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How Edibles Effect the Body

The effects of edibles are slow and unpredictable, and the impairment lasts much longer than inhaled cannabis. How long and how "high" a person feels after taking edibles depends on many factors.

Cannabis is consumed in many ways. Historically, the most common method has been smoking, but consumers are getting curious about cannabis-infused food and drinks, commonly known as “edibles.”

With edibles set to become legal for sale in Canada on October 17, 2019, it’s important for us to know how the effects of cannabis snacks differ from other consumption methods. Knowing what to expect with regards to how quickly impairment comes on and how long it lasts can help us stay in control of our experience and stay safe.

 

Cannabis Foods and Edibles

 

Cannabis contains over 100 cannabinoid compounds that produce a variety of effects1 2. The main active compound is delta-9-tetrahydrocannabinol (THC), and it is primarily responsible for the psychotropic effects or “high” of cannabis. The second most common cannabinoid is cannabidiol (CBD), which does not produce a high and is often sought after and studied for its therapeutic value.  

 

Learn More: A Medical Introduction to CBD

 

The intoxicating effects of cannabis depend mostly on how much THC a person consumes and how they take it in. The same dose of THC acts differently when eaten versus inhaled. Generally, inhaled cannabis starts to act more quickly and lasts a short time, while edibles take longer to kick in, and their effects last much longer.

Why Does THC Start to Act More Quickly When It Is Inhaled?

When cannabis is smoked, THC enters the bloodstream quickly through the lungs. From there, it takes only minutes for it to cross the blood-brain barrier and bind to CB1 receptors in the brain3. Researchers believe these CB1 receptors are where THC causes intoxication4.

While smoking or vaping give a fast onset of effects, the duration (or how long the effects last) is short. Inhaled cannabis typically peaks after approximately 15 minutes and lasts between one to three hours5.

In contrast, absorbing THC from edibles is slow and unpredictable. This is because THC must first pass through the stomach and digestive system, and then into the liver where it is converted into over 100 metabolites. Within the liver, most of the THC is converted to a metabolite called 11-OH-THC, which is psychotropic like THC. The liver also produces an inactive metabolite called THC-COOH, which does not produce a “high6.”

From the liver, THC and 11-OH-THC enter the bloodstream where they travel to receptors in the brain and body7. Peak concentrations of THC often show up in the blood about one to two hours after consuming an edible, although some studies show peaks as late as four to six hours8.

After this peak, it takes many more hours for the effects of the edible to taper off. Some people even experience a second peak due to a type of liver metabolism called “enterohepatic circulation.” This is a process that affects certain medicines, where a substance reaches the liver and gets converted to bile, then enters the small intestines to be absorbed into the bloodstream, and some gets pulled out of the blood to go back into the liver for a second round of processing9.

This unpredictability about when the effects will take hold and how long they will last means that edibles consumers need to plan for an extended period without driving or important responsibilities. The Alaska Department of Health recommends waiting at least 10 hours before doing activities that require alertness and good judgement. Some studies, however, have found that a very high dose of edible THC can cause impairment for up to 24 hours10.

 

Cannabis Edibles

Why Do Edibles Seem to Create a More Potent High Than Smoked or Vaped Cannabis?

Some research shows that the active by-product of THC that our liver produces from edibles (11-OH-THC) causes a more potent ”high” than the THC that we inhale11 12. 11-OH-THC can readily cross the blood-brain barrier13 and appears in the blood in higher quantities when THC is ingested than when it is inhaled14. This may explain, at least in part, why users report longer-lasting effects when ingesting edibles compared with smoking or vaping since the absorption process through the lungs only forms small amounts of super-potent 11-OH-THC15 16.

Does CBD Also Get Absorbed Differently through Edibles Than through Smoking?

The process of absorbing and metabolizing CBD is similar to THC. In edibles, CBD is mostly metabolized in the liver, although a large amount of the CBD that’s eaten remains unchanged and gets eliminated with other food waste17.

Once eaten, CBD takes about one hour to get into the bloodstream and stays there for about three to four hours18  19. While it’s circulating in the blood, CBD binds mostly to receptors in the muscles and tissues (rather than in the brain and central nervous system) and produces its anti-inflammatory effects throughout the body20.

What Factors Influence the Intensity of Edibles’ Effects?

The dose is a major factor that affects how edibles make us feel, especially the intensity and length of the effects. Controlling the dose is also one of the significant challenges of using edibles because the amount of THC present can vary greatly, even within the same product. Variations in dose are particularly hard to fine-tune with homemade edibles.

The amount of THC in homemade edibles depends on several things:

● The amount of THCA (a precursor to THC) that was present in the cannabis plant matter
● The decarboxylation process, which uses heat to transform the THCA into THC
● The infusion process, which extracts THC from the plant and absorbs it into an extraction medium, typically an oil

Each step that turns cannabis flower into an extract creates possibilities for inconsistency. Firstly, decarboxylation is usually not complete. Studies have found that up to 30% of THCA can be “lost” before and during decarboxylation as it converts into another (non-psychotropic) cannabinoid called CBN21. The infusion process also leaves behind variable amounts of THC that don’t become part of the extract. These losses aren’t predictable and change from batch-to-batch, making homemade edibles extremely difficult to dose with precision. When legalized edible products come onto the market, it will be easier to know how much THC you will consume, because licensed producers will test and label each batch after production.

