THE LICK - AKA MUSEODOSE

0.25µg/kg LSD | 42µg/kg psilocybin

[this post was originally stickied on /r/microdosing for almost two years before I removed it for several reasons, three of which: the members and visitors were not sufficiently educated or mature to be experimenting with microdosing, and sought to use the scientific air I provided as legitimating their psychedelic use as a mood enhancer, which is the wrong way to use it, and demonstrates a poor understanding of how psychedelics work. Second, the microdosing community had been completely invaded by people who wanted to never feel anything from it; and the point of my post here is based on low-psychoactive doses. Since I left that community and gave up on the word microdosing, I've renamed this kind of use and experimentation more appropriately--the lick.

However, this post has not been updated for 6 years as of 2019, and much has happened since its publication. This is the third reason I removed it: contradictory research was emerging from different labs, discrepancies which took years to be seriously acknowledged. If one takes the time to read the literature and understands the issues with psychedelics and neuroimaging (read: neurovascular coupling), one cannot come to a definite conclusion about how these drugs work in the brain presently, though many have tried.]

This is kept mostly for archival purposes.

The current breadth of psychedelic science is beyond the whims of this post, far exceeding Reddit's character limit, and above my best understanding. These references are starting points. Rather than feeling informed, think of these headers as a set of tools for guiding your experiments. I try and include relevant research though almost every point in this post could be expanded and supported with more resources.

Microdosing deserves the same care and attention and respect as does a trip to a foreign country. Research interactions between psychedelics and any medications you are taking. There is no health and safety information in this thread--you must inform yourself.

I'm not a doctor or any kind of medical professional. The efficacy and safety of psychedelic microdosing has not been thoroughly assessed, so the information here is for educational and research purposes only. This post is subject to periodic updates. I welcome and express my urge for any and all feedback.

Dosage Psychedelic potency is not regulated. Be cautious.

The threshold is equivalent to the dose at which a subjectively detectable effect becomes distinguishable from placebo. There may be some benefits to the immune system or some other obscure effects, but what is considered a genuine psychedelic state is rarely achieved at a sub-perceptual dose (something like 10ug for most people).

Since the micro dose is taken to be sub-perceptual, or sub-threshold, this post is about the next dose up.

weight table

Psilocybin: from The Pharmacology of Psilocybin [pdf]

"The threshold dose depends on interindividual differences, but may be in the range of 3 – 5 mg p.o. [aka oral] for a subjectively detectable sympathomimetic, but not hallucinogenic, effect as found in double-blind placebo-controlled trials."

Comparative potency of psilocybin, psilocin, mescaline and LSD [pdf]

"It is interesting that the relative potency of psilocin to psilocybin (1.48) is almost identical to the ratio of the molecular weight of the two drugs (1.4)."

Varying psilocybin, psilocin and baeocystin contents of psychoactive mushrooms (erowid)

For example, 0.2g of cubenses at an average of 0.6%/0.6% PI/PY ≃ 1.5mg/1.5mg, using erowid's numbers as a base. 1.5mg PI x 1.48 compares to 2.2mg PY, for a comparable PY dose of 3.7mg.

They can be ground into powder, and put in capsules or dumped into tea, and taken on a relatively empty stomach. Some say boil & strain, but if you drink the tea and the powder I see no reason to. The variety of factors involved are difficult to account for, so prior experience with the same batch helps gauge the dose.

LSD: from The Heretic [article]

"Fadiman claims the 'normal range' of an LSD dose varies, based on whether one is seeking a recreational experience (50 mcg), creative boost (100 mcg), therapeutic session (100-250 mcg) or face-to-face with “the Divine” (400 mcg)."

"Fadiman defines a micro-dose as 10 micrograms of LSD (or one-fifth the usual dose of mushrooms)."

Fadiman is playing it safe here. And since the purpose of microdosing is not exactly recreational, I argue that the (admittedly narrow) window could be from 15-20µg (±5µg, depending on aspects of your physiology, mindset and setting). Sandoz initially packaged Delysid in 25µg vials, though for quite different purposes.

Warning: A bitter/numbing blotter is not LSD. Test with Ehrlich's Reagent (store page).

In prose

Psychedelics and Religious Experience by Alan Watts (doc) is worth a read.

"every insight has degrees of intensity. There can be obvious1 and obvious2—and the latter comes on with shattering clarity, manifesting its implications in every sphere and dimension of our existence."

Elsewhere,

"LSD is an instrument which a person in any field of inquiry can use. Just as a microscope can help a biologist, LSD can remove the inhibitions to perception which prevent us from seeing the central relationships of the world."

---

"It’s not 'take psychedelics and you can understand quantum mechanics’. But if you understand quantum mechanics--and you take psychedelics--you may really understand quantum mechanics." - Fadiman [at 3:18]

Variations other than set and setting

Vollenweider et al. found a genetic polymorphism of the 5-HT2A receptor is present in 25% of the normal population. Mentioned here; at 35:23, and people with it tend to have a deficit in prepulse inhibition (PPI), and are overwhelmed with external stimuli (full text). This explains some of the variation in the tolerability and overall effects of psychedelics. Nichols et al. found a dopaminergic metabolite created in the second phase of LSD action (after 4hrs). 5-HT2A receptors are considered antipsychotic, so the genetic polymorphism might prevent effective modulation of the late dopaminergic phase. People either say that's when you do the really intense integration, and others get headaches and want a valium, and often "self-centered, suspicious, with ideas of reference or even paranoid convictions," (Freedman, 1984). Others get pure psychedelic euphoria for the whole 8 hours--says Nichols [43:30-48:35].

