Accurate Education - Marijuana (Cannabis): Oral Use (Tinctures & "Edibles")

Marijuana (Cannabis):

Oral Use (Tinctures & “Edibles”)

Orally ingested, “edible” forms of medical marijuana have become popular in other states in different forms with various potencies and combinations of cannabinoids. Louisiana law currently provides only for “gummy” products which are not recommended. Unfortunately, at the time of this writing there is no information regarding any additional edible products to be made available in the future.

Because edible forms of medical marijuana are prepared differently, leading to different constituents, and are metabolized differently, leading to different pharmacologic effects, it is important to understand how edible forms of medical marijuana differ from inhaled forms and pharmaceutical forms of medical marijuana.

See:

LA Marijuana Products: Introductory Principles
LA Marijuana Products: Edible Products
Links to Marijuana (Cannabis) Pages

See also:

Key to Links:

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The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship. Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

Marijuana – Oral Use

There are multiple ways to consume cannabis. The three most common methods are inhalation via smoking, inhalation via vaporization (vaping), and ingestion of edible products. Each method can impact the onset, intensity, and duration of its effects, including psychoactive effects, effects on organ systems, and the addictive potential and side effects associated with use.

With smoked cannabis, the psychoactive effects and peak THC blood levels occur in minutes, and the effects last approximately one to four hours. Vaping can be defined as “flameless heating of cannabis products without burning so that the cannabis resin is released as a vapor that is inhaled.” Vaping has a similar onset, peak, and duration as smoking and produces similar therapeutic effects. Eating cannabis (edibles) produces a different pharmacokinetic profile than smoking or vaping . When eating cannabis, onset of the cannabis effects is delayed to approximately 30 to 60 minutes, peak blood levels of THC occur approximately three hours later and the effects can last over six hours. Not only does ingesting cannabis work on a different timeline but its therapeutic and psychoactive effects differ also.

Popularity

In Colorado in 2014, edible cannabis- infused products accounted for about 45 percent of the total cannabis sales in the state. Because direct purchase of cannabinoid-infused oil or cannabis used to make homemade edibles is not tracked as an edibles purchase, the actual use of edibles is likely significantly underestimated. In a national study of adults in the US, 29.8 percent of people who had ever used cannabis reported consuming it in edible or beverage form.

Oral Use – Safety

In general, the use of ingestible cannabis-based products (edibles) is safe, although a couple of caveats apply. Due to differences in absorption characteristics with edibles, there may be a tendency for greater side effects. Edible products may be more difficult to predictably dose due to a variety of variables. These concerns are explored under “Oral Use – Pharmacokinetics” below. On the other hand, it has also been reported by some that edibles deliver a “high” that is calmer, more relaxing and better tolerated than smoking cannabis.

Gummies

Another caveat is the product itself as a variable impacting safety. Because they taste good and are presented as candy, gummies are not recommended due to their tendency to reinforce unnecessary increased dosing and greater potential for undesirable side effects. Furthermore, edibles are more likely to be accidentally ingested by children, pets or others who may mistake them for food. Does anyone think Percocet should be provided as a gummy?

Although gummies (or other marijuana-based products in the form of candy or other highly palatable food products) are not recommended, this is not to say that edible forms are not recommended. In fact, orally consumed edible cannabis-based products, particularly those with THC, offer distinct differences and advantages compared to vape products. For many, the orally ingested method of using cannabis based products is preferred for both improved effectiveness and tolerability.

Tinctures and RSO Products as Edibles

A recommended delivery form is cannabis extracts, also referred to as cannabis oils, which are produced by extracting cannabis flowers (inflorescences) and diluted. Extracts are consumed sublingually placed under the tongue and held before swallowing), via spray into the oral cavity, or further formulated into tablets and capsules. Each one of these forms has its own pharmacokinetics and absorption rate. Compared to smoking, extracts-based products are safer for use, provide longer lasting effects, and enable better dosing accuracy and reproducibility. Also, many clinical trials are based on administering extracts, rather than on smoking, and are better relied upon for their findings.

