THC for Post-Traumatic Stress Disorder

Overseen By Sarah Durack

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Wayne State University

Must not be taking: Dronabinol interactions

Disqualifiers: Pregnancy, TBI, Bipolar, Schizophrenia, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether dronabinol, a type of cannabinoid, can help treat post-traumatic stress disorder (PTSD). PTSD is an anxiety disorder that causes flashbacks, nightmares, and increased arousal after traumatic events. The study will examine if dronabinol affects how people process fear and emotions, potentially offering a new treatment option for PTSD and similar anxiety disorders. Participants will receive either dronabinol or a placebo before therapy sessions. This trial suits individuals whose primary concern is PTSD and who have experienced significant symptoms for at least a month. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on daily medications that have severe interactions with dronabinol. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that dronabinol, a type of THC (the main active component of cannabis), has been studied for treating PTSD symptoms. Some studies suggest that cannabis can help reduce PTSD symptoms and improve quality of life. Specifically, researchers have tested dronabinol for its effects on symptoms like nightmares. Although these studies are not conclusive, they indicate possible benefits.

Regarding safety, individuals familiar with cannabis generally tolerate inhaled THC well, suggesting that dronabinol might also be tolerated. However, prolonged cannabis use can sometimes lead to increased tolerance, requiring more to achieve the same effect.

As this is an early-stage trial, researchers are still gathering safety information. Early trials primarily focus on assessing a drug's safety. Dronabinol is approved for other uses, which might suggest it is relatively safe, but more research is needed to confirm its safety in the context of PTSD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike the standard treatments for PTSD, such as psychotherapy and medications like SSRIs, dronabinol offers a unique approach. Dronabinol is a synthetic form of THC, the active ingredient in cannabis, which may help reduce PTSD symptoms by interacting with the body's endocannabinoid system. Researchers are excited about dronabinol because it could potentially enhance the therapeutic effects of exposure therapy by reducing anxiety and improving emotional regulation during treatment sessions. This innovative approach could provide a new option for those who do not respond well to current treatments.

What evidence suggests that dronabinol might be an effective treatment for PTSD?

Studies have shown that cannabinoids, such as dronabinol, might help reduce stress and improve coping in people with PTSD. Some research suggests that dronabinol could alleviate symptoms like nightmares, which are common in PTSD. However, the evidence remains unclear, with much of it based on personal stories or small studies. Concerns exist that regular use of cannabis products might lead to tolerance, requiring higher doses to achieve the same effects over time. While early findings are promising, this trial will further investigate dronabinol's effectiveness in treating PTSD symptoms compared to a placebo. ^{1 2 3 4 6}

Who Is on the Research Team?

Christine A Rabinak, PhD

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with significant PTSD, where it's their primary concern. They must have experienced a traumatic event and be in good general health without serious cognitive impairments. It excludes pregnant or breastfeeding individuals, those with certain mental health conditions, severe substance use issues, allergies to cannabinoids, or MRI contraindications.

Inclusion Criteria

I am generally healthy with no serious brain health issues affecting my thinking or daily tasks.

You have experienced a traumatic event that meets certain criteria and has been identified through a checklist.

Willing and able to consent to study

Exclusion Criteria

You have been diagnosed with bipolar disorder, schizophrenia, or any related mental health conditions.

You have a history of developmental disorders that affect your ability to communicate and interact with others.

You must be right-handed or ambidextrous (able to use both hands equally).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-Treatment

Participants undergo behavioral tests and MR scans to establish baseline measures

2 weeks

2 visits (in-person)

Treatment

Participants undergo Prolonged Exposure (PE) sessions with either THC or placebo administered before sessions

10 weeks

12 visits (in-person)

Post-Treatment

Participants undergo post-treatment behavioral tests and MR scans to assess changes

1 week

2 visits (in-person)

Follow-up

Participants are monitored for therapeutic gains and relapse prevention

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol

Trial Overview The study tests the effects of Dronabinol (a synthetic THC) on memory retention related to fear extinction learning in PTSD patients compared to a placebo. The aim is to understand how cannabinoids affect emotional processing and brain activity patterns associated with PTSD treatment.

How Is the Trial Designed?

Group I: Dronabinol 7.5 milligram oral capsule Experimental Treatment 1 Intervention

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall. Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Group II: Placebo capsule Placebo Group 1 Intervention

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall. Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In an animal model for PTSD, a single dose of Δ9-THC (5 mg/kg) reduced anxiety-like behaviors shortly after administration but did not provide long-term benefits against PTSD-like symptoms seven days later.

The study found that while Δ9-THC decreased stress hormone levels (corticosterone), its early treatment did not prevent long-term stress responses, raising concerns about its clinical effectiveness and the complexity of endocannabinoid effects on trauma-related behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). Mayer, TA., Matar, MA., Kaplan, Z., et al.[2014]

In a study involving 10 outpatients with chronic PTSD, the addition of 5 mg of orally absorbable Δ(9)-THC twice a day was found to be safe and well tolerated, with only mild adverse effects reported.

