Why do different ingestion methods have different effects?

Cannabis can produce different effects depending on how you ingest it. The ingestion method you choose can determine the onset, the intensity and the duration of any psychoactive effects. As a result, you should choose the ingestion method best suited for your wellness goals.

Jointly has published some early data looking at which product types may be well-suited for which wellness goals. To see what we found, head over to Product Type Report: Volume 1.

When choosing your ingestion method, you should have an idea of how much cannabinoid will be incorporated into your body, how long before you feel the effects, and how long the effects are going to last. Of course, everybody is different. The best way to determine how an ingestion method affects you is to try it and record your experience with Jointly.

Different cannabis ingestion methods

Different cannabis ingestion methods can produce different subjective experiences, as well as different objective outcomes like levels of THC in the blood.

There are four primary ways to ingest cannabis: inhalation, oral, transdermal and through mucous membranes.

The active ingredients in cannabis can be taken in through the lungs. That is called inhalation.

Cannabis can be eaten and processed through the digestive tract. That is called oral ingestion.

The active ingredients can be put into a topical product and absorbed through the skin. That is called transdermal ingestion.

Or cannabinoids can be absorbed through mucous membranes like under the tongue, rectally or vaginally. When cannabis is consumed under the tongue, that is called sublingual or oromucosal ingestion.

Different ingestion methods have different pharmacokinetics. Pharmacokinetics refers to the way a drug is absorbed, distributed throughout the body, metabolized and then excreted from the body.

For example, if you use a cannabis-infused topical, minimal THC is absorbed into the bloodstream and the absorption is very slow. But if you inhale cannabis smoke, THC is absorbed into the bloodstream very rapidly.

Here's an overview of cannabis ingestion methods:

• Inhalation is the most common way people consume cannabis, and the active ingredients are absorbed through the lungs.
• Oral ingestion can produce long-lasting effects, but edibles can be a bit unpredictable due to different ways people metabolize THC.
• Transdermal or topical ingestion of CBD products are generally more effective than topical THC products.
• Rectal administration of THC has low bioavailability, but anecdotal reports indicate that it produces a long-lasting, slow onset high.

Why are edibles so potent?

The two most popular ingestion methods are oral ingestion and inhalation. Why does oral ingestion provide such long-lasting effects compared to inhalation? Why are edibles so potent?

When you orally ingest cannabis, you can have levels of 11-OH-THC (pronounced 11-hydroxy-THC) that are ten times higher than if you smoke or vape cannabis. Your body breaks down THC into other molecules (called metabolites) in order to eliminate it from your body. 11-OH-THC is the active metabolite of THC.

Typically, metabolites are less active than their parent molecule, but 11-OH-THC is actually more psychoactive than THC.

There are two reasons that edibles produce much higher levels of 11-OH-THC than smoking or vaping. The first reason is that the enzymes that metabolize THC to 11-OH-THC are present in the GI tract. As you digest an edible, these enzymes are producing this super potent metabolite.

The second factor is that all blood flow from your GI tract passes through your liver before entering general circulation. This process is called first pass metabolism. In the liver, THC is extensively metabolized into its active metabolite.

CBD is also metabolized by the liver, but not much is known about the pharmacological activity of its metabolites. In general, much less is known about the pharmacokinetics of CBD.

How do we know 11-OH-THC is more potent than THC?

In the 1970s, scientists were trying to figure out if THC or 11-OH-THC was more psychoactive.

They conducted a study in which they intravenously injected people with a fixed dose (1mg) of both molecules. With THC, subjects reached a 3 out of 10 on the highness scale. But with 11-OH-THC, subjects reached an 8 out of 10!

The active metabolite 11-OH-THC more readily crosses the blood brain barrier compared to THC, and may be responsible for the more intense, longer lasting effects of edibles.

The best way to take tinctures is sublingually

Cannabis tinctures were widespread throughout the medical world until the 1930s when law enforcement began to crack down on cannabis. Tinctures are made by extracting cannabinoids with alcohol or glycerin. Let's learn how to use cannabis tinctures.

Many feel the best way to take cannabis tinctures is sublingually. Sublingual ingestion means that the cannabinoids are absorbed through the oromucosal layer under your tongue, which allows the cannabinoids to rapidly enter your bloodstream and bypass first pass metabolism in your liver. Of course, any portion of the tincture that is swallowed is processed through the GI tract like an edible.

