CBD for Cannabis Effects

(SPECTRE Trial)

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

Trial Summary

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.

What data supports the effectiveness of the drug Cannabidiol (CBD) for cannabis effects?

Research suggests that high doses of CBD may help with conditions like social anxiety, insomnia, and epilepsy, and it can sometimes change the effects of THC, another compound in cannabis. However, the effects can vary, and more studies are needed to understand how CBD works with cannabis. ^{1 2 3 4 5}

Is CBD generally safe for human use?

CBD is generally well tolerated in humans, but it can cause side effects like sleepiness, diarrhea, and changes in appetite. It may also interact with other medications, especially those affecting the liver, so it's important to monitor for any adverse effects and consult with a healthcare provider. ^{2 4 6 7 8}

How does the drug Cannabidiol (CBD) differ from other treatments for cannabis effects?

Cannabidiol (CBD) is unique because it is a non-psychoactive component of cannabis that may counteract some of the psychoactive effects of THC, the main active ingredient in cannabis. Unlike other treatments, CBD does not produce a 'high' and is being studied for its potential to reduce anxiety and other negative effects associated with cannabis use. ^{9 10 11 12 13}

What is the purpose of this trial?

The purposes of this study are 1) to determine if CBD modulates THC-induced acute psychoactive effects at different CBD:THC ratios, compared with the control product (0:20, 20:20, 40:20, 80:20, 120:20) and 2) to determine if different doses of CBD modulate other THC induced behavioral effects, compared with the control product and 3)To explore qualitatively whether CBD modulates THC effects by mechanisms that are not detected with standard clinical research tools.

Research Team

Didier Jutras-Aswad, MD, MS

Principal Investigator

CRCHUM

Eligibility Criteria

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

I am between 21 and 49 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol in humans-the quest for therapeutic targets. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

3. Ireland pubmed.ncbi.nlm.nih.gov

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

5. United States 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. [2023]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Update on Cannabidiol Clinical Toxicity and Adverse Effects: A Systematic Review. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

9. Ireland pubmed.ncbi.nlm.nih.gov

Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer: feasibility and toxicity. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Acute effects of accelerated radiotherapy in combination with carbogen breathing and nicotinamide (ARCON). [2019]

11. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and tolerance of nicotinamide combined with radiation therapy in patients with glioblastoma multiforme. [2019]

12. Spain pubmed.ncbi.nlm.nih.gov

[Treatment of Bowen's disease of the penis with imiquimod 5% cream]. [2019]

13. India 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. [2021]