This completed double-blind, placebo-controlled trial (n=24) aimed to investigate the effects of co-administering MDMA with LSD in healthy subjects. The study, conducted by the University Hospital in Basel, Switzerland, assessed the acute subjective and autonomic effects of LSD alone and in combination with MDMA.
The trial employed a 4-period crossover design with four treatment conditions: 100 μg LSD + MDMA placebo, LSD placebo + 100 mg MDMA, 100 μg LSD + 100 mg MDMA, and LSD placebo + MDMA placebo. The study enrolled participants between the ages of 25 and 65, who demonstrated sufficient understanding of the German language, willingness to adhere to the study protocol, and refrained from consuming illicit psychoactive substances during the study. The primary outcome measures included assessing the intensity and duration of subjective effects, mood ratings, altered states of consciousness, and autonomic effects. Secondary outcome measures involved analyzing plasma levels of LSD, MDMA, blood-derived neurotrophic factor (BDNF), and oxytocin, administering psychological insight questionnaires and assessing the effect of moderation through personality traits. The trial began on January 1, 2021, and concluded on August 22, 2022.
Trial Details
LSD is a so-called "classic" or serotonergic hallucinogen or psychedelic. Its psychedelic effects are mainly attributed to its potent partial serotonin (5-HT) 5-HT2A receptor agonism. The effects of LSD have been frequently investigated in the past in both healthy participants and patients. Several of these studies described robust and sustained effects of LSD in patients suffering from addiction, anxiety and depression. The acute subjective effects elicited by LSD are mostly positive in humans. However, psychedelic substances like LSD may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of LSD used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors yet to be determined. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. Therefore, there is a need for methods which are capable of reducing bad drug effects while enhancing good drug effects to optimize a psychedelic experience. The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize LSD's effects profile by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.NCT Number NCT04516902
Sponsors & Collaborators
University of BaselThe University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.
MindMed
MindMed is one of the largest companies in the psychedelics space and is developing various psychedelics for mental health disorders.
Papers
Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participantsThis double-blind, randomized, placebo-controlled, crossover study (n=24) investigates the co-administration of MDMA (100mg) and LSD (100µg) compared to their individual use and placebo. Findings reveal that while the combination doesn't enhance the quality of subjective effects compared to LSD alone, it prolongs these effects, elevates plasma concentrations of LSD, and extends LSD's plasma elimination half-life. However, the combination also increases blood pressure, heart rate, and pupil size more than LSD alone. It does not improve the safety profile of LSD, indicating that combining MDMA and LSD may not offer substantial benefits over LSD alone in psychedelic-assisted therapy.
Measures Used
States of Consciousness QuestionnaireThe States of Consciousness Questionnaire (SOCQ) was developed to assess the occurrence features of the change in consciousness induced by psilocybin and includes the Mystical Experience Questionnaire (MEQ). The SOCQ consists of 100 items, 43 of which are from the MEQ.