The Science of Cannabis Edibles

Introduction

The medical versatility of the cannabis plant is legendary. Of particular interest are the extensive array of preparations that can be created using cannabis. Coupled with the various routes of administration available, this can lead many patients to ask, “what is the best way to use cannabis for my needs?”.

In this article we intend to give the reader the most accurate information about the different ways of consuming cannabis so that they make the most informed decisions. This topic will be dedicated to covering oral cannabis administration, in particular cannabis edibles. 

What are cannabis edibles?

When most of us talk about cannabis edibles, they are mostly referring to candies, baked goods, or other prepared food products. But here, we refer to edibles as anything that is consumed orally and gets absorbed in the mouth or GI tract.

This includes:

The image highlights the diversity found in cannabis edibles and oral cannabis formulations. In the image you can see Nabiximols (Sativex), cannabis infused cocktails, cannabis tea, and of course cannabis cookies.

Pharmacodynamics or edibles effects on the body

Whereas the acute effects CNS and physiological effects occur within minutes by the smoking or vaporization, in the case of oral ingestion the acute effects proceed on a time scale of hours. Acute oral administration results in a slower onset of action, lower peak blood levels of cannabinoids, and a longer duration of pharmacodynamic effects compared to smoking. The psychotropic effects or “high” occurs much more quickly by smoking than by the oral route, which is the reason why smoking appears to be the preferred route of administration by many, especially among non-medical users.

The subjective and physiological effects after controlled administration of nabiximols (Sativex®) or oral Δ9-THC have also been compared. Increases in systolic blood pressure occurred with low (5 mg) and high (15 mg) oral doses of THC, as well as nabiximols, with the effect peaking at around 3 h after administration. In contrast, diastolic blood pressure decreased between 4 and 8 h after dosing. Heart rate increased after all active treatments. A statistically significant increase in heart rate relative to placebo was observed after high-dose oral THC and high-dose nabiximols, but the authors indicated that the increases appeared to be less clinically significant than those typically seen with smoked cannabis. High-dose oral THC (15 mg Δ9-THC) and high-dose nabiximols were associated with significantly greater “good drug effects” compared to placebo, whereas low-dose nabiximols was associated with significantly higher “good drug effects” compared to 5 mg THC. A subjective feeling of a “high” was reported to be significantly greater after 15 mg oral THC compared to placebo and to 5 mg oral THC.

Pharmacokinetics or body’s effects on the edibles

Absorption, distribution, and metabolism determine the onset and duration of action of each dosage form. Absorption has the most variability, and is affected by product lipophilicity, bioavailability as well as the inherent organ tissue differences. Cannabinoids are lipophilic and have low water solubility. Therefore, for oral routes, they are best absorbed in the presence of fat, oils or polar solvents, such as ethanol.

Absorption

For orally administered prescription cannabinoid medicines such as synthetic Δ9-THC (dronabinol) only 10 to 20% of the administered dose enters the systemic circulation indicating extensive metabolism in liver.

A randomized, double-blind, placebo-controlled, cross-over trial that evaluated the pharmacokinetics of oral THC in 10 older patients with dementia (mean age 77 years) over a 12 week period reported that median time to reach the maximum blood concentration was between one and two hours with THC pharmacokinetics increasing linearly with increasing dose, but again with wide inter-individual variation.

Absorption from an oral dose of 20 mg Δ9-THC in a chocolate cookie was described as slow and unreliable, with a systemic availability of only 4 to 12%

After oral administration of chocolate cookies containing 40 mg CBD in healthy human subjects, mean plasma CBD levels ranged between 1.1 and 11 ng/mL after one hour. Bioavailability through the oral route was estimated at 6%.

Although, the oral bioavailability appears rather low studies have been conducted in mice that show ways to improve this using fat-rich formulations. The basic idea is that administration of cannabinoids with a fatty meal or in the form of a lipid-rich cannabis containing cookie may increase systemic exposure and therefore change the efficacy of the drug by turning a barely effective dose into a highly effective one, or even, a therapeutic dose into a toxic one. By exploiting the intestinal biochemistry to potentially transfer THC and CBD to the systemic circulation via the intestinal lymphatic system and therefore avoid hepatic first pass metabolism, which would explain the increased bioavailability with the lipid-based formulation.

