psychedelic microdosing

A variety of perceived benefits of psychedelic microdosing have been anecdotally claimed, such as beneficial effects on mood or well-being, anxiety, cognitive function, creativity, and productivity.{{cite journal | vauthors = Wong A, Raz A | title = Microdosing with classical psychedelics: Research trajectories and practical considerations | journal = Transcult Psychiatry | volume = 59 | issue = 5 | pages = 675–690 | date = October 2022 | pmid = 36317302 | doi = 10.1177/13634615221129115 | url = }}{{cite journal | vauthors = Bornemann J | title = The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being - An Early Review | journal = J Psychoactive Drugs | volume = 52 | issue = 4 | pages = 300–308 | date = 2020 | pmid = 32362269 | doi = 10.1080/02791072.2020.1761573 | url = | doi-access = free }}{{cite journal | vauthors = Polito V, Liknaitzky P | title = The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955-2021) and recommendations for the field | journal = Neurosci Biobehav Rev | volume = 139 | issue = | pages = 104706 | date = August 2022 | pmid = 35609684 | doi = 10.1016/j.neubiorev.2022.104706 | url = | doi-access = free }} In addition, people informally use microdosing to treat psychiatric conditions and it is being formally clinically studied for such purposes.{{cite book | last1=Totomanova | first1=Iva | last2=Haijen | first2=Eline C.H.M. | last3=Hurks | first3=Petra P.M. | last4=Ramaekers | first4=Johannes G. | last5=Kuypers | first5=Kim P.C. | title=International Review of Neurobiology | chapter=Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry? | publisher=Elsevier | date=2025 | doi=10.1016/bs.irn.2025.03.002 | url=https://linkinghub.elsevier.com/retrieve/pii/S0074774225000078 | access-date=27 April 2025 | page=}}{{cite journal | vauthors = Irizarry R, Winczura A, Dimassi O, Dhillon N, Minhas A, Larice J | title = Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis | journal = Cureus | volume = 14 | issue = 11 | pages = e31796 | date = November 2022 | pmid = 36569662 | pmc = 9779908 | doi = 10.7759/cureus.31796 | doi-access = free | url = }} Examples include for depression,{{cite journal | vauthors = Kuypers KP | title = The therapeutic potential of microdosing psychedelics in depression | journal = Ther Adv Psychopharmacol | volume = 10 | issue = | pages = 2045125320950567 | date = 2020 | pmid = 32922736 | pmc = 7457631 | doi = 10.1177/2045125320950567 | url = }} anxiety,{{cite journal | vauthors = Irizarry R, Winczura A, Dimassi O, Dhillon N, Minhas A, Larice J | title = Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis | journal = Cureus | volume = 14 | issue = 11 | pages = e31796 | date = November 2022 | pmid = 36569662 | pmc = 9779908 | doi = 10.7759/cureus.31796 | doi-access = free | url = }} obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), substance misuse, and schizophrenia,{{cite journal | vauthors = Wolf G, Singh S, Blakolmer K, Lerer L, Lifschytz T, Heresco-Levy U, Lotan A, Lerer B | title = Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation | journal = Mol Psychiatry | volume = 28 | issue = 1 | pages = 44–58 | date = January 2023 | pmid = 36280752 | doi = 10.1038/s41380-022-01832-z | url = }} among others. There is very little scientific research on microdosing or its effects as of 2024 however and the claimed beneficial effects of microdosing have largely not been scientifically validated.{{cite journal | vauthors = Kuypers KP, Ng L, Erritzoe D, Knudsen GM, Nichols CD, Nichols DE, Pani L, Soula A, Nutt D | title = Microdosing psychedelics: More questions than answers? An overview and suggestions for future research | journal = J Psychopharmacol | volume = 33 | issue = 9 | pages = 1039–1057 | date = September 2019 | pmid = 31303095 | pmc = 6732823 | doi = 10.1177/0269881119857204 | url = }}

LSD microdosing three times per week was found in a preliminary 2024 randomized controlled trial to increase sleep duration by 24{{nbsp}}minutes on average one day after the microdose (but not the same night of the dose).{{cite journal | vauthors = Murphy RJ, Muthukumaraswamy S, de Wit H | title = Microdosing Psychedelics: Current Evidence From Controlled Studies | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 500–511 | date = May 2024 | pmid = 38280630 | doi = 10.1016/j.bpsc.2024.01.002 | url = | doi-access = free }}{{cite journal | vauthors = Allen N, Jeremiah A, Murphy R, Sumner R, Forsyth A, Hoeh N, Menkes DB, Evans W, Muthukumaraswamy S, Sundram F, Roop P | title = LSD increases sleep duration the night after microdosing | journal = Transl Psychiatry | volume = 14 | issue = 1 | pages = 191 | date = April 2024 | pmid = 38622150 | pmc = 11018829 | doi = 10.1038/s41398-024-02900-4 | url = }} This included an increase in duration of REM sleep.

