THC for Post-Traumatic Stress Disorder
Recruiting in Palo Alto (17 mi)
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.
12345Is 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.
12356How 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.
24789Eligibility 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.
+2 more
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).
+11 more
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Dronabinol 7.5 milligram oral capsuleExperimental Treatment1 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 capsulePlacebo Group1 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, United States, Australia, 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 Australia as Marinol 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Eugene Applebaum College of Pharmacy and Health SciencesDetroit, MI
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Who Is Running the Clinical Trial?
Wayne State UniversityLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. [2021]Post-Traumatic Stress Disorder (PTSD) is a complex disorder involving dysregulation of stress-related hormones and neurotransmitter systems. Research focused on the endocannabinoid system (eCBS) for anxiety and stress regulation, cognitive and emotional responses modulation and aversive memories extinction, leading to the hypothesis that it could represent a possible alternative treatment target for PTSD. In this systematic review, we summarize evidence about the efficacy and safety of medicinal cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), and nabilone in PTSD treatment. The PRISMA statement guidelines were followed. A systematic literature search was conducted in MEDLINE/PubMed, Scopus and Web of Science by two independent researchers, who also performed data extraction and quality assessment. Among the initial 495 papers, 234 were screened for eligibility and 10 were included. Studies suggested that different medicinal cannabinoids at distinct doses and formulations could represent promising treatment strategies for the improvement of overall PTSD symptomatology as well as specific symptom domains (e.g., sleep disorders, arousal disturbances, suicidal thoughts), also influencing quality of life, pain and social impact. Although there is a robust rationale for treatment with drugs that target the eCBS and the results are promising, further studies are needed to investigate the safety and efficacy profile of their prolonged use.
Cannabis use and posttraumatic stress disorder comorbidity: Epidemiology, biology and the potential for novel treatment approaches. [2022]Cannabis use is increasing among some demographics in the United States and is tightly linked to anxiety, trauma, and stress reactivity at the epidemiological and biological level. Stress-coping motives are highly cited reasons for cannabis use. However, with increased cannabis use comes the increased susceptibility for cannabis use disorder (CUD). Indeed, CUD is highly comorbid with posttraumatic stress disorder (PTSD). Importantly, endogenous cannabinoid signaling systems play a key role in the regulation of stress reactivity and anxiety regulation, and preclinical data suggest deficiencies in this signaling system could contribute to the development of stress-related psychopathology. Furthermore, endocannabinoid deficiency states, either pre-existing or induced by trauma exposure, could provide explanatory insights into the high rates of comorbid cannabis use in patients with PTSD. Here we review clinical and preclinical literature related to the cannabis use-PTSD comorbidity, the role of endocannabinoids in the regulation of stress reactivity, and potential therapeutic implications of recent work in this area.
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]Nabilone is a synthetic cannabinoid that has shown promise for the treatment of posttraumatic stress disorder (PTSD)-related insomnia and nightmares as well as efficacy in the management of chronic pain. It has also been proposed for harm reduction in cannabis dependence. Its effectiveness for management of concurrent disorders in seriously mentally ill correctional populations has not been evaluated. This retrospective study of 104 male inmates with serious mental illness prescribed nabilone analyzes the indications, efficacy, and safety of its use. Medications discontinued with the initiation of nabilone were also reviewed. The results showed nabilone targeting a mean of 3.5 indications per patient, thus likely reducing polypharmacy risk. The mean final dosage was 4.0 mg. Results indicated significant improvement in PTSD-associated insomnia, nightmares, PTSD symptoms, and Global Assessment of Functioning and subjective improvement in chronic pain. Medications associated with greater risk for adverse effects or abuse than nabilone were often able to be discontinued with the initiation of nabilone, most often antipsychotics and sedative/hypnotics. There was no evidence of abuse within this high-risk population or reduction of efficacy when nabilone was given in powder form with water rather than as a capsule. This study supports the promise of nabilone as a safe, effective treatment for concurrent disorders in seriously mentally ill correctional populations. Prospective, randomized controlled trials are required to confirm our preliminary results. Follow-up in the community will be required to confirm effectiveness in harm reduction.
Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC). [2014]The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences.
Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review. [2019]Posttraumatic stress disorder (PTSD) is common in the general population, yet there are limitations to the effectiveness, tolerability, and acceptability of available first-line interventions. We review the extant knowledge on the effects of marijuana and other cannabinoids on PTSD. Potential therapeutic effects of these agents may largely derive from actions on the endocannabinoid system and we review major animal and human findings in this area. Preclinical and clinical studies generally support the biological plausibility for cannabinoids' potential therapeutic effects, but underscore heterogeneity in outcomes depending on dose, chemotype, and individual variation. Treatment outcome studies of whole plant marijuana and related cannabinoids on PTSD are limited and not methodologically rigorous, precluding conclusions about their potential therapeutic effects. Reported benefits for nightmares and sleep (particularly with synthetic cannabinoid nabilone) substantiate larger controlled trials to determine effectiveness and tolerability. Of concern, marijuana use has been linked to adverse psychiatric outcomes, including conditions commonly comorbid with PTSD such as depression, anxiety, psychosis, and substance misuse. Available evidence is stronger for marijuana's harmful effects on the development of psychosis and substance misuse than for the development of depression and anxiety. Marijuana use is also associated with worse treatment outcomes in naturalistic studies, and with maladaptive coping styles that may maintain PTSD symptoms. Known risks of marijuana thus currently outweigh unknown benefits for PTSD. Although controlled research on marijuana and other cannabinoids' effects on PTSD remains limited, rapid shifts in the legal landscape may now enable such studies, potentially opening new avenues in PTSD treatment research.
Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry. [2023]The current paucity of clinical evidence limits the use of cannabis-based medicinal products (CBMPs) in post-traumatic stress disorder (PTSD). This study investigates health-related quality of life (HRQoL) changes and adverse events in patients prescribed CBMPs for PTSD.
Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. [2020]Label="BACKGROUND">Posttraumatic stress disorder (PTSD) may stem from the formation of aberrant and enduring aversive memories. Some PTSD patients have recreationally used Cannabis, probably aiming at relieving their symptomatology. However, it is still largely unknown whether and how Cannabis or its psychotomimetic compound Δ9-tetrahydrocannabinol (THC) attenuates the aversive/traumatic memory outcomes. Here, we seek to review and discuss the effects of THC on aversive memory extinction and anxiety in healthy humans and PTSD patients.
Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. [2022]Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [(11)C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [(11)C]OMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [(11)C]OMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively--OMAR VT, anandamide and cortisol--correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.
Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. [2022]Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ(9)-tetrahydrocannabinol (THC) for chronic PTSD.