The legal highs

Dr Ioana Vlad

• What are they?

• How do patients present?

• How do we treat?

• What is all the fuss about?

Synthetic / emerging drugs

Issues

- readily available in retail stores and online

- cheap

- highly attractive packaging

- perceived as safe drugs

- party pills / herbal highs / legal highs /

nutritional supplements

- not easily detectable in urine or blood

samples

• Synthetic cannabinoids

• Synthetic cathinones

• Novel psychedelics / synthetic LSD

Synthetic / emerging drugs

Synthetic cannabinoids

Synthetic cannabinoids

• Usually marketed as incense sticks

• Smoked or ingested “with a carrier high in fat content”

• Labeled “not for human consumption”

Synthetic cannabinoids

• Spice• K2• Happy Tiger Incense• Blueberry spice• Purple rush• Banana cream nuke• Kronic

Synthetic cannabinoids ( ~ 460)

• structurally different from THC but same effect on cannabinoid receptors

Naphthoylindoles

JWH-018JWH-081JWH-250 AM-2201JWH-073JWH -200

CP-47497CP 47CP 497

Cyclohexylphenoles

Synthetic cannabinoids

• 1984 John Huffman University of Clemson (USA)

• 2004 “Spice” appeared in London - The Psyche Deli company

Advertised effects

• Euphoria / relaxation / laughter / feelings of joy

Clinical presentations

• Agitation / paranoid psychosis

• Seizures

• Nausea, vomiting

• Acute kidney injury

• Hypokalaemia / hyperglycaemia

• Hyperthermia

• SVT / cardiomyopathy / acute LVF / AMI

• Hypertension

Synthetic cathinones

- chemically similar to cathinone foundin the khat plant ofeastern Africa

- manufactured in China

Synthetic cathinones

- tablets or powder / swallowed, snorted or

injected

- most common - 3,4

methylenedioxypyrovalerone (MDPV),

mephedrone, methylone

3, 4-Methylenedioxypyrovalerone (MDPV) & other synthetic cathinones

effects similar to cocaine

/ amphetamines / MDMA

- sometimes labeled as

legal cocaine or legal

amphetamines

Developed in the 1960s for the

treatment of chronic fatigue, but

abandoned due to abuse and dependence

1969: Boehringer Ingelheim files a patent application for MDPV

2005: MDPV on recreational drugs markets and mentioned on

Drugs forum

MDPV timeline

2007: first seizure of MDPV as a recreational drug, by customs

officials in Germany (shipped from China)

2009: MDPV made illegal in Denmark

2010: UK

2011: USA, Australia

MDPV timeline

Sold as bath salts / insect repellant / research

chemical / plant food

Sold mostly on the internet,

but can also be found in adult

or herbal shops

Labeled “not for human consumption.”

Red DoveBlue SilkCloud NineOcean SnowLunar WaveVanilla Sky Ivory WaveWhite LightningScarfacePurple WaveStar DustHurricane Charlie

Euphoric

Anorectic

Aphrodisiac

Anxiogenic

Increases alertness

Inhibits sleep

Advertised effects

Advertised effects

“ Swim says he finds MDPV a wonderful compund for getting

things done, like cleaning the flat, getting long boring e-mails

written and sent and working through shitloads of Uni-grade

maths at hyperspeed. The lack of euphoria is almost concieved

as positive by SWIM as it doesn't distract him from the task at

hand."

"...lower doses of MDPV produces a clarity of thought far

superior to just about every other stimulant I've ever tried."

Clinical presentation dopamine-noadrenaline reuptake inhibitors (NDRI)

- Agitation / aggression / paranoid delusions with

violent behaviour / increased

alertness/awareness / insomnia

- Headache, confusion, seizures

- Movement disorders - bruxism / muscle spasms

- Abdominal pain

- Rhabdomyolysis, renal failure; hyponatraemia

- Tachycardia, hypertension, vasoconstriction –

STEMI

- Tachyarrhythmias

- Hyperthermia

quick onset

peak effects for 3 - 4 hours

tachycardia, hypertension, and mild

stimulation last 6 - 8 hours

MDPV

α-pyrrolidinopropiophenone (α-PPP)

