Drug and Alcohol Dependence 76 (2004) 297–304 The acute and sub-acute effects of ‘ecstasy’ (MDMA) on processing of facial expressions: preliminary findings Rosa Hoshi∗, Jatinder Bisla, H. Valerie Curran Clinical Psychopharmacology Unit, Sub-Department of Clinical Health Psychology, University College London, Gower Street, London WC1E 6BT, UK Received 6 April 2004; received in revised form 25 June 2004; accepted 30 June 2004 Abstract Rationale: There is evidence that serotonergic processes may modulate the processing of fearful facial expressions. It is therefore possible that the recreational drug ‘ecstasy’ (MDMA), which has marked serotonergic effects, may affect people’s ability to recognise human facial expressions portraying fear. Objective: The present study therefore aimed to determine whether ecstasy users differed from controls in fear recognition at two time points: shortly after taking the drug and a few days later. Methods: Sixteen ecstasy users and 21 controls were compared on a facial expression recognition task involving the 6 basic emotions (happiness, surprise, sadness, anger, fear and disgust) and on self-ratings of mood on the night of drug use (day 0) and 4 days later (day 4). Results: In recognising fearful facial expressions, ecstasy users were more accurate than controls on day 0 but less accurate than them on day 4 when compared with their overall ability to recognise other basic emotions. Accuracy of fear recognition on day 4 was negatively correlated with both years of ecstasy use and number of ecstasy tablets taken on a typical session. On self-rated aggression scales, ecstasy users scored lower than controls on day 0 and higher on day 4. Conclusions: These results support the notion that 5-HT plays a role in modulating the recognition of fearful facial expressions. Increased accuracy of fear recognition may relate to 5-HT release following ecstasy use on day 0, and decreased accuracy may reflect subsequent depletion of 5-HT mid-week. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: MDMA; Ecstasy; Serotonin; Fear recognition; Facial expressions 1. Introduction through these systems, MDMA’s main action is on the sero- tonergic (5-HT) system. After binding to the 5-HT trans- ±3,4-Methylenedioxymethamphetamine (MDMA, ‘ec- porter, the MDMA molecule is taken into the presynaptic stasy’) is used recreationally for its acute subjective effects cell where it stimulates the release of stored 5-HT and pre- that include euphoria, insightfulness, energy and feelings of vents its reuptake (Green et al., 1995). MDMA administra- closeness to others (Vollenweider et al., 1998; Harris et al., tion causes short-term attenuation of tryptophan hydroxylase, 2002). These subjective effects, described by many users as thus inhibiting the synthesis of new 5-HT. This may have im- feelings of empathy, appear unique to MDMA and have led plications for recreational users, as the possible depletion of to the suggestion that MDMA should be classified as a new brain 5-HT in the days following MDMA use may affect a class of psychoactive compounds known as ‘entactogens’ variety of functions modulated by 5-HT. (Nichols, 1986). The recognition of facial expressions is a “crucially im- MDMA causes the release of dopamine (DA) and nora- portant” element of social interaction (Harmer et al., 2003a). drenaline (NE), but whereas other stimulant drugs act mainly The six basic emotions—happiness, surprise, sadness, anger, fear and disgust—are consistently recognised across cultures ∗ Corresponding author. Tel.: +44 207 679 5938; fax: +44 207 916 1989. (Ekman, 1992) and there is some evidence that each may E-mail address: [email protected] (R. Hoshi). be modulated by different neural substrates (LeDoux, 2000). 0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.06.006 298 R. Hoshi et al. / Drug and Alcohol Dependence 76 (2004) 297–304 Manipulation of different neurotransmitters seems to affect and Lader, 1986), impulsivity self rating scale (ISRS; Bond processing of facial expressions differentially (e.g. Blair and and Lader, 1974) and a scale of subjective effects which cov- Curran, 1999). Harmer and colleagues have assessed the ef- ered common effects of recreational drugs including those fect of various 5-HT manipulations on recognition of facial specific to MDMA. A modified Beck depression inventory expressions. They found that on the one hand, increased (BDI; Beck, 1978) was used to assess how participants had release of 5-HT through either intravenous citalopram or been feeling over the last 3 days (Curran and Travill, 1997). tryptophan administration leads to improved recognition of fearful facial expressions (Harmer et al., 2003a; Attenburrow 2.4. Recognition of facial expressions (days 0 and 4) et al., 2003); on the other hand, reducing 5-HT by tryptophan depletion impaired recognition of fear (Harmer et al., 