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5% Discount on Legal Highs, Salvia Divinorum and Everything Else From The Coffeesh0p

I Finally Updated My Old Legal Highs Banner

I thought it was about time for a new version of my old, poor quality legal highs banner, which, if you’re at all inter­ested in legal highs, you’d prob­ably recog­nise in some shape or form. Pretty much everything in the ori­ginal pic was banned years ago, which means it’s no longer a photo of legal highs at all, but an image whose every pixel por­trays mis­in­form­a­tion, lies and irrel­ev­ance.

Take that, Ins­tagram hip­sters! Three bleak, abstract con­cepts por­trayed in a single shot without even trying.

I wonder though… If my ori­ginal image has been rendered totally obsol­ete by the gov­ern­ment waving their banning-stick all over the place, perhaps I should try file a claim for damages relat­ing to the total devalu­ation of my intel­lec­tual prop­erty? OR… I could harness that bitter, twisted rage that burns deep down inside me and channel it into some­thing pos­it­ively cre­at­ive, such as — oh, I don’t know — a new, up-to-date image to replace the pre­vi­ous one.

Here’s Legal Highs mk II then —  fea­tur­ing the hottest products as of Jan 2015 as well as far super­ior image quality:

Legal High incense products

Addi­tional details, metadata, etc can be found on the fol­low­ing Coffeesh0p blog entry: Coffesh0p Blog — Updated Legal Highs Photo

And of course, all the products are avail­able in the Legal Highs > Incense cat­egory.

#nofilter #selfIndulgentPrick #totalPrentenciousness

.

Posted in Drugs, Legislation | Tagged coffeesh0p, incense, legal highs, photography |

New Salvia Extraction Guide

I recently rewrote the old “How To Make Salvia Divinorum Extract” blog post and turned it into some­thing better. My old post, albeit very popular, lacked pic­tures and a few points could have cla­ri­fied a little better.

In this new guide, there are 39 pic­tures from start to finish, leaving nothing to the ima­gin­a­tion. The old blog post also talked about how you can jiggle the numbers round a bit to suit your own extrac­tion pro­ced­ure — well, this guide does it for you with the help of some inter­act­ive sliders. Not only will it cal­cu­late the final weight of extract you’ll end up with from the amount of leaves you have and the strength of extract you want to make, it also updates the article text through­out to give you rel­ev­ant instruc­tions based on the quant­it­ies you enter. :O

So, here it is: How To Make Salvia Extract

Do let me know what you think! Any feed­back, please leave it in the com­ments here..

Posted in Drugs |

I Might Be On Crack

Ok, I’m not really on crack, but that’s what it may seem like given how ridicu­lous the prize is for Coffeesh0p’s Feb­ru­ary Com­pet­i­tion.

(How’s that for maximum mar­ket­ing hype?).

Posted in Drugs |

Where I've Been; What I'm Up To

Where I've Been

Well, I’ve obvi­ously not been round here much. That’s because Jo & I have had zero free time thanks to our new baby — Felix is his name, and he’s now 6 months old. Anyone who follows my Flickr will have already been inund­ated with photos.

What I've Been Doing

I’ve just about managed to find a bit of time from some­where to write a couple of posts on the Coffeesh0p Blog. Here are a couple of posts you might find inter­est­ing:

I hope to do at least a few more posts along those lines, so keep an eye out.

I’ve also just set up a Coffeesh0p Face­book Page. Cur­rently, there’s a 10% off coupon code on there and a mini photo com­pet­i­tion you can get involved with to win some free­bies. If you use Face­book, you’d be doing me a favour by Liking our page — who knows, you may even enjoy it!.

Posted in Synchronium | Tagged coffeesh0p, facebook, research, salvia divinorum |

Entheogens In A New Light

Hi folks,

As is prob­ably obvious, I’ve taken a little break from blog­ging reg­u­larly to focus on my pho­to­graphy. So I thought today, I’d combine the two. I’ve taken some rather nice shots of some of our most inter­est­ing-looking entheo­gens and posted them below. Click­ing on them will open them full size so you can see all the detail.

Mexican Dream Herb

Mexican Dream HerbMexican Dream Herb Closeup

Wild Dagga

Wild DaggaWild Dagga Closeup

Inebriating Mint

Inebriating MintInebriating Mint Closeup

Blue Lotus

Blue Lotus
Blue Lotus Closeup

Peruvian Torch

Peruvian TorchPeruvian Torch Closeup

Red Clover

Red CloverRed Clover Closeup

Kanna

KannaKanna Closeup

Rose Petals

Rose PetalsRose Petals Closeup.

