Introduction and Aims
To assess the prevalence of use and subjective effect profile of methoxetamine among a group of polydrug users.
To assess the prevalence of use and subjective effect profile of methoxetamine among a group of polydrug users.
Cross-sectional, anonymous, online survey of UK-based polydrug users was conducted. Prevalence of lifetime, last year and last month use, sourcing of the drugs, motivations for use, and subjective effect and risk profile compared with that of ketamine were measured.
There were 7700 UK-based polydrug users, of whom 326 reported recent use of methoxetamine. Of the whole sample, 4.2% reported last 12 month use of methoxetamine compared with 24.5% for ketamine. The most common route of use was intranasal and the predominate effect described as psychedelic. Of the 15.5% of last year users of ketamine reporting last year use of methoxetamine, only 18.7% reported that they thought methoxetamine was less damaging to their kidneys or bladder than ketamine. Its broad effect profile, based on participants' first experience of use, was very similar to that of ketamine. Almost one-third of users reported that they did not intend to try the drug again.
Methoxetamine appears to have a broadly similar effect profile to that of ketamine. Only a minority of participants were motivated to use it because they believed it was less damaging to their kidneys or bladder than ketamine. The impact of the recent temporary banning order on availability and use of both methoxetamine and ketamine should be monitored carefully. [Winstock AR, Lawn W, Deluca P, Borschmann R. Methoxetamine: An early report on the motivations for use, effect profile and prevalence of use in a UK clubbing sample. Drug Alcohol Rev 2016;35:212–7]
Methoxetamine (MXE), an arylcyclohexylamine derivate of ketamine, is a novel synthetic psychedelic drug with a recent history of use in the UK and elsewhere. It was marketed as a safer, ‘legal’ alternative to the more widely used dissociative anaesthetic ketamine . MXE was the first drug to be subject to the UK government's new temporary banning for novel substances with abuse potential, which came into effect on 5 April 2012 . It was made permanently illegal in the UK in February 2013 . However, it is uncontrolled in most other countries, except Brazil, Japan, Russia, Germany, France and seven states in the USA . Data concerning Google searches for the terms ‘methoxetamine’ and ‘MXE’ suggest that popularity peaked in 2012 and has since declined .
There has been little research into MXE's chemistry, pharmacology and toxicology. Like ketamine, MXE is an antagonist of the N-methyl-D-aspartate (NMDA) receptor; however, it may also have affinity for the serotonin transporter and sigma receptors . Online fora [7,8], case reports of patients seeking emergency treatment [9–11] and phenomenological studies  suggest MXE has a similar effect to that of ketamine. However, the most significant difference in its effect profile appears to be the much slower onset of action (up to 90 min)  leading to potential inadvertent excessive dosing [4,9–11]. Of those calling the UK National Poisons Information Service about MXE use, the most commonly reported effects were agitation and tachycardia . In terms of prevalence of MXE use, there has been limited research, though Wood et al.  found that 6.4% of those attending a South London gay club had tried MXE at least once in their lifetime.
To the authors' knowledge, there are no quantitative studies of its effect profile among users. As part of a wider research project undertaken by Global Drug Survey (GDS) in conjunction with the dance music magazine and The Guardian newspaper, we sought to determine the prevalence of MXE use among a diverse sample of polydrug users in the UK. We also sought to explore the motivation for its use, provide a brief effect profile and determine the future intention of those who have already used the drug.
GDS annually designs and conducts anonymous, online surveys (https://www.globaldrugsurvey.com) to investigate trends in illicit drug use. In collaboration with our media partners, including MixMag, Fairfax Media and The Guardian, the survey is actively promoted via social networking sites such as Twitter, Facebook and Reddit for a period of approximately five weeks from its launch in mid-November each year. The research tool was based on previous work done by the research group. Further information about the utility, validity and limitations of the current methodology has been discussed elsewhere [16–19]. Ethical approval was received from the Joint South London and Maudsley and Institute of Psychiatry National Health Service (NHS) Research Ethics Committee.
