Testing the Interactive Effects of Delta-9-Tetrahydrocannabinol and Pregnenolone (THC-Preg)

The overall purpose of this study is to examine the effect of pregnenolone (PREG) on the acute psychosis-like and cognitive effects of Delta-9-tetrahydrocannabinol (THC). This will be tested by pretreating healthy individuals with PREG and then assessing their responses to THC.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Active Delta-9-THC; Drug: Placebo; Drug: Placebo; Drug: Active Pregnenolone

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Biological Studies Unit at the VA Connecticut Healthcare System, Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Exposed to cannabis at least once in lifetime.

Exclusion Criteria:

• Cannabis naive
• Individuals with a documented reaction/allergy to Pregnenolone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Delta-9-THC and Placebo Pregnenolone	Drug: Active Delta-9-THC; Active Delta-9-THC (0.036 mg/kg) given intravenously.; Drug: Placebo; A placebo dose given sublingually.; Drug: Placebo; Placebo dose given intravenously.
Experimental: Active Delta-9-THC and Active Pregnenolone	Drug: Active Delta-9-THC; Active Delta-9-THC (0.036 mg/kg) given intravenously.; Drug: Active Pregnenolone; A dose given sublingually.
Experimental: Placebo Delta-9-THC and Active Pregnenolone	Drug: Placebo; A placebo dose given sublingually.; Drug: Placebo; Placebo dose given intravenously.; Drug: Active Pregnenolone; A dose given sublingually.
Placebo Comparator: Placebo Delta-9-THC and Placebo Pregnenolone	Drug: Placebo; A placebo dose given sublingually.; Drug: Placebo; Placebo dose given intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	Positive, negative, and general symptoms will be assessed using the positive, negative, and general symptom subscales of the PANSS.	Baseline, +110, +180, and +240 minutes after start of THC Infusion

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-reported items and 9 clinician-rated items. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.	Baseline; +15, +110, +180, and +240 minutes after start of THC infusion
Visual Analog Scale (VAS)	Feeling states associated with cannabis intoxication will be measured using a self-reported visual analog scale of feeling states associated with cannabis effects (ex: "high," "calm," "anxious"). Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 11mm line. These data will be captured to validate that the experiment is relevant to cannabis effects.	Baseline; +15, +110, +180, and +240 minutes after start of THC infusion
Psychotomimetic States Inventory (PSI)	The PSI is a measure of drug induced psychotomimetic states. This self-reported 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.	Baseline; +110, +180, and +240 minutes after start of THC infusion
Cognitive Test Battery	Several computer tasks will be administered in order to evaluate the effects of cannabis on verbal learning and memory, visual recognition, spatial working memory, and working memory. The battery consists of five computer tasks that lasts no longer than 20 minutes in total.	25 minutes after start of THC infusion

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Deepak C D'Souza, MD, Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): June 24, 2019
• Study Completion (Actual): June 24, 2019

Study Registration Dates

• First Submitted: March 24, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimated): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cannabis; THC; Marijuana; Pregnenolone; PREG; Psychotic Disorders
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 1501015242