Buy MDMA pills okyo

__________________________

📍 Verified store!

📍 Guarantees! Quality! Reviews!

__________________________

▼▼ ▼▼ ▼▼ ▼▼ ▼▼ ▼▼ ▼▼

▲▲ ▲▲ ▲▲ ▲▲ ▲▲ ▲▲ ▲▲

Buy MDMA pills okyo

Official websites use. Share sensitive information only on official, secure websites. Maryland Ave. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its prosocial effects by increasing oxytocin. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA 1. Intranasal oxytocin 40 IU, but not 20 IU increased plasma oxytocin levels to MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria e. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects. In controlled studies, acute doses of MDMA increase self-reports of euphoria, friendliness and closeness to others Harris et al. MDMA also improves recognition of positive mental states, such as friendliness in others Hysek et al. Thus, MDMA may facilitate social behavior both by producing positive and pro-social subjective states, and by modulating sensitivity to positive and negative emotions in others. OT is a peptide important in mammalian social bonding Bos et al. In humans, other serotonergic drugs, such as d -fenfluramine also increase OT Lee et al. Some of these effects, such as enhanced recognition of positive emotions Marsh et al. Interestingly, although the drugs differed on many measures, both increased feelings of sociability. However, it is still unknown if the similarities between the two drugs were partially due to similar effects on endogenous oxytocin release. To our knowledge, there have been no studies in which MDMA and IN-OT were administered in the same subjects, to determine and physiological outcomes such as plasma OT levels and its time course of effects. Thus, in this study we tested single doses of oral MDMA 0. Potential participants completed an initial telephone and an in-person psychiatric evaluation and medical examination, including an electrocardiogram and physical examination. Inclusion criteria were: age between 18 and 35, at least a high school education, fluency in English, and BMI between 18 and Candidates were excluded if they smoked more than 10 tobacco cigarettes per day, if they had any significant cardiovascular, neurological, or major psychiatric illness including all Axis I disorders or sinus infection or other condition blocking access to the olfactory epithelium. Participants provided written informed consent prior to participation. They were told they might receive a stimulant such as amphetamine or ecstasy , a sedative such as Valium , a cannabinoid, a hormone such as OT , or placebo. Participants were instructed to consume their normal amount of caffeine before sessions, but were asked to refrain from tobacco use for 9 hrs, and other drug use for 48 hrs, prior to each session. Women not using hormonal contraceptives were tested only during the follicular phase days 2—14; White et al. Participants were debriefed following the study. This study was conducted according to the principles expressed in the Declaration of Helsinki. The study used a within-and-between-subjects, double-dummy design in which participants received two doses of MDMA 0. After an initial orientation session, participants completed four outpatient sessions separated by at least five days as a washout period Abraham et al, Dosing order was randomized. Blood samples were collected before and at several time points for 4 hours after drug administration. Plasma OT levels for a total of two participants in the 20 IU group were univariate outliers and likely occurred because of blood sampling issues resulting in hemolysis. These two participants were not included in the analyses. Sessions were conducted between h and h in order to minimize any diurnal variation in biological measures. Upon arrival participants provided urine and breath samples to confirm abstinence from alcohol as measured by an Alco-Sensor III Breathalyzer, Intoximeters Inc. Sessions were rescheduled if the participant tested positive for drugs. At h, pre-capsule measures of heart rate and blood pressure were obtained, a blood sample was obtained, and participants completed self-report mood and drug effects questionnaires see below. At h, participants ingested capsules containing either MDMA or placebo, and at h they received an intranasal spray containing either IN-OT or placebo see below. Physiological and subjective measures were obtained at , , , and h i. During times when no measures were scheduled the participants were allowed to relax and watch movies or read. At pm, the catheter was removed and the participants were discharged provided that their heart rate and blood pressure had returned to baseline levels. At each time point, the study nurse drew a 10 ml blood sample drawn into a pre-cooled purple top tube containing disodium EDTA. Prior to assaying, samples were first purified by solid phase extraction Seltzer et al This kit has been validated in a range of species and across different biological media including urine Wismer-Fries et al. The specificity of the antibody used in this