Comparison of Methamphetamine and MDMA Extended Access Self-administration: Acquisition, Maintenance, and Response Patterns

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine are two amphetamine derivatives with contrasting pharmacological profiles. Therefore, self- administration profiles might be expected to reflect these differences. Objectives. This study compared the latency and proportion to acquire self-administration, maintenance of self-administration, and within-session response patterns. Methods. Rats were given extended access (8-hour daily sessions) to either methamphetamine, MDMA or vehicle self-administration over a period of 10 consecutive days. A criterion based on the performance of the vehicle control group was used to determine acquisition of reliable MDMA and methamphetamine self-administration. In conjunction, for MDMA self-administration the infusion dose was halved for each rat that achieved a total of 85mg/kg for the remaining sessions. Temporal patterns of responding were assessed using hourly data of the first day of self-administration, the day following acquisition, and the final day of self-administration. Results. A greater proportion of rats in the methamphetamine group acquired self- administration and self-administration was acquired with a shorter latency compared to the MDMA group. Responding maintained by methamphetamine on day one was high. By the third day a pattern developed that was maintained throughout testing. The greatest proportion of responding occurring within the first hour of each daily test session. A progressive escalation of intake was also observed within the methamphetamine group. Responding maintained by MDMA was low on the first day, but by day 5 responding had increased with most of the responding within the session occurring during the first three hours. On day 10 the greatest amount of responding occurred during the first hour. No escalation of intake as a function of test day was observed for MDMA self-administration.</p>

Comparison of Methamphetamine and MDMA Extended Access Self-administration: Acquisition, Maintenance, and Response Patterns

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine are two amphetamine derivatives with contrasting pharmacological profiles. Therefore, self- administration profiles might be expected to reflect these differences. Objectives. This study compared the latency and proportion to acquire self-administration, maintenance of self-administration, and within-session response patterns. Methods. Rats were given extended access (8-hour daily sessions) to either methamphetamine, MDMA or vehicle self-administration over a period of 10 consecutive days. A criterion based on the performance of the vehicle control group was used to determine acquisition of reliable MDMA and methamphetamine self-administration. In conjunction, for MDMA self-administration the infusion dose was halved for each rat that achieved a total of 85mg/kg for the remaining sessions. Temporal patterns of responding were assessed using hourly data of the first day of self-administration, the day following acquisition, and the final day of self-administration. Results. A greater proportion of rats in the methamphetamine group acquired self- administration and self-administration was acquired with a shorter latency compared to the MDMA group. Responding maintained by methamphetamine on day one was high. By the third day a pattern developed that was maintained throughout testing. The greatest proportion of responding occurring within the first hour of each daily test session. A progressive escalation of intake was also observed within the methamphetamine group. Responding maintained by MDMA was low on the first day, but by day 5 responding had increased with most of the responding within the session occurring during the first three hours. On day 10 the greatest amount of responding occurred during the first hour. No escalation of intake as a function of test day was observed for MDMA self-administration.</p>

Gas Chromatography Multiresidue Method for Enantiomeric Fraction Determination of Psychoactive Substances in Effluents and River Surface Waters

Determination of psychoactive substances (PAS) and/or their metabolites in surface waters is crucial for environmental risk assessment, and disclosure of their enantiomeric fractions (EF) allows discrimination between consumption, direct disposal, and synthesis pathways. The aim of this study was to develop and validate an indirect method by gas chromatography coupled to mass spectrometry (GC–MS) based on derivatization using (R)-(−)-α-methoxy-α-(trifluoromethyl) phenylacetyl chloride as chiral derivatization reagent, for enantiomeric quantification of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxymethamphetamine (MDMA), norketamine, buphedrone (BPD), butylone, 3,4-dimethylmethcathinone (3,4-DMMC), 3-methylmethcathinone, and quantification of 1-benzylpiperazine and 1-(4-metoxyphenyl)-piperazine. The method allowed to evaluate the occurrence, spatial distribution, and the EF of the target chiral PAS in Portuguese surface waters and in effluents from 2 wastewater treatment plants (WWTP). For that, water samples were pre-concentrated by solid phase extraction using OASIS® MCX cartridges, derivatized and further analyzed by GC–MS. Both enantiomers of AMP, (R)-MDMA, (S)-MAMP, and the first eluted enantiomer of BPD (configuration not assigned) were found in surface waters, while effluent samples showed both enantiomers of MDMA, (S)-MAMP, (R)-AMP, and the first eluted enantiomer of BPD and 3,4-DMMC. According to our knowledge, this is the first multiresidue analytical method by CG–MS enrolling cathinones, amphetamines, and piperazines. The presence of illicit synthetic cathinones in Douro River estuary is here reported for the first time, along with other amphetamine derivatives. The potential of the method to monitor consumption of the target PAS was demonstrated.

