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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21DA061350-01 | U.S. NIH Grant/Contract | View source | |
| 195858 | Other Grant/Funding Number | CIHR |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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High-potency cannabis use is associated with public health risks, such as cannabis use disorder, psychotic disorders, and impaired cognition. Legal markets in the US and Canada are geared towards the commercialization of high-tetrahydrocannabinol (THC) products, including concentrates as high as 90-95%. The cannabis industry has resisted regulation of higher-potency products claiming that cannabis consumers naturally self-titrate their use, but the limited evidence to date suggests that even though consumers may use less cannabis as potency rises, consuming higher potency products still leads to greater THC consumption. The investigators will use a randomized crossover trial to evaluate the ability of 36 regular cannabis consumers (18 females and 18 males) to self-titrate the THC dose when vaping concentrates to achieve the desired psychoactive effects. The investigators will also characterize and compare the subjective, cognitive, physiological, and pharmacokinetic effects between cannabis concentrates of different potencies (30%, 60%, and 90% THC). Working with US scientists, the setting of this study will be Toronto, Canada, in the context of federal legalization of cannabis, unique access to cannabis products not available in the US for research purposes, and an encouraging regulatory environment. The investigators will test commercial products that are representative of the THC ranges available in the legal market. Aim 1: To evaluate the ability of regular cannabis consumers to self-titrate their THC dose when vaping concentrates of different potencies. The investigators will compare markers of titration (biological: THC blood levels; behavioral: inhalation topography; subjective: self-reported levels of intoxication) over a range of potencies for a comprehensive characterization of titration practice. The investigators hypothesize that participants will be able to partially but not proportionally reduce THC intake with increase in THC potency. In other words, the investigators anticipate that the proportional decrease in blood THC levels will be lower than the proportional increase in THC concentrations. Aim 2: To compare the cognitive impairment, physiological effects, and addiction liability of consuming lower versus higher THC potency concentrates. The investigators hypothesize that cognitive impairment and physiological effects will be less pronounced with lower-THC concentrates in a dose-response fashion. The investigators will also explore differences in addiction liability between potencies as higher THC concentrations may result in greater dysphoric reactions. These acute effects may be related to long term harms such as accidents, CVD events, and CUD. Exploratory Aim: To explore sex differences in titration efficiency, blood THC concentrations, cognitive impairment, physiological effects, and addiction liability. The investigators propose to analyze sex differences in our primary and secondary outcomes (e.g., whether females will be able to titrate more efficiently than males). This experimental evidence will provide data on the potential acute harms related to concentrates and inform policy decisions on the need to decrease access and/or prevent their initiation and implement information and education campaigns to increase awareness on the risks of using them.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liquid Cannabis Concentrate (30% THC) | Experimental |
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| Liquid Cannabis Concentrate (60% THC) | Experimental |
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| Liquid Cannabis Concentrate (90% THC) | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cannabis (30% THC Concentrate) | Drug | Participants will vape 30% THC concentration of liquid cannabis ad libitum. |
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| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (blood levels of THC and metabolites) | Blood concentrations (ng/mL) of THC, 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC), and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) will be collected for measurement of THC and metabolites. Information and comparison of the PK parameters of THC and its metabolites for each product | Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping. |
| Inhalation Topography | Number of puffs will be measured using the eTop device. | During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum. |
| Inhalation Topography | puff volume (cm^3) will be measured using the eTop device. | During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum |
| Inhalation Topography | puff duration (milliseconds and seconds) | During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum. |
| Inhalation Topography | inter and inter-puff intervals (seconds and minutes) will be measured using the eTop device | During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum. |
| Measure | Description | Time Frame |
|---|---|---|
| Visual Analog Scales (VAS) | A series of Visual Analog Scales (VAS) (ranging from 0 - 100) measuring subjective effects related to liking, high, good/bad effects, and rush. Minimum total score = 0, maximum total score = 2400. Higher/lower scores are item dependent, therefor total score is not indicative of better/worse outcome. | Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sergio Rueda, PhD | Contact | 416-535-8501 | 30742 | sergio.rueda@camh.ca |
| Victor Tang, MD | Contact | 416-535-8501 | 39137 | victor.tang@camh.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Addiction and Mental Health | Recruiting | Toronto | Ontario | M5T 1R8 | Canada |
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C587251 | nabiximols |
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This study is a double blind, randomized, cross-over human laboratory experiment evaluating the ability of participants who regularly consume cannabis to self-titrate their THC dose when vaping high-THC liquid concentrates of different potencies (30%, 60%, 90% THC).
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| Cannabis (60% THC Concentrate) | Drug | Participants will vape 60% THC concentration of liquid cannabis ad libitum. |
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| Cannabis (90% THC Concentrate) | Drug | Participants will vape 90% THC concentration of liquid cannabis ad libitum. |
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| Profile of Mood States (POMS) | Used to measure high/intoxication and pleasant/unpleasant cannabis effects. | Before vaping, and 1 hour and 2 hours after vaping. |
| Addiction Research Centre Inventory (ARCI) | Used to assess subjective effects of cannabis. | 1 hour and 2 hours after vaping |
| Cognitive Task - Sustained Attention | CANTAB's Rapid Visual Information Processing test asks participants to monitor a changing series of digits and to respond only when a target sequence of digits is presented. | Before vaping and 60 minutes after vaping. |
| Cognitive Task - Visuo-Spatial Working Memory | CANTAB's Spatial Working Memory test examines the maintenance and manipulation of visuospatial information. | Before vaping and 60 minutes after vaping. |
| Cognitive Task - Psychomotor Speed/Accuracy | CANTAB's Cognition Kit Digit Symbol Substitution (DSST) measures rapid information processing of symbols under a time limit and has been shown to be particularly sensitive to acute cannabis administration. | Before vaping and 60 minutes after vaping. |
| Physiological Effect - Heart Rate | Heart rate (bpm) will be measured. | Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping. |
| Physiological Effect - Blood Pressure | Systolic and diastolic blood pressure (mmHg) will be measured. | Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping. |
| Perceived Cannabis Effects Questions | A questionnaire used to assess the perceived effects of cannabis. | 5 hours After vaping. |
| Pharmacogenetic Variations | Following DNA extraction, genomic DNA will be genotyped using established methods to conduct pharmacogenomics assessments. Examples of genes with known or hypothesized roles in THC metabolism and/or response include CYP2C9 and CNR1, as well as those identified in genome-wide association studies of cannabis use traits (e.g. CHRNA2). | 10 minutes before vaping |
| Sex/Gender | Traditional Masculinity-Femininity Scale (TMF) | During baseline, prior to vaping |