LSD microdosing RCT

Self-experiment with sub-psychedelic doses of LSD; no benefit
nootropics, psychology, experiments, predictions, statistics, Silk-Road, Python, shell, Haskell, interview, R, power-analysis
2012-08-202019-06-25 finished certainty: likely importance: 6


Some early exper­i­men­tal stud­ies with LSD sug­gested that doses of LSD too small to cause any notice­able effects may improve mood and cre­ativ­i­ty. Prompted by recent dis­cus­sion of this claim and the purely anec­do­tal sub­se­quent evi­dence for it, I decided to run a well-pow­ered ran­dom­ized blind trial of 3-day LSD micro­doses from Sep­tem­ber 2012 to March 2013. No ben­e­fi­cial effects reached sta­tis­ti­cal-sig­nif­i­cance and there were wor­ri­some neg­a­tive trends. LSD micro­dos­ing did not help me.

Intrigued by old sci­en­tific results & many pos­i­tive anec­dotes since, I exper­i­mented with “micro­dos­ing” —tak­ing doses ~10μg, far below the level at which it causes its famous effects. At this dosage, the anec­dotes claim the usual generic spec­trum of pos­i­tive effects on mood, depres­sion, abil­ity to do work, etc. After research­ing the mat­ter a bit, I dis­cov­ered that as far as I could tell, since the orig­i­nal exper­i­ment in the 1960s, no one had ever done a blind or even a ran­dom­ized self­-­ex­per­i­ment on it.

The self­-­ex­per­i­ment was sim­ple: I cal­cu­lated how many doses I needed and whether the exper­i­ment was worth run­ning, ordered 2 250μg tabs off Silk Road 1, designed the exper­i­ment (I dis­solved one in dis­tilled water, put the solu­tion in one jar & tap water in the oth­er, and took them in pairs of 3-day block­s), ran it, and ana­lyzed it.

The results of my pre-spec­i­fied analy­sis:

  1. Sleep (us­ing my ):

    • laten­cy: none (p = 0.49)

    • total sleep: none (p = 0.12)

    • num­ber of awak­en­ings: none (p = 0.25)

    • morn­ing feel: increased (p = 0.011)

      There is an increase in “Morn­ing Feel” from 2.6 to 2.9, d = 0.42; cor­rect­ing for per­form­ing 7 dif­fer­ent tests, this result is not sta­tis­ti­cal­ly-sig­nif­i­cant (it does not sur­vive a (since ) nor the q-value approach to fam­i­ly-­wise cor­rec­tion).

  2. flash­card scores: none (p = 0.68)

  3. Mood/productivity: none (d=-0.18; p = 0.27)

  4. Cre­ativ­i­ty: none (d=-0.19; p = 0.28)

I con­cluded that if any­thing, the LSD micro­dos­ing may have done the oppo­site of what I want­ed.

Given that this is the oppo­site of almost all micro­dos­ing anec­dotes and this pat­tern sug­gests & , I strongly urge any future self­-­ex­per­i­menters to up their method­olog­i­cal rig­or, and espe­cially to blind their doses to avoid both placebo & effects. If they fear the con­se­quences of pub­li­ca­tion, then in the inter­ests of com­bat­ing the endemic pub­li­ca­tion bias1, I am will­ing to host their writeup on this page; my PGP key is avail­able.

Background

“…When I did 2 hits of acid, I had the exact oppo­site expe­ri­ence of see­ing God. The fact that such a tiny amount of a mere chem­i­cal could effect my ‘soul’ so pro­foundly was proof pos­i­tive that the soul is com­pletely mate­r­i­al. I already believed this intel­lec­tu­al­ly, but this expe­ri­ence solid­i­fied this knowl­edge into my very being. So per­son­al­ly, I would rec­om­mended exper­i­ment­ing with a psy­che­delic or two for those who wish to study Phi­los­o­phy.”

dar­ius42

I’ve long been inter­ested in psy­che­delics for the insights they may offer into our brains but I’d never actu­ally tried any. Besides being ille­gal and rel­a­tively expen­sive or hard to get, pro­po­nents have been clear that a “good trip” requires some­one expe­ri­enced to watch over you and an appro­pri­ate envi­ron­ment - nei­ther of which I had avail­able. So it’d always been some­thing to do lat­er, and pure curios­ity about the expe­ri­ence was not enough to break my iner­tia.

I say “curios­ity about the expe­ri­ence” because I am dubi­ous about the actual epis­temic value of the psy­che­delic expe­ri­ence; my inter­est, like William James, is in what I can learn from the expe­ri­ence about myself and reli­gion. The claims made by psy­cho­nauts are fre­quently extrav­a­gant and unjus­ti­fied; the tan­gi­ble ben­e­fits are either unre­lated to the truth of the expe­ri­ence (such as less­ened anx­i­ety of death), purely inter­nal (what one wants to do with one’s life), or true but unre­lated to the claims inferred from the expe­ri­ence and ver­i­fi­able in a non-psy­che­delic con­text (the inven­tion of ). Only a few expe­ri­ences could be used to show the objec­tive real­ity of any such expe­ri­ence such as meet­ing the “machine elves” under the influ­ence of , such as fac­tor­ing large primes (although given the rel­a­tive rar­ity of meet­ing them while using DMT, I esti­mate such an exper­i­ment could be fairly expen­sive to run). If one feels at one with every­thing in the uni­verse and decides to devote his life to feed­ing starv­ing chil­dren, his devo­tion to char­ity proves noth­ing about the uni­verse, and even if the expe­ri­ence were true at face-­val­ue, that would not be enough either - if one felt the oppo­site, that the uni­verse were not one, would that some­how make the starv­ing chil­dren OK? Sam Har­ris takes an approach very much like mine:

The mere exis­tence of psy­che­delics would seem to estab­lish the mate­r­ial basis of men­tal and spir­i­tual life beyond any doubt - for the intro­duc­tion of these sub­stances into the brain is the obvi­ous cause of any numi­nous apoc­a­lypse that fol­lows. It is pos­si­ble, how­ev­er, if not actu­ally plau­si­ble, to seize this datum from the other end and argue, and did in his clas­sic essay, , that the pri­mary func­tion of the brain could be elim­i­na­tive: its pur­pose could be to pre­vent some vast, transper­sonal dimen­sion of mind from flood­ing con­scious­ness, thereby allow­ing apes like our­selves to make their way in the world with­out being daz­zled at every step by vision­ary phe­nom­ena irrel­e­vant to their sur­vival. Hux­ley thought that if the brain were a kind of “reduc­ing valve” for “Mind at Large,” this would explain the effi­cacy of psy­che­delics: They could sim­ply be a mate­r­ial means of open­ing the tap.

…Un­for­tu­nate­ly, Hux­ley was oper­at­ing under the erro­neous assump­tion that psy­che­delics decrease brain activ­i­ty. How­ev­er, mod­ern tech­niques of neu­roimag­ing have shown that these drugs tend to increase activ­ity in many regions of the cor­tex (and in sub­cor­ti­cal struc­tures as well) [Note 1/24/12: a recent study on actu­ally lends some sup­port to Hux­ley’s view. –SH] . Still, the action of these drugs does not rule out dual­ism, or the exis­tence of realms of mind beyond the brain - but then noth­ing does. This is one of the prob­lems with views of this kind: They appear to be unfal­si­fi­able. [Phys­i­cal­ism, by con­trast, could be eas­ily fal­si­fied. If sci­ence ever estab­lished the exis­tence of ghosts, or rein­car­na­tion, or any other phe­nom­e­non which would place the human mind (in whole or in part) out­side the brain, phys­i­cal­ism would be dead. The fact that dual­ists can never say what would count as evi­dence against their views makes this ancient philo­soph­i­cal posi­tion very dif­fi­cult to dis­tin­guish from reli­gious faith.]

Of course, the brain does fil­ter an extra­or­di­nary amount of infor­ma­tion from con­scious­ness. And, like many who have taken these drugs, I can attest that psy­che­delics cer­tainly throw open the gates. Need­less to say, posit­ing the exis­tence of a “Mind at Large” is more tempt­ing in some states of con­scious­ness than in oth­ers. And the ques­tion of which view of real­ity we should priv­i­lege is, at times, worth con­sid­er­ing. But these drugs can also pro­duce men­tal states that are best viewed in clin­i­cal terms as forms of psy­chosis. As a gen­eral mat­ter, I believe we should be very slow to make con­clu­sions about the nature of the cos­mos based upon inner expe­ri­ence - no mat­ter how pro­found these expe­ri­ences seem.

The poten­tial “mys­ti­cal expe­ri­ence” or “encounter with God” has con­sid­er­able inter­est for me, though, and psy­che­delics com­monly trig­ger such expe­ri­ences. Even back when I was a very young child, I have always been athe­is­tic; at first, because reli­gions did­n’t seem like very good expla­na­tions of the world, but then because I read through var­i­ous scrip­tures & the Bible & higher Bib­li­cal crit­i­cism & phi­los­o­phy books with­out find­ing any­thing con­vinc­ing2. I always won­dered whether my dis­be­lief was due to rea­soned grounds as I claimed, or a sim­ple lack of the right expe­ri­ences: other peo­ple seem to have mys­ti­cal expe­ri­ences and find prayer sat­is­fac­tory and believe fer­vent­ly, and I spo­rad­i­cally hear of who have “road to Dam­as­cus” expe­ri­ences (like SF author hal­lu­ci­nat­ing and con­vert­ing to Catholi­cism after a heart attack). Spo­radic hal­lu­ci­na­tions are a poor ground for belief, as a men­tal hos­pi­tal demon­strates, but nev­er­the­less they are quite con­vinc­ing; it seems that for many, see­ing really is believ­ing. Many years lat­er, I have yet to have a mys­ti­cal or reli­gious or expe­ri­ence which could either con­vert me or leave me unmoved, and thus empir­i­cally set­tle the issue as to why I am an athe­ist - absence of expe­ri­ence, or rea­soned belief? Hence, it is tempt­ing to force the issue. (If you have a psilo­cy­bin-in­duced hal­lu­ci­na­tion of God and then become a the­ist, that’s a good piece of evi­dence that stuff like the argu­ment from evil or argu­ment from silence weren’t why you were an athe­ist. And so if you were claim­ing pre­vi­ously that they were, you were either lying or badly mis­tak­en.) : (“A Philoso­pher Defends Reli­gion”)

It is illu­mi­nat­ing to have the stark­ness of the oppo­si­tion between the­ism and the sec­u­lar out­look so clearly explained. My instinc­tively athe­is­tic per­spec­tive implies that if I ever found myself flooded with the con­vic­tion that what the says is true, the most likely expla­na­tion would be that I was los­ing my mind, not that I was being granted the gift of faith. From Planti­nga’s point of view, by con­trast, I suf­fer from a kind of spir­i­tual blind­ness from which I am unwill­ing to be cured.

Every­thing I’ve heard or read is con­sis­tent with what such expe­ri­ences seem to be: the brain in a very unusual state, mal­func­tion­ing in many respects and per­haps func­tion­ing bet­ter in a few other respects. No one expects to dis­cover a new truth about the uni­verse in the throes of delir­ium tremens or amphet­a­mine psy­chosis - isn’t it par­si­mo­nious to extend this to psy­che­delics as well? If there were some ‘truthi­ness’ to the states, I had to think: of the many thou­sands of mind-al­ter­ing sub­stances inves­ti­gated over the cen­turies, it would be quite remark­able if the few which grant access to new truths were also the very same ones which pro­duce pleas­ant or enjoy­able trips!

So the trip itself is of lit­tle direct val­ue, but the 3 cat­e­gories of effects I out­lined are. Every­one talks about Open­ness (see lat­er) and cre­ativ­ity in rela­tion to psy­che­delics (eg. Wired/dis­cus­sion). I would offer a more con­crete anal­o­gy: cre­ativ­ity is a kind of opti­miza­tion activ­ity like in which one searches through a vast num­ber of pos­si­bil­i­ties for the right thing.3 (This seems to be sim­i­lar to James L. Ken­t’s views.) In sim­u­lated anneal­ing, we can think of the pos­si­bil­i­ties as a dot­ted with moun­tains and val­leys, and we are try­ing to find the low­est point; we start at ran­dom points, and jump around ran­domly and see how low we wind up. How big are our jumps? This is the “tem­per­a­ture”. The tem­per­a­ture starts high, since we may be a very long way away from the low­est point, but as we get lower and closer to the sea, we turn down the tem­per­a­ture and start mak­ing small jumps so we don’t jump right back onto a moun­tain or some­thing like that. (Imag­ine look­ing through a dic­tio­nary: you flip through whole chunks to get the let­ter right, then you start flip­ping through pages so you don’t over­shoot, and finally you read through an indi­vid­ual page.) The tem­per­a­ture has to change, or we will waste a lot of time and may never find our tar­get: if the tem­per­a­ture is always high, no sooner have we found an excel­lent can­di­date than we have jumped half a con­ti­nent away, but if it’s always low, we will lit­er­ally inch around and not find the low point a few miles away. Sim­u­lated anneal­ing itself has been applied to neural net­works, so it may be more than just an anal­ogy to say our brains do some­thing sim­i­lar. At first you brain­storm, gen­er­at­ing myr­i­ads of dis­parate ideas, but you focus on a few can­di­dates, brain­storm vari­ants, and begin care­fully fine-­tun­ing them. You hope you don’t spend too much time tin­ker­ing that you miss your dead­line, but also that you don’t spend too lit­tle time brain­storm­ing that you miss some bril­liant ele­gant solu­tion.

