scholarly journals A Comparison of Acute Pharmacological Effects of Methylone and MDMA Administration in Humans and Oral Fluid Concentrations as Biomarkers of Exposure

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 788
Author(s):  
Lourdes Poyatos ◽  
Esther Papaseit ◽  
Eulalia Olesti ◽  
Clara Pérez-Mañá ◽  
Mireia Ventura ◽  
...  

Considered the β-keto analogue of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-Methylenedioxymethcathinone (methylone) is a synthetic cathinone. Over the years, methylone has been used as a substitute for conventional psychostimulants, such as MDMA. To date, little is known about the human pharmacology of methylone; the only available information has been provided by surveys or published intoxication reports. In the present observational–naturalistic study, we evaluate the acute subjective and physiological effects of methylone after oral self-administration in comparison to MDMA in healthy poly-drug users. Fourteen participants (10 males, 4 females) selected their single oral doses of methylone from 100 to 300 mg (n = 8, mean dose 187.5 mg) or MDMA from 75 to 100 mg (n = 6, mean dose 87.5 mg) based on their experience. Study variables were assessed at 0, 1, 2, and 4 h (h) and included vital signs (non-invasive blood pressure, heart rate, cutaneous temperature) and subjective effects using visual analogue scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI) short form, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) questionnaire. Additionally, oral fluid concentrations of methylone and MDMA were determined. Acute pharmacological effects produced by methylone followed the prototypical psychostimulant and empathogenic profile associated with MDMA, although they were less intense. Methylone concentrations in oral fluid can be considered a useful biomarker to detect acute exposure in oral fluid. Oral fluid concentrations of MDMA and methylone peaked at 2 h and concentrations of MDMA were in the range of those previously described in controlled studies. Our results demonstrate that the potential abuse liability of methylone is similar to that of MDMA in recreational subjects.

2021 ◽  
Vol 14 (2) ◽  
pp. 100
Author(s):  
Esther Papaseit ◽  
Eulalia Olesti ◽  
Clara Pérez-Mañá ◽  
Marta Torrens ◽  
Francina Fonseca ◽  
...  

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100–200 mg; mean 150 mg) or intranasally (n = 5, 50–100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lucia Martínez ◽  
Nunzia La Maida ◽  
Esther Papaseit ◽  
Clara Pérez-Mañá ◽  
Lourdes Poyatos ◽  
...  

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.


2016 ◽  
Vol 33 (S1) ◽  
pp. S115-S115 ◽  
Author(s):  
M. Farré ◽  
C. Perez-Maña ◽  
E. de Souza ◽  
J. Mateus ◽  
E. Theunisen ◽  
...  

IntroductionMephedrone is a synthetic cathinone derivative included in the class of “New-Novel Psychoactive Substances”. Synthetic cathinones are marketed as “bath salts” or “plant food” and gained notable popularity for similar effects to 4-methylenedioxymethamphetamine (MDMA, ecstasy), or amphetamines. Mephedrone is commonly consumed simultaneously with alcohol.Objectives and aimsThe aim of the present study was to evaluate the interactions between mephedrone and ethanol in humans.MethodsTwelve healthy male, recreational users of psychostimulants participated as outpatients in four experimental sessions. They received a single oral dose of mephedrone (200 mg) and alcohol (0.8 g/kg), mephedrone placebo and alcohol (0.8 g/kg), mephedrone (200 mg) and placebo alcohol, and both placebos. Design was double-blind, double-dummy, randomized, cross-over and controlled with placebo. Study variables included: vital signs (blood pressure, heart rate, temperature, and pupil diameter), subjective effects (visual analogue scales-VAS, ARCI-49 item short form, and VESSPA questionnaire).ResultsThe combination produced an increase in the cardiovascular effects of mephedrone and induced more intense feeling of euphoria and well-being in comparison to mephedrone and alcohol. Mephedrone reduced the drunkenness and sedation produced by alcohol.ConclusionsThese results are similar to those obtained with the combination of other psychostimulants as amphetamines and MDMA. Abuse liability of the combination is greater that induced by mephedrone.Disclosure of interestThe authors have not supplied their declaration of competing interest.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 257
Author(s):  
Nunzia La Maida ◽  
Esther Papaseit ◽  
Lucia Martínez ◽  
Clara Pérez-Mañá ◽  
Lourdes Poyatos ◽  
...  

Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.


