Digital Therapeutics for PTSD and Cannabis Use Disorder

(RISE-C Trial)

Recruiting at 5 trial locations

Overseen By Nicole A Short, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Nevada, Las Vegas

Disqualifiers: Pregnancy, Prisoner, Cognitive deficits, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 0

Duration: 9 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

683,000 women are sexually assaulted annually in the United States, half of whom develop chronic posttraumatic stress disorder (PTSD) and thus have markedly increased risk for cannabis use disorder (CUD). The current proposal will test the acceptability, initial efficacy, and mechanisms underlying a novel digital therapeutic targeting risk for PTSD-CUD, which could address the critical need for PTSD-CUD prevention for the 100,000 women who annually present for emergency care after sexual assault. In this research context, the applicant will receive key training in multisite, emergency-care based randomized clinical trials (RCTs), advanced statistical analyses for RCTs and ecological momentary assessment data, biobehavioral mechanisms underlying PTSD-CUD prevention, and professional development, launching her independent research career focused on reducing the public health burden of PTSD-CUD among sexual assault survivors by leveraging digital therapeutics.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Relaxation Control, Relaxation Techniques, Stress Management, Anxiety Reduction Methods, RISE Guide for PTSD and Cannabis Use Disorder?

Research shows that relaxation techniques can help reduce anxiety, which is a common issue in PTSD. A study found that relaxation therapy led to improvements in anxiety and depression, suggesting it might be helpful for managing PTSD symptoms. ^{1 2 3 4 5}

Is the digital therapeutic treatment for PTSD and cannabis use disorder safe for humans?

Relaxation techniques, including those used in digital therapeutics, have been studied for conditions like PTSD and panic disorder, showing mild therapeutic effects without significant adverse events. However, when cannabis formulations are involved, common side effects include dry mouth, drowsiness, and fatigue, especially with THC. ^{3 6 7 8 9}

How is the RISE Guide treatment for PTSD and Cannabis Use Disorder different from other treatments?

The RISE Guide treatment is unique because it focuses on digital therapeutic methods like relaxation techniques and stress management, which are non-drug approaches, unlike cannabis-based therapies that involve using cannabis compounds. This treatment offers a novel way to manage symptoms without the use of cannabis, which is often used in other PTSD treatments. ^{1 8 10 11 12}

Eligibility Criteria

This trial is for English-speaking women over 18 who have experienced a sexual assault within the last 72 hours and are seeking emergency care. They must use cannabis more than once weekly, have high anxiety sensitivity, own a smartphone with service for over a year, and be able to consent. Exclusions include living with the assailant, being an admitted patient or prisoner, cognitive impairments preventing informed consent, current pregnancy, no fixed address or prior enrollment.

Inclusion Criteria

I speak English.

Able to provide informed consent

Have a smartphone with continuous service >1 year

Exclusion Criteria

Prisoner

Previously enrolled

No sexual assault nurse examiner (SANE) examination

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a digital therapeutic intervention targeting anxiety sensitivity and PTSD-CUD risk, including a 3-week cognitive behavioral intervention followed by 6 weeks of ecological momentary intervention

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of PTSD symptoms, anxiety, depression, and cannabis use

6 months

Treatment Details

Interventions

• Relaxation Control
• RISE Guide

Trial Overview The study tests a new digital therapeutic called RISE Guide against Relaxation Control to prevent PTSD-CUD in women after sexual assault. It aims to evaluate user acceptability and effectiveness of these interventions in reducing PTSD-CUD risk among survivors presenting at emergency care sites.

Participant Groups

Group I: RISE Guide Experimental Treatment 1 Intervention

Brief cognitive behavioral intervention completed in the 3 weeks post-assault delivered via Internet on participants' smartphones targeting anxiety sensitivity, or fear of anxious arousal. Patients learn psychoeducation regarding the nature of stress, cognitive retraining to reduce negative interpretations of stress, and how to complete interoceptive exposures to reduce anxiety sensitivity. These skills are supported by 6 concurrent then subsequent weeks of ecological momentary intervention to deliver personalized intervention reminders based on symptoms.

Group II: Relaxation Active Control 1 Intervention

Patients will download the "Breathe2Relax" app, which delivers information about how to use diaphragm breathing (taking slow, deep breaths through the diaphragm) to manage stress. Participants will receive reminders to engage with the intervention. Participants will also receive ecological momentary intervention reminders to engage with the relaxation intervention.

Relaxation Control is already approved in United States, European Union for the following indications:

Approved in United States as Relaxation Control for:

• Anxiety
• Stress Management
• PTSD Symptoms Reduction

Approved in European Union as Relaxation Techniques for:

• Anxiety Disorders
• Stress Relief
• Post-Traumatic Stress Disorder Management

Who Is Running the Clinical Trial?

University of Nevada, Las Vegas

Lead Sponsor

Trials

81

Recruited

14,700+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Findings from Research

A 28-year-old female with complex D-PTSD experienced a remarkable 98.5% reduction in dissociative symptoms after 10 sessions of cannabis-assisted psychotherapy (CAP) over 5 months, indicating strong efficacy for this novel treatment.

The patient not only no longer met the criteria for D-PTSD but also reported sustained improvements for over 2 years, suggesting that CAP may offer long-lasting benefits similar to those seen with classic psychedelics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report. Ragnhildstveit, A., Kaiyo, M., Snyder, MB., et al.[2023]

In a study of 114 veterans undergoing cognitive processing therapy for PTSD, cannabis users initially reported higher PTSD symptom severity than nonusers, but both groups showed similar treatment outcomes after therapy.

The findings suggest that stopping cannabis use during treatment may lead to comparable improvements in PTSD symptoms for both cannabis users and nonusers, although further research is needed to assess long-term effects and the impact of resumed cannabis use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residential PTSD treatment outcomes during cognitive processing therapy for veterans with and without recent histories of cannabis use. Hale, AC., Bremer-Landau, J., Wright, TP., et al.[2021]

In a study of 23 subjects with panic disorder, diazepam was the only treatment that produced significant physiological changes, indicating its efficacy in reducing anxiety symptoms.

Relaxation therapy showed the largest improvements in self-reported anxiety and depression, suggesting it may be a beneficial approach for managing general anxiety in panic disorder, even though these changes were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled comparison of relaxation and diazepam in panic disorder. Taylor, CB., Kenigsberg, ML., Robinson, JM.[2013]

A pilot study involving 20 adults demonstrated that a microcomputer program effectively reduced anxiety levels, as measured by significant decreases in the Spielberger State Anxiety Scale and a visual analog anxiety scale after two 30-minute sessions.

The study suggests that using technology for relaxation and focused attention can be a promising approach for stress reduction, although further research is needed to confirm these findings and address limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microcomputer-assisted relaxation. Baer, L., Surman, OS.[2008]

A meta-analysis of 27 studies from 1997 to 2007 found that relaxation training, including techniques like meditation and progressive relaxation, has a medium to large effect size in reducing anxiety, with Cohen's d values of 0.57 and 0.51 for within and between group analyses, respectively.

The efficacy of relaxation training was found to be higher for meditation techniques, among volunteer participants, and in longer treatment durations, indicating that these factors can enhance the effectiveness of anxiety reduction strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relaxation training for anxiety: a ten-years systematic review with meta-analysis. Manzoni, GM., Pagnini, F., Castelnuovo, G., et al.[2022]

This study will assess the relaxation effects of 360-degree nature videos on 36 military personnel diagnosed with PTSD, comparing the effects of viewing these videos on a head-mounted display versus a PC screen against a control condition of just listening to natural sounds.

The research aims to determine if the duration of the video (five vs. ten minutes) influences relaxation levels, providing foundational data for future trials on innovative PTSD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nature videos for PTSD: protocol for a mixed-methods feasibility study. Knaust, T., Felnhofer, A., Kothgassner, OD., et al.[2022]

In a study involving 90 male Vietnam veterans with PTSD, various relaxation techniques were tested, but only 4 out of 21 measures showed any improvement, indicating limited effectiveness of the treatments.