Pharmacological Characterization of 4-Methylthioamphetamine Derivatives

Amphetamine derivatives have been used in a wide variety of pathologies because of their pharmacological properties as psychostimulants, entactogens, anorectics, and antidepressants. However, adverse cardiovascular effects (sympathomimetics) and substance abuse problems (psychotropic and hallucinogenic effects) have limited their use. 4-Methylthioamphetamine (MTA) is an amphetamine derivative that has shown to inhibit monoamine uptake and monoamine oxidase. However, the pharmacological characterization (neurochemical, behavioral, and safety) of its derivatives 4-ethylthioamphetamine (ETA) and 4-methylthio-phenil-2-butanamine (MT-But) have not been studied. In the current experiments, we show that ETA and MT-But do not increase locomotor activity and conditioned place preference with respect to MTA. At the neurochemical level, ETA and MT-But do not increase in vivo DA release in striatum, but ETA and MT-But affect the nucleus accumbens bioaccumulation of DA and DOPAC. Regarding cardiovascular effects, the administration of MTA and ETA increased the mean arterial pressure and only ETA significantly increases the heart rate. Our results show that the pharmacological and safety profiles of MTA are modulated by changing the methyl-thio group or the methyl group of the aminoethyl chain.

QUESTIONS OF DYNAMICS, FORENSIC MEDICAL AND FORENSIC CHEMICAL DIAGNOSTICS OF METHADONE POISONING IN SAINT PETERSBURG IN 2009-2018

Acute poisonings occupy one of the leading places in the structure of mortality due to external causes in the Russian Federation. In Saint Petersburg, there are consistently high rates of drug poisonings (especially methadone poisoning). Reports, statistical maps and other information of the Bureau of Forensic Medical Expertise for the period 2009 – 2018 were used for this study. The research methods were a selective copy of the data, including the results of a forensic chemical study, the calculation of statistical coefficients, descriptive. The analysis showed a decrease in mortality due to external causes in Saint Petersburg in 2009-2018, indicators (per 100 thousand of the population of Saint Petersburg) decreased gradually from 99,3 to 69,8. Acute poisoning of chemical etiology was in the 2nd place (24,9%) after mechanical injury. In the structure of acute poisoning of chemical etiology, the 1st place was occupied by fatal drug poisoning (45,1%). Their share was 28,7% in 2009-2011. It increased sharply up to 52,2% in the period 2012-2018 and began to change both qualitative and quantitative. In Saint Petersburg there were 19 fatal cases of methadone poisoning (0,04 per 100 thousand people) in 2009 and 599 cases (11,19 per 100 thousand people) in 2018. The number of forensic studies on the identification of methadone sharply increased (9 times). In almost half of the poisoning’s cases ethanol, other narcotic drugs (amphetamine derivatives, morphine, cocaine, etc.), as well as drugs and psychotropic substances (derivatives of barbituric acid, benzodiazepine, phenothiazine, etc.) were revealed along with methadone.Forensic medical diagnostics of methadone poisoning are based on the results of chromatography-mass spectrometry, morphological features (macro- and microscopic), analysis of the clinical picture (from medical documents), and consideration of the circumstances of the poisoning. The combined reception of methadone, ethanol and other narcotic and / or psychotropic drugs has a potentiating deprimative effect, aggravates the clinical and morphological picture of poisoning, which must be taken into account when diagnosing them.

Relationship Between Treatment Duration and Efficacy of Pharmacological Treatment for ADHD: A Meta-Analysis and Meta-Regression of 87 Randomized Controlled Clinical Trials

Objective: To determine the relationship between treatment duration and the efficacy of pharmacological treatment for reducing ADHD symptoms. Method: We conducted a systematic review of randomized, double-blind, placebo-controlled clinical trials investigating the efficacy of pharmacological interventions in patients with ADHD. The last bibliographic search was performed in April 15, 2019. The effect of treatment duration on efficacy was studied using meta-regression. Results: A total of 87 studies lasting from 3 to 28 weeks were included. Pharmacological treatment improved ADHD symptom severity by −7.35 points. Treatment duration did not moderate the efficacy of pharmacological treatment. Consistent results were found for psychostimulant drugs, methylphenidate, amphetamine derivatives, atomoxetine, and α2-agonists. A negative correlation was found between baseline ADHD severity efficacy (Coefficient = −.250, p = .013). Conclusion: The efficacy of pharmacological treatment for ADHD remains stable over time. A greater efficacy in more severe patients is suggested.

A Historical Overview Upon the Use of Amphetamine Derivatives in the Treatment of Obesity

Relatively few medications are available for the management of obesity and all are indicated as adjuncts to increased physical activity, caloric restriction and lifestyle modification. Among different weight-loss drugs, the most intriguing and controversial class is the one of anorexic amphetamines, due to their high efficiency but also relevant side-effects. Several previously approved anorexic amphetamines like fenfluramine, phenylpropanolamine, phenmetrazine and sibutramine have been withdrawn from the market due to unanticipated adverse effects. Nowadays only four amphetamine derivatives are approved for short-term treatment of obesity: amfepramone, benzphetamine, phendimetrazine and phentermine. The article provides an overview of both the history, and the current status, of the use of amphetamine derivatives in the obesity pharmacotherapy. J Pharm Care 2019; 7(3): 75-82.