Safety and Efficacy of Cannabidiol (CBD) for Symptoms of PTSD in Adults

Phase 2

Recruiting

• Conditions: PTSD
• Interventions: Drug: Cannabidiol Administered as Nantheia ATL5; Drug: Placebo

• Registration Number: NCT05269459
• Lead Sponsor: University of Nebraska

Brief Summary

Post-traumatic stress disorder (PTSD) is a psychiatric disorder than may develop following a traumatic event including serious incidents, natural or human-caused disasters, violence, death of a loved one, receipt of traumatic news, or serious illness/hospitalization. While half of US adults experience trauma in their lifetime, most do not develop PTSD. However, those who do develop the disorder may have significant impairments and risk for functional dysfunction across multiple domains. While short term symptoms are the most common, some individuals develop chronic PTSD. These individuals may experience frightening and intrusive thoughts and memories of the event (flashbacks), have sleep disturbances, feel numb or detached, and be easily startled (hypervigilance).

This trial is a double-blind placebo controlled study of cannabidiol (CBD) for symptoms of PTSD in adults using liquid structure Formulation (Nantheia ATL5). Participants complete three weeks of baseline data collection including assessments of activity and sleep. Intervention is Nantheia ATL5 or placebo. Dose is initiated at 400mg BID and maintained over 8 weeks. Standardized symptom profile measurements, clinician assessments, laboratory testing, collection of inflammatory biomarkers, and suicide screening is completed throughout. Age- and gender-matched healthy population participants are enrolled and complete baseline data collection only. All participants may complete optional functional magnetic resonance imaging (fMRI).

Detailed Description

Post-traumatic stress disorder (PTSD) is a psychiatric disorder than may develop following a traumatic event including serious incidents, natural or human-caused disasters, violence, death of a loved one, receipt of traumatic news, or serious illness/hospitalization. While half of US adults experience trauma in their lifetime, most do not develop PTSD. However, those who do develop the disorder may have significant impairments and risk for functional dysfunction across multiple domains. While short term symptoms are the most common, some individuals develop chronic PTSD. These individuals may experience frightening and intrusive thoughts and memories of the event (flashbacks), have sleep disturbances, feel numb or detached, and be easily startled (hypervigilance).

This trial is a single-site phase II, double-blind, placebo-controlled study of Nantheia ATL5 to study symptoms of Post-Traumatic Stress Disorder (PTSD) in adults. Participants will meet criteria for PTSD using the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Clinical Assessment of Pragmatics (CAPs-5) of ≥ 27. Suicidality is assessed using the Columbia Suicide Severity Rating Scale-Revised (CSSRS-R) at all study visits. Baseline psychopharmacotherapy and/or psychotherapy must be stable (unchanged) for 4 weeks prior to enrollment and should remain unchanged during study treatment. Effects of Nantheia ATL5 on self-reported quality of life (overall and health-related); functional status measurements of personal mobility and risk, and sleep dysfunction; neurobiological biomarkers of threat response (optional functional magnetic resonance imaging: fMRI), and serum inflammatory biomarkers (hs-CRP) implicated in PTSD pathophysiology will be assessed. Efficacy and tolerability will be assessed throughout intervention. Serum pregnancy (for participants of child bearing potential), urine drug screening, complete blood count (CBC), and Comprehensive Metabolic Panel are completed at every on-site visit. Optional consent will be sought from all PTSD and healthy population participants who agree to complete the functional magnetic resonance imaging (fMRI) procedures and providing an additional sample of blood to store for future unspecified research. Baseline characteristics of participants with PTSD will be evaluated overall and relative to participants without PTSD (healthy population) during a 3-week baseline period prior to randomization \[Nantheia ATL5 or placebo (PBO)\]. Healthy population participants will complete the study at end of baseline and participants with PTSD will be randomized 1:1 to Nantheia ATL5 or placebo (PBO). Study drug dose is initiated at 400mg BID and maintained for 8 weeks. Study drug is then withdrawn, and one week later safety measures including laboratory testing, assessment of AE's and CSSRS-R are repeated.

