Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

2C-B (4-bromo-2,5-dimethoxyphenethylamine, “Nexus”) is a phenylethylamine first synthesised by Alexander Shulgin in 1974 and has become one of the more widely used novel psychoactive substances (NPS) in Europe and Australia. Previous preclinical work suggests 2C-B modulates monoamine systems (inhibiting serotonin uptake and acting to a lesser extent on norepinephrine and dopamine transporters), alters dopamine metabolites in the nucleus accumbens, and produces dose-dependent effects on locomotion. Human data are limited and mixed: 2C-B has been variously classified as stimulant, hallucinogen, entactogen or empathogen, and it is frequently encountered as an adulterant of MDMA tablets. Its receptor profile is incompletely characterised, with reports of partial 5-HT-2A and 5-HT-2C activity and metabolism via monoamine oxidases and cytochrome P450 enzymes. This study aimed to characterise the acute emotional, subjective and cardiovascular effects of a single 20 mg oral dose of 2C-B in healthy recreational users, with particular interest in clarifying whether its effects fit an entactogenic profile, a psychedelic/hallucinogenic profile, or a mixture of both. González and colleagues set out to measure emotion processing (using validated picture and facial recognition tasks), spontaneous speech characteristics, a battery of subjective-effect questionnaires, vital signs and saliva concentrations over a 6-hour period after self-administration.

The study used an open, before–after design in which 20 healthy recreational 2C-B users (12 women) self-administered a single oral dose of 20 mg of 2C-B at approximately 14:00. Inclusion required prior 2C-B experience and abstinence from psychoactive substances for 48 hours; exclusion criteria included serious medical or psychiatric history, drug dependence (except tobacco), prior adverse reactions to 2C-B, and chronic medication. Ethical approval was obtained and participants provided informed consent; sessions were conducted in the home of an association member rather than a laboratory setting. Gas chromatography analysis by a harm-reduction NGO confirmed 95% purity of the material. Urine drug screens for common drugs were negative at baseline. Assessments occurred at baseline, at peak effects (approximately 1.5–3 h postdose, typically 1.5 h reported for peak neuropsychological testing) and at 6 h. The core neuropsychological/emotional measures were the International Affective Picture System (IAPS; 120 images in two counterbalanced sets, valence and arousal ratings), the Face Emotion Recognition Task (FERT; five emotions presented in graded intensity), and a 3-minute free-speech task (topics counterbalanced) recorded and later rated by five blinded psychologists on coherence, emotionality, depth and focus; syllable counts provided a measure of verbal fluency. Subjective effects were captured with multiple instruments: visual analogue scales (VAS), the Profile of Mood States (POMS), the Addiction Research Center Inventory (ARCI), the VESSPA-SEE questionnaire, and the Hallucinogenic Rating Scale (HRS) with timing as described above (some scales at 6 h summarised). Vital signs (heart rate and blood pressure) and saliva samples for 2C-B concentrations were taken at the same time points. Statistical analysis compared baseline versus peak (and baseline versus 6 h where applicable) using paired Student's t-tests for neuropsychological and questionnaire measures; vital signs were analysed with one-way repeated-measures ANOVA and Tukey post hoc tests. Independent-sample t-tests examined gender differences. Analyses were performed in SPSS 12.0 and significance was set at P < 0.05.

