Discussion
psychiatric, anxiety, Nausea
DISORDERS
The main finding of the present study was that MDMA co-administration did not relevantly alter acute psychedelic effects of LSD while producing greater autonomic effects compared with LSD alone. However, LSD + MDMA co-administration prolonged acute subjective effects compared with LSD alone. The prolonged LSD response is consistent with a higher plasma concentration of LSD (CTherefore, we hypothesized that adding MDMA to LSD would enhance positive mood effects and decrease anxiety that is associated with the LSD response. The same approach is also used by recreational substance users when combining MDMA and LSD in “candyflipping.” Contrary to our expectation, the present controlled study showed that the co-administration of LSD and MDMA and administration of LSD alone produced overall very similar subjective effects on the VAS, 5D-ASC, and MEQ. However, although no significant differences were seen, the addition of MDMA tended to nonsignificantly increase ratings of “happy,” “open,” and “trust” on the VAS and “well-being” on the AMRS, especially in the beginning of the experience compared with LSD alone. Additionally, ratings of “well-being” on the AMRS increased at the beginning of the drug response but dropped at 6 h when the MDMA effect ended. This may indicate some enhanced MDMA-typical subjective effects with the combination compared with LSD alone. Furthermore, we only tested single dose levels of both LSD and MDMA and co-administration at the same time. An LSD base dose of 100 µg has previously been used in several studies in healthy participants [LSD, MDMA, and their combination produced significant autonomic stimulant effects as reported previously [MDMA had no relevant effects on the quality of the acute response to LSD, whereas the LSD + MDMA combination resulted in a longer effect duration compared with LSD and MDMA alone. This can be explained by higher plasma concentrations (both CWe also evaluated selected interactive endocrine effects of LSD and MDMA. The marked release of oxytocin may mediate some of subjective effects of MDMA [The present study also provided insights into the ways in which neurotransmitters mediate subjective effects of psychoactive substances. LSD directly activates the serotonin 5-hydroxytryptamine-2A (5-HTWe found no indication of greater serotonin toxicity when MDMA and LSD were co-administered. MDMA did not increase thermogenic effects of LSD alone. Nausea was similarly frequent after the co-administration of LSD and MDMA and the administration of either substance alone.The role of dopamine in subjective effects of LSD remains unclear [The present study has several strengths. We used a relatively large study sample (Notwithstanding these strengths, the present study also has limitations. We used only one dose of LSD and MDMA. The study used a highly controlled hospital setting and included only healthy volunteers. Thus, people in different environments and patients with psychiatric disorders may respond differently to these substances. Finally, the outcome measures may not have been sufficiently sensitive to capture all aspects of a psychedelic experience and/or very subtle differences between acute effects of LSD + MDMA compared with LSD alone.