Posted in Drugs | Tagged blue lotus, entheogens, inebriating mint, kanna, mexican dream herb, peruvian torch, photography, red clover, rose petals, wild dagga |

Mexxxxxxxxxxxxxxy

It’s always excit­ing when a drug is banned, but the recent announce­ment by the Home Office con­cern­ing the immin­ent banning of the former ‘legal high’ meth­oxetam­ine set unpre­ced­en­ted levels of excite­ment and con­fu­sion by making it a new kind of illegal.

Under the pre­vi­ous system, if the British Gov­ern­ment wanted to ban a drug, they had to consult their gaggle of sci­ent­ists, doctors and other assor­ted experts col­lect­ively known as the ACMD, ignore their views, sack them for object­ing to being ignored, appointnew panel and then do what they were always going to do by banning the drug anyway. This cir­cum­ven­ted cum­ber­some bur­eau­cracy, and also allowed min­is­ters to tran­scend any remain­ing ties to object­ive reality by apply­ing such bans to chem­ic­als the exist­ence, let alone the effects, of which had not yet been proven.

Meth­oxetam­ine, pur­portedly syn­thes­ised by the inten­tion­ally mys­ter­i­ous under­ground chemist ‘M’, has emerged in the past two years as a “bladder-friendly” altern­at­ive to ket­am­ine, but is more widely known for raising the stupid-drug-name bar which every­one thought had peaked with “meow meow”, being dubbed “mexxy” and “roflcoptr”. Need­less to say, the putat­ive tox­ic­o­logy inform­a­tion presen­ted to promote the drug is highly ques­tion­able, as should be obvious

More recently meth­oxetam­ine has got the British tabloid press froth­ing after its alleged involve­ment in the death of two people. Need­less to say the post­mortem revealed both had meth­oxetam­ine and alcohol in their blood at the time of death. At the time of writing, no move has been made to ban alcohol.

Meth­oxetam­ine is the first sub­stance to be banned under what’s called a ‘tem­por­ary class drug order’, a new measure enshrined in legis­la­tion in Novem­ber 201. Making a sub­stance subject to an order effect­ively bans it for 12 months, offer­ing the gov­ern­ment the welcome oppor­tun­ity to ban the banned drug all over again in a years’ time.

 

Police Officer
“Yes! Even more crimes to solve!”

 

This isn’t how they put it. In their words the intro­duc­tion of an order is to allow time for the ACMD to perform tests and decide whether it should be per­man­ently con­trolled. During this time the man­u­fac­ture, supply and con­sump­tion of such a sub­stance subject to an order, the effects and impact of which are neces­sar­ily unknown, is pun­ish­able by prison sen­tences up to 14 years and an unlim­ited fine, the current penalty imposed for sup­ply­ing class B drugs such as amphet­am­ines.

But perhaps after said testing period the ban might be lifted? Current Home Sec­ret­ary Theresa May recently announced in some­what less than neutral terms, an upcom­ing review of legis­la­tion con­cern­ing ket­am­ine, stating that the review was promp­ted by “heightened public concern about the pop­ular­ity and poten­tial harms of ket­am­ine” and con­sid­er­ing the last major report into the legal status of a con­trolled sub­stance res­ul­ted in can­nabis being re-upgraded to a class B drug against the advise of the ACMD, it is looking unlikely that a radical rethink of drug-policy is taking place by our elected leaders in West­min­ster Palace.

This time the ACMD impli­citly admit that meth­oxetam­ine appears to be more dan­ger­ous than ket­am­ine and with the review of ket­am­ine looking likely to result in an upgrad­ing, the care­fully charged words spoken at the start of the ban set the tone for when in 12 months time, meth­oxetam­ine is per­man­ently con­trolled.
Since ket­am­ine was made a class C drug in 2006, its use has risen dra­mat­ic­ally indic­at­ing that the ban has made no impact on use and has act­ively driven people onto what the ACMD believe is an even more harmful drug, meth­oxetam­ine. As such, the decision not to let meth­oxetam­ine remain legal will, at best, have no impact on trends of use and at worst drive users to increas­ingly unsafe sub­stances.

This seems as good a time as ever to remind you that prior to his elec­tion, David Cameron act­ively spoke out against the absurdity of the war on drugs. I await his inter­ven­tion on this matter immin­ently.

[This article was written for Syn​chronium​.net by sliced­mind, who runs an eso­teric music blog here and, well, lets just say, owes me big time.].

Posted in Legislation | Tagged ACMD, legal highs, Legislation, methoxetamine, mexxy |

Photography II

I’ve created a page that auto­mat­ic­ally updates with my most recent photos on Flickr. There’s now a link to it at the top of every page, or you can get to it here: Pho­to­graphy.

Posted in Synchronium | Tagged photography |

Photography

Hi there!

These past several months have seen me busier than ever with moun­tain after moun­tain of busi­ness-related crap to climb; each bite-size chunk of finance-related bull­shit being as boring to write about as it is to chew through, so I’ll spare any further details.