Sample characteristics: Twenty participants (12 women) mean age 34.65 years (SD = 5.25), BMI 22.14 (SD = 2.56); 60% had a university degree. Mean prior recreational 2C-B use was 6.5 occasions (SD = 7.0). All reported prior use of several illicit drugs; baseline urine screens were negative and no intoxication signs were present at baseline. Neuropsychological/emotional tasks: In the IAPS, 2C-B produced a statistically significant reduction in valence ratings for negative images (P = 0.037), interpreted as increased unpleasantness or discomfort in response to negative stimuli; arousal ratings did not change significantly except for a trend toward increased arousal for negative stimuli (P = 0.11). No gender differences were found for IAPS ratings. In the FERT, participants made significantly more errors recognising expressions of happiness after 2C-B (P = 0.027); under 2C-B, fear became the most readily detected emotion. Men made more errors detecting anger than women (men mean 5.75 (SD = 2.12) vs women 3.75 (SD = 1.06), P = 0.035). Free speech: Verbal fluency (syllable count) did not change (baseline 474.74, SD = 216.23; peak 479.11, SD = 152.09; P = 0.936). Speech was rated as significantly more emotional after 2C-B (P = 0.012), with higher emotionality ratings in women (men mean 4.36 (SD = 0.84) vs women 5.57 (SD = 1.12), P = 0.042). Two female participants cried during the task and one male laughed uncontrollably; that male's speech was unintelligible and he was excluded from the speech analyses, yielding n = 19 for that outcome. Subjective questionnaires: VAS scores increased significantly for positive effects, perceptual changes and mild visual hallucinatory experiences at peak and/or in the 0–6 h summary; no gender differences on VAS were observed. On the ARCI, significant increases occurred in euphoria (MBG), dysphoria/somatic effects (LSD), and the amphetamine-sensitive scales (BG and A); sedation (PCAG) did not change. The VESSPA showed significant increases across all subscales, with the highest scores for pleasure and sociability and the lowest for psychosomatic anxiety and psychotic symptoms; men scored higher than women on the activity and energy subscale at 6 h (men 9.88 (SD = 4.91) vs women 5.00 (SD = 4.51); P = 0.041). POMS showed a significant reduction in anger under 2C-B (P = 0.042); no effects were detected on vigor, depression, tiredness, tension or friendship overall, although men showed a reduction in tiredness (men 0.50 (SD = 0.535) vs women 3.75 (SD = 3.19); P = 0.011). On the HRS (6 h summary), high scores appeared particularly for volition, intensity and perception, while cognition scored lowest. Physiology and saliva: Small but statistically significant sympathetic effects were observed at peak (1.5 h): heart rate increased by approximately 6 beats/min, systolic blood pressure by about 5 mmHg and diastolic pressure by about 4 mmHg; values returned to baseline by 6 h. No gender differences in vital signs were reported. Saliva 2C-B concentrations were detectable at 1.5 h (6.8 ng/mL) and 6 h (2.3 ng/mL).

González and colleagues interpret the pattern of findings as consistent with an entactogenic profile that includes psychedelic and mild hallucinogenic properties. They argue that reductions in self-reported anger (POMS) together with increased well-being and sociability (VAS and VESSPA) reflect serotonergic actions typically associated with entactogens. At the same time, impairment in affective face processing—worse recognition of positive expressions and increased reactivity to negative images—does not support a straightforward empathogenic effect and points to a more complex influence on emotional processing. The authors situate these results relative to previous work: some similarities exist with MDMA in subjective prosocial and euphoriant effects, but 2C-B differed from MDMA and amphetamine in that it did not increase verbal fluency or the POMS dimensions of vigor and friendship. The unexpected increase in discomfort to negative stimuli contrasts with typical amphetamine or MDMA effects and with anxiolytic-like responses to other drugs; González and colleagues note that this pattern has analogies with findings in depression and with certain acute effects of selective serotonin reuptake inhibitors, and they discuss potential roles for serotonergic receptors beyond 5-HT-2A (including 5-HT-2C and 5-HT-1A) in mediating these emotional-processing changes. Several limitations are acknowledged: the uncontrolled before–after design lacking placebo or active comparator, assessment in a nonexperimental/home setting, a limited number of evaluation time points, and a sample of experienced users which may limit generalisability to naïve individuals. The study used a single fixed dose for all participants; menstrual phase of female participants was not recorded despite observed gender differences; standard urine screening could not detect other NPS; and saliva/plasma pharmacokinetic data remain sparse. The authors caution that, although adverse events were limited in this experienced sample, substances with similar pharmacology can cause severe medical or psychiatric reactions in susceptible users, and long-term health effects are unknown. They call for further research into 2C-B's pharmacology, toxicity and potential therapeutic applications.

A single 20 mg oral dose of 2C-B in experienced recreational users produced a mixed profile: increased feelings of well-being and sociability, reduced anger, altered perceptual and mild hallucinogenic experiences, heightened emotional expression in speech, but also greater reactivity to negative stimuli and impaired recognition of positive facial expressions. González and colleagues conclude that these effects together support classification of 2C-B as entactogenic with psychedelic properties. They suggest a potential, tentative psychotherapeutic application in disorders involving aggression or altered affective processing, but emphasise that safety, pharmacology and medium–long term consequences are insufficiently characterised and that caution and further controlled research are required.