Psychedelics and microdosing are being͏͏ investigated͏͏ for potential͏͏ treatment of neurodegenerative disorders like͏͏ Alzheimer's disease.͏͏{{cite journal | vauthors = Vann Jones SA, O'Kelly A | title = Psychedelics as a Treatment for Alzheimer's Disease Dementia | journal = Front Synaptic Neurosci | volume = 12 | issue = | pages = 34 | date = 2020 | pmid = 32973482 | pmc = 7472664 | doi = 10.3389/fnsyn.2020.00034 | doi-access = free | url = }}{{cite journal | vauthors = Pilozzi A, Foster S, Mischoulon D, Fava M, Huang X | title = A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression | journal = Int J Mol Sci | volume = 24 | issue = 15 | date = August 2023 | page = 12513 | pmid = 37569888 | pmc = 10419627 | doi = 10.3390/ijms241512513 | doi-access = free | url = }} They are also being studied for treatment of depression in people with Alzheimer's disease. Certain psychedelics, like DOI and psilocybin, acting as serotonin 5-HT_2A receptor agonists, have been found to have potent anti-inflammatory effects at doses well below those that produce hallucinogenic effects in preclinical research and are being clinically investigated for the potential treatment of inflammatory conditions such as neuroinflammation.{{cite journal | vauthors = Nichols DE, Johnson MW, Nichols CD | title = Psychedelics as Medicines: An Emerging New Paradigm | journal = Clin Pharmacol Ther | volume = 101 | issue = 2 | pages = 209–219 | date = February 2017 | pmid = 28019026 | doi = 10.1002/cpt.557 | url = }}{{cite book | vauthors = Flanagan TW, Nichols CD | title = Disruptive Psychopharmacology | chapter = Psychedelics and Anti-inflammatory Activity in Animal Models | series = Current Topics in Behavioral Neurosciences | volume = 56 | pages = 229–245 | date = 2022 | pmid = 35546383 | doi = 10.1007/7854_2022_367 | isbn = 978-3-031-12183-8 | chapter-url = }}{{cite journal | vauthors = Nichols CD | title = Psychedelics as potent anti-inflammatory therapeutics | journal = Neuropharmacology | volume = 219 | issue = | pages = 109232 | date = November 2022 | pmid = 36007854 | doi = 10.1016/j.neuropharm.2022.109232 | url = | doi-access = free }}{{cite journal | vauthors = Flanagan TW, Nichols CD | title = Psychedelics as anti-inflammatory agents | journal = Int Rev Psychiatry | volume = 30 | issue = 4 | pages = 363–375 | date = August 2018 | pmid = 30102081 | doi = 10.1080/09540261.2018.1481827 | url = http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Therapeutic%20Effects%20of%20Psychedelics%2019/Flanagan%20Nichols%2018%20IntRevPsychiatry%20Psychedelics%20as%20anti-inflammatory%20agents.pdf}} The anti-inflammatory effects of psychedelics may be involved in the possible benefits of microdosing.{{cite journal | vauthors = Kinderlehrer DA | title = Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity | journal = Neuropsychiatr Dis Treat | volume = 21 | issue = | pages = 141–155 | date = 2025 | pmid = 39897712 | pmc = 11787777 | doi = 10.2147/NDT.S500337 | doi-access = free | url = }} LSD microdosing is being clinically studied in the treatment of Alzheimer's disease for its anti-inflammatory effects.{{cite journal | vauthors = Family N, Maillet EL, Williams LT, Krediet E, Carhart-Harris RL, Williams TM, Nichols CD, Goble DJ, Raz S | title = Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers | journal = Psychopharmacology (Berl) | volume = 237 | issue = 3 | pages = 841–853 | date = March 2020 | pmid = 31853557 | pmc = 7036065 | doi = 10.1007/s00213-019-05417-7 | url = }}