Contrary to expectation, due to processing the content and composition of extracts differ markedly from those in the inflorescence used to produce them. The main difference is not in the cannabinoid content (THC, CBD, CBG etc.), but rather in the content of the terpenes. This is largely due to the lower boiling temperatures of terpenes compared with cannabinoids and therefore these differences are greater in (in order of increasing boiling point): the monoterpenes (including myrcene, pinene, limonene, ocimene, and terpinolene), monoterpenoids linalool, terpineol, and geraniol), sesquiterpenes (including caryophyllene and humulene), and sesquiterpenoids (including nerolidol, guaiol, and bisabolol). It is mostly the monoterpines and monoterpenoids that are lost, there is much less reduction in the content of the sesquiterpene and sesquiterpenoids.

Therefore these terms “whole plant/full spectrum” extracts can be very misleading, creating the expectation that they represent the composition of the original plant. Similarly, clinical trials of oils specified by the strain used to form them may not be accurate.

To remedy this, the lost terpenes can be added back into the product. Given the number of steps wherein terpenes evaporate and given the need to separate terpene vapors from other gaseous components (e.g., solvent vapors), such collection of the lost terpenes by processing inflorescence may not be practically feasible. However, most terpenes of interest can be obtained from other sources, e.g., hops (myrcene), pine (pinene), and lavender (linalool).

Because of this, it is critical to evaluate a Certificate of Analysis (COA) for any cannabis-based product intended for oral use (this should be done for flowers or buds as well). Not only is it necessary to get a proper listing of constituents and not believe that it correlates with expectation based on the flower source, but COAs are available from the seller as required by LA law.

It should be noted that as more is learned about the benefits of specific terpenes and their sublingual and oral dosing, it is quite feasible to design products containing specifically desired combinations of terpenes for therapeutic use. In fact, such products are in process now but research is needed to confirm safety and effectiveness.

That being said, cannabis-based tinctures are currently available in several formulations and should be considered as edibles, especially when immediately swallowed as opposed to prolonged holding under the tongue as may be recommended. Also, the RSO vape products currently available in liquid form to be used with refillable cartridges for vaping can also be orally ingested when mixed with a food product with very careful attention to dosing.

Other Forms of Edibles

Although in LA the only cannabis-based products containing THC are gummies, tinctures and RSO products, other options may become available. Additionally, in January 2022 dried marijuana plant/flower buds will become available. Under the new LA legislation, pharmacies can dispense up to two and a half ounces of raw or crude cannabis every 14 days and this will allow for home processing into edible forms and food items. Techniques for this processing is beyond the scope of this website but the world of recreational cannabis users have developed culinary cannabis into an art form that enhances both palatability and bioavailability. In states where they are allowed, edibles can come in many forms— including baked goods, candies, gummies, chocolates, lozenges, and beverages—and may be homemade or prepared commercially.

Oral Use – Benefits and Effectiveness

Most of the research on the therapeutic effectiveness of oral ingestion of cannabinoids has been conducted using pharmaceutical preparations including dronabinol (Marinol) and nabilone (Cesamet), synthetic analogs of Δ9- THC, and nabiximols (Sativex), a cannabis-derived oromucosal spray containing Δ9-THC and CBD in a 1:1 ratio.

This research is supportive for oral cannabis use for muscle spasm and chronic pain, nausea and vomiting, epilepsy, appetite stimulation and several psychiatric disorders (e.g., post-traumatic stress disorder, anxiety and depression). To date, however, the research remains mostly focused on the cannabinoids THC and CBD with little research investigating the additional benefits that other cannabinoids and terpenes may provide.

Oral or buccal cannabinoids have far greater evidence of effectiveness than smoked cannabis does for the treatment of neuropathic pain and there is no evidence that smoked cannabis is a more effective analgesic than pharmaceutical cannabinoids. Pharmaceutical cannabinoids are also safer, with fewer cognitive effects.

