Cannabidiol as a Different Type of an Antipsychotic: Drug Delivery and Interaction Study

Study Overview
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Brief Summary
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Despite recent advances in the understanding and treatment of schizophrenia, this devastating disease still affects one percent of world's population. Existing antipsychotics reduce psychotic symptoms but are generally not very effective in treating so called negative symptoms such as blunted affect and social withdrawal or cognitive disturbances due to the disease. Furthermore, a significant portion of patients is refractory to all current treatments. Therefore new treatment strategies are needed. Several studies suggest a strong association between schizophrenia and the endocannabinoid system. This system mediates e.g. the pro-psychotic effects of the best-known ingredient of the cannabis plant - delta-tetrahydrocannabinol (Δ9-THC). While the pro-psychotic Δ9-THC is known to abet the onset of schizophrenia, another, non-psychotomimetic plant ingredient - cannabidiol - has recently been shown to exert antipsychotic effects similar to those of one of the most effective modern antipsychotics, amisulpride, but it induced significantly less side effects. In this phase I safety study, the investigators will evaluate the pharmacokinetics, pharmacoequivalence, and drug-drug interaction profile with current antipsychotics of a new tablet pharmaceutical preparation of cannabidiol in healthy volunteers.

Official Title
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Cannabidiol as a Different Type of an Antipsychotic: Drug Delivery and Interaction Study With Approved Antipsychotics in Vivo

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Cannabidiol CR
* Drug: Cannabidiol
* Drug: Amisulpride
* Drug: Olanzapine
* Drug: Quetiapine
* Drug: Risperidone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent given by the subject Both, female and male subjects may participate Age between 18 and 45 Negative drug screening at the time of screening Non-smoking In female participants in fertile age, reliable contraception, which means contraception's pearl-index is equal or smaller than 1. Body Mass Index between 18 and 30 Exclusion Criteria: Lack of accountability Any current psychiatric disorder through the Structured Clinical Interview for DSM-IV (SCID) at the time of screening Pregnancy or lactation phase in female at the time of screening Any known psychiatric or neurological illness in the participant's history. Known family history concerning psychiatric disorders Relevant use of cannabis (which is defined on the present state of knowledge as at the most five times lifetime-consumption and no consumption for at least one year) Severe physical (internal) or neurological illness, especially cardiovascular, renal, advanced respiratory, haematological or endocrinological failures or infectious diseases (acute hepatitis A, B or C or HIV) assessed at the time of the screening by the subject's history, clinical examination and laboratory testing, at the discretion of the investigator Consumption of any illicit drugs (except cannabis in history, see above)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cannabidiol<br>Cannabidiol capsule, 200 mg single dose | Drug: Cannabidiol<br> <br> |
| Experimental: Cannabidiol CR<br>Cannabidiol tablet, various dosages | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;|
| Experimental: Amisulpride and Cannabidiol CR<br>Interaction between Amisulpride and Cannabidiol CR | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;Drug: Amisulpride<br> <br> |
| Experimental: Olanzapine and Cannabidiol CR<br>Interaction between Olanzapine and Cannabidiol CR | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;Drug: Olanzapine<br> <br> |
| Experimental: Quetiapine and Cannabidiol CR<br>Interaction between Quetiapine and Cannabidiol CR | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;Drug: Quetiapine<br> <br> |
| Experimental: Risperidone and Cannabidiol CR<br>Interaction between Risperidone and Cannabidiol CR | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;Drug: Risperidone<br> <br> |
| Placebo Comparator: Cannabidiol CR and Placebo<br>Cannabidiol CR levels without interaction with antipsychotics | Drug: Cannabidiol CR<br> <br> * Other names: Arvisol;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of cannabidiol |  | up to 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) |  | up to 10 days | 
| serum antipsychotic concentration |  | baseline and after seven days |