As I’ve men­tioned before, Coffeesh0p is about to relaunch after being com­pletely over­hauled. This also means a tonne of new products and a tonne of new pic­tures to be taken for the site. Turns out it would cost far more to get someone else to take these photos than the cost of a new camera, so  in the interest of fiscal respons­ib­il­ity, I’m now “into pho­to­graphy”.

There’ll be lots of great product photos on the new site when it launches, but in the mean time, here’s some of my favour­ite photos taken in a per­sonal capa­city (click each for a larger version):

The Uni­ver­sity of Birm­ing­ham

Pylon & sub­sta­tion

Green & purple laser

Lake at night

Amanita mus­caria

Hyde Park, London

Birm­ing­ham Christ­mas Market

If you think they’re not shit, there are loads more here: http://​www​.flickr​.com/​p​h​o​t​o​s​/​s​y​n​c​h​r​o​n​i​u​m​/​p​a​g​e1/

As always, your opin­ions welcome in the com­ments below..

Posted in Drugs |

Squidgy Black

To cel­eb­rate the long-awaited return of Coffeesh0p’s Squidgy Black incense, I thought I’d share a nice high res­ol­u­tion pho­to­graph of it (click to enlarge):

Squidgy Black

(Until 3 PM tomor­row (Monday after­noon), we’re giving away 1g samples with all orders over £30).

Posted in Internet Marketing | Tagged coffeesh0p, incense, legal highs, Squidgy Black |

Ivory Wave Destined For Class B

Or at least that’s how the media will inev­it­ably sim­plify it for all you plebs out there, who couldn’t pos­sibly need to know, let alone under­stand, the exact wording of the law. On the 13th of Septem­ber, everyone’s favour­ite council of advisors, the Advis­ory Council on the Misuse of Drugs (ACMD) released their report on Desoxypi­pra­d­rol (2-DPMP), includ­ing advice for another broad ana­logue ban similar to the bans of the cath­inones & can­nabin­oids in the not too distant past.

Here’s the first part of the report, format­ted and presen­ted in lovely HTML (Annex 2 will be posted up soon.):

Consideration of Desoxypipradrol (2-DPMP) and related pipradrol compounds

Letter To The Home Secretary From The ACMD

13th Septem­ber 2011Dear Home Sec­ret­ary,

I write further to my cor­res­pond­ence of 29 October 2010 in rela­tion to the com­pound desoxypi­pra­d­rol (2-diphen­yl­methyl-piperid­ine, 2-DPMP). In its advice the Advis­ory Council on the Misuse of Drugs (ACMD) recom­men­ded that desoxypi­pra­d­rol, iden­ti­fied in samples of a product known as „Ivory Wave?, should be subject to an imme­di­ate ban under the Open General Import Licence. This advice was accep­ted by the Gov­ern­ment and a ban was imple­men­ted on 4 Novem­ber 2011.

The ACMD has con­sidered the avail­able evid­ence and can now provide you with sub­stant­ive con­sid­er­a­tion of the com­pound desoxypi­pra­d­rol and its related com­pounds. A short report is annexed to this letter.

The National Poisons Inform­a­tion Service in Edin­burgh high­lighted that a number of indi­vidu­als had presen­ted to the Royal Edin­burgh Infirm­ary in the summer of 2010 fol­low­ing use of desoxypi­pra­d­rol with symp­toms that were similar to amphet­am­ine tox­icity, but with pre­dom­in­ant neuro­psy­chi­at­ric fea­tures includ­ing:

  • Hal­lu­cin­a­tions
  • Para­noia
  • Severe Agit­a­tion

In some cases these effects per­sisted for several days after inges­tion.

In the attached report the ACMD has con­sidered the avail­able evid­ence from forensic pro­viders, the National Pro­gramme on Sub­stance Abuse Deaths, Clin­ical Tox­ic­o­logy Ser­vices, sci­entific research and Gov­ern­ment Depart­ments on the harms and sales of desoxypi­pra­d­rol.

The ACMD advises that the harms of desoxypi­pra­d­rol are com­men­sur­ate with other Class B drugs and recom­mend that it is con­trolled under the Misuse of Drugs Act 1971 as a Class B sub­stance and in Sched­ule 1 of the Misuse of Drugs Reg­u­la­tions 2001 (as amended). In addi­tion, the ACMD recom­mends that the struc­tur­ally related com­pounds diphen­yl­pro­linol (diphenyl-2- pyrrolid­inyl-meth­anol, D2PM) and its desoxy form 2-diphen­yl­methyl­pyrrolid­ine are con­trolled under the Misuse of Drugs Act 1971 as Class B sub­stances and sched­uled under the Misuse of Drugs Reg­u­la­tions 2001. The pro­posed generic defin­i­tion will ensure that desoxypi­pra­d­rol and all its related com­pounds, e.g. diphen­yl­pro­linol and diphen­yl­methyl­pyrrolid­ine, are fully cap­tured (see Annex 1 & 2). The ACMD under­stands that desoxypi­pra­d­rol and its related com­pounds do not have any medi­cinal uses; however, the ACMD has not form­ally con­sul­ted with the industry.

