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David Nutt FMedSci
Professor of Neuropsychopharmacology Imperial College London
Visiting Professor at the Open University UK and Maastricht University NL
Chair – drugscience.org.uk
Future Drug Use and Drug
Perspectives
Denmark 2019
Oct 30th 2009
Sacked but not
gagged
Telling the truth about drugs is a risky business
The big killers are not controlled
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Personal communication based on pubic health sources from Professor D. Nutt, Psychiatrist and Edmund J. Safra Professor of Neuropsychopharmacology, Imperial
College London
ONS. 2015. Deaths related to drug poisoning in England and Wales: 2015 registrations. Available at:
https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2015registrations#pa
racetamol-related-deaths-remain-stable-in-2015. Last accessed: February 2017.
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Drugs ranked according to total harm
Nutt King & Phillips Lancet Nov 2010
Alcohol
Cannabis
Tobacco
No correlation of UK Drugs Act or the UN
Conventions with drug harms
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0 20 40 60 80
UK
Dru
gs
Act
cla
ssif
icat
ion
ISCD results
A
C
B
U
linear r = 0.04
So the current UN Conventions and UK drugs laws
are not evidence-based – so immoral (and illegal)
What drives this dishonesty? Politics, the alcohol
industry, absolutist philosophies
That’s anther talk….
Prohibition leads to more harms
Many examples over the last century of how
prohibition has perverse consequences –
• Smoking opium → injecting heroin
• Ethanol prohibition → hooch and methanol
• Cannabis → skunk and synthetics (spice)
• Cocaine → crack
• MDMA → PMA/PMMA
• LSD/psilocybin → nBOMs etc.
• Heroin → synthetics AH7921 and fentanyls
As well as not reducing harm banning drugs severely impedes medical research
• Cannabis – pain, sleep, spasticity, cancer, PTSD
• Ecstasy (MDMA) – PTSD, Parkinson’s disease
• Psilocybin – depression, OCD, cluster headaches
• LSD – for terminal illnesses/ addiction
• Mephedrone & Naphyrone – for treatment of
depression and addiction
But current regulations make them
almost impossible to research
- So cant be resurrected from the
black hole of Schedule 1
How the 1971 UN Convention destroyed
research on psychedelics
1) Nutt, D.J, King, L.A. & Nichols, D.E. (2013) Effects of Schedule I drug laws on neuroscience research and treatment innovation, Nature Review Neuroscience, 14,
577- 585 Available at: http://www.nature.com/nrn/journal/v14/n8/abs/nrn3530.html (Accessed 31st Jan 2017)
2) Nutt, D. (2015) Illegal Drugs Laws: Clearing a 50-Year-Old Obstacle to Research, PLoS Biology, 13(1) Available at:
http://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1002047&type=printable (Accessed 31st Jan 2017)
Nature REVIEWS NEUROSCIENCE
June 2013
Novel 5-HT2A psychedelics
designed to escape UN ban
1P-LSD
Probably as
safe as LSD
N-BOM SERIES
Much more toxic due to
blocki of serotonin reuptake
and other effects
D9-THC➢ Induces anxiety
➢ Psychotic-like
effects.
➢ Impairs memory
and learning
CBD
cannabidiol➢ Reduces anxiety
➢ Anti-psychotic
effects
➢ Improves memory
and learning
Have opposite effects on cannabinoid receptors in
the brain
Perverse effects of cannabis prohibition
Vanishing CBD
d9THC
Decrease in CBD due to
prohibition → stronger
THC products
“skunk” with greater
profit margins
Increased high THC/no CBD
cannabis strains
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2002 2005 2008 2011
King et al 2005 Potter et al 2008 Hardwick/King Curran et al
2009
Police seizures Community sample
2008 – 80% skunk: CBD levels <0.1%; THC >15%.
