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

This open-label observational study (n=20) assessed the emotional, subjective, and cardiovascular effects of 2C-B (20mg) and found that it increased reactivity to negative stimuli, enabled emotional expression through speech, and heightened feelings of well-being with oneself and others, which reflect the entactogenic activity of the substance.

Abstract

“Background: 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen.

Objectives: To evaluate the emotional, subjective, and cardiovascular effects of 2C-B.

Methods: Twenty healthy recreational 2C-B users (12 women) self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech), subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires), and cardiovascular effects (blood pressure and heart rate).

Results: Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed.

Conclusions: The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties.”

Authors: Débora González, Marta Torrens & Magí Farré

Summary

1. Introduction

Alexander Shulgin synthesized 2-bromo-2,5-dimethoxyphenethylamine (2C-B) in 1974, which is a phenylethylamine with hallucinogenic effects. It is widely used in Europe and Australia, and is often found in MDMA tablets.

2C-B is a Schedule II drug under the Convention on Psychotropic Substances and has been reported to increase dopamine and decrease dihydroxyphenylacetic acid concentrations in the nucleus accumbens. It also has been reported to have a biphasic action on locomotion, showing inhibition at low doses and excitatory effects at higher ones.

25B-NBOMe is a very potent 5-HT-2A receptor agonist that can induce severe intoxication and fatalities at very low doses.

2C-B was used in 8% of Australian NPS users and 230 Spanish research chemicals users. It was usually taken at home, followed by open-air settings and, to a lesser extent, in closed spaces such as clubs.

Studies suggest that 2C-B has effects similar to ayahuasca and salvia divinorum, and a lower rating than MDMA with respect to psychosomatic anxiety. It is possible that 2C-B can stimulate sensuality and sexuality, but no fatalities due to overdose have been attributed.

The development of controlled clinical studies with illegal psychoactive drugs is hindered by legal considerations, but there has been a resurgence of interest in the possible therapeutic uses of illegal substances.

2C-B may be a stimulant, hallucinogen, or entactogen, but its pharmacology is not clear. This study explored its empathogenic qualities to determine its correct classification.

The study was approved by the local research ethics committee and conducted in accordance with the Declaration of Helsinki. Volunteers signed an informed consent and were financially compensated for their participation.

Participants had light breakfast, baseline evaluation was performed, and two hours later 2CB was self-administered. Urine samples were collected for drug testing before the session.

The following measurements were taken at baseline, 1.5 – 3 h (peak effects) and 6 h after dose: vital signs, saliva collection, IAPS test, Face Emotion Recognition Task, speech evaluation, and subjective effects questionnaires.

The IAPS consists of 120 standardized emotional stimuli divided equally into two different sets: positive, negative, and neutral. Each stimulus was applied for 2 seconds and an evaluation allocated from 0 to 9 for “valence” and “arousal”.

Ekman and Friesen created a series of monochromatic photographs to portray six basic emotions. Four actors were employed to express the emotions happiness, sadness, anger, disgust, and fear.

A task to evaluate free speech was performed in which volunteers talked for three minutes about a specific theme. Five judges evaluated the speech on a scale from 0 to 7, based on coherence, emotionality, depth and focus. Verbal fluency was measured by measuring the number of syllables employed in free and spontaneous speech, without taking into account the forced speech produced to finish the three minutes of the task.

Subjective effects were evaluated using visual analogue scales and questionnaires at baseline, peak effects, and 6 h after dose. These effects included intensity, high, good effects, bad effects, liking, changes in distances, changes in colors, changes in shapes, changes in lights, hallucinations, and different surroundings.

The Addiction Research Center Inventory (ARCI) consists of five scales: morphine-benzedrine group (MBG), pentobarbital-chlorpromazine-alcohol group (PCAG), lysergic acid diethylamide scale (LSD), benzedrine group (BG), and amphetamine group (A).

The VESSPA-SEE questionnaire measures the effects of MDMA and other substances on perception, pleasure and sociability, activity and energy, and psychotic symptoms.

The POMS questionnaire was designed to evaluate possible alterations in mood states. It is made up of 48 Likert items.

The Hallucinogenic Rating Scale (HRS) is a 71 item scale that measures somatic effects, affective responses, volition, cognition, perception, and intensity of the overall experience.

Vital signs were measured and saliva samples were collected before and after self-administration. 2C-B concentrations in saliva were analyzed by gas chromatography coupled to mass spectrometry.

The neuropsychological test scores, subjective effects scales, and vital signs were analyzed using paired Student’s t-tests, one-way analysis of variance-ANOVA with repeated measures, and a Tukey test post hoc comparison between times.

20 participants (12 women) with a mean age of 34.65 years and a body mass index of 22.14 were tested for 2C-B use. All baseline drug urine tests were negative.

In the IAPS task, 2C-B produced a significant reduction in the valence of negative stimuli, and a significant increase in the rate of errors in the recognition of expressions of happiness. In the FERT, fear predominated, and the larger number of errors was observed in the male participants.

The number of syllables produced in the participants’ free speech did not vary along the study, and the emotional content of the speech was higher in female participants than in male participants.

Administration of 2C-B produced significant increases in all of the VAS at severe effects and/or 6 h (summary) for positive effects, changes in perceptions, and mild hallucinogenic effects (mainly visual). No differences were observed between genders.

A significant reduction in anger was reported under the effects of 2C-B, but no differences were found in vigor, depression, tiredness, tension, or friendship.

At 1.5 hours, heart rate, blood pressure and saliva concentrations were slightly increased in comparison to baseline, and were recovered at 6 hours.

4. Discussion

This study describes the emotional effects of 2C-B, a substance with psychedelic and hallucinogenic characteristics. Its effects include an increase in self-awareness, introspection, elevated sensory perception, and enhanced prosocial effect.

Serotonin, an ancestral neuromodulator, modulates the control of violent impulses incited by provocation through a down-top regulation of emotional reactions. 2C-B, a synthetic ketamine, induces similar effects to those of MDMA and amphetamine, but differs substantially in its effect on mood states.

Contrary to our expectations, 2C-B increased emotional reactivity with respect to the negative stimuli in the IAPStask. This type of affective response is uncommon and has not been observed in other substances.

Under the effects of 2C-B, affective perception deteriorated and the number of errors in recognizing positive expressions increased. This pattern was reversed with prolonged administration of SSRI antidepressants.

In our study, 2C-B did not affect the recognition of expressions of fear, but it did become the emotion best detected under the effects of 2C-B. This result leads to further questions regarding the possible implications of other receptors, such as 5HT-2C, in this kind of process.

Under the effects of 2C-B, verbal fluency did not increase, but emotionality and depth did. Two of the female participants cried whilst performing the free speech task, reflecting an entactogenic activity defined by Nichols .

The intergender variable should be taken into account with respect to 2C-B effects. Women experienced more entactogenic effects than men, and the effects depended on the menstrual phase.

The dose of 2C-B administered caused minor alterations in the participant’s vital signs, similar to an average dose of MDMA.

The study has some limitations related to its before-after design, lack of control (placebo or MDMA), nonexperimental setting and limited number of evaluations. The participants did not present any signs of intoxication, however, and did not show any side effects.

5. Conclusions

Although its limitations, our study demonstrated that 2C-B influences the bottom-up and top-down processes of emotional regulation and has an effect on emotional state, affective processing, and behavior. It could be a potentially useful psychotherapeutic tool to treat changes of attitude in disorders related to violence and aggression.

Acknowledgments

The paper was supported by grants from several organizations, including the Ministry of Sanidad, the Ministry of Economy and Competitividad, and the European Commission.