The ACMD believes that there would be no con­flict­ing issues with placing the generic defin­i­tion in the Act as the three main drugs, desoxypi­pra­d­rol, diphen­yl­pro­linol (D2PM) and 2-diphen­yl­methyl­pyrrolid­ine can all be ana­lyt­ic­ally dis­tin­guished from one another and from other drugs in Sched­ule 2 Part II.

The pos­i­tional isomers of pipra­d­rol (diphenyl-2-piperid­ine­meth­anol), i.e. the diphenyl-3-piperid­ine­meth­anol and diphenyl-4- piperid­ine­meth­anol isomers would be Class B and in the absence of ref­er­ence stand­ards may not be readily dis­tin­guished from pipra­d­rol (Class C) using routine methods of ana­lysis (medi­cinal products con­tain­ing pipra­d­rol are no longer widely used and are not, as far as the ACMD are aware, avail­able in the UK). Whilst, it should be pos­sible to dis­tin­guish between pipra­d­rol isomers using tech­niques such as NMR, in the long term it would be support forensic ana­lysis to have ref­er­ence stand­ards of all the pipra­d­rol pos­i­tional isomers.

The ACMD recom­mends that the Home Office con­siders com­mis­sion­ing the pro­duc­tion of stand­ards through the Forensic Early Warning System.

Yours sin­cerely,

Pro­fessor Les Iversen FRS

(cc: Anne Milton – Par­lia­ment­ary Under Sec­ret­ary of State, Depart­ment of Health)

1. Background

In October 2010 the ACMD recom­men­ded to the Gov­ern­ment that, 2- diphen­yl­methyl-piperid­ine (2-DPMP, here referred to as desoxypi­pra­d­rol), which was being mar­keted at that time as “Ivory Wave”, should be subject to an imme­di­ate ban under the Open General Import Licence (OGIL). This advice was accep­ted by the Gov­ern­ment and a ban was imple­men­ted on 4 Novem­ber 2011

Pub­lished data on the effects of 2-DPMP are limited, although research on deriv­at­ives of desoxypi­pra­d­rol show that they exhibit a cocaine-like binding profile (Schmitt et al., 2008).

Cur­rently, there is no known medi­cinal use for this com­pound, although it was ori­gin­ally developed by Ciba-Geigy (Novartis) in 1953 to be used to wake patients fol­low­ing anaes­thesia (Belucci, 1955).

Desoxypipradrol & Pipradrol

This com­pound is related to pipra­d­rol, a pre­vi­ously-licensed medi­cine for treat­ment of Atten­tion Deficit Hyper­activ­ity Dis­order (ADHD), obesity and nar­co­lepsy. Pipra­d­rol is clas­si­fied under the Misuse of Drugs Act as a Class C sub­stance. Pipra­d­rol still used is some coun­tries, but its use is limited due to its abuse poten­tial; it is a dopam­ine and nore­pineph­rine reup­take inhib­itor.

Pipra­d­rol and its desoxy form have struc­tur­ally related pyrrolid­ine ana­logues (see below) such as diphen­yl­pro­linol (diphenyl-2-pyrrolid­inyl­meth­anol, D2PM), for which there have been a number of recor­ded cases of car­di­ovas­cu­lar and neuro­psy­chi­at­ric tox­icity asso­ci­ated with recre­ational use (Lidder et al., 2008, Wood et al., 2008, Wood et al., 2011), and 2-diphen­yl­methyl-pyrrolid­ine, cur­rently mar­keted, along with D2PM and various ana­logues, as chem­ical reagents for use as chiral cata­lysts in organic syn­thesis (Ber­telsen et al., 2005, Sigma-Aldrich, 2007).

ß-phenylmethylamphetamine

The two pairs of mater­i­als differ only by the size of the nitro­gen-con­tain­ing ring. Diphen­yl­pro­linol and its desoxy form have a five-membered (pyrrolid­ine) ring, while pipra­d­rol and its desoxy form have a six-membered (piperid­ine) ring. It seems that the two desoxy forms have par­tic­u­larly long-lasting effects as their struc­tures are res­ist­ant to meta­bol­ism, meaning that they have longer half-lives in the body. A common feature of these com­pounds is that they are struc­tur­ally related to ß-phenyl­methyl­amphet­am­ine, which is also a potent stim­u­lant with a long half life. However, these com­pounds differ from ß-phenyl­methyl­amphet­am­ine in that the nitro­gen atom is linked to the a- methyl group by two or three carbon atoms to form a ring.

