# International Drug Scheduling

The US FDA has issued a request for comment notification asking for input on ten compounds which are being considered for action by the World Health Organization. Under the 1971 Convention on Psychotropic Substances the WHO is tasked with recommending (to the United Nations) whether or not international controls should be enacted for various recreationally abused substances.
This is a chance to observe some of the sausage making for the fans of drug policy.

the Thirty-fifth Expert Committee on Drug Dependence will meet from 20 to 23 April 2009 to review the following substances:

1. Gamma-hydroxybutyric acid (GHB)
2. Ketamine
3. Dextromethorphan
4. N-benzylpiperazine (BZP)
5. 1-(3-trifluoromethylphenyl)piperazine (TFMPP)
6. 1-(3-chlorophenyl)piperazine (mCPP)
7. 1-(4-Methoxyphenyl)piperazine (MeOPP)
8. 1-(3,4-methylenedioxybenzyl)piperazine (MDBP)
9. Gamma-butyrolactone
10. 1,4-Butanediol

Clearly they are focused heavily on the piperazine derivatives which have both stimulant/euphoric and hallucinogenic properties, depending on the compound. Some of these were recently legal in NZ leading to a competitive marketing situation.
The last two are GHB prodrugs, meaning they are converted to GHB once ingested. There's some interesting research looking at just how this works, how it influences abuse potential relative to GHB, endogenous mechanisms which are affected by exogenous GHB, etc.
The report arising from the 2002 meeting of the Thirty-Third Expert Committee may give some flavor of the type of recommendations that are issued.
As I said, sausage making. Interesting to see how long it takes public policy to emerge in the wake of the emergence of recreational use bubbles/fads and in the wake of supporting scientific studies as well. This may or may not be informative to those who think that agencies regulate first and ask about the scope of the problem later.

• PalMD says:

GHB has a rather narrow "therapeutic" window. In the ER, I frequently saw youngish people come in completely comatose, get intubated, and then several hours later sit straight up, pull out their tube, and say, "I'm outta here".

• DrugMonkey says:

GHB has a rather narrow "therapeutic" window.
oh yeah! from what I can gather from my peeps in the research world it is just as difficult to deal with from an experimental perspective as you might conclude from the real world experience with humans. throw in the fact that recreational products don't exactly come with verified concentration information and....well. Must be a very...interesting....drug to try.
(in case anyone isn't clear on what PalMD is referring too, the dose which gets you the desired high effect is quite close to the dose which puts you into medical emergency. meaning not just the dose for wackaloon well-experienced users or strange individual difference but rather mean effects in the average user population.)

• Ketamine? Well, for fuck's sake!

• NM says:

Covenience stores in some places in NZ were selling BZP over the counter.

• DrugMonkey says:

Ketamine? Well, for fuck's sake!
assuming that even if Isis is being a smartacre here, there are some that don't know. yes, the dissociative anesthetic (mostly familiar in the veterinary setting, but also used in selected human conditions- children with burn injuries if i recall) ketamine is abused by not-insubstantial numbers of people. small by comparison to many other more familiar drugs of course.
for those with typical research U library access you might start with this one for the "why".
http://dx.doi.org/10.1016/j.drugalcdep.2008.01.024
I couldn't find it in the MAPS archive (see sidebar) but they do have enough to get you started on the typical user profile.

• Thanks, DM. I suppose I was being a bit facetious in my exclamation. We had an incident at my former MRU of some students stealing ketamine from a lab class. I am thankful it was not my lab class. When I am using it, I keep my ketamine vials nestled firmly to my bosom.
I suppose my exclamation came more from the structure of FDA's comment document. The questions seem a bit, well, inane. Perhaps you could educate those of us less familiar with the regulation of our precious controlled substances as to from whence these comments come and whence they go?

• juniorprof says:

but also used in selected human conditions- children with burn injuries if i recall
Ketamine use in the medical setting depends on where you are geographically. For instance, in the emergency room, up in Canada (well at least Quebec) ketamine is used quite a bit for pain management and for relatively simple, but still mildly invasive procedures. My understanding is that it is also used quite widely in Europe for the same purposes. The issue with ketamine not being used in the US is tied to abuse potential, as I understand it. This is somewhat unfortunate because it is an excellent pain management tool especially in the early hours after a severe injury. There is a rich literature out there on the use of ketamine for pain management in severely injured patients and it appears that the compound has good utility not only for acute pain but for blocking the transition to chronic pain conditions. Likely because it blocks some of the spinal sensitization processes that occur with a persistent noxious insult (you know, NMDA pharmacology and physiology -- its important).

• Chris says:

I can't pretend to know much about this (although I think I did most of those substances in college). The inclusion of Dextromethorphan on the list is interesting, though. I hope it doesn't go the pseudoephedrine route. then again, buying Sudafed isn't a big inconvenience, just a little one.

