THC for Stress

(ETS Trial)

Overseen By Hanna Molla

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Chicago

Must not be taking: Daily medications

Disqualifiers: Severe substance use, Psychosis, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if THC, a compound in cannabis, can reduce stress and negative memories. Participants will receive either THC or a placebo to compare effects. The trial is open to individuals aged 18-35 who have used cannabis occasionally without issues and use it no more than once a week. As an Early Phase 1 trial, this research focuses on understanding how THC works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that participants do not use medications daily, except for contraception. If you take medications daily, you may need to stop them to participate.

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

Research has shown that THC, the active ingredient in Marinol (dronabinol), is usually well-tolerated by most people. Some studies have explored its effects on anxiety and mental health. However, higher doses of THC can sometimes increase anxiety or cause other mental health issues, such as psychosis or schizophrenia, especially in those prone to these conditions.

Physically, some individuals have experienced changes in blood pressure, such as dizziness when standing up quickly. This occurs due to a drop in blood pressure upon standing, known as orthostatic hypotension. While these side effects can occur, they do not affect everyone.

This trial is in an early research phase, focusing on testing the treatment mainly for safety and side effects in a small group of healthy volunteers. This phase helps researchers understand how people might react to THC before conducting further studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about these THC treatments for stress because they offer a potential new way to manage stress symptoms using delta-9-tetrahydrocannabinol (THC), the active ingredient in cannabis. Unlike traditional stress treatments like antidepressants and anti-anxiety medications, which often work by altering neurotransmitter levels over several weeks, THC might provide quicker relief by directly interacting with the body's endocannabinoid system. This system plays a key role in regulating mood and stress responses. Additionally, using Marinol (dronabinol), a synthetic form of THC, allows precise dosing and avoids the smoking or vaping associated with cannabis use, making it a potentially safer option for stress management.

What evidence suggests that THC might be an effective treatment for stress?

Research has shown that THC, the main ingredient in cannabis, might help lower anxiety and stress. Some studies have found benefits for anxiety and depression, with nearly half showing positive effects. In one study, participants taking THC reported feeling much better. This trial will test different doses of THC, specifically 5 mg and 10 mg, to evaluate its effects on stress. THC affects the brain's system that controls mood and stress. However, THC can also raise heart rate and blood pressure, so its effects can differ. Overall, early findings suggest that THC might help manage stress and anxiety, but more research is needed to confirm these benefits. ^{3 4 6 7 8}

Who Is on the Research Team?

Harriet de Wit

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for individuals who are interested in how certain drugs might affect stress memories. Specific eligibility criteria details were not provided, so it's unclear who exactly can participate.

Inclusion Criteria

BMI between 19-29 kg/m2

I have used cannabis at least 4 times without bad reactions and use it no more than once a week now.

Exclusion Criteria

Current DSM IV Axis I disorder

I take daily medication other than for birth control.

I have a history of psychosis or mania.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo the TSST procedure and receive either THC or placebo during stress-memory retrieval sessions

2 weeks

3 sessions (in-person)

Follow-up

Participants are monitored for changes in emotional and physiological responses after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• THC

Trial Overview The study is testing the effects of two doses of THC (5mg and 10mg) compared to a placebo on how people respond to stressful memories. Researchers think that THC might help reduce these stress responses.

How Is the Trial Designed?

Group I: 5 mg delta-9-tetrahydrocannabinol (THC) Experimental Treatment 1 Intervention

Marinol (dronabinol)

Group II: 10 mg delta-9-tetrahydrocannabinol (THC) Experimental Treatment 1 Intervention

Marinol (dronabinol)

Group III: placebo Placebo Group 1 Intervention

Dextrose capsules

THC is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Dronabinol for:

• Appetite loss and weight loss in HIV
• Nausea and vomiting from chemotherapy

Approved in Canada as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Approved in European Union as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Cannabis has been found to have a relatively safe profile compared to other social drugs, with no catastrophic health effects reported despite its widespread use.

The main metabolite of THC, 11-OH-THC, contributes little to the overall effects of cannabis, and the minimum plasma level of THC associated with psychotropic effects is 25 ng/ml, indicating a specific threshold for its psychoactive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis--1988. Hollister, LE.[2019]

In a study involving 13 daily cannabis users, high-dose dronabinol (180-240 mg/day) was found to significantly reduce cannabis self-administration compared to placebo, indicating its potential effectiveness in treating cannabis use disorders.

Dronabinol also helped suppress withdrawal symptoms, suggesting that cannabinoid agonist medications could be a promising therapeutic option for individuals struggling with cannabis dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration. Schlienz, NJ., Lee, DC., Stitzer, ML., et al.[2019]

THC significantly increased immobility time in a forced swim-stress test, indicating that it may enhance susceptibility to stress and potentially increase the risk of depression.

The effect of THC on stress response was mediated through the CB(1) receptor, as blocking this receptor with the antagonist O-2050 reduced THC's impact on immobility and stress hormone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta(9)-tetrahydrocannabinol enhances an increase of plasma corticosterone levels induced by forced swim-stress. Sano, K., Koushi, E., Irie, K., et al.[2019]

Acute exposure to cannabinoids can increase stress hormone levels and affect stress responses in both humans and rodents, indicating a complex relationship between cannabis use and stress reactivity.

