•1991 - Alexander Shulgin published PiHKAL (and in 1997 – TiHKAL). •2000 -
BZP sold by legally Stargate until controlled in 2008. •2004 – K2 and Spice ...
Analogue Drugs In Australia 2012
Andrew Camilleri
Analogues History •1925 – International Opium Convention banned use of morphine and heroin.
Analogues History •1925 – International Opium Convention banned use of morphine and heroin. Alternate esters of morphine, such as dibenzoylmorphine , were manufactured to circumvent the Convention.
Analogues History •1925 – International Opium Convention banned use of morphine and heroin. Alternate esters of morphine, such as dibenzoylmorphine , were manufactured to circumvent the Convention. •1930 - The League of Nations passed analogue resolutions controlling all esters of morphine.
Analogues History •1972 – MDMA
MDA
PMA
Analogues History •1991 –Alexander Shulgin published PiHKAL
Analogues History •1991 –Alexander Shulgin published PiHKAL (in 1997, TiHKAL)
Analogues Structural Relationship to Dopamine Phenethylamine
Dopamine
Amphetamine
Cathinone
Analogues History •2000 – BZP sold legally by Stargate until controlled in 2008
BZP
Analogues History •2004 – K2 and Spice products emerge Originally developed in the 1960’s by Hebrew Uni (HU), 1970’s by Pfizer (CP) & 1980’s by Huffman (JWH) for analgesic effects.
RCS8
AM-2201
O
O
N
HU-210 HO
OH H
H
O
XLR11
THC
Analogues History •2007 - Cathinone products emerge in Australia Seizures in Europe of several methcathinone analogues but emergence, in Australia, from 2007 in Neorganics products.
4-methylmethcathinone
2-fluoromethamphetamine
Ethylcathinone
Main Drug Found In Illicit Tablets Ketamine 5%
Other 8% Ketamine 10%
2003
MA 20%
MA 10%
2007
MA 18%
2005
MDMA 72%
MDMA 62%
Ketamine 1%
Ketamine 1%
Other 5%
Other 3%
MA 3%
Other 7%
MDMA 82%
2008
MDMA 93%
Analogues History •2009 - MDMA Shortage 100 90
Percentage of Total Seizures
80 70 60 50 40 30 20 10 0
MDMA 2008/1 2008/2 2008/3 2008/4 2009/1 2009/2 2009/3 2009/4 2010/1 2010/2 2010/3 2010/4
Year/Quarter
MDMA Dosage in Tablets 120
100
87.4 80.6
80.0
mg
80
64.8
54.8
60
54.1 55.0
40
24.4 20
0 2003
2004
2005
2006
2007
Year
2008
2009
2010
Analogues History •2009-10 – MDMA detected in Wastewater
Chen C. et al 2011
Analogues History •2009-10 – Tablet composition changes dramatically 100 90
Percentage of Total Seizures
80
non-illicit drugs (caffeine, paracetamol etc)
70 60 50 40 30 20
MDMA
10 0 Year/Quarter
Analogues History •2009-10 – Tablet composition changes dramatically 100 90
non-illicit drugs (caffeine, paracetamol etc)
Percentage of Total Seizures
80 70 60 50
MDMA
40 30 20 10
MA
0 Year/Quarter
Analogues History •2009-10 – Tablet composition changes dramatically 100 designer drugs (total piperazines, cathinones, 2CI etc)
90
Percentage of Total Seizures
80 70
non-illicit drugs (caffeine, paracetamol etc)
60 50 40
MDMA
30 20 10
MA
0 Year/Quarter
Analogues History •2010 - Other ‘Legal Highs’ products begin rapidly emerging - Cathinones O CH3
4-methylmethcathinone (mephedrone, meow meow)
H3C
N CH3
H
O CH3
Other cathinone based drugs (eg flephedrone)
F
N CH3
H O
Naphyrone
N
O O
3,4-methylenedioxypyrovalerone (MDPV)
O
N
Analogues History •2010 - Other ‘Legal Highs’ products begin rapidly emerging - Cannabinoids Used in mining industry as not screened for in urine testing.
Analogues History •1972 - MDMA •1991 - Alexander Shulgin published PiHKAL (and in 1997 – TiHKAL) •2000 - BZP sold by legally Stargate until controlled in 2008 •2004 – K2 and Spice products emerge •2007 - Neorganics products emerge •2009 - MDMA Shortage •2010 - Other ‘Legal Highs’ products begin rapidly emerging
Analogues History •1972 - MDMA •1991 - Alexander Shulgin published PiHKAL (and in 1997 – TiHKAL) •2000 - BZP sold by legally Stargate until controlled in 2008 •2004 – K2 and Spice products emerge •2007 - Neorganics products emerge •2009 - MDMA Shortage •2010 - Other ‘Legal Highs’ products begin rapidly emerging 1997-2010 – 150 new substances identified in EU through their early warning system
Analogues History •1972 - MDMA •1991 - Alexander Shulgin published PiHKAL (and in 1997 – TiHKAL) •2000 - BZP sold by legally Stargate until controlled in 2008 •2004 – K2 and Spice products emerge •2007 - Neorganics products emerge •2009 - MDMA Shortage •2010 - Other ‘Legal Highs’ products begin rapidly emerging 1997-2010 – 150 new substances identified in EU through their early warning system 2010 - 41 new substances identified in EU (15 cathinones, 11 cannabinoids) 2011 - 49 new substances identified in EU, SA saw 20 new analogue drugs
Analogues Why are analogues a problem?
Analogues Why are analogues a problem?