Pipradrol Analogues

Various ana­logues of these com­pounds have been invest­ig­ated and found to have stim­u­lant prop­er­ties (Isbell, 1970 and US Patents). Simple modi­fic­a­tions, for example, addi­tion of halogen, alkyl or alkoxy groups on one or both of the phenyl rings or addi­tion of alkyl, alkenyl, haloal­kyl and hydroxyal­kyl groups on the nitro­gen atom have been repor­ted to produce com­pounds having a stim­u­lant effect on the CNS, which could lead to a range of “designer” forms.

Other modi­fic­a­tions that have been repor­ted in the lit­er­at­ure include repla­cing the piperid­ine ring with an azepane ring (7-membered ring), a mor­pholine ring or a pyrid­ine ring (Win­throp, 1961; Enyedy, 2003). The piperid­ine ring has also been mod­i­fied by sub­sti­tu­tion in the ring with an hydroxy group (Nodine, 1960), fusion of the piperid­ine ring with a benzene ring (Win­throp, 1961) and by sub­sti­tu­tion at the nitro­gen atom with an ethano bridge to form a bicyc­lic ring system (Wiki­pe­dia, 2011).

Almost all of the ana­logues invest­ig­ated are struc­tur­ally related to the 2-isomer of desoxypi­pra­d­rol, with 2 carbon atoms between the phenyl rings and the nitro­gen atom. The only excep­tions being the N-haloal­kyl deriv­at­ives of desoxypi­pra­d­rol and the pyrid­ine ana­logue in which the 2-, 3- and 4- isomers were all repor­ted to be active. No examples were found of com­pounds related to 1-diphen­yl­methyl­piperid­ine (N-diphen­yl­methyl- piperid­ine).

Whilst, it should be pos­sible to dis­tin­guish between pipra­d­rol isomers using tech­niques such as NMR, in the long term it would be support forensic ana­lysis to have ref­er­ence stand­ards of all the pipra­d­rol pos­i­tional isomers. The ACMD recom­mends that the Home Office con­siders com­mis­sion­ing the pro­duc­tion of stand­ards through the Forensic Early Warning System.

2. Use and prevalence

The National Poisons Inform­a­tion Service in Edin­burgh high­lighted that a number of indi­vidu­als had presen­ted to the Royal Edin­burgh Infirm­ary in the summer of 2010 fol­low­ing their use of desoxypi­pra­d­rol with symp­toms that were similar to amphet­am­ine tox­icity, but with pre­dom­in­ant neuro­psy­chi­at­ric fea­tures includ­ing:

  • Hal­lu­cin­a­tions
  • Para­noia
  • Severe Agit­a­tion

In some patients the symp­toms were still being mani­fes­ted 5 – 7 days after inges­tion and some patients presen­ted dir­ectly to psy­chi­at­ric ser­vices, bypassing A&E. There were approx­im­ately 12 cases over this period. It was sub­sequently repor­ted that 4 out of 5 of the Edin­burgh cases in whom con­firm­at­ory tox­ic­o­lo­gical screen­ing was carried out were pos­it­ive for desoxypi­pra­d­rol in urine/​blood con­firm­ing expos­ure.

The number of patients present­ing after con­firmed inges­tion of desoxypi­pra­d­rol after the summer of 2010 has dra­mat­ic­ally reduced in Edin­burgh with no cases in 2011 and data from the National Poisons Inform­a­tion Service (NPIS) sug­gests that there has also been a sig­ni­fic­ant reduc­tion nation­ally. However, as noted below cases of diphen­yl­pro­linol (D2PM) tox­icity con­tinue to occur.

So far 3 deaths have been linked to the use of desoxypipradrolb(awaiting final reports).

Data provided by the Home Office Centre for Applied Science and Tech­no­logy (CAST) under its Forensic Early Warning System (FEWS) repor­ted one sample of 2-DPMP (from a head-shop), 10 samples of D2PM and 4 samples of desoxy-D2PM (from test pur­chases) during the pilot study.

LGC Forensics repor­ted those samples of “Ivory Wave” it had seen in 2009 – 2011 con­tained dif­fer­ent active ingredi­ents includ­ing the cath­inone MDPV (methyl­e­ne­di­oxypyro­va­ler­one) then, after this became con­trolled, naphyrone, and when this too was con­trolled, desoxypi­pra­d­rol. More recently, diphen­yl­pro­linol has begun to appear in “legal high” products.

Desoxypi­pra­d­rol has been found as a white powder that is gen­er­ally taken by nasal insuf­fla­tion (sniff­ing the powder into the nose) or swal­low­ing after wrap­ping the powder in a cigar­ette paper (“bombing”) to avoid any unpleas­ant taste.

