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
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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
43
A single 100 mL dose of cannabis decoction is administered containing 1.8 mg THC and 2.7 mg CBD.
A single administration of 15 drops (045 mL) of cannabis oil containing 1.8 mg THC and 3.8 mg CBD.
100mg of vaporized cannabis is administered by Volcano vaporizer, wich containing 0.6-2 mg THC and 0.8-3 mg CBD
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration.
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Time to reach maximum serum concentration (Tmax) of THC
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From baseline to 24 hours after administration ( decoction, oil or vaporized cannabis )
Maximum oral fluid concentration (Cmax) of THC
Calculation of maximum concentration (ng/mL) oral fluid samples collected with a Salivette device at the same time points as serum. Ora liquid is collected 15 min before administration (time zero), at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after the oral formulation of cannabis (decoction or oil) and in the case of vaporized cannabis at 15 minutes before zero time (administration), at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Maximum oral fluid concentration (Cmax) of THCA
Calculation of maximum concentration (ng/mL) oral fluid samples collected with a Salivette device at the same time points as serum. Ora liquid is collected 15 min before administration (time zero), at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after the oral formulation of cannabis (decoction or oil) and in the case of vaporized cannabis at 15 minutes before zero time (administration), at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Maximum oral fluid concentration (Cmax) of CBD
Calculation of maximum concentration (ng/mL) oral fluid samples collected with a Salivette device at the same time points as serum. Ora liquid is collected 15 min before administration (time zero), at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after the oral formulation of cannabis (decoction or oil) and in the case of vaporized cannabis at 15 minutes before zero time (administration), at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Maximum oral fluid concentration (Cmax) of CBDA
Calculation of maximum concentration (ng/mL) oral fluid samples collected with a Salivette device at the same time points as serum. Ora liquid is collected 15 min before administration (time zero), at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours after the oral formulation of cannabis (decoction or oil) and in the case of vaporized cannabis at 15 minutes before zero time (administration), at 10, 20, 40, 1, 1.5,2,3,4,6,8 and 24 hours
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Time to reach maximum oral fluid concentration (Tmax) of THC
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Time to reach maximum oral fluid concentration (Tmax) of THCA
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Time to reach maximum oral fluid concentration (Tmax) of CBD
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Time to reach maximum oral fluid concentration (Tmax) of CBDA
Time to reach maximun concentration after decoction, oil or vaporized cannabis formulations
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Area under the concentration-time curve (AUC 0-24h) of THC oral fluid 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 hours
Time frame: 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
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 hours
Time frame: 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
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 hours
Time frame: 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
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 hours
Time frame: 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.
Urine was collected 15 minutes before administration (time zero) and then between 0-2 h, 2-4 h, 6 h-8 h, 8-10 h, and 10-24 h after administration of oral and vaporized formulations.
Time frame: 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.
Concentration in ng/patch. Samples were collected with dermal patches (5 x 5 cm areas) applied to the back and removed at different intervals such as: 0-2 h, 2-4 h, 4-6 h, 6-8 h, 8-10 h, 10-12 h and 12-24 h
Time frame: 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.
Concentration in ng/patch. Samples were collected with dermal patches (5 x 5 cm areas) applied to the back and removed at different intervals such as: 0-2 h, 2-4 h, 4-6 h, 6-8 h, 8-10 h, 10-12 h and 12-24 h
Time frame: From baseline to 24 hours after decoction, oil or vaporized cannabis administration
Change in blood pressure: Emax (peak/maximum effects) in blood pressure
Non-invasive systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) were repeatedly recorded at baseline (45 and 15 min) prior to decoction or oil administration, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. In case o vaporized cannabis were recorded at baseline (45 and 15 min) before and 10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after administration. Blood pressure measured in mmHg. .
Time frame: Differences from baseline to 24 hours
Change in Heart rate: Emax (peak/maximum effects) in Heart rate
Heart rate were repeatedly recorded at baseline (45 and 15 min) prior to decoction or oil administration, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. In case of vaporized cannabis were recorded at baseline (45 and 15 min) before and 10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after administration . Heart rate measured in beats per minute (bpm).
Time frame: Differences from baseline to 24 hours
Change in oral temperature: Emax (peak/maximum effects) in oral temperature
Oral temperature were repeatedly recorded at baseline (45 and 15 min) prior to decoction or oil administration, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. In case o vaporized cannabis were recorded at baseline (45 and 15 min) before and 10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after administration . Oral temperature measured in Celsius degrees (ºC).
Time frame: Differences from baseline to 24 hours
Change in Intensity of effects: Emax (peak/maximum effects) in Intensity of effects
Intensity of effects will be measured using a visual analog scale (0-100 mm) at baseline and 0.30, 1, 1.30, 2, 3, 4, 6,8, 10 and 24 h after oral cannabis administration, and at baseline ,10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after vaporized cannabis administration. Higher mm means more intensity of effects.
Time frame: Differences from baseline to 24 hours
Change in High feeling: Emax (peak/maximum effects) in High feeling
High will be measured using a visual analog scale 0-100 mm) at baseline and 0.30, 1, 1.30, 2, 3, 4, 6,8, 10 and 24 h after oral cannabis administration , and at baseline ,10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after vaporized cannabis administration. Higher mm means more high feeling.
Time frame: Differences from baseline to 24 hours
Change in Hunger: Emax (peak/maximum effects) in Hunger
Hunger will be measured using a visual analog scale (0-100 mm) at baseline and 0.30, 1, 1.30, 2, 3, 4, 6,8, 10 and 24 h after oral cannabis administration , and at baseline ,10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after vaporized cannabis administration. Higher mm means more hunger.
Time frame: Differences from baseline to 24 hours
Change in Drowsines: Emax (peak/maximum effects) in Drowsiness
Drowsiness will be measured using a visual analog scale (0-100 mm) at baseline and 0.30, 1, 1.30, 2, 3, 4, 6,8, 10 and 24 h after oral cannabis administration , and at baseline ,10, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after vaporized cannabis administration. Higher mm means more drowsiness.
Time frame: Differences from baseline to 24 hours
Change in global drug effects: Emax (peak/maximum effects) in global drug effects
Global drug effects will be measured using the short form (49 items) of the Addiction Research Center Inventory (ARCI) . This is a true/false response questionnaire with 49 items. The global results include five subscales (sedation, euphoria, dysphoria, intellectual efficiency and amphetamine-like effects. It is administered at baseline and 0.30, 1, 1.30, 2, 3, 4, 6,8, 10 and 24 h after oral cannabis administration , and at baseline, 20, 40 min and 1, 1.5, 2, 3, 4, 6, 8, and 24 h after vaporized cannabis administration. Scores range usually from a total of 12 to 57 points. More points mean more effects.
Time frame: Differences from baseline to 24 hours