And LSD? Per­haps doses large enough that you become so ‘cre­ative’ that you start see­ing what is not there are anal­o­gous to turn­ing the tem­per­a­ture up a thou­sand degrees: the fran­tic anneal­ing may hit upon some remote undis­cov­ered great idea (eg. PCR) but this will usu­ally just throw away all one’s cur­rent good results in favor of some ran­dom dreck. Gen­uine thought and break­throughs are the pin­na­cle of human thought, achieved after end­less labor and depen­dent on many dead­-ends, bits of knowl­edge, and intu­ited truths; ran­dom­ness seems like it would usu­ally make things much worse4, and in gen­er­al, phar­ma­co­log­i­cal inter­ven­tions . Think of dreams: 4 or 5 a night, hugely ran­dom - and only occa­sion­ally if ever do they deliver real insight or a valid idea. Isn’t it a stan­dard joke that you dis­cover the secret of the uni­verse or the per­fect song in a dream, wake up & write it down, and in the morn­ing it is worth­less? It’s prob­a­bly no acci­dent that dreams so rarely pro­duce use­ful insights and also parts of the brain - par­tic­u­larly parts of the pre­frontal cor­tex - are shut down or oper­at­ing dif­fer­ent­ly.

“Once in my life I had a math­e­mat­i­cal dream which proved cor­rect. I was twenty years old. I thought, my God, this is won­der­ful, I won’t have to work, it will all come in dreams! But it never hap­pened again.”

5 6

Microdosing

But if we turned up the tem­per­a­ture just a few degrees, we might wind up burn­ing our cake, but then again we might cook it to per­fec­tion. The­o­ret­i­cal spec­u­la­tion, of course, but with some plau­si­bil­ity to it.

The old research lit­er­a­ture is mixed but sug­gests that LSD does­n’t do much under 20μg. Nonethe­less, when I read “The Heretic” about James Fadi­man’s ideas about “micro-­dos­ing” and an ear­lier inter­view as well as Vice piece7 (I later read his The Psy­che­delic Explor­er’s Guide), and that it seemed to work well for a vari­ety of peo­ple, the old mus­ings came back to mind. A psy­che­delic LSD dose is 100μg+, and Fadi­man’s rec­om­mended micro-­doses 10μg. That puts micro-­doses well into the sub­-hal­lu­ci­na­tory range, and removes most of my safety con­cerns (since even if there were prob­lems with chronic LSD con­sump­tion, “the dose makes the poi­son”). Cer­tainly it sounds good:

“Micro-­dos­ing turns out to be a totally dif­fer­ent world,” Fadi­man extolled. “As some­one said, the rocks don’t glow, even a lit­tle bit. But what many peo­ple are report­ing is, at the end of the day, they say, ‘That was a really good day.’ You know, that kind of day when things kind of work. You’re doing a task you nor­mally could­n’t stand for two hours, but you do it for three or four. You eat prop­er­ly. Maybe you do one more set of reps. Just a good day. That seems to be what we’re dis­cov­er­ing.” Else­where Fadi­man has been more spe­cific about the log­books he’s received. One physi­cian reported that micro-­dos­ing got him “in touch with a deep place of ease and beau­ty.” A vocal­ist said she could bet­ter hear and chan­nel music. In gen­er­al, study par­tic­i­pants func­tioned nor­mally in their work and rela­tion­ships, Fadi­man has said, but with increased focus, cre­ativ­i­ty, and emo­tional clar­i­ty. Until he releases his data archive in a com­pre­hen­sive man­ner, it is, of course, not pos­si­ble to scru­ti­nize the valid­ity of his claim…“I just got a report from some­one who did this for six weeks,” Fadi­man said. “And his ques­tion to me was, ‘Is there any rea­son to stop?’” More laugh­ter through­out the hall, another adjust­ment of bifo­cal­s…it also allows him to fol­low the rec­om­men­da­tion of a long­time, now-de­ceased friend, , who, accord­ing to Fadi­man, called micro-­dos­ing “the most under­-re­searched area of psy­che­delics.”

Fadi­man was part of the team which ran the , admin­is­ter­ing 50μg doses of LSD - close, albeit not iden­ti­cal, to micro­dos­ing lev­els - to peo­ple work­ing on unsolved tech­ni­cal prob­lems, while they tried think­ing about the prob­lems again; they appar­ently often solved them. There are many fans of LSD micro­dos­ing in the rel­e­vant Blue­light.ru & Longecity & Red­dit 1/2/3/4 & Silk Road forum dis­cus­sions (though oth­ers won­der about tol­er­ance after repeated micro­dos­es). Fur­ther, LSD used to be pop­u­lar in Sil­i­con Val­ley and used by many com­put­ing pio­neers (see , Markoff 2005).

None of this, how­ever is par­tic­u­larly strong evi­dence. To address them in order:

  • the orig­i­nal exper­i­ment had unavoid­able flaws8; for exam­ple:

  • sub­se­quent anec­dotes all are nei­ther ran­dom nor blind:

    • we know placebo effects can be extremely pow­er­ful - see the Shulgin orange juice story - and that water or placebo can be mis­taken for LSD (, Lin­ton & Langs 1962, etc)
    • the anec­dotes typ­i­cally are using smaller than 50μg doses
    • they claim unquan­ti­fied ben­e­fits
    • psy­che­delic users are not famous for their reli­able anec­dotes & crit­i­cal think­ing
    • hap­haz­ard pro­ce­dures intro­duc­ing arbi­trar­ily large sys­tem­atic biases
    • the lack of ran­dom­iza­tion for­bids causal inter­pre­ta­tion (cor­re­la­tion ≠ cau­sa­tion)

Fol­lowup work so far has not indi­cated sub­stan­tial effects or ben­e­fits of psy­che­delic micro­dos­ing, with the bet­ter stud­ies find­ing fewer effects, con­tra­dic­tions between self­-re­ported ben­e­fits & objec­tively mea­sured vari­ables, and are con­sis­tent with sub­stan­tial placebo effects:

  • An unblinded exper­i­ment found improve­ment on 2 con­ver­gent & diver­gent think­ing cog­ni­tive tests although not a short Raven’s fluid intel­li­gence test ()
  • an analy­sis cat­e­go­rized ret­ro­spec­tive (cross-­sec­tion­al) free-re­sponse self­-re­ports in a micro­dos­ing sur­vey (Ander­son et al 2019), cat­e­go­riz­ing the free-re­sponses into a set of 46 ‘ben­e­fits’ and ‘chal­lenges’, with many report­ing ben­e­fits (eg Improved mood (26.6%)/Improved focus (14.8%)/Creativity (12.9%)/Self-efficacy (11.3%)/Improved energy (10.5%)/Social ben­e­fits (7.6%)/Cognitive ben­e­fits (5.8%))
  • a larg­er-s­cale analy­sis of unblinded unran­dom­ized vol­un­teers using self-reports/questionnaires in a lon­gi­tu­di­nal design () found small self­-re­ported cor­re­lates on dos­ing days imme­di­ately revert­ing to base­line on sub­se­quent days (but, inter­est­ing­ly, “Many of the vari­ables most expected to change in Study Two actu­ally showed rel­a­tively small changes in Study One. Con­versely most of the vari­ables that showed the largest changes in Study One were not those that par­tic­i­pants expected would change.”)
  • a blinded exper­i­ment of placebo/5–20μg LSD micro­doses found dis­tor­tion of time per­cep­tion but no self­-re­ported dif­fer­ences between con­di­tions (Yanakieva et al 2018; reported more fully in Fam­ily et al 20199)
  • another blinded exper­i­ment of placebo/6.5–26μg (Ber­shad et al 2019) found some sub­jec­tive­ly-re­ported mood effects but no effect on sev­eral cog­ni­tive mea­sures (RAT, dual n-back, & Digit Sym­bol Sub­sti­tu­tion Task)

In gen­er­al, I find it curi­ous that while sup­pos­edly some­thing like 5–10% of the Amer­i­can pop­u­la­tion has at some time taken a psy­che­delic and we know many tech fig­ures have used it, very few spe­cific break­throughs like PCR can be cred­ited to LSD use; of course many would not admit to LSD help­ing them out, but given the claimed large effect size and how many peo­ple have used LSD, there should still be more than the hand­ful of doc­u­mented anec­dotes. (For exam­ple, LSD began com­mer­cial dis­tri­b­u­tion in 1947; from 1948–2014, there were ~264 sci­ence Nobel Prizes exclud­ing Literature/Peace/Economics, hence one might expect ~13–26 Nobelists to have used LSD at some point in their life­time if they used at a sim­i­lar rate as the gen­eral pop­u­la­tion, and much more if LSD did con­tribute to key cre­ative break­throughs espe­cially given the tail effects, but as far as I know the only sci­ence Nobelists who have ever admit­ted—or even been said to have used LSD in some way pos­si­bly related to any impor­tant work—are 3 in num­ber: Richard Feyn­man, Kary Mullis for PCR, and pos­si­bly Fran­cis Crick for DNA. So if one wishes to rea­son from anec­dotes like them (gen­er­ously assum­ing those sto­ries are true), one might con­clude that psy­che­delics usage reduces your abil­ity to make sci­en­tific dis­cov­er­ies, OR=0.23 & p = 0.00610!)

Experiment

Design

LSD is an acute water-­sol­u­ble drug. This makes dos­ing easy: take a sin­gle dose of 250μg, dis­solve it in some water (re­frig­er­at­ed), and then con­sume 1/10th for a dose of 25μg. Some online anec­dotes micro­dose dai­ly, while oth­ers micro­dose every 2 or 3 days.

I ordered 2 tabs from Vita­Cat on Silk Road:

2 250μg doses of LSD on “Mayan” blot­ter paper, shipped from Ger­many in a sealed plas­tic sheet

He shipped them in an enve­lope in an air­tight sealed plas­tic sheet; I kept them refrig­er­at­ed, under­neath a box to block light, and kept sealed until I opened it and used the first one for a trip. The remain­ing tab was kept in the refrig­er­a­tor until a week lat­er. (Given that peo­ple rou­tinely stash tabs in books and other places, I doubt that the week did it much dam­age.) The next morn­ing, I added 25ml of dis­tilled water11 into an air­tight mason jar, dropped the blot­ter in, shook vig­or­ous­ly, refrig­er­ated overnight, and removed the blot­ter the next after­noon.

Self­-blind­ing a liq­uid is as straight­for­ward as self­-blind­ing pills: 2 opaque con­tain­ers (one marked; both kept in refrig­er­a­tor) into which a mil­li­liter drop­per puts a dose of LSD water and a dose of reg­u­lar water.

This sug­gests the fol­low­ing design: a ran­dom­ized dose on day 1, fol­lowed by days 2 and 3 off, then on day 4, drink­ing the sec­ond con­tain­er; on day 7, exam­ine the con­tain­ers record­ing whether active/placebo and final­ly, start­ing over as day 1 of a new pair of 3-day blocks. The power analy­sis (see next sec­tion) indi­cates >19 active days are desir­able, so 190+μg are need­ed; this can be diluted into an evenly divis­i­ble amount like 19ml of water and then 1ml extracted each day. 3 days seems to be the max­i­mum that most micro­dos­ing enthu­si­asts con­sider a dose active for, so there should­n’t be issues with tol­er­ance or car­ry­over. I ran this design by Dr. Fadi­man, who did not object. (This design can be seen as a : of the same sub­ject serv­ing as their own con­trol. No washout period to pro­tect against car­ry-over, though, since I did not expect notice­able effects 4 days out from a micro­dose, and my later analy­sis sug­gests there was none.)

Vita­Cat’s Mayan tabs were adver­tised as 250μg, and I diluted the remain­ing tab into 20ml of water, so nom­i­nally each 1ml dose would have 12.5μg of LSD, which is at least twice the level (5μg) a num­ber of peo­ple have claimed ben­e­fits from micro­dos­ing, so even if the tab was over­stated by 100μg, the dose should still be enough to pro­duce any effects.

