THC Titration of High-Potency Cannabis Concentrates

Официальное название

THC Titration of High-Potency Cannabis Concentrates: A Randomized Cross-Over Trial

Обзор

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.

Вмешательства

• Препарат Cannabis (30% THC Concentrate)
  Participants will vape 30% THC concentration of liquid cannabis ad libitum.
• Препарат Cannabis (60% THC Concentrate)
  Participants will vape 60% THC concentration of liquid cannabis ad libitum.
• Препарат Cannabis (90% THC Concentrate)
  Participants will vape 90% THC concentration of liquid cannabis ad libitum.

Первичные конечные точки

• Pharmacokinetics (blood levels of THC and metabolites) [Срок оценки: Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping.]
• Inhalation Topography [Срок оценки: During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum.]
• Inhalation Topography [Срок оценки: During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum]
• Inhalation Topography [Срок оценки: During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum.]
• Inhalation Topography [Срок оценки: During a 10-minute vaping session, participants will be asked to consume cannabis ad libitum.]

Вторичные конечные точки (11)

• Visual Analog Scales (VAS) [Срок оценки: Before vaping, 5-min after first inhalation, and at 5-, 30-, and at 60-minute intervals until 4 hours after vaping.]
• Profile of Mood States (POMS) [Срок оценки: Before vaping, and 1 hour and 2 hours after vaping.]
• Addiction Research Centre Inventory (ARCI) [Срок оценки: 1 hour and 2 hours after vaping]
• Cognitive Task - Sustained Attention [Срок оценки: Before vaping and 60 minutes after vaping.]
• Cognitive Task - Visuo-Spatial Working Memory [Срок оценки: Before vaping and 60 minutes after vaping.]
• Cognitive Task - Psychomotor Speed/Accuracy [Срок оценки: Before vaping and 60 minutes after vaping.]
• Physiological Effect - Heart Rate [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 5 hours After vaping.]
• Pharmacogenetic Variations [Срок оценки: 10 minutes before vaping]
• Sex/Gender [Срок оценки: During baseline, prior to vaping]

Критерии участия

Критерии включения

• Age 19-55 years.
• Frequency of primary exposure to cannabis 1-4 occasions per week, through any route of administration, over the past three months; participants must report experience with vaping high-potency liquid concentrates with more than 3 exposures to 90% THC and willingness to use such products in the study.
• Refrain from cannabis for 48 hours and from alcohol for 12 hours before visits.
• Agree not to drive a car for 24 hours after each visit.
• Abstain from recreational drugs for at least 48 hours prior to each visit.
• Abstain from any drugs not medically required.
• Well-controlled blood pressure for participants with hypertension.

Критерии исключения

• Pregnant/breastfeeding (women of childbearing potential must have a negative pregnancy test and report use of appropriate contraception).
• Evidence of cardiac arrhythmias/failure, ischaemic heart disease.
• Recent open heart/open chest surgery or cataract surgery.
• Evidence from Structured Clinical Interview for DSM-5 \[SCID-5-CT\] or clinical evaluation of lifetime psychotic disorder/schizophrenia or bipolar disorder; family history of a first-degree relative with a diagnosis of psychotic disorder or schizophrenia; history of psychiatric co-morbidities in the past year (major depression, anxiety disorder or suicide attempt in past year or current suicidal ideation) and current substance use disorder/dependence.
• Evidence of neurological illness (e.g., stroke, epilepsy, traumatic brain injury).
• Renal or hepatic abnormalities (self-report and blood hematology/chemistry); and
• Respiratory diseases, including asthma and physician-diagnosed lung disease.
• Taking prescribed medications that contain either THC or cannabidiol (CBD).
• Participation in another clinical or non-therapeutic study in the last three months.
• Bleeding disorders.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Другое

Центры проведения

Канада · 1 центр

• Centre for Addiction and Mental Health — Toronto

Идентификаторы

NCT: NCT07105449 · 2024-085 · 1R21DA061350-01 · 195858

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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