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| Name | Class |
|---|---|
| Fundació Recerca Institut Germans Trias i Pujol | UNKNOWN |
| Istituto Superiore di Sanità | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylone | Experimental | Methylone (3,4-methylenedioxy-N-methylcathinone) 200 mg, single dose, oral administration |
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| 3,4-methylenedioxymethamphetamine (MDMA) | Active Comparator | MDMA (3,4-methylenedioxymethamphetamine) 100 mg, single dose, oral administration |
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| Maltodextrin | Placebo Comparator | Placebo, single dose, oral administration |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylone | Drug | Single oral dose of 200 mg of methylone. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Differences from baseline to 24 hours after administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Differences from baseline to 24 hours after administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Magi Farré, MD, PhD | Germans Trias i Pujol Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Germans Trias i Pujol Hospital | Badalona | Barcelona | 08916 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36873994 | Derived | Poyatos L, Perez-Mana C, Hladun O, Nunez-Montero M, de la Rosa G, Martin S, Barriocanal AM, Carabias L, Kelmendi B, Taoussi O, Busardo FP, Fonseca F, Torrens M, Pichini S, Farre M, Papaseit E. Pharmacological effects of methylone and MDMA in humans. Front Pharmacol. 2023 Feb 17;14:1122861. doi: 10.3389/fphar.2023.1122861. eCollection 2023. |
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| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C400939 | methylone |
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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The protocol comprises a pilot study (n= 12) and a definitive study (n=17, 14 men and 3 women).
The pilot study was a phase I dose-finding study that included 4 cohorts of 3 subjects (cohort 1,2,3 and 5). The conditions of each cohort were: 50 and 100 mg of methylone and placebo in cohort 1 (n= 3); 100 and 150 mg of methylone and placebo in cohort 2 (n= 3); 150 and 200 mg of methylone and placebo in cohort 3 (n= 3); 200 mg of methylone, 100 mg of MDMA and placebo in cohort 5 (n= 3). For safety reasons in cohorts 1-2-3, lower doses were allocated before the higher doses.
After completion, the pilot study allowed defining the treatment conditions and interventions of the definitive study. The present definitive study was designed as double-blind, placebo-controlled, crossover and randomized. Each subject will participate in three experimental sessions, in each one treatment will be administered. Study treatment conditions are 200 mg of methylone, 100 mg of MDMA and placebo.
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Identical white hard gelatin capsules
| 3,4-methylenedioxymethamphetamine | Drug | Single oral dose of 100 mg of MDMA. |
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| Placebo | Drug | Single oral dose of placebo. |
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| 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). |
| 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Differences from baseline to 6 hours after administration |
| Organic Chemicals |