Combining ecstasy and ethanol: higher risk for toxicity? A review.

Ecstasy use is commonly combined with ethanol consumption. While combination drug use in general is correlated with a higher risk for toxicity, the risk of the specific combination of ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) and ethanol is largely unknown. Therefore, we have reviewed the literature on changes in MDMA pharmacokinetics and pharmacodynamics due to concurrent ethanol exposure in human, animal and in vitro studies. MDMA pharmacokinetics appear unaffected: the MDMA blood concentration after concurrent exposure to MDMA and ethanol was comparable to lone MDMA exposure in multiple human placebo-controlled studies. In contrast, MDMA pharmacodynamics were affected: locomotor activity increased and body temperature decreased after concurrent exposure to MDMA and ethanol compared to lone MDMA exposure. Importantly, these additional ethanol effects were consistently observed in multiple animal studies. Additional ethanol effects have also been reported on other pharmacodynamic aspects, but are inconclusive due to a low number of studies or due to inconsistent findings. These investigated pharmacodynamic aspects include monoamine brain concentrations, neurological (psychomotor function, memory, anxiety, reinforcing properties), cardiovascular, liver and endocrine effects. Although only a single or a few studies were available investigating these aspects, most studies indicated an aggravation of MDMA-induced effects upon concurrent ethanol exposure. In summary, concurrent ethanol exposure appears to increase the risk for MDMA toxicity. Increased toxicity is due to an aggravation of MDMA pharmacodynamics, while MDMA pharmacokinetics is largely unaffected. Although a significant attenuation of the MDMA-induced increase of body temperature was observed in animal studies, its relevance for human exposure remains unclear.

Cannabis and COVID-19: Reasons for Concern.

The lockdown measures implemented to curb the spread of SARS-CoV-2 may affect (illicit) drug consumption patterns. This rapid response study investigated changes in cannabis use in a non-probability sample of cannabis users in the Netherlands during the early lockdown period. We fielded an online cross-sectional survey 4-6 weeks after implementation of lockdown measures in the Netherlands on March 15, 2020. We measured self-reported \motives for changes in use, and assessed cannabis use frequency (use days), number of joints per typical use day, and route of administration in the periods before and after lockdown implementation. 1,563 cannabis users were recruited. Mean age was 32.7 ± 12.0 years; 66.3% were male and 67.9% used cannabis (almost) daily. In total, 41.3% of all respondents indicated that they had increased their cannabis use since the lockdown measures, 49.4% used as often as before, 6.6% used less often, and 2.8% stopped (temporarily). One-third of those who were not daily users before the lockdown became (almost) daily users. Before the lockdown, most respondents (91.4%) used cannabis in a joint mixed with tobacco and 87.6% still did so. Among users of joints, 39.4% reported an increase in the average number consumed per use day; 54.2% stayed the same and 6.4% used fewer joints. This rapid response study found evidence that during the lockdown more users increased rather than decreased cannabis consumption according to both frequency and quantity. These data highlight the need to invest more resources in supporting cessation, harm reduction, and monitoring longer term trends in cannabis use.