Purpose: Immunological; to examine basal immunological function in regular ecstasy users to see whether any long-term or residual effects on the immune system were present. Specific hypothesis tested - that repeated perturbation of cell-mediated immunity by repeated doses of MDMA might significantly reduce function of cell-mediated immunity in regular ecstasy users.

Design: Retrospective (non-experimental) between group design, with drug use (ecstasy use versus no ecstasy use) serving as between-subjects factor, with all participants undergoing blood draws on at least two points in time.

Subjects: 30 male ecstasy users and 24 non-drug users residing in or near Barcelona (Spain). Non-drug user controls were apparently recruited from healthy blood donors. No information is offered on recruitment method for ecstasy users, but past studies performed by this team have recruited people via word of mouth. Matching - Groups were matched on age and physiological characteristics.

Criteria for Inclusion - Ecstasy Users - Male, healthy, as determined via physical and psychiatric examination, with no current drug or alcohol dependence except nicotine, reported having used ecstasy at least 5 times in lifetime, and abstinence from any psychoactive substance on the study day, with abstinence verified by urinalysis. Non-Drug Users - Never having used any illicit drugs, matched on age and physical characteristics, possibly being male, though details of non-drug user gender not mentioned.

Drug Use Parameters - No information is provided beyond inclusionary criteria, though it is reported that 6 of 30 reported lifetime use of ecstasy at 5 to 50 times. No information is provided on average dose per use, frequency of use, duration of use or time since last use. Presumably time since last use was at least 1 day prior to study day, with abstinence verified via urinalysis. Other drugs - All ecstasy users used cannabis regularly, and at least some had used cocaine or methamphetamine at least once.

Group Demographics and Matched Variables - The authors matched ecstasy users and non-users on the basis of age, weight and height; it is unclear but seems likely that samples were matched on gender as well. Gender, as M/F ratio - Ecstasy users, 30/0, Non-Drug users, unknown (possibly 24/0). Age - Average age of ecstasy users was 24 years (range = 20-36 years). Information not provided on mean age of non-drug using controls, though it is stated that samples were matched by age. Weight, in kg - Ecstasy users weighed, on average, 67.9 kg (range = 56.5-86 kg). No information provided on weight of non-drug using controls. Height, in cm - Average height of ecstasy users was 175.4 cm (range = 167-189 cm.) No information provided about non-drug using controls. Education - No information on years of education, in years, for either sample.

Measures: Complete blood profile and cell count conducted on blood drawn from each participant at baseline. Number of lymphocytes counted by cytometer. Dual-color immunophenotyping used to detect immune cell types; helper-inducer, cytotoxic-suppressor, natural killer, mature B and T lymphocytes.

Analyses: Not clearly stated. It would appear that comparisons were made for each cell type separately, either using a one-way ANOVA with drug use (ecstasy use versus no drug use) as a between-subjects variable or via a two-sample t-test.

Results - Significant Differences Found: Number of NK cells in basal blood samples from ecstasy users was significantly lower than number of NK cells in non-drug users. There was a trend for lower numbers of lymphocytes, T cells and CD4 cells in baseline blood samples from ecstasy users than in non-drug using controls.

Results - No Significant Differences: Ecstasy users and non-drug using controls had similar amounts of CD8 cells and B cells, and while there was a trend for ecstasy users to have lower total numbers of lymphocytes, T cells and CD4 cells, they were not significantly different from cell counts done in non-drug using controls. Immunological function for all participants was within normal range.

Overall Effects: Immunological function in 30 male ecstasy users was compared with immunological function in 24 non-drug using blood donors matched with ecstasy users on age and physiological characteristics (possibly, but not necessarily, including gender). Cell counts were conducted on ecstasy users on a day of verified abstinence from ecstasy. Ecstasy users had significantly fewer natural killer (NK) cells than did non-drug using controls, and ecstasy users had lower numbers of lymphocytes, T cells and CD4 cells than controls, though not to a significant degree. However, no differences were found in numbers of CD8 or B cells, and immune function was within the normal range for all participants. The overall effects of these changes are that of reduced cell-mediated immunity, including greater susceptibility to infection. The authors' hypothesis is mostly confirmed, as some measures of cell-mediated immunity are lower in ecstasy users than in non-users. However, reduced immune function appears to affect specific cell types, and not the immune system generally.

Comments: To date, this is the first paper to compare specific immunological functions in regular ecstasy users with non-drug using controls. It is interesting to note that while MDMA acutely increases NK cell counts after administration (reported in same paper, also see Pacifici et al. 2000), chronic use of ecstasy and other drugs reduces NK cell count. On the other hand, acute reductions in lymphocyte count, lymphocyte reactivity and CD4 cell count after MDMA administration in healthy ecstasy users (reported earlier in the same paper and in Pacifici et al, 2000) is not associated with an increase in numbers of these cells after drug effects have ceased. In fact, there was a trend for reduced lymphocyte numbers in ecstasy users. Because all ecstasy users were also habitual cannabis users and consumed other drugs as well, it might be the case that some of the reduction in cell-mediated immunity is associated with use of other drugs, or with interactions between one or more substances. Because the findings were reported in a review of immunological studies conducted by the team, information on the drug use parameters and other demographic features of ecstasy users and controls are not presented here. It is hoped that in future, this information will be described in greater detail in other publications. Study limitations include retrospective study design, no examination of the effects of consumption of other drugs, and relatively small sample size. Since all ecstasy users were male, and this may have been true of non-drug users as well, it is unclear whether these findings can be extended to women.