Many medicinal cannabis patients however prefer to smoke or vape cannabis. A common reason for this is that inhaling cannabis provides a more immediate effect and dosing is easier to modulate. Regular cannabis users also find the effects of oral Δ9-THC to be qualitatively different from those of smoked cannabis. Naive users often report a greater incidence of negative side effects following the use of oral Δ9-THC products, especially at higher doses. This likely represents a dosing issue but may reflect the pharmacokinetics of cannabis.

Oral Use – Side Effects and Toxicity

Although cannabis is not considered to be lethal in the absence of extreme intake, episodes of severe cannabis-induced behavioral impairment are common, reportedly experienced by 65 percent of medicinal cannabis users. Edible products are responsible for the majority of health care visits due to cannabis side effects. Overuse episodes can be highly unpleasant experiences that can include cognitive and motor impairment, extreme sedation, cardiac stress, and vomiting. In extremes, high quantities of THC may cause transient severe anxiety, agitation and psychotic symptoms as hallucinations and delusions in some individuals. Generally, these psychotic symptoms last only for the duration of intoxication, but in some cases, these symptoms can persist for as long as several days.

Cannabis-induced psychosis is usually thought to be the result of over-consumption of THC, and most of the reported cases occur follow ingestion of edible forms of cannabis. A number of factors related to edibles contribute to over-consumption. Due to the high palatability of some edible products, people become encouraged to over-indulge and ingest higher doses than anticipated. This can occur especially with concentrated candy forms of edibles such as gummies and chocolate. Another concern is that many edible products available for retail sale are packaged in forms that may be appealing to children (e.g., gummy candies, lollipops, cookies). Thus, children, as well as adults and household pets, may over-consume.

While state laws often require that total milligrams of THC and number of servings be included on packages available for retail sale, a single chocolate bar can contain 100 milligrams of THC (10 servings of the maximum recommended dose of 10 mg/serving). As such, only a small amount of a product may be needed to reach the maximum recommended dose of 10 mg/serving. If the production of the edible is not closely monitored, leading to high concentrations and lack of consistency such as may occur with home preparations, unintentional high doses may be ingested. Accidental ingestion of cannabis edibles is common.

The metabolism of orally ingested cannabis also contributes to the potential for toxic side effects. Because it may take longer than may be expected for the initial effects of edibles to be felt (30 to 90 minutes), people may ingest additional doses prematurely leading to toxic side effects. This lack of consistency and the delayed effects may cause both new and experienced users of cannabis to consume higher than intended amounts of the drug. The pharmacokinetics of oral cannabis are also important contributors of side effects, see below.

Bioavailability

The “bioavailability” of a medication is the measure of how effectively administration of that medicine achieves blood levels. As a standard of definition, the bioavailability of a medication given directly intravenously is 100%. Other forms of administration, such as smoking, eating and application to skin, will be associated with less bioavailability. Bioavailability is generally described in terms of maximum time in the blood (Cmax) and maximum overall absorption into the blood (AUC – Area under the Curve). Tmax is the time necessary to reach the maximum blood concentration after administration of a medication.

Bioavailability is the degree and rate at which a substance is absorbed into the blood where it can be delivered to the organ systems necessary for therapeutic effects. The greater the bioavailability, the less product needs to be consumed to achieve a therapeutic effect. Bioavailability of cannabis products varies somewhat from individual to individual and is determined mostly by how it is consumed, including if it is ingested with food. It is also affected by the individual’s age, general health and the presence of gastrointestinal disorders. As a general guide based on method of use, the bioavailability of cannabis is:

Smoking: 25-30% bioavailability (Reports vary from 2-56%)
Vaporization: 30-60% bioavailability
Tinctures (sublingual): 40-50% bioavailability
Edibles: 5-12% bioavailability (Reports vary from 4-20%)

Oral Use – Pharmacokinetics & Pharmacodynamics

Pharmacokinetics – How the body acts on a drug
Pharmacodynamics – How a drug affects the body (and mind)

The pharmacokinetics (how the body absorbs and metabolizes a drug) of orally ingested cannabis products is very different from inhaled administration. Overall, eating results in a slower and more prolonged effect compared with inhaling or buccal (under the tongue) use. When inhaled through smoking or vaping, THC reaches the brain, takes initial effect within minutes, and shows peak effects in about 20 to 30 minutes, with psychoactive effects tapering off within 2 to 3 hours. Although it takes longer for the initial psychoactive effect of edibles (30 to 90 minutes) to be felt, the resulting “high” is longer-lasting, with a peak at 2 to 4 hours after ingestion. Factors such as weight, metabolism, gender, and eating habits also contribute to how soon and for how long someone will feel intoxicated following oral ingestion. The peak blood levels and therapeutic responses occurring later after ingestion and may not dissipate for up to 24 hours.

