DMT Study Skips Set and Setting

This week we take a closer look at a recent publication out of Yale and VA Connecticut Healthcare System. This exploratory study sought to ascertain the safety, tolerability and efficacy of DMT in a small group of participants.

D’Souza, D. C., Syed, S. A., Flynn, L. T., Safi-Aghdam, H., Cozzi, N. V., & Ranganathan, M. (2022). Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology, 1-9.

Link to the study. 

TL;DR

This exploratory study provides “support for DMT’s tolerability, safety, and potential rapid antidepressant effect.”

This study is intriguing because, in contrast to other trials of psychedelic therapies, it administered DMT in a typical hospital setting and without intensive psychotherapy.

If replicable, this could have significant repercussions for the cost-effectiveness and scalability of psychedelic therapies.

Caveats & Preliminaries

Caveats

It’s important to keep a few caveats at top-of-mind when interpreting studies like this. The most obvious limitations of the study are its open-label design, the small sample size (n = 10) and the fact that measurements of effect were only taken one day after dosing sessions. Many of the other limitations of the study are discussed by the authors and are recapitulated at the end of this write-up.

Preliminaries

Sample size: 

• Major Depressive Disorder (MDD): n= 7, 
• Healthy Controls (HC): n = 3
• Total: n = 10

Design: Open-label, fixed-order dose escalation study in both healthy volunteers and patients with treatment resistant major depressive disorder (MDD) using intravenous DMT.

Dosing: first dose 0.1 mg/kg; second dose 0.3 mg/kg. Doses were spaced out by at least 48 hours. Note that the psychedelic effects of DMT appear at around 0.2 mg/kg when given intravenously.

Notable exclusion criteria: participants did not have to be psychedelic naive. Rather, the investigators chose to exclude those who admit to “regular use of psychedelics,” among other exclusion criteria including pregnancy, drug dependence (current or recent), and use of OTC products with serotonergic properties.

Note that any emphasis within quotations below is our own.

Ready, skip set and setting, go!

What’s really intriguing about this study is the hands-off approach investigators took when it comes to set and setting. Let’s take a look at this in terms of psychological support or therapy and physical setting.

Psychotherapy

A distinguishing feature of this study is the lack of preparatory and integrative therapy provided. 

Participants in this study “met with the study psychiatrists for a preparatory session of about 45 min”. Here, volunteers were given information about the psychological effects of DMT, and study psychiatrists suggested approaches for navigating the experience. Participants suffering with MDD were “invited to discuss their mood symptoms and their depression history.” 

Investigators used the 2 hours or so between the subsiding of DMT’s effects and the time of discharge to ‘debrief’ patients with a psychiatrist. The day after drug sessions, participants received a telephone check-in to monitor for adverse events, check on well-being and to administer the HAMD-17 questionnaire for MDD participants. No structured integration program here.

Elements to ensure a mindset propitious to psychedelic-assisted therapy are not very present here (i.e., preparatory and integrative therapy was minimal). What about the physical environs, the setting element?

Physical Setting

DMT was administered in a typical hospital setting, with the investigators keen to note this: right down to the fact that they used hospital-issued linens. 

The investigators explain:

“Participants were dosed in a booth containing a medical-grade reclining chair and desk that was lit with overhead fluorescent lighting. There was no art adorning the room and no music was played. Participants were provided pillows and hospital-issued linens.”

The description of the test session protocol goes on to depict a decidedly clinical scene:

“The two psychiatrists stood on either side of the medical chair, with a research nurse and research assistants stood immediately behind the subject. After connecting the DMT-containing syringe to the intravenous port, the impending administration of DMT was announced.”

The DMT is then administered via intravenous push over a period of 30-60 seconds, with blood pressure measured at baseline and regularly following DMT administration and heart rate and pulse oximetry measured on a continuous basis.

Participants were simply asked how they were feeling while the aforementioned physiological recordings were taking place: “no psychotherapy was provided”.

So, no plush soft furnishings and muted tones: the surrounds are less ‘Anthropologie’, more like outpatient gastroenterology.

Tolerability, safety, preliminary efficacy

Tolerability

Using a score of 0-100 (where 100 = well tolerated and 0 = intolerable) participants rated DMT as well tolerated, with a score of 89.8 for the 0.1 mg/kg dose session and 71.11 for the 0.3 mg/kg dose. This isn’t surprising, given that investigators deem the 0.1 mg/kg to be a sub-hallucinogenic dose.

The tolerability data is presented in Figure S1 (Supplementary Material), with the three healthy controls participants to the left of the x axis, and the 6 MDD participants to the right. The low dose is in blue; the higher dose in red.