Wikipedia

Microdosing

"Microdose" redirects here. Not to be confused withMicrodose (album).

Microdosing,ormicro-dosing,involves the administration of sub-therapeutic doses ofdrugsto study their effects in humans, aiming to gather preliminary data on safety,pharmacokinetics,and potential therapeutic benefits without producing significant physiological effects. This is called a "Phase 0study "and is usually conducted before clinicalPhase Ito predict whether a drug is viable for the next phase of testing. Human microdosing aims to reduce the resources spent on non-viable drugs and the amount of testing done on animals.[1]

Less commonly, the term "microdosing" is also sometimes used to refer to precise dispensing of small amounts of a drug substance (e.g., a powder API) for a drug product (e.g., a capsule)[2]and, when the drug substance also happens to be liquid, this can potentially overlap what is termedmicrodispensing.For example,psychedelic microdosing.[3]

Techniques

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The basic approach is tolabela candidate drug using the radioisotopecarbon-14,[4]then administer the compound to human volunteers at levels typically about 100 times lower than the proposed therapeutic dosage (from around 1 to 100microgramsbut not above).[citation needed]

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:[5]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,[6]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,[7]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.

Psychedelic

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Main article:Psychedelic microdosing

Psychedelic microdosing is the practice of using sub-threshold doses (microdoses) ofserotonergicpsychedelic drugsin an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction,[8]though there is very little evidence supporting these purported effects as of 2019.[9]

Impact of psychedelic microdosing

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In 2021 it was reported in a study done that an increased conscientiousness was seen due to microdosing.[10]Microdosing was seen to have improved mental health after microdosing with psychedelics after 30 days.[11]More research is needed to ultimately decide whether or not microdosing helps those who suffer from depression and anxiety.[11]Microdosing has not seen to improve participants motor responses, attention, and cognitive problem-solving abilities.[11]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.[12]

In January 2006, the European Union Microdose AMS Partnership Programme (EUMAPP) was launched.[13]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.[14]

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.[15]

See also

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References

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  1. ^Burt T, Young G, Lee W, Kusuhara H, Langer O, Rowland M, et al. (November 2020). "Phase 0/microdosing approaches: time for mainstream application in drug development?".Nature Reviews. Drug Discovery.19(11): 801–818.doi:10.1038/s41573-020-0080-x.PMID32901140.
  2. ^Tablets & Capsules,March 2009. "Micro-dosing equipment fills niche in R&D, clinical trial materials".
  3. ^Gregoire C (13 January 2016)."Everything You Wanted to Know About Microdosing (But Were Afraid to Ask)".The Huffington Post.
  4. ^Babin V, Taran F, Audisio D (June 2022)."Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges".JACS Au.2(6): 1234–1251.doi:10.1021/jacsau.2c00030.PMC9241029.PMID35783167.
  5. ^Kutschera W (2023)."An overview of world-wide AMS facilities".Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms.538:87–94.Bibcode:2023NIMPB.538...87K.doi:10.1016/j.nimb.2023.02.016.
  6. ^"Accelerator Mass Spectrometry, C14 Dating, What is AMS?".Carbon Dating Service, AMS Miami - Beta Analytic.2015-04-14.Retrieved2023-05-31.
  7. ^Broek TA, Ognibene TJ, McFarlane KJ, Moreland KC, Brown TA, Bench G (July 2021)."Conversion of the LLNL/CAMS 1 MV biological AMS system to a semi-automated natural abundance14C spectrometer: system optimization and performance evaluation ".Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms.499(published 2021-05-21): 124–132.Bibcode:2021NIMPB.499..124B.doi:10.1016/j.nimb.2021.01.022.PMC10854407.PMID38344059.
  8. ^Fadiman J (2016-01-01)."Microdose research: without approvals, control groups, double blinds, staff or funding".Psychedelic Press.XV.
  9. ^Anderson T, Petranker R, Christopher A, Rosenbaum D, Weissman C, Dinh-Williams LA, et al. (July 2019)."Psychedelic microdosing benefits and challenges: an empirical codebook".Harm Reduction Journal.16(1): 43.doi:10.1186/s12954-019-0308-4.PMC6617883.PMID31288862.
  10. ^Dressler HM, Bright SJ, Polito V (2021-03-24)."Exploring the relationship between microdosing, personality and emotional insight: A prospective study".Journal of Psychedelic Studies.5(1): 9–16.doi:10.1556/2054.2021.00157.
  11. ^abcRootman JM, Kiraga M, Kryskow P, Harvey K, Stamets P, Santos-Brault E, et al. (June 2022)."Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls".Scientific Reports.12(1): 11091.Bibcode:2022NatSR..1211091R.doi:10.1038/s41598-022-14512-3.PMC9246852.PMID35773270.
  12. ^MD PG (2022-09-19)."The popularity of microdosing of psychedelics: What does the science say?".Harvard Health.Retrieved2024-04-16.
  13. ^"European Union Microdose AMS Partnership Programme".European Commission: CORDIS EU Research Results.
  14. ^Burt T, Yoshida K, Lappin G, Vuong L, John C, de Wildt SN, et al. (April 2016)."Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development".Clinical and Translational Science.9(2): 74–88.doi:10.1111/cts.12390.PMC5351314.PMID26918865.
  15. ^Okour M, Derimanov G, Barnett R, Fernandez E, Ferrer S, Gresham S, et al. (March 2018)."A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers".British Journal of Clinical Pharmacology.84(3): 482–489.doi:10.1111/bcp.13476.PMC5809343.PMID29168205.

Further reading

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  • Lappin G, Garner RC (June 2005). "The use of accelerator mass spectrometry to obtain early human ADME/PK data".Expert Opinion on Drug Metabolism & Toxicology.1(1): 23–31.doi:10.1517/17425255.1.1.23.PMID16922650.
  • Wilding IR, Bell JA (July 2005). "Improved early clinical development through human microdosing studies".Drug Discovery Today.10(13): 890–894.doi:10.1016/S1359-6446(05)03509-9.PMID15993808.
  • Lappin G, Wagner CC, Langer O, van de Merbel N (May 2009). "New ultrasensitive detection technologies and techniques for use in microdosing studies".Bioanalysis.1(2): 357–66.doi:10.4155/bio.09.40.PMID21083172.
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