Adam R. Winstock

Mephedrone: use, subjective effects and health risks.

AIMS To assess the patterns of use, subjective effect profile and dependence liability of mephedrone, supported by corroborative urine toxicology. DESIGN Cross-sectional structured telephone interview. SETTING UK-based drug users associated with the dance music scene. PARTICIPANTS A total of 100 mephedrone users, recruited through their involvement with the dance music scene. MEASUREMENTS Assessment of pattern of use, acute and after effects, DSM dependence criteria and gas chromatography-mass spectrometry urinalysis. FINDINGS Mephedrone consumption results in typical stimulant-related subjective effects: euphoria, increased concentration, talkativeness, urge to move, empathy, jaw clenching, reduced appetite and insomnia. Thirty per cent of the sample potentially met criteria for DSM-IV dependence and there was evidence of a strong compulsion to use the drug (47% had used the drug for 2 or more consecutive days). Self-reported recent consumption of mephedrone was confirmed by toxicological analysis in all of the 14 participants who submitted a urine sample. CONCLUSION Mephedrone has a high abuse and health risk liability, with increased tolerance, impaired control and a compulsion to use, the predominant reported dependence symptoms.

Synthetic cannabis: A comparison of patterns of use and effect profile with natural cannabis in a large global sample

BACKGROUND The last decade has seen the appearance of myriad novel psychoactive substances with diverse effect profiles. Synthetic cannabinoids are among the most recently identified but least researched of these substances. METHODS An anonymous online survey was conducted in 2011 using a quantitative structured research tool. Missing data (median 2%) were treated by available-case analysis. RESULTS Of 14,966 participants, 2513 (17%) reported use of synthetic cannabis. Of these, 980 (41% of 2417) reported its use in the last 12 months. Almost all recent synthetic cannabis users (99% of 975) reported ever use of natural cannabis. Synthetic cannabis reportedly had both a shorter duration of action (z=17.82, p<.001) and quicker time to peak onset of effect (z=-9.44, p<.001) than natural cannabis. Natural cannabis was preferred to synthetic cannabis by 93% of users, with natural cannabis rated as having greater pleasurable effects when high (t(930)=-37.1, p<.001, d=-1.22) and being more able to function after use (t(884)=-13.3, p<.001, d=-0.45). Synthetic cannabis was associated with more negative effects (t(859)=18.7, p<.001, d=0.64), hangover effects (t(854)=6.45, p<.001, d=0.22) and greater paranoia (t(889)=7.91, p<.001, d=0.27). CONCLUSIONS Users report a strong preference for natural over synthetic cannabis. The latter has a less desirable effect profile. Further research is required to determine longer term consequences of use and comparative dependence potential.

Ketamine - From medicine to misuse

This review describes the medical, research and recreational uses of ketamine, an anaesthetic derivative of phencyclidine that has dissociative, analgesic and psychedelic properties. Ketamine has a complex mechanism of action that is further complicated by stereoselectivity; however, antagonism of glutamate NDMA receptors is thought to underlie its analgesic, dissociative and neuroprotective effects. While ketamine use in medical and veterinary settings is well documented and has a good safety record, the increase in its unregulated use outside of such controlled environments is a cause for concern. The impact on higher centres in the brain, particularly altered perception of auditory, visual and painful stimuli, results in a general lack of responsive awareness that puts the recreational user at (often unrecognised) risk of personal harm. The perceptual and mood changes observed in those who have consumed ketamine are highly sensitive to age, dose, route of administration, previous experience and setting. At low doses, stimulant effects predominate and the effect of environmental conditions are significant; with higher doses, psychedelic effects predominate and the effect of the environment diminishes. The potential of ketamine as a novel clinical and research tool is matched by its abuse potential outside medical settings.

Areca nut‐abuse liability, dependence and public health

Abstract To define a dependence syndrome may convey attention upon a public health problems hitherto relatively ignored. It may, however, stigmatize substance use, especially when western diagnostic criteria are applied to essentially culture‐bound substances. However, when the pattern of use of a substance results in significant personal harm, then whether dependence exists or not is less important than developing an appropriate response, if its use is associated with significant morbidity and mortality. Such is the case with areca nut, the fourth most commonly used drug in the world after tobacco, alcohol and caffeine. In this paper I will explore its use and properties with respect to its abuse and dependence liability and consider the associated implications for public health.

