The purposes of the study are 1) To assess the abuse potential of methylone after controlled administration of a single oral dose of methylone 2) to evaluate subjective and physiological effects of methylone 3) to determine the pharmacokinetics parameters and metabolism of methylone.
Methylone is a synthetic cathinone that has been popularized as an alternative to other illegal psychostimulants as methylenedioxymethamphetamine (MDMA, ecstasy) or mephedrone. Chemically, methylone is a beta-keto analogue of ecstasy with similar pharmacological effects in animals. To date, the available data about the human pharmacology of methylone in humans is very scarce and is mainly provided by users' experience published in internet forums or intoxication reports. A pilot study was carried out to select the methylone dose used in this study. This current study is aimed 1) To assess the abuse potential of methylone after controlled administration of a single oral dose of methylone 2) to evaluate subjective and physiological effects of methylone 3) to determine the pharmacokinetics parameters and metabolism of methylone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
17
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain
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 30 min) prior to administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Blood pressure measured in mmHg.
Time frame: Differences from baseline to 24 hours after administration
Change in Heart rate: Emax (peak/maximum effects) in Heart rate
Heart rate was repeatedly recorded at baseline (45 and 30 min) prior to administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Heart rate measured in beats per minute (bpm).
Time frame: Differences from baseline to 24 hours after administration
Change in Oral temperature: Emax (peak/maximum effects) in Oral temperature
Oral temperature was repeatedly recorded at baseline (45 and 30 min) prior to administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Oral temperature measured in Celsius degrees (ºC).
Time frame: Differences from baseline to 24 hours after administration
Change in Pupil diameter: Emax (peak/maximum effects) in Pupil diameter
Pupil diameter was repeatedly recorded at baseline (45 and 30 min) prior to administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Pupil diameter measured in millimeters (mm).
Time frame: Differences from baseline to 24 hours after administration
Change in Maddox Wing score (MW): Emax (peak/maximum effects)
Maddox wing is a device that measures the balance of extraocular muscles and quantifies exophoria as an indicator of extraocular muscle relaxation. From 22 (exophoria) to 15 (esophoria). It is measured at baseline (45 and 30 min) prior to administration, and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h.
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Time frame: Differences from baseline to 24 hours after administration
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 (h) and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Higher mm means more intensity of effects.
Time frame: Differences from baseline to 24 hours after administration
Change in High: Emax (peak/maximum effects) in High feeling
High will be measured using a visual analog scale (0-100 mm) at baseline and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Higher mm means more high feeling.
Time frame: Differences from baseline to 24 hours after administration
Change in Stimulated: Emax (peak/maximum effects) in Stimulated feeling
Stimulation will be measured using a visual analog scale (0-100 mm) at baseline and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Higher mm means more stimulation.
Time frame: Differences from baseline to 24 hours after administration
Change in Liking: Emax (peak/maximum effects) in Liking feeling
Liking will be measured using a visual analog scale (0-100 mm) at baseline and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h after administration. Higher mm means more liking.
Time frame: Differences from baseline to 24 hours after administration
Change in global drug effects assessed with ARCI: 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 1, 2, 3, 4, 6, 8, and 10 h after 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 after administration
Change in global drug effects assessed with VESSPA: Emax (peak/maximum effects) in global drug effects
Global drug effects will be measured using the Evaluation of the Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE). This questionnaire consists of 36 items (0-4 score) that evaluate subjective effects related to stimulants such as MDMA. VESSPA includes six subscales (sedation, psychosomatic anxiety, changes in perception, pleasure and sociability, activity and energy, and psychotic symptoms). Scores of each subscale ranges from 0 to 24 (maximal effects) It is administered at baseline and 1, 2, 3, 4, 6, 8, and 10 h after administration.
Time frame: Differences from baseline to 24 hours after administration
Maximum plasma concentration (Cmax) of methylone
Calculation of maximum concentration of methylone (ng/mL) in samples collected from 15 min prior to administration (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after methylone administration
Maximum plasma concentration (Cmax) of MDMA
Calculation of maximum concentration of MDMA (ng/mL) in samples collected from 15 min prior to administration (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after MDMA administration
Time to reach maximum plasma concentration (Tmax) of methylone
Time (h) to reach maximum concentration of methylone in plasma after administration.
