Cannabis Edibles for Understanding Cannabis Use Effects

Overseen By Lindsay Howard

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: CYP inhibitors, CYP inducers, Warfarin, others

Disqualifiers: Illicit drug use, Allergies, Psychiatric condition, others

Compensation: Varies

Number of Visits: 9

Duration: 9 sessions

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will examine the pharmacokinetics and pharmacodynamics of delta-9-tetrahydrocannabinol (THC)-infused chocolates, gummies, and drinks. Healthy adults (N=40) will complete 9 drug administration sessions, including an overnight stay prior to each session. Participants will consume THC containing products in a fasted state; following drug administration, the participants will complete cognitive and psychomotor tasks, subjective assessments, have blood collected, and vital signs monitored.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that may interact with the study drug, including some that affect liver enzymes (CYP2CP and CYP3A4) and those with a narrow safety margin like warfarin. It's best to discuss your current medications with the study team to see if they are affected.

What data supports the effectiveness of the cannabis drug used in the trial?

Research shows that cannabis products with THC can increase feelings of intoxication and elation, while CBD may reduce tension without causing intoxication. Additionally, cannabinoids have shown potential as treatments for conditions like pain, multiple sclerosis, and appetite stimulation in serious illnesses. ^{1 2 3 4 5}

Is it safe to consume cannabis edibles?

Cannabis edibles, especially those with high THC levels, can cause intoxication and other side effects, but CBD may reduce these effects. Regular users report low levels of negative effects, but caution is advised due to potential risks with high THC exposure. ^{3 4 5 6 7}

How does the cannabis edible treatment differ from other treatments for cannabis use effects?

Cannabis edibles offer a unique way to experience the effects of cannabis through ingestion, which can lead to a slower onset but longer-lasting effects compared to smoking or vaping. This method allows for a more controlled dosage and may reduce respiratory risks associated with inhalation. ^{8 9 10 11 12}

Research Team

Tory Spindle, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for healthy adults aged 21-55 who have used THC-dominant cannabis before. They must not be pregnant, nursing, or have a history of significant health issues. Participants should not use other drugs or alcohol and must pass drug screenings. A BMI between 16 to 38 kg/m2 is required.

Inclusion Criteria

Have prior experience using THC-dominant cannabis

Have a body mass index (BMI) in the range of 16 to 38 kg/m2

I am between 21 and 55 years old.

Exclusion Criteria

Evidence of current psychiatric condition (based on MINI for DSM-5)

History of significant allergic reaction or significant hypersensitivity to cannabis or to any of the other ingredients in the study products

History of or current evidence of a significant medical condition that, in the opinion of the investigator or medical staff, will impact the participant's safety or interfere with study outcomes

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete 9 drug administration sessions with THC-infused edibles, including cognitive and psychomotor tasks, subjective assessments, blood collection, and vital signs monitoring.

9 sessions

9 visits (in-person, overnight stay)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabis
• Placebo

Trial Overview The study tests how the body processes and responds to THC-infused chocolates, gummies, and drinks in fasted individuals through cognitive tasks, blood tests, and vital sign monitoring over nine sessions with overnight stays.

Participant Groups

Group I: Low Dose Gummy Experimental Treatment 1 Intervention

Participants will self-administer a gummy containing 10mg THC

Group II: Low Dose Chocolate Experimental Treatment 1 Intervention

Participants will self-administer chocolate containing 10mg THC

Group III: Low Dose Beverage Experimental Treatment 1 Intervention

Participants will self-administer a beverage containing 10mg THC

Group IV: High Dose Gummy Experimental Treatment 1 Intervention

Participants will self-administer a gummy containing 25mg THC

Group V: High Dose Chocolate Experimental Treatment 1 Intervention

Participants will self-administer chocolate containing 25mg THC

Group VI: High Dose Beverage Experimental Treatment 1 Intervention

Participants will self-administer a beverage containing 25mg THC

Group VII: Placebo Gummy Placebo Group 1 Intervention

Participants will self-administer a gummy containing 0mg THC

Group VIII: Placebo Chocolate Placebo Group 1 Intervention

Participants will self-administer chocolate containing 0mg THC

Group IX: Placebo Beverage Placebo Group 1 Intervention

Participants will self-administer a beverage containing 0mg THC

Cannabis is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy

Approved in European Union as Cannabis for:

• Spasticity associated with multiple sclerosis
• Chronic pain

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study with 20 participants, it was found that telling individuals they received an edible cannabis lollipop containing THC (when it was actually a placebo) could induce a significant placebo effect on feelings of intoxication and negative mood.

This research is the first to show that edible forms of cannabis can produce a placebo effect, highlighting the psychological impact of expectations on perceived intoxication, even when no active THC is consumed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay. Loflin, MJE., Earleywine, M., Farmer, S., et al.[2018]

A meta-analysis of 72 controlled clinical trials indicates that cannabinoids have significant therapeutic potential for various conditions, including as antiemetics, appetite stimulants, and analgesics.

Cannabinoids may be beneficial in treating debilitating diseases such as cancer and AIDS, as well as neurological disorders like multiple sclerosis and epilepsy, highlighting their diverse applications in medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. Ben Amar, M.[2022]

Cannabis sativa, commonly known as marijuana, has a long history of use for therapeutic, intoxicating, and spiritual purposes, and its legal status is evolving, which may enhance understanding of its effects and challenges, particularly with potent extracts.

