Hippocampal Response to Acute Oral Doses of CBD During an fMRI Memory Task

Cannabidiol (CBD) is another cannabis plant derivative for which, like THC, there has been extensive research. Unlike THC however, CBD is non-intoxicating and non-psychedelic. CBD has antipsychotic effects. Logically, if CBD opposes THC effects, it may be a potential antipsychotic treatment. The purpose of this pilot research is to show target engagement of the hippocampus with the study drug (CBD versus placebo) in patients who have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder with psychosis compared to healthy controls.

The investigators conjecture that CBD may act both to modify THC effects and to reduce psychosis symptoms (at least in part) through downstream ECS-related mechanisms, both of which actions converge on the hippocampus, a region rich in CB1 receptors. As such, observing hippocampus activity levels using fMRI can be an effective means of measuring CBD target engagement within this pilot study context. The purpose of this pilot research is to show target engagement of the hippocampus with the study drug cannabidiol (CBD) versus placebo, in BSNIP Biotype 3 compared to Biotypes 1 and 2 and to healthy control subjects, during performance of an fMRI paired associated memory task. Here, investigators will use B-SNIP-based observations in already-characterized B-SNIP subjects, to predict in which individuals CBD engages a theoretically-based brain target. In turn (in future planned studies) such engagement may predict CBD treatment responders. At present, CBD is still an experimental drug for psychosis treatment (although now FDA-approved for treatment of specific types of childhood seizures), but one with a rather benign side-effect profile that could easily be added to ongoing antipsychotic treatment. The purpose of the study is to study response to a single, acute dose of CBD compared to placebo, under double-blind conditions in a small-scale pilot study.

Eligibility Criteria:
Inclusion Criteria:

* 18-50y/o
* Males and females of all races and ethnicities
* Able to provide written informed consent
* Able to read, speak, and understand English
* Meet DSM-IV (SCID-based) criteria for schizophrenia, schizoaffective disorder, bipolar I disorder with psychotic features OR healthy controlled with no diagnosed severe mental illness
* No history of adverse normal baseline values for liver function tests (LFTs)

Exclusion Criteria:

* Strongly left-handed individuals defined as a 60:40 or greater ratio of left to right hand preference (assessed using the Edinburgh Handedness Inventory)
* Premorbid intellectual ability estimate below 70 (WRAT-4, Word Reading subtest, age-corrected standardized score)
* Comorbid DSM-IV diagnosis of alcohol or substance abuse in prior 1 month or substance dependence in prior 3 months
* Neurological (e.g., seizure disorder, stroke, traumatic brain injury with a loss of consciousness ≥ 30min) or severe medical condition (e.g., decompensated cardiovascular disorder, AIDS) that may affect central nervous system function
* Concomitant medications that may interact with study drug adversely such as platelet inhibitors, benzodiazepines, or valproate
* Initial detection of abnormal liver function tests or previous medical history of abnormal liver function or liver disease
* Vulnerable populations (e.g., pregnant, nursing, incarcerated); unwilling to use reliable means of contraception
* High risk for suicide defined as more than 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded
* Current homicidal ideation with plan and intent such that outpatient care is precluded
* Positive result on breathalyzer or positive urine toxicology test for any substance, including CBD
* History of prior allergic reaction with CBD or CBD-containing products