In general, tinctures and oromucosal preparations produce higher concentrations of THC in the blood than orally consumed cannabis, but lower concentrations than inhaled cannabis.

Tinctures and oromucosal ingestion produce long lasting effects like edibles. However, because the cannabinoids are absorbed under your tongue and directly enter your bloodstream, sublingual tinctures have a much more rapid onset than edibles. Tinctures are well-suited for people who want rapid relief combined with long-lasting effects.

Rectal and vaginal ingestion

Cannabis suppositories are one of the earliest known ingestion methods, with evidence of both rectal and vaginal cannabis use dating back to 3000 B.C.E. in ancient Egypt. Today many people use rectal and vaginal weed suppositories to enhance intimacy or relieve pain.

In these ingestion methods, cannabinoids are absorbed through a mucous membrane and then enter the bloodstream. While there is not much research on the pharmacokinetics of vaginally ingested cannabis, many medical professionals consider cannabis suppositories to be an effective way of treating uterine pain, dyspareunia (pain during intercourse) or other gynecological issues.

Dr. Melanie Bone, an OBGYN who runs a medical cannabis practice in Florida, said, “The vagina has a mucosal surface with an immense ability to absorb. I take care of a lot of patients who have disease entities that would be helped by cannabinoids. I think it's a good delivery system.”

At present, no thorough studies or clinical trials have been conducted on the pharmacokinetics of rectally administered cannabis. Experiments in monkeys revealed that rectal THC had very low bioavailability. The rectal mucosa does not absorb cannabinoids very well. However, a prodrug of THC (THC-hemisuccinate) has much better bioavailability through rectal administration. A prodrug of THC means a drug that must be metabolized in order to become THC. Studies comparing oral ingestion (of THC) to rectal ingestion (of THC-hemisuccinate) found that the rectal route has about twice the bioavailability of the oral route. This increased bioavailability is due to “higher absorption and lower first-pass metabolism.”

Despite studies indicating that rectally administered THC does not have much bioavailability, there are plenty of anecdotal reports that rectal administration produces a long-lasting, slow onset high.

Transdermal or topical ingestion

Transdermal ingestion means absorbing the active ingredients through your skin. At present, no controlled clinical trials have been done on transdermal THC. The limited amount of animal trials suggest that dermal absorption of THC is slow and long-lasting but has poor bioavailability.

The slow absorption and poor bioavailability are because THC is highly lipophilic and hydrophobic. Lipophilic means that a chemical dissolves in fat. Hydrophobic means that a chemical repels water.

The skin has an aqueous (water) layer that THC has to penetrate to get into the blood stream. THC repels water, so only a limited amount of THC can pass through the skin. As a result, it takes about 90 minutes to reach peak plasma concentration, and those levels are sustained for about 48 hours. However, the peak plasma levels of THC remain low.

While THC has low bioavailability when absorbed through the skin, CBD is much less lipophilic and has been shown to penetrate the skin about ten times more than THC. Thus, topical CBD products are generally more effective than topical THC products.

Edibles and oral Ingestion

Edibles are one of the most common methods of consuming marijuana because they are discreet, don’t carry the same risks associated with smoking or vaping, and have long-lasting effects.

In general, edibles take about 30-90 minutes to take effect, and the psychoactive effects generally peak around 2-4 hours. Effects can last up to 12 hours. Different factors can affect the onset and duration of the high, like an individual’s weight, metabolism, biological sex and eating habits.

Edibles produce lower levels of THC in the blood compared to inhalation, and over a much longer time frame. Plasma concentrations of THC and 11-OH-THC peak about 2-4 hours after oral ingestion and decline over several days.

Oral ingestion has low bioavailability: only about 6-10% of THC reaches the general circulation due to extensive first pass metabolism by the liver.

We have established that oral ingestion of cannabis produces high levels of 11-OH-THC. However, there is significant individual variation in how people metabolize THC such that two people who eat the same dose of an edible can have completely different levels of 11-OH-THC in their blood.

While edibles don’t carry the same risks as smoking or vaping, they carry different risks. Due to the way THC is metabolized in oral ingestion, edibles can be a bit unpredictable. The slow onset of edibles means that people often accidentally consume more cannabis than they intend. As a result, edibles are responsible for the majority of emergency room visits due to cannabis intoxication.

However, edibles are ideal for people who want sustained effects over a long period of time.

How does oral ingestion compare to inhalation?

