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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


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 |


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 |


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).


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.

LD50 g/​kg
LD50 g/​kg
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​pedia​.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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