The benefits of microdosing may in part or full be a placebo mediated by positive expectancy effects.{{cite journal | vauthors = Polito V, Liknaitzky P | title = Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research | journal = J Psychopharmacol | volume = 38 | issue = 8 | pages = 701–711 | date = August 2024 | pmid = 38877715 | pmc = 11311906 | doi = 10.1177/02698811241254831 | url = }}{{cite journal | vauthors = Szigeti B, Heifets BD | title = Expectancy Effects in Psychedelic Trials | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 512–521 | date = May 2024 | pmid = 38387698 | doi = 10.1016/j.bpsc.2024.02.004 | url = }}{{cite journal | vauthors = Ona G, Bouso JC | title = Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review | journal = Neurosci Biobehav Rev | volume = 119 | issue = | pages = 194–203 | date = December 2020 | pmid = 33031815 | doi = 10.1016/j.neubiorev.2020.09.035 | url = }}{{cite journal | vauthors = Kaertner LS, Steinborn MB, Kettner H, Spriggs MJ, Roseman L, Buchborn T, Balaet M, Timmermann C, Erritzoe D, Carhart-Harris RL | title = Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing | journal = Sci Rep | volume = 11 | issue = 1 | pages = 1941 | date = January 2021 | pmid = 33479342 | pmc = 7820236 | doi = 10.1038/s41598-021-81446-7 | url = }} In people with major depressive disorder, placebos are known to produce substantial reductions in depressive symptoms all on their own and conventional antidepressants barely outperform placebos in clinical trials.{{cite journal | vauthors = Kirsch I | title = Placebo Effect in the Treatment of Depression and Anxiety | journal = Front Psychiatry | volume = 10 | issue = | pages = 407 | date = 2019 | pmid = 31249537 | pmc = 6584108 | doi = 10.3389/fpsyt.2019.00407 | doi-access = free | url = }}{{cite journal | vauthors = Moncrieff J, Kirsch I | title = Efficacy of antidepressants in adults | journal = BMJ | volume = 331 | issue = 7509 | pages = 155–157 | date = July 2005 | pmid = 16020858 | pmc = 558707 | doi = 10.1136/bmj.331.7509.155 }}{{cite journal|vauthors=Munkholm K, Paludan-Müller AS, Boesen K|title=Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis|journal=BMJ Open|volume=9|issue=6|pages=e024886|date=June 2019|pmid=31248914|pmc=6597641|doi=10.1136/bmjopen-2018-024886}} Some researchers have proposed that psychedelics, in general, may be active "super placebos" due to their powerful hallucinogenic effects and cultural associations.{{cite journal | vauthors = Dupuis D, Veissière S | title = Culture, context, and ethics in the therapeutic use of hallucinogens: Psychedelics as active super-placebos? | journal = Transcult Psychiatry | volume = 59 | issue = 5 | pages = 571–578 | date = October 2022 | pmid = 36263513 | doi = 10.1177/13634615221131465 | url = }}{{cite journal | vauthors = van Elk M, Yaden DB | title = Pharmacological, neural, and psychological mechanisms underlying psychedelics: A critical review | journal = Neurosci Biobehav Rev | volume = 140 | issue = | pages = 104793 | date = September 2022 | pmid = 35878791 | doi = 10.1016/j.neubiorev.2022.104793 | url = | quote = In addition, the strong prior expectations that many people have about psychedelics directly contribute to the psychedelic experience and as a consequence it has been suggested that psychedelics may act as a ‘super-placebo’ (Hartogsohn, 2016). Specifically, strong prior expectations (e.g., that a specific intervention will likely trigger a mystical experience) will increase the likelihood of having e.g., a mystical-type experience (Maij et al., 2019), and this placebo-effect is further boosted by the psychedelic-induced suggestibility. | hdl = 1887/3515020 | hdl-access = free }}

Tolerance and tachyphylaxis are known to rapidly develop to the hallucinogenic effects and to other effects of serotonergic psychedelics in both animals and humans.{{cite journal | vauthors = Halberstadt AL | title = Recent advances in the neuropsychopharmacology of serotonergic hallucinogens | journal = Behav Brain Res | volume = 277 | issue = | pages = 99–120 | date = January 2015 | pmid = 25036425 | pmc = 4642895 | doi = 10.1016/j.bbr.2014.07.016 | url = }}{{cite journal | vauthors = Nichols DE | title = Hallucinogens | journal = Pharmacol Ther | volume = 101 | issue = 2 | pages = 131–181 | date = February 2004 | pmid = 14761703 | doi = 10.1016/j.pharmthera.2003.11.002 | url = }}{{cite journal | vauthors = de la Fuente Revenga M, Jaster AM, McGinn J, Silva G, Saha S, González-Maeso J | title = Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice | journal = ACS Chem Neurosci | volume = 13 | issue = 16 | pages = 2436–2448 | date = August 2022 | pmid = 35900876 | pmc = 10411500 | doi = 10.1021/acschemneuro.2c00170 | url = }} This is thought to be mediated by rapid serotonin 5-HT_2A receptor downregulation that is very slow to recover. Tolerance and loss of effect could serve to limit the potential beneficial effects of psychedelic microdosing and this is a phenomenon that has been observed in existing clinical studies. More research is needed to further assess this issue.

