Microdosing

Abstract: Objectives: A volunteer trial was performed to compare the pharmacokinetics of 5 drugs-warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin-when administered at a microdose or pharmacologic dose. Each compound was chosen to represent a situation in which prediction of pharmacokinetics from either animal or in vitro studies (or both) was or is likely to be problematic. Methods: In a crossover design volunteers received (1) 1 of the 5 compounds as a microdose labeled with radioactive carbon (carbon 14) (100 I¼g), (2) the corresponding 14C-labeled therapeutic dose on a separate occasion, and (3) simultaneous administration of an intravenous 14C-labeled microdose and an oral therapeutic dose for ZK253, midazolam, and erythromycin. Analysis of 14C-labeled drugs in plasma was done by use of HPLC followed by accelerator mass spectrometry. Liquid chromatography-tandem mass spectrometry was used to measure plasma concentrations of ZK253, midazolam, and erythromycin at therapeutic concentrations, whereas HPLC-accelerator mass spectrometry was used to measure warfarin and diazepam concentrations. Results: Good concordance between microdose and therapeutic dose pharmacokinetics was observed for diazepam (half-life t1/2 of 45.1 hours, clearance CL of 1.38 L/h, and volume of distribution V of 90.1 L for 100 I¼g and t1/2 of 35.7 hours, CL of 1.3 L/h, and V of 123 L for 10 mg), midazolam (t1/2 of 4.87 hours, CL of 21.2 L/h, V of 145 L, and oral bioavailability F of 0.23 for 100 I¼g and t1/2 of 3.31 hours, CL of 20.4 L/h, V of 75 L, and F of 0.22 for 7.5 mg), and development compound ZK253 (F = <1% for both 100 I¼g and 50 mg). For warfarin, clearance was reasonably well predicted (0.17 L/h for 100 I¼g and 0.26 L/h for 5 mg), but the discrepancy observed in distribution (67 L for 100 I¼g and 17.9 L for 5 mg) was probably a result of high-affinity, low-capacity tissue binding. The oral microdose of erythromycin failed to provide detectable plasma levels as a result of possible acid lability in the stomach. Absolute bioavailability for the 3 compounds examined yielded excellent concordance with data from the literature or data generated in house. Conclusion: Overall, when used appropriately, microdosing offers the potential to aid in early drug candidate selection. © 2006 American Society for Clinical Pharmacology and Therapeutics.

Abstract: Background:In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cog...

Abstract: Microdosing psychedelics—the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin—is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses. This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity. In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity. Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = − 0.92) and negative emotionality (p = 0.009, r = − 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls. These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Abstract: IntroductionTaking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.MethodsDuring a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested.ResultsWe found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.ConclusionWhile this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.