Clinical studies have demonstrated that there is quite a bit of variability in how people respond to a dose of oral THC, such that creating an exact equivalence between a dose of THC in an inhaled product versus in an edible is “extremely difficult.”

The Colorado Department of Revenue tried to figure it out. They suggested that 1mg of THC in an edible produces a behavioral effect similar to 5.71mg of smokable THC.

It is also worth noting that many of the chemical compounds responsible for the entourage effect “are eliminated during the processes used to make oils and butters from cannabis, such that edibles may contain high amounts of THC and only a fraction of the cannabis plant’s other constituents.”

Inhalation

Inhalation is the most common way people consume cannabis. While most people think of smoking marijuana, inhalation covers everything from vaping flower, using oil pens, and dabbing concentrates.

If you want to try smoking flower, you can choose between smoking a joint or using another method like a pipe or a bong. If you want to invest in a pipe or bong, you can save some money by finding glassware on sale through an online smoke shop. If money is not an issue, consider purchasing a glass piece made by a local glass artist.

Back to ingestion methods: in inhalation, the active ingredients are absorbed through the lungs and rapidly taken up by the bloodstream, which delivers them to the brain. Cannabinoids reach their peak concentration in the blood and brain a few minutes after inhalation.

Interestingly, inhalation has similar pharmacokinetics to intravenous injection. The psychoactive effects typically peak about 15-30 minutes after ingestion and taper off within 2 to 3 hours.

The rapid onset of effects with inhalation has some distinct advantages. Because the effects begin nearly immediately, it is easy to avoid ingesting a higher dose than intended. Inhalation is also the ideal ingestion method for situations that need immediate relief. Of course, smoking and vaping cannabis likely increases cancer risk and causes lung damage. Lung health is important for overall health and well-being, so this ingestion method carries significant risks.

What happens when you smoke weed?

Flower is commonly smoked through a variety of devices including joints, pipes and bongs. When you smoke flower, you are only getting a portion of the total THC.

Research conducted by Mario Perez-Reyes, a psychiatric researcher at the University of North Carolina, estimated that about 20-37% of THC in a joint is actually consumed, and the rest is destroyed by the flame or lost in the smoking process.

Perez-Reyes also looked at marijuana smoked in a bong and found that about 40% of the THC in a bowl was consumed by the user, with about 20% destroyed by heat (pyrolysis) and about 40% of the THC remaining in the bowl and remaining plant material.

Comparing inhalation methods

Smoking produces more than 2000 compounds including nitrogenous compounds, ammonia and tar. Many of these compounds may be hazardous to health.

Vaporizers heat cannabis to a point below combustion. Vaping is associated with less exposure to toxins and decreased health risks. Additionally, vaporizers have been shown to produce greater subjective drug effects and higher blood THC levels than an equivalent dose of smoked cannabis.

A recent study exploring the effects of inhaled cannabis flower on migraines compared joints, pipes and vaporizers. They found that joints offered greater pain relief than pipes, but there was no difference between vaporizers and joints.

Cannabis concentrates

Concentrates are extracts of cannabis that contain higher levels of the active ingredients than whole flower. Naturally, smoking or vaping concentrates carry similar risks to smoking or vaping cannabis flower. The oldest cannabis concentrate is hashish, which was first mentioned around 900 C.E. by the Iraqi polymath Ibn Wahshiyya.

Hashish is produced by extracting the resin from cannabis flowers without a solvent. Most other concentrates are made using a solvent to extract the active ingredients. Butane, hexane and supercritical CO2 are common solvents. Researchers suggest that supercritical CO2 extractions are probably the safest form of dabbable concentrate because you avoid consuming toxic byproducts. Concentrates in the form of vape pens and dabbable extracts are relatively new and have not been extensively studied.

A study that did look at concentrates found that concentrates provided greater migraine relief than flower.

Do concentrates get you higher than flower?

Concentrates typically have much higher levels of THC. When you consume concentrates, your blood THC levels will be much higher than if you smoke flower, as will levels of 11-OH-THC.

However, a recent 2020 study on intoxication in flower versus concentrates found that blood THC levels did not track with intoxication levels. Flower and concentrate users were equally intoxicated. This finding could be due to tolerance, differences in how people metabolize THC, or it could indicate that the cannabinoid receptors become saturated, at which point there isn’t a further effect of higher THC levels.

At present, there is not enough research to know if consuming cannabis concentrates carry different health risks than other ingestion methods.

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