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 characterised 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 (15mg) 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 to placebo, as indexed by the Digit Symbol Substitution Test (DSST), Tower of London (TOL) and Spatial Memory Task (SMT). Neither compound produced empathogenic effects on the Multifaceted Empathy Test (MET). 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 categorisation of 2C-B as a subjectively ″lighter″ psychedelic. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B′s experiential overlaps.

Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience

“…The time course of the subjective quality of the psychedelic experience was assessed by tracking mean scores on ASC questions during the dosing session ( Figure 3 ). This time course was comparable to previous studies with psilocybin 55 , peaking about 2 hours after psilocybin administration ( Figure 3A ). Participants administered higher doses of midazolam did not experience a reduction in the magnitude or the duration of elevated ASC scores.…”

Psilocybin’s effects on cognition and creativity: A scoping review

“…measures; 1 negative acute finding was excluded because it followed intravenous psilocybin administration thereby making dosage comparison with oral administration meaningless; and 18 neutral and 7 negative acute findings were excluded because they lacked adequate dosage information. Overall, the excluded acute findings were primarily negative (56%) and neutral (41%) as opposed to positive (4%), thus demonstrating a pattern of outcomes that is consistent with those included in the figure . Effect sizes were reported in four (10%) of the included publications (Mallaroni et al, 2023;Mason et al, 2021;Prochazkova et al, 2018;Vollenweider et al, 2007). Mallaroni et al (2023) reported the following significant negative outcomes with large effect sizes during the acute phase following a 15-mg psilocybin macrodose: increased reaction time on the Tower of London Test 2021) reported significant impairments with large effect sizes during the acute phase following a 0.17 mg/kg psilocybin macrodose for the fluency measure (d = 0.80) on the Alternate Uses Task, and the fluency (d = 0.84) and convergent (d = 0.85) measures on the Picture Concept Task, and significant impairment with a medium effect size for the originality measure (d = 0.65) on the Picture Concept Task (all measures of creativity).…”

“…Overall, the excluded acute findings were primarily negative (56%) and neutral (41%) as opposed to positive (4%), thus demonstrating a pattern of outcomes that is consistent with those included in the figure . Effect sizes were reported in four (10%) of the included publications (Mallaroni et al, 2023;Mason et al, 2021;Prochazkova et al, 2018;Vollenweider et al, 2007). Mallaroni et al (2023) reported the following significant negative outcomes with large effect sizes during the acute phase following a 15-mg psilocybin macrodose: increased reaction time on the Tower of London Test 2021) reported significant impairments with large effect sizes during the acute phase following a 0.17 mg/kg psilocybin macrodose for the fluency measure (d = 0.80) on the Alternate Uses Task, and the fluency (d = 0.84) and convergent (d = 0.85) measures on the Picture Concept Task, and significant impairment with a medium effect size for the originality measure (d = 0.65) on the Picture Concept Task (all measures of creativity). The same study found that at 7-day follow-up, psilocybin resulted in significant impairment with a medium effect size for the convergent measure on the Picture Concept Task (d = 0.60) and significant enhancement with a medium effect size for the novel measure on the Alternate Uses Task (d = 0.52).…”

“…Effect sizes were reported in four (10%) of the included publications ( Mallaroni et al, 2023 ; Mason et al, 2021 ; Prochazkova et al, 2018 ; Vollenweider et al, 2007 ). Mallaroni et al (2023) reported the following significant negative outcomes with large effect sizes during the acute phase following a 15-mg psilocybin macrodose: increased reaction time on the Tower of London Test (a measure of higher-order executive function; d = 1.8), decreased correct ( d = 1.45) and total ( d = 1.5) responses on the Digit Symbol Substitution Test (a measure of lower order executive function), decreased correct responses on the Spatial Memory Test (a measure of lower order executive function) both immediately ( d = 1.34) and 30 minutes ( d = 1.43) following administration, increased reaction time on the Psychomotor Vigilance Task (a measure of foundational cognitive function; d = 0.81), and increased ratings of “impaired control and cognition” (a subjective measure of cognitive function; d = 1.93) on the Five Dimensional Altered States of Consciousness (5D-ASC) scale. Mason et al (2021) reported significant impairments with large effect sizes during the acute phase following a 0.17 mg/kg psilocybin macrodose for the fluency measure ( d = 0.80) on the Alternate Uses Task, and the fluency ( d = 0.84) and convergent ( d = 0.85) measures on the Picture Concept Task, and significant impairment with a medium effect size for the originality measure ( d = 0.65) on the Picture Concept Task (all measures of creativity).…”