Abram Hoffer, MDF, PHD, FRCP(C)

Rose, my wi f e, was convi nced t hat t hi ngs do not happen by chance, t hat
t hey ar e beshar ed, meant t o be. My good f r i end Wi l l i amPar sons who was t he
f i r st physi ci an t o conf i r mour 1955 f i ndi ngs t hat ni aci n l ower ed chol est er ol
l evel s al so uses t he t er mI t was meant t o be when he t al ks about how my
vi si t t o t he Mayo Cl i ni c as a guest l ect ur er i n 1956 and a chance
conver sat i on wi t h Pr of essor Howar d Rome at our Sat ur day ni ght di nner l ed t o
t hi s ver y i mpor t ant wor k. For i f t he Mayo cl i ni c had not under t aken t hat
f i r st st udy i t mi ght have never t aken of f t o become t he wor l d s gol d st andar d
f or l ower i ng chol est er ol and el evat i ng hi gh- densi t y l i po pr ot ei n chol est er ol
l evel s. Maybe t hey ar e bot h r i ght . And i t occur s t o me t hat what happened i n
Saskat chewan i n t he spr i ng of 1953 was beshar ed or meant t o be. Whet her i t
was meant t o be or not t o be i t was one t he most f or t unat e event s i n t he
hi st or y of psychi at r y, at l east , t hat i s my vi ew. I n our ni aci n chol est er ol
di scover y we wer e ver y f or t unat e t o have Wi l l i amPar sons J r
1
f r oma
pr est i gi ous medi cal gr oup l i ke t he Mayo Cl i ni c cor r obor at e our f i ndi ngs.
Unf or t unat el y i n psychi at r y no one equi val ent t o Dr Par sons has yet appear ed.

One hot , dust y, summer day i n Saskat oon, Saskat chewan, a st r ange
const el l at i on of event s came t oget her . I had been appoi nt ed Di r ect or of
Psychi at r i c Resear ch begi nni ng i n J ul y 1, 1950. I woul d be gi ven t i me t o
l ear n psychi at r y. I had compl et ed my Medi cal Degr ee, had my Ph. D. i n
Agr i cul t ur al Bi ochemi st r y and one year gener al r ot at i ng i nt er nshi p and of
cour se knew no psychi at r y. That was a maj or advant age because I di d not know
enough about psychi at r y t o be convi nced t hat one coul d not t ackl e such a
ser i ous t opi c as schi zophr eni a. Ther e i s a st or y about I r vi ne Langmui r , a
ver y f amous Amer i ca physi ci st , He j oi ned Gener al El ect r i c and was t ol d he
woul d be assi gned t he pr obl emof t he i ncandescent l i ght bul bs t hat bur ned out
t oo qui ckl y. They f or got t o t el l hi mt hat t hi s was not sol vabl e, as t hey had
t ol d ever y pr evi ous new physi ci st . Langmui r sol ved i t by evacuat i ng t he ai r
f r omt he bul bs so t hat t he car bon f i l ament di d not bur n up as qui ckl y. He
event ual l y became head of t hei r r esear ch di vi si on. No one t ol d me t hat t he
pr obl emof schi zophr eni a coul d not be sol ved. The second condi t i on was t hat I
woul d be abl e t o vi si t t he maj or psychi at r i c r esear ch l abor at or i es i n Canada
and t he Uni t ed St at es. Af t er our t our , I was l ef t wi t h t wo mai n i mpr essi ons.
The f i r st was t hat psychoanal ysi s was a bust and secondl y t hat t he onl y
i nt er est i ng t hi ngs I hear d wer e f r omNol an DC Lewi s, Chai r , Depar t ment of
Psychi at r y, Col umbi a Uni ver si t y and f r omHei nr i ch Kl uver , Pr of essor ,
Uni ver si t y of Chi cago who spoke about t hei r r esear ch wi t h mescal i ne. But I
di d not get any i dea how we woul d st ar t our r esear ch. Lucki l y I soon gave up
an ear l i er i dea t o st ar t psychosomat i c r esear ch.

The second maj or event was Humphr y Osmond s ar r i val . Humphr y and hi s
cl ose f r i end and col l eague J ohn Smyt hi es
2
had exami ned t he psychot omi met i c
exper i ence i nduced by mescal i ne and came t o t he concl usi on t hat i t r esembl ed
i n many ways t he exper i ence i nduced i n nor mal peopl e by schi zophr eni a. They
al so di scover ed t hat mescal i ne i s si mi l ar i n st r uct ur e t o adr enal i n and t hat

1 Parsons WB Jr Cholesterol Control Without Diet. The Niacin Solution,
Revised, Expanded, Second Edition,
Lilac Press, Scottsdale Arizona 85252-1356 2003


2 Osmond H & Smythies J Schizophrenia: a new approach J Mental Science
98;309-315:1952

l ed t o t hei r M hypot hesi s t hat per haps t he schi zophr eni c was suf f er i ng f r om
an endogenous pr oduct i on of a compound l i ke mescal i ne and somehow r el at ed t o
adr enal i n. When t hey pr esent ed t hi s vi ew t o t he l eader s i n t he f i el d i n
Engl and, especi al l y at t he Maudsl ey, t hey wer e r ebuf f ed. Si r Aubr ey Lewi s was
not i mpr essed. Si r Aubr ey knew t hat t he pr obl emwas not sol vabl e. Humphr y was
so f r ust r at ed t hat when J ane saw t he Saskat chewan ad i n t he London paper she
ur ged hi mt o l ook i nt o i t . Humphr y want ed t o get as f ar away as possi bl e f r om
Engl and and he t hought t hat Saskat chewan was f ar enough. He t hought t hat as
cl i ni cal di r ect or he woul d be abl e t o cont i nue hi s r esear ch i nt o mescal i ne.

Dur i ng our f i r st meet i ng Humphr y t ol d me about hi s r esear ch. I f ound i t
ver y i nt er est i ng. I t was t he f i r st new i dea I had hear d i n psychi at r y and i t
pr omi sed t o pr ovi de us wi t h a map t o gui de us i n our r esear ch i nt o
schi zophr eni a. Schi zophr eni a was our maj or pr obl em. Over hal f of our 5000
pat i ent s i n our hospi t al syst emwer e schi zophr eni c. Humphr y and I became
cl ose f r i ends and col l eagues t hat af t er noon. At t he end of t he af t er noon he
l ef t me hi s manuscr i pt , whi ch descr i bed hi s r esear ch and i deas f or f ur t her
r esear ch. Thi s was publ i shed i n t he J our nal of Ment al Sci ence, Engl and i n
1952. Our r ol es wer e cl ear . As Di r ect or of Resear ch I woul d have t o t ake on
maj or r esponsi bi l i t y t o exami ne t he hypot hesi s whi l e Humphr y had t o under t ake
t he ver y di f f i cul t t ask of br i ngi ng one of t he wor st hospi t al s i n t he wor l d
i nt o t he t went i et h cent ur y. But f r omt hat moment we wor ked t oget her and
shar ed al l our i deas ver y cl osel y and wi t h no hesi t at i on. The i dea Humphr y
and J ohn Smyt hi es had br ought t o me was excel l ent but we had t o f i nd a way t o
pur sue i t i n our sear ch f or t he schi zophr eni a t oxi n whi ch we wer e convi nced
r eal l y was pr esent i n t hese unf or t unat e pat i ent s. We wer e convi nced t hat t hey
wer e physi cal l y si ck.

Ther e i s a r ul e t hat chemi cal s wi t h si mi l ar st r uct ur e t end t o have
si mi l ar pr oper t i es. I t her ef or e deci ded t o st udy t he chemi st r y of ever y
hal l uci nogen di scussed i n t he l i t er at ur e. But bef or e I di d t hat Humphr y and I
l ai d down a r i gor ous def i ni t i on of what was an hal l uci nogen. We excl uded t he
anest het i cs. Usi ng our cr i t er i a I f ound about f i ve nat ur al compounds t hat
wer e hal l uci nogens. We i ncl uded pi nk or di scol or ed adr enal i ne t hat i n a f ew
ast hmat i c medi cal st udent s caused exper i ences t hat wer e si mi l ar t o t he
mescal i ne exper i ence. When I had f i ni shed gat her i ng al l t he dat a I wr ot e down
t he f or mul a of each one of t hese compounds except t hat of t he di scol or ed
adr enal i n. To my del i ght t hey wer e al l i ndol es or l i ke mescal i ne coul d
t heor et i cal l y be i ndol i zed i n t he body. I n t he meant i me we appl i ed t o Ot t awa
f or a smal l r esear ch gr ant t o hel p us wi t h our st udi es.

Our i deas wer e j ust as unpopul ar i n Canada as t hey had been i n
Engl and. When our pr oposal came bef or e t he commi t t ee i t was r ej ect ed. Hal f of
t he member s vet oed t he i dea and t he ot her hal f suppor t ed i t . The member s who
vet oed i t wer e t he t hr ee seni or Pr of essor s of Psychi at r y i n Canada and t he
t hr ee who suppor t ed i t wer e t he sci ent i f i c member s of t he commi t t ee. We wer e
gi ven t hat smal l gr ant onl y because t he Chai r man of t he commi t t ee, Dr . C
Rober t s, sent i t t o Pr of essor Nol an DC Lewi s, Chai r , Depar t ment of
Psychi at r y, Col umbi a Uni ver si t y, f or hi s opi ni on. Af t er he r ead i t he
r epor t ed back t hat we must be suppor t ed not j ust f or t he t wo year s we had
r equest ed but f or many year s. We got our gr ant not because our Canadi an
col l eagues suppor t ed us but because one of t he f or emost US psychi at r i st s had
t he vi si on t o see i t s pot ent i al . I had vi si t ed Dr Lewi s when I was i n New
Yor k i n J anuar y of 1951 as par t of my r esear ch t our of Canadi an and US
r esear ch est abl i shment s.

We or gani zed t he Saskat chewan Commi t t ee on Schi zophr eni a Resear ch and
had our f i r st meet i ng i n Saskat oon, i n a smal l r oomat t he back of t he
medi cal l i br ar y. We spent t he mor ni ng t al ki ng about schi zophr eni a, i t s
cl i ni cal f i ndi ngs, i t s si gni f i cance and how l i t t l e we knew i n t r eat i ng i t .
Ear l y i n t he af t er noon I pr esent ed our hypot hesi s t hat i ndol es coul d be
i nvol ved. Af t er I had f i ni shed my t al k Dr D Hut cheon asked us woul d we l i ke
t o know what t hat pi nk st uf f was i n det er i or at ed adr enal i ne. We wer e
el ect r i f i ed at hi s quest i on. He t ol d us i t was adr enochr ome. He was pr obabl y
t he onl y sci ent i st i n Canada who knew what i t was. He had done r esear ch f or
hi s PhD wi t h t hi s compound i n Engl and wi t h Pr of essor Bur ns. I t was an i ndol e.
Suddenl y we had our adr enochr ome hypot hesi s whi ch was Sear ch t he body of t he
schi zophr eni c pat i ent f or adr enochr ome, an i ndol e der i ved f r omadr enal i n. I t
was pi nk and si mi l ar i n st r uct ur e t o t he t hen known hal l uci nogens. The r est
of t he af t er noon was ver y exci t i ng as we di scussed t he i mpl i cat i ons and how
we mi ght t ackl e t he pr obl em. Pr of essor V. Woodf or d t ol d us t hat adr enochr ome
was an enzyme i nhi bi t or of t he Kr ebs cycl e and si nce t he B vi t ami ns wer e
i nvol ved i n t hese r eact i ons per haps t her e was some connect i on. I di d my PhD
on t hi ami n i n cer eal gr ai ns and was f ami l i ar wi t h vi t ami ns and t hei r
pr oper t i es. At t hi s meet i ng t he i dea of usi ng vi t ami ns ar ose. Al most
ever yt hi ng t hat or i gi nat ed f r omour r esear ch i n Saskat chewan can be t r aced
back t o t hat or i gi nal meet i ng and t he adr enochr ome hypot hesi s. I f Humphr y had
not come t o Saskat chewan i t i s l i kel y t hat none of our r esear ch woul d have
ever t aken of f and I woul d never have become or t homol ecul ar .

These ar e t he mai n event s, whi ch came t oget her at our f i r st meet i ng, an
amazi ng ser i es of coi nci dences.
1. A gover nment , l ed by Pr emi er T Dougl as, i nt er est ed i n moder ni zi ng t he
ment al hospi t al s and t r eat i ng t hei r pat i ent s bet t er .
2. My pr esence wi t h my pecul i ar backgr ound, my Ph D i n vi t ami ns and my
i gnor ance of psychi at r y.
3. Osmond s pr esence wi t h hi s uni que hypot hesi s and i nt er est i n t he
hal l uci nogens. And t he negat i ve r eact i on he f ound i n Engl and.
4. Pr of D Hut cheon who had st udi ed adr enochr ome.
5. No medi cal school . No one t o t el l us what we coul d not do.
6. At l east 500 hundr ed mi l es away f r omt he near est medi cal school .
7. No commi t t ees on et hi cs or on r esear ch.
9. Tot al suppor t f r omDr G D McKer r acher , Di r ect or of Psychi at r i c Ser vi ces
Br anch, Depar t ment of Publ i c Heal t h.


The or i gi nal M ( f or mescal i ne) hypot hesi s was devel oped by Osmond and
Smyt hi es. Hof f er Osmond and Smyt hi es
3
f or mul at ed t he adr enochr ome hypot hesi s.
Af t er 1952 our r esear ch was based upon t he hypot hesi s and i t s var i ous
der i vat i ves and i s a j oi nt ef f or t of Humphr y Osmond and me. We each had our
own ar eas of exper t i se.






3

Hoffer A, Osmond H & Smythies J. Schizophrenia: a new approach. II.
Results of a year's research. J Mental Science 100;29-45: 1954.

The adr enochr ome hypot hesi s of schi zophr eni a can be wr i t t en as t wo
si mpl e equat i ons
4
.

Adr enal i n adr enochr ome

Adr enochr ome schi zophr eni a

Thi s hypot hesi s can onl y be suppor t ed i f adr enochr ome i s made i n t he
body, i f i t i s an hal l uci nogen and i f any subst ance whi ch wi l l neut r al i ze i t s
ef f ect or i nhi bi t i t s f or mat i on i s t her apeut i c f or schi zophr eni a. I f t hese
ar e not t r ue t he hypot hesi s i s wr ong. We t her ef or e had t o cr eat e r esear ch
gr oups t o t est each of t hese sub post ul at es, a bi ochemi cal t eamt o exami ne
t he chemi st r y of t hese r eact i ons, a psychi at r i c t eamt o st udy i t s
hal l uci nogeni c pr oper t i es and a cl i ni cal t eamt o t est possi bl e subst ances
t hat woul d i nhi bi t t hi s r eact i on and be t her apeut i c. I n our book The
Hallucinogens we descr i be i n det ai l our r esear ch.

Is adrenochrome made in the body?

Af t er I di scover ed how t o make pur e cr yst al l i ne adr enochr ome our
bi ochemi cal t eaml ed by Dr R Heacock st udi ed i t s pr oper t i es and t he many
r eact i ons i n whi ch i t par t i ci pat ed. Dr Heacock became t he wor l d s exper t on
adr enochr ome and i t s der i vat i ves. Humphr y was ver y pl eased wi t h t he pur e
adr enochr ome, beaut i f ul cr yst al s whi ch wer e pur pl i sh r ed whi ch f or med a
br i ght r ed sol ut i on whi ch t ur ned yel l ow when oxi di zed by t he oxygen i n t he
ai r . I gave hi ma smal l amount of t he cr yst al s. I t was so st abl e i t coul d be
st or ed at r oomt emper at ur e. Humphr y had a subt l e sense of humor and enj oyed
t easi ng some of our i nt er nat i onal bi ochemi cal col l eagues. At meet i ngs he
woul d have t he vi al i n hi s pocket . He woul d t al k about adr enochr ome and
af t er t he col l eague had f i ni shed t el l i ng hi mt hat i t coul d not be made
st abl e, coul d not be cr yst al l i zed and coul d not be made i n t he body because
of i t s r emar kabl e i nst abi l i t y he woul d pul l out t he l i t t l e vi al of
cr yst al l i ne adr enochr ome and show i t t o t he di scomf i t ed aut hor i t y. Bef or e
t hat t he pr epar at i ons wer e ver y unst abl e and t he f i r st one made f or us had t o
st or ed at mi nus 40 Degr ees Cent i gr ade. But one day when I was i n Vancouver at
t he f acul t y cl ub Uni ver si t y of Br i t i sh Col umbi a I had l unch wi t h an Engl i sh
or gani c chemi st and I di scussed wi t h hi mt he pr obl ems wi t h unst abl e
adr enochr ome. He r epl i ed t hat usual l y unst abl e or gani c chemi cal s wer e not
pur e. That was t he answer . I suddenl y r eal i zed t hat t he si l ver used i n
conver t i ng adr enal i n t o adr enochr ome had not been r emoved. I i mmedi at el y
wr ot e a not e t o my chemi st ( not Dr Heacock who had not yet j oi ned us) t o t ake
t he adr enochr ome and t o pour a sol ut i on of t he adr enochr ome t hr ough a car bon
col umn t o st r i p al l t he si l ver out . When I came home I went t o t he l ab t o see
what had happened and di scover ed t hat my chemi st had not done i t . I was ver y
angr y. That af t er noon he came t o me and showed me t he f i r st ever pur e
cr yst al s. Taki ng out al l t he si l ver had made i t st abl e. Lat er we sent
sampl es t o Pr of Mar k Al chul e of Har var d and McLeans Hospi t al i n Bost on and t o
Dr S Udenf r i end of NI MH i n Washi ngt on DC. Lat er when NI MH was so anxi ous t o
pr ove us wr ong Dr Seymour Ket y r epor t ed at one of t he meet i ngs I at t ended
t hat Dr J ul i us Axel r od pr oved t hat adr enochr ome coul d not be made i n t he
body. He descr i bed wi t h gl ee how hi s f r i end and col l eague who l at er got t he
Nobel Pr i ze f or some of hi s ot her wor k had asked Udenf r i end f or a smal l

4 Hoffer A & Osmond H: The Hallucinogens. Academic Press, New York,
1967.


sampl e of our adr enochr ome. He di d not know how t o make i t hi msel f .
Udenf r i end woul d not do so. That di d not st op hi mand Axel r od st ol e some of
t he adr enochr ome cr yst al s f r omUdenf r i end s l abor at or y. Ket y t hought t hat was
hi l ar i ous.

Anot her l abor at or y devel oped an assay met hod f or adr enol ut i n, a r educed
der i vat i ve of adr enochr ome i n bl ood. Adr enochr ome i s r ecogni zed as a
const i t uent of t he body and i t s r ol e i n schi zophr eni a, Par ki nson s di sease,
and ot her degener at i ve di seases and i n hear t dysf unct i on i s bei ng exami ned.
Thi s i s descr i bed by Fost er and Hof f er
5
. On a posi t i ve not e i t i s an i nhi bi t or
of cel l di vi si on and i s bei ng used f or t r eat i ng cancer .

Our l abor at or y al so di scover ed kr ypt opyr r ol e i n t he ur i ne of
schi zophr eni c pat i ent s and t o a l esser degr ee i n ot her pat i ent s. We cal l ed i t
t he mauve f act or . I wi l l di scuss t hi s l at er .

Is adrenochrome an hallucinogen?

Pr of essor D Hut cheon synt hesi zed our f i r st f ew mi l l i gr ams of
adr enochr ome and t est ed i t s t oxi c pr oper t i es i n ani mal s. We wer e t hen r eady
t o st ar t our psychol ogi cal st udi es. Humphr y, our exper t i n hal l uci nogeni c
r eact i ons, vol unt eer ed t o be t he f i r st . I i nj ect ed hi msubcut aneousl y wi t h a
f ew mi cr ogr ams of adr enochr ome. Ther e was no r eact i on and about one hour
l at er Humphr y i nj ect ed me wi t h doubl e t hat dose. Agai n t her e was no r eact i on
and i t was hi s t ur n t o r ecei ve doubl e my dose. Event ual l y we bot h r eact ed.
Humphr y devel oped mi nor changes si mi l ar t o t hose i nduced by LSD. I became
depr essed and par anoi d f or t wo weeks. We t hen deci ded t o be much mor e car ef ul
because of t hi s pr ol onged r eact i on. The exper i ences ar e descr i bed i n our book
The Hallucinogens. A gr oup i n Czechosl ovaki a, usi ng our met hod f or maki ng
adr enochr ome, conduct ed doubl e bl i nd cont r ol l ed st udi es and conf i r med our
f i ndi ngs. Si nce t hen ever y ani mal gi ven adr enochr ome has shown t oxi c changes
i n behavi our f r ompi geons, r at s, cat s, t o spi der s and mor e.


Will compounds that inhibit adrenochrome formation or are antidotes to its
toxic effect be therapeutic?

Humphr y and I under st ood t hat most medi cal hypot heses t ur n out t o be
wr ong. But we wer e desper at e t o have a bet t er t r eat ment f or our pat i ent s. We
hoped t hat t he hypot hesi s was r easonabl y cor r ect and consi der ed how we mi ght
r ever se t he r eact i on i n t he body usi ng subst ances t hat wer e saf e and coul d be
t aken f or l ong per i ods of t i me. Schi zophr eni a i s a chr oni c di sease and needs
chr oni c pr event i on and t r eat ment . At our f i r st meet i ng of t he Saskat chewan
Commi t t ee on Schi zophr eni a Resear ch Pr of essor Ver non Woodf or d t ol d us about
t he essent i al r ol e B vi t ami ns pl ayed i n cel l bi ochemi st r y. Vi t ami n B- 3,
ni cot i ni c aci d and ni cot i nami de, l i ke al l B vi t ami ns, ar e ext r aor di nar i l y
saf e. I t pr event s and t r eat s pel l agr a and had been used spor adi cal l y t o t r eat
a number of ot her psychi at r i c pr obl ems, i ncl udi ng depr essi on, wi t h some
success. I t i s a met hyl accept or and t heor et i cal l y coul d decr ease t he
f or mat i on of adr enal i n f r omnor adr enal i n by decr easi ng t he met hyl gr oups
avai l abl e f or addi ng t o nor adr enal i n. Lat er we f ound t hat ni cot i ni c aci d
gi ven i nt r avenousl y t o epi l ept i c pat i ent s who had been f i r st i nj ect ed wi t h

5 Foster HD and Hoffer A: The two faces of L-dopa: benefits and adverse
side effects in the treatment of Encephalitis lethargica, Parkinsons
disease, multiple sclerosis and amyotrophic lateral sclerosis. Medical
Hypotheses 62; 177-181:2004.
adr enochr ome r ever sed t he abnor mal EEG pat t er n i nduced by t he adr enochr ome.
I t was an ef f ect i ve ant i dot e i n t hese st udi es. We obt ai ned suppl i es of pur e
ni cot i ni c aci d, ni cot i nami de, ascor bi c aci d. Vi t ami n B- 3 i s a component of
t he pyr i di ne di nucl eot i de cycl e whi ch i s i nvol ved i n at l east 200 r eact i ons
i n t he body. I t t akes par t i n oxi dat i on- r educt i on r eact i ons.

I t hi nk i t i s ver y i mpor t ant i n t est i ng new t r eat ment s t hat t he f i r st
one comes out posi t i ve. Thi s encour ages t he i nvest i gat or t o keep on t r yi ng.
Our f i r st case was posi t i ve. I had j ust r ecei ved f our f i f t y- pound bar r el s
each cont ai ni ng t he vi t ami ns we want ed t o t est . I t ook some of t hat pr eci ous
ni aci n t o Humphr y i n Weybur n. As we wer e vi si t i ng t he head psychi at r i st came
i n and t ol d Humphr y t hat Kennet h was dyi ng. A f ew cat at oni c schi zophr eni c
pat i ent s di ed and at aut opsy no r eason was f ound. Kennet h had i nsul i n coma
and ECT, whi ch had not hel ped. I suggest ed t hat we shoul d gi ve hi mt he t wo
vi t ami ns I had br ought wi t h me, ni aci n, vi t ami n C. We r ushed t o t he war d and
f ound Kennet h i n a coma. We pr ompt l y put i n a st omach t ube and pour ed i n 10
gr ams of ni aci n and 5 gr ams of vi t ami n C. The next day he sat up and dr ank
t he mi xt ur e and t hi r t y days l at er he was so wel l hi s par ent s i nsi st ed on
t aki ng hi mhome. I t r acked hi mdown about f i f t een year s l at er and f ound t hat
he coul d not r emember havi ng been i n t he hospi t al . He was a cont r act or and
had been Chai r man of t he Boar d of Tr ade of hi s smal l communi t y.

We t r eat ed 8 schi zophr eni c pat i ent s i n pi l ot t r i al s usi ng 1 gr amof
vi t ami n C af t er each of t hr ee meal s. Two wer e t r eat ed under my car e at t he
Munr o Wi ng, Gener al Hospi t al , Regi na, Saskat chewan and si x by Humphr y at t he
Saskat chewan Hospi t al , Weybur n. Al l ei ght r esponded wi t h r ecover y. Ther e wer e
no t oxi c r eact i ons. We t hen compl et ed si x doubl e bl i nd cont r ol l ed, r andomi zed
t r i al s bet ween 1953 and 1960 on adul t s and t wo on chi l dr en and showed t hat we
doubl ed t he t wo year s r ecover y r at e f r om35 t o 75 per cent . These wer e t he
f i r st doubl e bl i nd t r i al s conduct ed by psychi at r i st s. I t l ed event ual l y t o
or t homol ecul ar medi ci ne and psychi at r y, whi ch i s begi nni ng t o f l our i sh and i s
used wor l d wi de but onl y t o a smal l degr ee.

Reduci ng subst ances wi l l i nhi bi t t he oxi dat i ons of adr enal i n t o
adr enochr ome. Ascor bi c aci d has been used t o st abi l i ze adr enal i n sol ut i ons
but i t does not do t hi s ver y wel l . We di d not conduct any doubl e bl i nd
cont r ol l ed st udi es wi t h ascor bi c aci d but I use i t r out i nel y f or al l my
schi zophr eni c pat i ent s and amconvi nced t hat i t adds t o t he qual i t y of t he
r ecover y. I n 1952 a woman dyi ng f r ombr east cancer was admi t t ed psychot i c
wi t h a ser i ous i nf ect ed ul cer at ed br east ar ea f ol l owi ngs mast ect omy. Her
psychi at r i st was goi ng t o st ar t her on ECT f or her schi zophr eni c psychosi s. I
asked hi mt o wai t f or a f ew days and he agr eed t o wai t f or t wo days. I gave
her ascor bi c aci d 1 gr amever y hour . She st ar t ed on Sat ur day mor ni ng and on
Monday when she had been gi ven 45 gr ams her psychi at r i st f ound her ment al l y
nor mal and di schar ged her . Her ul cer at ed l esi on had st ar t ed t o heal . I n t hi s
case t her e i s no doubt t hat t he ascor bi c aci d cur ed her psychosi s. She di ed 6
mont hs l at er but r emai ned ment al l y nor mal .

Ot her r educi ng nat ur al compounds ought t o have si mi l ar pr oper t i es.
Thi s i ncl udes gl ut at hi one, N acet yl cyst ei ne, and vi t ami n E. Ther e ar e
i ndi cat i ons t hat t hey ar e hel pf ul but no cont r ol l ed t r i al s have been
r epor t ed. Recent st udi es show t hat schi zophr eni c pat i ent s have l ow bl ood
l evel s of t he ant i oxi dant s al bumi n, ur i c aci d and bi l i r ubi n.

The adr enochr ome hypot hesi s gener at ed a t r emendous amount of cr i t i ci sm
and host i l i t y f r omt he est abl i shment l ed by t he Nat i onal I nst i t ut e Ment al
Heal t h, Washi ngt on DC, and t he Amer i can Psychi at r i c Associ at i on. They cl ai med
t hat adr enochr ome coul d not be made i n t he body, t hat i t was not an
hal l uci nogen and t hat vi t ami n B3 had no mer i t i n t r eat ment . These power f ul
i nst i t ut es wer e wr ong on al l t hr ee count s but t hei r opposi t i on ef f ect i vel y
suppr essed r esear ch i nt o t hi s ar ea f or t he l ast 30 year s and onl y now i s i t
begi nni ng t o come out of t he shadows i nt o whi ch i t was f or ced by t hese
associ at i ons.

The f ol l owi ng anecdot e i l l ust r at es t he Amer i can Psychi at r i c Associ at i on
r eact i on t o our ni aci n schi zophr eni a cl ai ms. I n 1960 I was made a Fel l ow i n
t he APA because t hat year Dr . Ewen Camer on was Pr esi dent of t he APA, of t he
Canadi an Psychi at r i c Associ at i on and t he Wor l d Psychi at r i c Associ at i on. The
APA was hol di ng i t s annual meet i ng i n Mont r eal . I t was pol i t i cal l y wi se t o
upgr ade Canadi an member s. But I pl ayed no r ol e i n t he APA. I n 1971 I r ecei ved
a l et t er f r omt he Pr esi dent of APA advi si ng me t hat a compl ai nt had been
r egi st er ed agai nst me by a member t hat I was pr omot i ng a t r eat ment not
r ecogni zed by t he APA. Thei r commi t t ee on Et hi cs had i nst r uct ed hi mt o
r epr i mand me and t o ask me t o cease and desi st . Thi s annoyed me but was not a
t hr eat as I di d not have t o be a member t o pr act i ce. I wr ot e r equest i ng t he
name of t he compl ai nant and r eason f or t hei r compl ai nt , whi ch t he APA woul d
not gi ve me. I poi nt ed out t hat bef or e t hey had j udged me I shoul d have had
t he oppor t uni t y of appear i ng bef or e t hemand I demanded a hear i ng bef or e
t hei r commi t t ee. The pr esi dent r epl i ed t hat t hey wer e shor t of money and t hat
t he meet i ng coul d not be hel d f or anot her year . Event ual l y t hey agr eed t o
meet wi t h us i n Washi ngt on, DC. We met wi t h t hei r commi t t ee, whi ch i ncl uded
t hei r l egal counci l . At t he onset I opened t he meet i ng by t el l i ng t hemt hat
t hey had no j ur i sdi ct i on over what we wr ot e or di d and t hat t he cor r ect
commi t t ee t o have consi der ed t he i ssue was t he commi t t ee on t her apy and not
t he commi t t ee on et hi cs. They r epl i ed t hat t hey wer e wear i ng t wo hat s. One
hat was as t he commi t t ee on et hi cs and t he ot her hat was t hat t hey wer e
si mpl y our col l eagues and wer e i nt er est ed. I answer ed t hat i n t hat case I
onl y accept ed t he col l egi al hat and we wer e pr epar ed t o spend t he whol e day
di scussi ng our wor k wi t h t hem. We debat ed al l mor ni ng. I t was obvi ous t hat
t hey had not done any of t hei r homewor k. They had not r ead our paper s, and
t hey knew not hi ng about vi t ami ns but I di d di scover t hat t he compl ai nant ,
st i l l unnamed, had obj ect ed t o a paper I had wr i t t en cal l ed Fi ve Cal i f or ni a
Schi zophr eni cs
6
i n whi ch I gave t he case hi st or i es of f i ve pat i ent s, who
havi ng f ai l ed t o get wel l on t he best st andar d t r eat ment , r ecover ed when t hey
ar e gi ven or t homol ecul ar t r eat ment . At t he end of t he mor ni ng t hey asked us
t o wai t f or a f ew mi nut es whi l e t hey woul d deci de what t o do. They came back
much l at er and announced t hat t hey had not been abl e t o come t o a deci si on
and woul d l et us have i t i n t wo weeks. I st i l l have not hear d f r omt hem. They
r eal i zed t hey had no case t hat t hei r act i on had been i nappr opr i at e but t hey
wer e i nt el l i gent enough not t o gi ve us an answer because had t hey announced
t hat we had been et hi cal we coul d have used t hi s agai nst our cr i t i cs. But APA
di d not f or get and event ual l y i n t hei r i nf amous t ask f or ce r epor t dest r oyed
f or f our decades t he possi bi l i t y of i mpr oved t r eat ment f or schi zophr eni c
pat i ent s. I r esi gned my f el l owshi p i n t he APA on t he basi s t hat i t s act i on
had been i nappr opr i at e, unet hi cal and an at t empt t o censur e paper s l ong af t er
t hey had been publ i shed.

The adr enochr ome hypot hesi s has been and st i l l i s ver y f r ui t f ul i n
devel opi ng new i deas i n many f i el ds i n medi ci ne, not onl y i n schi zophr eni a.


6 Hoffer A: Five California schizophrenics. J Schizophrenia 1;209-
220:1967.

Research with the hallucinogens

Dr J ohn Smyt hi es and Humphr y began t o cor r espond wi t h Al dous Huxl ey.
Al dous want ed t o exper i ences t he r eact on t o mescal i ne. We had not yet st ar t ed
t o wor k wi t h LSD. The Amer i can Psychi at r i c Associ at i on was hol di ng i t s annual
meet i ng i n Los Angel es i n 1952 and Humphr y and I wer e t her e. Rose and I went
t o Hami l t on, Ont ar i o, pi cked up a new car t hr ough my br ot her - i n- l aw Ed Vi ckar
and dr ove down r out e number 66 t o Los Angel es. Humphr y had agr eed t o gi ve
Al dous some mescal i ne at hi s home af t er t he meet i ng was over and Rose and I
l ef t t he ci t y. Whi l e we wer e t her e we had di nner wi t h Al dous and Mar i a i n
t hei r l ovel y home on one of t he hi l l s i n Los Angel es. Al so pr esent was t he
gr eat hypnot i st Dr . Mi l t on Er i ckson. The r esul t of t hat exper i ence i s now
known wor l d wi de and cul mi nat ed i n t he t wo f amous Huxl ey books. I n hi s book
Doors to Perception Al dous Huxl ey r ef er r ed t o our wor k i n a l i t t l e f oot not e.
When Rose and I t our ed Gr eat Br i t ai n i n 1954 t o vi si t r esear ch cent er s my
name was al r eady f ai r l y wel l known j ust by t hat l i t t l e r ef er ence.

I met Al dous sever al t i mes af t er t hat but our r el at i onshi p was
pr i mar i l y t hr ough Humphr y and by cor r espondence. But t hr ough Huxl ey Humphr y
met Bi l l Wi l son cof ounder of Al cohol i cs Anonymous. I f i r st met Bi l l W. at a
New Yor k meet i ng. He was si t t i ng on my r i ght and Humphr y was on hi s r i ght .
Humphr y and I wer e exper i ment i ng wi t h l eukoadr enochr ome. Thi s i s a nont oxi c
r educed der i vat i ve of adr enochr ome whi ch Dr . R Heacock made i n our
l abor at or y. We want ed t o st udy i t s pr oper t i es. I cannot r emember our
r easoni ng but I amf ai r l y cer t ai n we f el t i t was not an hal l uci nogen. We made
up 3 mi l l i gr amt abl et s and deci ded t o use i t subl i ngual l y. We t est ed i t on a
number of f r i ends and col l eagues and i t ei t her di d not hi ng or had r emar kabl e
ant i - anxi et y pr oper t i es. We even i nt er est ed one of t he maj or dr ug compani es
who made a bat ch usi ng our f or mul a and we r an a l ong ser i es of t est s. But
t hey event ual l y woul d not t ake i t on because i t s act i on was not pr edi ct abl e.
Dr ug compani es l i ke dr ugs t hat al ways do somet hi ng even i f i t i s bad and
undesi r abl e f or t hen t hey ar e sur e i t has act i vi t y. Our r esear ch i s descr i bed
i n our book The Hallucinogens.

As we wer e si t t i ng l i st eni ng t o t he pr oceedi ngs Bi l l Wr emar ked t o
Humphr y t hat he was ver y t ense and we coul d see t hat he was not comf or t abl e.
Humphr y pr ompt l y gave Bi l l one of t hese 3 mi l l i gr amt abl et s. Bi l l pl aced i t
under hi s t ongue and about 20 mi nut es l at er he t ur ned t o Humphr y and sai d,
Now I know what you ar e t al ki ng about when you say you ar e r el axed. I t
had a r emar kabl e ef f ect on hi m. We l ef t hi ma subst ant i al suppl y and he used
i t f or sever al mont hs but event ual l y we r an out and deci ded t hat we coul d not
pur sue i t any f ur t her . Bi l l was once mor e i n t r oubl e wi t h hi s moods. By t hen
t he t hr ee of us had spent many hour s t al ki ng about our r esear ch, about
Al cohol i c Anonymous, about our use of LSD f or t r eat i ng al cohol i cs and our use
of ni aci n whi ch was benef i ci al f or many of t he pat i ent s. Bi l l was ver y
i mpr essed and he began t o t ake 1 gr amof ni aci n af t er each meal . Two weeks
l at er he was f r ee of hi s chr oni c t ensi on and depr essi on. He r emai ned on t hi s
vi t ami n unt i l he di ed. He was so ent husi ast i c t hat he began t o hand i t out t o
hi s f r i ends i n AA who al so suf f er ed many sympt oms of mood di sor der even
t hough t hey wer e not dr i nki ng. One eveni ng when I was vi si t i ng Bi l l at hi s
hot el he suddenl y pr oduced t hi r t y char t s and he sai d t hat he want ed t o show
me t he r esul t s of hi s r esear ch. I was sur pr i sed and pl eased. He t ol d me t hat
he had gi ven t he ni aci n t o 30 member s of AA. Af t er one mont h t en wer e. Af t er
t wo mont hs anot her t en wer e wel l but t he l ast t en had not r esponded. Thi s was
r emar kabl y l i ke t he dat a I had been seei ng. Bi l l W. out l i ned t he val ue of our
wor k wi t h ni aci n as a t r eat ment t o member s of t he I nt er nat i onal Doct or s i n AA
and t hat spr ead t he i dea t hr oughout AA. Bi l l Whad t o do t hi s out si de of hi s
associ at i on wi t h t he I nt er nat i onal Boar d because t hey wer e vi ol ent l y opposed
t o Bi l l t al ki ng about vi t ami ns
7
. One of t he doct or s on t he boar d was vi ol ent l y
opposed t o t he i dea t hat ni aci n coul d be hel pf ul but t hei r mai n concer n was
t hat Bi l l was not a doct or .

Bi l l wr ot e t wo pamphl et s cal l ed A Communi cat i on t o A. A. Physi ci ans, t he
f i r st one i n 1965( gr een cover ) . I t had a l i mi t ed ci r cul at i on and was f ol l owed
by t he second one i n 1968 ( yel l ow cover ) and t he l ast one ( whi t e cover ) by
Dr s. Edwi n Boyl e J r , Davi d Hawki ns and Russel l F Smi t h. Dr E Boyl e was one of
t he f i r st Amer i can physi ci ans, t hen wor ki ng at NI H, who hel ped pl an t he
Cor onar y Dr ug St udy whi ch est abl i shed ni aci n as t he gol d st andar d f or
l ower i ng chol est er ol l evel s. Davi d Hawki ns and Li nus Paul i ng co aut hor ed t he
cl assi cal book Orthomolecular Psychiatry. The f i r st cl i ni cal meet i ng on
or t homol ecul ar psychi at r y was hel d i n Long I sl and at Br unswi ck Hospi t al wher e
he was i n char ge of t he depar t ment of psychi at r y. Russel l
Smi t h was cl i ni cal di r ect or of a l ar ge hospi t al i n Det r oi t whi ch speci al i zed
i n t r eat i ng al cohol i cs. I n t he i nt r oduct i on t hey wr ot e Bi l l s f i r st
i nspi r at i on had a pr of ound i mpact t hr oughout t he wor l d as evi dence no onl y by
t he gr owt h of AA i t sel f and i t s af f ect on t he f i el d of al cohol i sm, but al so
i t s i mpact on t he f i el d of ment al heal t h i n gener al , wi t h AA t ype gr oup
t her apy havi ng become t he f or emost successf ul t r eat ment modal i t y. Bi l l and
t hose cl ose t o hi mf el t t hat he had a second i nspi r at i on when he r ecogni zed
t he i mpor t ance of cer t ai n vi t ami ns i n r et ur ni ng t he br ai n of some al cohol i c
t o nor mal f unct i oni ng. I t was Bi l l who saw t he f ar r eachi ng i mpl i cat i ons of
t hi s di scover y and br ought i t i nt o awar eness. Thi s agai n i s al r eady havi ng an
i mpact on t he ent i r e f i el d of ment al heal t h. The sci ent i f i c i mpor t ance of
t hi s di scover y was r ecogni zed by t he br i l l i ant Nobel Pr i ze Wi nni ng Pr of essor ,
Li nus Paul i ng, who t er med t hi s new devel opment , Or t homol ecul ar Psychi at r y

Because of Bi l l s i nt er est many AA doct or s became power f ul advocat es
of or t homol ecul ar medi ci ne. Bi l l s i deas wer e r ej ect ed by t he AA I nt er nat i onal
Headquar t er s because not bei ng a doct or he had no r i ght t o t al k about
vi t ami ns. To hel p hi mt he Huxl ey I nst i t ut e of Bi osoci al Resear ch gave hi ma
smal l gr ant t o pay f or secr et ar i al and ot her expenses. The AA doct or s deci ded
t o t est our cl ai ms, and wi t hout any demand f or doubl e bl i nd cont r ol l ed
st udi es t hey cr eat ed a commi t t ee. Each member of t he commi t t ee t r i ed ni aci n
on t hemsel ves and t he r esul t was so benef i ci al t hey appr oved i t s use. Bi l l W.
wi t h hi s enor mous i nf l uence was a maj or pl ayer i n t he devel opment of
or t homol ecul ar medi ci ne. He even r esur r ect ed t he name Vi t ami n B- 3 t o r epl ace
ni aci n and ni aci nami de. Whi l e pr epar i ng hi s mat er i al f or di st r i but i on he
asked us whet her t her e was anot her name f or i t . He di d not t hi nk t hat usi ng
t he cur r ent names woul d hel p. I r emember ed t hat i n 1937 when I t ook my f i r st
cl ass i n bi ochemi st r y pr of essor Roger Manni ng had di scussed t he vi t ami ns i n
t he or der i n whi ch t hey had been di scover ed. The f i r st was vi t ami n A, t hen
vi t ami n B. But i t t ur ned out t hat vi t ami n B consi st ed of a number of
vi t ami ns. The f i r st was t hi ami n, t he second r i bof l avi n and next i n l i ne was
ni aci n, whi ch was number , t hr ee. I suggest ed he cal l i t vi t ami n B- 3. Thi s i s
now t he accept ed common t er m.

Bi l l Humphr y and I wer e i nvol ved i n an unusual ser i es of event s.
Humphr y was t he Di r ect or of t he Bur eau of Resear ch i n Neur ol ogy and
Psychi at r y, New J er sey Neur opsychi at r i c I nst i t ut e, Pr i ncet on, New J er sey and
l i ved i n one of t he bui l di ngs whi l e J ane r emai ned i n Engl and. Whenever I went

7 Hartigan F: Bill W: A biography of alcoholics anonymous cofounder
Bill Wilson St. Martins Press, New York 2000.

east I woul d sl i p down t o Pr i ncet on and vi si t wi t h Humphr y f or a f ew days.
One eveni ng we met wi t h Bi l l at hi s hot el . I had i nvi t ed t he medi cal di r ect or
of a company t o come as wel l . Thi s physi ci an had asked me t o be a consul t ant
on a pr oduct f or whi ch t hey had t he pat ent s cal l ed NAD. I t was speci al l y
f or mul at ed so t hat i t was not di gest ed and dest r oyed i n t he st omach. The
company had been expl or i ng i t as a t r eat ment f or al cohol i smand had appl i ed
f or a pat ent but t he dat a needed a l ot of wor k. As soon as I l ear ned t hat
such a compound was avai l abl e I became ver y i nt er est ed, not i n usi ng i t f or
al cohol i cs but i n usi ng i t f or t r eat i ng schi zophr eni a. I had been dr eami ng
about i t f or a l ong t i me but was never abl e t o obt ai n any and t he pur e
pr oduct t aken by mout h was not act i ve. The company agr eed t o pr ovi de me wi t h
adequat e suppl i es.

The r esul t s on our pat i ent s wer e r emar kabl e. I t woul d pr oduce t he ki nd
of r esponse i n sever al days t hat I woul d expect i n sever al mont hs f r om
vi t ami n B- 3. Event ual l y t he company deci ded t hat t he new pat ent woul d be ver y
val uabl e and deci ded t hat I was no l onger needed. We t er mi nat ed our
r el at i onshi p. I sent t hemmy f i nal r epor t and i nf or med t hemt hat I woul d
br i ef l y r ef er t o NAD i n my t al k t o be gi ven at t he Wal dor f Ast or i a on t he
mechani smof act i on of t he hal l uci nogens. I was goi ng t o i nser t one sent ence
as par t of my ar gument . I t ol d t he company. They want ed me t o el i mi nat e t hat
sent ence st at i ng t hat i t woul d be an i nf r i ngement of t hei r t r ade secr et . They
of f er ed t o pay me an enor mous sumof money i f I woul d keep qui et .

Af t er vi si t i ng Humphr y I went back t o New Yor k t o pr epar e f or my t al k.
That mor ni ng t he company s l awyer cal l ed my hot el . He sai d he was wi t h t he
Ri char d Ni xon f i r mand want ed me t o come t o t hei r of f i ce on Wal l St r eet t o
di scuss t he mat t er . For t unat el y I cal l ed t he l awyer f or t he nascent Amer i can
Schi zophr eni a Associ at i on i nst ead. He advi sed me t o come t o hi s of f i ce, whi ch
was acr oss t he st r eet f r omt he Ri char d Ni xon f i r m. My l awyer and t he company
l awyer debat ed t he i ssue vi gor ousl y f or hal f a day and event ual l y t he company
l awyer consul t ed wi t h t he company pr esi dent who or der ed hi mt o wi t hdr aw t he
act i on. Had I gone t o t hei r of f i ce I woul d have been ser ved wi t h a subpoena
f or bi ddi ng me f r omgi vi ng my t al k at t he hot el . I di scover ed l at er t hat
pr ocess ser ver s wer e wai t i ng at each ent r ance t o t hei r bui l di ng. They r eal l y
had no gr ounds f or act i on. My l awyer t hen advi sed me t o hi de unt i l my
l ect ur e. He sai d t hat t he Ni xon f i r mwas honor abl e and woul d keep t hei r wor d
but t her e was not hi ng t o pr event t he company f r omseeki ng anot her f i r mand
st ar t i ng agai n. I i mmedi at el y cal l ed Bi l l at hi s hot el and asked hi mt o get
me a r oom. I cal l ed Humphr y who was comi ng i n t hat af t er noon and asked hi mt o
go t o my hot el t o pi ck up some t hi ngs f or me and br i ng i t t o Bi l l ' s hot el
r oom. Humphr y t hought t hi s was gr eat . Then my l awyer escor t ed me down i nt o
some subt er r anean t unnel wi t h a pr i vat e door i nt o t he subway. Once I mi ngl ed
wi t h t he cr owds I was saf e. I n t r ue spy f ashi on Humphr y wat ched ver y
car ef ul l y t o see i f he was bei ng f ol l owed. He wal ked ar ound t he bl ock whi ch
housed my hot el , t he Roger Smi t h on Lexi ngt on Ave, t hr ee t i mes bef or e
ent er i ng, i t s t r eat ment and so on. I cal l ed J ohn Osmundsen, Humphr y s good
f r i end who was seni or sci ence edi t or f or t he New Yor k Ti mes. I t ol d J ohn t hat
I woul d be speaki ng and t hat t her e was a chance t hat I woul d be ser ved wi t h a
subpoena bef or e I coul d gi ve my l ect ur e. J ohn pr omi sed he woul d be t her e. I
t hi nk he was exci t ed by t he pr ospect I mi ght be pr event ed f r omt al ki ng. J ohn
A Osmundsen was a j our nal i st who had wor ked f or t he New Yor k Ti mes, Li f e and
Look Magazi nes, on Publ i c Br oadcast i ng Tel evi si on and many ot her
i nst i t ut i ons. He was seni or sci ence edi t or f or t he Ti mes.

The next mor ni ng I del i ver ed my t al k. The f ol l owi ng day t he New Yor k
Ti mes car r i ed a f ul l page st or y on t he f i r st page of t he second sect i on
descr i bi ng my paper . That event mar ks one of t he maj or t ur ni ng poi nt s i n
or t homol ecul ar psychi at r y. For wi t hi n a f ew days bot h Humphr y and I wer e
r ecei vi ng enor mous number s of l et t er s, f i r st f r omt he east coast , t hen f r om
pl aces f ur t her west and i n a f ew days f r omt he f ar east . I r ecei ved as many
as t hr ee hundr ed l et t er s per week and had t o hi r e anot her secr et ar y t o handl e
t he l oad. Humphr y and I kept t hese l et t er s and l at er when we wer e or gani zi ng
t he Amer i can Schi zophr eni a Associ at i on we sent an appeal s l et t er t o al l t he
peopl e who had wr i t t en t o us. Wi t hi n a f ew weeks we r ecei ved about $70, 000.
Thi s was a r emar kabl e 6%yi el d. Wi t h t hi s money we wer e abl e t o est abl i sh t he
Amer i can Schi zophr eni a Associ at i on.

Bi l l W. was convi nced t hat ni aci n shoul d be an essent i al el ement of t he
AA pr ogr ambecause i t heal ed t he member s of t hei r chr oni c t ensi ons,
depr essi on, pai n and f at i gue. Pr obabl y t hese sympt oms wer e t he mai n r easons
why t hey became al cohol i cs i n t he f i r st pl ace. He t ol d Humphr y and me about a
home i n Det r oi t cal l ed Guest House. Thi s was a t r eat ment cent er f or al cohol i c
Cat hol i c pr i est s. I t had been t he pr i vat e home of a ver y weal t hy Det r oi t
r esi dent . We asked Bi l l whet her i t woul d be possi bl e t o vi si t Guest House. He
ar r anged t hi s and somet i me l at er we and Bi l l wer e guest s of t hi s l ovel y home
f or a coupl e of days. The pr i est s wer e al l member s of AA. One of t he pr i est s,
a f acul t y member of For dhamUni ver si t y, was del i ght ed t o meet us. He had
suf f er ed f r omsever e Mi gr ai ne al l hi s l i f e but soon af t er he st ar t ed t aki ng
ni aci n hi s mi gr ai ne headaches wer e gone. He i mmedi at el y became a conver t and
began t o pr osel yt i ze ni aci n even mor e t han Bi l l W. He was cal l ed Fat her
Ni aci n and t hey cal l ed me Doct or Ni aci n. I was mor e cl osel y i dent i f i ed wi t h
ni aci n t han Humphr y was because I was mor e cl osel y i nvol ved i n t he cl i ni cal
t r i al s. I was so wel l known i n Canada t hat one day a l et t er ar r i ved addr essed
t o Doct or Ni aci n. The post of f i ce had r e- addr essed i t . Guest House was
descr i bed i n t he book Fanni e Kahan wr ot e f or bot h of us cal l ed New Hope for
Alcoholics, Uni ver si t y Books, New Yor k, 1966.

Fat her Ni aci n l at er ar r anged a meet i ng at For dhamUni ver si t y t o di scuss
t he use of ni aci n i n t r eat ment . At t hat t i me we had an act i ve schi zophr eni cs
anonymous gr oup i n Saskat oon. Two of t hei r member s came t o t he meet i ng and
usi ng t he usual AA f or mat t ol d t he audi ence about t hei r own r ecover y f r om
schi zophr eni a.

Osmond and Smyt hi es f i r st st udi ed t he mescal i ne exper i ence because
t hey want ed t o know mor e about schi zophr eni a. Af t er A Hof mann di scover ed
l yser gi c aci d di et hyl ami de ( LSD) st udi es of i t s hal l uci nogeni c pr oper t i es
qui ckl y spr ead t hr ough Nor t h Amer i ca and West er n Eur ope. I t was used t o mi mi c
psychosi s and was cal l ed psychot omi met i c. That i s how we f i r st used i t i n
Saskat chewan. Ever y vol unt eer who t ook i t exposed hi msel f t o a t r ansi ent
shor t l i ved psychosi s whi ch coul d be t er mi nat ed qui ckl y when necessar y by
gi vi ng t hemni aci n ei t her i nt r avenousl y when i t wor ked mor e qui ckl y or
or al l y. Osmond was our seni or exper t i n t hese st udi es. I n or der t o st udy t he
phenomenon mor e i nt ensi vel y we cal l ed f or vol unt eer s, most l y Uni ver si t y
st udent s. A f ew sci ent i st s al so came, as di d some j our nal i st s. They wer e much
mor e ent er pr i si ng t han wer e psychi at r i st s but sever al of our psychi at r i c
col l eagues i n Saskat chewan al so vol unt eer ed. Vol unt eer s wer e not pai d. They
wer e sel ect ed ver y car ef ul l y. Af t er t hey vol unt eer ed t hey wer e exami ned
car ef ul l y t o make sur e t hey wer e not schi zophr eni c as we di d not want t o gi ve
i t t o anyone who was or mi ght become schi zophr eni c. We al so excl uded
r el at i ves who had f i r st or der schi zophr eni c r el at i ves. Af t er t hi s exami nat i on
t hey wer e advi sed t o t hi nk about i t f or one mont h and i f t hey st i l l want ed t o
do i t t hey woul d be accept ed and gi ven t he exper i ence i n a cont r ol l ed
set t i ng, usual l y a hospi t al . Thi s i s pr obabl y why we had no maj or adver se
af t er ef f ect s i n t he t en year s or so t hat we wer e st udyi ng t hese compounds.

My f i r st cal l f or vol unt eer s was made i n Regi na i n 1953. Nei l Agnew,
r esear ch psychol ogi st , was t he f i r st vol unt eer . We i nvi t ed a number of j uni or
member s of t he Regi na Boar d of Tr ade t o come t o t he hospi t al . I out l i ned what
we wer e doi ng and why. To my amazement ever y one vol unt eer ed. Fr omt hat st udy
Agnew and I publ i shed a r epor t wi t h evi dence t hat we coul d t er mi nat e t he
exper i ence usi ng ei t her ni aci n or ni aci nami de.

Our pol i cy was not t o gi ve t hese dr ugs t o pat i ent s. Schi zophr eni c
pat i ent s have enough t r oubl e wi t h t hei r i l l ness and we saw no need t o make
t hemwor se. Thi s i s i n shar p cont r ast t o st udi es i n New Yor k st at e wher e LSD
was gi ven t o schi zophr eni c pat i ent s. But event ual l y we became i nt er est ed i n
t r eat i ng our al cohol i c pat i ent s. One day af t er a l ong, t i r i ng and bor i ng
noi sy f l i ght f r omSaskat oon t o Ot t awa i n an ol d Nor t h St ar wi t h Rol l s Royce
engi nes, Humphr y and I ar r i ved at our hot el exhaust ed and near l y deaf and I
had a sever e col d. Many year s l at er I di agnosed mysel f mor e accur at el y as
havi ng had al l er gi c r eact i on t o mi l k and af t er t hat di scover y have had no
mor e col ds. I coul d not sl eep t hat ni ght . At 4: 00 AM i t occur r ed t o me t hat
per haps we mi ght hel p al cohol i cs by gi vi ng t hema cont r ol l ed dt s exper i ence.
I n Al cohol i cs Anonymous i t was accept ed t hat hi t t i ng bot t omwas of t en a
pr er equi si t e but nat ur al dt s was danger ous wi t h a hi gh deat h r at e. No dr ugs
wer e t hen avai l abl e. The pr obl emwi t h nat ur al dt s was t hat t oo of t en af t er
t hey r ecover ed t hey r emember ed l i t t l e of what had happened. I t hought t hat i f
we coul d i nduce a t er r i bl e, a r eal psychot omi met i c exper i ence, whi ch mi ght
r esembl e dt s, t hey woul d r ecover f r omt he exper i ence wi t h a per f ect memor y of
what happened and t hat t hi s mi ght get t hemr eady t o j oi n AA. When Humphr y
awoke I i mmedi at el y t al ked t o hi mabout i t and we bot h agr eed i t was an i dea
wor t h t r yi ng. Humphr y had sever al al cohol i c pat i ent s i n hi s hospi t al t hat had
been commi t t ed. We want ed t o i nduce a psychot omi met i c t r ansi ent exper i ence
usi ng LSD. We f ound t hat we had t o use 200 mi cr ogr ams wher eas nor mal
vol unt eer s r esponded t o 100 mi cr ogr ams.

Af t er Humphr y had t r eat ed about f i ve pat i ent s he t ol d me t hat t hey wer e
havi ng di f f i cul t y gi vi ng t hei r pat i ent s t hi s t er r i bl e exper i ence. Some of t he
pat i ent s wer e havi ng an unusual l y pl easant exper i ence. Thi s had occur r ed so
f r equent l y t hat Humphr y concl uded i t was a new phenomenon and t hat i t needed
a name. He had gi ven Al dous Huxl ey mescal i ne i n hi s home i n Cal i f or ni a i n
1953. I t hi nk wat chi ng what happened t o Huxl ey and hi s own exper i ence wi t h
mescal i ne and LSD sensi t i zed Humphr y t o t hi s di f f er ent t ype of exper i ence.
Al most ever yone bel i eved t hat LSD made ever yone psychot i c. Humphr y f i nal l y
concl uded t hat t he t er mpsychedel i c best expr essed what was happeni ng. He
announced t he name and descr i bed t he exper i ence i n hi s paper t o t he New Yor k
Academy of Sci ence i n 1957. Si nce t hen he i s best known i nt er nat i onal l y f or
t he name and f or havi ng been t he pi oneer .

Psychedel i c t her apy was t aken up ver y qui ckl y by many cent er s and
f l our i shed unt i l gover nment s shut i t down. Humphr y and I advi sed our
gover nment not t o do so but t hey pr ef er r ed t o l i st en t o t he advi ce of our
naysayer s and cr i t i cs who had never st udi ed t he phenomenon. The r esul t was
t hat we al l st opped t r eat i ng our al cohol i cs t hi s way. I t became i mpossi bl e t o
get LSD and t o use i t r esponsi bl y except of cour se on t he st r eet s wher e i t
has al ways been avai l abl e and not i n t he pur e f or mt hat Sandoz pr ovi ded. But
i t i s not f ai r t o Osmond t o consi der onl y hi s wor k wi t h psychedel i cs. Hi s
most i mpor t ant wor k or i gi nat ed f r omhi s or i gi nal i dea t hat he seeded i n t he
hospi t abl e r esear ch soi l i n Saskat chewan i n 1952. Thi s was t he i mpet us f or
t he maj or r esear ch we al l di d cul mi nat i ng i n or t homol ecul ar psychi at r y, t he
new par adi gm. The l i t er at ur e on psychedel i cs i s vast and gr owi ng qui ckl y and
t he BBC and t he Nat i onal Fi l mBoar d, Canada, made vi deos descr i bi ng i t s
hi st or y. I t i s sl owl y comi ng back i nt o use i n t he Uni t ed St at es, agai nst
i mmense opposi t i on.

Our LSD st udi es i n Regi na cr eat ed an oppor t uni t y t o st udy t he Nat i ve
Amer i can Chur ch of Nor t h Amer i ca. I n t he mi d 1950 s whi l e I was st i l l wor ki ng
at t he Gener al Hospi t al i n Regi na, Sask. , I got a cal l f r omt he l ocal paper
The Leader Post . The r epor t er t ol d me t hat t he CCF MP f r omPr i nce Al ber t had
asked a quest i on i n t he House of Commons i n Ot t awa about t he Nat i ve Amer i can
Chur ch of Nor t h Amer i ca and t hat t he Mi ni st er of Heal t h had r epl i ed t hat t he
gover nment of Canada was goi ng t o t ake i mmedi at e act i on t o deal wi t h t hi s
danger ous pr act i ce of t hese I ndi ans. He asked me what my opi ni on was about
t hi s. I knew about t he chur ch i n t he Uni t ed St at es whose member s used t he
Peyot e But t on ( whi ch cont ai ns mescal i ne) as par t of t hei r sacr ament and t he
hi st or y i n t he Uni t ed St at es of t r yi ng t o suppr ess t hi s r el i gi on and I was i n
agr eement wi t h t he Nat i ve Amer i cans t hat t hi s pr act i ce was not danger ous and
shoul d not be har assed nor suppr essed. I r epl i ed t o t he r epor t er t he act i on
of t he gover nment was nonsense. The next day I was quot ed al l acr oss Canada,
gi vi ng me t he f i r st t ast e of not or i et y f or speaki ng what I consi der ed t o be
t he t r ut h. At t he same t i me I wr ot e t o Tommy Dougl as i n Ot t awa compl ai ni ng
about hi s member Mr . Max Campbel l f or r ai si ng t he i ssue and I was not ver y
compl i ment ar y t o Mr . Campbel l . The gover nment di d not do anyt hi ng but I doubt
my st at ement had much t o do wi t h t hat . They pr obabl y had second sober
t hought s about t he i ssue. Lat er Mr . Campbel l and I became good f r i ends. He
had been gi ven a l oaded quest i on by t he Depar t ment of Heal t h who want ed t o
suppr ess t he use of Peyot e and t hey needed someone t o ask t he quest i on f or
whi ch t hey had al r eady pr epar ed t hei r answer . Max r eal i zed he had been used.

At t he same t i me I l ear ned t hat t he Red Pheasant t r i be was member s of
t hi s chur ch. I t hought t hi s woul d be a mar vel ous oppor t uni t y t o l ear n mor e
about i t f r omf i r st hand obser vat i on. Humphr y was equal l y i nt er est ed. I wr ot e
t o t hei r headquar t er s i n t he Uni t ed St at es. Si x mont hs l at er Mr . Fr ank Takes
Gun answer ed and want ed t o know why I was i nt er est ed. He t hought at f i r st
t hat I was wor ki ng f or t he f eder al gover nment t hat I mi ght be a spy. I
r eassur ed hi mt hat my i nt er est was ent i r el y r esear ch and had not hi ng t o do
wi t h t he gover nment vi ews. He agr eed and somet i me l at er t he Nat i ve Amer i can
Chur ch of Nor t h Amer i ca i nvi t ed me t o come and par t i ci pat e at one of t hei r
al l ni ght Sat ur day sessi ons. Humphr y and I pl anned t hi s car ef ul l y. About f our
of us went i ncl udi ng Humphr y, Duncan Bl ewet t , Pr of essor of Psychol ogy, Dr T
Weckowi t z and I . I deci ded t o be an obser ver wi t h a t ape r ecor der . Humphr y
vol unt eer ed t o t ake t he peyot e and t o become a member of t he gr oup. We spent
t he ni ght wi t h t hem. I was not as obser vant as I shoul d have been and sl ept
par t of t he t i me but Humphr y r emai ned wi de awake. He f ound t he exper i ence
f asci nat i ng and ver y educat i onal . I do r emember t hat at mi dni ght t he Chai r man
Fr ank Takes Gun sai d t hat bei ng mi dni ght when al l t he whi t es wer e asl eep was
a good t i me t o pr ay t o God f or he woul d be mor e apt t o hear t hem. The t ot al
exper i ence r ei nf or ced my ear l i er concl usi on t hat t he way t hese nat i ve
Canadi ans pr act i ce t hei r chur ch usi ng Peyot e was beni gn, saf e and cer t ai nl y
ver y val uabl e t o t hem. Lat er my si st er Fanni e Kahan st udi ed t he l i t er at ur e on
t he use of t he hal l uci nogen Peyot e, summar i zed i t and wr ot e up t he ent i r e
exper i ence wi t h chapt er s by Osmond, by me, by Bl ewet t , but we have not been
abl e t o f i nd anyone wi l l i ng t o publ i sh t he r esul t of t hat i nt er est i ng ni ght .

To t est t he t her apeut i c ef f i cacy of any t r eat ment , one must have ways
of det er mi ni ng whet her t her e has been a change and how much. Thi s can be done
by cl i ni cal exami nat i on but t hi s i s not or i ousl y i ncompl et e and i nexact and
one shoul d use mor e obj ect i ve t est s. Osmond and I asked Dr N Agnew t o cul l
t he psychol ogi cal l i t er at ur e and pul l out any avai l abl e t est s t hat we coul d
use. Af t er sever al year s of i nvest i gat i on and a l ot of money Agnew f i nal l y
concl uded t hat t her e wer e no psychol ogi cal t est s. Dur i ng our di scussi on he
r emar ked t hat t he r eason was t hat psychi at r i st s coul d not agr ee on di agnost i c
cr i t er i a nor how t o use t hem. I n ot her wor ds t her e was t oo much di agnost i c
i nconsi st ency f or any psychol ogi cal t est t o be devel oped. He was of cour se
cor r ect . Hi s concl usi on f or ced me f or t he f i r st t i me t o t hi nk about t he
pr ocess of di agnosi s. I came t o t he concl usi on t hat i t was si mpl y a mat t er of
aski ng t he cor r ect quest i on whi ch coul d be answer ed yes or no, a bi nar y
syst em. Thi s bei ng t r ue one coul d do as wel l by usi ng car ds cont ai ni ng
t he cor r ect quest i ons whi ch woul d be scor ed i nt o t r ue or f al se, Yes or No
cat egor i es. Humphr y agr eed t hat t hi s was a good i dea, and dr awi ng upon our
accumul at ed knowl edge of t he schi zophr eni c exper i ence, dr af t ed 145 quest i ons
t hat we t hought woul d expl or e t he exper ent i al wor l d of our pat i ent s. Thi s
became t he HOD t est , t he Hof f er Osmond Di agnost i c t est
8
. I t f ul l y f ul f i l l ed
our expect at i ons. We t est ed t housands of pat i ent s at al l of our uni t s and
f ound t hat i t pi cked out schi zophr eni c pat i ent s f r omal l ot her di agnost i c
gr oups ver y ef f i ci ent l y, ver y si mpl y and was ver y accept abl e t o our pat i ent s.
We ar e not psychol ogi st s and t her ef or e di d not f ol l ow t he usual psychol ogi cal
met hods but l at er when Humphr y was i n Pr i ncet on he and hi s psychol ogi st Dr . M
El Mel i gi devel oped a much mor e sophi st i cat ed t est t hey cal l ed t he
Exper i ent i al Wor l d I nvent or y ( EWI ) . Thi s was much super i or . We gave t housands
of my pat i ent s bot h of t hese t est s and event ual l y i f my di agnost i c ski l l s
wer e not adequat e and i f t he HOD di d not hel p I used t he EWI , whi ch was ver y
hel pf ul . Unf or t unat el y t he EWI was never used on a l ar ge scal e whi l e t he HOD
was avoi ded by psychol ogi st s and psychi at r i st s. The HOD t est i s ver y usef ul
i n eval uat i ng pr ogr ess wi t h t r eat ment . Ther e was a hi gh cor r el at i on bet ween
hi gh HOD scor es and t he pr esence of t he mauve f act or and r esponse t o vi t ami n
t r eat ment . I r r espect i ve of t he cl i ni cal di agnosi s, pat i ent s wi t h hi gh scor es
and mauve f act or i n t hei r ur i ne gener al l y r esponded ver y wel l t o
or t homol ecul ar t r eat ment . Many chi r opr act or s i n Sout hwest Uni t ed St at es ar e
usi ng t he HOD t est i n t hi s way.


Does inhibiting the reaction to adrenochrome help patients?

We hoped t o i nhi bi t t hi s r eact i on by sl owi ng down t he f or mat i on of nor
adr enal i n f r omwhi ch adr enal i n i s made i n t he body by addi ng met hyl gr oups
and by addi ng ant i oxi dant s ( r educi ng compounds such as vi t ami n C) t o sl ow t he
oxi dat i on of adr enal i n t o adr enochr ome. Al l t he nat ur al ant i oxi dant s ought t o
be ef f ect i ve but gl ut at hi one shoul d be especi al l y ef f ect i ve because i t
neut r al i zes adr enochr ome. Vi t ami n B- 3 i ncr eases t he nat ur al pr oduct i on of
gl ut at hi one i n t he body. We l ooked at t he r eact i ons t hat l ed t o adr enal i n
f r omnor adr enal i n and on t o adr enochr ome. We t hought t hat ni cot i ni c aci d,
vi t ami n B- 3, whi ch i s a met hyl accept or , mi ght decr ease t he met hyl at i on of
nor adr enal i n t o adr enal i n. Thi s vi t ami n al so had many ot her advant ages. I t
was avai l abl e, was saf e, coul d be t aken f or ever and had been used i n l ar ge
doses t o t r eat chr oni c pel l agr a when t he usual smal l vi t ami n doses had f ai l ed
t o do so. I t had one maj or di sadvant age. I t coul d not be pat ent ed. We
conduct ed t he f i r st doubl e bl i nd cont r ol l ed pr ospect i ve r andomi zed
t her apeut i c t r i al s and showed t hat we doubl ed t he 2- year r ecover y r at e when

8 Hoffer A, Kelm H & Osmond H: The Hoffer-Osmond Diagnostic test. RE
Krieger Publishing Co. Huntington, New York, 1975.

t hi s vi t ami n was added i n opt i mal doses t o t he t r eat ment pr ogr amof t hese
year s, most l y ECT. Thi s became t he basi s of or t homol ecul ar psychi at r y. Af t er
Li nus Paul i ng j oi ned us and publ i shed hi s paper i n Sci ence i n 1968, t hi s l ed
t o or t homol ecul ar psychi at r y.
The dat a whi ch shows how ef f ect i ve t hi s t r eat ment i s vol umi nous and wi del y
publ i shed but st i l l i gnor ed. Ther e ar e no dr ug compani es pushi ng ni aci n, as
i t cannot be pat ent ed.

An of f shoot of our ni aci n st udi es was t he di scover y by Al t shul , Hof f er
and St ephen
9
t hat t hi s vi t ami n i n l ar ge doses l ower ed chol est er ol l evel s.
Si nce t hen i t has been f ound t hat i t al so el evat es hi gh densi t y l i popr ot ei n
chol est er ol and l ower s t r i gl ycer i des as wel l as l i po A, al l ver y i mpor t ant .
I t nor mal i zes bl ood l i pi d l evel s and i s t he gol d st andar d and much super i or
and saf er t han t he st at i ns. Thi s 1955 ni aci n r epor t of t he ef f ect of ni aci n
on chol est er ol i s consi der ed t he f i r st maj or paper t o i ni t i at e t he new
vi t ami n par adi gmi n medi ci ne. The ol d par adi gmgr adual l y bei ng r epl aced i s
t he vi t ami ns- as- pr event i on par adi gm. I t i s bei ng r epl aced by t he vi t ami n- as-
t r eat ment par adi gm. Ni aci n i s t he f i r st vi t ami n r el eased by t he FDA i n l ar ge
or mega vi t ami n doses. They l ooked upon i t as a dr ug f or l ower i ng
chol est er ol .

Or t homol ecul ar t r eat ment has expanded much beyond i t s f i r st use i n
t r eat i ng schi zophr eni c pat i ent s. I t i s a f ul l scope t r eat ment f or ever y
aspect of psychi at r y and medi ci ne. I n my opi ni on or t homol ecul ar t heor y and
pr act i ce i s t he maj or cont r i but i on t hat has come f r omour Saskat chewan
r esear ch.


Involving the community

One of t he f i r st concl usi ons made by Dr DG McKer r acher i n t he l at e
1940 s was t hat t he ment al hospi t al had been moved t oo f ar f r omt he communi t y
f r omwhi ch t hese pat i ent s came. He est abl i shed t he Saskat chewan Pl an f or
bui l di ng smal l er hospi t al s al l acr oss t he pr ovi nce so t hat no one need t r avel
mor e t han 50 mi l es t o vi si t t hei r r el at i ves. Humphr y and I consi der ed t hi s a
ver y good pl an and had a smal l par t i n i t s devel opment . But we went somewhat
f ur t her and st ar t ed t o i nvol ve t he publ i c by cr eat i ng t he Amer i can
Schi zophr eni a Associ at i on, l at er cal l ed t he Huxl ey I nst i t ut e f or Bi osoci al
Resear ch, and f ol l owi ng t hat i n Canada t he Canadi an Schi zophr eni a Foundat i on
now known as t he I nt er nat i onal Schi zophr eni a Foundat i on. These associ at i ons
wer e cr eat ed t o pr ovi de accur at e i nf or mat i on about t he di sease and i t s
t r eat ment . We ar e t he onl y or gani zat i on i n Nor t h Amer i ca st i l l doi ng so. We
suppor t t he best t r eat ment avai l abl e, whi ch i s or t homol ecul ar . Humphr y and I
wer e f oundi ng member s; we wer e on t he boar d and of f i cer s at var i ous t i mes. We
al so t r avel ed t oget her a l ot l ooki ng f or f unds t o f ur t her our r esear ch and
went t o meet i ngs t oget her . Thi s gave us ampl e t i me t o t al k about our mut ual
act i vi t i es and i nt er est s.