It is con­sidered that 2-DPMP and its related com­pounds, as cap­tured under the generic defin­i­tion (see recom­mend­a­tion), have poten­tial social harms. It appears to the ACMD that such harms are likely in rela­tion to the impair­ment of func­tion through drug use (mood dis­orders, changes to life­style), loss of rela­tion­ships and the poten­tial harm to others (dir­ectly and indir­ectly).

3. Preclinical Data

In the 1950’s, Ciba-Geigy invest­ig­ated the effects of desoxypi­pra­d­rol, amphet­am­ine and d-methyl­amphet­am­ine on small animals (report kindly provided by Novartis). The LD50 is the dose, which kills 50% of the animals:

Table 1. Tox­icity of desoxypi­pra­d­rol and other com­pounds, meas­ured as LD50, to small animals.

Desoxypi­pra­d­rol
LD50 g/​kg
Amphet­am­ine
LD50 g/​kg
D-methyl­amphet­am­ine
LD50 g/​kg
Mouse iv*0.0200.0500.020
” sc0.0470.0600.080
” po0.0500.0700.150
Rat iv0.0150.0120.023
” sc0.0300.0120.015
” po0.0800.0130.025
Rab­bit iv0.0060.0400.030
” sc0.0070.0450.020
” po0.0800.1700.200

(*iv – intra­ven­ous, sc – sub­cu­taneous, po – orally)Table 1 shows that desoxypi­pra­d­rol is, in many cases, more toxic than amphet­am­ine and d-methyl­amphet­am­ine.

The Ciba-Geigy report (from the 1950s) also noted that desoxypi­pra­d­rol:

pro­duced a marked central arousal in various, non-anaes­thet­ised animals, con­sist­ing ini­tially of general agit­a­tion, sub­sequently a greater degree of increase in co-ordin­ated motil­ity, heightened reflexes, com­pelled move­ments and rel­at­ively slight res­pir­at­ory stim­u­la­tion.

This was easily dis­cern­ible object­ively in the normal mouse with the aid of the cage move­ment regis­tra­tion method. With this method the indi­vidual move­ments are registered dir­ectly and added up by means of a total­iser.

Figure 1. Effect­ive­ness of desoxypi­pra­d­rol in stim­u­lat­ing activ­ity in mice when when admin­istered sub­cu­taneously (heavy line) or orally (thin line)
(Figure repro­duced with kind per­mis­sion of Novartis)

The data show that desoxypi­pra­d­rol is effect­ive as a stim­u­lant in doses com­par­able to those for amphet­am­ine or methyl­amphet­am­ine – from 1 mg/​kg upwards. For the pur­poses of its research at the time, Novartis recom­men­ded an initial human dose of 1mg or less, (ca 0.014 mg/​kg). Anec­dotal inform­a­tion would suggest that the human dose is only a few mg, with 10mg or more being con­sidered harmful.

Exper­i­mental data sup­plied by Dr Colin Dav­id­son (St Georges, Uni­ver­sity of London, 2011) demon­strated that desoxypi­pra­d­rol potently stim­u­lated dopam­ine release from rat brain slices in vitro. Dopam­ine release was meas­ured from the region of the nucleus accum­bens, using carbon fibre micro­elec­trodes and fast cyclic voltam­metry to elec­tric­ally measure the oxid­a­tions of dopam­ine. The rate of recov­ery of stim­u­lated dopam­ine release also allowed meas­ure­ment of the action of the drug as an inhib­itor of the dopam­ine reup­take mech­an­ism. Dopam­ine release in the nucleus accum­bens is con­sidered to be a key target for psy­chos­tim­u­lant drugs.

Figure 2. Effect of desoxypi­pra­d­rol (10uM) on dopam­ine efflux in rat nucleus accum­bens

It also proved pos­sible to compare the potency of desoxypi­pra­d­rol with the psy­chos­tim­u­lant drug cocaine in the brain slice pre­par­a­tion. The results (Figure 3) indic­ate that desoxypi­pra­d­rol is both more effect­ive and more potent than cocaine in stim­u­lat­ing dopam­ine release and in inhib­it­ing its reup­take.

Figure 3. Com­par­ison of poten­cies of desoxypi­pra­d­rol and cocaine in releas­ing dopam­ine, and inhib­it­ing inac­tiv­a­tion in rat brain slice pre­par­a­tions (C. Dav­id­son, unpub­lished)

The results both from Novartis and from Dr Dav­id­son indic­ate that desoxypi­pra­d­rol is very potent and com­par­able to amphet­am­ine or methyl­amphet­am­ine in its poten­tial to cause acute tox­icity.

The avail­able human data also show it to be a long-lasting sub­stance, capable of eli­cit­ing agit­a­tion lasting for several days after a single dose.

