Cannabidiol for Social Anxiety Disorder

(CAN-SAD Trial)

Recruiting at 1 trial location

Overseen By Omar Rutledge, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts Institute of Technology

Must not be taking: Beta-blockers, Benzodiazepines, Cannabis

Disqualifiers: Bipolar, Schizophrenia, Diabetes, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a single dose of Epidiolex, a form of cannabidiol (CBD), can reduce anxiety in individuals diagnosed with social anxiety disorder (SAD). Participants will receive either a CBD dose or a placebo to compare effects. This study may suit those who have experienced social anxiety for some time and have not changed their medications in the past month. As a Phase 4 trial, Epidiolex is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that your current medications have been stable for the past 30 days, meaning no changes to dose or frequency. If you are taking beta-blockers or benzodiazepines, you must stop using them at least 2 weeks before participating.

What is the safety track record for Cannabidiol?

Research has shown that cannabidiol, the main ingredient in Epidiolex, is generally safe for people. Studies suggest it might help treat anxiety disorders, such as social anxiety disorder.

Regarding safety, the FDA has approved cannabidiol for treating certain types of epilepsy, indicating a well-understood safety profile. Other studies have identified common side effects, including fatigue, diarrhea, and changes in appetite or weight, which are usually mild.

Overall, research supports the safety of cannabidiol for use, with few serious side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about cannabidiol as a treatment for social anxiety disorder because it offers a natural, plant-derived alternative to traditional medications like SSRIs and benzodiazepines. Unlike these standard options, which often come with a host of side effects and require regular dosing, cannabidiol is being explored for its potential to provide relief with a single dose. Additionally, it interacts with the body's endocannabinoid system, which may offer a new mechanism of action by modulating anxiety differently than existing therapies.

What evidence suggests that this treatment might be an effective treatment for social anxiety disorder?

Research has shown that cannabidiol (CBD), which participants in this trial may receive, can help reduce symptoms of social anxiety disorder. In studies, people with social anxiety felt less anxious after taking CBD. For instance, one study found that teenagers with social anxiety felt less anxious after using CBD for four weeks. Another review found that taking CBD regularly can lower social anxiety symptoms. While some results vary, the overall evidence suggests that CBD might help reduce anxiety with few side effects. Participants in this trial may also receive a placebo, which serves as a comparison to evaluate CBD's effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

John Gabrieli, PhD

Principal Investigator

Massachusetts Institute of Technology

Are You a Good Fit for This Trial?

Adults aged 18-55 with social anxiety disorder, not using drugs or certain medications like beta-blockers and benzodiazepines recently. Participants must be fluent in English, right-hand dominant, have stable medication use for the last month, and women must test negative for pregnancy.

Inclusion Criteria

Ability and willingness to provide written informed consent

Current medications are stable for past 30 days (no changes to dose or frequency)

Negative result on urine drug screening

Exclusion Criteria

Presence of severe medical illness that would prevent completion of study procedures

I am not taking any medications that strongly interact with CYP3A4 or CYP2C19.

History of any traumatic brain injury

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single-dose of Epidiolex or placebo and undergo the Trier Social Stress Test (TSST)

1 day

1 visit (in-person)

Neuroimaging

Neuroimaging measures of emotional processing and self-referential processing are acquired using fMRI

Approximately 3.5 hours after drug administration

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol
• Placebo

Trial Overview The trial is testing if a single dose of Epidiolex (cannabidiol) can lower anxiety levels in people with social anxiety disorder. It measures psychological responses, physiological signs of stress, and brain activity changes.

How Is the Trial Designed?

Group I: Cannabidiol Active Control 1 Intervention

300mg Cannabidiol (3mL Epidiolex), oral, single-dose

Group II: Placebo Placebo Group 1 Intervention

Placebo (3mL sesame seed oil), oral, single-dose

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

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 European Union as Epidiolex for:

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

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Massachusetts Institute of Technology

Lead Sponsor

Trials

104

Recruited

12,810,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a study involving 24 treatment-naïve patients with Generalized Social Anxiety Disorder (SAD), a single dose of 600 mg of CBD significantly reduced anxiety and cognitive impairment during a public speaking test compared to a placebo group.

