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 Bon­fer­roni cor­rec­tion (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 psy­chi­atric ben­e­fit from use; 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 Bon­fer­roni cor­rec­tion (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 :

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

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
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

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

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:

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

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
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:

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.

Other 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

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  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
    ↩︎
  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.↩︎