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The History of Psychedelics

in Medicine

Dr Ben Sessa MBBS BSc MRCPsych

The Psychedelic Society of Leeds
2nd April 2015


What are psychedelic drugs?

The Ancient History of Spirituality and Shamanism

The First Psychedelic Era

The Cactus Years

The Second Psychedelic Era


The Dark Ages

The Third (present) Psychedelic Era

Renaissance and Culture

The Future for Psychedelics in Medicine & Human Culture

Why Medicine Needs Psychedelics

Legal highs, Psychonauts and Trip Reports

What are Psychedelic Drugs?

Classical psychedelics(5-HT2A receptor partial agonists)
LSD, Psilocybin, DMT, Mescaline

Entactogens (Serotonin receptor agonists)


Dissociative anaesthetics (NMDA-antagonists)

Ketamine, PCP

THC (Cannabinoid receptor agonist)

Ibogaine (Nicotinic receptor antagonist)
Salvia Divinorum (Kappa-Opioid receptor agonist)

What is a Psychedelic

Increased sensory perception and illusionary changes


Enhanced mental imagery

New associations and meanings of relationships and objects

Enables access to inner thoughts and feelings that are usually repressed

Ego dissolution

Increased affectivity

Dream-like experience, but in clear consciousness with full awareness of self and good memory of the

The Archaic History of

Spirituality and Shamanism

The First Psychedelic Era:

1890s 1940s
Mescaline and Laughing Gas

The Effects of the

Peyote Cactus
S. Wier Mitchell - American
neurologist and novelist

First published report of peyotes

psychological effects on humans

Also published on esoteric

subjects such as Gunshot
Wounds and Other Injuries of
Nerves and Researches Upon the
Venom of the Rattlesnake.

The pharmacology of the

Peyote Cactus
Louis Lewin - German pharmacologist

The first analysis of the cactus in 1894 by the

after whom the cactus was named, Louis Lewin.

One of the first scientists to recognise the links

between the pharmacology of plants and their
mental effects.

First to classify psychoactive drugs based on

their subjective effects

New words include: euphoriants, such as

heroin, the inebriants, such as alcohol and
phantastica, which later became the

Werner Stoll, referred to Hofmanns new

discovery as a phantastica (Stoll,1947).

Further descriptions of
Peyote Cactus
Henry Havelock-Ellis British
physician and psychologist

The Phenomena of Mescal Intoxication

(Havelock Ellis, 1897) and Mescal: A New
Artificial Paradise (Havelock Ellis, 1898).

Wrote extensively on the science of sex,

published the first medical textbook on
homosexuality and was reportedly
aroused by urolagnia.

Isolation of Mescaline
Arthur Carl Wilhelm
Heffter - German

1897: Isolates mescaline from

the peyote cactus.

The first Handbook of

Pharmacology(Heffter, 1898).

Heffter Research Institute.

Laughing Gas and



Brother of the
author Henry

The Varieties of
Experience (James,

Our normal waking

consciousness, rational
consciousness as we call it, is
but one special type of
consciousness, whilst all
about it, parted from it by
the filmiest of screens, there
lie potential forms of
consciousness entirely
different. We may go
through life without
suspecting their existence;
but apply the requisite
stimulus, and at a touch they
are there in all their

Synthesis of
(synthetic) Mescaline

Ernst Spth

- Austrian

Following the work of Lewin

and Heffter the race was on
to synthesise mescaline.

Spth achieved it first in 1919.

He died penniless after WWII

but now has a bust in the
Faculty of Chemistryof
theUniversity of Vienna.

Mescaline and
Eidetic Imagery
Heinrich Klver
German and American

Using mescaline as a
research tool discovered the
nature of eidetic imagery,
(Klver, 1928).

Described recurring
geometric patterns: lattices
checkerboards and
triangles) Cobwebs, tunnels
and spirals.

