Microdosing

A microdose is a dose of psycho*active compound so small as to be below the perceptual threshold, to receive the neurological benefits without impairing normal functioning. While microdosing is most often associated with controlled psychedelic substances such as L*S*D and psilocybin (the compound found in “magic mushrooms”) [1], it equally applies to legal psycho*active compounds such as nicotine, caffeine, aspirin, CBD (cannabidiol, extracted from the hemp plant), and β-Carbolines.

Although applicable to any psycho*active substance, the term “microdosing” has become rooted in psychedelics as a contrast to the practice of “macrodosing”: taking a fully perceptive dose of a psychedelic / hallucinogenic / deliriant / dissociative compound that significantly alters sensory perception, precipitates a non-ordinary state of consciousness, and triggers a subjective view of self-identity. Microdosing, whether with a psychedelic or psycho*active compound, is performed with a dose that is so low as to be either sub-perceptive or only slightly perceptive such that normal functioning is not impaired and the participant retains full agency of physical and psychological control.

For example with magic mushrooms (psilocybin), a macrodose is considered as 2-5g of mushrooms (10-25mg of psilocybin) while a microdose is 0.1-0.2 g of mushrooms (0.5-1.0μg of psilocybin).

Why Microdose?

Mood enhancement, decreased stress, cognitive and creative improvement, heightened sensory perception, higher empathy, increased mindfulness and awareness, easier attainment of flow state, improved memory and mental clarity [2]… while these results have not been thoroughly demonstrated in well-designed randomized controlled trials [3], the wealth of anecdotal reports and positive media coverage has led to the widely accepted public belief in the efficacy of psychedelic microdosing [4].

It is not clear whether the beneficial results of psychedelic microdosing are due to the powerful impact of the placebo effect [5], and the absence of controlled scientific evidence also means that the safety profile of psychedelic microdosing is not confirmed [6]. This has not prevented the public from pursuing psychedelic microdosing for the benefits listed above, as well as the treatment of serious mental disorders [7]. Tens of thousands of patients have even pursued microdosing to mitigate the withdrawal side-effects for patients tapering off of prescription antidepressants [8].

In short, microdosing is so popular because of the potential psychological and physiological benefits of a psychedelic macrodose without impairment of normal functioning, not to mention the myriad neurological health benefits (even in the case of a sub-perceptive dose). Many enthusiasts say that the goal of taking psychedelics is the attainment of the state of altered consciousness / perception / identity through a macrodose (or “hero’s dose”) [9], but such a journey is not pragmatic nor feasible for everybody.

How does Microdosing Work?

The compounds most often used in microdosing are those that interact strongly with the brain’s serotonin receptors (our mood regulator) [10]:
– Psilocybin (the active compound found in magic mushrooms)
– L*S*D (known as “acid”)
– DMT (the hallucinogenic component in ayahuasca)

Research has found that ingestion of these compounds increases cognitive flexibility [11], [12] & [13] and connectivity between regions of the brain responsible for thought (cortex), learning (thalamus), and cognitive control (claustrum)[14].

It is believed that these psychedelic compounds increase the diversity of neural pathways, enabling the formation of new thought patterns and alternate belief structures.

At macrodose levels, this change in brain state can result in an altered state of consciousness and perception. At microdose levels that are not sufficient to alter consciousness or perception, new thought patterns and belief structures can still emerge due to increased neural flexibility from the neuromodulatory effects of these compounds, especially when practiced over time.