LSD and psilocybin, the latter often in the form of psilocybin-containing mushrooms, are the most commonly used psychedelics in microdosing.{{cite journal | vauthors = Preller KH | title = The Effects of Low Doses of Lysergic Acid Diethylamide in Healthy Humans: Demystifying the Microdosing of Psychedelics | journal = Biological Psychiatry | volume = 86 | issue = 10 | pages = 736–737 | date = November 2019 | pmid = 31648681 | doi = 10.1016/j.biopsych.2019.08.021 | s2cid = 204800273 }} A microdose is considered to be between approximately one-twentieth to one-tenth of a typical recreational dose. Microdoses of psychedelics are 5 to 20{{nbsp}}μg for LSD, 1 to 5{{nbsp}}mg for psilocybin, 0.1 to 0.5{{nbsp}}g of psilocybin-containing mushrooms, and <75{{nbsp}}mg for mescaline.{{cite journal | vauthors = Lo DF, Zia H, Rajkumar P, Thakur A, O'Donnell H | title = Modern Psychedelic Microdosing Research on Mental Health: A Systematic Review | journal = Prim Care Companion CNS Disord | volume = 26 | issue = 1 | pages = | date = January 2024 | pmid = 38228068 | doi = 10.4088/PCC.23r03581 | url = }}{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biol Psychiatry Cogn Neurosci Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = https://www.biologicalpsychiatrycnni.org/action/showPdf?pii=S2451-9022%2824%2900020-X | doi-access = free }}{{cite book | vauthors = Liechti ME, Holze F | title = Disruptive Psychopharmacology | chapter = Dosing Psychedelics and MDMA | series = Curr Top Behav Neurosci | volume = 56 | pages = 3–21 | date = 2022 | pmid = 34734392 | doi = 10.1007/7854_2021_270 | isbn = 978-3-031-12183-8 | chapter-url = https://www.researchgate.net/publication/355943062}}{{cite journal | vauthors = Kozlowska U, Nichols C, Wiatr K, Figiel M | title = From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders | journal = J Neurochem | volume = 162 | issue = 1 | pages = 89–108 | date = July 2022 | pmid = 34519052 | doi = 10.1111/jnc.15509 | url = | quote = One dosing method of psychedelics is the use of so called “microdoses”—very low concentrations of various psychedelics that do not reach the threshold of perceivable behavioral effects. This is usually 10% of active recreational doses (e.g., 10–15 µg of LSD, or 0.1–0.3 g of dry “magic mushrooms”) taken up to three times per week.}} These psychedelics have perceptible psychedelic effects at minimum doses of 10 to 20{{nbsp}}μg for LSD, 3 to 5{{nbsp}}mg psilocybin, 0.5{{nbsp}}g psilocybin-containing mushrooms, and 100{{nbsp}}mg mescaline.

Side effects of psychedelic microdosing with LSD or psilocybin may include increased blood pressure, anxiety, cognitive impairment, and physiological discomfort.{{cite journal | vauthors = Modzelewski S, Stankiewicz A, Waszkiewicz N, Łukasiewicz K | title = Side effects of microdosing lysergic acid diethylamide and psilocybin: A systematic review of potential physiological and psychiatric outcomes | journal = Neuropharmacology | volume = 271 | issue = | pages = 110402 | date = June 2025 | pmid = 40058407 | doi = 10.1016/j.neuropharm.2025.110402 | url = https://www.researchgate.net/publication/389665189| doi-access = free }} The side effects of microdosing are generally infrequent, mild, dose-dependent, and short-lasting.

