Assessment of the Acute Effects of 2C‐B vs. Psilocybin on Subjective Experience, Mood, and Cognition
Pablo Mallaroni, Riccardo Paci, Sabrina Ritscher, Natasha L. Mason, Johannes T. Reckweg, Stefan W. Toennes, Eef L. Theunissen, Kim P. C. Kuypers, Johannes G. Ramaekers
Clinical Pharmacology & Therapeutics May 30, 2023 DOI: 10.1002/cpt.2958 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subjects, double-blind, placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Healthy psychedelic-experienced participants |
| Interventions | psilocybin placebo |
| Dose | 20 mg 2C-B, 15 mg psilocybin |
| Topics | Mescaline Psilocybin Serotonin |
| Keywords | Hallucinogen Placebo Cognition Mood Anhedonia Audiology Developmental psychology Clinical psychology |
| Citations | 34 |
| Key points | 2C‐B acts as a psychedelic of moderate experiential depth, with shorter duration and less dysphoria and ego dissolution than psilocybin, but similar psychomotor and memory impairments and pressor effects. |
Abstract
2,5‐dimethoxy‐4‐bromophenethylamine (2C‐B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C‐B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within‐subjects, double‐blind, placebo‐controlled study of 22 healthy psychedelic‐experienced participants. 2C‐B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C‐B induced transient pressor effects to a similar degree as psilocybin. The duration of self‐reported effects of 2C‐B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C‐B as a psychedelic of moderate experiential depth at doses given. Tailored dose‐effect studies are needed to discern the pharmacokinetic dependency of 2C‐B's experiential overlaps.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 27
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
- Psilocybin’s effects on cognition and creativity: A scoping review Journal of Psychopharmacology July 1, 2023
- Psilocybin for major depressive disorder: a systematic review of randomized controlled studies Frontiers in Psychiatry September 23, 2024
- Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis Clinical Pharmacokinetics 2025
- Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis. Scientific Reports June 26, 2024
and 22 more in the library
Cites 46
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 2000
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Psychopharmacology March 1, 2004
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine February 1, 2023
and 41 more in the library