Clinical trial NCT04841993: Pharmacokinetics and Pharmacological Effects of a Standardized Cannabis Preparation
Official title: Pharmacokinetics and Pharmacological Effects of a Standardized Cannabis Preparation in Healthy Adult Recreational Cannabis Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cannabis Use
Healthy Subjects
Keywords: medical cannabis
pharmacokinetics
acute effects
cannabis decoction
cannabis oil
vaporized cannabis
oral cannabis
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundació Institut Germans Trias i Pujol
name: Istituto Superiore di Sanità
First posted: 2021-04-12
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was unicentric, open-label, not randomized, not placebo controlled ,single blind. The study included three substudies (one for each formulation administration). The first one for decoction administration, the second one for oil administration, and finally, an experimental session was held for the administration of the standardized vaporized cannabis preparation. Each subject will participate in one experimental session. One treatment condition per subject (of two possible oral formulations and one inhaled / vaporized formulation of vaporized cannabis. Once the experimental session is over, the subjects have the possibility of being able to participate in the same study after a minimum washout period of 3 weeks.
Primary purpose: BASIC_SCIENCE

Brief summary: 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

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 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...).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maximum serum concentration (Cmax) of THC
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Maximum serum concentration (Cmax) of THCA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Maximum serum concentration (Cmax) of CBD
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Maximum serum concentration (Cmax) of CBDA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Time to reach maximum serum concentration (Tmax) of THC
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Time to reach maximum serum concentration (Tmax) of THCA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Time to reach maximum serum concentration (Tmax) of THC metabolites
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Time to reach maximum serum concentration (Tmax) of CBD
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Time to reach maximum serum concentration (Tmax) of CBDA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
measure: Area under the concentration-time curve (AUC 0-24 h) of THC in serum concentrations
timeFrame: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
measure: Area under the concentration-time curve (AUC 0-24 h) of THCA in serum concentrations
timeFrame: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
measure: Area under the concentration-time curve (AUC 0-24 h) of CBD in serum concentrations
timeFrame: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
measure: Area under the concentration-time curve (AUC 0-24 h) of CBDA in serum concentrations
timeFrame: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Secondary outcomes:
measure: Maximum oral fluid concentration (Cmax) of THC
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Maximum oral fluid concentration (Cmax) of THCA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Maximum oral fluid concentration (Cmax) of CBD
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Maximum oral fluid concentration (Cmax) of CBDA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Time to reach maximum oral fluid concentration (Tmax) of THC
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Time to reach maximum oral fluid concentration (Tmax) of THCA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Time to reach maximum oral fluid concentration (Tmax) of CBD
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Time to reach maximum oral fluid concentration (Tmax) of CBDA
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Area under the concentration-time curve (AUC 0-24h) of THC oral fluid concentrations
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Area under the concentration-time curve (AUC 0-24h) of THCA oral fluid concentrations
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Area under the concentration-time curve (AUC 0-24h) of CBD oral fluid concentrations
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Area under the concentration-time curve (AUC 0-24h) of CBDA oral fluid concentrations
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Total amount cannabis metabolites (THC-carboxy and THC-glucoronides, excreted in 24 h urine samples.
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Total concentration of THC present in sweat after oral and vaporized cannabis administration.
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Total concentration of CBD present in sweat after oral and vaporized cannabis administration.
timeFrame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
measure: Change in blood pressure: Emax (peak/maximum effects) in blood pressure
timeFrame: Differences from baseline to 24 hours
measure: Change in Heart rate: Emax (peak/maximum effects) in Heart rate
timeFrame: Differences from baseline to 24 hours
measure: Change in oral temperature: Emax (peak/maximum effects) in oral temperature
timeFrame: Differences from baseline to 24 hours
measure: Change in Intensity of effects: Emax (peak/maximum effects) in Intensity of effects
timeFrame: Differences from baseline to 24 hours
measure: Change in High feeling: Emax (peak/maximum effects) in High feeling
timeFrame: Differences from baseline to 24 hours
measure: Change in Hunger: Emax (peak/maximum effects) in Hunger
timeFrame: Differences from baseline to 24 hours
measure: Change in Drowsines: Emax (peak/maximum effects) in Drowsiness
timeFrame: Differences from baseline to 24 hours
measure: Change in global drug effects: Emax (peak/maximum effects) in global drug effects
timeFrame: Differences from baseline to 24 hours
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Magi Farré, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Busardo FP, Perez-Acevedo AP, Pacifici R, Mannocchi G, Gottardi M, Papaseit E, Perez-Mana C, Martin S, Poyatos L, Pichini S, Farre M. Disposition of Phytocannabinoids, Their Acidic Precursors and Their Metabolites in Biological Matrices of Healthy Individuals Treated with Vaporized Medical Cannabis. Pharmaceuticals (Basel). 2021 Jan 13;14(1):59. doi: 10.3390/ph14010059.
citation: Perez-Acevedo AP, Busardo FP, Pacifici R, Mannocchi G, Gottardi M, Poyatos L, Papaseit E, Perez-Mana C, Martin S, Di Trana A, Pichini S, Farre M. Disposition of Cannabidiol Metabolites in Serum and Urine from Healthy Individuals Treated with Pharmaceutical Preparations of Medical Cannabis. Pharmaceuticals (Basel). 2020 Dec 12;13(12):459. doi: 10.3390/ph13120459.
citation: Pichini S, Malaca S, Gottardi M, Perez-Acevedo AP, Papaseit E, Perez-Mana C, Farre M, Pacifici R, Tagliabracci A, Mannocchi G, Busardo FP. UHPLC-MS/MS analysis of cannabidiol metabolites in serum and urine samples. Application to an individual treated with medical cannabis. Talanta. 2021 Feb 1;223(Pt 2):121772. doi: 10.1016/j.talanta.2020.121772. Epub 2020 Oct 14.
citation: Perez-Acevedo AP, Pacifici R, Mannocchi G, Gottardi M, Poyatos L, Papaseit E, Perez-Mana C, Martin S, Busardo FP, Pichini S, Farre M. Disposition of cannabinoids and their metabolites in serum, oral fluid, sweat patch and urine from healthy individuals treated with pharmaceutical preparations of medical cannabis. Phytother Res. 2021 Mar;35(3):1646-1657. doi: 10.1002/ptr.6931. Epub 2020 Nov 6.