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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how smoked cannabis affects the body and its detection in the mouth. Researchers examine cannabis with varying amounts of THC (the component that causes a high) and CBD (commonly used for relaxation) to understand their effects. There are four groups: one with THC, one with CBD (CBD Cannabis), one with both (CBD + THC Cannabis), and a placebo group with no active ingredients. Individuals who occasionally use cannabis (once a week or less) and are not seeking treatment for their use might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that CBD (cannabidiol) is usually safe for people, though some may experience tiredness, diarrhea, or changes in appetite and weight. The FDA lacks extensive safety information on CBD, so awareness of these possible side effects is important.

For THC (delta-9-tetrahydrocannabinol), studies have indicated it can be harmful if swallowed, inhaled, or if it contacts the skin. It may also affect fertility and harm organs. THC is the primary component of cannabis that affects the mind.

When used together, CBD and THC are generally considered safe, especially compared to opioids. However, evidence suggests that CBD might enhance and prolong the effects of THC.

Overall, cannabis products containing CBD and THC are usually tolerated, but they carry potential risks. Prospective trial participants should carefully consider these risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this study because they explore the effects of different cannabis compounds on health in a new way. Unlike traditional pain management or anxiety treatments that might rely on opioids or benzodiazepines, this study uses smoked cannabis with varying combinations of CBD and THC. THC is known for its psychoactive effects, while CBD is non-psychoactive and may help reduce anxiety and inflammation. The study's unique approach allows for a direct comparison of the effects of CBD alone, THC alone, and their combination, offering potential insights into the role each plays in managing conditions more effectively and with potentially fewer side effects than current options. This could lead to more personalized and natural treatment alternatives in the future.

What evidence suggests that this trial's treatments could be effective?

Research has shown that cannabinoids, such as CBD and THC, can aid in managing conditions like chronic pain and symptoms of multiple sclerosis. In this trial, participants may receive cannabis containing both CBD and THC, which studies have found can reduce withdrawal symptoms and cravings. Another group will receive THC alone, known for its pain-relieving properties, with higher doses offering stronger relief. Participants may also receive CBD alone, which does not significantly affect daily activities, making it a suitable option for many. Additionally, combining CBD with THC might enhance THC's effects, potentially making them stronger and longer-lasting. ^{5 6 7 8 9}

Who Is on the Research Team?

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

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Therapeutic Effects of Cannabis and Cannabinoids - NCBI - NIH Cannabinoids are effective for chemotherapy-induced nausea/vomiting, chronic pain, and MS-related spasticity. Other conditions have inadequate information.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.16745

Efficacy of cannabidiol alone or in combination with Δ‐9‐ ... Nabiximols, which contains CBD and THC, demonstrated positive effects on cannabis withdrawal and craving symptoms.

3. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2023/02/cbd-may-increase-the-adverse-effects-of-thc-in-edible-cannabis-products-study-shows

CBD May Increase the Adverse Effects of THC in Edible ... The finding show that in edible cannabis products, CBD inhibits the metabolism, or breakdown, of THC, which may result in stronger and longer drug effects.

4. nature.com nature.com/articles/s41386-022-01478-z

Does cannabidiol make cannabis safer? A randomised ... These findings suggest that cannabis with a relatively high CBD:THC ratio may be less likely to have adverse effects than cannabis with a low CBD:THC ratio.

5. sciencedirect.com sciencedirect.com/science/article/pii/S030646032200274X

Perceptions about THC and CBD effects among adults with ... Despite such equivocal data, participants in our study endorsed expectancies that CBD-containing products are at least somewhat effective (and more effective ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393281/

Clinical Benefits and Safety of Medical Cannabis Products Two cannabinoids are of principal importance; delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive component, and also cannabidiol (CBD), considered ...

7. fda.gov fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

What to Know About Products Containing Cannabis and CBD The FDA has seen only limited data about CBD safety and these data point to real risks that need to be considered before taking CBD for any ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9294022/

Tetrahydrocannabinol and cannabidiol medicines for chronic ... THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse ...

9. fda.gov fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd

FDA Regulation of Cannabis and ... Safety of CBD in Humans – A Literature Review ... The most commonly known compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).