The increased availability of 4MMC to buy over the internet, combined with the declining quality of other drugs (like MDMA or cocaine) has contributed to a marked increase in mephedrone use in Europe and the UK. Of course, the prevalence of mephedrone use has since dropped from 4.4% to 0.5%. In part, this is due to the legal status of mephedrone. Additional to this, the Psychoactive Substance Act of 2016 (British Home Office 2016) restricting the production, sale and supply of new psychoactive substances. Naturalistic studies on humans demonstrate that mephedrone dramatically improves working memory, increases psychomotor speed, and causes a significant increase in «wanting».
Also, according to many different observational studies, forum reports and individual case reports, mephedrone use leads to increased mood, euphoria, improved concentration, increased information processing speed, increased talkativeness, increased energy, jaw clenching, increased empathy, decreased appetite and increased confidence and appreciation for music. As for side effects, the most common side effects of 4mmc use are cardiac, neurological, and psychiatric effects. Naturalistic studies on humans demonstrate that mephedrone dramatically improves working memory, increases psychomotor speed, and causes a significant increase in «wanting». To date, there are sporadic data regarding the subacute effects of mephedrone, with published data mostly based on surveys of recreational users. There have been studies on verbal memory and verbal fluency where it has been shown that mephedrone worsens test results relative to a control group. Also, the acute and subacute effects of mephedrone and MDMA in young users were studied. The results showed more negative effects of mephedrone relative to MDMA. However, all of these studies were cross-sectional and the data were retrospective. Furthermore, the study did not control for other possible confounding variables such as psychopathology, other substance use and lack of sleep due to use. In general, the results on sub-acute or similar to sub-acute effects of mephedrone indicate effects comparable to those of amphetamine and ecstasy or more adverse than those of ecstasy. In our study, we studied the subacute effects of mephedrone using volunteers who use mephedrone. We observed them over a period of time to see if those who used mephedrone differed from those who did not. The sample was divided into two groups. The scheme we used allowed us to distinguish the true subacute action of mephedrone from its chronic action and the subacute action of any other substance.
How did we conduct the study?
There were two groups in this study. The first group were those who decided to use mephedrone after a baseline assessment (21 volunteers), and the second group were those who decided to abstain throughout the study period (25 people). A total of 46 people (22 men and 24 women) between the ages of 19 and 36 participated in the study. Descriptive statistics of demographics, BIS-11, SCL-90-R, delayed discounting, DSM dependence, FAST and smoking status are presented in Table 1. No significant group differences were observed on any measure. FAST Fast Alcohol Screening Test, BIS-11 trait impulsivity, SCL-90-R psychopathology. The criterion for admitting participants to the study was the mandatory regular recreational use of mephedrone, at least once a month for a month. Each participant received nine Daily Rating Scale (DRS) envelopes. The experimenter contacted each participant daily for nine days. Participants completed the DRS form daily and sealed the envelope with the completed form (with the envelopes coded to ensure that their responses could not be cross-checked). Of the 21 participants who chose to use mephedrone during the testing period, 4 used it on the day of the baseline assessment, 7 used it on the second day of the experiment, and 10 used it on the third day of the experiment. Alcohol use was assessed through the four-item Fast Alcohol Screening Test (FAST). Past and current substance use was assessed with a questionnaire that requested participants to indicate if they had used a substance, and if so, the age of first use, time since last use, frequency of use and usual dose per session. Mephedrone craving was assessed with a 40-item questionnaire adapted from the Desires for Speed Questionnaire. A specific Mephedrone Questionnaire that included nine VAS items relating to attitudes to mephedrone, and seven items based on the DSM-IV-TR criteria for substance dependence was also administered. Psychopathology was assessed with the SCL-90-R, impulsivity was assessed with the BIS-11. Also, we performed a daily assessment of the following parameters: mood, cognition, hunger, sleep, physical and psychological problems, craving for mephedrone and consumption of any other psychoactive substances.
The data obtained and their interpretation
Our study is the first and only empirical experiment to examine the subacute effects of mephedrone in regular 4MMC users, where the above parameters were assessed daily and several baseline and associated factors were controlled. In the analysis of baseline data, the two groups did not differ in personality characteristics and psychopathology. The two groups were similar in previous mephedrone use. Negative mood was markedly elevated within four days of mephedrone use, and physical problems and fatigue were significantly elevated within two days or more of use. Also, there were significant differences in subacute effects when controlling for the combined use of alcohol, cannabis, and mephedrone.
Psychopathology, impulsivity, delayed discounting, sub- stance use, alcohol problems and demographics did not differ significantly between those who opted to consume mephedrone and those who did not. These data point to the true effect of mephedrone, not to an effect that is due to psychopathology or past drug use. The present results suggest that the sample in our study was more homogeneous than in previous experiments (such as Parrot and Huxster). Participants who chose not to use mephedrone during the study also reported higher levels of craving for mephedrone at baseline and also reported high levels of pleasure when using mephedrone. It is likely that participants who chose not to use mephedrone already knew they would not take it. These findings are consistent with Tiffany’s model of craving. According to this model, thoughts, actions or associations to substance use (for example questions about the substance as in the questionnaires administered) activate substance use action schemata. Also, our results show that mephedrone use during the study was not related to psychopathology, impulsivity, past use, or other demographic characteristics. Other differences determining participants’ affiliation with the desire to use have not been considered and are beyond the scope of this discussion. Nevertheless, it is interesting for future research to shed light on this issue, as it could have a significant impact on subjective experience.
Symptoms such as fatigue and physical problems increased markedly during the first 24 hours after mephedrone use, then tended to decrease. The results are similar to other studies of the subacute effects of MDMA with respect to cognitive impairment and negative mood. And the findings obtained by Parrott and Lasky confirmed our conclusions. However, some of the past studies did not control for associated factors such as sleep deprivation. Our study shows that these effects persist even after controlling for sleep deprivation. Subacute effects of paranoia differed significantly between groups, but were not significant after cannabis control, alcohol use, and sleep use, suggesting that paranoia is a symptom of these factors. Also, the subacute effects of mephedrone indicate an increased level of cognitive impairment. This is also consistent with the results of other studies of subacute effects of MDMA on cognitive impairment, in which no further statistically significant effects were found after controlling for sleep and other side effects. Most likely, this difference is due to the fact that sleep deprivation in combination with a psychoactive substance causes an increase in cognitive impairment. We demonstrate the importance of controlling for other possible comorbidities because some symptoms (e.g., increased paranoia and cognitive impairment) may be related to more than just substance use. This is very important in naturalistic studies in which polydrug use is more the norm than the exception.
Although our study design allowed us to control for differences between groups at baseline, a major limitation was the use of solely subjective measures. Despite this, measures of mood, impulsivity, and attraction were statistically significant between groups. We think that in the future it will be important to additionally record other daily events, increasing the number of criteria in the scales used. Also, it would be useful to record sleep hours to identify the degree of deprivation, as this could have a greater influence on the measured subacute effects. The present study provides more extensive evidence of the negative effects of mephedrone on humans. After controlling for restless sleep at baseline and subsequent combined alcohol and cannabis use, the effects of mephedrone are evident (including negative mood, physical problems, and fatigue). Our proposed experimental design allows us to identify and distinguish the true subacute effects of 4MMC from its chronic effects. Thus, we have provided the first clear indication of the extent and attraction of specific subacute effects of mephedrone in its users.