Chronic cannabis exposure appears to reduce stress reactivity and alter cortisol patterns in humans, suggesting potential long-term effects on stress management, but more research is needed to explore sex differences in these responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the effects of acute and chronic cannabinoid exposure on the stress response. Glodosky, NC., Cuttler, C., McLaughlin, RJ.[2022]

Cannabidiol (CBD) has been shown to effectively reduce the stress response in clinical trials, with seven double-blind placebo-controlled studies involving 232 participants demonstrating its efficacy and safety.

CBD works by enhancing the endocannabinoid system, which regulates the stress response, and its effectiveness is supported by both clinical and preclinical evidence, making it a promising treatment option for maladaptive stress responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Endocannabinoid Control of Stress with Cannabidiol. Henson, JD., Vitetta, L., Quezada, M., et al.[2021]

A study involving 21 healthy adults found that tetrahydrocannabivarin (THCV) has a favorable safety profile, with most adverse events being mild and euphoric mood being the most common side effect.

Preliminary results suggest that certain doses of THCV (specifically 12.5, 25, and 200 mg) may improve sustained attention, although the effects were not consistently dose-dependent and higher doses led to THC-like effects, which could result in positive urine drug screens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Two-Phase, Dose-Ranging, Placebo-Controlled Study of the Safety and Preliminary Test of Acute Effects of Oral &#916;8-Tetrahydrocannabivarin in Healthy Participants. Peters, EN., MacNair, L., Harrison, A., et al.[2023]

Footshock stress administered immediately before conditioning trials can prevent the aversive effects of a high dose of THC (1 mg/kg) in rats, suggesting that stress may alter the drug's impact on behavior.

While footshock stress enhances the anxiolytic effects of THC and URB597, it does not increase their rewarding properties, indicating that stress modifies THC's effects differently depending on the timing and context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of footshock stress on place conditioning produced by &#916;9-tetrahydrocannabinol and the fatty acid amide hydrolase (FAAH) inhibitor, URB597, in Sprague-Dawley rats. DeVuono, MV., Wills, KL., MacPherson, DV., et al.[2018]

In a study of 125 daily cannabis smokers, those with trauma exposure exhibited higher levels of cortisol and anxiety during stress tests, indicating that trauma can intensify stress responses in cannabis users.

Female cannabis smokers with trauma exposure showed greater cardiovascular stress responses compared to their male counterparts, highlighting the need for further research on how trauma and sex influence stress reactions in cannabis use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory. Chao, T., Radoncic, V., Hien, D., et al.[2019]

JWH-018, a synthetic cannabinoid, was found to reduce body temperature, locomotion, and pain sensitivity while increasing anxiety in outbred CD1 mice, indicating its psychoactive effects are similar to classical cannabinoid agonists.

Mice exposed to prenatal stress showed reduced sensitivity to the effects of JWH-018, suggesting that early stress can alter the long-term reactivity of the endocannabinoid system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral responses to acute and sub-chronic administration of the synthetic cannabinoid JWH-018 in adult mice prenatally exposed to corticosterone. Macrì, S., Lanuzza, L., Merola, G., et al.[2021]

Acute administration of delta 9-tetrahydrocannabinol (delta 9-THC) in mice leads to increased plasma corticosterone levels, suggesting a potential mechanism for its effects on stress and mood regulation.

The study found that delta 9-THC enhances the synthesis of serotonin (5-hydroxytryptamine) from tryptophan in the brain, indicating that corticosterone may play a role in mediating these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adrenalectomy reverses the effects of delta-9-THC on mouse brain 5-hydroxytryptamine turnover. Johnson, KM., Dewey, WL., Bloom, AS.[2018]

The endocannabinoid system plays a significant role in mood, stress, and cognitive functions, with cannabinoids like THC and CBD showing potential therapeutic effects in psychiatric conditions, although their effects can vary based on individual factors and dosages.

While some studies suggest cannabinoids may help reduce anxiety and depression symptoms in certain medical conditions, caution is advised, especially with THC, due to its potential to increase the risk of psychosis, particularly in younger individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects for the Use of Cannabinoids in Psychiatric Disorders. Graczyk, M., Łukowicz, M., Dzierzanowski, T.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40854216/

High-Concentration Delta-9-Tetrahydrocannabinol ... Among therapeutic studies, nearly half found benefits for anxiety (47%) and depression (48%), although some also found unfavorable associations ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10387818/

The Effectiveness and Adverse Events of Cannabidiol and ... Results: The median doses taken were 50.0 mg/day for CBD and 4.4 mg/day for THC. The total participant sample reported significantly improved ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165178125002008

Medicinal cannabis in the management of anxiety disorders THC significantly increased heart rate, blood pressure, and intoxication compared to placebo and CBD. Placebo significantly reduced anxiety immediately compared ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06471647?term=thc&viewType=Table&rank=1

Study Details | Effects of Drugs on Stress Memories Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124003342

Therapeutic potential of cannabidiol (CBD) in anxiety ... CBD-assisted therapy improved anxiety symptoms in patients with the disorder to varying degrees. 8 articles involving 245 patients with TRD were included in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06471647?term=dronabinol%20OR%20tetrahydronnabinol%20OR%20marinol&viewType=Table&rank=4

NCT06471647 | Effects of Drugs on Stress Memories A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38430618/

Does medicinal cannabis affect depression, anxiety, and ... No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher- ...

8. go.drugbank.com go.drugbank.com/drugs/DB00470

Dronabinol: Uses, Interactions, Mechanism of Action Its effects on blood pressure are inconsistent, but subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing.