Search

There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.

Neurorehabilitation in military populations is complicated by higher rates of PTSD and unique characteristics of military institutions. These factors can adversely impact the patient-therapist therapeutic alliance and engagement with the rehabilitation process leading to poorer outcomes. MDMA is a non-classical psychedelic with pro-social and fear regulating properties. MDMA-assisted therapy is being explored as a novel treatment for PTSD that potentially offers rapid symptom improvement and enhances therapeutic alliance.A review of MDMA-assisted therapy for PTSD is provided in the context of neurorehabilitation in military populations. The molecular mechanism of MDMA is outlined and a novel application of MDMA for neurorehabilitation is proposed.This is an expert review and synthesis of the literature.Results from late-stage clinical trials suggest MDMA-assisted therapy for PTSD would be of particular benefit for military populations with PTSD. The unique pro-social properties of MDMA could be leveraged to enhance the therapeutic alliance and patient engagement during neurorehabilitation.The unique qualities and benefits of MDMA and MDMA-assisted therapy for PTSD suggest relevant application in military personnel undergoing neurorehabilitation. There are many similarities in patient-therapist dynamics in PTSD treatment and neurorehabilitation. The properties of MDMA which enhance therapeutic alliance, downregulate fear, and increase cognitive flexibility would potentially benefit both military personnel with and without PTSD undergoing neurorehabilitation. [ABSTRACT FROM AUTHOR]

The 3,4‐methylenedioxymethamphetamine (MDMA) has long been used non‐medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio‐emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event‐related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio‐emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: The prosocial compound ± 3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has shown promise as an adjunct to psychotherapy in the treatment of post-traumatic stress disorder. MDMA increases positive responses to social images, and it has been suggested that the ability of MDMA to positively bias social perception may underlie its therapeutic efficacy as a psychotherapy adjunct. However, the effect of the compound on affective responses to positive or negative social feedback has not been tested. Aims: In this study, we aimed to test the effects of MDMA compared to placebo and the prototypical stimulant, methamphetamine (MA), on responses to positive and negative social feedback. Methods: This was a double-blind, placebo-controlled, crossover trial (NCT03790618), comparing the effects of two doses of MDMA (0.75 mg/kg, 1.5 mg/kg) to both placebo and MA (20 mg) on responses to a personalized social feedback task, similar to a dating app, in healthy adult volunteers ages 18–40 (N = 36, 18 women, 18 men). Results/Outcomes: The high dose of MDMA increased positive affective responses to social feedback. Conclusions/Interpretations: These findings suggest one process by which MDMA may facilitate social connection. Further work is needed to understand how MDMA affects responses to more generalized types of social feedback and to understand these effects in clinical populations. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However, there are no effective medications available to treat this symptom. Despite the lack of approved treatments for patients, there is a growing body of literature on the effects of several classes of drugs on social motivation in healthy volunteers that may be relevant to patients. The aim of this review is to synthesize these results in an effort to identify novel directions for the development of medications to treat reduced social motivation in schizophrenia. Study Design In this article, we review pharmacologic challenge studies addressing the acute effects of psychoactive drugs on social motivation in healthy volunteers and consider how these findings may be applied to deficits in social motivation in schizophrenia. We include studies testing amphetamines and 3,4-methylenedioxymethamphetamine (MDMA), opioids, cannabis, serotonergic psychedelics, antidepressants, benzodiazepines, and neuropeptides. Study Results We report that amphetamines, MDMA, and some opioid medications enhance social motivation in healthy adults and may represent promising avenues of investigation in schizophrenia. Conclusions Given the acute effects of these drugs on behavioral and performance-based measures of social motivation in healthy volunteers, they may be particularly beneficial as an adjunct to psychosocial training programs in patient populations. It remains to be determined how these medications affect patients with deficits in social motivation, and in which contexts they may be most effectively administered. [ABSTRACT FROM AUTHOR]

Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or behavior are poorly understood. Controlled laboratory studies with well-defined psychological constructs are valuable to understand how these drugs manifest their therapeutic benefit. However, there are substantial methodological differences between clinical studies investigating therapeutic outcome and laboratory studies investigating the processes that might underlie the therapeutic effects. Here, we examine some of these differences using the example of 3,4-methylenedioxymethamphetamine (MDMA). We review differences in expectancies, social and physical context, participant characteristics, pharmacological factors, and outcome measures in studies with participants who do or do not have psychiatric diagnoses. We describe the challenges and opportunities in translating findings from laboratory studies to the clinic and identify ways to bridge the gap between these approaches. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking is a well-known public health concern, and there is an urgent need to develop new treatments to reduce smoking or facilitate abstinence. One factor that is known to contribute to relapse is stress, making the stress response an important target for treatment. The neuropeptide oxytocin (OT) is believed to have stress-reducing effects, and in addition there is evidence that it reduces drug craving. The purpose of the present study was to examine the effects of intranasal OT on stress-induced cigarette craving in regular smokers after 12 h of abstinence. Method Daily smokers (n = 48) completed a stress induction task and a nonstressful control task at two different sessions, receiving intranasal OT (40 IU) or placebo (PBO) before or after the task. Subjects were randomly assigned to one of three groups: Group PP (n = 16) received PBO before and after the stress/control tasks, Group OP (n = 16) received OT before the tasks and PBO after, and Group PO (n = 16) received PBO before the tasks and OT shortly after completing the tasks. Cigarette craving as well as subjective and physiological responses to stress was assessed. Results OT did not alter responses to stress, whether it was administered before or after the stressful task, on measures of cigarette craving, anxiety, heart rate, blood pressure, and cortisol levels. Conclusions The current study findings do not support several previous reports that OT reduced either stress or drug craving. Implications This study finds a null result of the neuropeptide oxytocin on stress-induced cigarette craving. Reporting null findings is part of the process of identifying potential treatments for addictive disorders. [ABSTRACT FROM AUTHOR]