The Second Psychedelic Era:

1940s 1970s

Discovery of LSD

Interest in mescaline and psilocybin



The Heyday of Psychedelic Research

Popularisation of psychedelics


The discovery of LSD

Dr Albert Hofmann
1906 2008
Swiss Chemist
First synthesised LSD in 1938
Discovered psychedelic
properties in 1943
Campaigned for medical uses for
psychedelics until his death aged
102 years

Psychiatric Psychedelic


Psycholytic Psychotherapy

Psychedelic Psychotherapy / Peak and Mystical




Early Medical Uses for LSD


Self-experimentation by mental health

3. Psychedelic Psychotherapy

High dose single drug session

Mystical / Peak experience
Favoured in the US

4. Psycholytic Psychotherapy

Low doses
Frequent, regular sessions
Favoured in the UK

How do classical psychedelics work clinically?

Loosening of the ego
Access to the unconscious
Repressed memories
Can be worked through in real time

o Non-directive, supporting emerging experience

o Alternating inner focus & talking to therapists
o Encouraged to fully experience and express
whatever arises rather than avoiding or

Creation of positive set and setting

Preparation for sessions
Use of breath, music and therapeutic touch
Follow-up and integration

Ronald David Laing:

Advice for those wishing to become a

Read the works of Freud

Undergo personal analysis
Take LSD

Aldous Huxley and Humphrey Osmond:

Two very British intellectuals
To make this trivial world sublime
Take a half a gramme of phanerothyme

To sink in hell or soar angelic

Youll need a pinch of psychedelic


Dr Ronald Sandison:
British Psychiatrist and Psychoanalyst

Kingsley Hall - 1965-70

In 1965 became home to an

experiment by The Philadelphia
Association, run by RD Laing.

Based on the notion that

psychosis, a state of reality akin to
living in a waking dream, is not an

Psychosis is a state of trance

which could even be valued as
mystical or Shamanistic

Use of LSD and DMT

Psychedelics as tools for addictions


Psychosis (DTs)




"The only cure for Dipsomania is Religiomania

William James, The Varieties of Religious Experience, 1902

I consider LSD to be of some value to some people, and practically no damage to


Some Important Movers..

Max Rinkel and Robert Hyde: Boston
Psychopathic Hospital in 1950. First to
take LSD in America.
Hanscarl Leuner: In Germany, between 1955 and
1960. 1,300 sessions with LSD, mescaline and
Sidney Cohen: In 1960. Major review of 5000 subjects
and 25,000 drug sessions and finds rates of psychosis of
only 0.2% and suicide of 0.04%

Stanislav Grof: In 1965. Chief of Maryland Psychiatric

Institute. Psychedelics and death. Joan Halifax and Elizabeth

Other Important Movers.

Humphrey Osmond: Saskatchewan Mental Institute
Alcoholism. With Abram Hoffer and John Smythies.
John C. Lilly: Dolphins, Floatation Tanks, LSD
and Ketamine. From 1960 Late 1970s.
Oscar Janiger: Naturalistic experiments
with LSD on over 1000 people. Between
Milan Hausner: Between 1956 and 1974. Near Prague.
700 patients. 6000 psychedelic sessions.
Walter Pahnke: 1964. The March
Chapel Good Friday

Meta-analyses in the 1960s:

44 psychiatrists, 5000 subjects and 25,000 drug sessions:

Rate of psychosis: 0.2%
Rate of suicide of 0.04%
(Cohen S. (1960) LSD: side effects and complications. Journal of Nervous and Mental Disorders 130: 30-40)

700 psychedelic drug sessions:

One case of prolonged psychosis

(Chandler Al. & Hartman Ma. (1960) LSD-25 as a Facilitating Agent in Psychotherapy.AMA Arch Gen Psychiatry; 2(3):

350 patients over four years of outpatient treatments:

One attempted suicide
(Ling TM, Buckman J (1963) The Treatment of Anxiety with Lysergic Acid and Methylphenidate. Practitioner 191: 201-4)

Review of 20 years of psychedelic therapy in the UK, 4000 patients and 50,000
psychedelic drug-assisted sessions.
Two completed suicides
Thirty-seven patients with a prolonged psychosis
(Malleson, N. (1971) Acute Adverse Reactions to LSD in clinical and experimental use in the UK. Br J Psychiatry. 18(543):229-30)

"Treatment with LSD is not without acute adverse reactions, but given adequate
psychiatric supervision and proper conditions for its administration, the incidence of such
reactions is not great,"

Safety Profile of

Safety when using classical

psychedelics recreationally
Norwegian study:

2001-2004 US National Survey on Drug Use

130,000 randomly chosen people

22,000 people who had used psychedelics at least once.