Microdosing of non-serotonergic compounds works in the same manner, but through modulation of different neurotransmitters, e.g.:
– Ibogaine with Sigma receptors, that are involved with memory and emotion [15]
– Muscimol with GABA-A receptors, that have calming and sedative effects [16]
– Caffeine with Adrenergic (adrenaline) receptors [17]

Microdosing with Magi

The key ingredients in Magi™ nootropics are β-Carbolines, a class of naturally occurring organic compounds with psycho*active and neuroprotective properties, that are extracted and purified from the sacred plant Espand. The β-Carbolines that we formulated Magi™ nootropics with lightly interact with the brain’s serotonin receptors, but most strongly modulate Imidazoline receptors that are involved in sensory and perception [18]. They also inhibit Monoamine Oxidase (MAO), the enzyme that inactivates the brain’s neurotransmitters, which in turn affects the body’s serotonin (mood regulator), adrenaline (energy regulator), and dopamine (reward regulator) systems [19].

β-carbolines such as harmine [20] also exhibit anti-inflammatory activity in neurons [21] and promote neurogenesis by increasing levels of brain-derived neurotrophic factor (BDNF) [22] and human neural progenitor cells (hNPC) [23]. They interact with the sleep cycle via the pineal gland, the part of the brain that regulates the body’s circadian rhythm and are believed to play a role in the melatonin cycle of sleep [24].

At a macrodose level, β-Carbolines have been shown to induce disorientation, relaxation, and vivid thought patterns together with physical discomfort, sometimes to the point of nausea [25].

All Magi™ nootropics are formulated at a microdose level to avoid physical discomfort and disorientation. Some of our nootropics are lightly perceptive, such as Magi meditation aid that is formulated to induce a slight change in mood and sensory perception for meditative focus/unfocus (which some in our community have described as similar to the sense of relaxation after consuming a cup of matcha tea, or supplementation with theanine); and some of our nootropics are sub-perceptive, such as Magi neurogenesis which is formulated to provide only the cognitive health benefits of β-Carbolines without a change in sensation.

Supplement for The Good Mind: MAGI

Microdose Safety

Given the monoamine oxidase inhibitor (MAOi) properties of our Magi formulations, we recommend that you consume Magi nootropics with as close to an empty stomach as possible in order to minimize the risk of MAOi-tyramine interactions [26]. Tyramine is an amino acid that is present in some foods, notably fermented products such as aged cheeses, soy sauce, wine, beer, and certain meats and nuts [27], that can lead to hypertension and headaches at high levels in some people, particularly if not metabolized in the body by monoamine oxidase. Tyramine-related migraine concerns are estimated to affect 7% of the population [28] and tyramine-related hypertension concerns are estimated to affect 10% of the population [29].

The β-Carbolines in Magi nootropics are known as reversible inhibitors of monoamine oxidase (RIMAs) which are less concerning for tyramine interactions than pharmaceutical MAOi’s such as Marplan (isocarboxazid) and Nardil (phenelzine) [30], but we recommend erring on the side of caution. While best to avoid tyramine rich foods altogether when taking Magi nootropics, for convenience and in support of healthy habit formation, we recommend taking Magi nootropics on an empty stomach, either:

– First thing in the morning upon waking,
– Or last thing at night before bed

Microdose Protocol with Magi

“Habits are modern day-solutions to ancient desires. New versions of old vices.” – James Clear, author of Atomic Habits[31]

Whether your intention is to strengthen meditation practice, improve sleep hygiene, or improve brain health, we believe that ritual is critical to the formation of healthy habits. We recommend that you form a ritual around consumption of Magi nootropics either first thing in the morning upon waking, or last thing at night before bed while on as close to an empty stomach as possible.

For Magi nootropics that are sub-perceptive for facilitation of neurological health and sleep hygiene, we recommend consuming 1 pill per day; either upon waking or before sleeping for Magi neurogenesis, or before sleeping for Magi sleep aid.

For Magi nootropics that are lightly perceptive for facilitation of dream enhancement or meditation focus/unfocus, we recommend consuming 1 pill for 5 days in a row, followed by 2 days off; either upon waking or before sleeping for Magi meditation guide, or before sleeping for Magi dream enhancer. This 5:2 cycle is often known as the worker’s protocol:

Sunday	Monday	Tuesday	Wednesday	Thursday	Friday	Saturday
Off	On	On	On	On	On	Off