Cannabidiol for Psychosis

Recruiting at 1 trial location

Overseen By Kristin Cadenhead

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, San Diego

Must be taking: Antipsychotics

Must not be taking: Azelastine, Dronabinol, Valproic Acid

Disqualifiers: Neurological illness, Head injury, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a cannabidiol (CBD) oral solution can improve symptoms in individuals experiencing early psychosis, a mental disorder where understanding reality may be difficult. Participants will receive either the CBD solution or a placebo (a look-alike with no active ingredients) for eight weeks. The trial aims to determine if CBD can enhance mood, thinking, and behavior. Ideal candidates have experienced their first episode of psychosis or similar symptoms within the last two years and are currently stable with treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need treatment with Azelastine, Fluticasone, Dronabinol, Valproic Acid, or Divalproex Sodium.

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

Research has shown that Cannabidiol (CBD) is generally safe for people with psychosis. Studies have found that CBD can help reduce symptoms in those with schizophrenia and similar conditions. Importantly, these studies reported that participants did not experience serious side effects from using CBD.

In another study, researchers gave CBD to people at high risk of developing psychosis. The results suggested that short-term use of CBD improved their symptoms and was well-tolerated, meaning it did not cause significant negative effects.

Overall, current research suggests that CBD is a safe option for treating psychosis. However, it is always important to consult a healthcare provider before starting any new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for psychosis?

Most treatments for psychosis, like antipsychotics, work by altering dopamine levels in the brain. But cannabidiol (CBD) offers a different approach, potentially acting on the brain's endocannabinoid system, which could provide relief without the common side effects of traditional medications. Researchers are excited because CBD is a natural compound derived from cannabis plants, and it might offer a safer, more tolerable option for patients. Plus, the oral solution form allows for easy administration and precise dosing, making it an appealing alternative to current therapies.

What evidence suggests that Cannabidiol might be an effective treatment for psychosis?

Research has shown that cannabidiol (CBD) might help reduce symptoms of psychosis. Some studies found that doses between 600 and 1000 mg of CBD can lessen these symptoms in people with schizophrenia. This trial will test CBD as an augmentation treatment, with participants receiving either a Cannabidiol Oral Solution or a placebo. Additionally, people with early signs of psychosis have shown improvements when using CBD alongside their regular treatment. These findings offer hope that CBD could be a useful tool in managing symptoms of psychosis. ^{1 4 6 7 8}

Who Is on the Research Team?

Kristin Cadenhead, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adolescents and adults with early psychosis or related conditions, stable on treatment for at least 8 weeks. They must have mild symptoms, not be at high suicide risk, not pregnant or likely to become so without contraception, and free from substance abuse including THC/CBD.

Inclusion Criteria

My symptoms like delusions or hallucinations are not severe.

My diagnosis is one of the following: APS, psychosis, schizophreniform, schizophrenia, or schizoaffective.

I've been stable on my current psychosis treatment for at least 8 weeks.

Exclusion Criteria

You recently had a serious head injury.

I have another serious illness besides cancer.

High suicidal risk assessed by the The Columbia-Suicide Severity Rating Scale (C-SSRS)42

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive either Cannabidiol Oral Solution (CBD) or placebo as an add-on to antipsychotic medication in an 8-week double-blind trial

8 weeks

Pre-treatment, midpoint (week 4), and post-treatment (week 8) testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol Oral Solution

Trial Overview The study tests if Cannabidiol (CBD) oral solution improves symptoms of psychosis when added to standard treatment compared to a placebo. Participants are randomly assigned CBD or placebo for 8 weeks in a double-blind setup where neither they nor the researchers know who gets what.

How Is the Trial Designed?

Group I: Cannabidiol Augmentation Experimental Treatment 1 Intervention

The cannabidiol will be administered as an oral solution to be mixed in any fluid. The formulation is 100 mg/ml. It will be administered at 500 mg at bedtime X 1 week then 500 mg BID.

Group II: Placebo Augmentation Placebo Group 1 Intervention

Placebo will appear identical to the cannabidiol solution

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Center for Medicinal Cannabis Research

Collaborator

Trials

19

Recruited

630+

Published Research Related to This Trial

A qualitative study involving 15 youth in Early Psychosis Intervention programs revealed that most participants used CBD for reasons like pain relief and relaxation, often viewing it as a safer alternative to THC.

