Smoked Cannabis Effects Study

(S-TACOFS Trial)

Overseen By Ziva Cooper, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Must not be taking: Illicit drugs, others

Disqualifiers: Substance use disorder, Axis I, others

Compensation: Varies

Number of Visits: 1

Duration: 6 hours

22 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the pharmacokinetics and pharmacodynamics of inhaled cannabis with varying amounts of delta-9-tetrahydrocannabinol (THC), and cannabidiol (CBD) and to evaluate detection of recently smoked THC in oral fluid.

Will I have to stop taking my current medications?

The trial requires that you do not use any medications that may affect the study outcomes. If you are currently taking such medications, you may need to stop them to participate.

What data supports the effectiveness of the drug in the Smoked Cannabis Effects Study?

Research shows that cannabidiol (CBD) has anxiolytic (anxiety-reducing) and antipsychotic effects when taken in high doses, and it may also interact with THC to influence pain relief and movement. Additionally, CBD has been used effectively in treating epilepsy, as seen with the FDA-approved drug Epidiolex. ^{1 2 3 4 5}

Is smoked cannabis generally safe for humans?

Research shows that cannabidiol (CBD), a component of cannabis, is generally safe with most side effects being mild to moderate, such as sedation and sleep disturbances. However, there are potential serious adverse effects, especially when interacting with other medications, so caution and monitoring are advised. ^{4 6 7 8 9}

How is the Smoked Cannabis Effects Study drug different from other treatments?

This study explores the effects of smoked cannabis with different combinations of CBD and THC, which is unique because it uses vaporization to achieve faster effects compared to traditional oral administration. The combination of CBD and THC aims to balance the psychoactive effects of THC with the calming effects of CBD, offering a potentially novel approach to treatment. ^{2 10 11 12 13}

Research Team

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

This trial is for men and women aged 21-55 who are not pregnant or breastfeeding, with a BMI of 18.5-34kg/m2, use cannabis weekly to monthly without seeking treatment, and agree to use contraception. Excluded are those with significant illness, other substance abuse disorders besides nicotine/caffeine, current heavy medication users, or those with respiratory issues.

Inclusion Criteria

If you have a Body Mass Index (BMI) between 18.5 and 34 kg/m2, you are considered to be within the healthy weight range.

I have used cannabis once a week or less in the past month.

I am a man or a woman not pregnant or breastfeeding, aged 21-55.

Exclusion Criteria

Currently enrolled in another research protocol

My doctor has checked my health history and found no issues with using cannabis.

Have you used cannabis / marijuana in the last month?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled cannabis with varying amounts of THC and CBD, and placebo, to assess pharmacokinetics and pharmacodynamics

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• CBD Cannabis
• CBD + THC Cannabis
• Placebo Cannabis
• THC Cannabis

Trial Overview The study tests the effects of inhaled cannabis by comparing placebo (no THC/CBD), just THC (20 mg), just CBD (20 mg), and a combination of THC and CBD (20 mg each). It aims to understand how these substances affect the body and how they can be detected in oral fluid after smoking.

Participant Groups

Group I: 20 mg THC Experimental Treatment 1 Intervention

Smoked cannabis with THC

Group II: 20 mg CBD + 20 mg THC Experimental Treatment 1 Intervention

Smoked cannabis with CBD and THC

Group III: 20 mg CBD Experimental Treatment 1 Intervention

Smoked cannabis with CBD

Group IV: Placebo Placebo Group 1 Intervention

Smoked placebo cannabis

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

Approved in European Union as Epidiolex for:

• Severe myoclonic epilepsy in infancy (Dravet syndrome)
• Lennox-Gastaut syndrome

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Sativex for:

• Central neuropathic pain in multiple sclerosis
• Cancer-related pain

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

High doses of CBD can be effectively vaporized, with a maximum of 200 mg yielding about 40% availability in the vapor phase, which is significant for achieving faster therapeutic effects.

The study found that the vaporization efficiency of THC and CBD is dynamic and dose-dependent, meaning that the presence of one cannabinoid can affect the availability of the other, which is important for optimizing their combined therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation. Solowij, N., Broyd, SJ., van Hell, HH., et al.[2022]

In a study of 15 patients with treatment-resistant epilepsy, 12 weeks of treatment with pharmaceutical-grade cannabidiol (CBD) showed minor improvements in white matter integrity, specifically increasing fractional anisotropy in certain brain tracts.

The results suggest that while CBD may have some short-term effects on white matter structure, these changes are relatively minor and indicate that CBD's impact on brain integrity may not be significant in the context of treatment for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. Houston, JT., Nenert, R., Allendorfer, JB., et al.[2022]

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

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]

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]

Serious adverse effects (SAEs) from cannabidiol (CBD) are rare, with most being mild to moderate, and primarily include elevated liver enzymes, sedation, and respiratory infections, particularly when used with certain medications.

Elevated liver enzymes were specifically linked to the use of valproate, while sedation and lethargy were associated with clobazam, indicating that patients, especially those with epilepsy, should be closely monitored for potential drug-drug interactions when using CBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. Dos Santos, RG., Guimarães, FS., Crippa, JAS., et al.[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]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

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 involving 18 healthy adults, vaporized CBD and CBD-dominant cannabis produced noticeable subjective effects, such as increased enjoyment, while oral CBD did not show any significant effects compared to placebo.

Importantly, neither vaporized CBD nor CBD-dominant cannabis caused cognitive or psychomotor impairment, suggesting that these forms of CBD may be safer alternatives to THC-dominant products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. Spindle, TR., Cone, EJ., Goffi, E., et al.[2022]

From 1970 to 2017, the concentration of delta-9-tetrahydrocannabinol (THC) in cannabis has significantly increased, with an annual rise of 0.29% in herbal cannabis and 0.57% in cannabis resin, based on a review of 12 studies involving over 66,000 samples.

In contrast, the concentration of cannabidiol (CBD) remained stable over the same period, indicating that while THC levels are rising, the potential moderating effects of CBD on THC's impact may not be changing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta-analysis. Freeman, TP., Craft, S., Wilson, J., et al.[2022]

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]

References

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

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. [2022]

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

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. [2022]

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

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

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

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. [2021]

10. Mexico pubmed.ncbi.nlm.nih.gov

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

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Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta-analysis. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

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