Analogues Why are analogues a problem? Doses and contents unknown and vary
Combined with other chemicals (both active and inactive)
Listed contents inaccurate
Easy access
Easy access for all ages
No drug “dealer”
Analogues Where to next? •Will a return of MDMA, make the problem disappear? Tryptamines
Cathinones
BZP
Phenethylamines
Synthetic Cannabinoids
•Over 450 Synthetic cannabinoids, steroids, human growth hormones, ketamine, cocaine, pharmaceuticals, weight loss products etc…………
Analogues Where to next?
Analogues What are we doing to control analogues in Australia? •Listing all new substances as they arise can be time consuming and substance popularity can be short-lived.
Analogues What are we doing to control analogues in Australia? •Listing all new substances as they arise can be time consuming and substance popularity can be short-lived. •Using Analogue Provisions (differs in each state jurisdiction and Federally). A chemical which has “a substantially similar chemical structure to the substance, but differing in elemental composition due to the addition, deletion or replacement of any substituent element or group”
Analogues Issues meeting Legal Definitions • Chemical structure must be unambiguously determined This cannot always be determined by GCMS. Access to Standards to confirm this is not always possible. How far can a chemist go in saying something is substantially similar. O Me N
O
O
PAPP
O Me
Cathinone NH2
Analogues What are we doing to control analogues in Australia?
Analogues What are we doing to control analogues in Australia? •Listing all new substances as they arise can be time consuming and substance popularity can be short-lived. •Using Analogue Provisions (differs in each state jurisdiction and Federally). A chemical which has “a substantially similar chemical structure to the substance, but differing in elemental composition due to the addition, deletion or replacement of any substituent element or group” and/or having “substantially similar pharmacological effects” to a listed controlled substance
Analogues What are we doing to control analogues in Australia? •Listing all new substances as they arise can be time consuming and substance popularity can be short-lived. •Using Analogue Provisions (differs in each state jurisdiction and Federally). A chemical which has “a substantially similar chemical structure to the substance, but differing in elemental composition due to the addition, deletion or replacement of any substituent element or group” and/or having “substantially similar pharmacological effects” to a listed controlled substance
Structural similarity to a controlled drug does not guarantee activity eg phenethylamine
Analogues How do we keep pace? •DrugSAG committed to exchanging information about new substances as they are detected locally.
Analogues How do we keep pace? •DrugSAG committed to exchanging information about new substances as they are detected locally. •Use international databases and discussion forums to help identify unknowns.
Analogues How do we keep pace? •DrugSAG committed to exchanging information about new substances as they are detected locally. •Use international databases and discussion forums to help identify unknowns. •Share information with other agencies (in SA created SADEWS).
Unusual Seizure Alert Pills containing 2C-C and 2C-E
Contents of Seizure Seven whole light blue/purple speckled pills, which were poorly formed, each impressed with a “2-stripe” design.
Comments about the Seizure The tablets were irregular in shape and crumbly, however all seven pills visually appeared the same. Analysis of two individual pills revealed two distinct results. Pill one contained caffeine, dextromethorphan and 2C-C (2,5-dimethoxy-4-chloro-phenethylamine). 2C-C is a short-acting (4-8 hours) psychedelic chemical with a dosage of generally between 20-40mg. It is structurally similar to the more commonly encountered phenethylamines 2C-B and 2C-I. However it appears to be more powerful and longer acting than these two chemicals. The onset of effects can be delayed by 1-2 hours after consumption. Pill two contained dextromethorphan and 2C-E (2,5-dimethoxy-4-ethyl-phenethylamine). 2C-E has an effective duration of between 8-10 hours and a dosage of between 10-25mg. It is a strong acting psychedelic with effects becoming too intense and adverse at doses higher than 25mg, which can also increase the duration of effects.
Conclusions This seizure represents the first time that 2C-C and 2C-E have been detected in South Australia however, at this stage, this is an isolated seizure. Detections of 2C-C and 2C-E have been rare internationally and little is known about either chemical. This seizure follows a trend in the detection of “analogue” type chemicals in pills and capsules since a global Ecstasy (MDMA) shortage became apparent locally in the latter part of last year. Some of the “analogue” type chemicals recently detected locally include mephedrone (4-methylmethcathinone), 2C-I (2,5dimethoxy-4-iodo-phenethylamine) and 3,4-methylenedioxymethcathinone (methylone). Psychedelic chemicals are best described as enhancing visual and auditory perceptions/experiences and can create distortions but would not be considered truly hallucinogenic. While 2C-C is explicitly listed in the Controlled Substances (General) Regulations 2000, 2C-E is not. 2C-E however could conceivably be considered as an analogue of the listed chemical 2,5-dimethoxy-4-methyl-phenethylamine.
Analogues How do we keep pace? •DrugSAG committed to exchanging information about new substances as they are detected locally. •Use international databases and discussion forums to help identify unknowns. •Share information with other agencies (in SA created SADEWS). •Gather intelligence information from other sources.
Excretion (mg/d/1000 people)
Designer drugs in 2009-2011 wastewater
1. Population drug use in Australia: a wastewater analysis. Irvine RJ, Kostakis C, Felgate PD, Jaehne EJ, Chen C, White JM. Forensic Sci Int. 2011 Jul 15;210(1-3):69-73. Epub 2011 Mar 9 2. Marked Decline in 3,4-Methylenedioxymethamphetamine (MDMA) Based on Wastewater Analysis. Chen C, Kostakis C, Harpas P, Felgate PD, Irvine RJ, White JM. J Stud Alcohol Drugs. 2011 Sep;72(5):737-40
Analogues How do we keep pace? •DrugSAG committed to exchanging information about new substances as they are detected locally. •Use international databases and discussion forums to help identify unknowns. •Share information with other agencies (in SA created SADEWS). •Gather intelligence information from other sources. •Advise, inform and influence relevant authorities.
Analogues How do we keep pace? •Initial Toxicological screen did not pick up 25B-NBOMe
2C-B
Analogues Questions?
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