- detected in Germany in seized "ecstasy" tablets

4'-methyl-α-pyrrolidinopropiophenone (MPPP)

- Germany late 1990s / early 2000s

3',4'-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP)

- Germany late 1990s / early 2000s - imitation ecstasy pills

MDPV’s chemical ‘cousins’

• Naphyrone / O-2482 / naphthylpyrovalerone

– “Cosmic Blast” - marketed as a jewelrycleaner

– triple reuptake inhibitor (serotonin / noradr / dopamine)

– anecdotal reports of prolonged toxicity and severe hyperthermia

• Pentedrone, Alpha-PVP, 3,4-DMMC

Gen 2, 3 etc. of “bath salts”

What are the issues with MDPV?

What are the issues with MDPV?

"MDPV is the most compulsive drug swim has ever

done, he just can't stop hitting that pipe, it's worse

than fucking crack! He's been at it since 11am, 16

hours ago, and in that time he's done 150mg so far,

solely via the pipe, far too much!! He's still got over

300mg left, aargh!!! ...He's not even sure if he's still

enjoying it, don't think he is, but still he can't stop

hitting that pipe for some reason (though he does

know why really, dopamine = reward innit). Bloody

strange substance! Any swimer fancy coming round

and freeing swim of this bloody pipe?"

What are the issues with MDPV?

"MDPV is like the bastard with a whip you've got to

obey or you get hurt. Then you obey and get hurt

even worse. Finally, it's "Thank you sir may I have

another... thank you sir, may I have another... thank

you sir, may I have another..." and you wonder why

you've come to enjoy feeling like shit nearly every

waking moment. You vow never to touch MDPV again,

then an hour or two after it wears off you find yourself

eagerly using MDPV."

Novel psychedelics / NBOMe

Alexander Shulgin Albert Hofmann

Novel psychedelics / NBOMe

25B-NBOMe / 25I-NBOMe

derivatives of the 2C family of phenethylamine psychedelics

very potent partial agonists 5HT – 2A receptor

snorted or dissolved into a liquid and placed on blotter paper under the tongue

Novel psychedelics or synthetic LSD

90s – replacement for ecstasy

Colourful hallucinations

Feelings of empathy

Feelings of closeness with

others

Advertised effects

Effects

• Aggitation / extreme behaviours

• Tahycardia, hypertension

• Hyperthermia

• Seizures

• Metabolic acidosis

• Multiorgan failure

Effects

- onset ~15 min

- may last 6-10 hours

- active at very low

doses

Treatment

- Supportive care - benzodiazepines for agitation, seizures, tachycardia, and hypertension

- Significant hyperthemia may require passive or active cooling

- Consider checking electrolytes, renal and liver

function tests, cardiac markers, CK

- Observe until resolution of abnormal vital signs,

vomiting, and psychiatric symptoms

Legislation issues

- June 2011 – synthetic cannabinoids banned in

WA / QLD / VIC and then federal

- October 2011 – MDPV banned in USA and most

European countries

- February 2012 – WA bans MDPV

The problem: drugs could only be added to

the list once identified

DMECMethedroneEthedrone3-MOMC2-FMC2-FEC3-FMC3-FEC3-CMC3-BMCFlephedrone4-FECBrephedroneFMMC2,5-DMOMCbk-MDA2,3-MDMCMethyloneEthyloneO-2384α-PVP (O-2387)

4-MeMABP4-Me-NEB4-MethoxybuphedroneButyloneEutyloneBMDBbk-DMBDB5-Methylmethylone5-Methylethylone2-Methylbutylone5-MethylbutylonePentyloneMMPMEPbk-Methiopropamineα-Phthalimidopropiophenoneα-PPPα-PBPEDMC3,4-DMMC

• Urine drug screens will not pick them up

• Blood tests available

– Expensive

– Only for identified structures

Legislation issues

- Sept 2013 – NSW law banning “manufacture,

supply and advertising of psychoactive

substances (schedule 9)”

Take home messages

- drugs of abuse are forever changing

- manipulation of basic chemical

structures to avoid legal ramifications

- the classes of drugs more important than

names

- effects: psychoactive and sympathomimetic

- symptomatic management

-BZDs are a useful adjunct