Cannabidiol as a Treatment for Social Anxiety Disorder (R61)

NCT05571592 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 22-00568-R61
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The R61 will include two CBD dose levels vs placebo (PBO) and examine potential engagement with two primary targets in a 3-week randomized controlled trial design. Willing and eligible subjects will be randomized to one of three randomized double-blind treatments (n = 20 each group): 1) CBD 800 mg (400 mg twice daily), 2) CBD 400 mg (200 mg twice daily), or 3) PBO twice daily for three weeks. Participation is estimated at approximately 1 month from end of screening to endpoint for the primary R61 study period. This includes screening, baseline, week 2 stress task, Week 3 2-day imaging paradigm, and clinical safety assessments at weeks 2 and 3.

Conditions

Social Anxiety Disorder

Keywords

CBD; Cannabidiol

Outcome Measures

Primary Outcomes (3)

• Change in Stress Task-Induced Anxiety as Measured by Visual Analogue Mood Scale (VAMS)

  Participants rate their anxiety using the VAMS Anxiety Subscale, which assesses the intensity of anxiety over the previous few minutes. Higher scores indicate greater levels of anxiety. An increase in scores indicates anxiety increased during the observational period.

  Baseline Phase, Speech Phase (Week 2)

• Difference in Amygdala Beta-Weights in Activation in Response to Intensely Fearful Faces versus Neutral Faces as Measured by fMRI

  Amygdala beta-weights in activation will be measured by functional MRI while viewing both neutral face expression images and intensely fearful face expression images during a Fearful Faces task.

  Week 3

• Change in Clinician-Rated Liebowitz Social Anxiety Scale (LSAS) Score

  24-item questionnaire ranking Fear or Anxiety and Avoidance in a series of situations. Fear or Anxiety ranked on 4-point Likert scale, where: 0 = None, 1 = Mild, 2 = Moderate, and 3 = Severe. Avoidance ranked on a 4-point Likert scale, where: 0 = Never (0%), 1= Occasionally (1 -33%), 2 = Often (33 - 67%), and 3 = Usually (67 - 100%). Total scores range from 0 to 144; higher scores indicate greater severity of social anxiety: 0-54 = Mild social anxiety; 55-65 = Moderate social anxiety; 66-80 = Marked social anxiety; 81-95 = Severe social anxiety; Greater than 95 = Very severe social phobia (anxiety). An increase in scores indicates severity of social anxiety increased during the observational period.

  Day 1, Week 3

Secondary Outcomes (13)

• Difference in Ventromedial Prefrontal Cortex (vmPFC) Activation Accompanying Fear Extinction Recall During fMRI

  Week 3

• Mean Change in CBD Plasma Concentration from Pre-Treatment to Post-Treatment

  Immediately Pre-Dose, 60 Minutes Post-Dose (Up to Week 3)

• Change in Clinical Global Impression of Severity (CGI-S) Score

  Day 1, Week 3

• Change in Clinical Global Impression of Improvement (CGI-I) Score

  Day 1, Week 3

• Change in Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) Score

  Day 1, Week 3

Study Arms (3)

Cannabidiol 400mg

EXPERIMENTAL

Participants assigned to 200mg twice-daily (400mg/day) dose for 3 weeks.

Drug: Cannabidiol

Cannabidiol 800mg

EXPERIMENTAL

Participants assigned to 400mg twice-daily (800mg/day) dose for 3 weeks.

Drug: Cannabidiol

Placebo

PLACEBO COMPARATOR

Participants assigned to twice-daily placebo dose for 3 weeks.

Drug: Placebo

Interventions

Cannabidiol DRUG

Oral Capsule Formulation of CBD dissolved in a self-emulsifying drug technology called nanodomains, encapsulated within 1-ml softgel capsules, with a CBD purity ≥98%. Imported from Ananda Scientific

Also known as: Nantheia (A1002N5S) Softgel Capsules

Cannabidiol 400mg; Cannabidiol 800mg

Placebo DRUG

Drug: Placebo Placebo softgel capsule formulation.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female outpatients aged 18 to 45 years of age
• A primary mental health complaint (designated by the patient as the most important source of current distress and confirmed on Structured Clinical Interview for DSM-5 diagnoses by a certified clinical evaluator) of Social Anxiety Disorder (SAD), as defined by DSM-5 criteria
• Overall social anxiety severity defined by a Liebowitz Social Anxiety Scale (LSAS) score of at least 60
• Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol. Includes compliance with the requirements and restrictions listed in ICF and in the protocol (including consent to abstain from using marijuana, any cannabis-related products, or any tobacco products during the study).

