Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial

Rotz, Robin von; Schindowski, Eva M; Jungwirth, Johannes; Schuldt, Anna; Rieser, N.; Zahoranszky, Katharina; Seifritz, Erich; Nowak, Albina; Nowak, Peter; Jäncke, Lutz; Preller, Katrin H.; Vollenweider, Franz X.

doi:10.1016/j.eclinm.2022.101809

Cited by 154 publications

(140 citation statements)

References 24 publications

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“…Magnitudes of change were also appreciably lesser than those observed following the administration of MDMA and related amphetamines 40,95,96 . Whereas no differences in HR were observed for 15 mg psilocybin as previously described for similar doses 9,39,97,98 , we did not replicate the prior finding of elevated HR under 2C-B 35 , likely as a result of differing subject inclusion criteria. These preliminary findings therefore cautiously indicate that the 15 mg psilocybin and 20 mg 2C-B hold similar cardiovascular effects.…”

Section: Discussioncontrasting

confidence: 99%

Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition

Mallaroni

Mason

Reckweg

et al. 2023

Preprint

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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.

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Section: Discussioncontrasting

confidence: 99%

Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition

Mallaroni

Mason

Reckweg

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Magnitudes of change were also appreciably less than those observed following the administration of MDMA and related amphetamines 28 . Despite heart rate being significantly less under psilocybin than 2C‐B, no differences were observed for 15 mg psilocybin relative to placebo, as previously described for similar doses 2,25,46 In addition, we did not replicate the prior finding of elevated heart rate under 2C‐B, 22 likely as a result of differing subject inclusion criteria. Thus, given neither drug generated notable differences in relation to placebo, these preliminary findings therefore cautiously indicate that the 15 mg psilocybin and 20 mg 2C‐B hold similar cardiovascular effects.…”

Section: Discussioncontrasting

confidence: 69%

“…Classical psychedelics are a diverse set of psychoactive compounds characterized by their capacity to elicit profound alterations in waking consciousness, comprising changes to mood, cognition, and self‐referential awareness 1 . Preliminary evidence that compounds, such as psilocybin, are safe and efficacious treatments for neuropsychiatric disorders, such as major depressive disorder has fostered a renewed interest in their effects 2 …”

mentioning

confidence: 99%

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

Mallaroni

Mason

Reckweg

et al. 2023

Clin Pharma and Therapeutics

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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.

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“…This, along with prior experiences, introduces different types of selection biases. For example, inclusion criteria of a recent study were right-handedness, mild to moderate depressive symptoms without psychotic features, abstinence from medication, drugs and alcohol (including tapering-off anti-depressant medication, a challenge for many patients), good physical health, and no suicide risk (von Rotz et al, 2023). As a consequence, only very selective groups of patients are eligible for participating in these studies.…”

Section: Selection Biasmentioning

confidence: 99%

“…Despite these threats, the breaking blind problem is largely ignored in the literature, as evidenced by the fact that researchers rarely report on masking efficacy, i.e., the extent to which blinding was preserved (for systematic review, see: Muthukumaraswamy et al, 2021). For example, the very recently published, first placebo-controlled, double-blind RCT for psilocybin-assisted therapy in MDD (von Rotz et al, 2023) went through considerable efforts to mask treatment allocation, but did not assess or report whether blinding was successful. However, given that the authors' analyses reveal massive differences between groups in their subjective experiences (including oceanic boundlessness, anxious ego dissolution, auditory alterations, impaired cognition and control, and disembodiment), the study is clearly not double blind, and should not have been published as such.…”

Section: The Breaking Blind Problemmentioning

confidence: 99%

History repeating: A roadmap to address common problems in psychedelic science

Elk¹,

Fried²

2023

Preprint

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Research in the last decade has expressed considerable optimism about the clinical potential of psychedelics for the treatment of mental disorders. This optimism is reflected in a considerable increase in research papers, investments by pharmaceutical companies, patents, media coverage, as well as political and legislative changes. However, psychedelic science is facing serious challenges that threaten the validity of core findings and raise doubt regarding clinical efficacy and safety. In this paper, we introduce the 10 most pressing challenges, grouped into easy, moderate, and hard problems. We show how these problems threaten internal validity (treatment effects are due to factors unrelated to the treatment), external validity (lack of generalizability), construct validity (unclear working mechanism) or statistical conclusion validity (conclusions do not follow from the data and methods). These problems tend to co-occur in psychedelic studies, strongly limiting conclusions that can be drawn about the safety and efficacy of psychedelic therapy. We provide a roadmap for tackling these challenges in the next decade of psychedelic science, and share a checklist that researchers, journalists, funders, policy makers, and other stakeholders can use to assess the quality of psychedelic science. Addressing today’s problems is necessary to find out whether the optimism regarding the potential of psychedelics has been warranted and to avoid history repeating itself.

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Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial

Cited by 154 publications

References 24 publications

Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition

Assessment of the acute effects of 2C-B vs psilocybin on subjective experience, mood and cognition

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

History repeating: A roadmap to address common problems in psychedelic science

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