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What Happens in the Human Brain After Taking DMT?

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A growing number of psychedelic compounds are being explored clinically for the treatment of neurological conditions such as depression, anxiety and post-traumatic stress disorder (PTSD). One such promising chemical in this “psychedelics renaissance” is N,N-Dimethyltryptamine, or DMT.

DMT is a psychedelic compound that has been utilized in indigenous rituals for thousands of years. It is naturally produced by a variety of plant species, and is the primary psychedelic ingredient in ayahuasca.

In 1931, the chemist Richard Manske chemically synthesized DMT, but its hallucinogenic effects were not discovered or published in scientific literature until 1951.

DMT is an interesting psychedelic as, compared to other compounds in that same category, it produces short yet intense “trips” that can last for just a few minutes depending on the dose. The short duration of its effects is an appealing characteristic when exploring its use for psychedelic-assisted therapy.

Recently, the biotechnology company Small Pharma announced positive early results from a clinical trial testing pharmaceutical-grade synthetic DMT formulation in participants with major depressive disorder, or MDD. And according to Clinicaltrials.gov, a number of other trials are in progress to evaluate the safety, tolerability and efficacy of DMT in healthy participants, stroke patients, and individuals with alcohol use disorder, among other conditions.

How, exactly, DMT alters brain function to produce the effects observed so far in clinical trials is not yet clear, though a recent study from scientists at Imperial College London (Imperial) shed some light.

The research, published in PNAS, was led by Dr. Chris Timmermann at the Centre for Psychedelic Research at Imperial. It combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to explore the effects of DMT on the human brain.

What are EEG and fMRI?

EEG is a form of non-invasive electrophysiological monitoring. It measures electrical activity – also referred to as brain waves – generated by the brain via electrodes that are placed on the scalp. When neurons fire in sync, they generate an electrical field that quickly spreads through tissue, bone and the scalp. This electrical activity is detected by the electrodes, recorded, digitized and sent to an amplifier.

EEG is considered to have excellent temporal resolution, meaning it can accurately capture changes happening in the brain over time. This is important for understanding the dynamics of brain activity, but EEG is considered to have spatial resolution – i.e., it fails to present data on where changes in brain activity are happening.

In contrast to EEG, fMRI does not measure electrical responses. Instead, it is a technique based on the principle that the more active a brain region is, the greater the amount of blood flow to that region. fMRi measures changes in blood flow and oxygenation in different areas of the brain, and therefore provides high spatial temporal resolution.

EEG-fMRI combines both techniques to overcome the temporal and spatial limitations of using them separately. It is considered a mature cognitive neuroscience technique for multimodal brain imaging.

While Timmerman and colleagues’ study is not the first to image the brain while a participant is under the effects of psychedelics, it is the first to combine EEG and fMRI to image the brain under a “highly immersive” psychedelic experience. 

“Motivated by, and building on our previous research with psychedelics, the present work combined two complementary methods for imaging the brain imaging,” said Professor Robin Carhart-Harris, senior author of the study. Carhart-Harris is now a professor of neurology at the University of California, San Francisco. “fMRI allowed us to see the whole of the brain, including its deepest structures, and EEG helped us view the brain’s fine-grained rhythmic activity,” he continued.

Testing the effects of DMT on the brain

The Imperial team recruited a total of 20 healthy participants aged 33.5 years on average for the study.

After initial assessments ensured the physical and mental health criteria of the study were met, the participants visited the Imperial College Clinical Imaging Facility for two visits that were two weeks apart.

The first session consisted of continuous EEG-fMRI scanning for 28 minutes while the participant was resting. The DMT/placebo was administered after eight minutes. “In this initial session (task free), they received intravenous (IV) administration of either placebo (10 mL of sterile saline) or 20 mg DMT (in fumarate form dissolved in 10 mL of sterile saline) – injected over 30 seconds, and then flushed with 10 mL of saline over 15 seconds  – in a counter-balanced order (half of the participants received placebo and the other half received DMT),” Timmerman and colleagues described.

What is counterbalancing?

In simplest terms, counterbalancing is used to ensure that any effects observed in a study are not due to the order in which the interventions were presented.

After the scans, the participants were handed questionnaires, which were designed to evaluate the subjective effects they had experienced.

The second session replicated the first; except participants were asked to audibly rate the intensity of the drug’s effects every minute that they were in the scanner. “This article reports the results concerning the resting-state scans in which no intensity ratings were asked, while using intensity ratings collected in other (non-analyzed) scan runs as covariates for dynamic fMRI and EEG analysis,” the researchers said.

DMT breaks down the brain’s segregated networks of activity

The researchers found that DMT triggered changes within and between different brain regions. Under normal circumstances, brain activity is segregated into specific networks. After administration of DMT, the boundaries of these networks seem to collapse, resulting in what the authors describe as “global functional connectivity”. Compared to placebo, DMT administration significantly decreased the within-network integrity of all resting state networks, excluding the salience and limbic networks. The changes to activity were most prominent in brain areas linked with “higher level” functions, such as imagination.

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By simultaneously recording EEG and fMRI data, the researchers could study any changes in the types of electrical activity produced by the brain in conjunction with the fMRI measures of functional connectivity.

“Our results revealed that when a volunteer was on DMT there was a marked dysregulation of some of the brain rhythms that would ordinarily be dominant. The brain switched in its mode of functioning to something altogether more anarchic,” said Carhart-Harris.

“It will be fascinating to follow-up on these insights in the years to come. Psychedelics are proving to be extremely powerful scientific tools for furthering our understanding of how brain activity relates to conscious experience,” he added.

Reference: Timmermann C, Roseman L, Haridas S, et al. Human brain effects of DMT assessed via EEG-fMRI. PNAS. 2023;120(13):e2218949120. doi: 10.1073/pnas.2218949120