Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology

Hartogsohn, Ido

doi:10.1177/0269881116677852

Cited by 324 publications

(290 citation statements)

References 96 publications

(115 reference statements)

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“…Changes in the ratings of subjective measures that were observed in the present study are not necessarily related to a pharmacological effect of 5-MeO-DMT, but could have resulted from uncontrolled variables such as response expectancy of the participants prior to and after the session or the set and setting of drug administration (Carhart-Harris et al 2018;Hartogsohn 2016). Yet, the finding that the strength of actual psychedelic experience was positively correlated to changes in non-judgment and negatively correlated with symptoms of depression, stress and anxiety strongly suggest that the inhalation of 5-MeO-DMT contributed to changes in these subjective measures.…”

Section: Discussionmentioning

confidence: 68%

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Lancelotta²,

et al. 2019

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Rationale 5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce. Objectives The first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1β), as well as the acute psychedelic experience. Methods Assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Results 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment. Conclusion Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,Ndimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.

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Section: Discussionmentioning

confidence: 68%

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Lancelotta²,

et al. 2019

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“…Personality has previously been associated with response to psychedelics (Studerus et al, 2012; Hartogsohn, 2016; Barrett et al, 2017). For example, trait ‘absorption’ has been shown to be predictive of sensitivity to psychedelics (Studerus et al, 2012), and the same has also been shown in relation to the intensity of ‘actual’ NDEs (Twemlow and Gabbard, 1984).…”

Section: Discussionmentioning

confidence: 99%

DMT Models the Near-Death Experience

et al. 2018

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Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.

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“…One possible interpretation of these results is that participants felt more fatigued by the setting of the study under the influence of LSD, as they were sitting in their beds the whole day. Supporting this interpretation, a review of historical LSD research indicates that study results appear to be highly influenced by the setting of the study (Hartogsohn 2016), and recent research has shown heightened suggestibility under the drug (Carhart- Harris et al 2015) that may enhance the suggestion of "feeling sleepy" as the participants were confined to a bed throughout the day. Furthermore, the increase in vigilance reduction was not observed in participants in Bershad et al (2019), discussed below.…”

Section: Discussionmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

Family¹,

Maillet²,

Williams³

et al. 2019

Psychopharmacology

104

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Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT 2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease. Objective This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response. Methods This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).Results Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment. Conclusions Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer's disease (AD).

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Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology

Cited by 324 publications

References 96 publications

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

DMT Models the Near-Death Experience

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

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