Cannabidiol for Anxiety

Overseen By Rosemary Smith, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Staci Gruber, Ph.D.

Disqualifiers: Liver disease, Kidney disease, Neurological disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well cannabidiol (CBD), a compound from cannabis, treats anxiety. Participants will take a CBD solution under their tongue three times a day for four weeks, alongside their usual treatments. The study includes three groups: one taking full-spectrum CBD, another taking single-compound CBD, and a third taking a placebo (a fake treatment). This trial suits adults who experience moderate to severe anxiety and speak English fluently.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. Participants will use the CBD solution in addition to their normal treatment regimen.

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

Research has shown that cannabidiol (CBD) is generally safe for most people. Studies on both full-spectrum and single-compound CBD have found that side effects are usually mild, including dry mouth, diarrhea, reduced appetite, and drowsiness.

In one study, participants who took CBD experienced less anxiety without major physical or mental issues. Another study found that a single dose of CBD reduced anxiety for some individuals. However, research on CBD safety remains limited, so some risks might not be fully known yet.

Overall, CBD appears safe, especially at lower doses, and could be a viable option for treating anxiety. Consulting a healthcare provider is advisable to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of cannabidiol (CBD) treatments for anxiety because they offer a novel approach compared to traditional medications like SSRIs and benzodiazepines. Unlike these standard treatments, which often come with a range of side effects and a longer time to onset, CBD is derived from the cannabis plant and may offer a quicker onset of relief with a potentially better side effect profile. The trial is investigating both full-spectrum and single-compound CBD, with the full-spectrum variant containing a wider array of cannabis plant components, which might work together to enhance therapeutic effects, known as the "entourage effect." This could lead to more comprehensive anxiety relief compared to traditional single-compound approaches.

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

Research has shown that cannabidiol (CBD) can help reduce anxiety symptoms. In this trial, participants will receive either full-spectrum CBD, single-compound CBD, or a placebo. Studies have found that full-spectrum CBD, which contains various plant compounds, significantly lowered anxiety in patients. For example, one study found that CBD reduced anxiety caused by drugs and decreased stress hormone levels. Similarly, single-compound CBD, a more purified form, has also proven effective. It reduced anxiety in stressful situations, like public speaking, with results similar to some anxiety medications. Overall, both types of CBD have shown promise in managing anxiety with few side effects. ^{4 5 6 7 8}

Who Is on the Research Team?

Staci Gruber, PhD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

Adults who speak English fluently, are at least 18 years old, and experience moderate to severe anxiety can participate. They must not use cannabis products more than once a month, have an IQ above 75, no serious head injuries or loss of consciousness over five minutes. Pregnant individuals or those with serious medical conditions like liver disease cannot join.

Inclusion Criteria

I learned English before I was 5 years old.

I experience moderate to severe anxiety.

Provides informed consent

Exclusion Criteria

English is not my first language.

Pregnancy

Current use of cannabis or cannabinoid products >1x/month

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment (Stage 1: Open-label)

Participants receive a high-CBD containing compound for anxiety, self-administering 1 ml under the tongue three times daily for four weeks

4 weeks

4 visits (in-person)

Treatment (Stage 2: Double-blind)

Participants receive either full-spectrum CBD, single-compound CBD, or placebo, self-administering 1 ml under the tongue three times daily for four weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Full-Spectrum Cannabidiol
• Placebo
• Single-Compound Cannabidiol

Trial Overview The study is testing the effects of sublingual CBD on anxiety compared to a placebo. Participants will add either whole plant-derived CBD or a placebo to their regular treatment for four weeks and undergo weekly assessments plus additional evaluations before and after the trial period.

How Is the Trial Designed?

Group I: Single-Compound Cannabidiol Experimental Treatment 1 Intervention

1 ml of single-compound sublingual cannabidiol solution (10 mg/ml CBD) administered three times per day (TID) for four weeks.

Group II: Full-Spectrum Cannabidiol Experimental Treatment 1 Intervention

1 ml of full-spectrum sublingual cannabidiol solution (10 mg/ml CBD) administered three times per day (TID) for four weeks.

Group III: Placebo Placebo Group 1 Intervention

1 ml of placebo solution administered three times per day (TID) for four weeks.

Who Is Running the Clinical Trial?

Staci Gruber, Ph.D.

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

In a 12-week open-label trial involving 31 young people aged 12-25 with treatment-resistant anxiety disorders, cannabidiol (CBD) significantly reduced anxiety severity by 42.6%, as measured by the Overall Anxiety Severity and Impairment Scale (OASIS).

CBD was found to have an adequate safety profile, with 80.6% of participants reporting mild adverse events like fatigue and low mood, but no serious or unexpected adverse events were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for Treatment-Resistant Anxiety Disorders in Young People: An Open-Label Trial. Berger, M., Li, E., Rice, S., et al.[2022]

Laparoscopic common bile duct exploration (LCBDE) with primary CBD closure shows promising short- and long-term outcomes, with a similar overall complication rate and hospital stay compared to T-tube drainage, based on a study of 85 patients.

While the operating time for primary closure was longer and there was a slightly higher incidence of bile leakage, all cases of leakage were managed successfully without the need for further surgery, indicating that primary closure can be a safe option for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriate Patient Selection Is Essential for the Success of Primary Closure After Laparoscopic Common Bile Duct Exploration. Wen, SQ., Hu, QH., Wan, M., et al.[2022]

Direct cholangioscopy (DC) is a safe and effective technique for evaluating and treating biliary disease, with a high success rate of 93.1% for intended interventions across 100 procedures in 84 patients.