In addi­tion to the reports of tox­icity asso­ci­ated with the use of desoxypi­pra­d­rol noted above, there have also been reports of sig­ni­fic­ant tox­icity asso­ci­ated with the recre­ational use of the related com­pound diphen­yl­pro­linol (D2PM). In addi­tion, reports from forensic pro­viders suggest that D2PM has replaced desoxypi­pra­d­rol in many “Ivory Wave” products. The clin­ical tox­ic­o­logy service at Guy’s and St Thomas’ Hos­pital in London have doc­u­mented 6 cases of ana­lyt­ic­ally con­firmed D2PM tox­icity: 1 case in 2008 and 5 cases in 2010 / 2011 (Lidder et al., 2008, Wood et al., 2008, Wood et al., 2011). In these cases patients have presen­ted with a variety of symp­toms includ­ing:

  • chest pain
  • agit­a­tion
  • anxiety
  • insom­nia
  • hal­lu­cin­a­tions
  • para­noia

In many of these cases patients have had ongoing fea­tures, in par­tic­u­lar neuro-psy­chi­at­ric fea­tures such as anxiety, insom­nia and para­noia for up to 48 – 96 hours after use of D2PM.

4. Recommendation

The ACMD advises that the harms of desoxypi­pra­d­rol are com­men­sur­ate with other Class B drugs and recom­mend that it is con­trolled under the Misuse of Drugs Act 1971 as a Class B sub­stance and in Sched­ule 1 of the Misuse of Drugs Reg­u­la­tions 2001 (as amended). Fur­ther­more, we recom­mend that the struc­tur­ally related com­pounds diphen­yl­pro­linol (diphenyl-2-pyrrolid­inyl-meth­anol, D2PM) and its desoxy form 2-diphen­yl­methyl­pyrrolid­ine are sim­il­arly con­trolled under the Misuse of Drugs Act 1971 and sched­uled under the Misuse of Drugs Reg­u­la­tions 2001 by virtue of a generic defin­i­tion (see Annex 1 of the report) to ensure that desoxypi­pra­d­rol and related com­pounds, e.g. diphen­yl­pro­linol, diphen­yl­methyl­pyrrolid­ine, are fully cap­tured (see Annex 1 & 2).

The ACMD under­stands that desoxypi­pra­d­rol and its related com­pounds do not have any medi­cinal uses; however, the ACMD has not form­ally con­sul­ted with the industry.

The pro­posed generic defin­i­tion includes desoxypi­pra­d­rol and those ana­logues most likely to be pro­duced as altern­at­ives. Some of the com­pounds that fall within the scope of the pro­posed generic defin­i­tion contain a hydroxy group, which can be con­ver­ted to an ester or ether. Such com­pounds may have similar phar­ma­co­lo­gical prop­er­ties to the parent com­pound and there­fore it is recom­men­ded that esters and ethers of these com­pounds are also subject to control under the Misuse of Drugs Act, 1971.

Whilst, ideally, any generic defin­i­tion would include all pos­sible pos­i­tional isomers, this may mean that non-active com­pounds would also be con­trolled. Further, a defin­i­tion to cover all of these poten­tial ana­logues is feas­ible, but it would be very complex and pos­sibly dif­fi­cult to under­stand.

Under the defin­i­tion that the ACMD propose at Annex 1 esters and ethers of pipra­d­rol would not be con­trolled. This is because pipra­d­rol is spe­cific­ally excluded from the generic defin­i­tion and there­fore para­graph 2A would also not apply to pipra­d­rol. For con­sist­ency the ACMD advise the inclu­sion of esters and ethers of pipra­d­rol by moving pipra­d­rol from Sched­ule 2 Part III para­graph 1(a) to para­graph 1(b) so that para­graph 1(d) regard­ing esters or ethers would apply to pipra­d­rol.

The ACMD further advise that ste­reoi­somers should be con­trolled by Sched­ule 2 Part II para­graph 2. The three main drugs, desoxypi­pra­d­rol, diphen­yl­pro­linol (D2PM) and
2-diphen­yl­methyl­pyrrolid­ine all have ste­reoi­somers and most of the com­pounds covered by the generic defin­i­tion will also have ste­reoi­somers.

