Pharmacokinetics and Pharmacological Effects of a Standardized Cannabis Preparation in Healthy Adult Recreational Cannabis Users
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Time to reach maximum serum concentration (Tmax) of THCA
研究概览
简要总结
The purposes of the study are 1) to know the concentrations of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids in blood, urine, oral fluid and sweat after the experimental administration of a standardized cannabis preparation orally (decoction and oil) and vaporized 2) to evaluate the pharmacological acute effects and tolerability
详细描述
Medical cannabis" encompasses the use of cannabis and cannabinoids for therapeutic purposes. Includes drugs approved by regulatory agencies and pharmaceutical products. Recently, many countries have authorized the use of cannabis flower cups with a standardized amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and their acidic precursors (Δ-9-tetrahydrocannabinolic acid A [THCA] and cannabidiol acid [ CBDA]) for the treatment of different diseases. In Italy since January 2017 there has been for sale a standardized cannabis preparation produced by the Military Pharmaceutical Institute of Florence. This medicinal variety of cannabis sativa, known as FM2 has a variable THC and CBD percentage of between 5-8% and 7-12% respectively. To date, there are no studies on the pharmacokinetics of THC, CBD and other minor cannabinoids in conventional and unconventional biological matrices after oral administration of cannabis tea, cannabis oil and vaporized with the same medicinal preparation (FM2). The main objective is to know the concentrations of THC, CBD and metabolites, and other cannabinoids in blood, urine, oral fluid and sweat after the experimental administration of a standardized cannabis preparation orally (two formulations: cannabis tea and cannabis oil) and vaporized. In addition, the acute pharmacological effects and tolerability will be evaluated. Healthy recreational cannabis users with experience in oral use of cannabis will participate
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participant were aware of the cannabis preparation but not of the administered doses
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Understanding and accepting the study procedures and signing the informed consent.
- •Male and females healthy volunteers (18-45 years old.
- •History and physical examination showing no organic or psychiatric disorders.
- •The EKG and the blood chemistry and hematology at inclusion must be within the limits of normality. Minor or specific variations of the limits of normality are admitted if, in the opinion of the Principal Investigator, taking into account the state of science, they do not have clinical significance, do not pose a risk to the subjects and do not interfere with the evaluation of the product. These variations and their non-relevance will be specifically justified in writing.
- •Body weight between 50-90 kilograms. Lower or higher weights are allowed, in the opinion of the Principal Investigator or the collaborators designated by him and that do not pose a risk to the subjects and do not interfere with the objectives of the study.
- •BMI between 19-27 kg / m². Lower or higher BMIs are admitted, which in the opinion of the Principal Investigator or the collaborators designated by him that do not pose a risk to the subjects and do not interfere with the objectives of the study.
- •Women with a menstrual cycle that lasts between 26-32 days and is regular.
- •Subjects with social or recreational consumption of cannabis in the last 12 months and consumption of oral cannabis at least once in their life (eg cake, cookies, oils, infusion...).
排除标准
- •Not meeting the inclusion criteria.
- •History or clinical evidence of gastrointestinal, liver, kidney or other disorders that may involve an alteration in the absorption, distribution, metabolism or excretion of the drug, or that are suggestive of gastrointestinal irritation by drugs.
- •Current or previous history of Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) substance use disorder (except nicotine and mild cannabis use disorder or DSM-IV for substance use disorder or abuse).
- •Having donated blood in the previous 8 weeks, or having participated in clinical trials with drugs or nutraceuticals in the previous 12 weeks, except for having previously participated in this same study, in which a 3-week washout period is sufficient.
- •Having suffered any organic disease or major surgery in the three months prior to the start of the study.
- •Subjects who are intolerant or have had serious adverse reactions to cannabis.
- •Having taken medication regularly in the month prior to the study sessions, with the exception of vitamins, herbal remedies or dietary supplements that, in the opinion of the Principal Investigator or the collaborators designated by him, do not pose a risk to the subjects and do not interfere with the objectives of the study. Treatment with single doses of symptomatic medication in the week prior to the study sessions will not be grounds for exclusion if it is assumed that it has been completely eliminated on the day of the experimental session.
- •Smokers of more than 15 cigarettes a day.
- •Subjects who are uncapable of understanding the nature of the trial and the procedures they are required to follow.
- •Subjects with positive serology for hepatitis B, C or HIV.
- •Women who are pregnant or breastfeeding, or who use hormonal contraceptives or do not use reliable contraceptive measures during the study (such as abstinence, intrauterine devices, barrier methods or with a vasectomized partner).
- •Women with amenorrhea or severe premenstrual syndrome.
