Abuse Potential and Human Pharmacology of Methylone

NCT05488171 | Unknown Phase 1

• 1 other identifier: HUGTP/METI/FIS/1
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Substance Use; Healthy Subjects

Keywords

methylone; pharmacokinetics; acute effects; MDMA; abuse liability; human pharmacology

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (29)

• Change in Heart rate: Emax (peak/maximum effects) in Heart rate

  Differences from baseline to 24 hours after administration

• Change in Oral temperature: Emax (peak/maximum effects) in Oral temperature

  Differences from baseline to 24 hours after administration

• Change in Pupil diameter: Emax (peak/maximum effects) in Pupil diameter

  Differences from baseline to 24 hours after administration

• Change in Maddox Wing score (MW): Emax (peak/maximum effects)

  Differences from baseline to 24 hours after administration

• Change in Intensity of effects: Emax (peak/maximum effects) in Intensity of effects

  Differences from baseline to 24 hours after administration

Study Arms (3)

Methylone

EXPERIMENTAL

Methylone (3,4-methylenedioxy-N-methylcathinone) 200 mg, single dose, oral administration

Drug: Methylone

3,4-methylenedioxymethamphetamine (MDMA)

ACTIVE COMPARATOR

MDMA (3,4-methylenedioxymethamphetamine) 100 mg, single dose, oral administration

Drug: 3,4-methylenedioxymethamphetamine

Maltodextrin

PLACEBO COMPARATOR

Placebo, single dose, oral administration

Drug: Placebo

Interventions

Methylone DRUG

Single oral dose of 200 mg of methylone.

Also known as: 3,4-methylenedioxy-N-methylcathinone, MDMC

Methylone

3,4-methylenedioxymethamphetamine DRUG

Single oral dose of 100 mg of MDMA.

Also known as: MDMA, Ecstasy

3,4-methylenedioxymethamphetamine (MDMA)

Placebo DRUG

Single oral dose of placebo.

Also known as: Non active treatment

Maltodextrin

Eligibility Criteria

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

You may qualify if:

• Understanding and accepting all the study procedures and signing the informed consent.
• Healthy male and female volunteers aged between 18 and 45.
• Clinical history and physical examination demonstrating no organic or psychiatric disorders.
• The electrocardiogram and general blood and urine laboratory tests performed before the study must be within normal ranges. Minor or occasional changes from normal ranges are accepted if, in the investigator's opinion, considering the current state of the art, they are not clinically significant, are not life-threatening for the subjects and do not interfere with the product assessment. These changes and their non-relevance will be justified in writing specifically.
• Body weight between 50 and 90 kg and body mass index (BMI) between 19-27 kg/m². In case of women, they must weight at least 55 kg to participate. Lower or higher weights and/or BMIs will be accepted if the researchers consider that do not pose a risk to the subjects and do not interfere with the objectives of the study.
• Recreational use of methylone or other synthetic cathinones, amphetamines and/or ecstasy at least 6 occasions (two in the previous year) without serious adverse reactions.
• Women who have regular 26-32 day menstrual cycles (maximum 35 days). Participation only in follicular phase of menstrual cycle.
• Participants who agree to use reliable methods of contraception during the study such as abstinence, intrauterine devices, barrier methods with or without spermicide, or who have a vasectomized partner.

You may not qualify if:

• Present history of a substance use disorder according to Diagnostic and Statistical Manual for Mental Disorders (DSM-V), except for nicotine. Past history of mild substance use disorder (corresponding to substance abuse according to DSM-IV) could be included.
• Individual psychiatric history or schizophrenia in first-degree relatives.
• Previous or actual psychiatric disorders, alcoholism, abuse of prescription drugs or illegal substances or regular consumption of psychoactive drugs.
• Daily consumption of \>40 grams of alcohol and/or \>20 cigarettes.
• Blood donation 8 weeks before or participation in other clinical trials with drugs in the previous 12 weeks. In the exceptional case of having participated in this study, there is a washout period of 2 months.
• History of allergy or serious adverse reactions to medications and/or drugs.
• Pathological history or evidence of a preexisting condition (including gastrointestinal, liver, or kidney disorders) that may alter the absorption, distribution, metabolism or excretion of drugs or symptoms suggestive of drug-induced gastrointestinal irritation.
• Subjects unable to understand the nature, consequences of the study and the procedures requested to be followed.
• Subjects with positive serology to Hepatitis B, C or HIV.
• Having taken medication regularly in the month prior to the study sessions, excepting vitamins, herbal remedies or dietary supplements that, according to the researchers, do not pose a risk to the subjects and do not interfere in the objectives of the study. Single doses of symptomatic medication in the week prior to experimental sessions will be admitted if it is assumed that blood concentrations have been eliminated on the day of the experimental session.
• 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 Recerca 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 (1)

• 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.

  PMID: 36873994 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

methylone; N-Methyl-3,4-methylenedioxyamphetamine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Magi Farré, MD, PhD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical white hard gelatin capsules
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: August 4, 2022
• Study Start: December 1, 2021
• Primary Completion: July 31, 2022
• Study Completion: September 30, 2022
• Last Updated: August 8, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)