The addition of deep breathing exercises and thermal biofeedback did not significantly enhance the benefits of simple relaxation instructions, suggesting that basic relaxation techniques may be sufficient for mild therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacies of three relaxation regimens in the treatment of PTSD in Vietnam War veterans. Watson, CG., Tuorila, JR., Vickers, KS., et al.[2019]

In a study of 87 cannabis-using individuals with PTSD symptoms, those with high Hyperarousal (Cluster D) symptoms were more likely to use cannabis in response to increased anxiety and reported significant decreases in anxiety after use.

The findings suggest that negative reinforcement models, which propose that individuals use substances to alleviate negative feelings, are particularly applicable to those with elevated Cluster D symptoms, while the same relationship was only partially observed in individuals with other PTSD symptom clusters (B and C).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of PTSD clusters on cannabis use in a racially diverse trauma-exposed sample: An analysis from ecological momentary assessment. Buckner, JD., Jeffries, ER., Crosby, RD., et al.[2020]

In a study of 198 participants with anxiety disorders, treatment with various cannabis formulations significantly improved quality of life outcomes, including reductions in anxiety, depression, and fatigue, as well as enhanced social functioning.

Common adverse events reported included dry mouth, somnolence, and fatigue, with gastrointestinal issues more prevalent in formulations containing THC, indicating a need for careful consideration of cannabis formulation in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study. Stack, SK., Wheate, NJ., Moloney, NC., et al.[2023]

In a study of 150 participants with PTSD over one year, those using dispensary-obtained cannabis experienced a greater reduction in PTSD symptoms compared to those who did not use cannabis, suggesting potential efficacy of cannabis as a treatment.

Cannabis users were found to be 2.57 times more likely to no longer meet the criteria for PTSD by the end of the study, indicating a significant improvement in their condition compared to non-users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long-Term, Prospective, Therapeutic Impact of Cannabis on Post-Traumatic Stress Disorder. Bonn-Miller, MO., Brunstetter, M., Simonian, A., et al.[2023]

In a study of 404 medical cannabis users with PTSD, cannabis use resulted in over a 50% reduction in symptoms like intrusive thoughts and anxiety immediately after use, indicating its efficacy for short-term relief.

However, the study found that while cannabis provided temporary symptom relief, baseline PTSD symptoms remained constant over time, suggesting that it may not be a sustainable long-term treatment and that users may develop tolerance, requiring higher doses for anxiety relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. LaFrance, EM., Glodosky, NC., Bonn-Miller, M., et al.[2021]

Medical cannabis, particularly compounds like THC and CBD, shows potential therapeutic benefits for anxiety disorders and PTSD, with evidence suggesting it positively affects the brain's fear regulation pathways.

While medical cannabis appears to have a relatively safe profile for treating anxiety and PTSD, there is still limited scientific evidence supporting its effectiveness, leading to challenges in standardization and regulatory approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis update: Anxiety disorders and post-traumatic stress disorder. Haycraft, AL.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report. [2023]

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

Residential PTSD treatment outcomes during cognitive processing therapy for veterans with and without recent histories of cannabis use. [2021]

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

A controlled comparison of relaxation and diazepam in panic disorder. [2013]

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

Microcomputer-assisted relaxation. [2008]

5. England pubmed.ncbi.nlm.nih.gov

Relaxation training for anxiety: a ten-years systematic review with meta-analysis. [2022]

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

Nature videos for PTSD: protocol for a mixed-methods feasibility study. [2022]

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

The efficacies of three relaxation regimens in the treatment of PTSD in Vietnam War veterans. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The impact of PTSD clusters on cannabis use in a racially diverse trauma-exposed sample: An analysis from ecological momentary assessment. [2020]

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

The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study. [2023]

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

The Long-Term, Prospective, Therapeutic Impact of Cannabis on Post-Traumatic Stress Disorder. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. [2021]

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

Cannabis update: Anxiety disorders and post-traumatic stress disorder. [2023]