Effects of Acute MDMA Intoxication on Mood and Impulsivity: Role of the 5-HT2 and 5-HT1 Receptors

Wel, J.H.P. van; Kuypers, Kim P. C.; Theunissen, Eef L.; Bosker, Wendy M.; Bakker, Katja; Ramaekers, Johannes G.

doi:10.1371/journal.pone.0040187

Cited by 86 publications

(94 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The average scores during drug and placebo conditions were also comparable to those found in previous drug studies by our group using the same paradigms (e.g., (Kuypers et al 2007; van Wel et al 2012). Although present findings suggest that a single dose of 4-FA (100 mg) does not induce impulsive behavior, previous studies have shown that personal characteristics, like baseline performance and task-related characteristics like stimulus/response complexity, can play a role in drug-induced changes.…”

Section: Discussionsupporting

confidence: 87%

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

et al. 2018

View full text Add to dashboard Cite

BackgroundNew psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsivity and sensitivity to the rewarding effects of drugs have been considered as risk factors for drug abuse. In light of the popularity of 4-fluoroamphetamine (4-FA), it is important to assess whether 4-FA can lead to subjective drug liking and wanting, and impulsive behavior, all factors contributing to the abuse likelihood of a substance.MethodsA placebo-controlled 2-way crossover study in 12 healthy poly-drug using participants was conducted to test subjective and behavioral effects of 4-FA (100 mg). 4-FA concentrations were determined in serum up to 12 h after administration and two impulsivity tasks and two drug experience questionnaires assessing drug liking and wanting, and good and bad drug effect, were administered between 1 and 11 h post-administration.ResultsFindings showed that 4-FA did not affect impulsive behavior. Self-ratings of drug liking and wanting and good drug effect were increased 1 h after administration; this effect was absent 11 h after drug intake.Discussion and conclusionTo conclude, 4-FA (single dose) increased self-rated liking and wanting, which is known to contribute to the abuse likelihood of a substance; however, it left another factor impulsive behavior unaffected. It has to be noted that the current picture is limited and might change with increased sample size, and/or different 4-FA doses.Clinical trial registrationTrial acronym: 4-FA. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6164. Registration number: NTR6164 (Dutch clinical trial registry number).

show abstract

Section: Discussionsupporting

confidence: 87%

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Although reduced fear expression during extinction training does not predict lasting improvements in extinction, those lasting improvements require that MDMA is on-board during the extinction session (Young et al 2015). While it has been hypothesized that MDMA improves psychotherapy for PTSD through its acute positive effects on mood, these effects might be mitigated by MDMA's anxiogenic effects (Bershad et al 2016; van Wel et al 2012). The findings here and elsewhere suggest that subjective or behavioral responses to MDMA during extinction training may not predict lasting fear extinction outcomes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

et al. 2017

View full text Add to dashboard Cite

Rationale 3,4-methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD; particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. Objectives We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. Methods We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. Results MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's effect on extinction. Conclusions We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

show abstract

“…After MDMA, participants endorsed feeling ‘loving’ (Bedi et al, 2010; Frye et al, 2014; Kirkpatrick and de Wit, 2014; Kirkpatrick et al, 2014a; Kirkpatrick et al, 2014b; Wardle and de Wit, 2014; Wardle et al, 2014), ‘talkative ’(Hysek et al, 2012a; Hysek et al, 2012c; Tancer and Johanson, 2007; Tancer and Johanson, 2003), ‘extroverted’ (Gamma et al, 2000; Hysek et al, 2013; Hysek et al, 2014a; Hysek et al, 2011; Hysek et al, 2012c; Liechti et al, 2000b), ‘sociable’ (Bedi et al, 2009; Kirkpatrick et al, 2014a; Kirkpatrick et al, 2014b; Tancer and Johanson, 2003), ‘self-confident’ (Gamma et al, 2000; Harris et al, 2002; Hysek et al, 2013; Kirkpatrick and de Wit, 2014; Kirkpatrick et al, 2014b), ‘friendly’ (Johanson et al, 2006; Kirkpatrick et al, 2014a; Kirkpatrick et al, 2014b; Kuypers et al, 2013; Kuypers et al, 2011; Tancer and Johanson, 2007; Tancer and Johanson, 2003; van Wel et al, 2012), ‘playful’ (Bedi et al, 2010; Kirkpatrick et al, 2014a; Kirkpatrick et al, 2014b), ‘open’ (Hysek et al, 2012a; Hysek et al, 2012c; Schmid et al, 2014), ‘trusting’ (Schmid et al, 2014), ‘close to other people’ (Hysek et al, 2012a; Hysek et al, 2012b; Hysek et al, 2014a; Hysek et al, 2011; Kolbrich et al, 2008; Schmid et al, 2014) and ‘emotionally concerned’ (Kuypers et al, 2014). …”

Section: Effects Of Mdma On Social Feelings Processing and Behavmentioning

confidence: 99%

The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals

Kamilar-Britt

Bedi

2015

Neuroscience & Biobehavioral Reviews

118

127

View full text Add to dashboard Cite

Users of ±3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others’ positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use.

show abstract

Effects of Acute MDMA Intoxication on Mood and Impulsivity: Role of the 5-HT2 and 5-HT1 Receptors

Cited by 86 publications

References 52 publications

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

Drug liking and wanting, not impulsive action or reflection is increased by 4-fluoroamphetamine

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals

Contact Info

Product

Resources

About