Dosing Psychedelics and MDMA

Liechti, Matthias E.; Holze, Friederike

doi:10.1007/7854_2021_270

Cited by 18 publications

(15 citation statements)

References 84 publications

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“…After oral administration of 160 μg of LSD, the blood concentration of the substance was observed to be 4.16 ng/mL two hours later [ 22 ]. Similar results were obtained later [ 23 , 24 ], allowing an approximation of the maximum amount taken of more than 1.5 mg. For the eight reported patients in 1972, this is 7 times the maximum effective dose (250 μg [ 25 ]), which would presuppose moderate-severe intoxication. However, all patients survived with no adverse health consequences.…”

Section: Resultsmentioning

confidence: 99%

“…Second, the metabolites generated in the metabolization of the drug cause an inhibition of CYP2D6, which is the main MDMA-metabolizing enzyme, exposing the individual to drug intoxication and overdose of MDMA itself, in the case of repeated ingestions [ 40 ]. The effective oral dose in humans is 1–2 mg/kg [ 17 , 25 ]. Even at moderate doses, there are a number of potential health risks including cerebral hyperthermia, hyponatremia, or disseminated intravascular coagulation.…”

Section: Resultsmentioning

confidence: 99%

“…For the human species, 30–40 mg is considered to be a high dose of psilocybin [ 25 ], which, in comparison with the data reported in animals, suggests that we are a particularly sensitive species. the TDL 0 was established at 60 and 37 µg/kg orally and intraperitoneally, respectively, in a group of 16 volunteer subjects tested in 1960 [ 73 ].…”

Section: Resultsmentioning

confidence: 99%

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Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

Hernández

Rojas-Hernández

Quintana-Hernández

et al. 2023

Toxics

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Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

Hernández

Rojas-Hernández

Quintana-Hernández

et al. 2023

Toxics

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“…The R-syntax of this analysis is available on GitHub: https://github.com/TimHirschfeld/doseresponse_LSD. Blissful State, Insightfulness, and Changed Meaning of Percepts [28], but significantly higher rating scores for 200 µg compared to 100 µg on the scale Dread of Ego Dissolution (reflecting disembodiment and fear) [28], indicating a ceiling effect regarding positive subjective effects [65]. Despite considerable variability of effects, the present meta-analysis supports the suggestion that doses between 50 and 100 µg LSD base induce substantial psychological effects in most subjects -a dosage range currently used in most current clinical trials for therapeutic applications [65].…”

Section: Statistical Analysesmentioning

confidence: 99%

Dose-response relationships of LSD-induced subjective experiences in humans

Prugger

Hirschfeld

Majić

et al. 2022

Preprint

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Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the phenomenological states induced by LSD. Data extracted from articles identified by a systematic literature search following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We used a meta-regression approach to obtain estimates for linear dose-response relationships of questionnaire ratings after LSD administration to healthy, highly selected study participants in controlled settings for a dosage range between 25 μg and 200 μg. LSD doses positively correlated with ratings on most factors and scales of the questionnaires, with strongest responses for visionary phenomena such as audio-visual synesthesia and altered imagery, followed by positively perceived ego dissolution comprising depersonalization and derealization phenomena. Measures referring to mystical experiences exhibited weak modulations by dose. The established dose-response relationships in the given range may be used as general references for future experimental and clinical research on LSD with low to moderate dosages to relate observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.

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“…To an existing ketamine treatment regimen of an ambulatory anesthesiological day clinic for patients suffering from depression, we added a new enhanced scale to measure altered states of consciousness (ASCs)—the Altered State of Consciousness Inventory (ASCI) ( Reissmann et al, 2022 )—and the Beck Depression Inventory II (BDI-II) ( Beck et al, 2009 ). Regarding the dosing regimen, the dose level and frequency for the ketamine infusion were adjusted individually in close consultation with the patient with the overall goal to maximize antidepressant benefit—a novel dose regimen that we term personalized antidepressant dosing [for more general aspects on personalized dosing with psychedelics see Liechti and Holze (2021) ]. Regarding the measurement of opposite diminishing and non-judging, answers to the two questionnaire items of the ASCI for these concepts were analyzed to see if they relate to the BDI-II scores in the predicted ways.…”

Section: Introductionmentioning

confidence: 99%

Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study

Stocker

Hartmann²,

Reissmann

et al. 2022

Front. Pharmacol.

Self Cite

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Background: Cognition that is not dominated by thinking in terms of opposites (opposite diminishing) or by making judgments (non-judging) can be found both in Buddhist/mindfulness contexts and in mental states that are fostered by dissociative psychedelics (N-methyl-D-aspartate antagonists) such as ketamine. Especially for the Buddhist/mindfulness case, both opposite diminishing and non-judging have been proposed to relate to mental well-being. Whether ketamine-occasioned opposite diminishing and/or non-judging relate to increased mental well-being in the form of antidepressant response is unknown, and was investigated in the present study.Methods: In this open-label outpatient study, the dose level and frequency for the ketamine infusions were adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits—a novel dose regimen that we term personalized antidepressant dosing. In general, treatment started with an initial series of ketamine infusions with a dosage of 0.5 mg/kg body weight and was then adjusted (usually increased). A possible relationship between ketamine-induced antidepressant benefits and retrospectively reported peri-infusion experiences of opposite diminishing and non-judging was assessed based on a total of 45 ketamine-infusion treatment sessions from 11 different patients suffering from depression. Opposite diminishing and non-judging were measured with the two items from the Altered States of Consciousness Inventory (ASCI) that measure these concepts. Depression was measured with the Beck Depression Inventory (BDI-II).Results: Peri-infusion experiences of both opposite diminishing and non-judging were associated with antidepressant responses confirming our hypothesis. Furthermore, opposite diminishing and non-judging were closely related to one another while relating to antidepressant response in distinguishable ways.Conclusion: Future controlled randomized trials with dissociative and other psychedelics and with a larger number of participants are needed to establish the possible link of psychedelically induced opposite diminishing and non-judging with an antidepressant response more firmly.

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Dosing Psychedelics and MDMA

Cited by 18 publications

References 84 publications

Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

Dose-response relationships of LSD-induced subjective experiences in humans

Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study

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