Author(s):  
Vo Que Son ◽  
Do Tan A

Sensing, distributed computation and wireless communication are the essential building components of a Cyber-Physical System (CPS). Having many advantages such as mobility, low power, multi-hop routing, low latency, self-administration, utonomous data acquisition, and fault tolerance, Wireless Sensor Networks (WSNs) have gone beyond the scope of monitoring the environment and can be a way to support CPS. This paper presents the design, deployment, and empirical study of an eHealth system, which can remotely monitor vital signs from patients such as body temperature, blood pressure, SPO2, and heart rate. The primary contribution of this paper is the measurements of the proposed eHealth device that assesses the feasibility of WSNs for patient monitoring in hospitals in two aspects of communication and clinical sensing. Moreover, both simulation and experiment are used to investigate the performance of the design in many aspects such as networking reliability, sensing reliability, or end-to-end delay. The results show that the network achieved high reliability - nearly 97% while the sensing reliability of the vital signs can be obtained at approximately 98%. This indicates the feasibility and promise of using WSNs for continuous patient monitoring and clinical worsening detection in general hospital units.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e023850
Author(s):  
Catherine S Wall ◽  
Rose S Bono ◽  
Rebecca C Lester ◽  
Cosima Hoetger ◽  
Thokozeni Lipato ◽  
...  

IntroductionIn the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability.Methods and analysesParticipants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18–25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models.Ethics and disseminationThe Virginia Commonwealth University Institutional Review Board approved the study (VCU IRB: HM20007848). Dissemination channels for study findings include scientific journals, scientific meetings, and policy briefs.Trial registration numberNCT02937051.


CJEM ◽  
2013 ◽  
Vol 15 (05) ◽  
pp. 279-288 ◽  
Author(s):  
Frank Xavier Scheuermeyer ◽  
Gary Andolfatto ◽  
Hong Qian ◽  
Eric Grafstein

ABSTRACT Objectives: Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) as part of emergency department (ED) treatment. We compared adverse events (AEs) using a variety of sedation regimens. Methods: This was a retrospective analysis of a PSA safety audit in two urban EDs. Consecutive self-reported IDUs were identified, and structured data describing comorbidities, vital signs, sedation regimens (propofol [P], propofol-fentanyl [PF], fentanyl-midazolam [FM], ketofol [1:1 ketamine:propofol, KF], and ketamine-propofol [KP]) and AEs were collected. The primary outcome was the proportion of patients in each sedation group having an AE; the secondary outcome was the proportion of patients having a cardiovascular or respiratory AE. Results: Data were collected on 276 IDUs (78 P, 82 PF, 65 FM, 25 KF, and 26 KP), and 18 patients had AEs (6.5%, 95% CI 4.0–10.3). The AE rates were 0.0%, 8.5%, 9.2%, 12.0%, and 7.6%, respectively, with propofol having a significantly lower rate (Pearson coefficient 14.9, p = 0.007). The cardiovascular/respiratory AE rates were significantly different as well, with P, KP, and KF having the lowest rates (Pearson coefficient 13.3, p = 0.01). Conclusions: For IDU PSA, the overall AE rate was 6.5%, and propofol appeared to have a significantly lower rate.


PEDIATRICS ◽  
1978 ◽  
Vol 61 (5) ◽  
pp. 693-693
Author(s):  

Today, the great majority of cholera patients in the Infectious Diseases Hospital in Calcutta, India, are successfully being treated by oral rehydration. This switch over to oral fluid therapy, which in this hospital now saves about $50,000 every year in the cost of parenteral fluids alone, was the outcome of a study carried out by the Cholera Research Centre of the Indian Council of Medical Research, in collaboration with physicians in the Infectious Diseases Hospital, on the effectiveness of this treatment in cholera patients below the age of 5 years. The Cholera Research Centre, which is also in Calcutta, is a WHO Collaborating Centre for Reference and Research on Vibrios. The study showed that 92% of patients with moderate to severe dehydration responded well when given repeated small amounts (25-30 ml, every 10-15 minutes), rather than a single large volume (250 ml), of oral fluid. In this way, vomiting—which occurred invariably when the large volume was given—was found not to cause any problem. The Centre in the meantime developed a cheap and simple system for dispensing the ingredients (glucose-salts mixture) for oral rehydration in sealed polythene packets to facilitate distribution. Under the name of Chorosol, the packets—which cost about $0.10 each—have been very well received by medical and paramedical staff. The use of Chorosol in the field, in the management of cholera epidemics, has also been very successful.


1993 ◽  
Vol 8 (4) ◽  
pp. 201-208 ◽  
Author(s):  
D Warot ◽  
E Corruble ◽  
C Payan ◽  
JS Weil ◽  
AJ Puech

SummaryThe subjective, behavioral and physiological effects of modafinil (300 mg PO) a new central adrenergic stimulant, were compared with those of dextroamphetamine (15 mg PO), caffeine (300 mg PO) and placebo in a randomized double-blind cross-over study. Sixteen healthy volunteers participated in the study y: 8 males and 8 females with no history of drug abuse and moderate use of caffeine. Subjective and behavioral effects were studied using the Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS) and Visual Analog Scales before and 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of modafinil (300 mg) differed markedly from those of dextroamphetamine (15 mg). They were close to those produced by caffeine (300 mg). These results indicate that modafinil (300 mg) does not possess amphetamine-like subjective effects in a healthy population. If subjective feelings are related to drug abuse liability, it could be assumed that modafinil, at the dose used in therapeutics, does not possess any abuse liability comparable to amphetamine.


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