Microdosing

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Microdosing (rare in German translation microdosing ) describes the use of drugs or hallucinogenic drugs in extremely small doses . According to the dose-response relationship , some effects and side effects practically do not occur. Microdosing is used in the development of medicinal substances and in private settings by taking very low doses of hallucinogens that are barely perceptible in their effects.

Microdosing in drug development

Considerations for microdosing in the pharmaceutical industry and in medical circles began in the mid-1990s. By microdosing, typically the administration of one hundredth of the known and usual dosage, the distribution of drugs in the organism ( pharmacokinetics ) and certain effects of the drug, e.g. B. which receptors are occupied ( pharmacodynamics ) can be investigated with negligible side effects.

In 2006 the European Medicines Agency (EMEA) set the framework for clinical studies with microdosing in humans. The aim is to reduce or even avoid animal experiments, to estimate side effects in humans by extrapolation, and to achieve more effective drug development. The US Food and Drug Administration FDA issued similar guidelines. In the clinical context, microdosing is referred to as a "sub-therapeutic phase 0", in contrast to phase 1, in which a significantly higher effective dose is given. In order to follow the behavior of a microdose in the organism, highly sensitive measuring methods developed in recent years, some of which use radioactively labeled molecules, are used. In the meantime, some basic experimental studies (using molecules / pharmaceuticals that are well known in terms of their properties) have been carried out, in which it has been shown that minimal amounts of these molecules behave practically identically in the human organism as larger amounts. This shows that the microdosing method in the testing of pharmaceuticals is likely to have a brighter future.

Microdosing of hallucinogens

There is a trend from Silicon Valley to take the (illegal) drug LSD about twice a week in very small amounts in order to increase creativity and concentration and to reduce some psychiatric symptoms such as anxiety and depression or ADHD . Some users (“microdosers”) also report that it is easier to stop taking psychotropic drugs, e. B. Antidepressants. However, apart from a few rather vague reports from individuals, there is no scientific evidence to date to support these alleged effects. Studies of the kind undertaken in the 1950s and 1960s with small and very small doses of LSD tend to show disruptive effects on concentration and other mental abilities, also with regard to creativity. Most "microdosers" hardly report any side effects; on the other hand, however, disruptive effects on perception and mental abilities as well as depressive reactions and sleep disorders have been repeatedly described, especially when used over a period of weeks / months. The trend has now also arrived in Europe, typically in creative professions, for example in advertising agencies.

It is important to distinguish between three forms of so-called microdosing of hallucinogens. All three forms are documented in Internet entries as "microdosing". 1. The ingestion of a very low dose of a hallucinogen such as LSD (5–15 micrograms orally) or psilocybin (2–3 mg orally), with which no effect is noticeable, but is supposed to occur; 2. the regular intake of the aforementioned very low doses every three days for a period of weeks; 3. Taking small doses that produce a noticeable effect (such as 20–50 micrograms orally of LSD or 4–6 mg of psilocybin orally). This was also known as mini dosing . It is also important to distinguish between these three forms, as everything is often dealt with under the name microdosing and therefore very different forms of administration are thrown together. This of course makes it difficult or impossible to record and assess possible effects.

In addition to the early studies discussed above, only a few survey studies have addressed this phenomenon in the past two years. For example, the English Beckley Foundation and the Imperial College have been investigating since 2018 whether the reported effects of microdosing could be based on a placebo effect. Because of their generally more error-prone methodology, the conclusiveness of survey studies is limited.

A study (2019) that was carried out according to strict methodological standards and largely excluded placebo effects examined the effects of placebo administration in comparison with 5, 10, 15 and 20 micrograms of LSD ( per os ) in more than 50 healthy test subjects. No subjective effects above the random probability were found at any of the doses mentioned, but a significantly changed short-term perception was observed compared to the control group . The prolongation of the reproductive time of time intervals observed in the experiment is associated with increased attention and improved working memory. So far, regular administration of microdoses, e.g. B. every three days for several weeks. The latter study, however, also examined the (possible) effects of six doses every three days for a total of 18 days. However, these results have not yet been published. In summary, the state of research with regard to the possible effects of microdosing appears to be ambiguous.

literature

Individual evidence

  1. ^ A b G. Lappin: Microdosing: current and the future. In: Bioanalysis. Volume 2, number 3, March 2010, pp. 509-517, doi : 10.4155 / bio.09.177 , PMID 21083258 .
  2. ↑ T. Burt, K. Yoshida, G. Lappin, L. Vuong, C. John, SN de Wildt, Y. Sugiyama, M. Rowland: Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development. In: Clinical and translational science. Volume 9, Number 2, April 2016, pp. 74-88, doi : 10.1111 / cts.12390 , PMID 26918865 , PMC 5351314 (free full text).
  3. ^ M. Bergstrom: The Use of Microdosing in the Development of Small Organic and Protein Therapeutics. In: Journal of Nuclear Medicine . Volume 58, number 8, 08 2017, pp. 1188–1195, doi : 10.2967 / jnumed.116.188037 , PMID 28546333 .
  4. ^ European Medicines Agency: EMEA concept paper. (PDF) Retrieved March 8, 2019 .
  5. ^ AT Wotherspoon, M. Safavi-Naeini, RB Banati: Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety. In: Bioanalysis. Volume 9, number 23, December 2017, pp. 1913-1933, doi : 10.4155 / bio-2017-0137 , PMID 29171759 .
  6. ↑ T. Burt, CS John, JL Ruckle, LT Vuong: Phase-0 / microdosing studies using PET, AMS, and LC-MS / MS: a range of study methodologies and conduct considerations. Accelerating development of novel pharmaceuticals through safe testing in humans - a practical guide. In: Expert opinion on drug delivery. Volume 14, number 5, May 2017, pp. 657-672, doi : 10.1080 / 17425247.2016.1227786 , PMID 27564533 .
  7. ^ Passie, Torsten .: Science of Microdosing Psychedelics. Psychedelic Press, 2018, ISBN 0-9928088-8-X .
  8. ↑ Johanna Kuroczik: Drugs kick for the office . In: sueddeutsche.de . 2019, ISSN  0174-4917 ( sueddeutsche.de [accessed on March 8, 2019]).
  9. ↑ J. Fadiman, S. Korb: Might Microdosing Psychedelics Be Safe and Beneficial? An initial exploration. In: Journal of psychoactive drugs. [Electronic publication before printing] March 2019, doi : 10.1080 / 02791072.2019.1593561 , PMID 30925850 .
  10. ^ V. Polito, RJ Stevenson: A systematic study of microdosing psychedelics. In: PLOS ONE . Volume 14, number 2, 2019, p. E0211023, doi : 10.1371 / journal.pone.0211023 , PMID 30726251 , PMC 6364961 (free full text).
  11. ↑ T. Anderson, R. Petranker, D. Rosenbaum, CR Weissman, LA Dinh-Williams, K. Hui, E. Hapke, NA Color: Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. In: Psychopharmacology. Volume 236, Number 2, February 2019, pp. 731-740, doi : 10.1007 / s00213-018-5106-2 , PMID 30604183 .
  12. ↑ Courtney Garner: LSD microdosing: is it a placebo or does it improve cognition function and wellbeing? In: SciTech Europe. September 3, 2018, Retrieved March 8, 2019 (UK English).
  13. ↑ Steliana Yanakieva, Naya Polychroni u. a .: The effects of microdose LSD on time perception: a randomized, double-blind, placebo-controlled trial. In: Psychopharmacology. 236, 2019, p. 1159, doi : 10.1007 / s00213-018-5119-x .