The Therapeutic Potential of Classic Psychedelics

Psychedelic-assisted psychotherapy is an emerging treatment combining classic psychedelic substances, like psilocybin and lysergic acid diethylamide (LSD), with psychotherapy. Alongside recent findings suggesting the therapeutic potential of psychedelic-assisted psychotherapy for an array of psychiatric disorders, there appears to be a rapidly growing interest in psychedelics throughout clinical research. Unlike traditional psychiatric medications, these substances can provide highly meaningful and sustained therapeutic effects following a single dose. Drastically altering normal waking states of consciousness, they can lead to both highly positive experiences (e.g., 'mystical experiences,’ often involving the unification between ‘self’ and ‘universe’) and highly challenging experiences (colloquially referred to as ‘bad trips’).

Combining Classic and Atypical Psychedelics

As expected, psychedelic-induced challenging experiences can contribute to hesitancy toward psychedelic-assisted psychotherapy among healthcare providers and patients alike. However, anecdotal reports from recreational users have claimed that the co-use of the atypical psychedelic, 3,4-Methyl​enedioxy​ methamphetamine (MDMA, or ‘ecstasy’), with psilocybin (i.e., ‘hippy flipping’) or LSD (i.e., ‘candy flipping’) can enhance the psychedelic experience. If true, such findings may provide avenues to protect against challenging experiences in clinical settings. In a recent study published in Nature Scientific Reports, researchers from New York University (NYU) Langone Health, Imperial College London, and the University of California San Francisco examined whether the concurrent use of low or medium/high doses of MDMA with classic psychedelics (specifically, psilocybin or LSD) were associated with differences in challenging and positive experiences when compared to classic psychedelic use alone.

Concurrent Use of MDMA and Acute Challenging Experiences

The study found that, relative to classic psychedelics alone, the co-use of low-dose MDMA was associated with significantly less total challenging experiences, grief, and fear during the acute psychedelic experience. In alignment with recent findings, this relationship was not evident when comparing the co-use of medium-high dose MDMA to classic psychedelic use alone. Furthermore, regardless of dose, the co-use of MDMA was not related to significant differences in perceived physical distress, insanity, isolation, death, or paranoia during the acute psychedelic experience (Figure 1).

Concurrent Use of MDMA and Acute Positive Experiences

When compared to classic psychedelic use alone, co-use of low-dose MDMA was associated with significantly greater feelings of self-compassion, love, and gratitude. This relationship was not found for co-use of medium-high dose MDMA. Moreover, co-use of any dose of MDMA was not associated with significant differences in compassion or mystical-type experience (Figure 2).

Key Takeaways and Future Directions

1) When compared to classic psychedelic (specifically, psilocybin and LSD) use alone…

• Co-use of low-dose MDMA may help protect against challenging experiences (specifically, fear and grief) and enhance certain positive experiences (self-compassion, love, and gratitude) of the acute psychedelic experience
• Co-use of medium/high dose MDMA was not associated with reduced challenging aspects or enhanced positive elements of the acute psychedelic experience

2) If larger controlled studies confirm the present preliminary findings and establish its safety…

• Co-use of low-dose MDMA with classic psychedelics may help reduce acute distress and may also be implicated in reducing potential post-acute distress, functional impairment, and medical attention seeking following challenging psychedelic experiences
• Individuals with an elevated risk for challenging psychedelic experiences may benefit from MDMA co-administration in psychedelic-assisted therapies

3) Important limitations in this study include the use of a convenience sample, small sample size, and non-experimental design. Further research remains important for establishing the safety and potentially beneficial effects of using MDMA alongside psilocybin and LSD.