I n 1957 we f l ew t o Zur i ch, Swi t zer l and, t o par t i ci pat e i n t he Second
I nt er nat i onal Congr ess of Psychi at r y. Dr C J ung was t he Honor ar y Chai r of our
sect i on. The Col l egi umI nt er nat i onal e Neur o- Psychophar macol ogy was f or mal l y
i naugur at ed at t hat meet i ng wi t h Pr of essor E Rot hl i n t he f i r st Pr esi dent .

9 Altschul R, Hoffer A & Stephen JD: Influence of nicotinic acid on serum
cholesterol in man. Archives Biochemistry Biophysics. 54; 558-559:
1955.

Humphr y and I wer e t her e as f oundi ng member s. I t was an i nt er est i ng meet i ng.
We met Dr J ung, al so spoke t o Pr of essor Rot hl i n who advi sed us bot h t o spend
as much t i me as possi bl e on our r esear ch and as l i t t l e as possi bl e t r avel i ng
t o meet i ngs. Those wer e heady year s and i nvest i gat or s wer e spendi ng a l ot of
t i me t r avel i ng t o each ot her s meet i ngs usi ng t r avel f unds f r omeach ot her s
gr ant s and sayi ng t he same t hi ng over and over . Rot hl i n s advi ce was ver y
good and we di d t ake i t . On t he way home we vi si t ed Dr . Ti sel i us, Nobel
Laur eat e f or hi s wor k wi t h chr omat ogr aphi c anal ysi s. He was encour agi ng. We
had an hypot hesi s t hat coul d be used. Many had asked hi mt o become i nvol ved
i n t he sear ch f or t he schi zophr eni c t oxi n and i n ever y case he woul d ask hi s
bi ochemi cal st af f and how do we st ar t . How does one l ook f or one of per haps
50, 000 compounds t hat mi ght be pr esent i n t he body. No one had ever di scussed
wi t h hi many way of f i ndi ng out what mi ght be t he schi zophr eni c t oxi n.
Humphr y and I wer e encour aged by t hi s vi si t .


Dr Donald Johnson and How to Live With Schizophrenia

I nvol vi ng t he communi t y al so meant pr ovi di ng i t wi t h i nf or mat i on. Thi s
i s why we wr ot e our book How to Live with Schizophrenia
10
. Thi s was publ i shed
by Dr . Donal d J ohnson MP, conser vat i ve member . When I was sear chi ng f or al l
t he known hal l uci nogens I r an acr oss a pamphl et wr i t t en by Dr J ohnson cal l ed
The Hallucinogens. I t was a r evi ew of t he ef f ect s of hash. I wr ot e t o Dr
J ohnson and he i mmedi at el y sent me a copy. Thi s st ar t ed our cor r espondence
and l at er when I was i n Engl and he i nvi t ed me t o have t ea wi t h hi mi n t he
member s l ounge over l ooki ng t he Thames. Hi s st or y was i nt r i gui ng. He had
gi ven up t he pr act i ce of medi ci ne t o t ake l aw. Lat er he gave t hat up as wel l
and became an i nnkeeper . I n t he meant i me he had r un f or par l i ament on sever al
occasi ons f or t he conser vat i ve par t y and had not won el ect i on. One day at t he
i nn a wi ne sal esman of f er ed hi msome wi ne t o t ast e. He br oke one of t he
car di nal r ul es of t ast i ng wi nd f r oma st r anger ; never dr i nk f r oman open
bot t l e. Thi s t i me he di d. As he was about t o t ake hi s f i r st si p hi s wi f e came
i n and he of f er ed her a dr i nk. She t ook about one t hi r d and he f i ni shed t he
r est . That eveni ng he became psychot i c whi l e hi s wi f e f el t i l l . She cal l ed
f or hel p and he was commi t t ed t o a ment al hospi t al . On admi ssi ons he was t ol d
by t he admi t t i ng psychi at r i st t hat he had schi zophr eni a and t hat he woul d
never l eave hospi t al . But Dr J ohnson r ecover ed i n a f ew days wi t hout
medi cat i on. The cur r ent dr ugs wer e t hen not avai l abl e. The hospi t al woul d not
r el ease hi munt i l he sl i pped not es under hi s door whi ch event ual l y f ound
t hei r way t o hi s l awyer . The whol e epi sode puzzl ed hi mbecause he' d never
been i l l bef or e and coul d not bel i eve t hat he had a shor t l i ved epi sode of
schi zophr eni a. So he began t o sear ch t he l i t er at ur e and event ual l y concl uded
t hat t he wi ne sal esman had pl aced a hal l uci nogen i n hi s wi ne. He r epor t ed
t hi s t o t he pol i ce but t hey i gnor ed t he whol e epi sode. He t hen gave up hi s
i nn, became a book publ i sher and r an f or par l i ament and t hi s t i me he was
el ect ed. Dur i ng our t al k he suddenl y asked me i f I woul d wr i t e a book f or
hi m. Sur pr i sed I asked hi mwhat about . He r epl i ed about anyt hi ng. I r epl i ed
t hat I had not hi ng i n mi nd but t hen i t occur r ed t o me t hat we di d need a book
di r ect ed t o schi zophr eni c pat i ent s and t hei r f ami l i es. I t was al most
i mpossi bl e f or f ami l i es t o f i nd any i nf or mat i on except t he ol d t ext books

10 Hoffer A & Osmond H: How to Live With Schizophrenia. University
Books, New York, NY, 1966. Also published by Johnson, London, 1966.
Written by Fannie Kahan. New and Revised Ed. Citadel Press, New York,
NY, 1992. Revised. New Title Healing Schizophrenia CCNM Press, Toronto,
ON 2004.

whi ch descr i be onl y t he wor st chr oni c cases and ar e ver y di scour agi ng. I was
r emi nded of a young man who had been t r eat ed at Uni ver si t y Hospi t al i n
Saskat oon f or schi zophr eni a but had not been t ol d hi s di agnosi s. Af t er
di schar ge he was f ol l owed by hi s f ami l y doct or . Dur i ng hi s f i r st f ol l ow up
i nt er vi ew hi s doct or was cal l ed out and t he young man l ooked up hi s f i l e and
r ead t hat he had schi zophr eni a. He di d not know what i t meant but when he got
home he l ooked i t up i n t he di ct i onar y and r ead t hat i t was a hopel essl y
i ncur abl e chr oni c di sease. He shot hi msel f wi t h a r i f l e nar r owl y mi ssi ng hi s
hear t . I n hospi t al I saw hi m, st ar t ed hi mon vi t ami ns and expl ai ned what t he
condi t i on was. Had he been gi ven pr oper i nf or mat i on at t he hospi t al i n t he
f i r st pl ace he pr obabl y woul d not have made t he at t empt on hi s own l i f e. I
t ol d Dr . J ohnson t hat I woul d di scuss t hi s wi t h Humphr y Osmond and l et hi m
know. I t occur r ed t o me t hat Humphr y and I woul d wr i t e t he f i r st dr af t s of
t hi s book and t hat I woul d ask Fanni e Kahan, my si st er , t o r ewr i t e i t . I
asked her i f she woul d be i nt er est ed i n wr i t i ng i t so t hat t he aver age 12
year ol d coul d under st and. When I t ol d my f ami l y what I was pl anni ng, J ohn
suggest ed t hat we use t he t i t l e " How To" because How To books wer e becomi ng
popul ar . Humphr y and I di vi ded t he book i nt o sect i ons t hat we woul d each do
and af t er we wer e sat i sf i ed wi t h t he wor k we t ur ned i t over t o Fanni e and she
r ewr ot e t he ent i r e book. We want ed t o have t hr ee aut hor on t he t i t l e but DR
J ohnson adamant l y r ef used sayi ng t hat he want ed onl y doct or s as aut hor s. I
was sor r y about t hi s but had I i nsi st ed t her e woul d not have been any book.
Si nce t hen t hi s book has been r epubl i shed sever al t i mes and pr esent sal e must
be over 100, 000. I t was never a best sel l er but di d sel l sl owl y and st eadi l y
and i t di d save many peopl e s l i ves. The pr esent ver si on i s mi ne al one and i s
cal l ed Healing Schizophrenia. Humphr y was not abl e t o wr i t e af t er hi s st r oke
over 10 year s ago. My si st er Fanni e Kahan wr ot e t he f i nal ver si on of t hi s
book but t he publ i sher woul d not publ i sh wi t h her name on t he cover . The
r oyal t i es wer e spl i t t hr ee ways. Thi s was one of t he f i r st medi cal How To
books and t he f i r st one wr i t t en f or pat i ent s and t hei r f ami l i es. I t has sol d
si nce t hen at a sl ow but st eady pace. The new r evi sed edi t i on i s now
avai l abl e. We al so wor ked t oget her t o cr eat e t he J our nal publ i shed by t he
Canadi an Schi zophr eni a Foundat i on, now t he I nt er nat i onal Schi zophr eni a
Foundat i on and we shar ed aut hor shi p f or many paper s and books. Humphr y s
wr i t i ng ski l l s wer e i nval uabl e and I l ear ned a t r emendous amount f r omhi m. We
al so or gani zed t he Amer i can Schi zophr eni a Associ at i on, l at er r enamed t he
Huxl ey I nst i t ut e of Bi osoci al Resear ch. The HI BR t r ai ned hundr eds of doct or s
who at t ended weekend meet i ngs al l acr oss t he Uni t ed St at es.


Huxley Institute of Biosocial Research

About 1959 Humphr y cal l ed me f r omPr i ncet on. A mi ddl e aged man l anded
on t he hospi t al gr ounds i n a hel i copt er . He t ol d Humphr y about hi s son who
had been schi zophr eni c f r omchi l dhood. He had become weal t hy ent i r el y on hi s
own ef f or t , t aki ng l aw whi l e dr i vi ng a cab and event ual l y he bought t he
f ur ni t ur e f act or y wher e he had once been a wor ker . Humphr y t ol d hi mt o cal l
me and soon he di d. He want ed me t o t ake hi s son i n f or t r eat ment . I had a
f ew beds of my own and i n t hose year s we wer e not so desper at el y shor t of
beds as we ar e t oday. As I was wor ki ng f ul l t i me f or t he Gover nment I coul d
not char ge hi m. He i nsi st ed he woul d have t o gi ve me somet hi ng and soon a set
of out door f ur ni t ur e ar r i ved made i n hi s f act or y. For t y- f i ve year s l at er i t
i s st i l l i n excel l ent shape even t hough i t has been out door s i n t he wi nt er
and summer s i n Saskat chewan and si nce 1976 i n Vi ct or i a BC.

Humphr y had been cor r espondi ng wi t h Mr s. Mi r i amRot hschi l d i n London. I
met her i n 1954 when Rose and I wer e on our Rocker f el l er Foundat i on sponsor ed
t our . Bef or e dr i vi ng west t o Wal es we had di nner wi t h her and wi t h Dr . Der eck
Ri cht er . Dr Ri cht er had once consi der ed t he i ndol e t heor y of schi zophr eni a
but had concl uded t hat not enough i ndol es coul d be f or med i n t he body. He had
al so l ooked at adr enochr ome and had concl uded t hat i t was not made i n t he
body. Mr s. Rot hschi l d was a bi ochemi st who was st udyi ng t he bi ochemi st r y of
i nsect s. Humphr y had wr i t t en her about t he need f or an or gani zat i on f or
schi zophr eni c pat i ent s t hat woul d do f or t hemwhat t he cancer soci et y was
doi ng f or cancer pat i ent s. Mr s. Rot hschi l d r epl i ed t hat i f we coul d or gani ze
an I nt er nat i onal Schi zophr eni a Soci et y she woul d ask her br ot her s t o
cont r i but e. Fol l owi ng up t hi s i dea we spoke t o t he f at her about or gani zi ng
such a soci et y i n t he Uni t ed St at es. He agr eed and gave us 25, 000 dol l ar s
wi t h whi ch t o st ar t . For t unat el y about t hat t i me a New Yor k i nvest i gat i ve
j our nal i st , Cal Samr a, had cont act ed me and on l ear ni ng about t he vi t ami n
pr ogr ambecame ver y i nt er est ed. He was ver y i nt el l i gent and a ver y good
wr i t er . Humphr y and I deci ded t hat he woul d be our f i r st di r ect or , t he f at her
woul d be t he Chai r man of t he Boar d of t he Amer i can Schi zophr eni a Associ at i on
and bot h Humphr y and I woul d be f oundi ng member s of t he boar d. Cal Samr a knew
a l aw f i r mi n New Yor k and t hey agr eed t o act f or us pr o bono. One day
Humphr y and I and Cal met i n New Yor k i n a wal k up apar t ment wi t h our l awyer .
We dr af t ed our const i t ut i on and we wer e on our way.

