Assessment of the Acute Effects of 2C‐B vs. Psilocybin on Subjective Experience, Mood, and Cognition

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.

Synthesis and Structure–Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist

“…Despite encouraging anecdotal human data and some academic explorations, there was little focus on drug development of 2C-X phenethylamines. However, the potential value of this series may be illustrated by the recent report showing that a psychedelic oral dose of 2C-B (20 mg) tends to produce fewer experiences of anxious ego dissolution and cognitive impairment than psilocybin; these differences support earlier drug discrimination studies in rats, wherein 2-(2,5-dimethoxy-4-(propylthio)­phenyl)­ethan-1-amine (2C-T-7) and mescaline did not fully substitute for LSD and psilocybin, , yet 2C-T-7 fully substituted for the discriminative stimulus cue of the psychedelic phenylalkylamine 1-(2,5-dimethoxy-4-methylphenyl)­propan-2-amine (DOM) …”

Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis

“…A total of 21 studies ( n = 553) investigated memory performance under the influence of ayahuasca 79 , DOM 83 , 84 , LSA 72 , LSD 74 , 75 , 82 , 85 – 92 , 2C-B 93 and psilocybin 71 – 73 , 93 – 96 , utilizing 22 distinct memory tests. The majority of studies (1 LSA, 3 psilocybin, 6 LSD, 1 DOM) 72 – 74 , 82 , 84 , 85 , 88 – 90 , 95 , 96 did not show any acute effects of psychedelics on memory across fifteen tasks.…”

“…Twenty-four studies ( n = 503) applied 27 distinct tasks to assess the acute effects of Ayahuasca 79 , 97 , 98 , 2C-B 93 , LSD 80 , 81 , 87 – 89 , 99 – 107 , mescaline 108 and psilocybin 71 , 93 , 109 – 112 on executive functioning. Sixteen of the included studies (1 2C-B, 6 psilocybin, 10 LSD) 71 , 81 , 87 , 88 , 93 , 99 – 104 , 107 , 109 – 112 reported impaired executive functions across 19 tasks, while twelve studies (2 psilocybin, 3 ayahuasca, 7 LSD) 71 , 79 , 80 , 87 , 89 , 97 – 99 , 101 , 105 , 106 , 111 reported no effects across 15 tasks. Additionally, five studies (2 ayahuasca, 2 LSD, 1 mescaline) 79 , 97 , 99 , 101 , 108 showed improved performance across six tests.…”

“…Twenty-three studies ( n = 291) investigated the acute effects of DMT 69 , 77 , 78 , 113 , 2C-B 93 , mescaline 114 , LSD 74 , 80 , 81 , 90 , 115 – 118 , and psilocybin 70 , 76 , 93 , 95 , 109 , 119 – 123 , utilizing 18 distinct attention tasks. Among these studies, fifteen (2 DMT, 1 2C-B, 10 psilocybin, 3 LSD) 69 , 70 , 76 , 77 , 93 , 95 , 109 , 116 – 123 reported impaired attentional performance in 17 tasks, while nine studies (2 DMT, 6 LSD, 1 mescaline) 74 , 78 , 80 , 81 , 90 , 113 – 116 reported no effect across eleven tasks.…”

Cardiovascular safety of psychedelic medicine: current status and future directions

“…Data from clinical trials on the therapeutic use of mescaline are scarce. A recent study compared the immediate acute subjective, cognitive, and cardiovascular effects of 2,5-dimethoxy-4-bromophenethylamine (2C-B), a mescaline-derived hallucinogenic phenethylamine, with psilocybin in a group of 11 women [134]. The participants were given 20 mg of 2C-B, 15 mg of psilocybin, or a placebo on three separate occasions.…”