N,N-dimethyltryptamine (DMT) is a classical psychedelic with similar effects like LSD or psilocybin. Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. Therefore, the investigators will evaluate the efficacy of DMT on different pain qualities within a model of electrically induced pain in healthy participants. The analgesic effects will be compared to racemic ketamine (active control) and placebo within a cross-over design.
Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. For instance, it is unclear whether psychedelics possess acute antinociceptive effects or if they rather modulate secondary pain phenomena such as hyperalgesia, allodynia, and/or functional pain. Here, the investigators will employ a validated electrical stimulation model in healthy volunteers that produces acute nociceptive pain but also features of chronic pain such as hyperalgesia and allodynia. The model is established for the detailed assessment of the analgesic effect of known analgesics or new compounds. Thus, the investigators will evaluate the efficacy of N,N-dimethyltryptamine (DMT), a classical and naturally-occurring psychedelic, on different pain qualities within this model. DMT differs from other classical psychedelics in its very short elimination half-life. Due to its rapid metabolization by monoaminoxidases (MAO), DMT is not orally bioavailable in the absence of MAO-inhibitors and thus has to be administered continuously and intravenously. Recently, the investigators tested several continuous intravenous administration regimes of DMT that lead to the induction of a constant and rapidly adaptable psychedelic state. The regime allows to induce stable DMT effect that can be terminated rapidly. Due to this controllability, a continuous infusion of intravenous DMT is most suitable to assess time and concentration-dependent analgesic effects within the used pain model. The analgesic efficacy of DMT will be compared to ketamine, a known analgesic (positive control), and placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
18
A dose rate of 1.2 mg/min will be administered
A dose rate of 1.0 mg/min will be administered
A Placebo (saline infusion) will be administered.
Clinical Pharmacology & Toxicology, University Hospital Basel
Basel, Switzerland
RECRUITINGNumeric rating scale (NRS) scores (0 - 10)
Difference of the cumulative NRS scores (area under the effect curves (AUECs)) between the DMT, ketamine (active-control) and placebo condition. NRS 0 represents "no pain at all" whereas 10 represents "the worst pain ever possible".
Time frame: During the infusion (55minutes)
Area of hyperalgesia and allodynia
Difference of the cumulative areas of hyperalgesia and allodynia (Area under the effect curves (AUECs), in square centimeters \* minutes) between the DMT, ketamine and placebo condition.
Time frame: During the electrical stimulation (2 hours)
NRS scores after infusion
Difference of the cumulative NRS scores (Area under the effect curves (AUECs)) between the DMT, ketamine and placebo condition
Time frame: After stopping the infusion (65 minutes)
Association of subjective effect ratings with pain scores
Assessment of the correlation between subjective effect ratings and NRS pain scores, areas of hyperalgesia and allodynia. Subjective effects are measured on the subjective effects scale (SES) that ranges from 0 ( = no effects) to 10 ( = most extreme effects).
Time frame: During the electrical stimulation (2 hours)
Sensory and affective pain scores
Difference of retrospectively evaluated sensory and affective pain scores (Short version of the McGill Pain Questionnaire, SF-MPQ-D) between the DMT, ketamine and placebo condition. The SF-MPQ-D is scored from 0 (= no pain) to 3 (= strongest possible pain).
Time frame: Retrospective evaluation after the electrial stimulation at the end of each study session.
Association of psychedelic and mystical-type effects with pain scores
Correlation between psychedelic and mystical-type effects (Five Dimensional Altered states of consciousness (5D-ASC), States of Consciousness Questionnaire (SCQ)) with NRS pain scores and areas of hyperalgesia and allodynia.
Time frame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
Plasma levels of DMT and ketamine
Plasma levels of DMT and ketamine over time
Time frame: During the electrical stimulation (2 hours)
Association of the intensity of electrical currents with NRS pain scores
Association of the intensity of electrical currents (in mA) that induced a target baseline pain score (NRS) of 6/10 with NRS pain scores and areas of hyperalgesia and allodynia.
Time frame: During the electrical stimulation (2 hours)
Psychometric comparison between DMT, ketamine and placebo
Comparison of subjective effects, altered state of consciousness and mystical effect scores between DMT, ketamine, and placebo.
Time frame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
Effect modulation through personality traits
Effect modulation through personality traits (NEO-Five Factor Inventary (NEO-FFI), Saarbrücken Persönlichkeitsfragebogen (SPF), Elliots humility scale (EHS), Defense-style questionnaire-40 (DSQ-40), Connor-Davidson Resilience Scale (CD-RISC), Five Facet Mindfulness Scale (FFMQ), ABC Connectedness to Nature Scale, (ABC-CNS)).
Time frame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
Modulation of personality traits by acute subjective effects
Modulation of personality traits resilience (Connor-Davidson Resilience Scale, CD-RISC), mindfulness (Five Facet Mindfulness Questionnaire (FFMQ) and connectedness to nature (ABC-CNS) in association with acute subjective effects (Subjective Effects Scale (SES)) and psychedelic/mystical-type effects (Five Dimensional Altered States of consciousness Scale (5D-ASC), States of Consciousness Questionnaire (SCQ).
Time frame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
Autonomic effects
Autonomic effects over time (blood pressure in mmHg, heart rate in beats per minute)
Time frame: During the electrical stimulation (2 hours)
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