2011 - 75% of samples skunk: CBD =0.01%
% S
am
ple
s
2018 - >95% skunk
High THC low
CBD
➔ more
psychotic
symptoms
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Unusual
Experiences
Cognitive
Disorganisation
Introvertive
Anhedonia
Impulsive Non-
conformity
OL
IFE
Sco
re
No Cannabis
THC only
THC + CBD
Morgan & Curran, 2008 Brit J Psychiatry
**
*
We have known for a long time that cannabis
prohibition leads to greater harms
Skunk has different brain
effects from herbal
FMRI imaging -
Large perturbation of insula connectivity with skunk
Wall et al 2019 Journal of Psychopharmacology
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Intoxicated Not intoxicated
Dela
yed
pro
se r
ecall
Low CBD:THC
High CBD:THC
group x day p=0.047
Morgan, Schafer, Freeman & Curran (2010) Brit J Psychiatry
*
And greater cognitive impairments
Memory –
prose
recall
Did this
make the UK
government
take stock
on policies?
NO!
In fact they made
it worse!
Testing prisoners for cannabis
➔ Synthetic cannabinoids =
Opening Pandora’s box
Because cannabis is illegal and users are prosecuted and prisoners are tested
➔ (logically) seek legal alternatives
And there are very many potential
synthetic cannabinoids…
RCS-4 AB-001 XLR-11 5F-PB-22 ADB-CHMINACA 5F-AMB
heteroaromatic
core
alkyl
substituent pendant
group
~2010 2015Some prisons estimate up to 90% of inmates now
using “spice” regularly despite their now being
illegal
And corrupting up to 5% of prison officers
Head shops used to sell “bubbles”
and “sparkle”
= weak stimulants e.g.
methiopropamine
Now all sales on black market
➔ synthetic cannabinoids
When spice hits the streets
Another example of prohibition failure
→rise of PMA/PMMA deaths in UK
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1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Novel psychoactive substances
PMA
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Number of drug-related deaths where selected substances were
mentioned on the death certificate, England and Wales
PMA is sold as “ecstasy” i.e. MDMA
PMAMDMA
Production of MDMA (ecstasy)
MDMASafrole
From sassafras oil
Alternative precursors → different products
Anethole PMA
PMMA
From aniseed oil
Seizure of massive quantity of safrole in Thailand in 2008 → reduction
in supply of MDMA
So underground chemists turn to other precursors such as aniseed oil
With disastrous consequences
Safrole MDMA
PMMA
PMA and PMMA
• Not typical stimulants
• Slow onset of actions → overdose
• Block monoamine oxidase inhibitor so can get serotonin
syndrome
→ hyperthermia, brain and muscle damage and
death
An example of how the “war on drugs” leads to collateral
deaths.
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Cannabis
Benzodiazepine analogues
Novel amphetamines
Mephedrone
MPA
Synthetic cathinones
Piperazines
Benzofurans
Amphetamine
MDMA
Cocaine/crack
Ketamine
PMA/PMMA
GHB/GBL
SCRAs
AMT
Heroin
Index of fatal toxicity Ln(Tf)
King and Corkery Journal of Psychopharmacology 2017
Comparative toxicity of drugs
Log scale
The remarkable impact of mephedrone
to reduce UK stimulant deaths
Police complicity: The Scunthorpe two (17/03/10)
Two young men found dead
“Officers believe both lads had M-CAT (mephedrone) and
also had access to heroin substitute methadone which they
used to bring them down from the high of mephedrone”
- they had also been drinking heavily until 2am
Nick's dad wept as he urged youngsters to avoid the drug…
"I don't want him to be labelled a druggie because he wasn't.
He was just on a night out with friends enjoying himself, a
normal, caring, hard-working lad.“” (The Sun, 17/03/10)
Media clamor to get the drug banned
It looks like amphetamine..
→ make it Class B like amphetamine
(could have been worse since they could have decreed
its effects were like MDMA = class A !)
.. and users describe effects somewhat like amphetamine
ACMD “Consideration of the cathinones” report March 2010
But the antismoking drug bupropion
(Zyban) also looks like amphetamine
For which there is no evidence of abuse, toxicity or harms
– so had to be exempted from the new law!