Combined with edibles’ slow-to-peak high, the unpredictability of THC dosage in homemade treats often leads to over-consumption.  Many reported cases of distress from THC (intense feelings of panic, paranoia and fears that the high will never stop) occur after taking an edible22 23 24.

Bioavailability is another factor that influences the effect of edibles. The bioavailability of THC means how much of the dose in the edible actually enters the bloodstream and is available to affect the brain and body. The oral bioavailability of cannabinoids can vary a lot. For example, one small study found that ingestion of 20 mg THC in a chocolate cookie resulted in a 4 – 12 % bioavailability25. That means some people got three times more THC in their system than others.

Cannabinoids, including THC and CBD, are highly lipophilic, meaning they tend to combine with fats. This means that THC becomes more bioavailable if it is eaten with fats, oils or substances with a similar chemical structure, such as ethanol26.

One study found that THC dissolved in sesame oil resulted in up to 20% oral bioavailability27. Another showed that CBD eaten with fats increased bioavailability up to six times more than CBD eaten without fats28.

Some studies have found that blood plasma levels of CBD were increased when CBD was administered with food compared to CBD taken on an empty stomach, even when a meal was eaten one hour after taking CBD29.

Oral bioavailability is also influenced by individual factors such as how quickly a person's body absorbs and metabolizes food in general.

 

Cannabis-Infused Edibles

How Long Does THC Intoxication Last?

There is no definitive answer to this question. When you’re planning to consume edibles, two things to consider are how long you will be intoxicated and how long THC and its metabolites will be detected in your blood and oral fluids.

How long a person feels “high” mostly depends on how much THC has been eaten, how it is ingested (e.g., on an empty versus full stomach) and the person’s unique metabolism rate. In one study where participants ate 20 mg of THC in a chocolate cookie, the feeling of being “high” was reported as early as 30 minutes after ingestion. The peak “high” effects occurred between two to four hours and declined to low levels after six hours30.

Similarly, subjects who drank milk containing 16.5 mg or 45.7 mg of THC reported the onset of feeling “high” within an hour31. Peak effects occurred between two to four hours and faded to low levels after 10 hours32. People reported their effects were more intense with a higher THC dose, with the most intense effects reported after consuming the highest dose of 45.7 mg of THC.

This same study also tested the ability of each participant to read and interpret road signs, as well as their driving capabilities using a simulator. Participants’ abilities were impaired in every test, with the most noticeable impairment being from one to five and a half hours after drinking the THC-infused milk. Impairment was most substantial with the highest dose of 45.7 mg with impairment still reported a full 24 hours after consumption33. Although the subjects may not have felt intoxicated anymore, the tests showed that their reaction speed and judgement were still affected the day after taking the large dose, though not as much as during their peak effects.

Blood plasma levels of THC and its metabolic by-products were also tested in this study. The blood tests showed that THC concentration peaked at approximately one hour, declined to low levels after six hours, and was still detectable at 10 hours after ingestion. 11-OH-THC peaked at a point between one to four hours and tapered off somewhat after six hours. For the highest dose of THC (47.5 mg), this potent metabolite was still detectable at 24 hours after taking the edible34.

Summary

Edibles, or cannabis-infused food or drinks, are becoming a popular method for using cannabis. Unlike smoking, the effects of edibles are slow and unpredictable, and the impairment lasts much longer. How long and how “high” a person feels after taking edibles depends mostly on how much THC they consume, as well as the bioavailability of their particular THC product and their unique individual speed of metabolism. Sometimes, the way that THC is stored and recirculated in the body can also lead to THC showing up in a person’s system a long time after taking an edible. All of these factors need to be considered for edibles users to plan when they can be safe.

 

 

References

[1] Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A. Targeting the endocannabinoid system: future therapeutic strategies. Drug Discov Today. 2017;22(1):105-110.

[2] Morales P, Hurst DP, Reggio PH. Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131.

[3] Huestis MA, Henningfield JE, Cone EJ. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol. 1992;16(5):276-282.

[4] Gui H, Tong Q, Qu W, Mao CM, Dai SM. The endocannabinoid system and its therapeutic implications in rheumatoid arthritis. Int Immunopharmacol. 2015;26(1):86-91.

[5] Huestis MA, Henningfield JE, Cone EJ. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol. 1992;16(5):276-282.

[6] Huestis MA. Human Cannabinoid Pharmacokinetics. Chemistry & biodiversity. 2007;4(8):1770-1804.

[7] Pertwee RG, Cascio MG. Known pharmacological actions of delta-9-tetrahydrocannabinol and of four other chemical constituents of cannabis that activate cannabinoid receptors. In: Pertwee RG, ed. Handbook of cannabis. Oxford, UK: Oxford University Press; 2014.

