CBD for Cannabis Effects

(SPECTRE Trial)

Recruiting at 1 trial location

Overseen By Didier Jutras-Aswad, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Cannabis, Cannabinoids

Disqualifiers: Severe psychiatric, Liver disease, Hypertension, Kidney disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how varying amounts of CBD (cannabidiol) affect the psychoactive effects of THC, the main ingredient in cannabis responsible for the "high." Researchers are testing different CBD:THC ratios to observe changes in THC's effects and sensations. Individuals who have tried cannabis but are not regular users (less than three days in the last month) might be suitable for this study. Participants will attend several sessions to test different CBD:THC combinations. As a Phase 1 and Phase 2 trial, the study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that might interact with cannabis at least 7 days before the experimental sessions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CBD is generally safe for people, with most experiencing only minor side effects. Common side effects include fatigue, diarrhea, or changes in appetite, but these are usually mild.

In this trial, researchers are testing different amounts of CBD combined with THC. The combination appears safe, but it is important to note that THC can affect mood or behavior due to its psychoactive effects.

As this study is in its early stages, the focus is on how the body processes the treatment and identifying any side effects. This careful testing is a positive step to ensure the treatment's safety for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Cannabidiol (CBD) to manage cannabis effects because it offers a unique approach compared to traditional treatments. Unlike typical options that may focus on behavioral therapies or pharmacological interventions to reduce cannabis dependence or manage its effects, CBD directly interacts with the body's endocannabinoid system. This interaction holds potential for balancing the psychoactive effects of THC, the component of cannabis responsible for the "high." By modulating these effects, CBD could offer a more targeted and potentially safer way to address issues related to cannabis use, which is why researchers are keen to explore its possibilities.

What evidence suggests that this trial's treatments could be effective for modulating THC-induced effects?

Research shows that CBD (cannabidiol) might reduce the "high" feeling caused by THC, the component of cannabis responsible for this sensation. Studies have found that CBD can lower anxiety from cannabis use. In these studies, participants using CBD reported feeling less anxious and had lower stress hormone levels. Some research also suggests that CBD might help with symptoms like confusion or hallucinations. While more research is needed, these findings suggest that CBD could balance some effects of THC. In this trial, participants will join different groups to receive various doses of CBD:THC ratios, allowing researchers to evaluate the effects of CBD on THC-induced experiences. ^{6 7 8 9 10}

Who Is on the Research Team?

Didier Jutras-Aswad, MD, MS

Principal Investigator

CRCHUM

Are You a Good Fit for This Trial?

This trial is for adults aged 21-49 who have used cannabis at least once but not more than three times in the past month. They must understand English or French, agree to study procedures, and women must use birth control if they can have children. People with certain lung function levels can join.

Inclusion Criteria

You have consumed cannabis in the past and not more than three days during the last month.

I am between 21 and 49 years old.

Females must be postmenopausal (12 months of natural amenorrhea and 45 years or older), have had a documented surgical sterilization procedure, or for those of childbearing potential they must provide a negative pregnancy test result at screening and each visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of CBD:THC ratios (20:20 mg, 40:20 mg, 80:20 mg, 120:20 mg) and a control product (0:20 mg) over five study visits.

5 weeks

5 visits (in-person), with at least 1 week between each visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol

Trial Overview

The study tests how CBD affects THC's psychoactive and behavioral effects by comparing different CBD:THC ratios (0:20, 20:20, 40:20, 80:20, 120:20) to a control product. It aims to find out if CBD changes THC effects that aren't usually caught by standard research tools.

How Is the Trial Designed?

Group I: CBD:THC Group 5 Experimental Treatment 1 Intervention

Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

Group II: CBD:THC Group 4 Experimental Treatment 1 Intervention

Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

Group III: CBD:THC Group 3 Experimental Treatment 1 Intervention

Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

Group IV: CBD:THC Group 2 Experimental Treatment 1 Intervention

Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

Group V: CBD:THC Group 1 Experimental Treatment 1 Intervention

Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Published Research Related to This Trial

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

A systematic review of 51 clinical studies indicates that cannabidiol (CBD) is generally well tolerated in humans, with most adverse events (AEs) being mild to moderate, such as diarrhea and sedation.