Psychedelics, including LSD, psilocybin, dimethyltryptamine (DMT), mescaline, and many others,{{cite book | last1=Luethi | first1=Dino | last2=Liechti | first2=Matthias E. | title=5-HT2B Receptors | chapter=Drugs of Abuse Affecting 5-HT2B Receptors | publisher=Springer International Publishing | publication-place=Cham | volume=35 | date=2021 | isbn=978-3-030-55919-9 | doi=10.1007/978-3-030-55920-5_16 | chapter-url=http://link.springer.com/10.1007/978-3-030-55920-5_16 | access-date=27 April 2025 | pages=277–289}}{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nat Commun | volume = 14 | issue = 1 | pages = 8221 | date = December 2023 | pmid = 38102107 | pmc = 10724237 | doi = 10.1038/s41467-023-44016-1 }} are potent serotonin 5-HT_2B receptor agonists in addition to the serotonin 5-HT_2A receptor agonism that mediates their hallucinogenic effects.{{cite journal | vauthors = Tagen M, Mantuani D, van Heerden L, Holstein A, Klumpers LE, Knowles R | title = The risk of chronic psychedelic and MDMA microdosing for valvular heart disease | journal = J Psychopharmacol | volume = 37 | issue = 9 | pages = 876–890 | date = September 2023 | pmid = 37572027 | doi = 10.1177/02698811231190865 | url = }}{{cite journal | vauthors = Wsół A | title = Cardiovascular safety of psychedelic medicine: current status and future directions | journal = Pharmacol Rep | volume = 75 | issue = 6 | pages = 1362–1380 | date = December 2023 | pmid = 37874530 | pmc = 10661823 | doi = 10.1007/s43440-023-00539-4 | url = }}{{cite journal | vauthors = Rouaud A, Calder AE, Hasler G | title = Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins | journal = J Psychopharmacol | volume = 38 | issue = 3 | pages = 217–224 | date = March 2024 | pmid = 38214279 | pmc = 10944580 | doi = 10.1177/02698811231225609 }}{{cite journal | vauthors = McIntyre RS | title = Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agents | journal = Expert Opin Drug Saf | volume = 22 | issue = 10 | pages = 881–883 | date = 2023 | pmid = 37581427 | doi = 10.1080/14740338.2023.2248883 | url = }} Long-term use of potent serotonin 5-HT_2B receptor agonists like fenfluramine, methysergide, ergotamine, cabergoline, pergolide, and MDMA is known to produce serious organ toxicity including cardiac fibrosis, valvulopathy, and pulmonary hypertension.{{cite journal | vauthors = Hutcheson JD, Setola V, Roth BL, Merryman WD | title = Serotonin receptors and heart valve disease--it was meant 2B | journal = Pharmacol Ther | volume = 132 | issue = 2 | pages = 146–157 | date = November 2011 | pmid = 21440001 | pmc = 3179857 | doi = 10.1016/j.pharmthera.2011.03.008 | url = }}{{cite journal | vauthors = Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD | title = 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery | journal = J Med Chem | volume = 66 | issue = 16 | pages = 11027–11039 | date = August 2023 | pmid = 37584406 | pmc = 11073569 | doi = 10.1021/acs.jmedchem.3c01178 | url = }}{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonergic drugs and valvular heart disease | journal = Expert Opin Drug Saf | volume = 8 | issue = 3 | pages = 317–329 | date = May 2009 | pmid = 19505264 | pmc = 2695569 | doi = 10.1517/14740330902931524 | url = }}{{cite journal | vauthors = Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, Revankar C, Robers M, Doucette C, Roth BL | title = Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment | journal = Mol Pharmacol | volume = 76 | issue = 4 | pages = 710–722 | date = October 2009 | pmid = 19570945 | pmc = 2769050 | doi = 10.1124/mol.109.058057 | url = }} Conversely, certain other serotonin 5-HT_2B receptor agonists, such as guanfacine, ropinirole, and oxymetazoline, have not been associated with such toxicities, perhaps due to factors like biased agonism and/or inadequate potency or exposure.{{cite journal | vauthors = Elangbam CS | title = Drug-induced valvulopathy: an update | journal = Toxicol Pathol | volume = 38 | issue = 6 | pages = 837–848 | date = October 2010 | pmid = 20716786 | doi = 10.1177/0192623310378027 | url = }}{{cite journal | vauthors = Dumotier BM, Urban L | title = Preclinical mitigation of 5-HT2B agonism-related cardiac valvulopathy revisited | journal = J Pharmacol Toxicol Methods | volume = 128 | issue = | pages = 107542 | date = 2024 | pmid = 39032441 | doi = 10.1016/j.vascn.2024.107542 | url = }} Due to potent serotonin 5-HT_2B receptor agonism, long-term use of psychedelics, for instance microdosing, might produce heart and other organ toxicity. Conversely, infrequent macrodoses of psychedelics are thought to be safe.