I took one addi­tional step: tem­porar­ily sus­pend­ing my lithium self­-­ex­per­i­ment. There are many most­ly-neg­a­tive opin­ions online about the inter­ac­tions of LSD & lithi­um, although most com­menters seem to be talk­ing about ther­a­peu­tic doses of lithium - which are 10-15x larger than the 10mg of lithium oro­tate which I may have been tak­ing if it was­n’t a placebo week. (It later turned out that it was indeed a placebo week so my pre­cau­tion was unnec­es­sary.) But there is no point in risk­ing the described neg­a­tive effects or the weak­en­ing of the trip, so 2 weeks before, the exper­i­ment was paused. Obvi­ously I can’t prove that this is suf­fi­cient, but I think it was enough: I was tak­ing 10mg oro­tate every other day (on aver­age) and the anec­dotes which caused me to place it on hold were from peo­ple tak­ing psy­chi­atric doses which are closer to 500mg, and they gen­er­ally seem to think that the effect of lithium did­n’t last for months (which is con­sis­tent with the fairly fast metab­o­lism of lithium in the body, ~24 hour half-life); as well, I stopped it weeks before the trip, which went fine, which was itself a week before start­ing micro­dos­ing. So for the lithium to have been a prob­lem, one would have to pos­tu­late that the lev­els of lithi­um, already 2 orders of mag­ni­tude below those claimed to cause prob­lems, did not notice­ably inter­fere with the trip, but some­how did inter­fere with results spread over 6 months after­wards.

The listed ben­e­fits are to mood, pro­duc­tiv­i­ty, and cre­ativ­i­ty. We might also want to check other met­rics to see if any LSD ben­e­fit came at a cost. So I will use my usual met­rics plus a new cre­ativ­ity one:

  • Zeo sleep data (pri­mar­i­ly: laten­cy, total sleep, num­ber of awak­en­ings, morn­ing feel)

    I expect lit­tle or no effect on these 4 met­rics, or the more obscure ones like sleep com­po­si­tion (light/REM/deep per­cent­ages). Two-­tailed tests.

  • per­for­mance

    Aver­age grade of cards reviewed on a given day; I expect no effect or a ben­e­fit (the sim­u­lated anneal­ing anal­ogy sounds like it might also work for mem­o­ry). One-­tailed.

  • mood/productivity self­-rat­ing: 1-5

    3 is a nor­mal day, 2 below-av­er­age, 4 a very good day, 5 fan­tas­tic etc. The major pre­dic­tion of the micro­dose the­ory is that mood/productivity/creativity will increase, so the final analy­sis should exploit our prior and use a one-­tailed test that the rat­ings will increase (since high­er=­bet­ter).

  • cre­ativ­ity rat­ing: 1-3

    Sim­i­lar. This is not a met­ric I cur­rently track, but would be a new one. One-­tailed.

  • active/placebo pre­dic­tion

    A pre­dic­tion recorded at the end of each block on Pre­dic­tion­Book.­com; this is not a depen­dent vari­able, but a check for whether there is a reli­ably notice­able sub­jec­tive effect.

  • Before/after ques­tion­naires

    Open­ness is one of the Big Five per­son­al­ity traits, roughly linked with cre­ativ­i­ty, inter­est in nov­elty and vari­ety; while (think self­-dis­ci­pline & hard-­work) tends to increase with age, Open­ness seems to decrease. Per­son­al­ity traits, like IQ, are noto­ri­ously hard to change & pre­dic­tive of many things about a per­son. MacLean et al 2011, a rare RCT of , found that Open­ness was still increased a few per­cent­age points >1 year after dos­ing. (While not that large in mag­ni­tude, MacLean et al 2011 com­pares it with the reduc­tion in Open­ness over 4 decades and increase from suc­cess­ful anti­de­pres­sants or sub­stance abuse treat­men­t.) The effect seemed to be dri­ven by those report­ing a mys­ti­cal expe­ri­ence; despite iden­ti­cal start­ing Open­ness, those report­ing a non-mys­ti­cal expe­ri­ence seemed to see theirs fall. The study has many weak­nesses, but was still the best such study I knew of up to that point. A later RCT on LSD, Carhart-Har­ris et al 2016, found large effects 2 weeks after 75μg on both Open­ness and opti­mism (d = 0.16/0.56 respec­tive­ly). Schmid & Liechti 2017, on the other hand, saw a smaller increase which was not main­tained 12 months lat­er.

    Since to max­i­mize effec­tive­ness, any full trip should be taken before micro-­dos­ing, this sug­gest 3 sam­ples: before-trip, after-trip, after-mi­cro-­dos­ing.

    My first long Big Five sur­vey result (us­ing Per­son­al­ity Project) in early 2012 put my Open­ness at the 87^th per­centile; the sec­ond, 2 days after the trip, was iden­ti­cal (87th per­centile). Since I had no mys­tic expe­ri­ence, this is con­sis­tent with MacLean et al 2011’s analy­sis. A third fol­lowup in March 2013, after the micro­dos­ing exper­i­ment, put me at the 93rd per­centile (need­less to say, the con­fi­dence inter­vals for all 3 over­lap due to the per­centile rank­ing being based on rel­a­tively few ques­tions: ~6 for each per­son­al­ity fac­tor).

We don’t need to worry about time-of-­day effects. The LSD micro­doses were at sim­i­lar times each day (right after get­ting up). All the depen­dent vari­ables were gen­er­ally recorded/done at con­sis­tent times, except for the spaced rep­e­ti­tion scores since I some­times reviewed in the after­noon, but I’ve already inves­ti­gated time-of-­day effects in my spaced rep­e­ti­tion per­for­mance and they are triv­ially small both in my dataset & in a mul­ti­-mil­lion-re­view dataset drawn from thou­sands of Mnemosyne users.

Limitations

There are 3 major poten­tial prob­lems with this exper­i­ment: the results may not gen­er­al­ize beyond me, the tabs may not have con­tained sub­stan­tial lev­els of LSD, and the LSD may have degraded while being stored.

Validity

The first prob­lem is inher­ent to the design and can­not be fixed with­out other peo­ple (who are not me) run­ning com­pa­ra­ble exper­i­ments. When n = 1, as it does here, you are deal­ing with results that may be of high which means that inside the exper­i­ment, the con­clu­sion of the analy­sis is (in this case, “I did not ben­e­fit in these spe­cific ways from LSD micro­dos­ing”), but it is dif­fi­cult or impos­si­ble to know what the is (“peo­ple do not ben­e­fit in these spe­cific ways from LSD micro­dos­ing”). This is a gen­eral prob­lem with my . I am not very opti­mistic that there will be any repli­ca­tions of this exper­i­ment: it seems no one else has tried this in the 60 years or so since LSD was banned, any­one who does so may not pub­lish their results, and most peo­ple are not as patient as I am in run­ning self­-­ex­per­i­ments.

Now, we can still spec­u­late about how my results might gen­er­al­ize to other peo­ple. If LSD micro­dos­ing worked for only a small frac­tion of the pop­u­la­tion, where are all the neg­a­tive anec­dotes? You see some neg­a­tive ones, sure, but very few in gen­eral (I’d guess well under 10% of anec­dotes). Or, is there any a pri­ori rea­son to expect LSD micro­dos­ing to have a lot of vari­a­tion from per­son to per­son? Does the fact that I had an enjoy­able and prob­lem-free trip sug­gest I am a “respon­der” (as­sum­ing micro­dos­ing does work)? Which does one con­sider more plau­si­ble: that my n = 1 dat­a­point is explained by inter­per­sonal vari­a­tion and I just hap­pened to both blind it and be the unlucky guy who nat­u­rally does­n’t ben­e­fit, or that inter­per­sonal vari­a­tion is irrel­e­vant and the stark dif­fer­ence between my dat­a­point and the anec­dotes is fully explained by the method­olog­i­cal prob­lems & other biases which hap­pen when peo­ple don’t use ran­dom­iza­tion & blind­ing? Per­son­al­ly, I see stuff like placebo effects all the time in research (in fact, you could argue that my is about demon­strat­ing that sim­ple expectancy effects can be worth >6 points on IQ test­s), and so I don’t just con­sider the sec­ond expla­na­tion to be pos­si­ble, I con­sider it to be the default expla­na­tion. For me, anec­dotes about sup­ple­ments are con­sid­ered placebo/expectancy/non-randomization/publication-bias/underpowered/biased-recall/etc until proven inno­cent.

Dosage

Any

The next ques­tion is, how can I be sure I got LSD? A dark­net mar­ket is not exactly a lab-qual­ity sup­pli­er.

The answer is that I can­not be sure, any more than any­one get­ting LSD from a non-lab source (which is every­one) can be sure. All I can say is that the sell­er, Vita­Cat, was rep­utable; the Avengers reg­u­larly lab-tested wares (ap­par­ently a Nether­lands lab) to keep sell­ers hon­est and Vita­Cat’s pre­mium Mayan tabs passed the lab tests twice and even up until the end in Octo­ber 2013 his LSD was con­sid­ered one of, if not the, best LSD on SR, and very strong as he claimed12; in gen­er­al, the FBI reported in the SR1 court case high qual­ity lev­els for their pur­chases of LSD among other drugs; the price was not too good to be true (quite the oppo­site); the phys­i­cal small size of the tabs meant that it had to be some highly psy­choac­tive chem­i­cal; my trip using one tab matched reports of LSD trips very closely (and in par­tic­u­lar trip reports used claimed doses of >150μg), and did not match the RC trip descrip­tions I’ve read; there was no bit­ter taste indica­tive of pos­si­ble alter­na­tive hal­lu­cino­gens; the Span­ish lab Energy Con­trol began test­ing purity & dosage in April 2014 and by March 2015 had tested 15 LSD tabs sold on the DNMs, find­ing 100% to be LSD, with mean doses of 123.6μg±40.5μg, range 53-195μg (Caudevilla et al 2016) con­sis­tent with the dosages they are usu­ally sold at. On the other hand, Dutch gov­ern­ment test­ing reports that for LSD sam­ples bought online/offline and sub­mit­ted for test­ing by users, around half were not LSD but a dif­fer­ent psy­choac­tive, with doses at 35μg±36 (van der Gouwe et al 2016). Per­son­al­ly, I would be sur­prised if what I bought was not LSD.

Lab test­ing is not avail­able in the USA (as of 2003) accord­ing to Erowid, and Ecsta­sy­Data will not test LSD (“we can not reli­ably iden­tify [LSD] because of the many iso­mers and related chem­i­cals that look sim­i­lar in a mass spec­trom­e­ter”) or report dose esti­mates - not that I was keen on pay­ing $100, wait­ing 3+ weeks, and using up a tab or two. I decided to also not (from eztest or Ama­zon) because I could not afford the 5-tab pur­chase (when the LSD Avengers call Vita­Cat a “pre­mium” or “elite” sell­er, they weren’t kid­ding), and all an Ehrlich test could tell me was whether there was any alka­loid chem­i­cal in it (which was some­thing I could fig­ure out for myself just by tak­ing a tab), and not even whether it was LSD, and not the dose - which is what I actu­ally needed to know. If I had been able to afford more tabs, I prob­a­bly would’ve done a test any­way (it would at least have reas­sured me I was­n’t get­ting an RC), but I only had 2 tabs. I needed 1 for the micro­dos­es, and 1 to trip with, so… Between trip­ping and test­ing, it was an easy choice.

Useful dose?

Drugs typ­i­cally fol­low s of some sort, some­times with inter­est­ing shapes like the U-curve of the for stim­u­lants. Is it pos­si­ble that the results might be due to falling into a bad place in LSD micro­dos­ing’s curve, what­ever it is?

It’s pos­si­ble that doses might be an issue. But my prob­lem is that even with a dose-re­sponse curve, I should have seen some­thing in the results. Gen­er­al­ly, bio­log­i­cal ‘thresh­olds’ aren’t some magic binary switch where 10μg does noth­ing what­so­ever and 11μg is day and night dif­fer­ence - they’re just slopes that incline faster in that region. They do not look like binary cir­cuits where at 10μg they do absolutely noth­ing and then at 15μg go to the moon. If I saw zero pos­i­tive effects, on a large sam­ple size, at 10-12μg, why would I expect a huge dif­fer­ence on 25μg espe­cially when the orig­i­nal evi­dence for LSD micro­dos­ing is so weak and ques­tion­able? If 15μg was bet­ter than 12, then I should have observed some­thing like a medium effect. If 20μg was bet­ter than 12, I should have observed some­thing like a smal­l­-medium effect. If 30μg was best, I should have seen signs of a small effect, pos­si­bly not sta­tis­ti­cal­ly-sig­nif­i­cant, but clear point-­value shifts. I observed none of that. Vita­Cat’s tab should’ve been no lower than 200μg, which would still yield 19 micro­doses well above the appar­ent thresh­old of 5μg; even if it was just 100μg, that would still be above 5μg per micro­dose.

I am also sus­pi­cious of this response because there is no solid evi­dence of what the dose-re­sponse curve would be for micro­dos­ing, even just the basic shape, much less spe­cific dose lev­els that some­one could tell me that my dose was all wrong and worth­less. And it’s such a con­ve­nient ful­ly-­gen­eral excuse, a : “Xμg did­n’t work for you? Must’ve taken the wrong dose! Try again with [more/less]!” (But …)

Try again? Well, it is the obvi­ous sec­ond exper­i­ment, try­ing mul­ti­ple lev­els of doses (eg. 1, 2, and 3ml dos­es). But I’m not doing a sec­ond one: it took some­thing like 6 months to get any level of cer­tainty with the dose I was using, and if I bought more tabs, then that’s even more oppor­tu­nity to argue that I bought bunk LSD or that the tabs dif­fered in dose etc. Given that I did­n’t see any ben­e­fits, I sim­ply can­not jus­tify tak­ing more time to explore a poten­tial sup­ple­ment which failed the first test. It does­n’t begin to pass the cost-benefit/VoI test for me.

I sug­gest that any­one try­ing their own exper­i­ment also try mul­ti­ple dosages. But only if they are already blind­ing & ran­dom­iz­ing. Not every method­olog­i­cal improve­ment is of equal val­ue.

Degradation

Hav­ing got­ten LSD, could the LSD have then been destroyed in prepa­ra­tion or stor­age? For exam­ple, in the com­ments, a Jes­sica Darko claims:

But more dam­ag­ing is that the drug degrades quickly and is very sen­si­tive to its envi­ron­ment. It degrades in the pres­ence of oxy­gen, heat and light. A com­mon house fridge pro­vides all three- the door is opened at least once a day (to get your dose) let­ting light in. The con­tainer is open to the air which pro­vides oxy­gen, and while a fridge is cool, it is does not absolutely pre­vent degra­da­tion of the drug due to heat. I’ve seen stor­age rec­om­men­da­tions for this drug involv­ing sealed, light opaque con­tain­ers, kept frozen in an ice­box and the admo­ni­tion that this will only pre­serve it for a few weeks.

If freez­ing can­not store safely LSD for more than a few weeks, then clearly it is hope­less to expect micro­doses to last the few months of the exper­i­ment.

LSD does have a rep­u­ta­tion for being frag­ile. How­ev­er, Dark­o’s claims seem to be entirely false and an excel­lent exam­ple of . If LSD really did degrade within weeks under the most opti­mal con­di­tions (and pre­sum­ably just days under more nor­mal con­di­tion­s), how did any­one ever con­sume LSD? Drug sup­ply chains do not oper­ate so fast that they can whisk LSD from the chemist to the user in just a few days. If LSD really did degrade within days, how did any­one ever buy LSD off SR? We can read about LSD dis­tri­b­u­tion chains in places like in the trial tran­scripts for William Leonard Pickard and there is no indi­ca­tion of LSD requir­ing ultra­-­fast deliv­ery or being ultra­-­time-sen­si­tive. No one in any of the forum threads or web pages on LSD micro­dos­ing states that break­down is a con­cern if stored in the dark or refrig­er­ated (as I did); Fadi­man does not men­tion it as a con­cern in his book, and he did not men­tion it as a poten­tial issue when I sent him the exper­i­ment design with time-s­cale. If the claim was even remotely true, it is dif­fi­cult to see how Earth & Fire Erowid could find a vial of LSD which “After 55 years, stored at vary­ing room tem­per­a­tures, the LSD seemed to be fully potent.” remarks in TiHKAL that “As a salt, in water, cold, and free from air and light expo­sure, it [LSD] is sta­ble indef­i­nite­ly.” And it’s dif­fi­cult to see how Li et al 1998 (to bor­row ) could reach results like the fol­low­ing:

A con­trolled study was under­taken to deter­mine the sta­bil­ity of LSD in pooled urine sam­ples.[71] The con­cen­tra­tions of LSD in urine sam­ples were fol­lowed over time at var­i­ous tem­per­a­tures, in dif­fer­ent types of stor­age con­tain­ers, at var­i­ous expo­sures to dif­fer­ent wave­lengths of light, and at vary­ing pH val­ues. These stud­ies demon­strated no sig­nif­i­cant loss in LSD con­cen­tra­tion at 25°C [77°F] for up to four weeks. After four weeks of incu­ba­tion, a 30% loss in LSD con­cen­tra­tion at 37°C [98.6°F] and up to a 40% at 45°C [113°F] were observed. Urine for­ti­fied with LSD and stored in amber glass or non­trans­par­ent poly­eth­yl­ene con­tain­ers showed no change in con­cen­tra­tion under any light con­di­tions. Sta­bil­ity of LSD in trans­par­ent con­tain­ers under light was depen­dent on the dis­tance between the light source and the sam­ples, the wave­length of light, expo­sure time, and the inten­sity of light. After pro­longed expo­sure to heat in alka­line pH con­di­tions, 10 to 15% of the par­ent LSD epimer­ized to iso-LSD. Under acidic con­di­tions, less than 5% of the LSD was con­verted to iso-LSD.

Power calculation

The descrip­tions are that the effects are strong & notice­able, so a large sug­gests a small exper­i­ment; but with 6 met­rics, we will want to cor­rect for (which need will lower the required p-value in our one-­tailed test­s). We’ll assume a large effect size, p = 0.01, and / exper­i­men­tal design13:

library(pwr)
pwr.t.test(d=0.8,type="paired",power=0.80,alternative="greater",sig.level=0.01)

     Paired t test power calculation

              n = 18.47818

19 pairs means 19 active and 19 placebo dos­es, 38 days total. This does not seem unduly oner­ous, but note that we’re assum­ing LSD has a strong effect since if we cut the effect size in half to d = 0.4 (a medi­um-s­mall effect) we need 66 pairs or 132 days! (If the effects were over­sold so d = 0.4 was the cor­rect esti­mate, and we went with 19 pairs, we would not have an 80% chance of detect­ing the effect but rather a 24% chance. Oh well. “We do what we can, because, we must - for the peo­ple who are still alive.”)

How we treat indi­vid­ual days will mat­ter: do we aver­age the data for each block of 3 days into a sin­gle data point, or do we treat each dose as result­ing in 3 data points - the effect on the first day, the less­ened effect on the sec­ond day, and the weak­est effect on the third day? (And then the next dose.) The lat­ter seems to be a bet­ter strat­e­gy, and so with 250μg we get 25 doses of 10μg, each dose is 3 days so as much as 75 days for active and a sim­i­lar amount for place­bo. (75 pairs gives us a sim­i­lar power cal­cu­la­tion all the way down to d = 0.4.)

In ret­ro­spect (after observ­ing the trends which did­n’t reach sig­nif­i­cance), since I spec­i­fied 7 met­rics, it prob­a­bly would have been bet­ter to be con­ser­v­a­tive and spec­ify a sig­nif­i­cance-level of sig.level=(0.05/7) or 0.0071 rather than sig.level=0.05/5 or 0.0100.

VoI

For back­ground on “value of infor­ma­tion” cal­cu­la­tions, see the Adder­all cal­cu­la­tion.

With back­ground, design, and power cal­cu­la­tion out of the way, we can cal­cu­late costs & val­ues.

  1. Cost of reg­u­lar LSD micro­dos­ing

    A check of list­ings on the indi­cates that 300μg can be bought for 5-6btc or $45; 300μg trans­lates to 30 dos­es, or 90 days if I fol­low the 3-day dose pat­tern some rec­om­mend; the yearly cost of LSD is then . Dis­counted at 5% annu­al­ly, the net-present-value/lifetime-cost of switch­ing to LSD would be . We can reuse this fig­ure as the poten­tial ben­e­fit of LSD micro­dos­es, since if the effect is pos­i­tive and large enough to notice, then it seems worth roughly 50 cents a day!

    There are 3 major cat­e­gories of addi­tional costs: the med­ical risk one runs dur­ing the exper­i­ment (prin­ci­pally men­tal), the legal risk, and the rep­u­ta­tional risk.

    1. Schiz­o­phre­nia and other issues:

      Ear­lier, I looked into research bear­ing on the rela­tion of , and con­cluded that the evi­dence was most con­sis­tent with LSD hav­ing small health risks (that is, the dam­aged or ill sought out all sorts of drugs includ­ing LSD, but LSD did not cause the dam­age or at best caused the ill­ness to sur­face ear­lier) with some cor­re­la­tions of ; this was over the gen­eral LSD pop­u­la­tion includ­ing brain-fry­ing large dos­es, so the risk for micro­doses ought to be much small­er. Much later it occurred to me that the rar­ity of using LSD along with sheer small size of LSD actu­ally reduces the risk of con­sump­tion com­pared to many other prod­ucts, sim­ply because dan­ger­ous doses of many con­t­a­m­i­nants or poi­sons won’t fit: blot­ters report­edly max out at ~500μg. Com­pare that with, say, pirac­etam where peo­ple take <3g of pow­der dai­ly; if the pirac­etam was just 0.3% con­t­a­m­i­nants, that’s as much as 1mg of the stuff - but a blot­ter can’t even hold 1mg of any sub­stance, much less an active dose of some sub­stance plus acci­den­tal con­t­a­m­i­na­tion. Over­all, I feel com­fort­able round­ing it to zero. To esti­mate the pos­si­ble impact on schiz­o­phre­nia, I looked into esti­mates of hal­lu­cino­gen con­sump­tion and found that esti­mates ranged from 7-12% of the entire Amer­i­can pop­u­la­tion (~22-38 mil­lion peo­ple) had con­sumed at some point, which over some­thing like a 60-year lifes­pan (teenager to very old adult) implies some­thing like 600,000 hal­lu­cino­gen ‘vir­gins’ per year (a fig­ure echoed in one of Fadi­man’s arti­cles).

    2. Pris­on:

      Search­ing, I found a 1994 fed­eral Sen­tenc­ing Com­mis­sion doc­u­ment list­ing 83 sen­tences involv­ing LSD that year (while search­ing I also found some infor­ma­tion indi­cat­ing that 400μg is con­sid­ered 1 dose, so the micro­dose exper­i­ment would involve <1 dose!); news arti­cles sug­gest many (most?) of those would be for sell­ers and man­u­fac­tur­ers, so a fur­ther analy­sis would reduce the risk accord­ing­ly. In any case, even if we mul­ti­ply by 50 for each state, sug­gest­ing a rough esti­mate of 1 in 145 chance of being con­vict­ed. Leniency could be expected for a first-­time non-vi­o­lent non-­traf­fick­ing offend­er, so we could set the cost of this out­come at per­haps just $100,000, or an expected loss/cost of $700.

    3. Social con­se­quences:

      Some rep­u­ta­tional effects are clearly neg­a­tive: a use of LSD would be a big issue in some roles like run­ning for elected office or being CEO of a large com­pany (un­less one is a sec­u­lar saint like ), espe­cially since I would obvi­ously be unable to make an excuse like “youth­ful exper­i­men­ta­tion” or “a momen­tary lapse of judg­ment”, this writeup demon­strat­ing that my use was thor­oughly pre­med­i­tat­ed; how­ev­er, this does not bother me inas­much as I am unfit­ted by both tem­pera­ment and tal­ent for such posi­tions. (Some­thing sim­i­lar could be said about secu­rity clear­ances.) In many more con­ser­v­a­tive regions, it would be a sub­stan­tial neg­a­tive, but I am already a poor fit for such regions and I don’t know whether an LSD use would be very neg­a­tive at the mar­gin, or whether any of my exper­i­ments or essays have already done the dam­age.

      On the pos­i­tive side, how­ev­er: in some groups or regions like Cal­i­for­nia (which may yet lie in my future), a use of LSD may be a net pos­i­tive as it indi­cates val­ued qual­i­ties like open-­mind­ed­ness. The life­time con­sump­tion rate implies that some­thing like 12% of the pop­u­la­tion would not judge me harshly for any use. That I have been care­ful and respon­si­ble in my exper­i­men­ta­tion, and had mul­ti­ple pur­poses in addi­tion to mere recre­ation, will lessen the offense for many peo­ple (but pos­si­bly would increase my guilt in the eyes of oth­er­s). There are many famous LSD users like , , , Fran­cis Crick, etc, but they seem to have dis­cussed their drug use only after achiev­ing main­stream suc­cess; worse, the famous users all seem to have been asso­ci­ated with the 1960s or with com­put­ers, sug­gest­ing tol­er­ance for them may be a pass­ing phase and younger peo­ple not so lenient (but on the other hand, efforts are actu­ally suc­ceed­ing before and dur­ing 2012, sug­gest­ing that Amer­ica may be more tol­er­ant in the future).

