Bath Salts And Plant Food

Question 0

Explain the influence of the Internet on drug sales

Answer 0

 in the late 2000’s, drug enforcement/tes&ng agencies noted a rise in mephedrone use
 one of the first drugs to be marketed successfully primarily via the internet
 sold as bath salts, plant food, research chemicals with a warning “Not for human consump&on.”
 at the &me, its chemical structure made it completely legal to sell in most countries
 anonymous purchasing and delivery directly to buyer (some with 90- minute delivery guarantee) made it aOrac&ve to many including those who wanted to experiment
 now one of the most commonly consumed drugs

Question 1

What determines if a drug is legal?

Answer 1

 what determines whether a drug is illegal or not?
 o@en legality of drugs is based on their specific chemical structure
 therefore, if structure is changed sufficiently, it may no longer be considered illegal
 thus we have “designer” drugs
 dangers
 no acute animal or human tes&ng
 no long-term tes&ng
 no idea of LD50
 dosing found by trial and error
 interes&ng side effects - a contaminant of a designer opioid drug caused Parkinsonism in its users - now used as inves&ga&ve tool to induce Parkinsonism in animals models

Question 2

What is mephadrone

Answer 2

 marketed as bath salts, plant food, meow meow, miaow, MMC hammer, MCAT
 mephedrone = 4-methylmethcathinone
 cathinone is a naturally occurring drug found in
the plant khat
 khat was made illegal in several countries due to hospitaliza&on of many users, so chemists made a khat deriva&ve in early 2000’s
 first appeared available online for purchase in 2007

Question 3

Where does mephadrone come from

Answer 3

 majority seems to be coming from China and bordering countries in South East Asia, possibly UK
 although star&ng compounds are available, no self-synthesis (by individuals) seems to occur
 analysis of samples shows most are > 95% purity
 adulterants included lidocaine, benzocaine,
caffeine and acetaminophen
 some in tablet form are sold as ecstasy tablets

Question 4

What are the trends in mephadrone use

Answer 4

 mephedrone use has spiked as the MDMA content of ecstasy and purity of cocaine has recently decreased
 it can be ordered over the internet and is s&ll legal in many countries although star&ng to see bans in EU countries
 was aggressively marketed on internet sites by drug distributors as a safe alterna&ve drug - coverage by media also helped
 newer offshoots of chemically modified mephedrone are now emerging as more and more countries make it illegal- second genera&on “legal highs”

Question 5

What is the role of the media with mephadrone

Answer 5

 this chart indicates the number of newspaper ar&cles on mephedrone in UK
 there is some argument that ar&cles that highlight the danger of drugs end up causing more use rather than le

Question 6

Explain the trends in seizures of illegal drugs

Answer 6

 in 2010 seizure of cathinone derivates (mostly mephedrone) was greater than MDMA and piperazine combined
 no seizures as early as 2008/2009
currently no data to show how

banning of drug in UK has affected seizure

decrease in MDMA seizures corresponds with drop in purity in recent years

Question 7

What is the structure of mephadrone

Answer 7

 mephedrone (4-methylmethcathinone) is semi-synthe&c derived from cathinone
 cathinone and its deriva&ves are known as beta ketonated amphetamines
 differs from cathinone by methyla&on of amine group and benzene ring
 laOer may give the compound some MDMA-like effects
 ketone group makes it more polar and slower than amphetamine to cross the BBB

Question 8

What is the administration of mephadrone

Answer 8

 most common routes are snor&ng and swallowing
 but reports of enemas and IV injec&ons
 snor&ng most popular and is associated with greater risk of abuse and binge use
 with oral use, onset is slower but the effects may last up to 4 hours
 many users will snort for fast onset and then swallow to get the long-las&ng effects

Question 9

What are the self reported effects of mephadrone

Answer 9

 self-reported effects include:
 intense s&mula&on, alertness and euphoria
 empathy, sociability, talka&veness
 intensifica&on of sensory experiences
 moderate sexual arousal
 analgesia
 perceptual distor&ons (higher doses only)

Question 10

What are the side effects of mephadrone

Answer 10

 nose/throat bleeds with insuffla&on
 “mephedrone sweats” - increased body temperature and
swea&ng
 GI disturbance if swallowed - nausea, vomi&ng, stomach aches
 CNS effects similar to cocaine, amphetamine including anxiety, agita&on, paranoia, short-term psychosis, teeth grinding
 elevated heart rate and blood pressure, vasoconstric&on leading to cold/blue fingers