A 2020 study evaluated the pharmacodynamic effects of multiple oral cannabis doses in a group of infrequent cannabis users. The THC doses (10, 25, or 50 mg) administered in this study represent common doses found in commercially-available oral cannabis products. The 10 mg dose has been set as the standard unit dose or “serving size” for cannabis edibles sold at retail outlets in several U.S. states (e.g., Colorado) as well as Canada, while many oral cannabis products contain 25–50 mg in a single package.

Study participants were give brownies that contained 0, 10, 25, or 50 mg THC. The cannabis used to prepare the THC brownies contained 11 % total THC, 0.1 % cannabidiol, and 0.8 % cannabinol. The cannabis was ground into a powder using a food processor and were subsequently heated for 30 min at 250 °F (130 °C) to catalyze decarboxylation of inactive tetra-hydrocannabinolic acid (THC-A) to the psychoactive form, THC. Participants were instructed to consume the entire brownie within five minutes.

The 10 mg dose did not result in significant performance deficits relative to placebo. However, the 25 and 50 mg doses produced moderate to severe impairment on all performance measures. On average, subjective drug effects became perceptible 30 minutes after brownie ingestion and peaked 1.5–3 hours after ingestion. Effects on cognitive and psychomotor performance followed a similar pattern, as peak impairment on cognitive measures were detected between 2 – 5 hours after ingestion, depending on the task and dose. In contrast, peak subjective and cognitive effects of inhaled cannabis occur within 10 – 30 min of inhalation.

Dosage comparisons revealed that, compared to placebo, the 10 mg dose significantly increased ratings of drug effect and good drug effect. The 25 mg dose increased ratings of drug effect, unpleasant drug effect, good drug effect, heart racing, anxious/nervous, sleepy/tired, hungry/have munchies and decreased ratings of alertness. The 50 mg dose increased ratings of drug effect, unpleasant drug effect, good drug effect, sick, heart racing, anxious/nervous, paranoid, sleepy/tired, irritable, restless, hungry/have munchies and decreased ratings of alertness compared to placebo.

Female participants had significantly higher ratings of sick, heart racing, and anxious/ nervous compared with males. Other studies have also found that women exhibit greater sensitivity to acute effects from smoking cannabis compared to men.

Another important finding from this study was the considerable inter-individual variability in pharmacodynamic effects of cannabis, despite the fact that all participants were infrequent users. Some users displayed impaired performance after ingestion of the 10mg THC dose, even though, on average, this dose did not alter performance relative to placebo. However, some users had little to no impairment following ingestion of the highest dose (50 mg THC), which produced drastic alterations in performance in the majority of participants.

The more prolonged effects of oral cannabis products, especially those of impairment, impart a high risk for triggering accidental acute overdose, particularly among infrequent users. In fact, oral products are responsible for the majority of emergency room visits related to cannabis use.

See: THC Pharmacokinetics

See: CBD Pharmacokinetics

11-OH-THC

Subsequent to oral ingestion the gut and liver metabolizes THC into 11-OH-THC, very potent THC metabolite which is formed in much higher levels after ingesting edibles compared with inhalation and buccal/sublingual administration. It has been reported that only 20% of inhaled THC is metabolized into 11-OH-THC whereas up to 100% of orally ingested THC is converted to 11-OH-THC, mostly on its first pass through the liver when initially absorbed from the gut. 11-OH-THC is equally or more potent than THC and is present at higher blood levels when THC is ingested orally compare to when it is inhaled. The 11-OH-THC is likely responsible for the stronger and longer-lasting drug effect of edibles.

