Drugs, legal and illegal Dr Tim M WilliamsClinical Director – Specialised Services AWP Mental Health NHS Trust

4th July 2014 – Wills Hall, Bristol.

Drug and alcohol harms

Alcohol

Alcohol affordability index, 1980-2010.

Appleby J BMJ 2012;344:bmj.e2634

©2012 by British Medical Journal Publishing Group

Real spending on alcohol in UK, 1964-2010.

Appleby J BMJ 2012;344:bmj.e2634

©2012 by British Medical Journal Publishing Group

Hospital admissions wholly attributable to alcohol in England, 2002 to 2010

Appleby J BMJ 2012;344:bmj.e2634

©2012 by British Medical Journal Publishing Group

The Scots leads the world

Leon and McCambridge, Lancet 2006 (updated)Leon and McCambridge, Lancet 2006 (updated)

Alcohol withdrawalTime since last drink tremor

nausea and vomitinganxiety, irritability, depression BP, pulse, tempinsomniatransient hallucinations/illusions

48 hours seizures (7 - 48 hours)

72 hours Delirium tremens (peak onset 48 - 72 hours after last drink or reduction).

Tremor, hallucinations, confusion, plus delusions, insomnia and agitation, autonomic hyperactivity

What to do when abstinent?

•Relapse Prevention essential

•Not usually offered by statutory/specialist services

•12 weeks treatment only in my service

•Medication???▫Disulfiram, acamprasate, naltrexone▫nalmefene currently hit the headlines

Alcohol harms (is a downer)

Immediate Risks Longer term

• Accidents▫ Head injuries▫ Driving▫ Death (esp drowning /

RTA)

• Vulnerability▫ to exploitation / date

rape

• Heart▫ Seen more in Russia

• Liver• Pancreas • Brain / neurons• Heart• Vessels / kidney’s• GI tract• Sexual dysfunction• Addictive potential

▫ Minority: 3-5% dependence

• Mental health▫ Massive co-morbidity

“Drugs”

UK drug use

Opioids

Benzodiazepines and opioids

•Benzodiazepines plus methadone or buprenorphine - higher opioid toxicity symptoms (Nielsen et al, 2007 Addiction)

- greater peak effects on performance measures (Lintzeris et al, 2006 J. Clin. Psychopharmacology)

- higher mortality among patients co-prescribed methadone and benzodiazepines (McCowan et al, 2009 BMJ)

Gabapentin misuse Smith et al Br J Gen Pract. 2012

Aug;62(601):406-7. • “In primary care, an increasing number and

urgency of prescription requests cannot necessarily be explained by the increased number of cases of neuropathic pain”

5.2% of people in SM services using gabapentin

Mean daily dose 1343mg Of 1400 post-mortems

48 had gabapentin 36 of whom also had morphine/ methadone

▫Is fatal in overdose and unlike opioids or benzo’s is irreversible

Opioid harms (are downers)

Immediate Risks Longer term

• Respiratory arrest▫ Esp when mixed with

alcohol and other downers

• Accidents

• Vulnerability▫ to exploitation

• Crime and poverty▫ Big overlap

• Addictive potential▫ Yes

• Mental health?

• IV use▫ BBV’s

• Smoked▫ COPD

Cocaine

Cocaine (crack) and other stimulants•Difficult to engage•Difficult to treat•High mental health co-morbidity

Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007

380

Psychostimulants did not improve cocaine use, craving, or treatment retention in comparision to placebo

Cocaine harms (is an upper)

Immediate risks Longer term

• CVS risks▫ Could trigger a CVS

event

• Psychosis▫ Could trigger an event

• Specific Risks▫ Nothing acute

• Addictive potential – very potent

• Long-term risks▫ prominent CVS risks MI,

stroke▫ COPD (crack)▫ Nasal septum (snorted

cocaine)

NPS

…….or novel psychoactive substances (NPS)

…….or “club drugs”

…….or “legal highs”

Source- NTA ‘Club drugs: emerging risks and trends’ Dec 2012

3,4 Methylenedioxmethamphetamine (MDMA)

• The recreational drug Ecstasy• Onset 20 minutes• Effects last 2-5 hours• Particular empathogenic /

entactogenic qualities• Physiologically safe in therapeutic

applications

How dangerous is MDMA when used recreationally?

• Between 1997 and 2000 in the UK:• 81 deaths were attributed in part to ecstasy(Schifano F. 2003)

But....

• 59% also included opiates• 60% included alcohol• Only 7% involved MDMA alone; • That is six deaths in three years• After some 300 million ecstasy tablets were consumed by

over a million people.

• And remember: this is NOT clinical use. This is the uncontrolled recreational use of ‘ecstasy’.

4.8% of British soldiers returning from combat in Iraq met the criteria for PTSD (Iversen et al 2009)

US soldiers returning from service in Iraq and/or Afghanistan, the incidence of PTSD is as high as 18%. (Hoge et al 2004)

More returning soldiers from Iraq and Afghanistan have committed suicide from untreated PTSD than ever died in the conflict out there.

2009 - MAPS / Mithoefer MDMA for PTSD Study:

Hypotheses:

1. MDMA subjects will show improved rates of PTSD. 2. MDMA will not be associated with neurotoxicity.

Michael and Annie Mithoefer,

Baseline measurements

Introductory Sessions

First MDMA / Placebo Session

Four non-drug sessions

Second MDMA / placebo session

Four non-drug sessions

Measurements

Measurements Measurement

Two Month Follow-up

THREEYEAR FOLLOW-UP:

Mithoefer © 2009

34

Placebo MDMA0

10

20

30

40

50

60

70

80

90

100

Baseline

final

% w

ith P

TSD

Results for Hypothesis One:% meeting PTSD diagnosis – pre/post

MDMA harms (is an upper)

Immediate risks Longer term

• CVS risks▫ Could trigger a CVS

event

• Psychosis▫ Could trigger an event

• Specific Risks▫ Hyperthermia▫ ?water intoxication

• Addictive potential – very unlikely due to high tolerance

• Very little data on long-term risks▫ no CVS risks recorded▫ No consistent evidence

of long-term memory deficits. Short term reversible deficits recognised.