The risk of cardiac valvulopathy and toxicity with long-term use of psychedelics is, aside from the case of MDMA, theoretical and has largely not been assessed or demonstrated in animals or humans.{{cite web | last=Roihuvuo | first=Elias | title=Classical psychedelics and NBOMes as serotonin 2B receptor agonists: Valvulopathogenic signaling pathways and cardiac safety concerns | publisher=Itä-Suomen yliopisto | date=31 January 2022 | url=https://erepo.uef.fi/items/09fb2e57-a98e-4ec0-9de5-90e5267c6ed6 | access-date=27 April 2025}} It is notable in this regard that findings on the serotonin 5-HT_2B receptor agonism of psychedelics including LSD, psilocybin, mescaline, and dimethyltryptamine (DMT) are conflicting, with some studies finding them to be potent serotonin 5-HT_2B receptor agonists and others finding them to be very weak or negligible serotonin 5-HT_2B receptor agonists, depending on the study and assay. The cardiac toxicity of serotonin 5-HT_2B receptor activation has been specifically linked to extracellular regulating kinase 2 (ERK2) signaling and not necessarily to other downstream signaling pathways. LSD has been found to have low activity on a valvulopathogenic ERK2 serotonin 5-HT_2B receptor agonism readout relative to known or suspected valvopathogens like norfenfluramine, pergolide, methylergonovine (methylergometrine), ergonovine (ergometrine), cabergoline, dihydroergotamine, and ergotamine. This was in terms of both activational potency ({{Abbrlink|EC₅₀|half-maximal effective concentration}} = 110{{nbsp}}nM vs. 1.0–20{{nbsp}}nM, respectively) and efficacy ({{Abbrlink|E_max|half-maximal effective concentration}} = 39% vs. 53–79%, respectively). Conversely, other psychedelics like psilocin, DMT, and mescaline have not been assessed in terms of this assay as of 2022. However, other research suggests that the toxicity may not be specifically or exclusively dependent on ERK2 signaling. More research is needed to determine whether long-term frequent use of psychedelics, including microdosing, may cause cardiac valvulopathy and other related toxicities.

Selective serotonin 5-HT_2A receptor agonists that do not activate the serotonin 5-HT_2B receptor or other serotonin receptors, such as 25CN-NBOH, DMBMPP, and LPH-5, have been developed and are being studied.{{cite journal | vauthors = Duan W, Cao D, Wang S, Cheng J | title = Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants | journal = Chem Rev | volume = 124 | issue = 1 | pages = 124–163 | date = January 2024 | pmid = 38033123 | doi = 10.1021/acs.chemrev.3c00375 | url = }}{{cite journal | last=Peplow | first=Mark | title=Next-generation psychedelics: should new agents skip the trip? | journal=Nature Biotechnology | volume=42 | issue=6 | date=2024 | issn=1087-0156 | doi=10.1038/s41587-024-02285-1 | pages=827–830 | pmid=38831049 | quote=Another problem is that some classical psychedelics are also agonists of the 5-HT2B receptor, which is expressed in heart tissue and can cause long-term cardiac problems. Kristensen’s company Lophora aims to solve that with its lead compound LPH-5, a phenylethylamine derivative with an extra molecular ring that makes it less flexible. LPH-5 has a 60-fold higher selectivity for 5-HT2A over 5-HT2B.}} Selective serotonin 5-HT_2A receptor agonists are expected to avoid the cardiac risks of serotonin 5-HT_2B receptor activation. In addition, selective serotonin 5-HT_2B receptor antagonists, including peripherally selective drugs like VU0530244, are being investigated and developed for potential medical use.{{cite journal | vauthors = Padhariya K, Bhandare R, Canney D, Velingkar V | title = Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists | journal = Cardiovasc Hematol Disord Drug Targets | volume = 17 | issue = 2 | pages = 86–104 | date = 2017 | pmid = 28676029 | doi = 10.2174/1871529X17666170703115111 | url = }}{{cite journal | vauthors = Löfdahl A, Tornling G, Wigén J, Larsson-Callerfelt AK, Wenglén C, Westergren-Thorsson G | title = Pathological Insight into 5-HT2B Receptor Activation in Fibrosing Interstitial Lung Diseases | journal = Int J Mol Sci | volume = 22 | issue = 1 | date = December 2020 | page = 225 | pmid = 33379351 | pmc = 7796180 | doi = 10.3390/ijms22010225 | doi-access = free | url = }} Selective serotonin 5-HT_2B receptor antagonism has been found to fully prevent the cardiotoxicity of dexnorfenfluramine in animal studies, but clinical studies are needed.{{cite journal | vauthors = Dini G, Di Cara G, Ferrara P, Striano P, Verrotti A | title = Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding | journal = Neuropsychiatric Disease and Treatment | volume = 19 | issue = | pages = 2013–2025 | date = 2023 | pmid = 37790801 | pmc = 10543412 | doi = 10.2147/NDT.S417676 | doi-access = free }}{{cite journal | vauthors = Ayme-Dietrich E, Lawson R, Côté F, de Tapia C, Da Silva S, Ebel C, Hechler B, Gachet C, Guyonnet J, Rouillard H, Stoltz J, Quentin E, Banas S, Daubeuf F, Frossard N, Gasser B, Mazzucotelli JP, Hermine O, Maroteaux L, Monassier L | title = The role of 5-HT_2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors | journal = British Journal of Pharmacology | volume = 174 | issue = 22 | pages = 4123–4139 | date = November 2017 | pmid = 28806488 | pmc = 5680644 | doi = 10.1111/bph.13981 }}