11-OH-THC is also likely responsible for many of the differences in the effects of oral ingestion of THC versus other means of administration. 11-OH-THC is psychoactive and contributes to the effects of THC on thought processing, mood and euphoria (the “high” of marijuana), but may offer a calmer or different manifestation of the high. It may also contribute to some of the side effects of cannabis ingestion, including anxiety. The full profile of benefits and side effects of 11-OH-THC is not known at this time.

11-OH-THC diffuses into the brain more readily than THC does and its effects are perceived more rapidly than with THC. 11-OH-THC is subsequently metabolized into THC-COOH, which is inactive, and ultimately excreted into feces (65%) and urine (20%). THC is significantly metabolized with just one pass through the liver, the “first pass effect,” which is why formulations that are ingested orally and must pass through the liver before entering the blood have less bioavailability than other formulations.

Although some research reports no significant pharmacokinetic interactions when THC is co-administered with CBD, other research suggests that CBD at doses >15 mg inhibits CYP2C and CYP3A liver enzymes, thus reducing first-pass metabolism to 11-OH-THC. This may explain reports that CBD reduces side effects associated with THC.

THC is also metabolized in the brain with 11-OH-THC being the primary metabolite. Levels of 11-OH-THC can persist in the brain contributing to prolonged effects after administration of THC. As such, 11-OH-THC is a significant contributor to the effects of ingested THC products but not so much with vaped or buccal administered products.

After THC enters the blood, it quickly distributes from the blood to other body tissues and only a small fraction of it remains in the blood. The THC that remains available in the blood passes through the liver where it is converted by the CYP450 oxidase enzymes to 11-OH-THC and other metabolites. However, the larger fraction of THC in other tissues does not contribute significantly to blood levels of 11-OH-THC and therefore, overall, not much 11-OH-THC is initially formed with inhalation. The levels of 11-OH-THC in the blood after smoking cannabis is only about 5% of THC levels, probably not enough to contribute significant psychoactive effects from the 11-OH-THC.

However, after taking cannabis orally, the average levels of 11-OH-THC vary from 25% of THC to more than 300% of THC levels, depending on the study and an individual’s metabolic differences. Given that some people will have 3 times higher blood levels of 11-OH-THC than THC after ingesting cannabis-based products, the therapeutic response, especially the psychoactive effects, may be quite different from inhaling them. Whether 11-OH-THC contributes qualitative or quantitative differences psychoactively from THC is as of yet unclear, although because 11-OH-THC enters the brain from the blood more quickly than THC, onset of effects are faster with 11-OH-THC. That being said, experienced cannabis users will most often attest to a significantly different psychoactive experience from ingesting vs. inhaling the same cannabis product.

As with the psychoactive effects of THC vs 11-OH-THC, nothing is known about the analgesic or other therapeutic benefits achieved by one vs the other. To date, no studies appear to be available that compare analgesic benefits of inhaling vs ingestion of cannabis aside from the differences in onset and persistence of psychoactive effects. One may surmise that the analgesic benefits may parallel the timing pattern of psychoactive effects but research is lacking.

Furthermore, there is a difference when an edible is taken on an empty or full stomach:

Fasting Condition

THC and CBD are both rapidly absorbed in the fasting condition, reaching their peak plasma concentrations at about 1.5 hours (this time is called the tmax). When taken on an empty stomach the onset of peak effect is faster but will not last as long. It is also commonly reported that eating edibles, especially gummies, on an empty stomach is associated with greater side effects, especially anxiety, compared with eating them with a full stomach.

Fed Condition

Under fed conditions, both of these cannabinoids take much longer to absorb, with peak plasma concentrations not occurring until about 4 hours after dosing. However, looking at the total extent of absorption, people who eat a meal before dosing actually have more cannabinoids absorbed, or greater bioavailability. Absorption is 2.8-fold higher for THC and 4.1-fold higher for CBD after a meal. This may impact both the therapeutic benefits as well as the side effect profile of ingested cannabinoids.