The active compounds Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been identified, with Δ9-THC being responsible for psychoactive effects and CBD being non-intoxicating, making it a focus for potential clinical applications without the risk of abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin. Canseco-Alba, A., Rodríguez-Manzo, G.[2023]

In a study of 99 regular cannabis users, those who consumed a THC+CBD edible product reported similar positive effects (like intoxication and elation) as those who consumed a THC-only product, but with lower THC consumption and plasma levels.

Participants using CBD-dominant products experienced less intoxication compared to those using THC-dominant products, suggesting that CBD may mitigate some of the intoxicating effects of THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid Exposure and Subjective Effects of THC and CBD in Edible Cannabis Products. Gibson, LP., Mueller, RL., Winiger, EA., et al.[2022]

In a study involving 3,341 participants who recorded nearly 20,000 cannabis sessions, patients reported an average symptom improvement of 3.5 on an 11-point scale, indicating that cannabis can effectively alleviate various health symptoms.

Dried cannabis flower was found to provide greater symptom relief compared to other forms, and higher levels of THC were linked to better symptom improvement, while CBD levels did not significantly impact symptom changes or side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association between Cannabis Product Characteristics and Symptom Relief. Stith, SS., Vigil, JM., Brockelman, F., et al.[2020]

A study of 511 samples from various hemp food products in Germany found that while hemp beverages and seeds generally contain safe levels of THC, some hemp food supplements can have dangerously high THC levels, with 18% of samples exceeding the lowest observed adverse effect level (LOAEL).

There has been a significant decrease in THC content in hemp food supplements from 2018 to 2021, but tea products have shown an increase in THC levels, suggesting a need for better regulation of these products to ensure consumer safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time Trends of Tetrahydrocannabinol (THC) in a 2008-2021 German National Survey of Hemp Food Products. Dräger, H., Barthlott, I., Golombek, P., et al.[2022]

A significant portion of cannabis products (58.5%) lacked information on CBD content, and most products (72-100%) with CBD fell into the highly intoxicating THC:CBD ratio category (≥1:1), suggesting that patients may experience enhanced acute effects and intoxication.

Medical and recreational cannabis products are largely similar, posing a risk for patients seeking therapeutic benefits, as they may inadvertently consume high-potency products that lead to unwanted side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot. Pennypacker, SD., Cunnane, K., Cash, MC., et al.[2022]

In a 6-month randomized placebo-controlled trial with 81 healthy volunteers, different formulations of lutein, zeaxanthin, and meso-zeaxanthin significantly increased serum carotenoid levels compared to placebo, indicating their efficacy in enhancing bioavailability.

The micromicellar formulation of zeaxanthin and meso-zeaxanthin diacetates showed a notably higher increase in serum concentrations compared to traditional formulations, suggesting it is a promising advancement for improving the absorption of these carotenoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study. Green-Gomez, M., Prado-Cabrero, A., Moran, R., et al.[2020]

This systematic review analyzed 11 studies on the acute effects of plant ingestion, revealing that such intake can significantly influence gene expression related to immune response, inflammation, metabolism, and cancer.

The findings suggest that acute plant consumption may impact various health pathways, highlighting the need for further research to validate these effects and explore the short-term health benefits of dietary plants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of dietary plant nutrients on transcriptome profiles: evidence from human studies. Jamshidi, N., Mantri, N., Cohen, MM.[2020]

The study found that olive oil significantly enhances the absorption of carotenoids compared to coconut oil, with bioaccessibility rates of 24.0% for olive oil versus 14.9% for coconut oil.

Emulsified fats improve carotenoid absorption, showing a 40% increase in plasma carotenoid levels compared to nonemulsified fats, highlighting the importance of both fat type and emulsification in dietary strategies for optimizing nutrient absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dietary fat type and emulsification on carotenoid absorption: a randomized crossover trial. Yao, Y., Yang, Z., Yin, B., et al.[2023]

Oleogels made with organic candelilla wax significantly improved the physicochemical properties of cookies, such as texture and moisture content, while reducing fat migration, indicating a successful alternative to traditional fats.

Cookies made with 70% oleogel (C70) were the most favored in sensory evaluations, suggesting that oleogels can enhance both the nutritional profile and consumer acceptance of baked goods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Fat Replacement by Using Organic-Candelilla-Wax-Based Oleogels on the Physicochemical and Sensorial Properties of a Model Cookie. Flores-García, CL., Medina-Herrera, N., Rodríguez-Romero, BA., et al.[2023]

Carotenoids, such as beta-carotene and lycopene, are important micronutrients in our diet, and their bioavailability can be influenced by food processing, storage, and cooking methods.

The review highlights that certain technological changes in food preparation can enhance the absorption of carotenoids, suggesting that how we prepare our food can significantly impact their nutritional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Maiani, G., Castón, MJ., Catasta, G., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. [2022]

3. Mexico pubmed.ncbi.nlm.nih.gov

Cannabis: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Cannabinoid Exposure and Subjective Effects of THC and CBD in Edible Cannabis Products. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The Association between Cannabis Product Characteristics and Symptom Relief. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Time Trends of Tetrahydrocannabinol (THC) in a 2008-2021 German National Survey of Hemp Food Products. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Acute effects of dietary plant nutrients on transcriptome profiles: evidence from human studies. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of dietary fat type and emulsification on carotenoid absorption: a randomized crossover trial. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Fat Replacement by Using Organic-Candelilla-Wax-Based Oleogels on the Physicochemical and Sensorial Properties of a Model Cookie. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. [2022]