Psychedelic microdosing is a form of drug microdosing in which sub-

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic doses of

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s like

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

and

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

are taken for claimed cognitive and emotional benefits.

Uses, research, and effects

A variety of perceived benefits of psychedelic microdosing have been anecdotally claimed, such as beneficial effects on mood or

well-being Well-being is what is Intrinsic value (ethics), ultimately good for a person. Also called "welfare" and "quality of life", it is a measure of how well life is going for someone. It is a central goal of many individual and societal endeavors. ...

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

cognitive function Cognitive skills are skills of the mind, as opposed to other types of skills such as motor skills, social skills or life skills. Some examples of cognitive skills are literacy, self-reflection, logical reasoning, abstract thinking, critical th ...

creativity Creativity is the ability to form novel and valuable Idea, ideas or works using one's imagination. Products of creativity may be intangible (e.g. an idea, scientific theory, Literature, literary work, musical composition, or joke), or a physica ...

, and

productivity Productivity is the efficiency of production of goods or services expressed by some measure. Measurements of productivity are often expressed as a ratio of an aggregate output to a single input or an aggregate input used in a production proce ...

. In addition, people informally use microdosing to treat

psychiatric condition A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s and it is being formally clinically studied for such purposes. Examples include for depression,

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

(OCD),

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD), substance misuse, and

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

, among others. There is very little

scientific research The scientific method is an empirical method for acquiring knowledge that has been referred to while doing science since at least the 17th century. Historically, it was developed through the centuries from the ancient and medieval world. The ...

on microdosing or its effects as of 2024 however and the claimed beneficial effects of microdosing have largely not been scientifically validated. LSD microdosing three times per week was found in a preliminary 2024 randomized controlled trial to increase sleep duration by 24minutes on average one day after the microdose (but not the same night of the dose). This included an increase in duration of

REM sleep Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals (including humans) and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the s ...

. Psychedelics and microdosing are being͏͏ investigated͏͏ for potential͏͏ treatment of

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s like͏͏

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

.͏͏ They are also being studied for treatment of depression in people with Alzheimer's disease. Certain psychedelics, like DOI and

, acting as

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s, have been found to have potent

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

effects at doses well below those that produce hallucinogenic effects in

preclinical research In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and dr ...

and are being clinically investigated for the potential treatment of

inflammatory condition Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

s such as

neuroinflammation Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS ''et al.'' Molecular imaging of ...

. The anti-inflammatory effects of psychedelics may be involved in the possible benefits of microdosing. LSD microdosing is being clinically studied in the treatment of Alzheimer's disease for its anti-inflammatory effects. The benefits of microdosing may in part or full be a

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

mediated by positive expectancy effects. In people with major depressive disorder, placebos are known to produce substantial reductions in depressive symptoms all on their own and conventional

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s barely outperform placebos in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s. Some researchers have proposed that psychedelics, in general, may be active " super placebos" due to their powerful hallucinogenic effects and cultural associations. Tolerance and tachyphylaxis are known to rapidly develop to the hallucinogenic effects and to other effects of serotonergic psychedelics in both animals and humans. This is thought to be mediated by rapid serotonin 5-HT_2A receptor

downregulation In biochemistry, in the biology, biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell (biology), cell decreases the production and quantities of its cellular ...

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.

Dosage and administration

and

, the latter often in the form of psilocybin-containing mushrooms, are the most commonly used psychedelics in microdosing. A microdose is considered to be between approximately one-twentieth to one-tenth of a typical recreational dose. Microdoses of psychedelics are 5 to 20μg for LSD, 1 to 5mg for psilocybin, 0.1 to 0.5g of psilocybin-containing mushrooms, and <75mg for

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

. These psychedelics have perceptible psychedelic effects at minimum doses of 10 to 20μg for LSD, 3 to 5mg psilocybin, 0.5g psilocybin-containing mushrooms, and 100mg mescaline.

Side effects

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of psychedelic microdosing with LSD or psilocybin may include increased blood pressure,

, cognitive impairment, and physiological discomfort. The side effects of microdosing are generally infrequent, mild, dose-dependent, and short-lasting.

Long-term toxicity

Psychedelics, including LSD, psilocybin,

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT),

, and many others, are potent

5-HT_2B receptor

s in addition to the serotonin 5-HT_2A receptor agonism that mediates their

ic effects. Long-term use of potent serotonin 5-HT_2B receptor agonists like

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

, methysergide,

ergotamine Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitter ...

, cabergoline, pergolide, and

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

is known to produce serious

organ Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

including cardiac fibrosis, valvulopathy, and

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

. Conversely, certain other serotonin 5-HT_2B receptor agonists, such as

guanfacine Guanfacine, sold under the brand name Tenex ( immediate-release) and Intuniv ( extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Co ...

, ropinirole, and oxymetazoline, have not been associated with such toxicities, perhaps due to factors like biased agonism and/or inadequate potency or exposure. 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. It is notable in this regard that findings on the serotonin 5-HT_2B receptor agonism of psychedelics including LSD, psilocybin, mescaline, and

(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 An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...

. 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

. This was in terms of both activational potency ( = 110nM vs. 1.0–20nM, respectively) and

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...

( = 39% vs. 53–79%, respectively). Conversely, other psychedelics like

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

, 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 receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s, such as

25CN-NBOH 25CN-NBOH, also known as NBOH-2C-CN, is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. It is a member of the NBOMe family of psychedelic drug, psychedel ...

, DMBMPP, and LPH-5, have been developed and are being studied. 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

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.peripherally selective drugs like VU0530244, are being investigated and developed for potential medical use. 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.

Pharmacology

The clinical

pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

and

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of microdosed LSD have been studied.

History

According to psychedelic researcher Matthew J. Baggott in 2023, the first documented instance of psychedelic microdosing may be the

Grateful Dead The Grateful Dead was an American rock music, rock band formed in Palo Alto, California, in 1965. Known for their eclectic style that fused elements of rock, blues, jazz, Folk music, folk, country music, country, bluegrass music, bluegrass, roc ...

's use of low and sub-psychedelic doses of DOM as a mild

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

in the late 1960s. However, studies of the effects of very low doses of psychedelics date back as early as 1955. Albert Hofmann first mentioned psychedelic microdosing and possible therapeutic benefits of the intervention like

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

, and mild stimulant effects in a 1976 ''

High Times ''High Times'' was an American monthly magazine (and cannabis brand) that advocates the legalization of cannabis as well as other counterculture ideas. The magazine was founded in 1974 by Tom Forcade. The magazine had its own book publishing d ...

'' interview. He is said to have taken microdoses of LSD for most of the later years of his life. 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''. 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''. There has been a dramatic increase in interest in psychedelic microdosing as well as

into the practice since 2018.

Society and culture

Psychedelic microdosing is frequently discussed on online forums such as the r/microdosing community on

Reddit Reddit ( ) is an American Proprietary software, proprietary social news news aggregator, aggregation and Internet forum, forum Social media, social media platform. Registered users (commonly referred to as "redditors") submit content to the ...

References

External links

The Ultimate Guide to Microdosing Psychedelics - Tripsitter

Can Psychedelics Increase the Risk of Heart Disease? - Tripsitter

r/microdosing - Reddit
(and subreddi
wiki
{{DEFAULTSORT:Psychedelic Microdosing Psychedelia Psychedelic drug research