Between 23 November and 23 December 2011, a total of 15 500 responses were received, of which 7700 were from the UK. Core data regarding basic demographics and prevalence of lifetime (ever used) and recent use (last year and number of days in the last month) of a large number of substances including MXE were collected. We also sought to determine motivations for the use of MXE and to profile MXE using a series of broad descriptors among those respondents who reported that MXE was the drug that had most recently been tried for the first time. These descriptors were successfully utilised in a recent risk assessment of mephedrone [20,21] and included: ‘pleasurable high’ of the drug, the ‘negative effects of the drug when high’, the ‘strength of effect’, the ‘urge to want more of the drug when using’ and ‘value for money’.
Our recruitment strategy is an example of purposive sampling. We acknowledge that this has significant limitations, most notably with respect to response bias whereby there will be inherent differences between those who participate and those who do not. It is more likely that individuals will respond to surveys if they see topics or items that are of interest to them, and thus by definition will differ from those who do not participate. Therefore, as participants in our survey may have a greater interest in or experience with drugs, they may not be representative of the wider population.
Seven thousand seven hundred responses were received from UK residents. Five thousand three hundred sixty-seven (69.7%) were male. The median age was 26 and the mean was 28.3 years [standard deviation (SD) = 9.1]. More than two-thirds (68.4%) were aged 30 years or younger. Of the respondents, 92.1% were white. There were 72.9% who were working and 39.5% were studying (respondents could endorse more than one option). A total of 3334 (44.6%) reported going clubbing at least once per month. Of these, 3242 (97.2%) reported last year use of alcohol, 2481 (74.4%) of tobacco, 2274 (68.2%) of cannabis, 1881 (56.4%) of 3,4-methylenedioxy-methamphetamine (MDMA), 1801 (54.0%) of cocaine, 1305 (39.1%) of ketamine and 212 (6.4%) of MXE. The prevalence of use of MXE compared with ketamine is provided in Table 1.
|Ever used (%)||Mean age first used||Last 12 months use||Last month use||Average number of days used in last month|
|MXE||376 (4.9%)||24.1 (SD = 6.9)||326 (4.2%)||197 (2.6%)||Mean = 1.72 (SD = 3.5); mode = 1 (range 1–30)|
|Ketamine||3621 (47%)||21.8 (SD = 5.5)||1888 (24.5%)||7171 (9.3%)||Mean = 1.88 (SD = 3.0); mode = 1 (range 1–30)|
Of those reporting MXE use in the last twelve months, 266 (81.6%) were male, the mean age was 24.9 (SD = 71.8), 295 (90.5%) were white, 255 (78.2%) were heterosexual, 30 (9.2%) homosexual, 24 (7.4%) bisexual and 10 (3.1%) preferring not to answer (7 cases missing). One hundred ninety-two (58.8%) were working, 153 (46.9%) were studying and 143 (43.9%) had a degree or higher academic qualification. One hundred ninety-seven (2.6%) reported use in the last month, with the modal days of use being 1 (50.2%). Fifty (25.4%) last month users reported use on four or more days in the last month. A subsample of last year MXE users were asked about their motivation for trying MXE. Of 1855 last year ketamine users, 278 (15%) reported having ever tried MXE in the last 12 months. Two hundred three (75.2%) reported it was easier to get hold of than ketamine, 50 (18.7%) reported they believe it was less damaging to their kidneys or bladder, 42 (15.7%) said they preferred the effect of MXE to ketamine and 64 (23.8%) considered it to be better value for money than ketamine. Seventy-nine (41.8%) reported a range of other motivations most commonly curiosity, dissatisfaction with the ketamine purity and notably being exposed to it accidentally after being sold it as ketamine.
More detailed information was obtained on 179 (144 male, 81.4%) people who reported that MXE was the last new drug that they had tried for the first time. Of these, 140 (78.2%) reported use of ketamine in the last 12 months. First use of MXE was reported as occurring in 2011 for over 90% of those reporting use. One hundred fifty-nine (88.8%) reported first use via the intranasal route, 15 (8.4%) oral and 5 (2.2%) via the transbuccal, sublingual or rectal routes. One hundred forty-four (81.4%) reported the effect to be predominantly psychedelic (‘like ketamine’), 17 (9.6%) predominantly a depressant (alcohol/gamma-Hydroxybutyric acid (GHB) like), 7 (4%) empathogen like (like MDMA), 8 (4.5%) mostly stimulant like (cocaine/amphetamine) and 1 (0.6%) cannabis like. Additional information regarding its effect profile and source on that first occasion was also obtained. Eighty-seven (48.6%) reported obtaining MXE from a friend, 58 (32.4%) from a website, 23 (12.8%) from a dealer and 11 (6.1%) from either a family member or head shop. Participants were asked to rate MXE out of 10 (0 = low; 10 = high) across a range of broad descriptors; the ‘pleasurable high’ of the drug, the ‘negative effects of the drug when high’, the ‘strength of effect’, the risk of harm following a session ‘comedown after use’, the ‘urge to want more of the drug when using’ and value for money. These were modified from questions used in our 2010 risk assessment of mephedrone . For comparison, we provide the matching responses of those who reported that ketamine was the last new drug they had tried for the first time. Four hundred ninety-six (88.1%) reported obtaining ketamine from a friend on that first occasion, with 43 (7.6%) from a dealer. The results are shown in Table 2. Regarding repeated use of MXE, 59 (33.5%) reported that they had already used the drug again since that first occasion, 23 (13.1%) reported they planned to use MXE again with 58 (32.4%) reporting they did not plan to use it gain. Thirty-six (20.5%) were unsure. For comparison regarding repeated use of ketamine, 166 (29.5%) reported that they had already used the drug again since that first occasion, 52 (9.3%) reported they planned to use ketamine again with 219 (39%) reporting they did not plan to use it again. One hundred twenty-five (22.2%) were unsure.
|Mean score ‘urge to use more of the drugs when using’ (% ranking 7/10 or higher)||Mean score value for money (% ranking 7/10 or higher)||Mean score strength of effect (% ranking 7/10 or higher)||Mean score risk of harm following a session (% ranking 7/10 or higher)||Mean score the pleasurable high (% ranking 7/10 or higher)||Mean score comedown after use (% ranking 7/10 or higher)||Mean score negative effects when high (% ranking 7/10 or higher)|
|(n = 179)||(10.9%)||(50.4%)||(73.4%)||(17.9%)||(32.8%)||(10.2%)||(14.5%)|
|(n = 558)||(11.9%)||(50.2%)||(69.8%)||(18.9%)||(40.4%)||(11.1%)||(24.8%)|
This paper highlights for the first time the effect profile among current users of MXE and its relative popularity among a relatively large UK clubbing sample.
Results show that almost 5% of the whole sample had ever used MXE, and the vast majority started in 2011. However, its prevalence of use was significantly less compared with those who have ever tried ketamine (47%). Notably, prevalence of past month use of ketamine was higher than that for MXE (2.6% vs. 9.3%).
MXE was found to have a similar effect profile to ketamine, confirming previous findings  and it appears to be attractive to recreational ketamine users. Given these findings and that it is considered easier to acquire than ketamine, it is interesting that it has not reached the same popularity.
Overall, one-third of users have used MXE more than once; however, a similar proportion also reported they did not plan to use it again. Experimental use among majority appears most likely the pattern of use, though as with ketamine, risk of compulsive use among a minority remains.
The effect profile for the first time use of MXE versus ketamine is remarkably similar, with low urge to use more of the drug, low come down after use, high strength of effect and pleasurable high, while relatively low negative effects when high. Whether the effect profile would change with repeated use and whether the same development of tolerance within session of use that can be seen with ketamine also seen among users of MXE is uncertain.