Despite their positive perceptions of CBD, many users were unaware of potential health risks, highlighting the need for education on the benefits and risks of CBD use among this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives toward cannabidiol (CBD) among youth in Early Psychosis Intervention programs: A qualitative study. Ghelani, A.[2023]

A survey of 70 patients with psychotic disorders revealed that 86% were willing to try cannabidiol (CBD) as a treatment, indicating a high level of acceptability among this group.

Most patients believed that CBD could improve their symptoms and have fewer side effects compared to traditional antipsychotic medications, suggesting that CBD may be a promising alternative treatment option for psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of cannabidiol in patients with psychosis. Chesney, E., Lamper, D., Lloyd, M., et al.[2023]

In a study involving 32 clinical high-risk for psychosis (CHR) patients and 26 healthy controls, CBD treatment (600 mg/day) showed an intermediate effect on cortisol reactivity to stress compared to placebo, suggesting potential benefits in managing stress responses in CHR patients.

While CBD did not significantly differ from placebo in cortisol reactivity, it indicated a trend towards normalizing stress responses, highlighting the need for further research on CBD's effects on anxiety and psychosis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis. Appiah-Kusi, E., Petros, N., Wilson, R., et al.[2022]

A clinical trial involving 120 individuals with early psychosis will investigate the effectiveness of 1000 mg of cannabidiol (CBD) as an adjunct treatment over 8 weeks, focusing on symptoms and neurocognition.

Preliminary evidence suggests that CBD may improve positive symptoms of psychosis and potentially help with negative symptoms and cognitive function, while being well tolerated compared to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol versus placebo as adjunctive treatment in early psychosis: study protocol for randomized controlled trial. Dixon, T., Cadenhead, KS.[2023]

Cannabidiol (CBD), a component of cannabis, may have antipsychotic properties that could help in treating psychosis, despite cannabis use being linked to an increased risk of developing such conditions.

A targeted literature review of various studies, including animal and human research, indicates that CBD shows promise as a potential treatment for psychotic symptoms and disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol as a potential treatment for psychosis. Schubart, CD., Sommer, IE., Fusar-Poli, P., et al.[2014]

This study is evaluating the efficacy of cannabidiol (600 mg) compared to risperidone (4 mg) in treating early psychosis in 130 patients who also use cannabis, aiming to assess both psychotic symptoms and cannabis cessation over a seven-week period.

The trial's outcomes could lead to new treatment options for patients with dual diagnosis of psychosis and cannabis use, as current pharmacological treatments are lacking for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial. Rasmussen, JØ., Jennum, P., Linnet, K., et al.[2023]

A single oral dose of 600 mg of cannabidiol significantly increased hippocampal glutamate levels and reduced symptom severity in 13 patients with psychosis, indicating its potential antipsychotic effects.

The study suggests a link between increased glutamate levels and decreased psychotic symptoms, providing new insights into how cannabidiol may work in the brain to alleviate psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol modulation of hippocampal glutamate in early psychosis. O'Neill, A., Annibale, L., Blest-Hopley, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6843725/

Cannabidiol as a potential treatment for psychosis - PMC THC can be used as an experimental model of psychosis in humans because its acute administration in healthy individuals can induce transient psychotic-like ...

2. nature.com nature.com/articles/s41386-025-02175-3

Does cannabidiol reduce the adverse effects of cannabis in ... Data from clinical trials suggest that CBD (at doses between 600 and 1000 mg) can reduce psychotic symptoms in people with schizophrenia [24,25, ...

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07789-w

Cannabidiol versus placebo as adjunctive treatment in early ... Patients who meet the criteria for attenuated psychosis syndrome (APS) have up to a 30% risk of conversion to a full psychotic syndrome within 2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8799523/

A Scoping Review of the Use of Cannabidiol in Psychiatric ... Results. 3.1. Psychotic Disorders. There is a growing body of evidence that the endocannabinoid system is implicated in the pathophysiology of psychosis ( ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04411225

NCT04411225 | Effects of Cannabidiol (CBD) Versus ... This scale will be used to assess subsyndromal psychotic symptoms in participants who are diagnosed as Clinical High Risk for Psychosis. Positive and Negative ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol No adverse effects were reported in this study. Psychosis and bipolar disorder. Various studies on CBD and psychosis have been conducted. For instance, an ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201823003854

Adverse events of epidiolex: A real-world drug safety ... Pimavanserin, a novel 5-HT2A receptor antagonist, has been approved for the treatment of Parkinson's disease psychosis (PDP). This study aims to conduct a ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/wps.21253

Effects of cannabidiol on symptoms in people at clinical ... Our findings indicate that short-term treatment with CBD can ameliorate the symptoms of CHR state for psychosis, and is well tolerated. These ...