Popularized in the late 90s rave scene, mixing MDMA and LSD, also known as candy flipping, remains hugely popular among psychonauts and partygoers today.
Described anecdotally as “one of the most amazing and enjoyable mind-altering experiences,” researchers are curious whether MDMA could improve outcomes in LSD-assisted therapy. A recent University Hospital Basel (UHB) trial investigated this possibility, marking the first clinical study to compare MDMA and LSD with their combination. The results were published in Nature.
“The acute subjective effects of lysergic acid diethylamide (LSD) are mostly positive; however, negative effects, such as anxiety, may occur,” says Isabelle Straunmann, a PhD in Clinical Research at UHB who led the study. “MDMA produces marked positive subjective effects and we hypothesized that when combined with LSD it can induce an overall more positive experience than LSD alone.”
Twenty-four study participants were randomly assigned four different treatment conditions – MDMA, LSD, MDMA and LSD combined, or a placebo – without being told which they received. Treatments were provided in a calm, supported hospital environment, and participants were given rating scale scores to measure mood and drug-related effects.
Participants who received a combination of LSD and MDMA scored higher on measures of well-being, happiness and trust during their experience, compared to those who took LSD alone. However, these differences were small and non-significant according to statistical scientific analysis. The study authors therefore concluded MDMA didn’t “relevantly” impact the psychedelic effects of LSD, though their results indicated “some enhanced MDMA-typical subjective effects with the combination compared with LSD alone.”
The study participants who took the combination “actually did feel many effects that recreational users reported,” says Straunmann. “However, LSD alone already induces these effects quite strongly, so we could not see a difference between the conditions.”
Longer-lasting effects were observed following MDMA and LSD combined compared to either substance on its own. The authors speculated that because MDMA interacts with enzymes that break down LSD, it causes LSD to remain in the bloodstream longer.
Physiological measurements showed heart rate and blood pressure increased most substantially following the combination treatment. Clinically, Staunmann explained this finding “could be relevant in patients who have other underlying diseases such as hypertension… [but] other than that, we did not see anything, which would indicate that the co-administration of LSD+MDMA would be problematic.”
In regards to safety, drugs harm-reduction expert Adam Waugh commented that, “the combination of MDMA and LSD is generally viewed as a low risk combination, in the sense it isn’t likely to cause harm to someone’s physical health.” Nonetheless, he noted that psychologically “MDMA can increase the intensity of a trip substantially – which for some people can lead to an overwhelming experience.”
Although LSD is considered relatively physically safe, potential psychological side effects
have raised concern about its use in psychedelic therapy. For instance, anxiety was noted as a significant side effect during LSD-therapy in another recent UHB clinical study.
Psychiatrist and MDMA researcher Dr. Ben Sessa believes MDMA could theoretically mitigate this risk. Hypothetically, you would expect MDMA to inhibit the fear response which may occur with LSD,” he says. “Anecdotal evidence from recreational users would support this as people who use MDMA with psychedelics report it makes the trip more manageable.”
Brain scans show MDMA decreases activity in the amygdala, a structure that detects fear and threat. Moreover, MDMA increases the production of oxytocin, sometimes called “love molecule,” which is a chemical messenger important for empathy and bonding. With a capacity to subside fear and decrease amygdala activity, oxytocin has been proposed to treat anxiety disorders.
In the context of psychedelic therapy, Staumann says, “[MDMA and LSD] could be a combination for patients who have never experienced an altered state of consciousness and who are frightened of such an experience, no matter the specific clinical indication,” says Staumann.
The authors also proposed MDMA could increase long-term patient benefits, based on previous research. For instance, an Imperial College London trial found patients who had decreased anxiety during psilocybin therapy showed more significant antidepressant effects five weeks following their treatment.
Other studies have found that increased positivity during psychedelic experiences can improve patient outcomes. According to Sessa, LSD and MDMA’s capacity to increase euphoria, openness, and mood could “from a psychological aspect expect LSD and MDMA to work synergistically.”
The study results also demonstrated a biological synergy, with oxytocin concentrations highest in participants’ blood samples following the combination treatment. However, the authors highlighted that such changes didn’t produce any clinically noticeable effects.
MDMA’s prospects for improving LSD warrants further research despite the study’s nonsignificant findings, wrote the authors. They explained how their study design could have influenced their results. For instance, they suggested MDMA’s impact could have been more prominent with a larger LSD dose or if provided at a different time point during the participant’s LSD experience.
“You could look at this study and say the hypothesis is wrong. You could also say that if the conditions were different you could have got a different response,” says Sessa. “I think you still have lots of anecdotal evidence to suggest the two work well and therefore much more research is needed.”
Beyond MDMA and LSD, forum sites such as Reddit and Erowid describe a myriad of different psychedelic drug cocktails. Other recreational MDMA combinations, or “flips,” include “hippie flipping” with psilocybin mushrooms and “kitty flipping” with ketamine. Similar to the candy flip, such mixtures are commended in anecdotal reports.
Going forward, Staumann anticipates her lab will investigate the effects of co-administering MDMA with other psychedelic compounds, looking at what they may offer for the rapidly evolving psychedelic therapy landscape.