Time frame: From baseline to 24 hours after methylone administration
Time to reach maximum plasma concentration (Tmax) of MDMA
Time (h) to reach maximum concentration of MDMA in plasma after administration.
Time frame: From baseline to 24 hours after MDMA administration
Area under the concentration-time curve (AUC 0-24 h) of methylone in plasma concentrations
Calculation of AUC with samples collected from 15 min prior (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours after methylone administration.
Time frame: From baseline to 24 hours after methylone administration
Area under the concentration-time curve (AUC 0-24 h) of MDMA in plasma concentrations
Calculation of AUC with samples collected from 15 min prior (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours after MDMA administration.
Time frame: From baseline to 24 hours after MDMA administration
Maximum oral fluid concentration (Cmax) of methylone
Calculation of maximum concentration (ng/mL) of methylone in oral fluid (saliva) samples collected with a Salivette device at the same time points as serum. Oral fluid is collected 15 min before administration (time 0), at to 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after methylone administration
Maximum oral fluid concentration (Cmax) of MDMA
Calculation of maximum concentration (ng/mL) of MDMA in oral fluid (saliva) samples collected with a Salivette device at the same time points as serum. Oral fluid is collected 15 min before administration (time 0), at to 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after MDMA administration
Time to reach maximum oral fluid concentration (Tmax) of methylone
Time (h) to reach maximum concentration of methylone in oral fluid after administration.
Time frame: From baseline to 24 hours after methylone administration
Time to reach maximum oral fluid concentration (Tmax) of MDMA
Time (h) to reach maximum concentration of MDMA in oral fluid after administration.
Time frame: From baseline to 24 hours after MDMA administration
Area under the concentration-time curve (AUC 0-24h) of methylone oral fluid concentrations
Calculation of AUC with oral fluid samples collected from 15 min prior to methylone administration (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after methylone administration
Area under the concentration-time curve (AUC 0-24h) of MDMA oral fluid concentrations
Calculation of AUC with oral fluid samples collected from 15 min prior to MDMA administration (time 0) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours.
Time frame: From baseline to 24 hours after MDMA administration
Total amount methylone excreted in 24 h urine samples.
Urine was collected 15 minutes before administration (time 0) and then between 0-4 h, 4-8 h, 8-12 h, and 12-24 h after methylone administration.
Time frame: From baseline to 24 hours after methylone administration
Total amount MDMA excreted in 24 h urine samples.
Urine was collected 15 minutes before administration (time 0) and then between 0-4 h, 4-8 h, 8-12 h, and 12-24 h after MDMA administration.
Time frame: From baseline to 24 hours after MDMA administration
Total concentration of methylone present in sweat
Concentration of methylone 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, 0-4 h, 0-6 h, 0-8 h, and 0-10 h, 10-12 h.
Time frame: From baseline to 12 hours after methylone administration
Total concentration of MDMA present in sweat
Concentration of MDMA 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, 0-4 h, 0-6 h, 0-8 h, and 0-10 h, 10-12 h.
Time frame: From baseline to 12 hours after MDMA administration
Pharmacological class identification
In the pharmacological class identification questionnaire, the participant selects the pharmacological class that better describes the administered drug. This questionnaire is administered 8 h after administration.
Time frame: Only administered 8 hours after administration
Change in psychomotor vigilance task (PVT): Emax (peak/maximum effects)
Test will be performed using specific computer software that assesses simple reaction time to a numeric stimulus. Results are milliseconds (increased simple reaction time is related to worst psychomotor performance) It is measured at baseline (45 and 30 min) prior to administration, and at 1 and 2 h.
Time frame: Differences from baseline to 2 hours after administration
Psychiatric evaluation using Young Mania Rating Scale (YMRS)
YMRS (11 items) assessing manic symptoms from 0 to 4 (total score from 0 to 44). It is measured at baseline (30 min) prior to administration, and at 0.5, 1, 4, and 6 h after administration. A higher score indicates a higher severity of mania.
Time frame: Differences from baseline to 6 hours after administration