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

48 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug THC for stress?

Research shows that THC can increase stress hormone levels under stressful conditions, which might not be beneficial for stress relief. However, other cannabinoids like CBD have been shown to reduce stress responses effectively, suggesting that while THC might not be ideal for stress, other components of cannabis could be helpful. ^{1 2 3 4 5}

Is THC generally safe for humans?

THC has been widely used and is generally considered safe compared to other social drugs, with no catastrophic health effects noted. However, it can increase stress hormone levels under stress, may worsen anxiety or mood disorders, and could increase the risk of psychosis, especially in young people. ^{1 3 4 6 7}

How does the drug THC differ from other treatments for stress?

THC is unique because it interacts with the body's cannabinoid receptors, particularly the CB1 receptor, to influence stress hormone levels, which can increase susceptibility to stress under certain conditions. This mechanism is different from other stress treatments that may not target the endocannabinoid system. ^{3 8 9 10 11}

What is the purpose of this trial?

There is evidence that cannabinoids, including delta-9-tetrahydrocannabinol (THC), reduce responses to acute stress and fear-related stimuli, but few studies have examined the effects of THC on memories of stressful experiences. The researchers hypothesize that THC will attenuate behavioral and physiological responses to negative valence stimuli, including memories of aversive experiences.

Research Team

Harriet de Wit

Principal Investigator

University of Chicago

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Prospects for the Use of Cannabinoids in Psychiatric Disorders. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

Delta(9)-tetrahydrocannabinol enhances an increase of plasma corticosterone levels induced by forced swim-stress. [2019]

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

A review of the effects of acute and chronic cannabinoid exposure on the stress response. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Enhancing Endocannabinoid Control of Stress with Cannabidiol. [2021]

6. Denmark pubmed.ncbi.nlm.nih.gov

Cannabis--1988. [2019]

7. United States 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. [2023]

8. Germany 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. [2018]

9. United States 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. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Adrenalectomy reverses the effects of delta-9-THC on mouse brain 5-hydroxytryptamine turnover. [2018]

11. Ireland pubmed.ncbi.nlm.nih.gov

Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory. [2019]