Effects of MDMA Co-administration on the Response to LSD in Healthy Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The acute subjective effects of serotonin (5-HT)2A receptor stimulation with lysergic acid
      diethylamide (LSD) in humans are mostly positive. However, negative effects such as anxiety,
      paranoid thinking or loss of trust towards other people are common effects, depending on the
      dose administered, the personality traits of the person consuming it (set), or the
      environment in which LSD is taken (setting). Negative psychedelic effects may cause acute
      distress to the subject and acute anxiety has been linked to less favourable long-term
      outcomes in patients experimentally treated with LSD or similar substances for the treatment
      of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA)
      reliably induces positive mood up to euphoria, comfort, empathy, and feelings of trust. If
      administered in combination with LSD, MDMA may increase positive subjective drug effects
      including positive mood, empathy, and trust and reduce negative emotions and anxiety
      associated with LSD and overall produce a more positive over negative experience. The present
      study will assess subjective and autonomic effects of LSD alone and in combination with MDMA.
    

Detailed description: 
      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.
    

Intervention name(s): Lysergic Acid Diethylamide; 3,4-methylenedioxymethamphetamine; LSD Placebo; MDMA Placebo
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): A moderate dose of 100 μg LSD will be administered.; A moderate dose of 100 mg MDMA will be administered.; Pure alcohol instead of an alcoholic solution containing LSD; Mannitol capsules instead of capsules containing MDMA
Other intervention name(s): LSD; MDMA
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine; Lysergic Acid Diethylamide
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions:
100 μg LSD+MDMA placebo
LSD placebo +100 mg MDMA
100 μg LSD + 100 mg MDMA
LSD placebo+ MDMA placebo
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science