2003b). The participants performed the facial expression recogni- Recognition of facial expressions has not, to our knowl- tion task on both days of the study. The task used the stimuli edge, ever been assessed in MDMA users. Thus, in light of from the facial expressions of emotions: stimuli and tests the findings described above, the current study was designed (FEEST; Young et al., 2002). There were 30 stimuli featur- to address the hypothesis that enhanced 5-HT following acute ing a male face showing the 6 basic emotions—happiness, MDMA ingestion would selectively improve recognition of surprise, sadness, anger, fear and disgust—from the Ekman fearful facial expressions and that several days later depletion and Friesen (1976) series. These basic emotions are used to of 5-HT would lead to a selective impairment of fear recog- create stimuli that are morphed from one emotion to another nition. In addition, we expected to replicate previous studies in five stages (10, 30, 50, 70, 90%). The expressions morphed that demonstrated increased self-rated aggression and depres- are anger to happiness, happiness to surprise, surprise to fear, sion 4 days after ecstasy use (Verheyden et al., 2002; Curran fear to sadness, sadness to disgust and disgust back to anger. et al., 2004). All stimuli involved the face JJ (Ekman and Friesen, 1976). The task was performed on lap top computers and con- sisted of six blocks. In each block, the 30 morphed stimuli 2. Materials and methods were presented in a pseudo-random order. Constraints were in place to ensure that no more than two stimuli with the same 2.1. Design and participants majority emotion appeared together. Each stimulus appeared An independent group, repeated measures design was used on the screen for 500 ms. The task was specially programmed to compare ecstasy users with controls on two test sessions: with a response facility whereby the six emotions were ar- the night of drug use (day 0) and 4 days later (day 4). Both ranged in an equilateral hexagon in the centre of the right the ecstasy users and the control participants were recruited hand side of the screen next to the faces which were pre- in clubs and parties using the snowball sampling technique sented on the left hand side of the screen. This arrangement (Solowij et al., 1992). In this way all participants were re- was such that each emotion was equidistant from the central cruited from the same social settings and increased the like- cursor base. Participants were asked to choose the emotion lihood of matching groups on the use of other drugs. The that corresponded with the facial expression by clicking on it study was approved by the institutional ethics committee and with the mouse, as quickly and accurately as they could. The all participants gave written informed consent both on day 0 position of the emotions around the hexagon changed on each and on day 4. occasion to avoid any response bias, and the mouse cursor re- turned automatically to the centre of the hexagon before each 2.2. Procedure stimulus was presented. This response facility was designed to both lessen the working memory load required to remem- On the evening of day 0 participants were taken individ- ber six different response keys and ensure that the response ually to a quiet room where they were first given an infor- to each emotion required equal motor movement. Both re- mation sheet. If they were willing to participate they were sponse and reaction time were automatically recorded, and asked for written consent. They then completed the assess- recognition accuracy and reaction times used in the analysis ments detailed below. Arrangements were made for the next were calculated from the correct responses to the stimuli that test session 4 days later, which was generally carried out at had a dominant percentage (90 or 70%) of each emotion. the participant’s home. Informed consent was obtained once Each participant’s pulse rate was taken at both test ses- again on day 4, then the day 0 assessments were repeated sions. along with trait measures of mood and a drug use history interview. 3. Additional assessments on day 4 2.3. Mood assessments (days 0 and 4) 3.1. Trait measures and pre-morbid IQ Current mood state was assessed on both days with the following visual analogue scales: mood rating scale (MRS; The hospital anxiety and depression scale (HADS; Bond and Lader, 1974), aggression rating scale (ARS; Bond Zigmond and Snaith, 1983) was used to index trait anxiety R. Hoshi et al. / Drug and Alcohol Dependence 76 (2004) 297–304 299 and depression, the aggression questionnaire (AQ; Buss and (6 males, 15 females). There was a significant difference be- Perry, 1992) was used to index trait aggression, and the Bar- tween the number of males and females in each group (χ2 = ratt impulsivity scale (BIS; Barratt and Patton, 1983)was 4.26, P = 0.039).