Acute pharmacological effects of 2C-B in humans: An observational study

This open-label observational study (n=16) assessed the acute subjective, physiological, and pharmacokinetic effects of 2C-B (10, 15, or 20 mg), and found that it produces a constellation of psychedelic-psychostimulant like effects. Mood changes were more prominent than perceptual changes, and the profile of physiological effects entailed a moderate increase of blood pressure and heart rate parameters that were lower than that of MDMA by comparison.

Abstract

“Introduction: 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine- 2A (5-HT2A), 5-hydroxytryptamine-2B (5-HT2B), and 5-hydroxytryptamine-2C (5-HT2C) receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B.

Methods: Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg). Vital signs (blood pressure and heart rate) were measured at baseline 1, 2, 3, 4, and 6 hours (h). Each participant completed subjective effects using three rating scales: the visual analog scale (VAS), the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h), and the Hallucinogenic Rating Scale (maximum effects along 6 h). Oral fluid (saliva) was collected to assess 2C-B and cortisol concentrations during 24 h.

Results: Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated), and changes in perceptions (distances, colors, shapes, and lights) and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively.

Discussion: Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.”

Authors: Esther Papaseit, Magí Farré, Clara Pérez-Mañá, Marta Torrens, Mireia Ventura, Mitona Pujadas, Rafael De La Torre & Débora González

Summary

INTRODUCTION

Psychedelics can be divided into two classes: serotonergic hallucinogens and phenylethylamines. Recent research has identified many new psychoactive substances.

Novel psychedelics include the 2C-series and its structural analogs, including N-Benzylphenethylamines (NBOMes). 2C-B is one of the oldest and best known 2C-type drugs, and has gained popularity among electronic music party goers. 2-CB was added to Schedule II of the 1971 Convention on Psychotropic Substances by the UN Commission on Narcotic Drugs in 2001. It is considered an NPS in some Latin American countries.

2C-B, as other hallucinogenic phenethylamines, is a partial agonist of 5HT2A , 5HT2B , and 5HT2C receptors, and is metabolized to an alcoholic metabolite and a carboxylated metabolite. The active metabolite is 2C-B, while the rest are inactive or nearly so.

Data concerning prevalence and patterns of use of novel psychedelics are limited. In 2013, almost half of the respondents to the Global Drug Survey reported lifetime use of at least one NPS, and the most frequent substance employed was 2C-B. 2C-B is a popular nightlife NPS in Central and South America, with a life-time use of 5.1 and 2.7%, respectively. 6.3% of previous 12 month 2C-drug users suffered difficult/negative experiences while under the influence of psychedelics.

Limited clinical research has been conducted in humans about 2C-B, with the clinical presentation including typical hallucinations (tactile, visual, and auditory) and neuropsychiatric symptoms (anxiety, agitation, and confusion). The present study assessed the acute pharmacological effects and oral fluid pharmacokinetics of 2C-B in humans.

Participants

Sixteen healthy volunteers used 2C-B at least once in their lives. None had any serious medical or mental disorders.

Participants were recruited through the Association for the Study of States of Consciousness (PHI) and signed an informed consent prior to any study-related procedure.

Design and Treatments

A non-controlled prospective observational study was conducted in which subjects ingested a capsule that they brought to the testing site themselves, which contained 2C-B at 95% purity with no toxic adulterants. They chose a mean 2C-B dose of 15.94 mg.

Procedures

All subjects were trained prior to participation in the study, and were asked to abstain from all drug use 48 hours prior to the study session. The study took place at a member’s home and included ambience music, and subjects were instructed not to talk about the effects of the substance during the session.

Subjective Effects

Visual analog scales were used to rate intensity, good effects, bad effects, liking, changes in distances, changes in colors, changes in shapes, changes in lights, hallucinations, and different body feeling.

The ARCI is a 49-item questionnaire that is sensitive to the effects of five drugs: pentobarbital, chlorpromazine, alcohol, lysergic acid diethylamide, morphine-benzedrine, and amphetamine.

The HRS includes 100 items distributed in six scales: somaesthesia, affect, volition, cognition, perception, and intensity.