assay has been repeatedly validated via high-performance liquid chromatography HPLC and results across different species and biological media indicate that the assay antibody binds only to intact OT and does not show cross-reactivity with other peptide hormones Wismer-Fries et al. This assay should be considered a reliable but conservative measure of OT, since the assay antibody responds primarily to the intact OT molecule and not to OT metabolites Seltzer and Ziegler, Participants completed subjective effect questionnaires before and at several time points after capsule and nasal spray administration. Drugs were administered in randomized order, under double-blind conditions. Capsules and nasal sprays were prepared by The University of Chicago Hospitals investigational pharmacy. MDMA powder 0. Placebo capsules contained only lactose. These MDMA doses were selected based on our previous studies indicating that the drug reliably increases positive mood and alters emotional processing at these doses Bedi et al. Intranasal OT 20 and 40 IU doses were prepared within 24 hours of use. The doses of 20 and 40 IU IN-OT were chosen based on previous studies utilizing intranasally administered OT and the structurally similar neuropeptide, vasopressin Bos et al. Nasal sprays were administered by trained personnel in four doses to each nostril over the course of 15 minutes. During the administration, participants sat comfortably in reclined position, with their heads tilted back to maximize absorption. To characterize the acute effects of MDMA, subjective, cardiovascular, and plasma data were analyzed with repeated measures analyses of variance ANOVAs with two within-subject factors. The within-subjects factors were Drug Dose placebo, 0. Planned t-tests were conducted to compare mean responses between the doses: 1 placebo versus all active MDMA doses and 2 0. Similarly, to characterize the acute effects if IN-OT, subjective, cardiovascular, and plasma data were analyzed with ANOVAs with two within-subject factors and one between-subjects factor. Planned t-tests were conducted to compare mean responses between the doses: 1 placebo and active OT in each OT dose level group and 2 20 IU group versus 40 IU group. For all analyses and comparisons, p values were considered statistically significant at less than 0. In total, 14 volunteers 2 Female, 12 Male completed the study. They were They had used MDMA a mean of Mean peak plasma concentrations were reached at 90— min after capsule ingestion, and all 14 participants showed some increase in OT levels following the larger MDMA dose Figure 1 ; bottom left panel. The closed arrow denotes time of capsule administration. The open arrow denotes time of nasal spray administration. Error bars represent one SEM. Individual responses to each active nasal spray are shown in Figure 1 bottom middle and right panels. Peak cardiovascular effects occurred between 90 and min. MDMA produced robust increases on several self-reported ratings of euphoria and feelings of sociability. MDMA-related mean SEM heart rate, blood pressure, and self-report ratings over the entire session, calculated as change from pre-capsule. Selected mean scores on subjective ratings following administration of MDMA or placebo as a function of dose and time. Mean ratings over the course of the entire session for all cardiovascular and self-report measures following IN-OT administration are provided in Table 2. Overall neither dose of IN-OT 20 or 40 IU produced systematic changes in heart rate, blood pressure, or subjective effects compared to placebo. Oxytocin-related mean SEM heart rate, blood pressure, and self-report ratings over the entire session, calculated as change from pre-capsule. There were no significant differences between oxytocin and placebo. None of the subjective or cardiovascular responses to MDMA 0. Following the larger MDMA dose i. Interestingly, there was substantial individual variability in both the magnitude and time course of MDMA-induced plasma OT response. Intranasal OT 40 IU produced only a brief elevation in plasma OT, detectable only at 30 and 60 minutes after administration. Compared to MDMA 1. The larger MDMA dose increased plasma OT concentrations, although there was variability in response patterns across participants. Plasma OT was significantly elevated within 60 minutes following capsule administration i. The magnitude and time course are consistent with previous studies Dumont et al. The lower dose of MDMA 0. These data indicate that future studies investigating the pro-social effects of MDMA should use relatively larger doses. It is not known whether this variability in plasma response was related to individual differences in pharmacokinetics of the drug or to differences in sensitivity to MDMA-related prosocial behavioral effects. Unfortunately, one limitation of this study is that we did not include measures of social behavior or response to social stimuli. However, a post hoc analysis revealed that MDMA-induced increases in heart rate significantly covaried with some prosocial