Age-dependent Effects of Smoked and Oral Delta-9-THC

Study Overview
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Brief Summary
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This study will assess the age-dependent effects of smoked and oral THC on abuse liability, intoxication, analgesia and impairment as a function of age.

Detailed Description
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The overall objective of this placebo-controlled, outpatient study is to compare the dose-dependent effects of smoked and oral THC on analgesia and endpoints directly related to adverse consequences of use including abuse liability, intoxication, and impairment as a function of age and sex.

Official Title
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Sex- and AGE-dependent Effects of Smoked and Oral Delta-9-THC

Conditions
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Pain, Abuse, Drug, Intoxication; Cannabinoids

Intervention / Treatment
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* Drug: Cannabis
* Drug: Dronabinol
* Drug: Smoked Placebo
* Drug: Oral Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female aged 18-65 years according to the below criteria: EMERGING ADULTS: 18-25 years of age (+/- one year) MIDDLE-AGED ADULTS: 35-45 years of age (+/- one year) LATE MIDDLE-AGED ADULTS: 55-65 years of age (+/- one year) Report weekly-monthly use of cannabis (with primary mode of use via inhalation) over the past 6 months prior to screening Not currently seeking treatment for their cannabis use No reported clinically significant adverse effects with cannabis use Have a Body Mass Index from 18.5 - 34kg/m2 Able to perform all study procedures FEMALES: Currently practicing an effective form of birth control if pre-menopausal Exclusion Criteria: Meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders-5) criteria for any substance use disorder other than nicotine and mild cannabis use disorder Report using other illicit drugs in the prior 4 weeks Evidence of severe psychiatric illness (e.g. mood disorder with functional impairment or suicide risk, schizophrenia) or medical condition (i.e., hypertension) judged by the study physician (and PI to put the participant at greater risk of experiencing adverse events due to completion of study procedures, interfere with their ability to participate in the study, or their capacity to provide informed consent. Current predominant licit use of medical cannabis Current use of prescription or regular use of over the counter medications (with the exception of hormonal contraceptives and hormone replacement therapy). Current use of herbal supplements that may affect study outcomes or interact with study drug (i.e., St Johns wort, kava, L-tryptophan, melatonin) If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process are not within the normal range and / or reveal any significant illness (e.g., hypertension) as judged by the study physician and to put the participant at greater risk of experiencing adverse events due to completion of study procedures Current pain Pregnancy is exclusionary due to the possible effects of the study medication on fetal development History of an allergic reaction or adverse reaction to cannabis is exclusionary. Currently enrolled in another research protocol Not using a contraceptive method (hormonal or barrier methods) The evaluating physician reviews all medical assessments along with medical history. Any disorders that might make cannabis administration hazardous are exclusionary. Intolerance to lactose and sesame (ingredients in the oral THC preparation) Insensitivity to the Cold Pressor Test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a randomized, double-blind, placebo-controlled study. All participants will complete all dose conditions in a randomized order.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator: Placebo<br>Smoked Cannabis (0 mg THC) Oral placebo (0 mg THC) | Drug: Smoked Placebo<br>* Placebo Cannabis<br>* Other names: Placebo smoked cannabis (no THC);Drug: Oral Placebo<br>* Oral Placebo<br>|
| Experimental: Experimental: Low strength cannabis<br>Smoked Cannabis (10 mg THC) Oral placebo (0 mg THC) | Drug: Cannabis<br>* smoked cannabis<br>* Other names: Smoked cannabis with THC;Drug: Oral Placebo<br>* Oral Placebo<br>|
| Experimental: Experimental: Higher strength cannabis<br>Smoked Cannabis (20 mg THC) Oral placebo (0 mg THC) | Drug: Cannabis<br>* smoked cannabis<br>* Other names: Smoked cannabis with THC;Drug: Oral Placebo<br>* Oral Placebo<br>|
| Experimental: Experimental: Low strength oral THC<br>Smoked Cannabis (0 mg THC) Oral THC (10 mg THC) | Drug: Dronabinol<br>* Oral delta-9-THC<br>* Other names: Delta-9-THC;Drug: Smoked Placebo<br>* Placebo Cannabis<br>* Other names: Placebo smoked cannabis (no THC);|
| Experimental: Experimental: Higher strength oral THC<br>Smoked Cannabis (0 mg THC) Oral THC (20 mg THC) | Drug: Dronabinol<br>* Oral delta-9-THC<br>* Other names: Delta-9-THC;Drug: Smoked Placebo<br>* Placebo Cannabis<br>* Other names: Placebo smoked cannabis (no THC);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject-rated drug effects | Average and peak subjective ratings of drug effects associated with abuse liability and intoxication as measured using visual analogue scales (VAS; 1-100mm). | 6 hours | 
| Analgesia as measured using the Cold Pressor Test | Peak and average pain threshold and tolerance assessed using the Cold Pressor Test | 6 hours | 
| Impairment | The primary outcome measure for performance will be the peak difference from baseline scores of the Global Impairment Score | 6 hours | 
| Pharmacokinetics of THC and metabolites | Plasma levels of THC, 11-OH-THC, and THCCOOH | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Cannabis, Delta-9-THC, Age, Sex