Pharmacokinetics and Pharmacological Effects of a Standardized Cannabis Preparation

NCT04841993 | Completed Phase 1

• 1 other identifier: HUGTP/CANNMED/1
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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

Conditions

Cannabis Use; Healthy Subjects

Keywords

medical cannabis; pharmacokinetics; acute effects; cannabis decoction; cannabis oil; vaporized cannabis; oral cannabis

Outcome Measures

Primary Outcomes (13)

• Maximum serum concentration (Cmax) of THC

  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.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Maximum serum concentration (Cmax) of THCA

  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.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Maximum serum concentration (Cmax) of CBD

  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.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Maximum serum concentration (Cmax) of CBDA

  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.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Time to reach maximum serum concentration (Tmax) of THC

  Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Time to reach maximum serum concentration (Tmax) of THCA

  Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Time to reach maximum serum concentration (Tmax) of THC metabolites

  Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Time to reach maximum serum concentration (Tmax) of CBD

  Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Time to reach maximum serum concentration (Tmax) of CBDA

  Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration.

• Area under the concentration-time curve (AUC 0-24 h) of THC in serum concentrations

  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.

  From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )

• Area under the concentration-time curve (AUC 0-24 h) of THCA in serum concentrations

  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.

  From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )

• Area under the concentration-time curve (AUC 0-24 h) of CBD in serum concentrations

  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.

  From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )

• Area under the concentration-time curve (AUC 0-24 h) of CBDA in serum concentrations

  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.

  From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )

Secondary Outcomes (23)

• Maximum oral fluid concentration (Cmax) of THC

  From baseline to 24 hours after decoction, oil or vaporized cannabis administration

• 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

Study Arms (3)

Oral formulation: Cannabis decoction

EXPERIMENTAL

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.

Drug: Cannabis decoction

Oral formulation: Cannabis oil

EXPERIMENTAL

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.

Drug: Cannabis oil

Vaporized formulation: Cannabis vaporized

EXPERIMENTAL

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 .

Drug: Vaporized cannabis

Interventions

Cannabis decoction DRUG

A single 100 mL dose of cannabis decoction is administered containing 1.8 mg THC and 2.7 mg CBD.

Also known as: Cannabis tea

Oral formulation: Cannabis decoction

Cannabis oil DRUG

A single administration of 15 drops (045 mL) of cannabis oil containing 1.8 mg THC and 3.8 mg CBD.

Oral formulation: Cannabis oil

Vaporized cannabis DRUG

100mg of vaporized cannabis is administered by Volcano vaporizer, wich containing 0.6-2 mg THC and 0.8-3 mg CBD

Also known as: Inhaled cannabis

Vaporized formulation: Cannabis vaporized

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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…).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Germans Trias i Pujol Hospital: lead
• Fundació Institut Germans Trias i Pujol: collaborator
• Istituto Superiore di Sanità: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

Related Publications (4)

• 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.

  PMID: 33451073 RESULT

• 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.

  PMID: 33322849 RESULT

• 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.

  PMID: 33298281 RESULT

• 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.

  PMID: 33155722 RESULT

MeSH Terms

Interventions

nabiximols

Study Officials

• Magi Farré, MD, PhD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant were aware of the cannabis preparation but not of the administered doses
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: April 12, 2021
• Study Start: December 10, 2018
• Primary Completion: December 18, 2019
• Study Completion: February 28, 2021
• Last Updated: April 12, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)