The findings suggest that for most users, the promotion of MXE as a safer alternative  was not a significant motivator for use. This is reassuring as such ‘health-conscious’ promotion of a novel psychoactive substance was an unwelcome addition to the marketing ploys of distribution sites. There is strong evidence linking heavy and frequent ketamine use with urinary problems in humans [18,22,23] and animals , which poses a serious danger for regular users. Recently, it has been demonstrated that in mice, 3 months of daily 30 mg kg−1 MXE leads to substantial bladder and renal toxicity, including inflammatory changes and fibrosis in the bladder . These effects are similar to those seen in animal models testing toxic effects of chronic ketamine, suggesting MXE may not be safer than ketamine, in terms of bladder and renal toxicity. Furthermore, there is preliminary evidence from the GDS that self-reported MXE use is associated with likelihood of urinary problems , although this result needs to be verified in solely MXE users. Chronic ketamine use also leads to neurocognitive impairments [27,28]. There is limited research into the cognitive effects of MXE, though three cases of acute MXE causing cerebellar toxicity  and cases of dissociation and catatonia have been reported . More research is needed to investigate the chronic effects of MXE on cognition and the bladder, as this study only speaks to the acute effects and motivators of use of MXE.
Given information concerning toxicology is relatively limited; the same harm reduction advice applies to MXE as for ketamine and any novel psychoactive drug of whose content and potency the user is uncertain of. These are similar to those recommended in a British Medical Journal editorial concerning mephedrone just before it was legislated against in 2010 . The key messages for users are that the risks of harm are greater in those with underlying physical and psychiatric pathologies and that use should be avoided in combination with prescribed medications and other drugs and alcohol. Users should be advised to avoid first experimenting with MXE and not to use it on their own.
That most people obtained MXE from a friend or from a website confirms findings from other studies on novel psychoactive substances on the importance of these two sources and in particular of the Internet as a distribution channel for legal compounds [31,32]. It also highlights the attraction of legal alternatives to already used drugs as it has happened in the recent past for cannabis (synthetic cannabinoids) and cocaine/ecstasy (mephedrone), although legality is not the only motivator for taking novel substances . Follow-up studies will be required to determine whether the ban reduces marketing and availability and is an effective deterrent to use.
Finally, this study confirms the usefulness of conducting survey of key informants and early experimenters to quickly garner essential information on novel, emerging psychoactive substances [17,20,21,34].
The study, although of a good size, is limited by the self-nominating nature of the sample and the self-report methodology. These limitations and others are discussed fully in Winstock et al. [16,18,35]. We have previously shown that self-report studies among dance drug-using populations may be a valid and effective tool for monitoring drug trends and detecting the appearance of new drugs [17,35]. Drug users who respond to online drug surveys promoted by the popular press and specialist dance music magazines can be seen to represent a sentinel population of drug users likely to represent harder end of users. We accept that when judged against traditional epidemiological criteria for a good public health surveillance system, this method has significant limitations, not least because it recruits from a self-nominating population that is relatively poorly characterised. In addition, it relies upon population self-reported experiences with a substance whose true composition is uncertain. High levels of polydrug use, confounding effects from other substances and recall bias are all significant issues [17,18]. No further information was obtained on dose and there was an absence of detailed effect profiling, which is an area that the research team is currently exploring. It is also very possible that the effect profile with psychedelics will change with repeated episodes of use. However, the very early stages of the appearance of new drug approaches such as these are often the only initial ways of accessing date rapidly and efficiently. We believe our approaches can usefully guide future research as well as inform those who choose to use novel substances.
We would like to thank Luke Mitcheson for his support over the years in helping run these surveys and the thousands of participants who give so generously of their time each year. We would also like to thank the staff at MixMag and The Guardian. Finally, we would like to thank Stuart Newman for his programming skills and patience.
Conflict of interest declared. Dr Winstock is founder and managing director of Global Drug Survey, the independent drug use data exchange hub that conducted the study. No external funding was received for this study. All authors have approved the final manuscript.
A. R. W. devised the study and developed the questionnaire. A. R. W. oversaw the data collection. A. R. W. and P. D. conducted the statistical analysis and A. R. W., P. D., W. L. and R. B. contributed to the preparation of the manuscript and approved the final draft.