      All con­sid­ered: I am not sure what the rep­u­ta­tional cost would be, nor do I have good ways to esti­mate it, and given the invis­i­bil­ity of many rep­u­ta­tional costs - how do you know when some­one did­n’t offer some­thing to you or how peo­ple are bad-­mouthing you? - I may never know the actual cost to me (com­pared to, say, being arrested for LSD pos­ses­sion).

  2. How much will the exper­i­ment cost to run?

    The pro­ce­dure each morn­ing uses up no more than 5 min­utes so dol­lars of time. The sleep, spaced rep­e­ti­tion, and mood/productivity data I already col­lect, and the cre­ativ­ity self­-rat­ing is another few sec­onds, and so not worth cal­cu­lat­ing. I’m not sure if I have an appro­pri­ate dropper/syringe avail­able; that and other sup­plies might tack on another $10. So dol­lars.

  3. Pri­ors:

    The accu­racy of the infor­ma­tion ranges 20-80% depend­ing on the effect size; since it’s inline with my pre­vi­ous knowl­edge of LSD and based on more than a hand­ful of anec­dotes, I would be some­what opti­mistic about there being an effect, so a 50% chance the effect exists.

  4. Value of Infor­ma­tion

    Power times prior times ben­e­fit minus cost of exper­i­men­ta­tion: -405 to +720. If we cut out the legal risk, the range is +295-1420 and the exper­i­ment well worth doing; our esti­mate of the legal risk and the effect size deter­mine whether we find it worth doing.

Data

Before start­ing the micro­dos­ing exper­i­ment, I used the first tab for a clas­sic trip. The trip was both edu­ca­tional and enjoy­able and what I expected based on the trip reports I’d read on Erowid and many other places (I may post my writeup at some point), albeit I did not have the mys­ti­cal or peak expe­ri­ence I was really hop­ing for, nor did I change my mind sub­stan­tially on any­thing in the back­ground sec­tion.

I then waited roughly a week to reduce poten­tial tol­er­ance before start­ing the micro­dos­ing exper­i­ment prop­er.

  1. Zeroth block (be­fore-after trip­ping, exclud­ing the trip day): 17,18,19 Sep­tem­ber: 0

    20,21,22 Sep­tem­ber: 1

  2. First block: 2,3,2012-10-04: 0

    Sec­ond block: 5,6,7 Octo­ber: 1 (pre­dic­tion: placebo then active, 45%)

  3. First block: 20,21,22 Octo­ber: 1

    Sec­ond block: 24,25,26: 0 (55%)

  4. First block: 27,28,29: 0

    Sec­ond block: 4,5,6 Novem­ber: 1 (60%)

  5. First block: 7,8,9 Novem­ber: 1

    Sec­ond block: 15,16,17 Novem­ber: 0 (40%)

  6. First block: 19,20,21 Novem­ber: 0

    Sec­ond block: 22,23,24: 1 (40%)

  7. First block: 26,27,28 Novem­ber: 0

    Sec­ond block: 2,3,4 Decem­ber: 1 (60%)

  8. First block: 5,6,7 Decem­ber: 1

    Sec­ond block: 8,9,10 Decem­ber: 0 (40%)

  9. First block: 11,12,13 Decem­ber: 0

    Sec­ond block: 14,15,16 Decem­ber: 1 (40%)

  10. First block: 17,18,19 Decem­ber: 1

    Sec­ond block: 20,21,22 Decem­ber: 0 (50%)

  11. First block: 2012-12-31, 1, 2, Jan­u­ary 2013: 0

    Sec­ond block: 3, 4, 5 Jan­u­ary: 1 (40%)

  12. First block: 6, 7, 8 Jan­u­ary: 1

    Sec­ond block: 9, 10, 11 Jan­u­ary: 0 (50%)

  13. First block: 12, 13, 14 Jan­u­ary: 1

    Sec­ond block: 15, 16, 17 Jan­u­ary: 0 (40%)

  14. First block: 18, 19, 20 Jan­u­ary: 1

    Sec­ond block: 22, 23, 24 Jan­u­ary: 0 (60%)

  15. First block: 25, 26, 27 Jan­u­ary: 0

    Sec­ond block: 28, 29, 30 Jan­u­ary: 1 (40%)

  16. First block: 31 Jan­u­ary, 1, 2 Feb­ru­ary: 0

    Sec­ond block: 3, 4, 5 Feb­ru­ary: 1 (65%)

  17. First block: 6, 7, 8 Feb­ru­ary: 0

    Sec­ond block: 10, 11, 12 Feb­ru­ary: 1 (50%)

  18. First block: 13, 14, 15 Feb­ru­ary: 1

    Sec­ond block: 16, 17, 18 Feb­ru­ary: 0 (40%)

  19. First block: 20,21,22 Feb­ru­ary: 1

    Sec­ond block: 23,24,25 Feb­ru­ary: 0 (60%)

  20. First block: 26,27,28 Feb­ru­ary: 0

    Sec­ond block: 1,2,3 March: 1 (60%)

  21. First block: 4,5,6 Feb­ru­ary: 0

    Sec­ond block: 7,8,9 Feb­ru­ary: 1 (75%)

Sub­jec­tive­ly, I noticed noth­ing in the LSD blocks: no “pos­i­tive effects”, no body load, noth­ing like “hard to focus”, visu­al­iz­ing things was not “effort­less”, I did not feel “I could grasp con­cepts much faster”, nor that I was “more tired, spacier, and very apa­thetic” in the con­trol blocks.

Fadiman comments

After I com­pleted the exper­i­ment and pre­pared the data, but before doing any analy­sis (be­sides the pre­dic­tion accu­racy to check the blind­ing), as a form of , I emailed Fadi­man the fol­low­ing ques­tions & ask­ing per­mis­sion to quote him, and he replied:

1. You’ve seen my plan­ning and method­ol­ogy write up, and I’ve attached the cur­rent ver­sion of my full writeup with every­thing I’ve added or changed since (mostly more back­ground, a log of dates, that sort of thing) if you want to reread it. Do you have any objec­tions to how I did it?

Most impor­tant: I am deeply impressed and pleased with your totally orig­i­nal and clev­erly designed exper­i­ment. That you are able to add a dou­ble-blind to a one per­son self­-s­tudy is a delight in itself. I am incred­i­bly happy to see how many dif­fer­ent ways you went at this. In terms of the gen­eral write up, I hap­pened to be an ardent fan of a mix of data, per­sonal reflec­tion and obser­va­tion. Sci­en­tific writ­ing all too often does every­thing it can to make the sub­ject under scrutiny as dull as pos­si­ble in the writ­ing, as unin­ter­est­ing as pos­si­ble, and heaven for­bid, to include any gen­uinely real and per­sonal com­men­tary. So I love the way you did it exact­ly. The changes all seem to me expan­sions and improve­ments.

2. Have you or any­one else as far as you know, done a long blind/randomized/both self­-­ex­per­i­ment on LSD micro­dos­ing?

Short answer. No. Long answer: no one. Longest answer - the num­ber of peo­ple are doing self­-­ex­per­i­ments with LSD and other psy­che­delics and even MDMA is expand­ing. No one is even approach­ing what you’re doing.

3. If the results turn out to be non-s­ta­tis­ti­cal­ly-sig­nif­i­cant or have very small effect sizes, why do you think they might have turned out that way? Which rea­sons would you have most con­fi­dence in as an expla­na­tion of null results?

I do have some guesses as to why non-sig­nif­i­cance might occur, and that is putting aside just the obvi­ous sta­tis­ti­cal pos­si­bil­ity of using small sam­ple sizes. I will be actu­ally very con­tent to see null results since it will force me and oth­ers to dig more deeply for pos­si­ble rea­sons. So far, you are the first who might pro­duce such results and cer­tainly since you’re the first dou­ble-blind, it adds to the value of what you’re doing. As you prob­a­bly know there’s a big con­tro­versy in the reg­u­lar med­ical lit­er­a­ture about how many seri­ous drug stud­ies of multi­bil­lion-­dol­lar drugs and up with no [sta­tis­ti­cal­ly-]sig­nif­i­cant dif­fer­ences a few years out from their sales launch and almost always from uni­ver­si­ty-based stud­ies, not being paid by the phar­ma­ceu­ti­cal com­pa­ny.

In psy­che­delic stud­ies, 100% suc­cess rates are much harder to describe to non-psy­che­delic audi­ences used to more con­ven­tional and much lower suc­cess rates about almost every­thing.

One pos­si­ble rea­son, that only you can answer, and you may have done so in the body of the text, but if so I missed it. I’m not sure that you took a cou­ple of non-blind micro-­doses before­hand to be sure that you could notice a dif­fer­ence with every placebo and pos­i­tive inten­tion going with you to notice the dif­fer­ence to estab­lish a per­sonal base­line of aware­ness of the sub­stance. If that was not done, then it’s not at all clear that the very sim­ple mea­sure­ments used on a daily basis were sen­si­tive enough to pick up days on and days off. The more usual stud­ies from other peo­ple that I’ve seen, (none of them even attempt­ing a dou­ble-blind or any blind at all,) are look­ing for a set of inter­nal changes that they have pre­vi­ously expe­ri­enced. These may be as sub­tle as eat­ing a health­ier lunch, doing a few more reps at a gym, being able to focus on the task an hour longer and so forth. I have a cou­ple of write-ups in my book and when you get to them, you can see that we’re deal­ing with fairly intri­cate inter­nal mea­sures which you also cover in detail now and then in your per­sonal com­men­taries.

That’s my favorite pos­si­ble rea­son. Another is that, while some peo­ple are very aware on the day of the micro-­dose, oth­ers are clear that it is a two-­day expe­ri­ence, and a few even longer. If even a tiny residue of the micro-­dose is still active at the time of the next dose, it might make it harder to dis­tin­guish and on from an off day.

How­ev­er, I’m also aware that also for some peo­ple, the dose is too low.

The report in my book that I find most charm­ing, a woman who’s been micro-­dos­ing for about 8 years - except dur­ing her preg­nancy - uses 20 µg, which for me would be per­cep­tu­al. So an alter­na­tive rea­son, even though the least inter­est­ing one, is that your dose was too low. A few peo­ple had felt it was bet­ter to drop down to 7 or 8µg to not get too high. Human vari­abil­i­ty.

I’m sure I can come up with more com­pli­cated rea­sons, but you asked what my thoughts were before we com­pleted the analy­sis and there you are.

4. Do you expect the results to turn out pos­i­tive? (By pos­i­tive here, I mean sta­tis­ti­cal­ly-sig­nif­i­cant after mul­ti­ple cor­rec­tion and d > 0.1.) How much so?

I did expect the results to turn out pos­i­tive because there are real effects that have been report­ed, not only in my lit­tle stud­ies, but for the past few thou­sand years in indige­nous soci­eties who of course have exper­i­mented with micro-­doses and every other con­ceiv­able form of use.

As to how [sta­tis­ti­cal­ly-]sig­nif­i­cant the sta­tis­ti­cal break­out would be - I’ve not really thought much about it. This was your study and your level of sta­tis­ti­cal sophis­ti­ca­tion clearly exceeds my own. I tend to be some­what sus­pi­cious of any study where the sta­tis­tics are fairly exotic, since I know from watch­ing my grad­u­ate stu­dents PhD dis­ser­ta­tions, that when really sim­ple and almost intu­itively obvi­ous sta­tis­tics don’t show results, they start to shop around until they find some­thing that gives them a pos­i­tive result even if it’s a sta­tis­tic that nobody else seems to know about. I watch sta­tis­ti­cal con­sul­tants assure stu­dents that they will find some­thing that will jus­tify hir­ing them. Is this pure sci­ence as God and Descartes would have it? Not in my book but hey, the real world is never as clean as the data derived from it.

5. Are you will­ing to be quoted on any of the above?

Of course, you are free to quote me in any­thing you write, and I’m free to com­plain that I was quoted out of con­text or any­thing else I choose to say to cover my tail. But in this case, you did the work - you asked me to review the work - and there­fore my review becomes part of the total pack­age.

I did this for much the same rea­son as I wrote down the exact met­rics and analy­sis in advance: to spec­ify what results are expect­ed, how one will inter­pret them, and to elim­i­nate the temp­ta­tion to fudge or mod­ify or spin or self­-de­ceive about any of it.