The treatment led to significant improvements in overall symptom severity, sleep quality, frequency of nightmares, and hyperarousal symptoms associated with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Roitman, P., Mechoulam, R., Cooper-Kazaz, R., et al.[2022]

In a study of 162 patients with PTSD using cannabis-based medicinal products (CBMPs), significant improvements in health-related quality of life, including reductions in PTSD symptoms, sleep issues, and anxiety, were observed over 6 months.

While 20.37% of patients reported adverse events, most were mild to moderate, with insomnia and fatigue being the most common, suggesting that CBMPs are generally safe and acceptable for use in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry. Pillai, M., Erridge, S., Bapir, L., et al.[2023]

Cannabis use is increasingly linked to anxiety and stress, with many individuals using it as a coping mechanism, but this can lead to a higher risk of developing cannabis use disorder (CUD), especially among those with posttraumatic stress disorder (PTSD).

Endocannabinoid signaling plays a crucial role in managing stress and anxiety, and deficiencies in this system may contribute to the high rates of cannabis use among PTSD patients, suggesting potential therapeutic avenues for addressing these comorbid conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis use and posttraumatic stress disorder comorbidity: Epidemiology, biology and the potential for novel treatment approaches. Kondev, V., Winters, N., Patel, S.[2022]

Low doses of THC can enhance the extinction of aversive memories and reduce anxiety in both healthy individuals and PTSD patients, likely by activating cannabinoid type-1 receptors in the brain.

Combining THC with CBD may provide anxiety relief while minimizing the risk of adverse effects associated with higher THC doses, although the specific effects on memory reconsolidation remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. Raymundi, AM., da Silva, TR., Sohn, JMB., et al.[2020]

Current evidence suggests that while cannabinoids, including marijuana, may have potential therapeutic effects for PTSD, the research is limited and lacks methodological rigor, making it difficult to draw definitive conclusions about their effectiveness.

Marijuana use is associated with several adverse psychiatric outcomes, particularly an increased risk of psychosis and substance misuse, which raises concerns about its overall safety for individuals with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review. Steenkamp, MM., Blessing, EM., Galatzer-Levy, IR., et al.[2019]

In a study of 104 male inmates with serious mental illness, nabilone demonstrated significant improvements in PTSD-related insomnia, nightmares, and overall functioning, suggesting it is an effective treatment option for these symptoms.

Nabilone also allowed for the discontinuation of other medications with higher risks of adverse effects, such as antipsychotics and sedatives, indicating its potential to reduce polypharmacy and improve safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation. Cameron, C., Watson, D., Robinson, J.[2022]

Individuals with PTSD showed significantly higher levels of CB1 receptor availability in the brain compared to healthy controls and trauma-exposed controls, indicating a potential dysregulation of the endocannabinoid system in PTSD.

Lower levels of the endocannabinoid anandamide were found in PTSD patients, suggesting that impaired anandamide signaling may contribute to the disorder, and this could lead to new treatment options targeting the endocannabinoid system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Neumeister, A., Normandin, MD., Pietrzak, RH., et al.[2022]

A systematic review of 10 studies suggests that medicinal cannabinoids like CBD, Δ9-THC, and nabilone may improve overall PTSD symptoms and specific issues such as sleep disorders and arousal disturbances, potentially enhancing quality of life.

While the results are promising for using cannabinoids as a treatment for PTSD, more research is necessary to fully understand the safety and long-term efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. Steardo, L., Carbone, EA., Menculini, G., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8222769/

Cannabis in the management of PTSD: a systematic review This results in lower stress levels and better patient coping, ultimately reducing remission rates [14],[16],[20]. Current systematic reviews [21]–[25] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04448808

Treating Nightmares in Posttraumatic Stress Disorder With ... This randomized controlled exploratory phase II trial will test the hypothesis that oral dronabinol improves nightmares (primary outcome) and other PTSD ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6007739/

A review of medical marijuana for the treatment of ... Conflicting data exist for the use of marijuana for PTSD; however, current evidence is limited to anecdotal experiences, case reports, and observational studies ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0887618522001050

Posttraumatic stress disorder, sleep and medical cannabis ... Between-person analyses showed that individuals who used MC products with higher CBD concentrations reported fewer early awakenings. These preliminary results ...

5. ptsd.va.gov ptsd.va.gov/professional/treat/cooccurring/marijuana_ptsd_vets.asp

Cannabis Use and PTSD Among Veterans However, data suggest that continued use of cannabis among individuals with PTSD may lead to negative consequences, including development of cannabis tolerance ...

6. karger.com karger.com/mca/article/7/1/149/912500/Controlled-Inhalation-of-Tetrahydrocannabinol

Controlled Inhalation of Tetrahydrocannabinol ... Inhalation of THC is well tolerated and useful for managing symptoms of PTSD in cannabis-experienced individuals.