Study Timeline

• Study First Submitted: 2022-02-24
• Study First Submitted QC: 2022-03-04
• Study First Posted: 2022-03-08
• Study Start: 2022-12-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-23
• Last Update Posted: 2025-05-28
• Primary Completion: 2028-12
• Study Completion: 2029-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cannabidiol Administered as Nantheia ATL5 Group	Cannabidiol Administered as Nantheia ATL5	Cannabidiol (CBD) as Liquid Structure Formulation Nantheia ATL5 400mg will be administered twice a day in 100mg softgel capsules to CBD Group. Each 100mg softgel contains 10% CBD.
Placebo Group	Placebo	Matching placebo capsules will be administered twice a day to Placebo Group.

Primary Outcome Measures

Name	Time	Method
Post-traumatic Stress Disorder Symptom Rating	Baseline and 8 weeks	Structured clinician-administered rating of post-traumatic stress disorder (PTSD) symptoms' severity using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; CAPS-5) Scale. This instrument assesses 20 PTSD symptoms. Each symptom is scored 0 - 4, then symptom scores are totaled. Higher scores indicate greater symptom severity.

Secondary Outcome Measures

Name	Time	Method
Post-traumatic Stress Disorder Symptom Symptom Cluster Rating	Baseline and 8 weeks	The cluster scores (symptom domains) are subscales of the CAPS-5 (outcome 1). The CAPS-5 has 20 items, each scored 0-4. The sum of items 1-5 represent cluster B (intrusion symptoms); items 6-7 represent cluster C (avoidance symptoms); items 8-14 represent cluster D (cognitions and mood symptoms); and items 15-20 represent cluster E (arousal and reactivity symptoms). Score ranges are: Cluster B 0-20, Cluster C 0-8, Cluster D 0-28, and Cluster E 0-24.; The total of the cluster scores (B+C+D+E) is the total CAPS-5 score.; Higher scores indicate greater symptom severity.
Post-traumatic Stress Disorder Symptom Rating (Self-reported)	Baseline and 8 weeks	Self-reported rating of post-traumatic stress disorder (PTSD) symptom severity using the PTSD Checklist for DSM-5 (PCL-5). This instrument the 20 items corresponding to the DSM-5 symptom criteria for PTSD. Each item is scored 0 - 4, then symptom scores are totaled. Higher scores indicate greater symptom severity.
Clinical Global Impression Post-traumatic Stress Disorder - Severity	Baseline and 8 weeks	Clinical Global Impression Post-traumatic Stress Disorder (PTSD) Symptom Severity (CGI-S) is the assessment by clinicians of the severity of PTSD symptoms based on their experience with adults with PTSD. The CGI-S is scored on a scale of 0 to 7 (0 is "not assessed," 1 is "very much improved and 7 is "very much worse.") Higher scores indicate Higher scores indicate more severe illness.
Clinical Global Impression - Improvement	Baseline and 8 weeks	Clinical Global Impression-Improvement (CGI-I) is the assessment by clinicians of the degree of post-traumatic stress disorder (PTSD) symptom improvement based on their experience with the population. It is rated without regard for relatedness to study treatment. The CGI-I is rated on a scale of 0 to 7 (0 is "not assessed," 1 is "very much improved and 7 is"very much worse.") Higher scores indicate worsening of symptoms.
Anxiety Severity Rating	Baseline and 8 weeks	Clinician-rated assessment of anxiety symptoms using the Hamilton Anxiety Rating Scale (HAM-A). This instrument assesses 14 psychic (mental agitation and psychological distress) and somatic (related physical complaints) anxiety items. Each item is scored from 0 - 4, then symptom scores are totaled. Higher scores indicate greater anxiety severity.
Depression Symptoms Rating	Baseline and 8 weeks	Clinician-rated assessment of depressive symptoms using the Hamilton Depression Rating Scale (HAM-D). This instrument assesses mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each item is scored on a 3 or 5 point scale, depending on the item, then item scores are totaled. Higher scores indicate greater depressive symptoms.
Global Functioning Disability Questionnaire	Baseline and 8 weeks	Participant-reported assessment of global functioning (an individual's overall ability to cope with daily life and maintain social, occupational, and psychological well-being) using the Sheehan Disability Scale (SDS). This instrument assesses functional impairment in work/school, social life, and family/home life. Each area is scored 0 - 10, then area scores are totaled. Higher scores indicate greater functioning disability.
Quality of Life Health Survey	Baseline and 8 weeks	Participant-reported measure of quality of life using the Short Form 36-Item Health Survey (SF-36). This instrument assesses physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each item is scored 0 - 100, then item scores are totaled. Higher scores indicate greater better health.

Trial Locations

Locations (1)

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States