Muddying the waters – should we ban naphyrone?

The ACMD recently recommended banning naphyrone. Relatively unheard of until the banning of mephedrone, it is now being sold as the new legal alternative, though one small survey of products found that most of what is sold as naphyrone – or as NRG-1/energy– is in fact mephedrone or similar substances [Brandt et al 2010]. The ACMD itself supports these findings:  “Limited samples of test purchasing would suggest that the prevalence of the compound naphyrone is currently relatively low and makes up a relatively small percentage of the total compounds found in marketed ‘legal highs’".

If there is little use of naphyrone by the public, why do the ACMD wish to ban it?  Is there evidence of harm?  Judging by the ACMD report, the answer is no - they could find little if any evidence of human harm from naphyrone and they present no evidence of toxicity in animals either. The ACMD decision was made on the grounds that it has a (weak) chemical similarity to mephedrone and other cathinones and is 10 more potent than some of these. “The ACMD believe that naphyrone is likely to exhibit a similar spectrum of harmful effects as the other previously controlled cathinones. The data that are available for naphyrone suggest that its high potency, in comparison with the other cathinones, is likely to be associated with a higher risk of accidental overdose" [my emphasis].

An interesting choice of words and one which bears comparison with Brown’s public pronouncements as Prime Minister demanding cannabis upgrading three years ago: “the greater damage it appears to be doing…is that there is a stronger case for sending out a signal that cannabis use is … lethal forms of cannabis such as skunk” [my emphasis].

The ACMD disagreed with this analysis that the potency of cannabis warranted Class B status [Rawlins et al 2008] as greater potency only results in more toxicity if drugs are taken in equal doses. Suppliers of naphyrone understand this and the unit dose sold is proportionately lower than that for mephedrone for this reason.

To reduce accidental harms, users need to be provided both with education on drugs and their harms and the option to know what they are taking. Whilst I was chair of the ACMD last year, we recommended to government that we should gather evidence about the efficacy and value of testing schemes for drugs that have been tried in the Netherlands and Australia. The suggestion was dismissed without justification by the then Home Secretary. Hopefully, the ACMD can present the suggestion again to the new government which may be more receptive.

A major problem with the ACMD report is its lack of critical appraisal of the science behind naphyrone. The pharmacology on which the ban is recommended is that it blocks brain reuptake sites for the neurotransmitters noradrenaline, 5HT (serotonin) and dopamine. Such actions are a feature of antidepressant rather than stimulant actions. Based on the ACMD's logic then, potential new antidepressants such as NS2359 [Wilens et al 2008] as well as established ones such as bupropion, venlafaxine and even imipramine could be the next to be banned by the ACMD!  Needless to say, these drugs do not have abuse liability.

Another important consideration is that the development of naphyrone was driven by a desire to find new treatments for addiction [Meltzer et al 2006].  Such research will inevitably suffer once the compounds are outlawed – another perverse consequence that must always be taken into account [see Precaution or perversion: eight harms of the precautionary principle]. MDMA (ecstasy) was originally developed as adjunctive treatment in psychiatric therapy. This research stopped when it was made illegal in the 1970s and has only just been resumed – with major benefits emerging [Mithofer et al].

The case for banning naphyrone is weakened by the fact that that most products sold as naphyrone are in fact mephedrone or related substances [Brandt et al 2010], which are already illegal. Indeed, this legislative approach may increase awareness of naphyrone as an alternative to mephedrone and we may see an increase in use in the weeks before it is made illegal as happened with mephedrone [Measham et al 2010, Drug and Alcohol Today]. This is, of course, assuming thatthe government goes with the ACMD recommendations, which seems certain as no UK government has ever resisted a request to impose more legal constraints on drugs.

The emergence of naphyrone as a potentially more dangerous variant of mephedrone raises further questions about the value of banning mephedrone in the first place when it was already widely used without causing a great deal of harm [see Hysteria and hubris: lessons on drug control from the Scunthorpe Two]. As predicted by me and many others, making it illegal has only displaced interest to other compounds about which less is known and which are potentially more dangerous.  I discussed these perverse consequences of prohibition in an earlier blog [Precaution or perversion: eight harms of the precautionary principle].

Once naphyrone is banned, what will be the next 'legal high'? I don’t know but I can guarantee many chemists and manufacturers already do. Will these new compounds be banned without any testing of pharmacology or any knowledge of harms?  What is an appropriate threshold of harm that should lead to a drug being considered for banning? These are important scientific and social issues that the ACMD need to develop guidelines to address; I hope that they are doing so.

Brandt, S. D., Sumnall, H. R., Measham, F., Cole, J. (2010). The confusing case of NRG-1. British Medical Journal. 341:c3564.

Wilens TE, Klint T, Adler L, West S, Wesnes K, Graff O, Mikkelsen B. A randomized controlled trial of a novel mixed monoamine reuptake inhibitor in adults with ADHD. Behav Brain Funct. 2008 Jun 13;4:24.