Microdosing

The basic approach is to label a candidate drug using the radio isotope carbon-14,{{cite journal | vauthors = Babin V, Taran F, Audisio D | title = Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges | journal = JACS Au | volume = 2 | issue = 6 | pages = 1234–1251 | date = June 2022 | pmid = 35783167 | pmc = 9241029 | doi = 10.1021/jacsau.2c00030 }} then administer the compound to human volunteers at levels typically about 100 times lower than the proposed therapeutic dosage (from around 1 to 100 micrograms but not above).{{cn|date=May 2024}}

As only microdose levels of the drug are used, analytical methods are limited. Extreme sensitivity is needed. Accelerator mass spectrometry (AMS) is the most common method for microdose analysis. AMS was developed in the late 1970s from two distinct research threads with a common goal:{{Cite journal |last=Kutschera |first=Walter |date=2023 |title=An overview of world-wide AMS facilities |journal=Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms |volume=538 |pages=87–94 |doi=10.1016/j.nimb.2023.02.016 |bibcode=2023NIMPB.538...87K |url=https://www.sciencedirect.com/science/article/abs/pii/S0168583X23000526|url-access=subscription }} an improvement in radiocarbon dating that would make efficient use of datable material and that would extend the routine and maximum reach of radiocarbon dating. AMS is routinely used in geochronology and archaeology,{{Cite web |date=2015-04-14 |title=Accelerator Mass Spectrometry, C14 Dating, What is AMS? |url=https://www.radiocarbon.com/accelerator-mass-spectrometry.htm |access-date=2023-05-31 |website=Carbon Dating Service, AMS Miami - Beta Analytic |language=en}} but biological applications began appearing in 1990 mainly due to the work of scientists at Lawrence Livermore National Laboratory. AMS service is now more accessible for biochemical quantitation from several private companies and non-commercial access to AMS is available at the National Institutes of Health (NIH) Research Resource at Lawrence Livermore National Laboratory,{{cite journal | vauthors = Broek TA, Ognibene TJ, McFarlane KJ, Moreland KC, Brown TA, Bench G | title = Conversion of the LLNL/CAMS 1 MV biological AMS system to a semi-automated natural abundance ¹⁴C spectrometer: system optimization and performance evaluation | journal = Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms| volume = 499 | pages = 124–132 | date = July 2021 | pmid = 38344059 | pmc = 10854407 | doi = 10.1016/j.nimb.2021.01.022 | bibcode = 2021NIMPB.499..124B | publication-date = 2021-05-21 }} or through the development of smaller affordable spectrometers. AMS does not measure the radioactivity of carbon-14 in microdose samples. AMS, like other mass spectrometry methods, measures ionic species according to mass-to-charge ratio.

{{main|Psychedelic microdosing}}

Psychedelic microdosing is the practice of using sub-threshold doses (microdoses) of serotonergic psychedelic drugs in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction,{{cn|date=January 2025}} though there is very little evidence supporting these purported effects as of 2019. {{cite journal | vauthors = Anderson T, Petranker R, Christopher A, Rosenbaum D, Weissman C, Dinh-Williams LA, Hui K, Hapke E | title = Psychedelic microdosing benefits and challenges: an empirical codebook | journal = Harm Reduction Journal | volume = 16 | issue = 1 | pages = 43 | date = July 2019 | pmid = 31288862 | pmc = 6617883 | doi = 10.1186/s12954-019-0308-4 | doi-access = free }}