subjective effects e. This suggests that variability in physiological response to MDMA may partially explain variability in its prosocial effects and will need to be further examined in future studies. MDMA also dose-dependently increased ratings of euphoria i. The current results do not support this hypothesis. Nevertheless, this is consistent with previous studies indicating that plasma OT levels were not correlated with several measures of pro-social feelings and behavior Hysek et al. However, the differences in statistical approaches between the current study and Dumont et al. Of course, it is unclear whether the presence — or absence — of a significant correlational relationship between hormone levels and subjective response would support a true physiological link between MDMA-related subjective response and oxytocin levels in the plasma. Regardless, these data suggest that MDMA produces many of its prosocial subjective effects through other neurochemical mechanisms. For example, a recent study indicates that both MDMA and exogenous oxytocin produces pro-social behavior via involvement of vasopressin receptors Ramos et al. The ability of oxytocin to target homologous brain vasopressin receptors may also explain how exogenous oxytocin reverses social deficits found in oxytocin-receptor knock-out mice Sala et al. Intranasal OT also increased plasma OT levels, albeit to a lesser extent. However, responses were less variable than the OT levels after MDMA 7 of the 8 subjects exhibited peak response 30 min after administration, compared to a range of peak response times for MDMA. We did not observe an increase in plasma OT following the 20 IU dose. Future investigations might investigate a wider range of intranasal doses using a within-subjects design and larger sample size. The current results should be interpreted in the context of several potential limitations. One limitation of our study, and others investigating the central effects of OT, is that we measured OT levels in plasma, and we do not know how these levels correspond to OT levels in the brain. It has been shown that OT and the closely related nanopeptide, arginine vasopressin, can be measured in cerebral spinal fluid CSF after intranasal administration Born et al. Future studies should further investigate the correspondence of central and peripheral OT levels and how these might relate to prosocial behaviors. Another limitation of the current study is that we utilized different routes of administration for OT intranasal and MDMA oral. This difference makes it potentially difficult to directly compare the effects of the two drugs due to differences in rates of absorption and distribution. However, in order to minimize expectancies, participants received both a capsule and a nasal spray during each session. Finally, the formulation of IN-OT used in the current study i. This difference may influence absorption rates of the drug and thus, future studies directly comparing MDMA and IN-OT might utilize a range of oxytocin formulations. The larger dose of intranasal OT also increased plasma OT levels but these increases were relatively low and short-lived compared to those produced by MDMA. Additionally, MDMA-induced increases in mean plasma OT concentrations were unrelated with mean levels of subjective sociability in our study. MDMA-related subjective effects may be mediated by mechanisms that are not reflected in plasma OT levels, such as central OT, vasopressin, or monoamine neurotransmitter signaling. Thus, future studies will need to parse out contributions of monoamine and central neuropeptide brain pathways to the prosocial effects of MDMA. These data provide further information about the pharmacokinetics of plasma OT following administration of two drugs believed to produce prosocial behavioral effects in humans. No funding agency was involved in the design of the study, analysis of the data, or preparation of the manuscript. MK and SF managed and competed the literature searches and analyses. MK wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. As a library, NLM provides access to scientific literature. Published in final edited form as: Psychoneuroendocrinology. Find articles by Matthew G Kirkpatrick. Find articles by Sunday M Francis. Find articles by Royce Lee. Find articles by Harriet de Wit. Find articles by Suma Jacob. Issue date Aug. All rights reserved. The publisher's version of this article is available at Psychoneuroendocrinology. Open in a new tab. Drug Condition Placebo 0. Conflicts of Interest: The authors declare they have no conflicts of interest. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans

Buy MDMA pills okyo

Drug smuggling is a serious crime. Violators will be severely punished, regardless of who will use the drug as well as its amount. Don't even think about bringing drugs to Japan. Japan Customs X guide line. Skip to Content. Site Map Japanese. About Us. Procedure and Form. Other Information. Top of Page Top of Page. Notice Privacy Policy Inquiry. Illegal Drug. Drug mule. Designer Drug.

Buy MDMA pills okyo