研究组 & 干预措施
Oral formulation: Cannabis decoction
From a standardized preparation cannabis Cannabis FM2 (THC) (~ 6%) and (CBD) (~ 8%) ,cannabis decoction will be prepared at the moment by putting female inflorescences in cold water brought to a boil, boiling for 15 minutes and using 500 mg of medicinal cannabis for 500 ml of water.
干预措施: Cannabis decoction (Drug)
Oral formulation: Cannabis oil
From a standardized preparation cannabis Cannabis FM2 (THC) (~ 6%) and (CBD) (~ 8%), cannabis oil is prepared the day before the experimental session with 500 mg of female inflorescences in 5 ml of olive oil from the European Pharmacopoeia, heating in a water bath (approximately 98 ° C) for 120 minutes and cooling the oil samples. at room temperature.
干预措施: Cannabis oil (Drug)
Vaporized formulation: Cannabis vaporized
From a standardized preparation cannabis Cannabis FM2 (THC) (~ 6%) and (CBD) (~ 8%), 100 mg of Cannabis inflorescences of FM2 standardized cannabis were administered through Volcano vaporizer .
干预措施: Vaporized cannabis (Drug)
结局指标
主要结局
Time to reach maximum serum concentration (Tmax) of THCA
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Time to reach maximum serum concentration (Tmax) of CBD
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Maximum serum concentration (Cmax) of THC
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Calculation of maximum concentration (ng/mL) in samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Maximum serum concentration (Cmax) of THCA
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Calculation of maximum concentration (ng/mL) in samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Maximum serum concentration (Cmax) of CBD
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Calculation of maximum concentration (ng/mL) in samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Maximum serum concentration (Cmax) of CBDA
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Calculation of maximum concentration (ng/mL) in samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Time to reach maximum serum concentration (Tmax) of THC
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Area under the concentration-time curve (AUC 0-24 h) of THC in serum concentrations
时间窗: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Calculation of AUC with samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Time to reach maximum serum concentration (Tmax) of THC metabolites
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Time to reach maximum serum concentration (Tmax) of CBDA
时间窗: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Area under the concentration-time curve (AUC 0-24 h) of CBD in serum concentrations
时间窗: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Calculation of AUC with samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Area under the concentration-time curve (AUC 0-24 h) of CBDA in serum concentrations
时间窗: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Calculation of AUC with samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
Area under the concentration-time curve (AUC 0-24 h) of THCA in serum concentrations
时间窗: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Calculation of AUC with samples collected from 15 min prior to administration (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after oral cannabis formulation ( decoction or oil). In the case of vaporized cannabis, serum samples are collected 15 minutes before, at time zero (administration), and at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours.
次要结局
- Maximum oral fluid concentration (Cmax) of THC(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Time to reach maximum oral fluid concentration (Tmax) of CBDA(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Area under the concentration-time curve (AUC 0-24h) of CBD oral fluid concentrations(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Total concentration of THC present in sweat after oral and vaporized cannabis administration.(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Change in High feeling: Emax (peak/maximum effects) in High feeling(Differences from baseline to 24 hours)
- Maximum oral fluid concentration (Cmax) of THCA(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Maximum oral fluid concentration (Cmax) of CBD(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Maximum oral fluid concentration (Cmax) of CBDA(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Time to reach maximum oral fluid concentration (Tmax) of THC(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Time to reach maximum oral fluid concentration (Tmax) of THCA(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Time to reach maximum oral fluid concentration (Tmax) of CBD(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Area under the concentration-time curve (AUC 0-24h) of CBDA oral fluid concentrations(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Total concentration of CBD present in sweat after oral and vaporized cannabis administration.(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Change in Heart rate: Emax (peak/maximum effects) in Heart rate(Differences from baseline to 24 hours)
- Area under the concentration-time curve (AUC 0-24h) of THC oral fluid concentrations(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Area under the concentration-time curve (AUC 0-24h) of THCA oral fluid concentrations(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Total amount cannabis metabolites (THC-carboxy and THC-glucoronides, excreted in 24 h urine samples.(From baseline to 24 hours after decoction, oil or vaporized cannabis administration)
- Change in blood pressure: Emax (peak/maximum effects) in blood pressure(Differences from baseline to 24 hours)
- Change in oral temperature: Emax (peak/maximum effects) in oral temperature(Differences from baseline to 24 hours)
- Change in Intensity of effects: Emax (peak/maximum effects) in Intensity of effects(Differences from baseline to 24 hours)
- Change in Hunger: Emax (peak/maximum effects) in Hunger(Differences from baseline to 24 hours)
- Change in Drowsines: Emax (peak/maximum effects) in Drowsiness(Differences from baseline to 24 hours)
- Change in global drug effects: Emax (peak/maximum effects) in global drug effects(Differences from baseline to 24 hours)