THC for Post-Traumatic Stress Disorder

Overseen By Sarah Durack

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Wayne State University

Must not be taking: Dronabinol interactions

Disqualifiers: Pregnancy, TBI, Bipolar, Schizophrenia, others

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing whether cannabinoids, like THC, can help people with PTSD manage their fear and anxiety. PTSD patients often struggle with severe symptoms that are hard to treat. The study will see if these compounds can change how the brain processes fear signals, potentially leading to better treatments. Cannabinoids have shown potential in reducing PTSD symptoms such as anxiety, sleep disturbances, and hyperarousal in preliminary studies.

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.

What evidence supports the effectiveness of the drug THC for treating PTSD?

Research suggests that THC and other cannabinoids may help improve PTSD symptoms like sleep disorders and anxiety by acting on the endocannabinoid system, which is involved in stress and emotional regulation. However, the evidence is mixed, with some studies showing short-term benefits and others highlighting potential risks, indicating that more research is needed to fully understand its effectiveness and safety. ^{1 2 3 4 5}

Is THC generally safe for humans?

Research on THC and other cannabinoids suggests they may help with PTSD symptoms like sleep issues and nightmares, but there are concerns about potential side effects such as depression, anxiety, and substance misuse. More studies are needed to fully understand the safety of long-term use. ^{1 2 3 5 6}

How does the drug Dronabinol differ from other treatments for PTSD?

Dronabinol, which contains THC, is unique because it targets the endocannabinoid system, potentially helping to regulate stress and anxiety by affecting memory and emotional responses. Unlike traditional PTSD treatments, which often focus on serotonin or norepinephrine pathways, Dronabinol's action on cannabinoid receptors offers a novel approach, although its long-term efficacy and safety are still under investigation. ^{3 4 7 8 9}

Research Team

Christine A Rabinak, PhD

Principal Investigator

Wayne State University

Eligibility Criteria

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.

I am between 18 and 60 years old.

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).

Trial Timeline

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)

Treatment Details

Interventions

• Dronabinol (Cannabinoid)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. [2021]

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

Cannabis use and posttraumatic stress disorder comorbidity: Epidemiology, biology and the potential for novel treatment approaches. [2022]

4. United States 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). [2014]

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

Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. [2020]

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

Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. [2022]