CBD for Cannabidiol

Overseen By Catherine Boyle, BA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hartford Hospital

Must not be taking: Platelet inhibitors, benzodiazepines

Disqualifiers: Substance abuse, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day per visit

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabidiol (CBD), a non-psychoactive compound in cannabis, might aid individuals with certain mental health conditions. Researchers aim to determine if CBD positively affects the brain in those with schizophrenia, schizoaffective disorder, or bipolar disorder with psychosis, compared to individuals without these conditions. Participants will receive either CBD or a placebo (a harmless pill with no active drug) to assess its effects. Individuals diagnosed with one of these conditions or those who are healthy without severe mental illness, and who meet other criteria, might be suitable for this study. As a Phase 1, Phase 2 trial, this study seeks to understand how CBD works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking mental health research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications, but it does exclude those taking medications that might interact negatively with the study drug, such as platelet inhibitors, benzodiazepines, or valproate.

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

Previous studies have shown that CBD is safe and well-tolerated by people. Research indicates that CBD usually does not cause serious side effects. For example, one study found no harmful effects when treating people with psychosis or bipolar disorder. Another study supported CBD's safety, noting that it is well-tolerated even in individuals with mental health conditions like schizophrenia. In some cases, CBD might increase the effects of THC, but this typically occurs when both substances are used together. Overall, current research suggests CBD is generally safe for use, especially when used alone. ^{1 2 3 4 5}

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

Researchers are excited about using CBD for psychosis because it offers a different approach from traditional antipsychotic medications, which often target dopamine receptors. CBD, or cannabidiol, is believed to impact the endocannabinoid system, potentially providing relief without the common side effects associated with typical antipsychotics, like weight gain and sedation. Additionally, CBD is being studied for its potential neuroprotective and anti-inflammatory effects, which could offer broader benefits for patients. This new mechanism of action might provide a fresh option for those who haven't responded well to existing treatments.

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

Research suggests that CBD (cannabidiol) might help reduce symptoms of psychosis in individuals with conditions like schizophrenia and bipolar disorder. In this trial, participants will receive both a 600mg CBD dose and a placebo dose on separate days, with doses randomized and double-blind. Some studies have shown that when combined with other treatments, CBD can improve symptoms based on scales measuring psychotic symptoms and overall clinical impressions. Known for its antipsychotic effects, CBD might help reduce symptoms of psychosis. It also has properties that can lower anxiety and inflammation, potentially supporting its use in treating mental health issues. However, more research is needed to fully understand its long-term effects and optimal use. ^{2 3 4 6 7}

Who Is on the Research Team?

Godfrey Pearlson, MD

Principal Investigator

Founding Director Olin Research Center; Professor Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychotic features, as well as healthy individuals without severe mental illness. Participants must have normal liver function and be able to consent and understand English. Excluded are those allergic to CBD, left-handed individuals (as defined by a specific test), recent substance abusers, those at high risk of suicide or homicide, with certain neurological/medical conditions or on interacting medications.

Inclusion Criteria

You have been diagnosed with schizophrenia, schizoaffective disorder, bipolar I disorder with psychotic features, or any other severe mental illness. Or, you are a healthy individual with no diagnosed severe mental illness.

18-50y/o

Able to provide written informed consent

Exclusion Criteria

You have had an allergic reaction to CBD or products that contain CBD in the past.

You strongly prefer to use your left hand for most activities, according to a hand preference test.

You have been diagnosed with alcohol or drug abuse or dependence within the past month or three months, as determined by the DSM-IV guidelines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single, acute dose of CBD or placebo under double-blind conditions

1 day per visit

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 hours post drug administration

What Are the Treatments Tested in This Trial?

Interventions

• CBD
• Placebo

Trial Overview The study investigates the effects of CBD versus a placebo on the hippocampus during an fMRI memory task in patients with certain psychiatric disorders compared to healthy controls. It aims to demonstrate whether CBD can engage brain targets related to psychosis and if it has potential antipsychotic properties.

How Is the Trial Designed?

Group I: Patients with psychosis Experimental Treatment 2 Interventions

People who are part of a dimensionally-organized psychosis sample spanning several serious mental illness diagnoses including schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder. Eligible participants will be scheduled for two dose visits where they will receive a 600mg CBD dose on one day and a placebo dose on the other day. Doses will be randomized and double-blind. Doses will be administered via oral gel capsules.

Group II: Healthy controls Experimental Treatment 2 Interventions

People who do not have a diagnosis of schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder. Eligible participants will be scheduled for two dose visits where they will receive a 600mg CBD dose on one day and a placebo dose on the other day. Doses will be randomized and double-blind. Doses will be administered via oral gel capsules.

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

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Hartford Hospital

Lead Sponsor

Trials

140

Recruited

19,700+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., et al.[2021]

In a study involving 20 healthy Beagle dogs, repeated oral administration of plant-derived cannabidiol (CBD) was well tolerated, with no significant safety concerns noted over 28 days, although higher doses (12 mg/kg) led to mild gastrointestinal side effects.

The pharmacokinetics of CBD showed a dose-dependent increase in systemic exposure and plasma concentrations, reaching steady state after two weeks, which can inform future dosing strategies for CBD in veterinary medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. Vaughn, DM., Paulionis, LJ., Kulpa, JE.[2021]

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

Cannabidiol (CBD), specifically in its oral formulation Epidiolex, has been shown to have very low abuse potential and is unlikely to cause physical dependence, as demonstrated by studies in rats and nonhuman primates that showed no significant self-administration or withdrawal signs after chronic treatment.

The pharmacokinetic studies confirmed that the doses used in the experiments resulted in therapeutically relevant plasma levels, supporting the safety and efficacy of CBD for treating seizures in severe forms of epilepsy without the risks associated with addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. Gray, RA., Heal, DJ., Maguire, DR., 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 Whether CBD can actually alter the course of the disorder and prevent the onset of psychosis will require larger-scale clinical trials over longer durations.

2. oxfordhealthbrc.nihr.ac.uk oxfordhealthbrc.nihr.ac.uk/new-study-explores-cannabidiols-effects-in-people-with-schizophrenia/

New study explores cannabidiol's effects in people with ... Dr Dominic Oliver said: “Our findings suggest that CBD can intensify the effects of THC in people with schizophrenia and cannabis use disorder.

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

A Scoping Review of the Use of Cannabidiol in Psychiatric ... Adjunct CBD led to a significant improvement in psychotic symptoms and clinical impression as measured by the PANSS and Clinical Global Impression Scale, in ...

4. cureus.com cureus.com/articles/382078-the-relationship-between-cannabis-use-and-schizophrenia-as-a-risk-factor-or-for-its-therapeutic-potential-a-systematic-review-of-evidence

The Relationship Between Cannabis Use and ... CBD might reduce psychotic symptoms in patients with schizophrenia as well as have anxiolytic, anti-inflammatory, and neuroprotective properties ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0272735825000479

The differential effects of medicinal cannabis on mental ... Most consistently, high doses of CBD were followed by some acute relief in anxiety, while CBD + THC combinations alleviated withdrawal in cannabis use disorder ...

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. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2017.17030325

Cannabidiol (CBD) as an Adjunctive Therapy in ... Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and ...