Background: The opioid drug buprenorphine has been shown to modify responses to emotional stimuli and may have antidepressant properties. In preclinical studies, it shows antidepressant-like and anxiolytic-like effects, and a handful of clinical studies suggest it may reduce symptoms of depression in patients. We have shown that low doses of buprenorphine reduce responses to negative emotional stimuli in healthy adults. Here we extended these findings to individuals with symptoms of depression and anxiety. Methods: We examined the effects of buprenorphine on attention to emotional facial expressions and ratings of and psychophysiological responses to emotional images in adults with a range of mood symptomatology. Volunteers (n = 38) were recruited with low, mild, moderate, and severe scores on the Depression-Anxiety-Stress Scale. They attended 2 laboratory sessions during which they received either placebo or 0.2 mg sublingual buprenorphine in randomized order under doubleblind conditions. During peak drug effect, participants completed a visual attention task assessing responses to emotional faces and a picture-rating task assessing responses to emotional images with and without social content. Results: Buprenorphine reduced attention to fearful facial expressions as it did in our previous study, and the emotion-specific effect was especially pronounced in individuals with high Depression-Anxiety-Stress Scale scores. The drug also increased ratings of positivity of images with social content, but this effect was less strong in individuals with higher Depression-Anxiety-Stress Scale scores. Conclusions: These results suggest low doses of buprenorphine may reduce some dimensions of responses to negative emotional stimuli in individuals high on depression or anxiety, while leaving other dimensions unaffected. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is a well-known public health concern, and there is an urgent need to develop new treatments to reduce smoking or facilitate abstinence. One factor that is known to contribute to relapse is stress, making the stress response an important target for treatment. The neuropeptide oxytocin (OT) is believed to have stress-reducing effects, and in addition there is evidence that it reduces drug craving. The purpose of the present study was to examine the effects of intranasal OT on stress-induced cigarette craving in regular smokers after 12 h of abstinence.Method: Daily smokers (n = 48) completed a stress induction task and a nonstressful control task at two different sessions, receiving intranasal OT (40 IU) or placebo (PBO) before or after the task. Subjects were randomly assigned to one of three groups: Group PP (n = 16) received PBO before and after the stress/control tasks, Group OP (n = 16) received OT before the tasks and PBO after, and Group PO (n = 16) received PBO before the tasks and OT shortly after completing the tasks. Cigarette craving as well as subjective and physiological responses to stress was assessed.Results: OT did not alter responses to stress, whether it was administered before or after the stressful task, on measures of cigarette craving, anxiety, heart rate, blood pressure, and cortisol levels.Conclusions: The current study findings do not support several previous reports that OT reduced either stress or drug craving.Implications: This study finds a null result of the neuropeptide oxytocin on stress-induced cigarette craving. Reporting null findings is part of the process of identifying potential treatments for addictive disorders. [ABSTRACT FROM AUTHOR]

Background: Social disequilibrium, or disrupted social homeostasis, underlies many behavioral disorders, including problematic drug use. One way to study the relationship between drug use and social homeostasis is to determine whether single doses of psychoactive drugs relieve some of the discomfort of social isolation and promote social connection., Methods: In this narrative review, we discuss challenges and opportunities in studying the relationship between psychoactive drugs and social homeostasis. Using the examples of opioids and amphetamines, we discuss the evidence that drugs alleviate dysphoria related to lack of social connection or produce pro-social effects that improve connection., Results: With regard to opioid drugs, we report that mu opioid agonists and kappa opioid antagonists reduce distress from social isolation, and mu opioid agonists enhance social reward. Amphetamine-like stimulant drugs, including MDMA, do not seem to act by reducing the distress of social isolation, but they have notable prosocial effects that increase both motivation for social contact and the pleasure derived from interacting socially., Conclusions: Many questions remain in understanding interactions between drugs and social equilibrium, including whether these effects contribute to problematic drug use. We identify gaps in knowledge, including the effects of drug withdrawal or dependence on social function, or the responses of individuals with psychiatric symptomatology. Understanding these actions on social processes will help to develop novel pharmacologic treatments for clinical problems related to social disequilibrium., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cigarette smoking is a well-known public health concern, and there is an urgent need to develop new treatments to reduce smoking or facilitate abstinence. One factor that is known to contribute to relapse is stress, making the stress response an important target for treatment. The neuropeptide oxytocin (OT) is believed to have stress-reducing effects, and in addition there is evidence that it reduces drug craving. The purpose of the present study was to examine the effects of intranasal OT on stress-induced cigarette craving in regular smokers after 12 h of abstinence., Method: Daily smokers (n = 48) completed a stress induction task and a nonstressful control task at two different sessions, receiving intranasal OT (40 IU) or placebo (PBO) before or after the task. Subjects were randomly assigned to one of three groups: Group PP (n = 16) received PBO before and after the stress/control tasks, Group OP (n = 16) received OT before the tasks and PBO after, and Group PO (n = 16) received PBO before the tasks and OT shortly after completing the tasks. Cigarette craving as well as subjective and physiological responses to stress was assessed., Results: OT did not alter responses to stress, whether it was administered before or after the stressful task, on measures of cigarette craving, anxiety, heart rate, blood pressure, and cortisol levels., Conclusions: The current study findings do not support several previous reports that OT reduced either stress or drug craving., Implications: This study finds a null result of the neuropeptide oxytocin on stress-induced cigarette craving. Reporting null findings is part of the process of identifying potential treatments for addictive disorders., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)