[8] Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics. 2003;42(4):327-360.

[9] Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics. 2003;42(4):327-360.

[10] Ménétrey A, Augsburger M, Favrat B, et al. Assessment of Driving Capability Through the Use of Clinical and Psychomotor Tests in Relation to Blood Cannabinoids Levels Following Oral Administration of 20 mg Dronabinol or of a Cannabis Decoction Made with 20 or 60 mg Δ9-THC*. Journal of Analytical Toxicology. 2005;29(5):327-338.

[11] Hollister LE. Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of delta9-tetrahydrocannabinol. Pharmacology. 1974;11(1):3-11.

[12] Hollister LE, Gillespie HK, Ohlsson A, Lindgren JE, Wahlen A, Agurell S. Do Plasma Concentrations of Δ9-Tetrahydrocannabinol Reflect the Degree of Intoxication? The Journal of Clinical Pharmacology. 1981;21(S1):171S-177S.

[13] Mura P, Kintz P, Dumestre V, Raul S, Hauet T. THC can be detected in brain while absent in blood. J Anal Toxicol. 2005;29(8):842-843.

[14] Huestis MA, Henningfield JE, Cone EJ. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol. 1992;16(5):276-282.

[15] Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics. 2003;42(4):327-360.

[16] Hollister LE, Gillespie HK, Ohlsson A, Lindgren JE, Wahlen A, Agurell S. Do Plasma Concentrations of Δ9-Tetrahydrocannabinol Reflect the Degree of Intoxication? The Journal of Clinical Pharmacology. 1981;21(S1):171S-177S.

[17] Huestis MA. Human Cannabinoid Pharmacokinetics. Chemistry & biodiversity. 2007;4(8):1770-1804.

[18] Huestis MA. Human Cannabinoid Pharmacokinetics. Chemistry & biodiversity. 2007;4(8):1770-1804.

[19] Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Frontiers in Pharmacology. 2018;9(1365):1-13.

[20] Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia (Copenhagen). 2014;55(6):791-802.

[21] Iffland K, Carus M, Grotehermen F. Decarboxylation of Tetrahydrocannabolic Acid (THCA) to active THC. European Industrial Hemp Association. 2016.

[22] Bui QM, Simpson S, Nordstrom K. Psychiatric and medical management of marijuana intoxication in the emergency department. West J Emerg Med. 2015;16(3):414-417.

[23] Favrat B, Menetrey A, Augsburger M, et al. Two cases of "cannabis acute psychosis" following the administration of oral cannabis. BMC Psychiatry. 2005;5:17.

[24] Hudak M, Severn D, Nordstrom K. Edible Cannabis–Induced Psychosis: Intoxication and Beyond. American Journal of Psychiatry. 2015;172(9):911-912.

[25] Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. 1980;28(3):409-416.

[26] MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018;49:12-19.

[27] Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clinical Pharmacology & Therapeutics. 1983;34(3):352-363.

[28] Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Frontiers in Pharmacology. 2018;9(1365):1-13.

[29] Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Frontiers in Pharmacology. 2018;9(1365):1-13.

[30] Hollister LE, Gillespie HK, Ohlsson A, Lindgren JE, Wahlen A, Agurell S. Do Plasma Concentrations of Δ9-Tetrahydrocannabinol Reflect the Degree of Intoxication? The Journal of Clinical Pharmacology. 1981;21(S1):171S-177S.

[31] Ménétrey A, Augsburger M, Favrat B, et al. Assessment of Driving Capability Through the Use of Clinical and Psychomotor Tests in Relation to Blood Cannabinoids Levels Following Oral Administration of 20 mg Dronabinol or of a Cannabis Decoction Made with 20 or 60 mg Δ9-THC*. Journal of Analytical Toxicology. 2005;29(5):327-338.

[32] Ménétrey A, Augsburger M, Favrat B, et al. Assessment of Driving Capability Through the Use of Clinical and Psychomotor Tests in Relation to Blood Cannabinoids Levels Following Oral Administration of 20 mg Dronabinol or of a Cannabis Decoction Made with 20 or 60 mg Δ9-THC*. Journal of Analytical Toxicology. 2005;29(5):327-338.

[33] Ménétrey A, Augsburger M, Favrat B, et al. Assessment of Driving Capability Through the Use of Clinical and Psychomotor Tests in Relation to Blood Cannabinoids Levels Following Oral Administration of 20 mg Dronabinol or of a Cannabis Decoction Made with 20 or 60 mg Δ9-THC*. Journal of Analytical Toxicology. 2005;29(5):327-338.

[34] Ménétrey A, Augsburger M, Favrat B, et al. Assessment of Driving Capability Through the Use of Clinical and Psychomotor Tests in Relation to Blood Cannabinoids Levels Following Oral Administration of 20 mg Dronabinol or of a Cannabis Decoction Made with 20 or 60 mg Δ9-THC*. Journal of Analytical Toxicology. 2005;29(5):327-338.