THC for Psychosis Risk

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Psychotropic medications

Disqualifiers: Major DSM-IV disorder, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a family history of psychosis (a mental disorder where individuals lose contact with reality) affects the body's reaction to THC, the main psychoactive component of cannabis. Participants will receive either a placebo (a treatment with no active ingredient), a very low dose, or a low dose of THC to observe their body's response. The study seeks individuals who have tried cannabis at least once and are healthy, with one group having a family member diagnosed with psychosis and the other group having no family history of psychosis. Those with a family member diagnosed with psychosis who have tried cannabis before may be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding THC's effects on individuals, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that participants have not been treated with psychotropic medications for major psychiatric or neurological illness for at least 6 months. If you are currently on such medications, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that THC, the active component of cannabis, can sometimes link to psychosis, especially with frequent or high use. However, this study uses low and very low doses. Studies indicate that lower doses of THC carry fewer risks, but monitoring for any signs of psychosis, such as hallucinations, remains important.

People with a family history of psychosis might react more strongly to THC. Despite the small doses in this study, caution is advised. As an early phase study, it aims to explore the safety of these low doses in people. While past evidence suggests low doses are safer, this study will gather more information to enhance understanding. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike typical treatments for psychosis risk, which often involve antipsychotic medications targeting dopamine receptors, the treatments in this trial use THC, a compound found in cannabis, in low and very low doses. Researchers are excited about these treatments because they explore a new avenue by potentially modulating the endocannabinoid system, offering a different mechanism of action. This could be particularly beneficial for individuals with a family history of psychosis, where traditional medications may not be as effective or may have challenging side effects. By investigating both low and very low doses, researchers hope to find the sweet spot where benefits are maximized while minimizing potential risks associated with THC use.

What evidence suggests that this trial's treatments could be effective for psychosis risk?

Research has shown that THC, the active ingredient in cannabis, can affect mental health. It links to a higher risk of conditions like schizophrenia and psychosis. Studies indicate that regular cannabis use can increase the chance of developing these mental health issues. Even small amounts of THC might harm mental health. However, the effects of very low doses of THC remain unclear due to limited study. This trial will explore the effects of low-dose THC, very low-dose THC, and a placebo on individuals with and without a family history of psychosis. Current evidence suggests caution with THC, especially for those with a family history of psychosis. ^{3 4 6 7 8}

Who Is on the Research Team?

Mohini Ranganathan, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for people who have tried cannabis at least once and are medically and mentally healthy. They must also have a relative with a confirmed psychotic disorder. It's not specified who can't join, but typically those with health issues that could interfere would be excluded.

Inclusion Criteria

Exposure to cannabis at least once in their lifetime

Medically and psychiatrically healthy based on screening

I have a family member with a confirmed psychotic disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive placebo, very low dose THC, and low dose THC interventions to study the cannabinoid system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose THC
• Placebo
• Very Low Dose THC

Trial Overview The study aims to see if having a family history of psychosis affects how the body responds to THC, an active component of cannabis. Participants will receive either very low dose THC, low dose THC, or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: No Family History of Psychosis (FHN) Experimental Treatment 3 Interventions

Individuals recruited with no history of psychosis in the family. They will receive the placebo, very low dose THC, and low dose THC interventions.

Group II: Family History of Psychosis (FHP) Experimental Treatment 3 Interventions

Individuals with a family member with a confirmed diagnosis of psychosis. They will receive the placebo, very low dose THC, and low dose THC interventions.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Citations

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

High-Concentration Delta-9-Tetrahydrocannabinol ... No therapeutic studies reported favorable results for psychosis or schizophrenia. For anxiety and depression, 53% and 41% of nontherapeutic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2424288/

Cannabis use and the risk of developing a psychotic disorder There is now reasonable evidence from longitudinal studies that regular cannabis use predicts an increased risk of schizophrenia and of reporting psychotic ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/15504263.2023.2226588

Recommendations for Reducing the Risk of Cannabis Use- ... We reviewed evidence on cannabis use-related risk factors for psychosis outcomes at different stages toward recommendations for risk reduction.

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2832297

Convergence of Cannabis and Psychosis on the ... This cohort study investigates the association between cannabis and the midbrain dopamine pathway involved in psychosis.

5. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30093-6/fulltext

Δ 9 -tetrahydrocannabinol: harmful even in low doses? On the one hand, a host of literature indicates detrimental effects on areas such as mental health (eg, increased risk of schizophrenia and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2801827/

High-potency cannabis and the risk of psychosis - PMC However, psychosis was associated with more frequent and longer use of cannabis. This confirms previous suggestions that the risks of both transient psychotic ...

7. nature.com nature.com/articles/s44220-024-00261-x

Assessing rates and predictors of cannabis-associated ... Considering that individuals presenting with acute cannabis-induced psychosis are at high risk of converting to a psychotic disorder (for ...

8. psychiatrypodcast.com psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-240-cannabis-thc-psychosis-risk

Cannabis and Psychosis: Understanding THC's Impact on ... The onset of psychotic symptoms coincided with this change in use, leading to a diagnosis of cannabis-induced psychosis and severe cannabis use ...