Oral Fluid Concentrations of 2C-B and Cortisol

Oral fluid samples were collected and analyzed for 2C-B and cortisol concentrations at baseline, 1, 2, 3, 4, 6, 16, and 24 h after administration.

Statistical Analysis

Differences with respect to baseline were calculated for vital signs and subjective effects, and maximum effects and time needed to reach maximum effects were calculated for 2C-B and cortisol oral fluid concentrations over time.

The statistical analysis presented was performed without considering the influence of dose and gender, and a detailed comparison between different time points was performed by means of a one-way repeated measures ANOVA, with time condition as factor.

A one-way repeated measures ANOVA was performed with time condition as factor. A Dunnett post hoc test was performed to compare 2 and 6 h with baseline.

Participants

A total of 16 healthy subjects participated in the study. They had a mean age of 33.25 3.7 years, weighed 63.81 11.59 kg, and had a mean body mass index of 21.69 kg/m2.

Vital Signs/Physiological Effects

Changes in vital signs/physiological outcomes were shown in Table 1 and Figure 1A. Maximum effects were +19 mmHg, +13 mmHg, and +13 bpm, respectively, for SBP, DBP, and HR.

2C-B produced robust changes in most subjective effects measured by VAS, ARCI, and VESSPA-SEE. The highest scores were obtained for intensity, high, good effects, and different body feeling scales, and the lowest scores were obtained for hallucinations, changes in hearing, and unreal surroundings.

After 2C-B administration, significant changes were observed in all ARCI subscales, except for PCAG (sedation). The most marked increases compared to baseline were found for MBG (euphoria) and A (amphetamine) subscales, and modest increases were detected for LSD (dysphoria and somatic symptoms) and BG (intellectual efficiency and energy) subscales.

2C-B oral fluid concentrations increased rapidly after 2C-B ingestion, reached a peak 1 h after self-administration, and decreased rapidly from 2 to 6 h after ingestion.

Cortisol concentrations increased after 2C-B administration, but decreased abruptly from 3 to 4 h after administration.

DISCUSSION

This study assessed the acute pharmacological effects of 2C-B in a non-controlled setting. It found that 2C-B produces psychedelic-psychostimulant like effects and that self-administration of 2C-B at the narrow dose range studied (10 – 20 mg) in healthy experienced users is relatively safe.

In a non-controlled setting, 2C-B produced moderate increases of blood pressure and heart rate, but lower than those of MDMA, amphetamines, and related compounds administered in controlled conditions.

Subjects under 2C-B effects reported euphoria, activation and a psychedelic experience consisting of a temporary altered state of consciousness. Euphoria was more prominent than perceptual changes, and the mean VAS ratings of liking, good effects, and high were even greater than those determined in experimental conditions for MDMA. 2C-B resulted in increases in the LSD subscale and somatic VAS scales, as well as in increases in rating scores. In contrast, fear and visual hallucinations were not experienced, and sedation was unremarkable.

HRS scores were similar to those reported by recreational psychedelic users, and the highest scores were obtained for intensity, volition and affect subscales.

2C-B produces psychedelic effects such as dizziness, drowsiness, confusion, changes in distances, colors, shapes, lights, different body feelings, different surroundings, unreal body feelings, and unreal surroundings, and visual hallucinations.

The human pharmacokinetics of 2C-B has not yet been fully resolved. However, oral fluid samples can be used to study 2C-B pharmacokinetics, and 2C-B can be detected in oral fluid at very low concentrations up to 16 – 24 h after self-administration.

After 2C-B administration, cortisol concentrations increased slightly, but not significantly. For other serotonergic psychedelics, a market increase in cortisol concentrations has been detected.

The study was open label without a lack of control/placebo, included a small sample of experienced psychedelic drug users, and used a relatively low-moderate dose of 2-C-B. The findings may not apply to other routes of 2C-B administration, and should be extrapolated with caution to the general population.

CONCLUSION

This work presents a preliminary approach to the acute physiological and subjective effects and pharmacokinetics of 2C-B. The results suggest that 2C-B induces psychedelic/psychostimulant like effects in experienced drug users.

FUNDING

This work was supported by several projects and grants, including the Plan Nacional Sobre Drogas, 2009I047) and the Suport Grups de Recerca AGAUR-Gencat.