OPEN Foundation

M. Pujadas

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

March 13, 2018 / New substances, Other substances, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

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. 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. 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. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.
Papaseit, E., Farré, M., Perez-Maña, C., Torrens, M., Ventura, M., Pujadas, M., … & González, D. (2018). Acute pharmacological effects of 2C-B in humans: An observational study. Frontiers in Pharmacology, 9, 206. 10.3389/fphar.2018.00206
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MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

July 11, 2017 / MDMA, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , , ,

Abstract

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.
Puxty, D. J., Ramaekers, J. G., de la Torre, R., Farré, M., Pizarro, N., Pujadas, M., & Kuypers, K. P. (2017). MDMA-induced dissociative state not mediated by the 5-HT2A receptor. Frontiers in pharmacology, 8, 455. 10.3389/fphar.2017.00455
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Human Pharmacology of Mephedrone in Comparison to MDMA

May 20, 2016 / Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Publications, Safety, Toxicology / By / , , , , , ,

Abstract

Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-metylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone, and its relative abuse liability, compared to MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentrations values for mephedrone and MDMA peaked at 1.25 and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by users.

Papaseit, E., Pérez-Mañá, C., Mateus, J. A., Pujadas, M., Fonseca, F., Torrens, M., … & Farré, M. (2016). Human Pharmacology of Mephedrone in Comparison to MDMA. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. http://dx.doi.org/10.1038/npp.2016.75
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30 April - Q&A with Rick Strassman

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