One explanation proposed by the “Professor of Pot” for the greater side effects often associated with using edibles on an empty stomach lies with the explanation that with the proportionally greater amount of CBD absorbed in the fed state there is a larger CBD:THC+11-OH-THC ratio. CBD is known to reduce the anxiety and side effects of THC.

In conclusion, it is generally recommended to ingest edible cannabis-based product on a full stomach, especially if side effects are experienced when ingesting them on an empty stomach.

Commercial Edibles

For medicinal cannabis consumers, knowing the precise amounts and relative concentrations of THC, CBD, terpenes and other cannabinoids in edibles is vital, as this information largely determines the therapeutic effects that users will experience. Yet, despite the value of including CBD and other constituents besides just THC in edibles intended for medicinal use, few edible manufacturers report even the CBD content of their products, let alone the terpenes or other cannabinoids. Further, even among products reported to contain CBD, studies report that many products contain only trace amounts or none at all due to lack of regulatory quality oversight in the manufacturing of these products.

Home-made Edibles

A common practice among recreational user of marijuana is to bake products such as cookies, cakes, brownies, omelettes and quiches made using plant forms of marijuana. In preparing the marijuana for cooking, the flowers or buds are often processed first by heating in butter, ghee or oil to extract the THC in order to avoid having to consume plant parts in the edible product.

However, a cannabis plant contains hundreds of chemical constituents, including more than 100 cannabinoids, terpenes and other pharmacologically active constituents which may function together (the “entourage effect”) to produce a greater therapeutic effect than any single constituent. Many of these constituents may be eliminated during the processes used to make oils and butters from cannabis, so while these edibles may contain high amounts of THC they may contain only a fraction of the cannabis plant’s other desirable constituents. This in turn may reduce the medicinal value of the edible.

It’s also important to remember when cooking cannabis that terpenes can be destroyed by high temperatures, so always cook it “low and slow.” The goal is to ensure that the terpenes remain intact through the cooking or baking process to obtain the unique, special benefits they offer.

Cannabis Strains:

When starting with marijuana flowers or buds in the preparation of an edible product it is important to realize that different strains (or cultivars) have different amounts and balances of pharmaceutically active constituents which will affect their therapeutic responses.

Of the three species of cannabis identified (Cannabis sativa, C. indica, and C. ruderalis), C. sativa contains higher THC than CBD levels while the C. indica is richer in CBD compared to THC. However, the distinction between Sativa and Indica is very blurred at this time due to heavy cross-breeding by growers. As such it is not always very helpful to rely on a supposed strain type to predict a therapeutic response.

See: Marijuana (Cannabis): Botanical

Cannabis species have been found to fall into three general chemotypes (chemical compositions) based on genetically-determined THC:CBD ratios:

Category I: Relatively high total THC and low total CBD
Category II: THC:CBD ratios near equal (1:1)
Category III: Relatively low total THC and high total CBD

CBD reduces the psychotropic actions of THC, possibly by inhibiting THC metabolism and the formation of its primary psychoactive metabolite, 11-OH-THC. To summarize, a higher THC:CBD ratio is associated with more prominent psychoactive symptoms, whereas lower THC:CBD ratio suppresses psychoactive symptoms and has more sedative and relaxing effects.

In addition, the terpenes and minor cannabinoids content will also impact the therapeutic effects of a given flower or bud.

Reminder: Harm Reduction:

Do not operate dangerous equipment or perform potentially dangerous activities after use
Do not combine with tobacco
Do not use with alcohol, opioids, or sedating drugs
Keep cannabis safely stored under lock and key
The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing up to 9% THC.

Driving:

Cannabis users should be advised not to drive for at least:

Three to four (3 to 4) hours after smoking
Six (6) hours after oral ingestion
Eight (8) hours if they experience a subjective “high”

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

References:

Medical Marijuana – Prescribing Guidelines

Medical Marijuana – Oral Use

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Accurate Education – Marijuana (Cannabis): Oral Use (Tinctures & “Edibles”)