While DC allows for direct examination of the bile ducts, its effectiveness is limited to the main bile duct, as access to proximal intrahepatic ducts beyond the bifurcation was only feasible in 10.8% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of direct transnasal cholangioscopy with standard ultraslim endoscopes: results of a large cohort study. Meves, V., Ell, C., Pohl, J.[2013]

Endoscopic dissection of the distal biliary tract (EDBT) was successfully performed in 48 out of 49 patients who experienced failed cannulation of the common bile duct, demonstrating its efficacy as a new technique.

The procedure was found to be safe, with no major complications such as perforation or uncontrolled bleeding, and only minor issues like pancreatitis occurring in a few cases, likely due to the careful endoscopic visualization during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic suprapapillary blunt dissection of the distal common bile duct in cases of difficult cannulation: a pilot series. Hashiba, K., D'Assunção, MA., Armellini, S., et al.[2006]

In a study comparing the effects of cannabidiol (CBD) on anxiety in male and female rats, it was found that female rats showed a significant response to CBD only during the late diestrus phase of their estrous cycle, requiring a much lower dose than males.

Both sexes exhibited anxiolytic-like effects from CBD, but the differences in responsiveness suggest that hormonal fluctuations in females may influence the drug's effectiveness, highlighting the need for sex-specific considerations in CBD treatment for anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze. Fabris, D., Carvalho, MC., Brandão, ML., et al.[2023]

A study of 27 patients undergoing 3D laparoscopic common bile duct exploration (LCBDE) showed that this single-stage procedure is safe and feasible, with no conversions to open surgery, readmissions, or mortality reported.

The use of 3D technology and absorbable barbed sutures in LCBDE resulted in a low complication rate, with only one case of bile leak and one retained stone, suggesting that this method is a viable alternative to the traditional two-stage approach involving ERCP and laparoscopic cholecystectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3D Laparoscopic common bile duct exploration with primary repair by absorbable barbed suture is safe and feasible. Tan, YP., Lim, C., Junnarkar, SP., et al.[2022]

A systematic review of eight studies, including six randomized controlled trials, suggests that cannabidiol (CBD) may be effective in reducing anxiety symptoms in various anxiety disorders, with doses ranging from 6 mg to 400 mg.

CBD was generally well-tolerated with minimal side effects, primarily fatigue and sedation, indicating its potential as a safe alternative therapy for anxiety management, although further research is needed for standardized dosing and efficacy assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cannabidiol in anxiety and anxiety-related disorders. Skelley, JW., Deas, CM., Curren, Z., et al.[2022]

In a study involving 32 healthy college students, single doses of cannabidiol (CBD) ranging from 150 to 600 mg did not significantly reduce test anxiety (TA) or general anxiety compared to a placebo.

This research is the first to show that CBD does not alleviate test anxiety, suggesting that further studies are needed to explore the specific conditions and mechanisms under which CBD may provide anxiety relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-Blind, Randomized, Placebo-Controlled Test of the Effects of Cannabidiol on Experiences of Test Anxiety Among College Students. Stanley, TB., Ferretti, ML., Bonn-Miller, MO., et al.[2023]

The transcystic common bile duct (CBD) decompression cannula is a safe and effective alternative to T-tube insertion after laparoscopic CBD exploration, used in 12 patients without any instances of postoperative dislodgement.

This method allows for primary closure of the choledochotomy, potentially accelerating recovery and reducing hospital stays, with a median stay of 4 days, compared to traditional T-tube drainage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcystic biliary decompression after direct laparoscopic exploration of the common bile duct. Hensman, C., Crosthwaite, G., Cuschieri, A.[2019]

A systematic review of 87 studies found that cannabidiol (CBD) had no effect on anxiety outcomes in 70.3% of observations, indicating that its efficacy for anxiety reduction may not be consistent across different studies and species.

There was no clear relationship between CBD drug levels and anxiety outcomes, suggesting that dosing recommendations for anxiety treatment cannot be straightforwardly established and further research is needed to clarify its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool. Kwee, CM., van Gerven, JM., Bongaerts, FL., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9628346/

open-label data from a two-stage, phase 2 clinical trial To date, only one double-blind clinical trial has examined CBD for anxiety; teenagers with SAD exhibited reduced anxiety following 4 weeks of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124003342

Therapeutic potential of cannabidiol (CBD) in anxiety ... A randomized clinical trial (RCT) demonstrated that CBD reduced drug-induced anxiety and salivary cortisol levels in patients (Hurd et al., 2019). Moreover, CBD ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40868129/

Clinical and Cognitive Improvement Following Treatment ... Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over ...

4. health.harvard.edu health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-201808242496

Cannabidiol (CBD): What we know and what we don't Anxiety: Studies and clinical trials are exploring the common report that CBD can reduce anxiety. Insomnia: Studies suggest that CBD may ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1876201824001667

A double blind multicenter randomized clinical trial Nanodispersible CBD oral solution was effective treating mild to moderate anxiety. · Nanodispersible CBD reduced GAD-7 and HAM-A scores (primary outcome).

6. library.samhsa.gov library.samhsa.gov/sites/default/files/pep22-06-04-003.pdf

Cannabidiol (CBD) – Potential Harms, Side Effects, and ... Many concerns have been raised about CBD use, particularly with regard to over-the-counter CBD products, as there are limited data on their safety and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol The only observed side effects were reduced sucrose preference, reduced food consumption and body weight in the nonoperated animals treated with CBD (50 mg/kg).

8. mayoclinic.org mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700

CBD: Safe and effective? CBD use also carries some risks. Though it's often well-tolerated, CBD can cause side effects, such as dry mouth, diarrhea, reduced appetite, drowsiness and ...