The effects of CBD allowed SAD patients to perform similarly to healthy controls in terms of anxiety levels and discomfort, suggesting that CBD may be an effective treatment option for managing symptoms of social anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Bergamaschi, MM., Queiroz, RH., Chagas, MH., et al.[2022]

In a study involving 10 treatment-naïve patients with generalized social anxiety disorder, a single oral dose of 400 mg of cannabidiol (CBD) significantly reduced subjective anxiety compared to a placebo.

The anxiolytic effects of CBD were linked to changes in brain activity, specifically decreased blood flow in areas like the left parahippocampal gyrus and increased activity in the right posterior cingulate gyrus, suggesting a mechanism involving limbic and paralimbic brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Crippa, JA., Derenusson, GN., Ferrari, TB., et al.[2022]

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]

In a double-blind study involving 37 Japanese teenagers with social anxiety disorder, daily treatment with 300 mg of cannabidiol (CBD) for 4 weeks significantly reduced anxiety symptoms.

The effectiveness of CBD was measured using established scales, showing promise as a non-addictive treatment option for social anxiety disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders. Masataka, N.[2020]

Cannabidiol (CBD) has been found to effectively reduce social anxiety at intermediate doses (300-600 mg), while lower or higher doses do not have the same effect, indicating a dose-dependent response.

Delta-9-tetrahydrocannabinol (THC) can either reduce or increase social anxiety depending on the dose, with lower doses showing a reduction and higher doses leading to an increase, suggesting that CBD may help mitigate the anxiety-inducing effects of THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety. Rosário, BDA., Lemes, JA., de Lima, MP., et al.[2023]

A study involving 61 healthy young adults found that a single oral dose of cannabidiol (CBD) did not reduce fear reactivity during a carbon dioxide challenge, indicating that CBD may not be effective for this purpose.

Despite previous evidence suggesting CBD can reduce anxiety, this research highlights that it does not impact self-reported fear or physiological responses, marking a significant finding in the understanding of CBD's effects on fear in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled test of the effects of cannabidiol on fear elicited by a 10% carbon dioxide-enriched air breathing challenge. Leen-Feldner, EW., Bynion, TM., Eglit, GML., et al.[2022]

Cannabidiol (CBD) shows promise as a treatment for social anxiety disorder (SAD), significantly reducing anxiety in both healthy volunteers and individuals with SAD without causing sedation, based on a systematic review of existing literature.

Chronic administration of CBD has been shown to decrease social anxiety symptoms in individuals with SAD, indicating its potential as a viable alternative to current treatments, though further research is needed to determine optimal dosing and long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety. Fliegel, DK., Lichenstein, SD.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9983614/

Systematic literature review of human studies assessing ... These results suggest that repeated administration of CBD is effective in decreasing social anxiety symptoms, consistent with prior studies ...

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

Therapeutic potential of cannabidiol (CBD) in anxiety ... Our findings suggest that CBD has promising efficacy in treating specific anxiety symptoms (including GAD, SAD, OCD, and PTSD) in addition to standard ...

3. nature.com nature.com/articles/s43856-022-00202-8

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 ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05823753

NCT05823753 | Cannabidiol to Reduce Anxiety Reactivity Higher scores reflect greater levels of anxiety. A standardized mean difference (SMD) decrease of 0.3 or greater in favor of CBD (either 300 mg/d or 900 mg/d) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11595441/

The Impact of Cannabidiol Treatment on Anxiety Disorders Despite these conflicting outcomes, the data suggest that CBD may reduce anxiety with minimal adverse effects when compared to a placebo.

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

An Update on Safety and Side Effects of Cannabidiol Some studies indicate that under certain circumstances, CBD acute anxiolytic effects in rats were reversed after repeated 14-day administration of CBD. However, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04086342

CHI-902 for Treatment of Social Anxiety Disorder This randomized doubleblind, placebo-controlled trial of CBD in adults with SAD will evaluate the efficacy, tolerability and safety of CBD oil (CHI-902) in SAD.

8. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/2055/randomized-placebo-controlled-trial/

Randomized placebo controlled trial to determine the ... Randomized placebo controlled trial to determine the biological signature of cannabidiol as a treatment for social anxiety disorder · Brief description of study.