5-HT transporter polymorphisms and liver enzyme abnormalities also affect the way it acts on the body.

Memory

Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning [pdf]:

"Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBOMe or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear."

"effective doses of hallucinogens may provide excessive stimulation of 5-HT2A receptors in PFC, leading to speculation that perhaps subhallucinogenic dosages of 5-HT2A agonists might facilitate working memory. [...]

LSD produced a robust enhancement of CR acquisition at conditioned stimulus (CS)-unconditioned stimulus (US) intervals that generated low rates of CR acquisition in vehicle controls (Harvey et al., 1988). Through control experiments, it was determined that the enhancement of CR acquisition promoted by the hallucinogens was due to enhanced associative learning. [...]

Harvey speculates that because the rate of learning is an index of task difficulty, activation of the 5-HT2A receptor may have a proportionately greater effect as task difficulty places greater demands on attentional and associative processes."

Note: being in a classroom, for example, would produce such an effect--you will generally have a higher cognitive load in a lecture room than at home. Cognitive load strengthens assimilation and accommodation of new information into existing schemas.

Psychedelic-induced gene expression [pdf] (see Fig. 1) - mentioned by Dr. Vollenweider here, at 32:54.

The EGR2 gene is an indication of myelin growth. Myelin speeds neuronal action potentials and helps synchronize neighboring cells, as well as provide neurons with essential nutrients from the blood while simultaneously emptying cellular waste, among other essential roles. 5-HT receptors are all over these cells.

Dopamine, norepinephrine and cognitive load

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders by F. X. V. & M.K. [pdf]:

"The classical hallucinogens are comprised of three main chemical classes: the plant-derived tryptamines (for example, psilocybin) and phenethylamines (for example, mescaline), and the semisynthetic ergolines (for example, LSD). [...] In contrast to the tryptamines, the ergolines also show high intrinsic activity at dopamine D2 receptors and at α-adrenergic receptors."

LSD's direct binding to adrenergic and dopaminergic receptors produce a more direct sympathomimetic effect. Psilocybin does affect these systems, but more so indirectly.

Vollenweider found increased DA levels in the basal ganglia after oral psilocybin administration [pdf] (an indirect action through 5-HT receptors)--also found increased levels of cortisol, prolactin and thyroid stimulating hormone [pdf]. Prolactin-dopamine oscillations may engage a learning process resulting in overall decreased impulsive aggression, which may persist for weeks, or months. This indirect DA action contributes to psilocybin's more organic emotional experience, coming on as a result of some prior process, as does for many merely being aware of one's consuming an ancient, worshipped, natural mycological panacea, which has been known to inspire arcane states of righteous reverence. Though this 'natural' essence becomes half-irrelevant when we consider that the LSD experience is no less brilliant, and can be as enchanting and beatific as psilocybin, exerting its effects on much of the same neurophysiology.

Aditionally, 2C receptor activation in GABAergic neurons may stabilize dopaminergic VTA neurons, which could theoretically enhance resilience to social defeat stress [pdf].

The locus coeruleus plays a key role. This is the brain's norepinephrine center known to activate during perception of novelty. More on the LC [pdf].

Nichols - Psychedelic Science [at 29:34]:

"Psychedelics don't change its basic firing rate, but they enhance it's burst firing. So they make it burst fire more intensely and longer for things that normally would not produce novelty."

Hyper/hypo-frontality is a complicated picture. This will have to wait. Preliminarily, ignoring Carhart-Harris' work on the default mode and resting states (since mL is not intended for resting), and focusing on research with more external validity, we find PET studies which reveal marked increases in glucose utilization in the right frontomedial, frontolateral, and in the anterior cingulate (known for modulating the disagreeableness of pain), and notably also in the medial temporal lobes (having to do with declarative memory).

Anxiolytic effects

Vollenweider et. al. on psilocybin and decreased amygdala reactivity [pdf]:

"we found that the psilocybin-induced increase in positive mood state was related to the psilocybin induced decrease in right amygdala reactivity. Given the dependence of psilocybin-induced mood changes on 5-HT2A receptors, these results indicate that 5-HT2A receptor stimulation critically underlies the observed effects of psilocybin on right amygdala reactivity."

Decreased right prefrontal activity has been found in depressed patients experiencing negative emotions. Psychedelic increases in right prefrontal activity may contribute to modulating the right amygdala.

In order to overcome anxieties, one should enter a phobic situation while in a relatively relaxed state. Enhancement of fear extinction has indeed be demonstrated with psilocybin, and may be a result of enhanced associative learning (see Memory).

The Dorsal Raphe Nucleus is known to play a role in fear/anxiety, and in the psychedelic state the Raphe stops firing,

Classical psychedelics' potent anti-inflammatory effects [pdf] are of major therapeutic value. Briefly, consider the role of inflammatory mediators like TNF-α in depression. This path has recently been explored in research [pdf]. Inflammation is also said to play an important role in social rejection, this may also be a factor contributing to anxiolytic effects.