Metabolism

In contrast to the limited metabolism of Δ9-THC to the 11-hydroxy metabolite through smoking, oral administration of Δ9-THC results in a significantly higher metabolism of Δ9-THC to 11-hydroxy-THC resulting in similar plasma concentrations of Δ9-THC and 11-hydroxy Δ9-THC through the oral route. Blood levels of active 11-hydroxy metabolite through oral administration, are about three times higher than those seen with smoking. Furthermore, 11-hydroxy- Δ9- THC has been reported to be as psychoactive or even more psychoactive than the parent THC. Which could explain both the beneficial effects from cannabis edibles in medical patients and the adverse effects in recreational users that consume “too much”.

Excretion

Following oral administration, THC and its metabolites are excreted in both the feces and the urine. Biliary excretion is the major route of elimination, with about half of a radio-labelled THC dose being recovered from the feces within 72 hours in contrast to the 10 to 15% recovered from urine. Plasma clearance of CBD is similar to that of THC. A large portion of administered CBD is excreted intact or as its glucuronide form. 16% of an administered dose of CBD was recovered in the urine as intact or conjugated CBD within 72 h, while 33% of an administered dose of CBD was recovered mostly unchanged (accompanied by several mono-, di-hydroxylated and mono-carboxylic metabolites) in the feces within 72 h.

Benefits of taking edibles

Edible cannabis products have become extremely popular in places where they have become legal for medical and recreational use. A study published in the Journal of Substance Use and Misuse researched consumers perception of edible cannabis. They found that most participants preferred edibles to smoking cannabis because there was no smell from smoke and no second-hand smoke. Other reasons included convenience, discreetness, longer-lasting highs, less intense highs, and edible’s ability to aid in relaxation and reduce anxiety more so than smoking cannabis.

With cannabis edibles always remember the adage “start low and go slow”

Disadvantages and precautions from using edibles

Concerns and dislikes about edibles included delayed effects, unexpected highs, the unpredictability of the high, and inconsistency of distribution of cannabis in the product.

Front line health care workers and emergency room physicians are not fans of edibles. In Colorado for example, the bulk of the spike in cannabis-related emergency visits were the result of edibles —toddlers and children ingesting them accidentally, or adolescents and adults suffering severe physical and psychological effects.

The overall disadvantage of cannabis use on different organ systems remains a confusing issue. This is due in large part to the different experimental methodologies employed. For example, a longitudinal cohort study reported that cannabis use was not associated with progression of liver disease, as measured with the AST-to-platelet ratio index (APRI) score, in individuals with HIV-Hepatitis C co-infection. While other studies suggest there is a small but significant increase in liver fibrosis from cannabis use.

Best ways to take cannabis edibles

Conclusion or take away

Oral cannabis or cannabis edibles are a good way to consume cannabis for medicinal purposes in an environment where smoking is frowned upon. Additionally, it not only provides a longer lasting therapeutic effect, but also may lessen if dosed correctly many of the adverse effects associated with cannabis consumption, such as anxiety, increased heart-rate, etc. So, edible cannabis is a fantastic option for those people who would like to try this out instead of smoking or vaporization.


References

Brown S. Emergency physicians and public health experts call for tight regulations on cannabis edibles and concentrates. CMAJ. 2019.

Cuttler C, Spradlin A. Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU). PLoS One. 2017.

Barrus DG, Capogrossi KL, Cates SC, et al. Tasty THC: Promises and Challenges of Cannabis Edibles. Methods Rep RTI Press. 2016.

Lamy FR, Daniulaityte R, Sheth A, et al. “Those edibles hit hard”: Exploration of Twitter data on cannabis edibles in the U.S. Drug Alcohol Depend. 2016.

Bertha K. Madras. Are THC Levels in Oral Fluids and Blood Plasma Comparable after Oral Ingestion of Edibles Containing Cannabis or THC? Clinical Chemistry Mar. 2017.

Matthew N. Newmeyer, Madeleine J. Swortwood, Maria Andersson, Osama A. Abulseoud, Karl B. Scheidweiler, Marilyn A. Huestis. Cannabis Edibles: Blood and Oral Fluid Cannabinoid Pharmacokinetics and Evaluation of Oral Fluid Screening Devices for Predicting Δ9-Tetrahydrocannabinol in Blood and Oral Fluid following Cannabis Brownie Administration. Clinical Chemistry. 2017.

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