You may not qualify if:

• Known allergy or hypersensitivity to CBD or any of the excipients
• A lifetime history of bipolar disorder, schizophrenia, psychosis, or delusional disorders; obsessive-compulsive disorder or an eating disorder in the past 12 months; neurocognitive disorders, intellectual disabilities, communication disorders or other cognitive dysfunction that could interfere with capacity to engage in therapy or complete study procedures; major depressive disorder, substance or alcohol use disorder (other than nicotine) in the last 6 months.
• Positive urine toxicology for illicit drugs and/or cannabinoids, or self-reported use of CBD, THC or marijuana in the past 4 weeks prior to baseline
• Patients with significant suicidal ideation (assessed by CSSRS SI score greater than 2) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
• Patients must be free of concurrent psychotropic medications including antipsychotics, anticonvulsants, benzodiazepines, and opioids, and medications that both have a narrow therapeutic index as determined by the study clinician, and are also substrates or moderate to strong inhibitors of CYP2C9, CYP2C19, CYP3A5, CYP3A7, UGT1A9, UGT2B7, CYP2C8, CYP1A2 or CYP2B6, or are strong inducers of CYP3A4 or CYP2C19, for at least 4 weeks prior to initiation of randomized treatment.
• Inability to understand study procedures or informed consent process, or significant personality dysfunction likely to interfere with study participation (assessed during the clinical interview) or inability to comply with study procedures (such as planned extended travel) assessed on clinical interview.
• Serious current unstable medical illness, or a condition for which hospitalization may be likely within the next year as assessed by medical history and physical exam. If any questions about medical safety emerge with screening procedures, consent will be formally obtained to contact patient's PCP in order to determine whether any medical concerns making participation unsafe or not feasible (such as need for extended inpatient care or medications with concern for significant drug interactions and/or safe utilization of CBD) are present.
• Clinically significant abnormal physical examination, vital signs or 12 lead ECG at screening. Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening.
• Pregnant women (to be ruled out by urine ß-HCG) and women of childbearing potential who are not using medically accepted forms of contraception (such as IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months). Men must also be using at least one medically accepted form of contraception.
• Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of SAD. Prohibited psychotherapy includes CBT, DBT, ACT, mindfulness-based approaches or psychodynamic therapy focusing on exploring specific, dynamic causes of the SAD symptomatology and providing management skills. General supportive therapy initiated greater than 3 months prior is acceptable.
• Has received an investigational drug or used an invasive investigational medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before Day 1
• Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
• Contraindications for MRI including metal implants, surgical clips, probability of metal fragments, or braces that are prohibited due to severe risk of injury.
• Left-handed
• A prior history of a diagnosis of moderate to severe hepatic dysfunction or current bilirubin \>=1.5X ULN and/or ALT or AST as 2X ULN, and/or if clinically significant signs and symptoms that are together suggestive of significant hepatic injury (i.e., nausea, vomiting, right upper quadrant pain, anorexia, fatigue, jaundice, dark urine).

Sponsors & Collaborators

• Ananda Scientific: collaborator
• NYU Langone Health: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Phobia, Social

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Naomi Simon, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Esther Blessing, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: January 26, 2023
• Primary Completion: November 26, 2025
• Study Completion: December 3, 2025
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: This data will be made available within twelve months of database lock or following publication of primary manuscript, whichever occurs first.
• Access Criteria: A de-identified dataset can be readily shared without the need of a Data Use Agreement (DUA) and facilitates book-keeping, making it the preferred data sharing plan. NYU SoM is committed to creating limited access public use datasets in accordance with NIH specifications. All study data will be made available via a data archive accessible through a public website hosted and maintained by NYU SoM. Web archived data may also be available as downloadable content, facilitating access to the research data.

Locations

US (1)