ACMD “Consideration of the cathinones” report March 2010
But all other cathinones now illegal
So pharmaceutical companies will
never be able to economically
develop newer more effective
versions of bupropion – research
field now dead
Monkey dust?
n-ethylpentylone
Maybe 10x more
potent than MDMA
Ketamine
• Tolerance & Dependence with repeated use
– + bladder damage/ functional brain changes
• Recreational use → Class B in UK
• → methoxetamine = safer alternative – probably
• → media hysteria → ban of all possible alternatives even
if much safer than ketamine
How the black market kills
Nov 2016 in Kent
Robert goes to score some
cannabis
Gets offered “ecstasy” as
well -- takes it
Dies as its fentanyl not
ecstasy
Which is why we need testing NOW
Acryloyl fentanyl • 23 analytically confirmed associated deaths reported
by Sweden between April and August 2016
W-18 • seizures of W-18 for example - counterfeit heroin
– linked to a recent spate of “heroin” overdoses across Australia
U-47700• In tablets in Scotland
• “Another powerful painkiller found in Prince's System:
U-47700 as well as fentanyl”
http://kstp.com/news/prince-u-47700-painkiller-
system-toxicology-drug-synthetic-opioid/4204272/
New synthetic opioids
• Number of fentanyl
exhibits
DEA National
Forensic Laboratory
Information System
• Peak in 2006 due to
supply from an illicit
lab in Mexico
Huge problem in USA and Canada
• injectable anaesthetic products
– occasional misuse by medical professionals or from
access to diverted product
• transdermal patches present greater risk
– large amount of material within patch (milligrams)
– discarded after use (72 hr) but significant residual
drug
– cut up and smoked/swallowed, or extracted for
injection
– unpredictable dosage, so risk of overdose and death
Pharmaceutical fentanyls
• Fentanyl
– 0.1mg iv equivalent to 10mg iv morphine i.e.(x100)
• Alfentanil
– potency ~0.3x fentanyl, very rapid onset, short action
• Remifentanil
– 2x fentanyl, rapid onset & recovery
• Sufentanil
– 5x fentanyl, most potent analogue used in humans
• Carfentanil
– 100x fentanyl, fast acting, limited to veterinary use
– explored by military as an ‘incapacitating agent’
• Lofentanil
– 120x fentanyl, long lasting, mainly used for research
Legitimate fentanyls
The worrying rise of fentanyls
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Fentanyl 75 of which
carfentanil 27
1 50x >1000x
• in stimulants
– in cocaine and ‘crystal meth’
– Connecticut June’16: ‘coke’ – 12 users, 3
deaths, 4 in intensive care
• in benzodiazepines
– fake ‘Xanax’ (Alprazolam + paracetamol)
• in e-cigarette liquids
– with synthetic cannabinoids
Fentanyls found in other illicit drugs
Much higher potency than heroin
–1 gram fentanyl ≈ 20 g diamorphine ≈ 50 g
‘street’ heroin
1 kg fentanyl from China costs ~$5,000
–equivalent to 50kg street heroin
distribution value (as 50kg ‘heroin’) ~ $5M
–short supply chain, few ‘middle men’, so
nearly all profit
• other fentanyl analogues even greater
potency
Big money to be made in fentanyls
Some ways forward
Restoring reason re cannabis
Dutch coffee shops → separate hard and soft drug market
→ medical cannabis also
US states. Israel, Canada, Uruguay, Germany, Spain
→ medical cannabis
some → legal recreational cannabis
Others lag behind on medical cannabis for fear of slippage into
recreational use despite having amongst highest percent
recreational users in the world
Drug testing
Regulated market gives best resultsDrugScience Policy MCDA results – cannabis
44Rogeberg et al 2018 International J of Drug Policy
Saving the world from drink?
Alcohol ➔ 3.5 million premature
deaths per year – many in young
people
Neuroscience can give us a safer
“synthetic” alcohol
New Scientist 2006
The Scientist Jan 2011
But would this now be legal in the
UK?
Do you want it Denmark?
Replace alcohol with nitrous oxide?
• Strong and fast pleasurable effect
• Rapid recovery, over in mins, so back in control
• → so lower risk of assault than when drunk for
hours
• Safer to drive home
• No hangover – less loss of work time
• Less toxic to the body
• Less addictive
Thanks and questions?
For the truth about drugs visit
www.DrugScience.org.uk
Or read my book …