{{Update|section|date=July 2024}}

In 2021 it was reported in a study done that an increased conscientiousness was seen due to microdosing. {{Cite journal |last1=Dressler |first1=Hannah M. |last2=Bright |first2=Stephen J. |last3=Polito |first3=Vince |date=2021-03-24 |title=Exploring the relationship between microdosing, personality and emotional insight: A prospective study |url=https://akjournals.com/view/journals/2054/5/1/article-p9.xml |journal=Journal of Psychedelic Studies |language=en |volume=5 |issue=1 |pages=9–16 |doi=10.1556/2054.2021.00157|doi-access=free }} Microdosing was seen to have improved mental health after microdosing with psychedelics after 30 days.{{cite journal | vauthors = Rootman JM, Kiraga M, Kryskow P, Harvey K, Stamets P, Santos-Brault E, Kuypers KP, Walsh Z | title = Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls | journal = Scientific Reports | volume = 12 | issue = 1 | pages = 11091 | date = June 2022 | pmid = 35773270 | pmc = 9246852 | doi = 10.1038/s41598-022-14512-3 | bibcode = 2022NatSR..1211091R }} More research is needed to ultimately decide whether or not microdosing helps those who suffer from depression and anxiety. Microdosing has not seen to improve participants motor responses, attention, and cognitive problem-solving abilities. Microdosing is still under investigation as to whether it works or not. Researchers are investigating into microdosing more and more, the placebo effect causes difficulties in research on this topic.{{Cite web |last=MD |first=Peter Grinspoon |date=2022-09-19 |title=The popularity of microdosing of psychedelics: What does the science say? |url=https://www.health.harvard.edu/blog/the-popularity-of-microdosing-of-psychedelics-what-does-the-science-say-202209192819 |access-date=2024-04-16 |website=Harvard Health |language=en}}

In January 2006, the European Union Microdose AMS Partnership Programme (EUMAPP) was launched.{{Cite web|date=|title=European Union Microdose AMS Partnership Programme|url=https://cordis.europa.eu/project/id/18672|archive-url=|archive-date=|access-date=|website=European Commission: CORDIS EU Research Results}} Ten organizations from five different countries (United Kingdom, Sweden, Netherlands, France, and Poland) will study various approaches to the basic AMS technique. The study is set to be published in 2009.{{cite journal | vauthors = Burt T, Yoshida K, Lappin G, Vuong L, John C, de Wildt SN, Sugiyama Y, Rowland M | title = Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development | journal = Clinical and Translational Science | volume = 9 | issue = 2 | pages = 74–88 | date = April 2016 | pmid = 26918865 | pmc = 5351314 | doi = 10.1111/cts.12390 }}

One of the most meaningful potential outcomes of Phase-0/Microdosing studies is the early termination of development. In 2017, Okour et al published the first example in literature of a termination of an oral drug based on IV microdose data.{{cite journal | vauthors = Okour M, Derimanov G, Barnett R, Fernandez E, Ferrer S, Gresham S, Hossain M, Gamo FJ, Koh G, Pereira A, Rolfe K, Wong D, Young G, Rami H, Haselden J | title = A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers | journal = British Journal of Clinical Pharmacology | volume = 84 | issue = 3 | pages = 482–489 | date = March 2018 | pmid = 29168205 | pmc = 5809343 | doi = 10.1111/bcp.13476 }}

• Pharmacology

{{Reflist}}

{{refbegin}}

• {{cite journal | vauthors = Lappin G, Garner RC | title = The use of accelerator mass spectrometry to obtain early human ADME/PK data | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 1 | issue = 1 | pages = 23–31 | date = June 2005 | pmid = 16922650 | doi = 10.1517/17425255.1.1.23 }}
• {{cite journal | vauthors = Wilding IR, Bell JA | title = Improved early clinical development through human microdosing studies | journal = Drug Discovery Today | date = July 2005 | volume = 10 | issue = 13| pages = 890–894 | doi = 10.1016/S1359-6446(05)03509-9 | pmid = 15993808 }}
• {{cite journal | vauthors = Lappin G, Wagner CC, Langer O, van de Merbel N | title = New ultrasensitive detection technologies and techniques for use in microdosing studies | journal = Bioanalysis | volume = 1 | issue = 2 | pages = 357–66 | date = May 2009 | pmid = 21083172 | doi = 10.4155/bio.09.40 }}

{{refend}}

• [http://www.nc3rs.org.uk/downloaddoc.asp?id=339&page=193&skin=0 Review article on microdosing as a means of reducing the use of animals in drug testing (PDF format)] {{Webarchive|url=https://web.archive.org/web/20070928142705/http://www.nc3rs.org.uk/downloaddoc.asp?id=339&page=193&skin=0 |date=2007-09-28 }}
• [http://ec.europa.eu/research/headlines/news/article_06_01_20_en.html EU announcement of EUMAPP project]

Category:Pharmacokinetics

Category:Clinical research

Category:Alternatives to animal testing