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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is studying CBD, a non-intoxicating cannabis compound, to see if it can help reduce psychosis symptoms in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. CBD works by affecting brain areas involved in mood and perception. Cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis and is associated with fewer side effects than conventional antipsychotic drugs.

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.

What data supports the effectiveness of the drug Epidiolex (CBD) for treating conditions?

Epidiolex, a form of CBD, is approved by the FDA for treating two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in children. This approval is based on its demonstrated ability to reduce seizures in these conditions. ^{1 2 3 4 5}

Is CBD (Cannabidiol) generally safe for humans?

CBD, particularly in the form of Epidiolex, has been studied for safety and shows very low potential for abuse or physical dependence. Clinical trials have not reported significant withdrawal symptoms, indicating it is generally safe for human use. ^{1 2 3 5 6}

How is the drug Epidiolex unique compared to other treatments for epilepsy?

Epidiolex is unique because it is the only FDA-approved cannabidiol (CBD) drug specifically for treating two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in children. Unlike other CBD products, Epidiolex has undergone rigorous clinical trials to ensure its safety and effectiveness. ^{1 2 5 6 7}

Research Team

Godfrey Pearlson, MD

Principal Investigator

Founding Director Olin Research Center; Professor Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. [2021]

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

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. [2022]

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

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. [2021]

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

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

6. United States 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. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Cannabidiol: pharmacology and therapeutic targets. [2022]