Analysis

Preparation

Prepar­ing the data:

Needed to extract Mnemosyne scores for the past 175 days; for any addi­tional analy­sis, I’ll want even more days which were nei­ther active nor con­trol so I extract even more days than that (back 451 days). Using a Mnemosyne script in the devel­op­ment repos­i­to­ry, I set the time inter­val:

+++ mnemosyne/mnemosyne/example_scripts/export_stats.py 2013-03-10 21:54:04 +0000
@@ -12,7 +12,7 @@
 data_dir = None
 mnemosyne = Mnemosyne(data_dir)

-for n in range(-10, 0):
+for n in range(-275, -1):
     start_of_day = mnemosyne.database().start_of_day_n_days_ago(abs(n))

Then run it, extract­ing the aver­age grade & trans­form­ing the days I did­n’t review for R:

./bin/python ./mnemosyne/example_scripts/export_stats.py \
     | cut -d ' ' -f 2 | sed -e 's/None/NA/' > ~/mnemosyne.csv

In R I read in a hand-trimmed Zeo export (lsd.csv), parse dates, add in the Mnemosyne daily grades, the mood/productivity & cre­ativ­ity daily self­-rat­ings, and write it all back out:

lsd <- read.csv("lsd.csv")
lsd$Date <- as.Date(lsd$Date, format="%m/%d/%Y")
# Zeo's CSV export silently omits missing days; look for them to hand-edit empty rows in
# which(!((as.Date("2012-06-09"):as.Date("2012-09-15")) %in% lsd$Date))
mnemo <- read.table("mnemosyne.csv")
lsd$Mnemosyne <- NA
lsd$Mnemosyne <- mnemo$V1
mp <- read.csv("mp.csv")
lsd$MP <- NA
lsd$MP <- mp$MP
creativity <- read.table("creativity.csv")
lsd$Creativity <- NA
lsd$Creativity <- creativity$V1
write.csv(lsd, file="lsd.csv", row.names=FALSE)

Blinding

How suc­cess­ful was the blind­ing: could I guess whether I had got­ten a LSD or a place­bo? A com­par­i­son of the log score shows my self­-assess­ments were only slightly bet­ter than ran­dom (eg. remove the last pre­dic­tion, and the ran­dom guesser per­forms equally or bet­ter):

let predictions = [(True,  0.45),(False, 0.55),(True,  0.60),(False, 0.40),(True,  0.40),(True,  0.60),
                   (False, 0.40),(True,  0.40),(False, 0.50),(True,  0.40),(False, 0.50),(False, 0.40),
                   (False, 0.60),(True,  0.40),(True,  0.65),(True,  0.50),(False, 0.40),(False, 0.60),
                   (True,  0.60),(True,  0.75)]
logScore ps = sum $ map (\(result,p) -> if result then log p else log (1-p)) ps

logScore predictions
 -13.4685

log 0.50 * fromIntegral (length predictions)
 -13.8629

Graphing data

Below are the 8 main depen­dent vari­ables, depicted over time & col­ored by whether it fell in a dose 3-day block or control/placebo block. In descend­ing order of impor­tance:

Daily self­-rat­ing of mood+­work accom­plished, 1-5 (higher is bet­ter)
Daily self­-rat­ing of creativity/good-ideas, 1-3 (higher is bet­ter)
Aver­aged recall per­for­mance of Mnemosyne flash­cards, 0-5 (higher is bet­ter)

The 5 sleep vari­ables:

Num­ber of times awoken in a night as recorded by my Zeo (lower is bet­ter)
Total min­utes spent awake after falling asleep (low­er=­bet­ter)
Daily self­-rat­ing about how well-rested I feel imme­di­ately upon awak­en­ing (high­er=­bet­ter)
Total min­utes between putting on Zeo head­set & enter­ing sleep (low­er=­bet­ter)
Total min­utes spent asleep (high­er=­bet­ter)

Testing the metrics

Results from the mul­ti­vari­ate regres­sion:

  1. Sleep:

    • laten­cy: none

    • total sleep: none

    • num­ber of awak­en­ings: none

    • morn­ing feel: increased

      There is an increase in “Morn­ing Feel” from 2.6 to 2.9, d = 0.43, p = 0.011; cor­rect­ing for per­form­ing 7 dif­fer­ent tests, this result is not sta­tis­ti­cal­ly-sig­nif­i­cant (it does not sur­vive a (since ) nor the q-value approach to fam­i­ly-­wise cor­rec­tion). The post hoc MANOVA con­firms that there is het­ero­gene­ity between days between days (p = 0.036), and it is prob­a­bly being dri­ven mostly or entirely by the morn­ing feel.

  2. Flash­card scores: none

  3. Mood/productivity: none (d=-0.18)

  4. Cre­ativ­i­ty: none (d=-0.19)

  5. active/placebo pre­dic­tion: see pre­vi­ous sec­tion

  6. Before/after Open­ness: see pre­vi­ous sec­tion

For ease of inter­pre­ta­tion, the results of the regres­sion in a table:

Vari­able Effect p-value Coef­fi­cien­t’s sign is…
MP -0.14 0.27 worse
Creativity - 0.12 0.28 worse
Mnemosyne - 0.00 0.68 worse
Total.Z 14.3 0.12 bet­ter
Time.to.Z 2.04 0.49 worse
Time.in.Wake 2.78 0.29 worse
Awakenings 0.64 0.25 worse
Morning.Feel 0.37 0.01 bet­ter

Conclusion

Over­all, there seems to have been no mean­ing­ful effects, and wor­ri­some trends. I will not be inves­ti­gat­ing LSD micro­dos­ing fur­ther, as it is highly likely to be a waste of time.

Source code

The full analy­sis, using a fol­lowed by :

R> lsd <- read.csv("https://www.gwern.net/docs/personal/2013-gwern-lsdmicrodose.csv")
R> # filter out baseline
R> lsd <- lsd[!is.na(lsd$LSD),]

R> l <- lm(cbind(MP, Creativity, Mnemosyne, Total.Z, Time.to.Z, Time.in.Wake, Awakenings, Morning.Feel)
            ~ LSD, data=lsd); summary(l)
Response MP :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   3.0339     0.0898   33.79   <2e-16
LSD          -0.1430     0.1293   -1.11     0.27

Residual standard error: 0.69 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0108,    Adjusted R-squared:  0.00197
F-statistic: 1.22 on 1 and 112 DF,  p-value: 0.271


Response Creativity :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   1.4068     0.0734    19.2   <2e-16
LSD          -0.1159     0.1056    -1.1     0.28

Residual standard error: 0.564 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0106,    Adjusted R-squared:  0.00179
F-statistic:  1.2 on 1 and 112 DF,  p-value: 0.275


Response Mnemosyne :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)  3.82558    0.01625  235.40   <2e-16
LSD         -0.00958    0.02340   -0.41     0.68

Residual standard error: 0.125 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0015,    Adjusted R-squared:  -0.00742
F-statistic: 0.168 on 1 and 112 DF,  p-value: 0.683


Response Total.Z :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   519.80       6.36   81.67   <2e-16
LSD            14.28       9.16    1.56     0.12

Residual standard error: 48.9 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0212,    Adjusted R-squared:  0.0125
F-statistic: 2.43 on 1 and 112 DF,  p-value: 0.122


Response Time.to.Z :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    26.58       2.05   12.95   <2e-16
LSD             2.04       2.95    0.69     0.49

Residual standard error: 15.8 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.00425,   Adjusted R-squared:  -0.00464
F-statistic: 0.478 on 1 and 112 DF,  p-value: 0.491


Response Time.in.Wake :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    21.93       1.80   12.17   <2e-16
LSD             2.78       2.59    1.07     0.29

Residual standard error: 13.8 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0101,    Adjusted R-squared:  0.00128
F-statistic: 1.15 on 1 and 112 DF,  p-value: 0.287


Response Awakenings :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    7.237      0.382   18.96   <2e-16
LSD            0.635      0.550    1.16     0.25

Residual standard error: 2.93 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0118,    Adjusted R-squared:  0.00297
F-statistic: 1.34 on 1 and 112 DF,  p-value: 0.25


Response Morning.Feel :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    2.593      0.100   25.92   <2e-16
LSD            0.370      0.144    2.57    0.011

Residual standard error: 0.769 on 112 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0557,    Adjusted R-squared:  0.0473
F-statistic: 6.61 on 1 and 112 DF,  p-value: 0.0114

R> summary(manova(l))
           Df Pillai approx F num Df den Df Pr(>F)
LSD         1  0.142     2.17      8    105  0.036
Residuals 112

R> # MP is the most important metric; what is the effect size (Cohen's d) here?
R> (mean(lsd[lsd$LSD==1,]$MP) - mean(lsd[lsd$LSD==0,]$MP)) / sd(lsd$MP)
[1] -0.1782
R> (mean(lsd[lsd$LSD==1,]$Creativity) - mean(lsd[lsd$LSD==0,]$Creativity)) / sd(lsd$Creativity)
[1] -0.1921

None of the p-val­ues are greater than the nor­mal cut­off after mul­ti­ple-­cor­rec­tion, although Morning.Feel comes close:

R> p.adjust(c(0.27, 0.28, 0.68, 0.12, 0.49, 0.29, 0.25, 0.011), method="BH") < 0.05
[1] FALSE FALSE FALSE FALSE FALSE FALSE FALSE FALSE

Final­ly, I plot the 8 graph­ics seen in the pre­vi­ous sec­tion:

R> png(file="~/wiki/images/nootropics/lsd-totalz.png", width = 780, height = 680)
R> qplot(Date, Total.Z, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-timetoz.png", width = 780, height = 680)
R> qplot(Date, Time.to.Z, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-timeinwake.png", width = 780, height = 680)
R> qplot(Date, Time.in.Wake, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-awakenings.png", width = 780, height = 680)
R> qplot(Date, Awakenings, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-morningfeel.png", width = 780, height = 680)
R> qplot(Date, Morning.Feel, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-mnemosyne.png", width = 780, height = 680)
R> qplot(Date, Mnemosyne, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-mp.png", width = 780, height = 680)
R> qplot(Date, MP, color=LSD, data=lsd)
R> dev.off()
R> png(file="~/wiki/images/nootropics/lsd-creativity.png", width = 780, height = 680)
R> qplot(Date, Creativity, color=LSD, data=lsd)
R> dev.off()

Microdose effect length

One final detail to go with the pre­vi­ous analy­sis is to take a look at whether there were issues with 3-day blocks being a bad choice.

I clas­si­fied by hand each day in the rel­e­vant period by how many days dis­tant it was from the pre­ced­ing LSD micro­dose (that is, the first day of an LSD block is 0, the sec­ond day is 1, the third day is 2, and so on up to 7, and past that I just round down to 7). The idea is that this lets us ask for a lin­ear fit relat­ing MP on days which are n dis­tant from a LSD micro­dose and see if there’s any appar­ent trend - it may be that we failed to see a sta­tis­ti­cal­ly-sig­nif­i­cant rela­tion­ship because we lumped in all days togeth­er.

model1 <- lm(MP ~ DaysSince, data=lsd); summary(model1)

Residuals:
    Min      1Q  Median      3Q     Max
-1.0760 -0.8587  0.0171  0.1413  1.1413

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   2.8587     0.0986    29.0   <2e-16
DaysSince     0.0310     0.0206     1.5     0.13

Residual standard error: 0.712 on 173 degrees of freedom
  (99 observations deleted due to missingness)
Multiple R-squared: 0.0129, Adjusted R-squared: 0.00721
F-statistic: 2.26 on 1 and 173 DF,  p-value: 0.134

plot(jitter(lsd$MP, 0.5) ~ lsd$DaysSince, xlab="Increasing time since a microdose", ylab="Mood/productivity")
abline(model1)
MP regressed against how long ago the last LSD micro­dose was - if it was help­ing, we would expect MP to decrease as we get fur­ther away from the last dose.