The clinical pharmacodynamics and pharmacokinetics of microdosed LSD have been studied.{{cite journal | vauthors = Morse JD, Jeong SH, Murphy RJ, Muthukumaraswamy SD, Sumner RL | title = Pharmacokinetics and pharmacodynamics of sublingual microdosed lysergic acid diethylamide in healthy adult volunteers | journal = J Psychopharmacol | volume = | issue = | pages = 2698811251330747 | date = April 2025 | pmid = 40251818 | doi = 10.1177/02698811251330747 | url = | doi-access = free }}

According to psychedelic researcher Matthew J. Baggott in 2023, the first documented instance of psychedelic microdosing may be the Grateful Dead's use of low and sub-psychedelic doses of DOM as a mild stimulant in the late 1960s.{{cite journal | vauthors = Baggott MJ | title=Learning about STP: A Forgotten Psychedelic from the Summer of Love | journal=History of Pharmacy and Pharmaceuticals | volume=65 | issue=1 | date=1 October 2023 | issn=2694-3034 | doi=10.3368/hopp.65.1.93 | doi-access=free | pages=93–116 | url=https://hopp.uwpress.org/content/wphopp/65/1/93.full.pdf | access-date=26 January 2025 | quote=The Grateful Dead learned they could use small amounts as a stimulant, an effect they used extensively during the recording of the album Aoxomoxoa in 1968 and 1969.143 The use of lower doses of DOM echoed DOET’s “psychic energizer” effects and may be the first documented use of subpsychedelic doses of a psychedelic for cognitive enhancement, a practice that is now called microdosing.144}} However, studies of the effects of very low doses of psychedelics date back as early as 1955.{{cite journal | last1=Abramson | first1=H. A. | last2=Kornetsky | first2=C. | last3=Jarvik | first3=M. E. | last4=Kaufman | first4=M. R. | last5=Ferguson | first5=M. W. | title=Lysergic Acid Diethylamide (Lsd-25): Xi. Content Analysis of Clinical Reactions | journal=The Journal of Psychology | volume=40 | issue=1 | date=1955 | issn=0022-3980 | doi=10.1080/00223980.1955.9712963 | pages=53–60 | url=http://www.tandfonline.com/doi/abs/10.1080/00223980.1955.9712963 | access-date=27 April 2025| url-access=subscription }} Albert Hofmann first mentioned psychedelic microdosing and possible therapeutic benefits of the intervention like euphoria, antidepressant, and mild stimulant effects in a 1976 High Times interview.{{cite book | last=Kuypers | first=Kim P. C. | title=Modern CNS Drug Discovery | chapter=Microdosing Psychedelics as a Promising New Pharmacotherapeutic | publisher=Springer Nature Switzerland | publication-place=Cham | date=2024 | isbn=978-3-031-61991-5 | doi=10.1007/978-3-031-61992-2_26 | url=https://link.springer.com/10.1007/978-3-031-61992-2_26 | access-date=28 May 2025 | page=407–436 | quote=Decades earlier, Albert Hofmann, the “discoverer” of LSD and its hallucinogenic effects, mentioned that “very small doses, perhaps 25 micrograms,” could be useful as an antidepressant (Ghose 2015; Horowitz 1976) or as a substitute for Ritalin (Fadiman 2017; Horowitz 1976). [...] Abramson et al. (1955) who conducted a range of experiments with LSD in the 1950s combined the data of 141 experimental sessions in 31 participants; eight of them received a dose between 1 and 25 mcg of LSD. [...]}}{{cite web | author=Archaic Revival | title=Beyond the Hype: Challenging the Effectiveness of Microdosing Schedules | website=Tripsitter | date=28 August 2023 | url=https://tripsitter.com/microdosing/schedule/ | access-date=27 April 2025 | quote = James Fadiman first ignited the microdosing craze with his 2011 book, The Psychedelic Explorer’s Guide. Before this book, microdosing was largely unknown — though Albert Hofmann first mentioned the practice in a 1976 High Times article.}}{{cite magazine | author=Michael Horowitz | title=Interview: Albert Hofmann | magazine=High Times | number=11 | date=July 1976 | pages=24–28, 31, 81 | url=https://web.archive.org/web/20250505231257/https://bibliography.maps.org/resources/download/13725 | quote = High Times: What general medical uses might LSD be marketed for in the future? Hofmann: Very small doses, perhaps 25 micrograms, could be useful as a euphoriant or antidepressant.}} He is said to have taken microdoses of LSD for most of the later years of his life.{{cite web | last=Cooke | first=Justin | title=The Ultimate Guide to Microdosing Psychedelics | website=Tripsitter | date=16 January 2021 | url=https://tripsitter.com/microdosing/ | access-date=27 April 2025 | quote = Albert Hofmann, Ph.D. — the man who invented LSD — took microdoses of the substance for most of the later years of his life. He lived to the ripe old age of 102.}} James Fadiman was responsible for introducing the modern paradigm and phenomenon of psychedelic microdosing, which had previously been largely unknown, with his 2011 book The Psychedelic Explorer's Guide.{{cite journal | last1=Marks | first1=Mason | last2=Cohen | first2=I Glenn | last3=Perez-Reyzin | first3=Jonathan | last4=Angelatos | first4=David | title=Microdosing Psychedelics Under Local, State, and Federal Law | website=Scholarship Repository | date=13 January 2025 | volume=103 | page=573 | url=https://ir.law.fsu.edu/articles/821/ | access-date=27 April 2025 | quote = Despite this history, microdosing, as practiced today, is a relatively new trend that traces its roots to James Fadiman's 2011 book, which contains several case reports from people who report having microdosed. 252 The practice was also popularized by Ayelet Waldman in her autobiographical book, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life.253 Though people have likely microdosed for centuries in Mexico and elsewhere throughout the world, Fadiman and Waldman brought this mode of psychedelics consumption to a larger audience, garnering the media attention that has perpetuated the trend, and ultimately triggering an explosion of scientific research into microdosing since 2018.254}}{{cite book | last=Fadiman | first=James | title=The Psychedelic Explorer's Guide: Safe, Therapeutic, and Sacred Journeys | publisher=Simon and Schuster | date=18 May 2011 | isbn=978-1-59477-936-7 | url=https://books.google.com/books?id=_V0oDwAAQBAJ&q=%2522The+Psychedelic+Explorer%2527s+Guide%2522 | access-date=27 April 2025 | page=}} Ayelet Waldman additionally helped to popularize microdosing with her 2017 book A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life.{{cite book | last=Waldman | first=Ayelet | title=A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life | publisher=Knopf Doubleday Publishing Group | date=9 January 2018 | isbn=978-1-101-97372-1 | url=https://books.google.com/books?id=5KZJDwAAQBAJ | access-date=27 April 2025 | page=}} There has been a dramatic increase in interest in psychedelic microdosing as well as scientific research into the practice since 2018.