While serious AEs are rare, they can occur, particularly when CBD is taken with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review. Madeo, G., Kapoor, A., Giorgetti, R., et al.[2023]

CBD can enhance the pain-relieving effects of THC, particularly in terms of antinociception, but these effects are small and vary depending on the timing of administration and the specific tests used.

CBD inhibits the metabolism of THC, with a more pronounced effect observed in female rats compared to males, suggesting that sex differences may play a role in how CBD interacts with THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity. Britch, SC., Wiley, JL., Yu, Z., et al.[2018]

Nicotinamide was well tolerated in seven patients with glioblastoma multiforme undergoing radiation therapy, showing no adverse effects on blood pressure, heart rhythm, or body temperature.

The pharmacokinetic study indicated that nicotinamide reached peak plasma levels above 100 mg/l within 45 minutes, suggesting that the timing of drug administration could enhance the effectiveness of radiation therapy, although tumor response is still to be evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and tolerance of nicotinamide combined with radiation therapy in patients with glioblastoma multiforme. Cartei, F., Danesi, R., Ducci, F., et al.[2019]

A systematic review of 34 studies found that high doses of cannabidiol (CBD) may be effective in treating conditions like social anxiety disorder, insomnia, and epilepsy, particularly at doses between 150-600 mg/day.

The review also highlighted that CBD can interact with ∆9-THC in complex ways, sometimes enhancing and other times inhibiting its effects, indicating the need for careful dosing and consideration of CBD's role in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol in humans-the quest for therapeutic targets. Zhornitsky, S., Potvin, S.[2022]

In a study involving 18 healthy adults, a CBD-dominant cannabis extract produced stronger adverse effects, such as increased anxiety and cognitive impairment, compared to a Δ9-THC-dominant extract, despite both containing the same dose of Δ9-THC (20 mg).

The findings suggest that CBD may inhibit the metabolism of Δ9-THC, leading to higher plasma concentrations and more pronounced effects, challenging the belief that CBD mitigates the negative effects of Δ9-THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial. Zamarripa, CA., Spindle, TR., Surujunarain, R., et al.[2023]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

In a study of 74 head and neck cancer patients, combining radiotherapy with carbogen and nicotinamide was found to be a generally safe treatment, although some patients experienced increased skin reactions and mucosal damage, particularly with accelerated treatment schedules.

While nicotinamide was associated with side effects like nausea and vomiting in a significant number of patients, the overall treatment was manageable, and preliminary tumor control rates were promising, suggesting further clinical testing is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer: feasibility and toxicity. Kaanders, JH., Pop, LA., Marres, HA., et al.[2019]

A treatment regimen combining accelerated radiotherapy with carbogen and high-dose nicotinamide (NAM) was evaluated in six patients with head and neck squamous cell carcinomas, showing that this approach is feasible and tolerable.

While the treatment was generally well-received, some patients experienced side effects such as nausea and vomiting, and one patient with preexisting heart disease faced severe hypotension and renal dysfunction, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of accelerated radiotherapy in combination with carbogen breathing and nicotinamide (ARCON). Zackrisson, B., Franzén, L., Henriksson, R., et al.[2019]

Topical application of imiquimod 5% cream, used three times a week for five weeks, shows promise as an alternative treatment for Bowen's disease, a type of intraepithelial neoplasm of the penis.

Imiquimod acts as an immune response modifier with indirect antiviral and antitumor effects, and it has been associated with few adverse effects, making it a potentially safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of Bowen's disease of the penis with imiquimod 5% cream]. de Diego Rodríguez, E., Villanueva Peña, A., Hernández Castrillo, A., et al.[2019]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

In a randomized study, daily applications of 5% imiquimod cream resulted in a 75% clearance rate of lesions in female patients with molluscum contagiosum and a 50% clearance rate in those with external genital warts, demonstrating its efficacy in treating these conditions.

The most common side effect was erythema, occurring in 24% of patients, while other side effects included excoriation (16%), erosions (10%), and pain (4%), indicating that while imiquimod is effective, it can also cause notable adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study on the use of imiquimod for the treatment of genital molluscum contagiosum and genital warts in female patients. Puri, N.[2021]

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