MDMA Appears To Reduce ‘Challenging Experiences’ Associated With Psilocybin And LSD, Study Finds

While using psilocybin mushrooms or LSD can provide enjoyable sensations and useful insights, such trips can sometimes come with uncomfortable effects—including intense grief and fear. But pairing psychedelics with a small dose of MDMA, a new study says, seems to both reduce those feelings of discomfort and highlight more positive aspects of the experience.

The study, conducted by researchers at New York University’s Langone Center for Psychedelic Medicine and the Centre for Psychedelic Research at Imperial College London, was published last week in the peer-reviewed journal Scientific Reports. Its findings suggest that “co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences,” potentially allowing for better treatment of certain mental health disorders.

“Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear,” authors wrote, “as well as increased self-compassion, love, and gratitude.”

To arrive at the results, researchers surveyed 698 people who had recently used psilocybin or LSD. Of those, 27 reported co-using MDMA with the psychedelics. Analyzing participants’ reported experiences, along with dose levels of the substances taken, the team then compared the reported effects of co-use to those of using a psychedelic by itself.

Effects varied greatly by dosage. For example, taking a low dose of MDMA along with psilocybin or LSD “was associated with significantly lower levels of total challenging experience,” compared to people who hadn’t used MDMA. But that difference disappeared when participants took medium to high doses of MDMA. Similar results were observed for grief and fear.

Small amounts of MDMA also seemed to amplify positive experiences, for example leading to “higher levels of self-compassion, feelings of love, and experiences of gratitude.”

For some feelings—including compassion and “mystical-type experiences”—there was no significant difference between the psychedelics-only group and those who co-used MDMA, “suggesting that these experiences may be unaffected,” authors wrote. “However, it is noteworthy that (compared with LSD/psilocybin alone) co-use of low dose MDMA was associated with relatively higher mean scores for compassion and relatively lower mean scores for total mystical-type experience.”

Other results were complicated to parse, they added, and underscore the need for further research.

Aside from the study’s implications for people who use drugs, the findings may also allow more people to benefit from psychedelic therapies. Both psilocybin and LSD have “therapeutic potential for treating psychiatric disorders and mental health concerns,” the study acknowledges, but psychedelic experiences can be hard to control precisely. That, aside from the substances’ legal status, can make both patients and therapists wary.

“A primary concern associated with classic psychedelics relates to their alteration of consciousness,” the study says, “which can range from highly positive ‘peak’ experiences to psychologically challenging experiences (often referred to as ‘bad trips’), such as grief, paranoia, and fear.”

In one clinical trial, for example, “79% of individuals reported experiencing sadness, 56% reported experiencing anxiousness, and 77% reported experiencing emotional or physical suffering,” researchers noted. “Among healthy individuals that were administered psilocybin, 31% of individuals reported experiencing strong or extreme fear and 22% reported that a significant portion or their entire psilocybin experience was characterized by anxiety or unpleasant psychological struggle.”

“Although challenging experiences are sometimes described as ultimately beneficial or therapeutic,” the study explains, “these experiences can sometimes contribute to post-acute distress, functional impairment, and medical attention seeking.” In the worst cases, there are “reports of psychiatric diagnoses, suicidality, and harm to self and others during and after challenging psychedelic experiences.”

Understandably, those side effects are cause for concern. They’re “commonly noted as a reason that health care providers and users are reluctant to suggest or receive treatment with classic psychedelics.”

As the new paper acknowledges, several past studies have reported on co-use of psilocybin or LSD along with MDMA, with some findings overlapping with the current study.

“Co-use of 3,4-methylenedioxymethamphetamine (MDMA) with psilocybin (referred to as ‘hippy flipping’) and LSD (referred to as ‘candy flipping’) is one method that is reportedly used to reduce challenging experiences and enhance positive experiences,” it says. “MDMA, a potent serotonergic entactogen/empathogen, induces the release of serotonin, norepinephrine, dopamine, vasopressin, and oxytocin; dampens amygdala blood flow; decreases feelings of fear and sadness; and may increase positive feelings, including love, compassion, and self-compassion.”

The findings seem to corroborate what many people who use psychedelics already believe. Past research has found rates of such MDMA co-use ranging from 8 percent to 52 percent of people who’ve used LSD or psilocybin in their lifetimes, depending on the study. “Among polydrug users in the United Kingdom participants reported co-using LSD and MDMA to improve the effect of LSD and ease its aftereffects.”

All three substances—LSD, psilocybin and MDMA—are currently classified as Schedule I controlled substances under federal law, which for decades has hampered research efforts. But amid more indications that the drugs could be potent treatment tools for a variety of mental health disorders, lawmakers and regulators are warming to reform.

A year ago, the Biden administration said it was “actively exploring” the possibility of creating a federal task force to investigate the therapeutic potential of psilocybin, MDMA and others ahead of the anticipated approval of the substances for prescription use. Bipartisan congressional lawmakers, state legislators and military veterans had previously sent letters to the head of the U.S. Department of Health and Human Services (HHS) urging regulators to consider establishing an “interagency taskforce on the proper use and deployment of psychedelic medicine and therapy.”

Lawmakers at the time noted that even National Institute on Drug Abuse (NIDA) Director Nora Volkow had said that the “train has left the station” on psychedelics and had written that “people are going to use them regardless of whether regulators act.”

Sens. Cory Booker (D-NJ) and Brian Schatz (D-HI) separately pushed top federal officials to provide an update on research into the therapeutic potential of psychedelics, arguing that ongoing federal prohibition has stymied studies.

The Drug Enforcement Administration (DEA) late last year proposed higher manufacturing quotas for MDMA, LSD, psilocyn, mescaline and other substances to be used for research. “DEA is committed to ensuring an adequate and uninterrupted supply of controlled substances in order to meet the estimated legitimate medical, scientific, research, and industrial needs of the U.S., for lawful export requirements, and for the establishment and maintenance of reserve stocks,” the agency said at the time.

DEA nevertheless again rejected a petition to reschedule psilocybin as well as a doctor’s request for a federal waiver to obtain and administer the psychedelic to terminally ill patients, prompting a new set of legal challenges in federal court.

Meanwhile, a federally funded study published earlier this month found psychedelics (and marijuana) use at historic highs among U.S. adults. Use among minors, however, has stayed relatively flat.

In February of this year, Australia legalized psilocybin and MDMA for use by prescription.

Photo courtesy of Wikimedia.