Mephedrone: still available and twice the price

In April, 2010, the β ketoamfetamine stimulant mephedrone (4-methylmethcathinone) and several similar compounds were classified as Class B substances in the UK under the Misuse of Drugs Act. Legislation was prom pted by public health concerns, with the expectation that these controls would limit availability and use. As part of our group’s ongoing research into new synthetic drugs, we did an online survey of 150 mephedrone users (average age 24 years) in June, 2010. We have compared our fi ndings with those from a previous online survey we did in November, 2009, and a telephone interview of users in 2010 before the legislation. Our key objective in this comparison was to assess whether the new legislative control of mephedrone had aff ected its availability and use. Of the 150 respondents to the 2010 survey, 95 (63%) reported that they had continued to use mephedrone since the law had changed. 52 of these respondents (55%) said that they intended to continue using the same amount of mephedrone, and 38 (40%) reported that they would now use less. 85 respondents (57%) had bought mephedrone from a dealer, an increase of almost 40% from the 41% who had reported purchasing from a dealer in the telephone study of users done before legislation. In the current 2010 survey, the mean price per gram paid for mephedrone was £16 (mode, £20), compared with a mean price of £10 when the drug was obtainable online before legislation. These fi ndings suggest that classifi cation of mephedrone has had a limited eff ect on controlling its availability and use. Before the introduction of the legislation, users generally obtained mephedrone via the internet. Now they buy it from street dealers, on average at double the price. We suspect that, in time, there are likely to be reductions in purity, and increases in health harms.

5-Year Trends in Use of Hallucinogens and Other Adjunct Drugs among UK Dance Drug Users

Aims: To describe and assess trends in the use of hallucinogens and other adjunct drugs over a 5-year period. Design: Repeated-measures cross-sectional survey. Setting and Participants: Annual magazine-based survey targeting people who use drugs in dance contexts. Measurements: Lifetime use prevalence (ever used); age of first use; current use prevalence (any use within the last month), and extent of use within the last month (number of days used) for LSD, psilocybin, ketamine, GHB and nitrates. Findings: Prevalence increases for psilocybin, ketamine, GHB and nitrates use have been detected, with a sharp recent rise in current psilocybin use in 2002–2003 contrasting with more gradual and comprehensive evidence of increased ketamine use throughout the period 1999–2003. The declining prevalence of LSD use in general population surveys is replicated in this sentinel population study. Conclusions: The rise in prevalence of hallucinogen and other adjunct drugs identified among dance drug users may be mirrored by wider prevalence increases among young people with a consequent need to study these trends carefully and to develop effective interventions, where required.

THE PREVALENCE AND NATURAL HISTORY OF URINARY SYMPTOMS AMONG RECREATIONAL KETAMINE USERS

Study Type – Symptom prevalence (prospective cohort)

Use of Silk Road, the online drug marketplace, in the United Kingdom, Australia and the United States

AIMS To investigate the prevalence of awareness of the online illicit drug marketplace Silk Road (SR), consumption of drugs purchased from SR and reasons for use and non-use of SR. DESIGN AND SETTING Global Drug Survey: purposive sample collected in late 2012. PARTICIPANTS The base sample (n = 9470) reported recent drug purchase and resided in the United Kingdom (n = 4315, median age 24, 76% male), Australia (n = 2761, median age 32, 76% male) or the United States (n = 2394, median age 21, 80% male). MEASUREMENTS Online questionnaire. FINDINGS A total of 65% of US, 53% of Australian and 40% of UK respondents had heard of SR; 18% of US, 10% of UK and 7% of Australian respondents had consumed drugs purchased through SR. Across the three countries, 3,4-methylenedioxy-N-methylamphetamine (MDMA) was the most commonly purchased drug (53-60%), followed by cannabis (34-51%), lysergic acid diethylamide (LSD) (29-45%) and the 2C family (16%-27%). The most common reasons for purchasing from SR were wider range (75-89%), better quality (72-77%), greater convenience (67-69%) and the use of vendor rating systems (60-65%). The most common reasons for avoiding SR purchase were adequate drug access (63-68%) and fear of being caught (41-53%). Logistic regressions found that, compared with people from the UK, Australians [odds ratio (OR) = 3.37; 95% confidence interval (CI) = 2.29, 4.97) and Americans (OR = 1.46; 95% CI = 1.10, 1.94) were more likely to use SR due to lower prices; and to avoid SR purchase due to fear of being caught (Australia: OR = 1.65; 95% CI = 1.39, 1.96; USA: OR = 1.62; 95% CI = 1.37, 1.92). CONCLUSIONS While reasons for Silk Road use accord with broader online commerce trends (range, quality, convenience, ratings), its appeal to drug purchasers is moderated by country-specific deterrents and market characteristics.

What should be done about mephedrone

We should focus on crafting the most effective public health response

Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population

Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was con.rmed by using urinary drug screening preand post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 ± 0.29 to 1.43 ± 0.41 pmol/l), but fell in other participants (1.23 ± 0.42 to 1.16 ± 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 ± 0.29 to 2.43 ± 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 ± 0.36 pmol/l to 1.89 ± 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p= 0.001 and p= 0.003, respectively) and between change in urinary osmolality (p< 0.001) and MDMA use, with the pattern of change being consistent with the induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA. This report demonstrates SIADH in ecstasy-using ‘clubbers’, which has important clinical implications.