• DrugMonkey says:

Chris@#8: Abel Pharmboy talked about dextromethorphan abuse a little bit here.
Isis@#6: I'm not sure why you think these "inane"? Keep in mind that this is a general structure for any drugs that might be under consideration. There are many compounds which have clinical (ketamine) or research (mCPP) or household/industrial (GBL used to be widely available as a solvent agent, I think the FDA started trying to control GBL-containing products in 1999) utility that become a recreational drug of concern. Regulation at the national and international level tries to balance factors when deciding what to do. Do the member states use the compounds for legitimate purposes? That's pretty important. Is the recreational abuse problem so tiny that it isn't worth addressing? Again, pretty critical. Are there newer and better research tools available that could pretty much replace the older ones?
I'm not an expert on even the FDA processes but I've seen a little bit of the process recently. Some FDA people in regulatory affairs have actually been presenting posters and so I can start to see how they develop a position. It isn't rocket science. They try to get the best information on all the relevant factors to inform whether additional controls of a given substance are needed or worth the costs.
I was alerted to this particular call as a grantee of NIDA but the notice was published in the Federal Register so I suppose anyone in the US who cares to offer an opinion is invited... I wouldn't be surprised if our good friends at MAPS chimed in on the piperazine derivatives, for example.

• leigh says:

ghb is indeed hard to study thanks to that pesky narrow TI. and that also complicates recreational use for same reason- not too hard to overdose while trying to achieve that high... we've already been through that in the comments section though.
ketamine sedation is associated with emergence delirium, that may be a hindrance to its prevalent medical use.
i guess i still find it interesting that dextromethorphan is on the list- i wasn't aware that was such an issue now. guess it's been a while since i was a teenager.

• Becca says:

Ketamine is a pretty facinating drug. I don't envy the people doing cost-benefit analysis on control measures for that one.
Out of curiosity, does anyone know how recreational drug abuse vs. drug-abuse-to-facilitate-crimes is weighted in these sorts of policy decisions?

• DrugMonkey says:

drug-abuse-to-facilitate-crimes
Are you talking about GHB or other mickeys to facilitate sexual assault or something?
I can't say I have any insight into how various "harms" associated with specific compounds might be compared. I would imagine that the questions would focus on "what are the harms?" and "what is the scope of each harm in terms of people and $$?". • Becca says: Yes indeed. The thing is date-rape, from a sheer -only cost-benefit analysis fails. It's not an easy thing to evaluate. • DrugMonkey says: But this may be a time when I did say in terms of "people and \)s" you know. But you have to be realistic about the way public policy really works. everyone has their pet issue that doesn't get enough attention,$$ or research or whatever in their opinion. The motivating factors can by highly variable- one issue may rise to the top because it happens to one highly salient famous person but in aggregate affects populations at a lower rate than another issue.
drug-facilitate sexual assault was one of those issues that got a LOT of play in the popular media a few years back but honestly, whenever I've seen data the actual scope seems much smaller than the subjective impression created by media attention.
kinda like the past few years have been all METH, METH, METH when cocaine dependence may be just as prevalent if not more so.
so I actually credit national or international efforts that try to get a rational look at all the relevant factors before jumping into a new regulatory approach. Legislation by Time Magazine articles is no way to go...

• Becca says:

Pshaw. DM, you say that like letting popular opinion determine policy is a bad thing, you anti-democratic petty dictator, you.
😉
Seriously though, I have a creeping suspicion that drug scheduling will always have a lot more to do with public perception of problems than with rational cost-benefit analysis of human suffering. The drug war still has a lot to answer for (e.g. discrepencies between punishment for coke vs. crack) and this is one of those areas which seems doomed to somewhat flawed approaches. Unless of course the real concern with drug control never was the suffering caused by drugs, but with the disruption to the social order.

• Klem says:

Thanks for posting this DM!
Given the enormous magnitude of the global health problems that the WHO is mandated to address, it's hard to see how they find resources to debate about rarely used substances that are available over-the-counter in many countries with marginal public health consequences.
Becca, "Alcohol Is Most Common 'Date Rape' Drug" - spiked drinks have rarely happened but the phenomenon appears to be largely a moral panic myth. BTW, alcohol is the only drug consistently shown to increase violence.
Also Becca, check out the history of cannabis prohibition in the US, from a USC law prof. All science-friendly readers will get a tragicomic kick from 'bat man' - the first US gov 'Official Expert' on marijuana!
In the Netherlands 'bars' sell ethanol, 'coffee shops' sell cannabis, and 'smart shops' sell psilocybin mushrooms and a variety of other herbal psychoactives. All these places are clean, taxed and regulated. Society functions fine. Of course there are details to discuss, but this sort of open, regulated market in psychoactives could be implemented immediately any country - likely without even changing any laws, as on paper drug policy in all countries is supposed to be guided by evidence-based public health.
This quote from the Transform Drug Policy Foundation website fits most of the public health professionals that I have met, frustrated but silent, waiting for scientists or somebody to speak out...
As Julian Critchley (Ex- director of the UK Anti-Drug Co-Ordination Unit) said recently;
�I think what was truly depressing about my time in the civil service was that the professionals I met from every sector held the same view: the illegality of drugs causes far more problems for society and the individual than it solves. Yet publicly, all those people were forced to repeat the mantra that the Government would be "tough on drugs", even though they all knew that the policy was causing harm.�

• drugmonkey says:

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