More gen­er­al­ly, we can re-run the mul­ti­vari­ate regres­sion with days-s­ince as another pre­dic­tor and see if it adds any­thing:

R> l1 <- lm(cbind(MP, Creativity, Mnemosyne, Total.Z, Time.to.Z, Time.in.Wake, Awakenings, Morning.Feel)
             ~ LSD + DaysSince, data=lsd); summary(l1)
Response MP :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   3.2090     0.2980   10.77   <2e-16
LSD          -0.2847     0.2639   -1.08     0.28
DaysSince    -0.0323     0.0524   -0.62     0.54

Residual standard error: 0.692 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0142,    Adjusted R-squared:  -0.00358
F-statistic: 0.798 on 2 and 111 DF,  p-value: 0.453


Response Creativity :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   1.2435     0.2434    5.11  1.4e-06
LSD           0.0162     0.2155    0.08     0.94
DaysSince     0.0301     0.0428    0.70     0.48

Residual standard error: 0.565 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.015, Adjusted R-squared:  -0.00273
F-statistic: 0.846 on 2 and 111 DF,  p-value: 0.432


Response Mnemosyne :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)  3.80753    0.05400   70.51   <2e-16
LSD          0.00502    0.04781    0.10     0.92
DaysSince    0.00333    0.00949    0.35     0.73

Residual standard error: 0.125 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0026,    Adjusted R-squared:  -0.0154
F-statistic: 0.145 on 2 and 111 DF,  p-value: 0.865


Response Total.Z :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   545.47      21.01   25.97   <2e-16
LSD            -6.49      18.60   -0.35     0.73
DaysSince      -4.73       3.69   -1.28     0.20

Residual standard error: 48.7 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0355,    Adjusted R-squared:  0.0181
F-statistic: 2.04 on 2 and 111 DF,  p-value: 0.135


Response Time.to.Z :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    32.69       6.80    4.81  4.8e-06
LSD            -2.91       6.02   -0.48     0.63
DaysSince      -1.13       1.19   -0.94     0.35

Residual standard error: 15.8 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0122,    Adjusted R-squared:  -0.00562
F-statistic: 0.684 on 2 and 111 DF,  p-value: 0.506


Response Time.in.Wake :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)   26.155      5.978    4.38  2.7e-05
LSD           -0.639      5.292   -0.12     0.90
DaysSince     -0.779      1.051   -0.74     0.46

Residual standard error: 13.9 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.015, Adjusted R-squared:  -0.00275
F-statistic: 0.845 on 2 and 111 DF,  p-value: 0.432


Response Awakenings :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    9.374      1.251    7.49  1.8e-11
LSD           -1.093      1.108   -0.99    0.326
DaysSince     -0.394      0.220   -1.79    0.076

Residual standard error: 2.9 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0396,    Adjusted R-squared:  0.0223
F-statistic: 2.29 on 2 and 111 DF,  p-value: 0.106


Response Morning.Feel :

Coefficients:
            Estimate Std. Error t value Pr(>|t|)
(Intercept)    2.181      0.330    6.61  1.4e-09
LSD            0.704      0.292    2.41    0.018
DaysSince      0.076      0.058    1.31    0.193

Residual standard error: 0.766 on 111 degrees of freedom
  (13 observations deleted due to missingness)
Multiple R-squared:  0.0701,    Adjusted R-squared:  0.0533
F-statistic: 4.18 on 2 and 111 DF,  p-value: 0.0177

R> summary(manova(l1))
           Df Pillai approx F num Df den Df Pr(>F)
LSD         1  0.142     2.15      8    104  0.038
DaysSince   1  0.076     1.07      8    104  0.390
Residuals 111

None of the esti­mates are sta­tis­ti­cal­ly-sig­nif­i­cant, but the MANOVA sug­gests that there’s mod­est evi­dence that the amount of time since a dose mat­ters. To sum­ma­rize the results for using DaysSince as well in a neat lit­tle table:

Vari­able Effect p-value Coef­fi­cien­t’s sign is…
MP -0.03 0.54 worse
Creativity 0.03 0.48 bet­ter
Mnemosyne 0.00 0.73
Total.Z -4.73 0.20 worse
Time.to.Z -1.13 0.35 bet­ter
Time.in.Wake -0.78 0.46 bet­ter
Awakenings -0.39 0.07 bet­ter
Morning.Feel 0.08 0.19 bet­ter

Do we get a bet­ter fit if we omit days “too far” from the micro­dose, rea­son­ing that the effects would’ve stopped? Look­ing just at MP to keep things sim­ple:

R> for (i in 7:2) { print(summary(lm(MP ~ DaysSince, data=lsd[!(lsd$DaysSince>=i),]))); }
days removed cor­re­la­tion p
+0.03100 0.13
7th +0.00418 0.90
6,7 -0.00514 0.89
5,6,7 -0.05220 0.32
4,5,6,7 -0.06680 0.35
3,4,5,6,7 -0.17400 0.11
2,3,4,5,6,7 +0.00000 1.00

Obvi­ously the p-val­ues are mean­ing­less in this appli­ca­tion; more impor­tant­ly, the rever­sal of coef­fi­cient sign and chang­ing coef­fi­cient size & sig­nif­i­cance don’t sug­gest any­thing in par­tic­u­lar to me about dose peri­od.

Appendices

Trip report

In Sep­tem­ber 2012, I pre­pared a table of SR1 LSD ven­dors & prod­ucts. When Vita­Cat’s list­ings went up, I added them in and they were no-brainer to order. I ordered a 2-tab Mayan on the 5th and they arrived on the 19th barely within my pre­dicted time period of 2 weeks (but they did arrive). I rather liked their stealth pack­ag­ing, that would not have occurred to me. My main com­plaint was that I was expect­ing it to arrive by the 15th or 16th, and when I PMed the ven­dor for the track­ing num­ber (I had paid for that), he never replied. More than a lit­tle annoy­ing at the time, but the pack­age did arrive, so I decided to leave a 5-s­tar review after my trip.

I spent the next day doing the first tab. I should men­tion I have never done any psy­che­delics before, so I can’t really judge from my expe­ri­ence whether they were 250μg as adver­tised (at least with most other drugs I’ve used, the first use is the strongest, I don’t have any other trips to com­pare to, and there is much between-­sub­ject vari­a­tion). It was a long and exhaust­ing day, so I will just sketch it. I had a light break­fast, went through my check­list of prepa­ra­tions: empty cam­era, back up com­put­er, clean up, shower & dress nice­ly, hide modafinil & other tab of LSD, and then review the trip plan - med­i­ta­tion, music, and walk.

At 1:25PM I fin­ished prepa­ra­tions, took the tab sub­lin­gual­ly, and went out­side with my blan­ket to med­i­tate. I noticed no taste beyond the paper. It was an extremely nice day out, with a very bright sun but a cool steady breeze off the water. I was dis­ap­pointed in the first hour when noth­ing seemed to be hap­pen­ing dur­ing my med­i­ta­tion except I found it unusu­ally easy to con­cen­trate. I won­dered if my slight mus­cle tremors were relat­ed, but I find the half-lo­tus pos­ture dif­fi­cult so that is not unusu­al. By 1:54 I fin­ished med­i­tat­ing. A lit­tle dis­ap­pointed that after half an hour, noth­ing seemed to be hap­pen­ing, I headed inside for some music.

The music was unusu­ally absorbing; but within 15 min­utes (by 2:26), a vague tired­ness like I needed a nap, a headache, and some nau­sea had built up. At 2:45, I made myself a PB&J sand­wich, but the bad feel­ing does­n’t go away so I decide it’s a good time to go for a long walk. (I check my pupils in the mir­ror before going. They seem a lit­tle big­ger but I was­n’t sure if I was imag­in­ing it - I don’t reg­u­larly check my pupils’ dila­tion.)

The walk at 2:50 makes me feel a lit­tle bet­ter within 10 min­utes. Dur­ing the walk, I notice my body seems to be feel­ing ‘mechan­i­cal’ and my move­ments weak­er, with my skin feel­ing like a flesh glove (if that metaphor makes sense), although at the same time, the bright sun­light and cool wind feel excep­tion­ally vivid to my sens­es; I was reminded of when I went sky­div­ing and on the way down, the world seemed to ‘pop’. Appar­ently the acid­head term for this is ‘body load’. My nor­mal chat­ter of thoughts and intro­spec­tion slowed down con­sid­er­ably, per­haps because the walk was mak­ing me feel much bet­ter and I was try­ing to enjoy the raw sen­sa­tions. I was relieved that the LSD was not a bust as I had begun to fear, since that would force a hard choice (con­tinue the micro­dos­ing exper­i­ment with LSD of unknown qual­ity or quan­ti­ty, or aban­don it by using the sec­ond tab to see if the first tab was a fluke?). One per­sis­tent prob­lem was my jaw or neck mus­cles seemed to be rigid or clench­ing and I had to keep relax­ing them or they would cre­ate a sort of wan­t-­to-vomit feel­ing, which was pretty strange when I focused on it. But I still was­n’t impressed by the expe­ri­ence.

In no real hurry at all, by 3:25 I got to the end of the road where there’s a beau­ti­ful view of the inlet and the sky. As I usu­ally do on this walk, I hap­pened to spend a lit­tle time cloud-watch­ing, and I real­ized that the clouds were strob­ing like stop-an­i­ma­tion as I focused on indi­vid­ual patch­es; in par­tic­u­lar, I real­ized that I could force a visual flip (like the young/old woman opti­cal illu­sion or the rab­bit-­duck illu­sion) from see­ing a sky of blue with thin clouds to a roil­ing storm­scape where the blue was the black, and the white clouds were just the illu­mi­nated under­side. Quite inter­est­ing, and an unex­pected inver­sion. I also could tem­porar­ily force by visu­al­iz­ing and will­ing the clouds to form claw or grasp­ing hands or vaguely human-­like shapes.

This absorbed my atten­tion for half an hour or so until a guy on the pier asked if I was OK (I hope just because I’d been lay­ing look­ing like I was tak­ing a nap and not because I was vis­i­bly trip­ping). I waved him off suc­cess­fully but I decided it was a good time to head back. The walk back was entirely unevent­ful, although I stopped at the grove of trees by my place to watch the clouds some more from a longer per­spec­tive.

Back home, I spent the next 2-3 hours lis­ten­ing to music by tracks, which while plan­ning I had thought would sound bet­ter on LSD. I was right - the expe­ri­ence was amaz­ing. Lying in bed with my eyes blind­folded and just lis­ten­ing care­ful­ly, I have never fol­lowed the music so well, or been so moved emo­tion­ally or phys­i­cally by it. My mis­an­thropic soul was moved twice to tears.

Entirely wrung out by the expe­ri­ence, I went out to watch the sun­set over the creek with the cat and rumi­nate over the day. This actu­ally turned out to be almost as mean­ing­ful, since I real­ized as the cat gam­boled over our lit­tle hill of a few tons of rocks that a cat or fox play­ing on a pile of rocks as the sun set was a good metaphor for my own life. (I am a thor­ough-­go­ing athe­ist, and as I pre­dict­ed, I had no real mys­ti­cal expe­ri­ence and I remained an athe­ist.) This real­iza­tion made me feel bet­ter.

When I went in, I was sit­ting in the bath­room think­ing how my expec­ta­tions were guid­ing the visual effects, and I thought to myself, “Speak­ing of parei­do­lia, I bet even this orange-bleach-s­tained towel could become some­thing inter­est­ing if I focus hard enough” and after a few min­utes I real­ized that I could see the stains as the Tibetan under­world god and see the flames flicker behind the tow­el. (Yama is not impor­tant to me and I do not think about him, so I don’t know how he came to mind. For a report in mid­dle or high school long ago, I had drawn by hand a large albeit stripped down copy of a Yama man­dala because his design was really cool. I guess it stuck!)

After that I watched (I pre­fer it to 2001: A Space Odyssey, and needed to rewatch it for my Gainax research), which was as excel­lent as I remem­bered. I noticed a num­ber of things this time around that I had­n’t the first time, like the pro­tag­o­nist employ­ing his sword train­ing in deal­ing with an assas­sin - echo­ing the gen­eral theme of him draw­ing on the train­ing & space pro­gram he had pre­vi­ously con­sid­ered use­less. I also think I under­stand his attempted rape bet­ter: through­out the movie appear dichotomies between peace & war, good and bad - the space pro­gram is peace­ful but used to spark war, tech­nol­ogy is what lifts up man but also used to hurt and kill, etc. The pro­tag­o­nist befriends the woman and orphan, but there can be a thin line between love and desire.

By 9:39, I fin­ished it and then did some dual n-back to see how bad my per­for­mance was 9-10 hours after dos­ing (av­er­age: 50/20/41/42/47). Some generic read­ing and chat­ting online rounded off my day. By this point, I felt pretty much fine except for some odd fine motor con­trol issues: typ­ing had become sur­pris­ingly chal­leng­ing as I had to think about it. But I was kind of tired from all the new expe­ri­ence, so I went to bed - where­upon I suf­fered mas­sive insom­nia. This appar­ently isn’t an unknown effect, although the reports I read did not empha­size it, and I should have planned on going to bed more like 3AM. Oh well. A les­son is learned but the dam­age is irre­versible.

(To quan­tify what I mean by insom­nia, here are the Zeo num­bers: I went to bed at 12:50AM, took 2.1 hours to fall asleep, slept for only 7.4 hours, awoke 8 times, and self­-rated my morn­ing feel at 1. All of these val­ues are extreme for me: in z-s­cores, the last 4 are respec­tively 8.713 (!), -0.7232, 0.5249, & -2.304.)

