or alcohol. Of course, another problem is that a person may take a weak opioid, then take Tylenol at some point, and have much stronger effects than expected. Perhaps the real kicker is that paracetamol/Tylenol/acetaminophen may not even be that effective for many people with pain.

This leads to an ethical question for many doctors, as they can reasonably ask themselves, “Why should I prescribe this, when it won’t work for most people and could end up becoming dangerous?” It’s certainly a fine balancing act; individuals can respond very differently to the same drug at the same dosage, and healthcare professionals are often mindful of this factor. Excessive acetaminophen/Tylenol dosing is also common in hospitals, perhaps due to the relatively beningn nature of acetaminophen in healthcare settings.

Mixing Medical Cannabis with Other Medications

We don’t precisely know all the different cross-reactions between medical marijuana and other drugs due to the lack of research, but we can safely say there likely will be. Cannabis, although it can be used to wean and taper a person off of opioids, may well have negative reactions with painkillers like propoxyphene (found in Darvocet, Darvon), buprenorphine (Butrans, Buprenex), buprenorphine (Subutex), and naloxone (Suboxone, which also contains buprenorphine).

Cannabis also has negative interactions with alcohol, benzodiazepines like Clobazam  – often used for epilepsy – and may have a drug-drug interaction. CBD and benzos are both metabolized by the same liver enzyme (cytochrome P450) and barbiturates, which may interact with THC (but not necessarily CBD). The reason why cannabis may have a negative interaction with these other drugs is that they are all central nervous system (CNS) depressants, and cannabis may potentiate this effect.

Many doctors and pharmacists may also recommend patients avoid other drugs that affect cytochrome enzymes in the body. Patients who cannot metabolize CYP2C9 properly may want to be careful with amiodarone, cimetidine, and fluoxetine, as the body may inhibit THC elimination. Meanwhile, rifampin, which is a CYP3A4 inducer, may reduce THC levels.

As for cannabidiol (CBD), which is a substrate of CYP3A4 and CYP2C19, may also be inhibited by rifampin, with CBD levels in the blood reduced by 50% or more when ingested alongside CBD. Both tetrahydrocannabinol (THC) and CBD may have limited ability to inhibit the activity of CYP450 enzymes, although this is more often associated with CBD than THC.

Interestingly enough, smoked marijuana (as opposed to oral administration) has been shown to increase the metabolism of theophylline and chlorpromazine. This suggests that cannabis could have applicactions in chronic obstructive pulmonary disease (COPD), asthma, and psychosis. Counterintuitively, this means that, despite all the potential harms smoking burning carbon matter of any kind can do, some people may find more benefit in smoking cannabis (please note that this is a theory only).

Can I Overdose on Marijuana?

Overall, we can safely assume that smoking any substance is going to be bad for most people’s health. As acetaminophen is usually orally administered, it could be considered safer than smoking cannabis in this regard. However, acetaminophen use, even when used on its own, has caused overdoses and killed people. On the other hand, no one has died via overdose on cannabis alone.

Furthermore, there are other methods of delivery to avoid the negative effects of smoking marijuana. Many popular forms of ingestion include edibles, oils, and tinctures. Cannabis can even be applied topically as lotion or oil to provide relief for aching joints, sore muscles, and muscle spasms.

Acetaminophen vs. Medical Marijuana for Mental Health

When it comes to the chances of overdose and death, cannabis is safer than acetaminophen for relieving physical aches and pains. But what about other concerns, like mental health?

Acetaminophen and its Effect on Mental Health

Some people have claimed paracetamol may be useful for emotional pain, but no studies have proven this true. There are also some case studies associated with acute psychosis, codeine, and acetaminophen, but there isn’t anything definitive. Other studies have even suggested that over-the-counter painkillers may impair the brain’s ability to detect errors. Overall, there doesn’t seem to be any significant relationship between acetaminophen and mental health issues, but this isn’t an area that’s been researched very much.

Medical Marijuana for Mental Health

Cannabis and mental health, on the other hand, has an interesting relationship. Although there is no definitive evidence that cannabis is a cause of mental health issues for anyone, it doesn’t mean that it might not be a confounding factor for certain types of mental illness. Those who suffer from or have a family history of schizophrenia, for example, may want to avoid THC (although CBD may be an antipsychotic and can help those with schizophrenia). Similarly, for those with bipolar disorder, THC should ideally be avoided, especially during any manic phases.

Age may be a factor in the relationship between medical cannabis and mental health as well, as early, non-medical cannabis use by adolescents may cause some sort of neurological decline. However, for older people with fully-developed brains, cannabinoids may promote neurogenesis and antidepressant-like effects. Cannabis and its benefits and problems with a mental health need to be researched further.

Is Medical Marijuana Safer Than Paracetamol?

In terms of the potential of getting a fatal overdose, yes, medical marijuana is has a better safety profile. Using a cupboard full of cannabis on its own won’t kill you, whereas a cabinet full of Tylenol and other acetaminophen-containing products could if taken in sufficient amounts.

On the other hand, using cannabis (and THC in particular) and operating heavy machinery is not recommended. This is not usually a problem when it comes to paracetamol, which does not normally affect day-to-day activities due to its lack of psychoactivity.

More research needs to be conducted on mental health to come to a definitive conclusion. For children, it seems that acetaminophen could be preferable to higher doses of THC due to its psychoactivity. Still, for adults suffering from body aches, medical marijuana might have some uses.

Another issue is at play here: “Are we making a fair and equal comparison?” We’re judging one drug, acetaminophen, with all the various moving parts and cannabinoids that make up the cannabis plant. Some cannabinoids could be safer than others on their own. For example, THC used alone is very uncomfortable for many people. On the other hand, the entourage effect could well be providing a buffer against some of the more harmful aspects of cannabinoids taken by themselves. Perhaps we should be asking, “Is CBD safer than paracetamol? What about THC, cannabigerol (CBG), cannabichromene (CBC), and so on?”

Comparing one, highly purified, manufactured drug with a medicine that hasn’t been purified and has several different cannabinoids, terpenoids, and flavonoids doesn’t necessarily seem fair. Rather, we ought to start looking at cannabis’s efficacy vs. other drugs and medications, both when cannabinoids and terpenoids are working together and working separately. This is the only way we’re going to get a true grasp of cannabis’s safety and efficacy profile, and where it is harmful and helpful.

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