Clinical trial NCT06180759: Acute Analgesic Effects of DMT on Experimentally Induced Pain in Healthy Participants
Official title: Acute Analgesic Effects of DMT on Experimentally Induced Acute Nociceptive Pain, Hyperalgesia and Allodynia in Healthy Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-12-22
Enrollment: 18
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: On 3 separate days, participants will be administered DMT, ketamine or placebo in a randomized, counter-balanced order. Their effect on experimentally induced acute pain will be evaluated and compared.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age between 25 and 75 years old
2. Sufficient understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study 6. Willing not to operate heavy machinery for 24 hours after the study session.

7. Willing to use effective birth control throughout study participation 8. Body mass index between 18-29 kg/m2 and body weight within 50 - 90kg

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder or bipolar disorder in first-degree relatives
4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
5. Hallucinogenic and/or dissociative substance use (not including cannabis) more than 15 times or any time within the previous two months
6. Pregnancy or current breastfeeding
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medication that may interfere with the effects of the study medication
9. Tobacco smoking (\>10 cigarettes/day)
10. Consumption of alcoholic beverages (\>20 drinks/week)

Primary outcomes:
measure: Numeric rating scale (NRS) scores (0 - 10)
timeFrame: During the infusion (55minutes)
Secondary outcomes:
measure: Area of hyperalgesia and allodynia
timeFrame: During the electrical stimulation (2 hours)
measure: NRS scores after infusion
timeFrame: After stopping the infusion (65 minutes)
measure: Association of subjective effect ratings with pain scores
timeFrame: During the electrical stimulation (2 hours)
measure: Sensory and affective pain scores
timeFrame: Retrospective evaluation after the electrial stimulation at the end of each study session.
measure: Association of psychedelic and mystical-type effects with pain scores
timeFrame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
measure: Plasma levels of DMT and ketamine
timeFrame: During the electrical stimulation (2 hours)
measure: Association of the intensity of electrical currents with NRS pain scores
timeFrame: During the electrical stimulation (2 hours)
measure: Psychometric comparison between DMT, ketamine and placebo
timeFrame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
measure: Effect modulation through personality traits
timeFrame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
measure: Modulation of personality traits by acute subjective effects
timeFrame: During the electrical stimulation (2 hours) and retrospective evaluation at the end of each study session.
measure: Autonomic effects
timeFrame: During the electrical stimulation (2 hours)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Clinical Pharmacology & Toxicology, University Hospital Basel
Study officials:
References: