The potential of Psychedelic for treatment of mental illness lecture

David Erritzoe, Imperial College London

Neuropharmacology, Hammersmith Hospital – imaging centre – PET + MRI Scan
Trying to understand addiction with functional task. Looking at opiod, dopamine, serotonin
pathways.
Drugs looking first line at depression.
4 classic – DMT, mescaline, psilocybin (magic mushroom), LSD
What is a psychedelic?
A drug which, without causing physical addiction, craving, major physiological disturbance,
delirium, disorientation, or amnesia, more or less reliably produceds though, mood, and
perceptual changes otherwise rarely experience except in dreams…
Psychedelic Drugs Reconsidered.

Grinspoon, Lester, and Bakalar, James B. (1997).

Psychedelic first coined 1957

1967 – psychedelic banned in US – a lot of it was political such as Nixon prodrug
1897 – mescaline first isolated from cacti
1919 -mescaline first synthesised
1943 – LSD psychoactive effects discovered – A. Hofmann – tasted it and went high. He was
very influential for use in addiction, depression.
1958: psilocybin first isolated and synthesised by A. hofmann
Psychedelic trials were difficult to regulate under scientific regulation
John Hopkin – key area for the research
How does it work?
Serotonin receptor (type 2A) in postsynapse – more efficacy on this synapse the more of a
psychedelic effect.
More 2a receptor in cortex of brian
Nutt et al 2010, Lancet – Used a harm scale to see harm on the user and others 16 different
parameters such as harm to organs – alcohol is the most harmful to others
LSD and mushroom – not as harmful as cocaine and heroin – LSD are less likely to cause
dependence -serotenergic
Dopaminergic drugs such as MDMA tend to create more of an addiction
Hendricks et al, 2015 – Most drugs are causing an increase in psychological distress but
psychedelic showed a decrease
Walter Pahnke – he compared the psychological peak to non drug related mystical
experience:
- Sense of unity
- Transcendence of time and space
- Deeply felt positive mood
- Sense of sacaredness
- Paradoxicality
- Ineffability
- Transiency – continuation of life thought – soul
Abraham Maslow
1962 – Walter Pahnke – Good Friday experience – psilocybin vs control. A lot of had deep
psychological experiences.
Interest of this compound to profound and novel modulation of consciousness – degree of
mystical experience predicted positive changes including meaningfulness and increase in
openness. Debatable about using the word ‘mystical’ due to the religious nature of the
word. (Griffiths et al 2006,08, Maclean et al, 11)
Studies at Imperial – 12 healthy volunteers to test tolerability + dose testing
30 healthy volunteers – mock MRI
Cerebal blood flow on psilocybin – Default mode network – decreased under psilocybin –
important for use being mindful about ourselves.
What about mindfulness meditation with this drug? Any different responses?
fMRI – to understand functional connectivity to see synchronous activity in brain
‘Overstable’ state in depression – PCC to MPFC connectivity in depression is greater -
psilocybin decreased this
When the networks develop the brain network becomes more separate and more clearly
defined.
Adult – matured solve things in a sorted way.
Psilocybin more integrated communication
Psilocybin with psychological support for treatment resistant depression : an open feasibility
study – open label pilot study, two dose psilocybin(10mg + 25mg), one week apart
Screening, preparation(2x), guiding, integration << method of conducting the study. They
control the set and setting.
Depends on where you are can affect how well your psychedelic works
This is for people who have severe depression which is not being helped by current
treatment options.
Decorated different clinical rooms to see the effects of setting differences in the effects of
the psychedelic
Small trial with 20 people – 6 women and 14 men. 44+-11 age
Carhart-Harris et al, 2017
QIDS score – a depression severity score
1 week later showed a decrease in depression but after there was a mess of date with
patients having varying results but on average there is a decrease in depression. This is to
check the tolerability of psychedelic. However, no control studies done but could be done in
the future.
Post experience showed long term improvements. There is a lasting effect.
Ketamine is being used in psychiatry now. But ketamine rebound long term compared to
psychedelics.
Openness – to other ways of thinking. Psychadelics were more open
Personality change? – There is a slight change in personality – people becoming more
confident.
Neuroticism – possible link between blunted 5-HT2A
Measuring personality showed decrease in neuroticism, more open, not much change in
consciousness.
Two facets openness to actions and ideas increase.
People felt more connected to family and friends and even strangers. Common theme is
connectiveness. Lot of things that people with addiction have lost.
LSD is a bit more dirty – dopaminergic effects
fMRI – may be affected
Setting up microdose studies – full blown psychedelic and do online study.
Tolerance – hard to compare for psychedelic