DMT Research: Could the ‘Spirit Molecule’ help treat alcohol addiction?

DMT, short for N, N-dimethyltryptamine, is a short-acting, potent psychedelic. Also known as the "spirit molecule", DMT's reported powerful and transformative effects have sparked research interest in its use for psychedelic therapy. A research group at University College London (UCL) aims to understand how DMT's psychological benefits could relate to brain activity changes.

The project is being undertaken by the UNITy (Understanding Neuroplasticity Induced by Tryptamines) research group, based at UCL's Department of Psychology and Language Science.

Using fMRI, a brain-imaging technique that measures blood flow, the team will measure the study participants' brain activity one week before and after DMT. Participants will record their mood, cognition, and behaviour over the study course to see whether these factors correlate with brain activity changes.

"We expect these changes to correspond with increases in wellbeing, as measured by follow-up questionnaires in the months after the DMT experience," wrote Marcus Glennon, a Ph.D. student at UCL and study contributor. "This would provide us with a potential biomarker for the therapeutic potential of psychedelics, whilst also helping us understand the effects of psychedelics on the brain."

Biomarkers are biological measures that predict how someone might respond to a certain treatment or drug. By helping determine which brain networks may be most relevant for its beneficial effects, the team hopes their findings could be a useful biomarker in developing DMT therapies.

The team will also investigate whether DMT could be useful in decreasing alcohol addiction through interfering with memory reconsolidation. Memory reconsolidation is when memories associated with a behaviour are brought to the surface, allowing an opportunity for the behaviour to be relearned.

"Addiction disorders are not inherent, despite people perhaps having particular genetic predispositions to them. Ultimately, they are learned behaviours. If they can be learnt, they can be unlearned, under the right conditions," says Glennon.

The study will recruit 120 participants with high levels of alcohol use to investigate this potential. Half the participants will receive the memory intervention, and half without. Within these groups, half will receive DMT and half a placebo.

Because DMT increases flexibility in brain pathways, the team thinks it could optimise the chances for re-learning memories and behaviour in the intervention. In turn, reducing participants' heavy drinking behaviours.

"The cues we show participants will feature images of alcohol in order to reactivate, and therefore destabilize the memory trace," explained Glennon.

"We will then administer DMT, a drug thought to significantly enhance plasticity in the brain, potentially enabling us to change maladaptive, addiction-sustaining memories."

In line with this suggestion, another UCL study found ketamine helped reduce excessive alcohol use following a memory reconsolidation intervention in heavy drinkers. Ketamine is also believed to increase the brain's flexibility.

Glennon described how DMT, particularly, is well-suited for this paradigm because "the short-lasting but intense effects of DMT will fit very comfortably into the proposed 'reconsolidation window’."

In the week before and after DMT, participants in both the "healthy" and "hazardous drinking" cohorts will watch a movie while in the fMRI scanner. Though this brain imaging approach is less common, the team thinks it will better reflect the brain's natural state, in which it's constantly being exposed to sounds and images from the environment.

The team will also assess the direct impact of DMT on brain activity, taking scans of participants' brains 20 minutes before and during the infusion. No movies will be shown during these scans.

Going forward, study participants are soon to be recruited, attempting to reach as diverse a population as possible. Glennon noted their sample will likely be biased by those with a previous history of positive psychedelic experiences. However, he noted “although far from ideal, this is how many areas of human research start out; in select groups of people. Once we have a clearer idea of the effects of these substances, future studies can gradually loosen the exclusion criteria to incorporate people with more varied backgrounds and traits.”

In a recent Phase 2 trial, DMT had rapidly acting and sustained benefits in patients with depression. Promising preclinical results are also showing DMT could be helpful for neurological disorders, such as stroke and brain injury. By helping understand DMT's mechanism, the researchers hope their study findings could be hugely useful for developing these clinical trials and therapies further.

"We anticipate that our findings will provide the first mechanistic insights into the broad-scale effects of psychedelic substances on the human brain, offering invaluable knowledge for the accelerated development of therapeutic applications," they write on their website.

Looking ahead, the team estimates their data collection could take anywhere from three to five years. Once available, their findings will provide a large-scale DMT dataset, which they will keep open-source "for the world to enjoy," as quoted by Glennon.

The study is being led by Dr Ravi Das from the Clinical Psychopharmacology Unit and Dr Jeremy Skipper from the Language Action and Brain Lab at UCL. Alongside a team of PhD students, they will be combining their expertise in psychopharmacology and neuroimaging, respectively, to conduct this immense interdisciplinary project.