Probing the Cannabinoid System in Individuals With a Family History of Psychosis

Study Overview
=================
Brief Summary
-----------------
The overall purpose of this study is to determine whether a family history of psychosis is associated with an altered cannabinoid system. This will be tested by studying individuals with and without a family history of psychosis and comparing their responses to delta 9-tetrahydrocannabinol (THC), a probe of the cannabinoid system. We hypothesize, that compared to controls with no family history of psychoses, individuals with a family history of psychoses will have an altered response to THC.

Official Title
-----------------
Probing the Cannabinoid System in Individuals With a Family History of Psychosis

Conditions
-----------------
Psychosis, Cannabis Use, THC, Marijuana, Schizophrenia

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Very Low Dose THC
* Drug: Low Dose THC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria FHP: Exposure to cannabis at least once in their lifetime Medically and psychiatrically healthy based on screening Having one relative with a confirmed psychotic disorder Exclusion Criteria FHP: Current or lifetime major DSM-IV Axis I disorder Current or lifetime treatment (at least 6 months) with psychotropic medications for major psychiatric or neurological illness Major or unstable medical illness that might impact safety of the subject in the study Cannabis naive IQ less than 85 Less than a high school diploma or its educational equivalent Pregnancy or lactation Major current or recent (<6 weeks) psychosocial stressors. Inclusion Criteria FHN : Exposure to cannabis at least once in their lifetime Medically and psychiatrically healthy based on screening Exclusion Criteria FHN: Having a family member with psychosis Current or lifetime major DSM-IV Axis I disorder Current or lifetime treatment (at least 6 months) with psychotropic medications for major psychiatric or neurological illness Major or unstable medical illness that might impact safety of the subject in the study Cannabis naive IQ less than 85 Less than a high school diploma or its educational equivalent Pregnancy or lactation Major current or recent (<6 weeks) psychosocial stressors.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: No Family History of Psychosis (FHN)<br>Individuals recruited with no history of psychosis in the family. They will receive the placebo, very low dose THC, and low dose THC interventions. | Drug: Placebo<br>* placebo<br>Drug: Very Low Dose THC<br>* Subjects will receive 0.010mg/kg.<br>* Other names: delta 9-tetrahydrocannabinol;Drug: Low Dose THC<br>* Subjects will receive 0.018 mg/kg over 20 minutes.<br>* Other names: delta 9-tetrahydrocannabinol;|
| Experimental: Family History of Psychosis (FHP)<br>Individuals with a family member with a confirmed diagnosis of psychosis. They will receive the placebo, very low dose THC, and low dose THC interventions. | Drug: Placebo<br>* placebo<br>Drug: Very Low Dose THC<br>* Subjects will receive 0.010mg/kg.<br>* Other names: delta 9-tetrahydrocannabinol;Drug: Low Dose THC<br>* Subjects will receive 0.018 mg/kg over 20 minutes.<br>* Other names: delta 9-tetrahydrocannabinol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptom Scale for Schizophrenia (PANSS) | Positive, negative and general symptoms will be assessed using the positive, negative and general symptoms subscales of the PANSS. | -30 min from administration of THC | 
| Positive and Negative Symptom Scale for Schizophrenia (PANSS) | Positive, negative and general symptoms will be assessed using the positive, negative and general symptoms subscales of the PANSS. | +80 min from administration of THC | 
| Positive and Negative Symptom Scale for Schizophrenia (PANSS) | Positive, negative and general symptoms will be assessed using the positive, negative and general symptoms subscales of the PANSS. | +150 min of administration of THC | 
| Positive and Negative Symptom Scale for Schizophrenia (PANSS) | Positive, negative and general symptoms will be assessed using the positive, negative and general symptoms subscales of the PANSS. | +240 min of administration of THC | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Administered Dissociative Symptoms Scale (CADSS) | Perceptual alterations will be measured using the CADSS. This is a scale consisting of 19 self-report items and 8 clinician-rated items (0=not at all, 4=extremely). The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment. | -30 min, +15 min, +80 min, +150 min, +240 min | 
| Visual Analog Scale (VAS) | Feeling states associated with cannabis intoxication will be measured using a self-reported visual analogue scale of four feeling states (high, anxious, calm and relaxed, and tired) associated with cannabis effects. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 11 mm line (0=not at all, 100=extremely). These data will be captured to validate that the experiment is relevant to cannabis effects. | -30 min, +15 min, +80 min, +150 min, +240 min | 
| Hopkins Verbal Learning Test (HVLT) | The HVLT is a 12 word list that is semantically organized. The task consists of 5 trials, an interference list, and free delayed recall and recognition. A different version of the AVLT will be administered on each test day and counterbalanced across subjects. | +50 min | 
| Psychotomimetic States Inventory (PSI) | The PSI is a measure of drug induced psychotomimetic states. This self-report scale consists of 28 items rated 0 (not at all) to 3 (extremely) and will facilitate the characterization of a wide range of dissociative/hallucinatory phenomena as well as cognitive disorganization associated with the administration of THC. | -30 min, +240 min |