MDMA/Ecstasy adulterants

•An emerging problem▫Need to develop new harm minimisation

messages.▫Specific advise for coroners essential

•PMA (para-Methoxyamphetamine or 4-MA)▫1 hour onset

•PMMA (para-Methoxy-N-methylamphetamine)▫Linked to deaths, ?less toxic than PMA

PMA / PMMA (is an upper) Immediate risks Longer term

• CVS risks▫ ?Could trigger a CVS

event

• Psychosis▫ ?Could trigger an event

• Specific Risks▫ Hyperthermia (greater

than MDMA)

• Addictive potential ?

• No data on long-term risks

Mephedrone 4-MMC, MMCat, Miaow, Meow Meow, Bubble,

• 4-Methylmethcathinone (4-MMC)

• Stimulant, appeared in or around 2007 (Sweden)

• Sold as powder, crystals or sometimes capsules

• Made illegal from 16/04/10 (Class B). Price nearly doubled

• Had bypassed regulations as ‘plant food’, ‘not for human consumption’

The Scunthorpe two: Louis Wainwright and Nicholas Smith

Died from taking methadone not mephedrone with significant quantities of alcohol

• Professor Sheila Bird, of the Medical Research Council's Biostatistics Unit in Cambridge “deaths from cocaine fell in the first six months of 2009 to 66, a statistically significant drop from 95 in the same period of 2008”

Mephedrone harms (is an upper)

Immediate risks Longer term

• CVS risks▫ Could trigger a CVS

event

• Psychosis▫ Could trigger an event

• ?Specific risk of vasoconstriction

• Specific come down risk and suicide

• Addictive potential

• Very little data on long-term risks▫ Likely CVS risks▫ ?mental health

K, ketamine• and

methoxetamine?

The Observer Sunday 17 April 2011

Every parent's worst nightmare: how ketamine killed our daughterBright, popular, rebellious and creative, 21-year-old Louise Cattell had everything to live for. Then she made a fatal mistake. She took the party drug ketamine and was found dead in the bath by her flatmate.

Ketamine harms (is a downer)

Immediate Risks Longer term

• Accidents▫ especially drowning ▫ and hypothermia▫ driving

• Vulnerability▫ to exploitation

• However is generally a very safe drug used in a medical context

• Stimulant at low doses

• Bladder problems▫ Thickening▫ Urgency▫ ‘K-cramps’▫ Eventually dysfunctional

bladder

• Addictive potential▫ Users 1-12g a day

• Mental health?

GHB, GBL and 1,4-BD

Confusingly sometimes referred to as “liquid ecstasy”

GHB/GBL harms (is a downer)

immediate Longer term

• Respiratory depressant▫ Very dangerous with

alcohol▫ Narrow therapeutic

window

• Accidents▫ Much like alcohol▫ Disinhibits and poor

perception of risks

• Addictive

• Withdrawal syndrome▫ Like alcohol but worse▫ Severe seizures ▫ ?baclofen to treat

KhatMain active ingredients are cathine and cathinone

Khat harms (is an upper)

Immediate risks

• CVS risks▫ Precipitate event

• Psychosis▫ Minor risk▫ But mixed with PTSD

increased

Longer term

• CVS risks▫ Early MI▫ Early stroke

• Dependence▫ Small minority

• GI cancers??▫ Oral▫ oesophageal

M-Cat, madcat and now M2 ie 3,4,DMMC (are stimulants)

See what the are doing here:

• cathinone (in khat)• methcathinone (m-cat)• 4-methylmethcathinone (mephedrone)• 3,4-dimethylmethcathinone (“M2”)

Harms??Immediate Longer term

• CVS

• Mental health

• Specific risks?▫ Anaphylaxis▫ Respiratory??

• CVS

• Mental health

• Dependence

Can include 6-APB in this category (unhelpfully often called “benzofury”)6-(2-aminopropyl)benzofuran

2-CB (MDMA like)

The Sun 24/1/13

“Krokodil”

•CNN -“flesh-eating zombie drug”•USA Today -“Flesh-Rotting ‘Krokodil’

Drug Emerges in USA,”•GQ – “flesh-eating

heroin substitute that has found favour with Russia's homeless, and now "krokodil" has come to Britain.”

“Krockadil” (desomorphine)Immediate Longer term

• CVS▫ Resp depression +

death

• Mental health

• Specific risks?▫ “flesh eating”??

• CVS

• Mental health

• Dependence▫ absolutely

Reports in Russia of homemade ‘krokodil’ by mixing codeine with chemicals such as gasoline, red phosphorus, and hydrochloric acid. Extremely unlikely to be found in Europe and US due to easy availability of opioids

Other drugs (not uppers or downers)

Cannabinoids hallucinogens

• Respiratory if smoked

• Psychosis▫ Precipitated - yes▫ Cause - probably no

• Anxiety

• Amotivational▫ Definitely

• Mushrooms (psilocybin), Acid (LSD)▫ Low risk

• Salvia divinorum▫ Slightly different but

still low risk

• MDA▫ A bit more of a

stimulant(MDMA like)

End