Question 11

Explain deaths due to mephadrone

Answer 11

 Since 2010, 60 deaths in UK linked to mephedrone - some “violent” suicides - gunshot wounds and hangings
 48 of these had posi&ve test for mephedrone
 sudden death related to cardiovascular issues are a
concern - tachycardia, hypertension, chest pain
 unclear as to whether it caused death - o@en part of drug cocktail including alcohol, cannabis, amphetamine

Question 12

What is hyponatremia

Answer 12

one of the deaths so far:
 29 yr-old male
 CT scan showed significant cerebral edema
 hyponatremia with serum sodium of 125 mmol/L (135 - 145 normal)  water intoxica&on
 seizure followed by cerebellar tonsillar hernia&on - cerebellum squeezes through opening at base of skull -pressure on brain stem interferes with respira&on and heart beat
 no other drugs were found

Question 13

What is the implication of mephadrone eased with other drugs

Answer 13

  co-use reported in 72 pa&ents seeking medical treatment
  most common clinical signs in ER:
  agita&on (39%)
  palpita&ons (25%)
  vomi&ng (14%)
  chest pain (12.5%)
self-limi&ng seizure (7%)


Question 14

What is the mechanism of mephadrone

Answer 14



Mephedrone has been found to be a potent inhibitor of dopamine, noradrenaline and serotonin transporters
can be transported into the nerve ending by these transporters where it can facilitate neurotransmiOer release

Question 15

What is the overall effect of mephadrone

Answer 15

 preferen&ally affects serotonin levels but will increase dopamine levels as well
 acts like a hybrid of amphetamine and MDMA
 note - these bars represent the AUC - the area under the curve - of increases in dopamine, not simply the peak
 they are more representa&ve of the total amount of neurotransmiOer released
 how do we know what is causing these increases in levels? transporter or effects on release?

Question 16

How is mephadrone effect in transporter measured

Answer 16

 we know that transporters are involved because mephedrone will inhibit the transport of neurotransmiOers into nerve terminals
use of a synaptosome prepara&on -

grind up brain &ssue
 nerve ending are sheared off and spontaneously form a sealed vesicle
 transporters are s&ll ac&ve and can accumulate neurotransmiOer

Question 17

What is mephadrone effect on uptake

Answer 17

 use radioac&vely labeled neurotransmiOers
 will accumulate in synaptosomes because of transporters
 addi&on of increasing doses of mephedrone results in less and less of serotonin or dopamine accumula&on because it inhibits the transporter
 therefore good preliminary evidence that transporters are inhibited

Question 18

How do we know mephadrone reverses the transporter

Answer 18

 Take the synaptosomes and load them with an synthe&c neurotransmiOer-like molecule ([3H]MPP+) that can be transported by the transporter proteins
 Add mephedrone to the exterior and see if any of the substance that was on the inside ends up on the outside of the synaptosomes
 It was found that increasing doses of mephedrone led to more and more MPP+ being transported from inside to outside via DAT

Question 19

What is the cardiovascular effects of mephadrone

Answer 19

 cardiovascular effects have been tested in 3 mg/kg animal models
 heart rate and arterial pressure remains significantly elevated for prolonged periods of &me a@er subcutaneous injec&on
 heart rate peaks of 30 and 39% higher than saline at 3 and 15 mg/kg
 arterial pressure at 10-15 and 20-25% increase at low and high doses respec&vely

Question 20

Effects of mephadrone and dependence

Answer 20

 cardiovascular effects have been tested in 3 mg/kg animal models
 heart rate and arterial pressure remains significantly elevated for prolonged periods of &me a@er subcutaneous injec&on
 heart rate peaks of 30 and 39% higher than saline at 3 and 15 mg/kg
 arterial pressure at 10-15 and 20-25% increase at low and high doses respec&vely

Question 21

What is MDI

Answer 21

 MDAI (5,6-methylenedioxy-2-aminoindane)
 a rigid analogue of amphetamine that provides the same
empathe&c feelings as MDMA
 very limited informa&on about the aminoindanes
 older studies (1991) suggest less neurotoxicity than MDMA
 about equally potent to MDMA in inhibi&ng serotonin transport - also inhibits dopamine and noradrenaline transport but with significantly lower potency than MDMA
 reports of very liOle s&mulatory effect
 thought to be part of the next wave of legal highs

Question 22

What is NRG

Answer 22

 NRG - also known as methylenedioxyprovalerone (MDPV)/ naphyrone - “Ivory Wave”
 a white/off white powder o@en mixed with the anesthe&c lignocaine
 primarily s&mulant effects –block of serotonin/dopamine uptake thought to be primary mechanism – does not induce release from vesicles
 Seems to mimic the effects of cocaine but is drama&cally more potent and provides greater dopamine release
 ini&al euphoria but linked with cardiovascular and psychiatric issues - chest pains, tachycardia, paranoia, hallucina&ons and psychosis