Clinical trial NCT05488171: Abuse Potential and Human Pharmacology of Methylone
Official title: Abuse Potential and Human Pharmacology of Methylone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Substance Use
Healthy Subjects
Keywords: methylone
pharmacokinetics
acute effects
MDMA
abuse liability
human pharmacology
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundació Recerca Institut Germans Trias i Pujol
name: Istituto Superiore di Sanità
First posted: 2022-08-04
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Having had any somatic disease or having undergone major surgery in the 3 months prior to inclusion in the trial.
* 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.

Primary outcomes:
measure: Change in blood pressure: Emax (peak/maximum effects) in blood pressure
timeFrame: Differences from baseline to 24 hours after administration
Secondary outcomes:
measure: Change in Heart rate: Emax (peak/maximum effects) in Heart rate
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Oral temperature: Emax (peak/maximum effects) in Oral temperature
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Pupil diameter: Emax (peak/maximum effects) in Pupil diameter
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Maddox Wing score (MW): Emax (peak/maximum effects)
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Intensity of effects: Emax (peak/maximum effects) in Intensity of effects
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in High: Emax (peak/maximum effects) in High feeling
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Stimulated: Emax (peak/maximum effects) in Stimulated feeling
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in Liking: Emax (peak/maximum effects) in Liking feeling
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in global drug effects assessed with ARCI: Emax (peak/maximum effects) in global drug effects
timeFrame: Differences from baseline to 24 hours after administration
measure: Change in global drug effects assessed with VESSPA: Emax (peak/maximum effects) in global drug effects
timeFrame: Differences from baseline to 24 hours after administration
measure: Maximum plasma concentration (Cmax) of methylone
timeFrame: From baseline to 24 hours after methylone administration
measure: Maximum plasma concentration (Cmax) of MDMA
timeFrame: From baseline to 24 hours after MDMA administration
measure: Time to reach maximum plasma concentration (Tmax) of methylone
timeFrame: From baseline to 24 hours after methylone administration
measure: Time to reach maximum plasma concentration (Tmax) of MDMA
timeFrame: From baseline to 24 hours after MDMA administration
measure: Area under the concentration-time curve (AUC 0-24 h) of methylone in plasma concentrations
timeFrame: From baseline to 24 hours after methylone administration
measure: Area under the concentration-time curve (AUC 0-24 h) of MDMA in plasma concentrations
timeFrame: From baseline to 24 hours after MDMA administration
measure: Maximum oral fluid concentration (Cmax) of methylone
timeFrame: From baseline to 24 hours after methylone administration
measure: Maximum oral fluid concentration (Cmax) of MDMA
timeFrame: From baseline to 24 hours after MDMA administration
measure: Time to reach maximum oral fluid concentration (Tmax) of methylone
timeFrame: From baseline to 24 hours after methylone administration
measure: Time to reach maximum oral fluid concentration (Tmax) of MDMA
timeFrame: From baseline to 24 hours after MDMA administration
measure: Area under the concentration-time curve (AUC 0-24h) of methylone oral fluid concentrations
timeFrame: From baseline to 24 hours after methylone administration
measure: Area under the concentration-time curve (AUC 0-24h) of MDMA oral fluid concentrations
timeFrame: From baseline to 24 hours after MDMA administration
measure: Total amount methylone excreted in 24 h urine samples.
timeFrame: From baseline to 24 hours after methylone administration
measure: Total amount MDMA excreted in 24 h urine samples.
timeFrame: From baseline to 24 hours after MDMA administration
measure: Total concentration of methylone present in sweat
timeFrame: From baseline to 12 hours after methylone administration
measure: Total concentration of MDMA present in sweat
timeFrame: From baseline to 12 hours after MDMA administration
measure: Pharmacological class identification
timeFrame: Only administered 8 hours after administration
measure: Change in psychomotor vigilance task (PVT): Emax (peak/maximum effects)
timeFrame: Differences from baseline to 2 hours after administration
measure: Psychiatric evaluation using Young Mania Rating Scale (YMRS)
timeFrame: Differences from baseline to 6 hours after administration
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Magi Farré, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: