Acute Analgesic Effects of DMT on Experimentally Induced Pain in Healthy Participants

NCT ID: NCT06180759

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-23
• Study Completion Date: 2025-09-28

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Intravenous infusion of DMT

Participants will be administered intravenous DMT.

Group Type: EXPERIMENTAL

Intravenous infusion of DMT

Intervention Type: DRUG

A dose rate of 1.2 mg/min will be administered

Intravenous infusion of ketamine

Participants will be administered intravenous racemic ketamine.

Group Type: ACTIVE_COMPARATOR

Intravenous infusion of ketamine

Intervention Type: DRUG

A dose rate of 1.0 mg/min will be administered

Intravenous infusion of placebo

Participants will be administered intravenous lacebo (saline infusion).

Group Type: PLACEBO_COMPARATOR

Intravenous infusion of placebo

Intervention Type: DRUG

A Placebo (saline infusion) will be administered.

Interventions

Intravenous infusion of DMT

A dose rate of 1.2 mg/min will be administered

Intervention Type: DRUG

Intravenous infusion of ketamine

A dose rate of 1.0 mg/min will be administered

Intervention Type: DRUG

Intravenous infusion of placebo

A Placebo (saline infusion) will be administered.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Pharmacology & Toxicology, University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Facility Contacts

Severin B Vogt, Dr.med.

Role: primary

severinbenjamin.vogt@usb.ch

+41 61 268 68 66 ext. +41

Matthias E Liechti, Prof.

Role: backup

matthias.liechti@usb.ch

+41 61 268 68 68 ext. +41

Other Identifiers

BASEC 2023-01813

Identifier Type: -

Identifier Source: org_study_id