Cal event ual l y became pr esi dent and put hi msel f whol ehear t edl y i nt o our
associ at i on. We publ i shed a newsl et t er whi ch he edi t ed and wr ot e and we began
our f i r st dr i ve f or money. We sent a l et t er t o ever y per son who had ever
cont act ed Humphr y and me and t o our amazement t ook i n about 70, 000 dol l ar s.
We wer e at l ast f i r ml y l aunched. We hel d our second sci ent i f i c meet i ng i n
I r el and. Our benef act or owned a cast l e near Shannon Ai r por t and of f er ed i t t o
us f or t he meet i ng. But sever al year s l at er we and our benef act or par t ed but
on condi t i on t hat t he 25, 000 he had gi ven us be gi ven t o a Psychi at r i c
Hospi t al f or a bi ochemi cal st udy whi ch I consi der ed t ot al l y wast ef ul but we
had no choi ce. We wer e on our own. That year I i nvi t ed Mr . Ben Webst er t o
j oi n us as our t r easur er . Lat er we became t he Huxl ey I nst i t ut e of Bi osoci al
Resear ch wi t h t he appr oval of t he Huxl ey f ami l y. Humphr y was a ver y act i ve
member on our boar d and at our meet i ngs unt i l t he HI BR col l apsed some year s
ago due t o l ack of i nt er est and money. Thi s was one of t he obj ect i ves of t he
NI MH who consi der ed us a maj or i r r i t ant and a bur r under t hei r saddl e. NI MH
had US gover nment money and t he Uni t ed St at es psychi at r i c est abl i shment
depended on t hemf or t hei r r esear ch moni es.

Our execut i ve di r ect or , af t er Cal Samr a l ef t , ar r anged f or some of us
t o meet wi t h a smal l r epr esent at i on f r omNI MH. We met i n Washi ngt on, DC. On
our si de we had Li nus Paul i ng, Humphr y Osmond, our execut i ve di r ect or and f or
t he NI MH Dr Mor r i s Li pt on, who had chai r ed t he r emar kabl e Task For ce of t he
Amer i can Psychi at r i c Associ at i on whi ch had r oundl y denounced our wor k and had
publ i shed a most r emar kabl e document , r emar kabl e f or i t s t ot al l y di shonest
account of what we had been doi ng and cl ai mi ng. The most r abi d r epubl i can i n
t he Uni t ed St at es woul d pr obabl y have done a mor e honest j ob i n at t acki ng t he
Democr at i c Par t y. Humphr y and I r epl i ed t o t hi s cor r upt document but f ew pai d
any at t ent i on
11
. I t became t he hol y wr i t , t he bi bl e, f or t he ant i
or t homol ecul ar movement .


11 Hoffer A and Osmond H. Megavitamin Therapy. In Reply To The American
Psychiatric Association Task Force Report on Megavitamin and
Orthomolecular Therapy in Psychiatry. Canadian Schizophrenia
Foundation, August 1976.

The mor ni ng was not pl easant . Seymour Ket y and Dr . Lor en Mosher wer e
pr esent . Wi t hout any not i ce Dr . Ket y i nt r oduced our benef act or who got up t o
t al k about how my t r eat ment had not hel ped hi s son. I n f act af t er I had hi m
wi t h me f or a mont h he was ver y much bet t er and hi s mot her was ver y pl eased
wi t h t he out come. But our benef act or coul d not f i nd any physi ci an who woul d
car r y on t he t r eat ment af t er hi s son came home and he sl owl y r el apsed. I
coul d not descr i be t he case because I had been hi s doct or . Ket y had used our
benef act or as a t ool and I suspect had been i nst r ument al i n t he spl i t t hat
occur r ed bet ween hi mand t he r est of our boar d of t he ASA. Mor r i s Li pt on
mai nt ai ned t hat he was a bi ochemi st because he had done r esear ch wor k i n t he
l abor at or y wher e El vehj emhad pr oved t hat ni aci n was vi t ami n B- 3. But he knew
l i t t l e chemi st r y and when he made a st at ement t hat even a f i r st year
chemi st r y st udent shoul d not have made, Paul i ng, t he wor l d s gr eat est
chemi st , t he t wo- t i me Nobel wi nner , t he f i r st f or chemi st r y, r oundl y ber at ed
hi mf or hi s i gnor ance. Mosher was equal l y host i l e. He t ol d us t hat i n hi s
vi ew even i f ever y psychi at r i st i n t he Uni t ed St at es used or t homol ecul ar
t r eat ment he woul d st i l l not bel i eve i t had any val ue. Mosher was Di r ect or of
t he Schi zophr eni a Sect i on of NI MH. Thi s I t hought was ver y appr opr i at e si nce
he di d not bel i eve such a di sease exi st ed and he was t ot al l y opposed t o any
f or mof chemi cal i nt er vent i on. Thi s meet i ng di d not r esol ve any of our
di f f i cul t i es and NI MH r emai ned sol i dl y opposed t o ever yt hi ng t hat we di d.
Li pt on t ol d me pr i vat el y t hat he woul d never publ i sh any paper of mi ne no
mat t er how good i t was and as Associ at e Edi t or of t he American Journal of
Psychiatry he r emai ned t r ue t o hi s wor d. Recent l y Dr . Mosher t ol d one of my
acquai nt ances t hat t he onl y r eason I had got t en good r esul t s was because I
had car ef ul l y pr esel ect ed onl y t hose pat i ent s who woul d have got t en wel l
anyway. I know no one so ski l l f ul t hat he coul d pr esel ect t he ones who wer e
goi ng t o get wel l . And our pl acebo cont r ol gr oup, whi ch i s supposed t o
el i mi nat e bi as, showed t hat onl y one t hi r d of t hi s gr oup was wel l t wo year s
l at er . Thi s was t he unr easonabl e and host i l e cr i t i ci smt hat was appl i ed t o
our wor k.


The Mauve factor (kryptopyrrole) test
12
,
13


We wer e t r eat i ng al cohol i c pat i ent s wi t h t he psychedel i c exper i ence
usi ng LSD. I t occur r ed t o me t hat i n t he same way t hat LSD r epr oduced some of
t he char act er i st i cs of schi zophr eni a as was poi nt ed out by Osmond and
Smyt hi es t hat t her e mi ght be a si mi l ar change i n t hei r bi ochemi st r y. We
t est ed t hi s i dea by col l ect i ng t hei r ur i ne bef or e and af t er t hey had t aken
t he LSD. I n t he f i r st pat i ent we t est ed we f ound a new bi ochemi cal on t he
paper chr omat ogr amt hat had not been pr esent i n t he base l i ne sampl e of
ur i ne. Af t er we showed i t was not LSD, we st udi ed t he ur i ne of a l ar ge number
of pat i ent s i n our t hr ee r esear ch hospi t al s and f ound t hat i t was f ound
chi ef l y i n schi zophr eni c pat i ent s but t o a smal l er degr ee i n ot her pat i ent s.
I t was f ound r ar el y i n nor mal subj ect s but was f ound i n pat i ent s under sever e
st r ess f r omcancer . Because i t st ai ned mauve we cal l ed i t t he mauve f act or

12 Hoffer A & Mahon M: The presence of unidentified substances in the
urine of psychiatric patients. J. Neuropsychiatry 2; 331-362: 1961.

13 Hoffer A & Osmond H: The relationship between an unknown factor (US)
in the urine of subjects and HOD test results. J Neuropsychiatry 2;
363-368:1961.

and t he condi t i on i n whi ch i t was f ound we cal l ed Mal var i a
14
. Lat er we
i dent i f i ed i t as a kr ypt opyr r ol e but t hat was onl y par t i al l y cor r ect and
r ecent r esear ch i s r eveal i ng i t s t r ue i dent i t y.

Af t er t en year s at Weybur n i n Saskat chewan, Dr Osmond became Di r ect or
of The Bur eau of Resear ch i n Neur ol ogy and Psychi at r y i n Pr i ncet on. Thi s
bur eau had been or gani zed by Dr Nol an DC Lewi s, t he gr eat Amer i can
psychi at r i st , Chai r , Col umbi a Uni ver si t y. Dr CC Pf ei f f er i n Osmond s r esear ch
gr oup devel oped a quant i t at i ve t est whi ch has been ver y f r ui t f ul . Today t he
st udy of t hi s mauve f act or has been expanded as i t i s f ound i n near l y hal f of
t he cases of i nf ant i l e aut i sm. I t i s a mar ker f or oxi dat i ve st r ess. I t bi nds
bot h zi nc and pyr i doxi ne and pr oduces a doubl e def i ci ency.

We f ound t hat pat i ent s who excr et ed t hi s f act or r esembl ed our schi zophr eni c
pat i ent s mor e t han t hey di d non- schi zophr eni c pat i ent s. They scor ed i n t he
schi zophr eni c r ange usi ng t he HOD t est and r esponded wel l t o megavi t ami n t her apy.
Thi s suggest s t hat we ar e r eal l y l ooki ng at a homogeneous di sease. Car l Pf ei f f er
cal l ed i t pyr r ol ur i a.

A good hypot hesi s i n sci ence i s ver y r ar e. By good I do not mean
cor r ect . Hypot heses t end t o be evanescent and ar e modi f i ed as new i nf or mat i on
accumul at es. Good means t hat i t di r ect s usef ul r esear ch and l eads t o usef ul
di scover i es. The or i gi nal t oxi n M hypot hesi s by Osmond and Smyt hi es i s one of
t hese r ar e good hypot heses. Newer and bet t er ones wi l l r epl ace i t s f ol l ow up
hypot hesi s by Hof f er , Osmond and Smyt hi es.

The New Yor k Ti mes summar i zed an amazi ng par adi gmshi f t i n hypot hesi s
about hear t di sease. The cur r ent bel i ef i s t hat pl aque i s r esponsi bl e and f or
t hat r eason mechani cal met hods have been used t o r emove t he obst r uct i on,
r epl ace vessel s, and enl ar ge t hemwi t h bal l oons and t o use st i nt s. But
evi dence i s devel opi ng t hat t hese met hods ar e no bet t er i n i ncr easi ng
l ongevi t y t han ar e met hods f or l ower i ng chol est er ol . Had t he i nvest i gat or s
used ni aci n as t he chol est er ol - l ower i ng agent t hey woul d have f ound a
si gni f i cant i mpr ovement compar ed t o t he sur gi cal t echni ques. I n t he New Yor k
Ti mes Sunday Mar ch 28, 2004, under t he t i t l e The Li mi t s of Openi ng Ar t er i es
t he edi t or i al l ament s Thi s pr of ound change i n t hi nki ng about car di ovascul ar
pr obl ems makes us year n f or t he day when t her e can be much wi der t est i ng of
one t her apy agai nst anot her t o i dent i f y t hose t hat wor k best f r omt hose t hat
may be over sol d. I n t he same edi t i on Thomas L Fr i edman concl udes t hat 9/ 11
was not a f ai l ur e of i nt el l i gence. I t was a f ai l ur e of i magi nat i on. I f t hese
t wo vi ews had been f ol l owed or t homol ecul ar medi ci ne woul d by now be wel l
est abl i shed. Due t o t he l ack of i magi nat i on and f ai l ur e t o r un compar i son
t r i al s we ar e st i l l st r uggl i ng t o have i t est abl i shed.




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14 Hoffer A & Osmond H: Malvaria: a new psychiatric disease. Acta
Psychiatrica Scandinavica 39; 335-366:1963.