No abstract

MDMA (±3,4-methylenedioxymethamphetamine, 'ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N ¼ 65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, 'High' and 'Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA.

Aggression is a behavior with evolutionary origins, but is often both destructive and maladaptive in today's society. Research over the past several decades has confirmed the involvement of neurotransmitter function in aggressive behavior. This research has centered around the "serotonin hypothesis." As this literature continues to grow, guided by pre-clinical research and aided by the application of increasingly sophisticated neuroimaging methodology, a more complex picture has emerged. As current pharmacological and therapeutic interventions are effective but imperfect, it is hoped that new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behavior.

The effects of 20 IU oxytocin support the hypothesis that altered neuroendocrine function in polydipsic patients contributes to their psychiatric illness. Further studies are warranted to confirm these findings and assess if oxytocin treatment improves social functioning in this subset. This is the first psychopharmacologic study to compare different doses of oxytocin in the same subject, thus the significance of the opposing responses is unclear.

No abstract

The practice of "microdosing", or the use of repeated, very low doses of LSD to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment. Methods. The present study was designed to examine the effects of a single low dose of LSD (13 micrograms) vs placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, aged 18-35, participated in two fMRI scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state BOLD and ASL scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed. Results. LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala -middle frontal gyrus connectivity strength. Conclusions. These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug's purported antidepressant effect. NCT03790358

No abstract

MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. 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. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5 mg/kg), intranasal oxytocin (20 IU or 40 IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5 mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7 pg/ml at approximately 90–120 minutes, compared to 18.6 pg/ml after placebo. Intranasal oxytocin (40 IU, but not 20 IU) increased plasma oxytocin levels to 48.0 pg/ml, 30–60 min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., ‘High’ and ‘Like Drug’), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. 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.