5. References

  1. Bel­lucci G. (1955); (2-Diphen­yl­methyl-piperid­ine hydro­chlor­ide and the methyl ester of 2-chloro-2-phenyl-2-(2-piperidyl)-acetic acid), drugs with waking effect in anaes­thesia. Minerva Anestesiolo­gica 21: 125 – 8.
  2. Ber­telsen S, Halland N, Bach­mann S, Marigo M, Braunton A, Jør­gensen KA. (2005); Organocata­lytic asym­met­ric a-brom­in­a­tion of alde­hydes and ketones. Chem­ical Com­mu­nic­a­tions 4821 – 4823.
  3. Enyedy IJ, Sakamuri S, Zaman WA, Johnson KM, Wang S. (2003); Phar­ma­co­phore-based dis­cov­ery of sub­sti­tuted pyridines as novel dopam­ine trans­porter inhib­it­ors. Bioor­ganic & Medi­cinal Chem­istry Letters;13:513 – 517.
  4. Hoff­mann K, Heer J. (1958); 2-Diphen­yl­methyl-piperid­ine com­pounds. US Patent 2,826,583.
  5. Hoff­mann K, Heer J. (1958); Piperidines and their man­u­fac­ture. US Patent 2,849,453.
  6. Hoffman K. (1962); 1-Ethyl-2-diphen­yl­methyl-piperidines. US Patent 3,048,594.
  7. Hoff­mann K, Heer J. (1960); Sub­sti­tuted 2-diphen­yl­methyl-piperid­ine com­pounds. US Patent 2,957,879.
  8. Isbell H, Chrus­ciel TS. (1970); Depend­ence Liab­il­ity of Non-Nar­cotic Drugs. Bul­letin of the World Health Organ­isa­tion; 43: Sup­ple­ment, pages 76 – 77.
  9. Lidder S, Dargan P, Sexton M, Button J, Ramsey J, Holt D, Wood D. (2008); Car­di­ovas­cu­lar tox­icity asso­ci­ated with recre­ational use of diphen­yl­pro­linol (diphenyl-2-pyrrolid­ine­meth­anol [D2PM]). Journal of Medical Tox­ic­o­logy; 4(3):167 – 9.
  10. Nodine JH, Bodi T, Slap J, Levy HA, Siegler PE. (1960); Pre­lim­in­ary trial of a new stim­u­lant SCH 5472 in ambu­lat­ory patients with depres­sion, exhaus­tion, or hyper­som­nia syn­drome. Anti­bi­otic Medi­cine and Clin­ical Therapy ; 7:771 – 6.
  11. Novartis (1955) Inform­a­tion on Prep. No. 14?469 (desoxypi­pra­d­rol), a new syn­thetic stim­u­lant with central point of applic­a­tion.
  12. Schmitt KC, Zhen J, Kharkar P, Mishra M, Chen N, Dutta AK, Reith ME. (2008); Inter­ac­tion of cocaine-, ben­ztropine-, and GBR12909-like com­pounds with wild-type and mutant human dopam­ine trans­port­ers: molecu­lar fea­tures that dif­fer­en­tially determ­ine ant­ag­on­ist-binding prop­er­ties; Journal of Neuro­chem­istry 107: 928 – 40.
  13. Sigma-Aldrich Co. (2007) “Organocata­lysis”, Chem­istry files, vol 7, No.
  14. Wiki­pe­dia entry for AL-1095. <http://​en​.wiki​pe​dia​.org/​w​i​k​i​/​A​L​-​1​095>; 2011 [accessed 25.08.11].
  15. Win­throp SO. (1960) a-(3-Morpholyl)-benzhydrol and its salts. US Patent 2,947,749.
  16. Win­throp SO. (1961); 3-Ben­zhy­dryl­mor­pholine and salts thereof, and method of pre­par­ing said com­pounds. US Patent 2,993,895.
  17. Win­throp SO, Humber LG. (1961); Central Stim­u­lants. Cyc­lized Diphen­yl­iso­p­ro­pyl­am­ines. Journal of Organic Chem­istry 26: 2834 – 6.
  18. Wood DM, Davies S, Puchnarewicz, Holt DW, Dargan PI. A case series of indi­vidu­als with ana­lyt­ic­ally con­firmed acute diphenyl-2- pyrrolid­ine­meth­anol (D2PM) tox­icity. Manu­script sub­mit­ted for pub­lic­a­tion.
  19. Wood DM, Puchnarewicz M, Holt DW, Ramsey J, Dargan PI. (2011); Detec­tion of the pre­cursor ben­zo­phen­one in indi­vidu­als who have used legal highs con­tain­ing diphenyl-2-pyyrrolid­ine­meth­anol (D2PM). Basic & Clin­ical Phar­ma­co­logy & Tox­ic­o­logy; 109 (Suppl. 1): 86.

Annex 1

Proposed generic definition

Any com­pound (not being pipra­d­rol) struc­tur­ally derived from piperid­ine, pyrrolid­ine, azepane, mor­pholine or pyrid­ine by sub­sti­tu­tion on a ring carbon atom with a diphen­yl­methyl group, whether or not the com­pound is further mod­i­fied in any of the fol­low­ing ways, that is to say,

  1. by sub­sti­tu­tion in any of the phenyl rings to any extent with alkyl, alkoxy, haloal­kyl or halide groups;
  2. by sub­sti­tu­tion on the methyl carbon atom with an alkyl, hydroxyal­kyl or hydroxy group;
  3. by sub­sti­tu­tion on the ring nitro­gen atom with an alkyl, alkenyl, haloal­kyl or hydroxyal­kyl group.

.

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