No negative link between the use of psychedelic drugs and anxiety

disorders, mood disorders, and psychosis.

After adjusting for other risk factors, lifetime use of classical

psychedelics associated with lower rates of outpatient mental health
treatment and psychiatric medicine prescription.

Krebs TS, Johansen P- (2013) Psychedelics and Mental Health: A Population Study. PLoS ONE 8(8): e63972.

Safety when using classical

psychedelics recreationally
Whilst some evidence suggests that psychedelics might have a
negative effect on mental health for some individuals or groups this
is counterbalanced at a population level by positive effects on most

"Early speculation that psychedelics might lead to mental health

problems was based on a small number of case reports and did not
take into account either the widespread use of psychedelics or the
not infrequent rate of mental health problems in the general
Krebs TS, Johansen P- (2013) Psychedelics and Mental Health: A Population Study. PLoS ONE 8(8): e63972.

Safety when using classical

psychedelics clinically

Physiological risks

Virtually zero

Psychosis and Suicide

Dependency risks

Hallucinogen Persisting

Very low
Very low

Perception Disorder (HPPD) Rare

Sessa, B. (2012) The Risks and Safety of Psychedelic Drugs. From The Psychedelic
Renaissance. Chapter 2, PP 32-34. Muswell Hill Press, London.

Risks when using classical

psychedelics clinically

Physiological risks


Psychosis and Suicide Low

Dependency risks

Hallucinogen Persisting


Perception Disorder (HPPD)



LSD is banned in 1966. Virtually all

research stops.

The Dark Ages:

1971 - 1990

Along Comes MDMA

Leo Zeff:
Psychologist and Jungian
psychotherapist based in
Had used LSD in his practice
until 1966.
Had retired until introduced
MDMA in 1976 by Dr
Alexander Sasha Shulgin.

David E. Nichols,
and Alexander
Shulgin publish the
first report into the
psychoactivity of
MDMA in humans
in 1978.

3,4 Methylenedioxymethamphetamine

Short acting (two to five hours)

Minimal perceptual distortions
Almost always pleasurable
Safe in therapeutic applications
Easier than LSD to control clinically

Allows user to access repressed

traumatic memories without being
overwhelmed by the usual negative

Use of MDMA in the

1970s and 80s

Used by 1960s psychedelic

therapists when LSD was banned

Couples Therapy

Became scheduled in 1985

Particularly good for PTSD

Greer, G. (1985) Using MDMA in psychotherapy.
Advances: Journal of the Institute for the Advancement of Health,2(2), 57-59


In 1985 MDMA is banned.

..all research stops.

The Third Psychedelic Era:

1990 present day

Psychedelic Renaissance

Psilocybin > LSD

MDMA: Clinical Applications

New Psychedelic Culture:

Conferences and meetings
Legal Highs
Challenging the War on Drugs

The clinical
Burden of PTSD

The lifetime prevalence between 6% and 10%

Up to 15% in combat countries

Very disabling

Polypharmacy common

High rates of self-harm and suicide

Poor engagement on psychological inputs

50% treatment resistance


Psychedelics as tools for

LSD for alcoholism Meta-Analysis
Krebs, T.S and Johansen, P.O. (2012)Lysergic acid diethylamide (LSD) for
alcoholism: a meta-analysis of randomized controlled trials.Journal of
Psychopharmacology, 9 March 2012

Review of psychedelic treatments for addictions

Bogenschutz, M. P. & Pommy, J. A. (2012) Re-Examining the Therapeutic Potential of
Classical Hallucinogens in the Treatment of Addictions. Drug Testing and Analysis
Drug Testing and Analysis 4 (7-8) 543-555

Double-Blind RCT for Ketamine-Assisted Psychotherapy for alcohol and

Opiate addictions
Krupitsky, E.M. & Grinenko, A.Y. (1997). Ketamine psychedelic therapy (KPT): a
review of the results of ten years of research. Journal of Psychoactive Drugs 29 (2):

Contemporary Psychedelic Research:

Completed Studies
DMT human dose-response study
Strassman,R.J. (1996) Human psychopharmacology of N,N-dimethyltryptamine. Behav. Brain Res.73, 121-124 )
Psilocybin to treat Obsessive Compulsive Disorder
Moreno FA, Wiegand CB, Taitano EK & Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients
with obsessive-compulsive disorder. .J Clin Psychiatry.2006;67:17351740 )
Psilocybin and the Spiritual Experience
Griffiths, R.R., Richards, W.A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical experiences
having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187, 268283
MDMA to treat PTSD
Mithoefer et al (2013) Durability of Improvement in PTSD Symptoms and absence of harmful effects or drug
dependency after MDMA-assisted Psychotherapy: A Prospective Long-Term Follow-up Study. J
Psychopharmacol, 2013. 27:28-39
Psilocybin to treat Anxiety in end-stage cancer
Grob, C., Chopra, A.L. Danforth, M.C. Hagerty, C.R. McKay, A.L. Halberstadt, and G.R. Greer (2010) Pilot Study of
Psilocybin Treatment for Anxiety in Advanced-stage Cancer Patients[with G.S.].Arch Gen Psychiatry, 68(1):71-78
LSD to treat Anxiety in end-stage cancer
Gasser, P.


Further Studies Underway

MDMA Therapy for PTSD in War Veterans, USA

MDMA Therapy for PTSD for Boulder, USA
MDMA Therapy for PTSD Israel
MDMA Therapy for PTSD Canada
MDMA for anxiety associated with Autism
Psilocybin-Assisted Psychotherapy for nicotine addiction, Johns
Hopkins, USA
Psilocybin-Assisted Psychotherapy for alcohol addiction,
Psilocybin-Assisted Psychotherapy for end-stage cancer, Johns
Hopkins, USA
Psilocybin-Assisted Psychotherapy for end-stage cancer, Johns
Hopkins, USA
Ibogaine Therapy as a treatment for addictions, San Diego, USA
Ayahuasca Therapy as a treatment for addictions, Canada

Current Research Movers

Contemporary Psychedelic
Research in the UK

Bristol Psilocybin Project 2009

Imperial Psilocybin Project 2012
Imperial MDMA fMRI Project 2012
Imperial Depression Psilocybin 2014
Cardiff MDMA for PTSD 2014
Oxford Ketamine Project 2012
Imperial LSD Project 2014

The Cardiff
MDMA project
Ben Sessa, Mat Hoskins and Jon Bisson
Cardiff University Hospital Medical School
David Nutt Imperial College, London
CUBRIC, MAPS and Imperial University,
Double-blind, placebo controlled crossover fMRI study of combat veterans with chronic
treatment-resistant PTSD.

Twenty-four subjects will receive two fMRI scans; one with 125mg of MDMA and a second, two weeks
later, with an inactive placebo.
Measure the neurobiological correlates of MDMA vs. Placebo using four behavioural paradigms, which
relate directly to the symptoms of PTSD.

Recall of autobiographical memories

Social judgements paradigm
Exposure to fearful faces
Traumatic script cue paradigm.

Participants recruited from the University Hospital of Wales Veterans Service, screened according to
safety and diagnostic suitability criteria and randomly allocated into one of two groups.

Contemporary Renaissance of Psychedelic



If you want to learn

more about psychedelics
psychedelic research in
This years speakers include:

David Nichols
David Nutt
Daniel Pinchbeck
Jonathan Ott
Roland Griffiths
Torsten Passie
Amanda Feilding
Rick Doblin
Robin Carhart-Harris
Rupert McShane
Ann Shulgin
Matt Johnson
Teri Krebs
Dale Pendell
Hattie Wells
Andrew Feldmar
Alicia Danforth
Ben Sessa

And about 130 others!

Novel Psychoactive Agents,

Research Chemicals, Designer
Drugs and Legal Highs

Buying Drugs
On the Internet:

Rapid and discreet postage.

Arrive within 24 hours.
A highly competitive

Mephedrone and other

Synthetic Cathinones
Mephedrone - 4-methylmethcathinone (4-MMC) or 4methylephedrone
1929: First synthesised. Chemically similar to khat plant
2003: Rediscovered and largely manufactured in China
2007: Sold as Research Chemical on the internet. Similar
effects to MDMA, amphetamines and cocaine.
2009: Legal High shops, in response to low quality of ecstasy
and cocaine.
2010: Made illegal in UK (without adequate ACMD
Few formal studies into the psychological and/or
behavioural effects on humans or animals.

MDPV, Methylenedioxypyrovalerone,
Methedrone (para-methoxymethcathinone, PMMC)
Methylone (3,4-methylenedioxy-N-methylcathinone, MDMC)
Naphyrone (NRG-1)
Pentedrone and Pentylone (NRG-3)

From Silk Road to Shiny Flakes

Open and Dark net drug sales

Knowingly illegal.
Uses encrypted Tor browser.
Untraceable (?)
Payment by Bitcoins.

Phenethylamine-based drugs

2C-C, 2,5-dimethoxy-4-chlorophenethylamine
2C-D, 2,5-dimethoxy-4-methyl-phenethylamine
2C-E, 2,5-dimethoxy-4-ethyl-phenethylamine
2C-G, 3,4-dimethyl-2,5-dimethoxyphenethylamine
2C-I, 2,5-dimethoxy-4-iodophenethylamine
2C-T-2, 2,5-dimethoxy-4-ethylthiophenethylamine
2C-T-4, 2,5-dimethyoxy-4-(i)-propylthiophenethylamine
2C-T-7, 2,5-dimethoxy-4-(n)-propylthiophenethylamine
2C-T-21, 2,5-dimethoxy-4-(2-fluoroethylthio)phenethylamine
DOB, 2,5-dimethoxy-4-bromoamphetamine
DOC, 2,5-dimethoxy-4-chloroamphetamine
DOI, 2,5-dimethoxy-4-iodoamphetamine
DOM, 2,5-dimethoxy-4-methylamphetamine
TMA-2, 2,4,5-Trimethoxyamphetamine
TMA-6, 2,4,6-Trimethoxyamphetamine
NBOMe-2C-C, 25C-NBOMe, "Pandora"
NBOMe-2C-I, 25I-NBOMe, "Solaris"
NBOMe-2C-D, 25D-NBOMe, "Divination"

Classical Tryptamine derivatives

4-HO-MET, 4-hydroxy-N-methyl-N-ethyltryptamine
5-MeO-AMT, 5-methoxy-alpha-methyltryptamine
4-Acetoxy-DMT, 4-acetoxy-dimethyltryptamine
5-MeO-MiPT, 5-methoxy-methylisopropyltryptamine
4-HO-MiPT, 4-hydroxy-N-methyl-N-isopropyltryptamine
5-MeO-DiPT, 5-methoxy-di-isopropyltryptamine (also known as
"Foxy" or "Foxy Methoxy)

Often misrepresented as LSD (which is

physiologically very safe) 5-MeO-AMT can
be harmful or fatal. May cause changes in
blood pressure.

Synthetic Cocaine Substitutes:

Dichloropane ((-)-2-Carbomethoxy-3-(3,4-dichlorophenyl) tropane, RTI111, O-401)
Similar effects and structurally similar to cocaine. But with a slower onset and
longer duration of action.

()-2-Carboisopropoxy-3-(4-iodophenyl) tropane (RTI-121, IPCIT)
Potent and long-lasting. A single dose can last for over ten hours. (Which
restricts its abuse potential).

A potent monoamine reuptake inhibitor. Five times more potent than cocaine.
Fast onset of effects and short duration of action. The closest to cocaine itself
out of all the drugs in the RTI series.

Salvia, Kratom, Iboga, Kava Kava, Ayahuasca, Datura, mushrooms,
toads, sponges, flies, fish etc.

Synthetic Cannabinoids

Initially thought to be herbs: Coastal Jackbean, Blue Egyptian water lily, dwarf skullcap,
lion's tail, lotus and honeyweed.

But actually it is: synthetic

cannabinoids, most often
cannabicyclohexanol, JWH018, JWH-073, or HU-210,
sprayed onto a herbal base.
Potent CB1 agonists.
Nothing like cannabis!

Psychonauts, Drug User Forums,

Trip Reports and blogs
DOSE: T+ 0:00
T+ 0:001.2 mg buccal 25I-NBOMe
(blotter /
T+ 8:00 5 mg
Pharms - Clonazepam
T+ 8:00 3 mg
Pharms - Buprenorphine
T+ 8:00 50 mg oral
T+ 8:00 3 glasses oral
Alcohol - Beer/Wine
T+ 8:00 3 joints/cigs
smoked Cannabis

T 0:00 - 2 blotters are placed between the gums and cheek, one on top and one on the bottom lip. This is not
complexed but since it is the hydrochloride salt of 25-I, it is well absorbed if proper buccal technique is observed. I
personally recommend keeping the blotters in contact with the gums/cheeks in various positions even as the drugs
effects come on.
T+0:30 - Although many say this is a slow-to-develop experience, I have noticed the familiar shimmer and
intensifying of colors while also feeling a building energy - some friends have noted this come up as 'frightening' in
intensity but compared to the 2C line it is just a small buildup of energy.
T+1:00 - I decide it is time to prepare a shower as I find the effects building and building. My pupils are already
dilating at this point and I can feel fluctuations in body temperature much more. There is a bubbling in the stomach
that I would not call nausea by any means - just something I noted. In fact food/hunger is not only perfectly normal
but strangely enjoyable tripping on 25-I, whereas with LSD and most other psychedelics I find any unnatural foods
bizarre and unappealing. As I shower I also note the physical pleasure of this chemical coming on - I can imagine it
would be a potent aphrodisiac used in the right setting.
T+2:00 - I decide to take a night time bike ride with headphones - great idea! I am feeling the euphoria kicking in full
force now and combined with the small but noticeable 2C-x energy I venture deep into the woods. At this point I can
not fully see because the visuals are multiplying rapidly. I stop and smoke a cigarette and contemplate how hard it is
for an American to find secluded nature anymore. I feel apologetic for paving over natural landscapes and natural
beauty with our suburban and urban centers. At this point I note my euphoria is stronger than anything I have felt in
my life previously (possibly due to the extreme affinity for this molecule to certain receptors).
T+3:00 - Time dilation has begun and the entire world is awash in patterns and tracers. A note about pattern
recognition. Visually, at least, this chemical seems to play tricks with the brains system of 'filling in' periphery. Usually
when I focus on a point the brain fills in the rest of my vision with memory and logical assumptions - while on 25-I
this trick of the mind is exposed. I focus on a point and it becomes almost 4-D in clarity as the entire periphery flows
with reccurring patterns the mind inserts to fill in the lack of visual stimuli. These are not like any other visuals I have
seen which are usually purely geometrical - they are also MC Escher-esque in repetition - rows and rows of horses
marching into shadows of other rows of horses - tree branches interconnecting and exploding out in ways that defy
physics, etc.
T+4:00 - At this point time becomes of no concern. I walk around the street with my dogs and feel extreme empathy
and understanding towards them. It is as if we are linked. Conversation with some friends at this point is very fun as I
can interact with an almost unnoticeable amount of confusion - as we all know other psychedelics that produce such
profound effects also seem to profoundly affect communication and thought. 25-I, at moderate-strong dosages
seems to leave my sanity and social abilities intact which still rewarding the user with incredible physical/mental
euphoria and inexplicably beautiful visuals.

Risks and Safety

Old Hippies and

Grandmas drugs

LSD: 60 years of toxicity data.

MDMA: 25 years of toxicity data.

Cannabis: 3000 years of toxicity


Todays kids prefer: Bubble

Generic white powder

Safe to buy
Safe to carry
Why get busted carrying LSD, MDMA or

3D Molecular Printing

The War On (some) Drugs

Health, Crime, Social Disorder, Cost


Opposition to Reform:

The drinks industry

Moral argument

The mafia / organised crime

The Cognitive Liberty Argument

The Forefather of
Psychedelic Therapy
in Britain?
The future may teach us how to
exercise a direct influence, by
means of particular chemical
substances, upon the neural
apparatus. It may be that there
are other still undreamt of
possibilities of therapy.
From An Outline of Psychoanalysis

Sigmund Freud
London 1938.