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?

The purpose of this study is to test whether a single-dose of Epidiolex (cannabidiol) is associated with reduced psychological, physiological, and neuroimaging measures of anxiety in people diagnosed with social anxiety disorder (SAD).

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.

How does the drug cannabidiol (CBD) differ from other treatments for social anxiety disorder?

Cannabidiol (CBD) is unique because it is a non-addictive component of the cannabis plant that reduces anxiety without causing sedation, unlike many traditional anxiety medications. It also acts quickly and has a lower risk of abuse, making it a promising alternative for those who do not respond well to existing treatments. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug Cannabidiol (CBD) for treating social anxiety disorder?

Research shows that CBD can significantly reduce anxiety in people with social anxiety disorder, as seen in studies where it decreased anxiety during public speaking and improved symptoms over a four-week period. CBD is also noted for its rapid action and lack of sedating side effects, making it a promising option for those who do not respond well to traditional treatments. ^{1 2 4 6 7}

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

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]

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 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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety. [2023]

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

Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Germany pubmed.ncbi.nlm.nih.gov

Subjective, behavioral and neurobiological effects of cannabis and cannabinoids in social anxiety. [2023]

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

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. [2022]

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

Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze. [2023]

7. Germany 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. [2022]