DMTx: The First Results...

Tolerable, safe, and highly effective...

So, just last week, the Imperial College Centre for Psychedelic Research finally published a pre-print of the world’s first pilot study of extended-state DMT, which has come to be known as DMTx. This comes almost seven years after Rick Strassman and myself proposed a retooling of target-controlled intravenous infusion — the technology used to maintain a stable brain concentration of anaesthetic drugs during surgery — for extending the DMT state from a few minutes to potentially much much longer…

If you haven’t already done so, I suggest you read my two posts on the origins and theory behind DMTx:

The Origins and Theory Behind DMTx — Part 1

The Origins and Theory Behind DMTx — Part 2

As well as extending the duration of a what’s normally a 5-10 minute trip, our hope was that, as brain DMT levels stabilised, so would the trip, potentially allowing more detailed analysis and even mapping of the DMT space’s structure and content, performing experiments, as well as establishing communication with the entities that reside within the space, whatever their origin or nature.

The study, lead by PhD student Lisa Luan under the supervision of Dr. Chris Timmermann, recruited 11 volunteers with previous experience with DMT (entirely sensible), who received up to four different dose regimens.

You can download the pre-print here: https://psyarxiv.com/vg4dp

As we proposed in our 2016 paper (LINK), the bolus-elimination-transfer (BET) protocol was employed, in which an initial bolus (i.e. relatively large dose injected within 30 seconds) was used to rapidly bring the brain DMT concentration to the desired level, followed by a programmed infusion for 29 minutes at a rate designed to compensate for the drug’s metabolism and elimination and thus achieve a relatively stable concentration and, hopefully, subjective experience. To achieve a “high dose” breakthrough state, our model suggested an initial bolus of 25 mg, followed by a maintenance infusion rate beginning at 2.5 mg/min, which was lowered every two minutes until reaching 0.93 mg/min as the final rate.

Using their much improved pharmacokinetic model, developed by a specialist pharmacokinetics research group at the University of Gothenburg, their initial boluses ranged from 6 mg at the lowest dose up to 18 mg at the high end — pretty close to what Rick and myself envisaged. They used a constant, unadjusted, maintenance infusion rate ranging from 0.63 (lowest dose) to 1.88 mg/min (highest dose) — again, this is in the ball park of what our model suggested.

The intensity of the subjective effects was reported by the volunteers in real time at intervals throughout the infusion and, as hoped and predicted, increased very rapidly to a peak level before stabilising at a slightly lower level, suggesting that brain DMT levels were also relatively stable.

Also, whilst heart rate and anxiety levels increased sharply at the beginning of the infusion, they soon settled at normal levels, indicating that, at least with these experienced volunteers, extended-state DMT is well-tolerated and neither physiologically nor psychologically overwhelming.

After the infusion sessions ended, volunteers were also asked to complete the Altered States Questionnaire (ASC) and the Mystical Effects Questionnaire (MEQ-30). Interestingly, whilst ratings of immersion, visual imagery, and entity encounters increased with dosage, ego dissolution remained low at even the highest dose level.

I find this feature of the deep DMT experience particularly intriguing, and Terence McKenna commented on it several times:

“The strange thing about DMT is that it doesn’t affect your mind in the ordinary sense. You’re not ecstatic or freed of anxiety. You’re exactly who you were before this started happening with all your neurosis, fears, doubts…”

Unlike with high doses of other psychedelics, such as LSD, the ego seems to be largely spared, whilst all manner of wild imagery unfolds behind the eyelids. As far as I can interpret the results of the team’s recent DMT functional imaging study (LINK), there’s nothing in the data that jumps out and explains this. In prior studies with both LSD (LINK) and psilocybin (LINK), ego dissolution was shown to be correlated with disruption of the default mode network (DMN) and increased global functional connectivity. Comparable effects on network connectivity were observed in this latest functional imaging study with DMT, so it’s not clear to me why the ego appears to remain intact at even the highest dose levels in this extended-state study.

Of course, it’s not so much where you go but who you meet there that many DMT users are particular fascinated by, and there appeared to be no shortage of entity encounters in this study. Noticeably, at the highest dose level, the entities seemed to make a more prominent appearance around 10 minutes into the infusion.

Without details as to the nature of these entities, it’s hard to draw any conclusions from this, but it’s worth noting that this would normally be well after the peak of a regular DMT trip, as the effects were rapidly diminishing. It would be interesting to see if particular types of entities appear at these later time points and thus might be unique to the extended-state experience. We’re currently planning a moderated online discussion with some of the study volunteers, probably for next month, when we’ll have a chance to get into the entity encounters in much more detail. Watch this space!

Perhaps the most contentious result from this study was the claim that the volunteers experienced “short-term psychological tolerance” since, whilst the blood plasma DMT concentration rose slightly throughout the infusion, the intensity of subjective effects remained stable.

Of course, this is in apparent conflict with Rick Strassman’s 1996 study which showed a complete lack of subjective tolerance to closely-spaced bolus doses (LINK). However, I think we need to remain somewhat circumspect in how we interpret these results, for a couple of reasons.

As the authors rightly point out, it’s plausible that the drop off in subjective intensity relative to DMT plasma concentration is related more to psychological habituation than physiological tolerance. In other words, as the volunteers become more accustomed to the DMT state over time, the perceived intensity remains stable or even falls slightly, despite a modest increase in DMT levels in the brain.

Also, as we discussed in our 2016 paper, in Rick Strassman’s 1994 paper (LINK), the inter-subject variability in subjective response to a particular dose was 45% lower than the variability in blood plasma DMT concentration, suggesting that a fairly broad brain concentration window will elicit a similar subjective intensity. Once a subject reaches a particular level of subjective effect, intensity increases much more slowly than any increase in blood DMT concentration. In other words, particularly at higher dose levels, the relationship between brain DMT concentration and subjective effect intensity is expected to be sub-linear. For example, if the brain DMT concentration gradually increases by 15-20% over the course of the infusion (as in the highest dose level in this study), we might expect the subjective intensity to increase by only 5-10% (even without any kind of tolerance), which might not be reflected as an increase on a 10 point scale. Factoring in possible psychological habituation, it wouldn’t even be surprising if we saw a drop in perceived intensity. Obviously, as the infusion times are extended, any subjective tolerance — if it’s really there — will manifest more clearly. I’d say the jury is still out on this one.

Overall, this is undoubtedly a landmark study which, whilst small and limited in scope, demonstrates unequivocally that using target-controlled intravenous infusion to extend and stabilised the DMT state not only works well, but is both safe and tolerable — at least up to 30 minutes in experienced users. Of course, this isn’t something to be tried at home. Yet…

Rick Strassman’s volunteer ‘Sara’, after one of her high dose trips, reported:

"I went directly into deep space. They knew I was coming back and they were ready for me. They told me there were many things they could share with us when we learn how to make more extended contact..."

Well, here we are.