High dose psilocybin is associated with positive subjective effects in healthy volunteers

Nicholas, Christopher R.; Henriquez, Kelsey M.; Gassman, Michele; Cooper, Karen M.; Müller, Daniel; Hetzel, Scott; Brown, Randall; Cozzi, Nicholas V.; Thomas, Chantelle; Hutson, Paul R.

doi:10.1177/0269881118780713

Cited by 67 publications

(60 citation statements)

References 39 publications

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“…Similarly as on the 5D-ASC scale, quality and extent of ratings on the MEQ did not significantly differ between several doses of LSD doses in patients in the compassionate use group. In contrast, hallucinogen dose strongly predicted mystical-type experiences (Lyvers and Meester, 2012; Studerus et al, 2012) and a dose response in MEQ total score was observed in healthy participants after psilocybin (Nicholas et al, 2018). With regard to the extent of mystical-type experiences and acute alterations of consciousness, the present data suggest that lower doses of LSD could be used to achieve similar acute effects in this setting.…”

Section: Discussionmentioning

confidence: 91%

“…Nonetheless, LSD produced a numerically higher proportion of complete mystical experiences in the compassionate use group than in healthy volunteers and in patients in the laboratory setting. Positive long-term effects of hallucinogens have been associated with their ability to acutely induce profound insights and mystical-type experiences (Nicholas et al, 2018; Schmid and Liechti, 2018), but whether these and which particular aspects of mystical-type experiences are critical for a possible therapeutic effect needs further evaluation. Similarly as on the 5D-ASC scale, quality and extent of ratings on the MEQ did not significantly differ between several doses of LSD doses in patients in the compassionate use group.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, LSD and MDMA acutely induce prosocial effects, which may be beneficial during substance-assisted psychotherapy. Additionally, hallucinogen-induced mystical-type experiences have been associated with persisting positive changes in healthy volunteers (Griffiths et al, 2006, 2008, 2018; Nicholas et al, 2018; Schmid and Liechti, 2018;) and patients (Garcia-Romeu et al, 2015, 2019; Griffiths et al, 2016), and acute substance-induced effects may mediate persisting therapeutic effects (Griffiths et al, 2016). While the research subjects were tested alone in the clinical studies, therapy sessions are conducted in a group setting in the Swiss compassionate use programme.…”

Section: Introductionmentioning

confidence: 99%

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Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Schmid

Gasser

Oehen³

et al. 2020

J Psychopharmacol

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Background: Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) were used in psychotherapy in the 1960s–1980s, and are currently being re-investigated as treatments for several psychiatric disorders. In Switzerland, limited medical use of these substances is possible in patients not responding to other treatments (compassionate use). Methods: This study aimed to describe patient characteristics, treatment indications and acute alterations of mind in patients receiving LSD (100–200 µg) and/or MDMA (100–175 mg) within the Swiss compassionate use programme from 2014–2018. Acute effects were assessed using the 5 Dimensions of Altered States of Consciousness scale and the Mystical Experience Questionnaire, and compared with those in healthy volunteers administered with LSD or MDMA and patients treated alone with LSD in clinical trials. Results: Eighteen patients (including 12 women and six men, aged 29–77 years) were treated in group settings. Indications mostly included posttraumatic stress disorder and major depression. Generally, a drug-assisted session was conducted every 3.5 months after 3–10 psychotherapy sessions. LSD induced pronounced alterations of consciousness on the 5 Dimensions of Altered States of Consciousness scale, and mystical-type experiences with increases in all scales on the Mystical Experience Questionnaire. Effects were largely comparable between patients in the compassionate use programme and patients or healthy subjects treated alone in a research setting. Conclusion: LSD and MDMA are currently used medically in Switzerland mainly in patients with posttraumatic stress disorder and depression in group settings, producing similar acute responses as in research subjects. The data may serve as a basis for further controlled studies of substance-assisted psychotherapy.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Schmid

Gasser

Oehen³

et al. 2020

J Psychopharmacol

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“…Studies that only reported post-treatment data without a baseline measurement or a relevant control group (e.g. persisting effects at post-treatment for a single-group design; Nicholas et al, 2018) were excluded. Principal investigators of completed clinical trials were contacted regarding available results.…”

Section: Methodsmentioning

confidence: 99%

Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

et al. 2020

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Background Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias. Methods We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain. Results A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects. Conclusions High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

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“…Clinical trials in recent years have shown that oral doses of the psychedelic compound psilocybin, the 4‐phosphoryl ester of N,N ‐dimethyltryptamine (DMT), via its active metabolite psilocin (4‐hydroxy‐DMT), produces persistent positive psychological effects and has value as a psychotherapeutic agent for anxiety and depression 1–4 . However, the relatively gradual approach to peak effects (90–120 min for oral dosing) and the 5–8 h duration of action requires the commitment of trained clinical staff to attend the patient or experimental subject for at least the entire acute phase 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

Cozzi

Daley²

2020

Drug Testing and Analysis

Self Cite

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Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4-phosphoryl ester of N,Ndimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT-containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorders require high-purity water-soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2-(1Hindol-3-yl)-N,N-dimethyl-2-oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatographymass spectrometry (GC-MS), 1 H and 13 C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, residual solvent analysis by GC headspace sampling, X-ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma-mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.

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High dose psilocybin is associated with positive subjective effects in healthy volunteers

Abstract: High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

Cited by 67 publications

References 39 publications

Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

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