Over­all, a good expe­ri­ence as I expected espe­cially since I expe­ri­enced no law enforce­ment trou­ble and so far have expe­ri­enced no flash­backs. But I’m not sure I’ll ever need to do a LSD trip again (the sec­ond tab is for the micro­dose exper­i­men­t), and I don’t under­stand how peo­ple can do it on even a monthly basis, for a num­ber of rea­sons: LSD isn’t cheap, for starter; I felt it was too pow­er­ful an expe­ri­ence to undergo for friv­o­lous rea­sons (I def­i­nitely see why it was inves­ti­gated in con­nec­tion with brain­wash­ing); and in par­tic­u­lar, one should­n’t weaken it but save it for when one has ques­tions or needs.

In ret­ro­spect, 250μg may have been too high and respon­si­ble for the ‘body load’ and the insom­nia. I’ve felt some­what sim­i­lar feel­ings with too-high doses of stim­u­lants and nootrop­ics. (I don’t regard it as a big deal, though: the insom­nia was much more unpleas­ant, and I think could have been dealt with by stay­ing up lat­er.) Oth­er­wise, the dose was OK. As I said, I had planned things and hid­den any­thing incrim­i­nat­ing and had already done the risk analy­sis, so I was­n’t wor­ried about police. It was a beau­ti­ful day out, few peo­ple were around, and I knew I was safe (and also that think­ing I was safe helped make me be safe - ‘’, right?). Plus, I am a rel­a­tively calm & emo­tion­ally con­trolled, so I fig­ured I had less rea­son to fear turn­ing out like the cliched ‘friend pan­ick­ing in the woods after a dose’. It seemed to work out.

I did­n’t write it up the next day because I was still feel­ing poorly from the insom­nia, but the day after that. Hope­fully the dis­tance does not dis­tort too much.

Comments

Dis­cussing with a third party the above trip report in Octo­ber 2013:

I am sur­prised that your pre­dic­tions for becom­ing a the­ist after the expe­ri­ence were so high! I’m also sur­prised that you would con­tinue with the exper­i­ment regard­less. I would have thought that this would rep­re­sent a destruc­tion of some kind of sacred val­ues.

I have a healthy respect for the power of mate­r­ial con­di­tions. I’m not the sort of per­son to think “sure, plenty of other peo­ple found reli­gion after hallucinating/taking-drugs/etc, but I’m sure I’m immune!” I’d rather be a the­ist know­ing they’re believ­ing for irra­tional rea­sons and that it’s an , than an athe­ist unsure whether it’s belief or alief.

Much of your expe­ri­ence sounds famil­iar, so there you go. The visual effect is inter­est­ing, it makes it so much more clear that high­-level con­cepts do feed back down into lower level per­cep­tions.

Yes, like an ultra­-pow­er­ful ver­sion of visual illu­sions, par­tic­u­larly the . I won­der if any of the peo­ple in illu­sions are had taken psy­che­delics at some point and been impressed by the top-­down influ­ence of appar­ent­ly-bot­tom-up process­es?

Music is indeed incred­i­ble. I usu­ally assume 12 hours of sleep­less­ness after dos­ing, FYI.

“My mis­an­thropic soul was moved twice to tears.” - This inter­ests me the most, largely because you self­-i­den­tify as mis­an­throp­ic. I’m curi­ous where that comes from, whether this is some­thing you endorse, and whether this expe­ri­ence has changed that in any way.

It comes from a sort of ‘every­one on the Inter­net is wrong’ feel­ing. For bet­ter or worse, I spend a lot of time inter­act­ing with peo­ple who are igno­rant, unaware of the huge flaws in their beliefs and approach­es, biased, uncal­i­brat­ed, and unin­clined to do any­thing about this. (LW is not excluded here. How many times have I spent 5 sec­onds in Google to con­firm or dis­con­firm a claim, which another com­menter was too lazy to do? I think the list I was keep­ing is up to 30 entries or so.)

The com­ments on my LSD micro­dos­ing exper­i­ment bring this out in dra­matic relief: every­one is eager to find some flaw, no mat­ter how improb­a­ble, which will let them dis­miss the results com­pletely and not update in the slight­est bit. Will any of them do a bet­ter exper­i­ment to improve the claimed fatal flaw? Nope. I can’t even except Fadi­man here. While he did­n’t give me any of the bull­shit a lot of peo­ple did, I asked him before I posted it whether he or any­one else had attempted to repli­cate my exper­i­ment. No one had. To empha­size that: Fadi­man is a trained psy­chol­o­gist who appre­ci­ates the need for sys­tem­atic data col­lec­tion + ran­dom­iza­tion + blind­ing with easy access to LSD who is keenly inter­ested in micro­dos­ing inas­much as he has done micro­dos­ing for decades while pub­licly pro­fess­ing its val­ue, who under­stands & admires my pro­ce­dure and has had at least half a year to repli­cate my exper­i­ment him­self - and has not done so!

It’s not like this is a triv­ial issue for him, it’s his decades-­long career at this point. It’s not like it’s a triv­ial ques­tion for micro­dos­ing users, micro­dos­ing is a has­sle which comes with real legal risk & cost. Yet…

Have you noticed any last­ing effects in gen­er­al?

I felt bet­ter about myself for a lit­tle while, but I think it wore off. The most notice­able last­ing effect so far has been anger at the bla­tant intel­lec­tual dis­hon­esty of many pro-LSD com­menters.


  1. As of March 2017, I have been con­tacted by at least 5 peo­ple plan­ning blinded or unblinded LSD micro­dos­ing exper­i­ments; unfor­tu­nate­ly, none have reported results.↩︎

  2. As opposed to other things, like beau­ti­ful - I am still an admirer of the Old Tes­ta­men­t’s .↩︎

  3. , Carhart-Har­ris & Nutt 2017 makes a sim­i­lar anal­ogy but apply­ing it to the com­mon descrip­tion of the anti-de­pres­sive ben­e­fits of psy­che­delics as being like “reset­ting your brain”:

    In the con­text of 5-HT2AR sig­nalling and how this may inform on the func­tion of brain sero­ton­in, one may think of enhanc­ing 5-HT2AR sig­nalling as anal­o­gous to increas­ing the tem­per­a­ture (or excitabil­i­ty) of the brain; indeed, the exci­ta­tory effect of 5-HT2AR sig­nalling has long been recog­nised (; ). Extend­ing this anal­ogy to the process of anneal­ing (i.e. whereby a metal is heated to make it more mal­leable) - one may think of 5-HT2AR sig­nalling as func­tion­ing to induce an entropic state char­ac­terised by enhanced flex­i­bil­ity and mal­leabil­ity dur­ing which work can be done that, upon cool­ing, may leave a last­ing change (Gop­nik, 2010). Viewed through the lens of the pop­u­lar Bayesian brain model of brain func­tion (), one could see this 5-HT2AR-­me­di­ated entropic state as work­ing to ‘reset’ rein­forced pri­ors in depres­sion - such as pes­simistic beliefs and neg­a­tive self­-per­cep­tions (). See Carhart-Har­ris et al. (2017b) [un­pub­lished: “Psilo­cy­bin for treat­men­t-re­sis­tant depres­sion: fMRI-measured brain mech­a­nisms”] for recent neu­ro­bi­o­log­i­cal sup­port for this idea

    ↩︎
  4. in Psy­chi­a­try and the Human Con­di­tion on psy­che­delics:

    Cre­ativ­ity is here seen [by psy­che­delic pro­po­nents] as some­thing to be lib­er­at­ed. It is some­times claimed that by ren­der­ing appar­ently peak expe­ri­ences more com­mon and con­trol­lable, drugs may allow the attain­ment of a ‘higher’ form of human evo­lu­tion. Sorry to be bor­ing, but: Evo­lu­tion­ary the­ory takes exactly the oppo­site view to [Al­dous] Hux­ley - instead of humans ‘nat­u­rally’ know­ing every­thing and evolv­ing the abil­ity to expe­ri­ence less; biol­ogy sees the start­ing point in insen­tient, inert mat­ter and regards the capac­ity to per­ceive any­thing at all as hav­ing evolved grad­u­ally over many mil­lions of years. Knowl­edge is cer­tainly not out there wait­ing to burst in on our minds as soon as intox­i­ca­tion lets it through. Rather, the capac­ity to attain knowl­edge, to per­ceive, and to be aware of our per­cep­tions, are all adap­ta­tions that have been painstak­ingly con­structed over an evo­lu­tion­ary timescale. Nei­ther is sci­en­tific cre­ativ­ity spon­ta­neous, nat­ural or pre-­formed; it is attained by con­struc­tive human striv­ing - some­thing made, not a spon­ta­neous fact of nature. No sci­en­tific break­throughs have ever come from igno­rant and une­d­u­cated prodi­gies who hap­pened to be intox­i­cat­ed. Nei­ther does cre­ativ­ity in sci­ence emerge like a beau­ti­ful but­ter­fly break­ing from a chrysalis of social con­ven­tion, rather it is some­thing con­structed by efforts and gifts (and luck) - includ­ing the efforts and gifts of col­leagues. Sci­ence requires knowl­edge and skill as well as the right state of mind.

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  5. Jan­u­ary 14, 1974, in “Con­ver­sa­tions with Gian-­Carlo Rota”; as quoted on pg262 of Tur­ing’s Cathe­dral (2012) by ↩︎

  6. Although Ulam may be excep­tional in hav­ing even one dream. , (1945), pg27

    Let us come to math­e­mati­cians. One of them, Mail­let, started a first inquiry as to their meth­ods of work. One famous ques­tion, in par­tic­u­lar, was already raised by him that of the “math­e­mat­i­cal dream”, it hav­ing been sug­gested often that the solu­tion of prob­lems that have defied inves­ti­ga­tion may appear in dreams. Though not assert­ing the absolute non-ex­is­tence of “math­e­mat­i­cal dreams,” Mail­let’s inquiry shows that they can­not be con­sid­ered as hav­ing a seri­ous sig­nif­i­cance. Only one remark­able obser­va­tion is reported by the promi­nent Amer­i­can math­e­mati­cian, Leonard Eugene Dick­son, who can pos­i­tively assert its accu­ra­cy….Ex­cept for that very curi­ous case, most of the 69 cor­re­spon­dents who answered Mail­let on that ques­tion never expe­ri­enced any math­e­mat­i­cal dream (I never did) or, in that line, dreamed of wholly absurd things, or were unable to state pre­cisely the ques­tion they hap­pened to dream of. Five dreamed of quite naive argu­ments. There is one more pos­i­tive answer; but it is dif­fi­cult to take account of it, as its author remains anony­mous.

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  7. LSD micro­dos­ing has, if any­thing, become even trendier since I ran my self­-­ex­per­i­ment. Addi­tional media pieces include Wired’s “Would you take LSD to give you a boost at work? WIRED takes a trip inside the world of micro­dos­ing”, Vox, Wash­ing­ton Post, Reset.me, GQ, NYT, BBC, Verge, The Econ­o­mist↩︎

  8. I don’t blame them for this, since they were abruptly inter­rupted by a higher power before they could do any­thing but a pilot exper­i­ment (and barely even that). But the flaws can’t be ignored or wished away.↩︎

  9. Fam­ily et al 2019 amus­ingly notes “The placebo group had a remark­ably high num­ber of ner­vous sys­tem and psy­chi­atric TEAEs [Treat­ment Emer­gent Adverse Events]. One inter­pre­ta­tion of these results is that LSD’s well-­known pro­file cre­ated an expectancy bias” & ref­er­ences Polito & Steven­son 2019.↩︎

  10. Treat­ing it as a pro­por­tions test and test­ing against the lower bound of 5% life­time preva­lence:

    prop.test(3, 264, p=0.05)
    #     1-sample proportions test with continuity correction
    #
    # data:  3 out of 264, null probability 0.05
    # X-squared = 7.5032, df = 1, p-value = 0.006159
    # alternative hypothesis: true p is not equal to 0.05
    # 95% confidence interval:
    #  0.002939376324 0.035612495762
    # sample estimates:
    #             p
    # 0.01136363636
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  11. LSD is neu­tral­ized by ; later I learned chlo­rine is not added to my well, so this pre­cau­tion was unnec­es­sary.↩︎

  12. An impor­tant point, since most ordi­nary LSD tabs, as mea­sured by the DEA (re­ported in its Micro­gram pub­li­ca­tion) and other sources, are closer to 100μg than 250μg.↩︎

  13. Because this is a cross-over design with repeated AB/BA pairs, I could legit­i­mately treat this as a repeat­ed-mea­sures sit­u­a­tion and use a paired t-test. But as it turns out, using a more con­ser­v­a­tive two-sam­ple t-test was not going to change any­thing in our con­clu­sion. A paired t-test is more pow­er­ful than a two-sam­ple t-test, so when we know that the paired _t_t-test turned in non-sig­nif­i­cant p-val­ues (as they did), we then know what the two-sam­ple tests would say: they will just give even more non-s­ta­tis­ti­cal­ly-sig­nif­i­cant results than the paired did.↩︎