Psychedelic microdosing is frequently discussed on online forums such as the r/microdosing community on Reddit.{{cite journal | vauthors = Bornemann J | title = The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being - An Early Review | journal = J Psychoactive Drugs | volume = 52 | issue = 4 | pages = 300–308 | date = 2020 | pmid = 32362269 | doi = 10.1080/02791072.2020.1761573 | url = | doi-access = free }}{{cite journal | vauthors = Pop IA, Gielens E, Kottmann H, Achterberg P | title = Exploring the discourses around microdosing psychedelics within the r/microdosing online community | journal = Soc Sci Med | volume = 347 | issue = | pages = 116702 | date = April 2024 | pmid = 38520826 | doi = 10.1016/j.socscimed.2024.116702 | url = | doi-access = free }}

• Psychedelic drug § Psychedelic afterglows
• Nootropic
• Psychedelic therapy
• List of investigational hallucinogens and entactogens

{{Reflist}}

• [https://tripsitter.com/microdosing/ The Ultimate Guide to Microdosing Psychedelics - Tripsitter]
• [https://tripsitter.com/heart-disease/ Can Psychedelics Increase the Risk of Heart Disease? - Tripsitter]
• [http://reddit.com/r/microdosing/ r/microdosing - Reddit] (and subreddit [https://www.reddit.com/r/microdosing/wiki/index/ wiki])

{{Psychedelics}}

{{Drug use}}

{{Serotonin receptor modulators}}

{{DEFAULTSORT:Psychedelic Microdosing}}

Category:Psychedelia

Category:Psychedelic drug research