N,N-dimethyltryptamine, more commonly known as DMT, is an exceptionally fast-acting and powerful psychedelic. DMT can be ingested by drinking the entheogenic brew ayahuasca, injected intravenously, intramuscularly or through inhalation. It is produced endogenously in a variety of plants and animals, including in humans. DMT exerts physiological effects that go beyond its mind-altering effects, as discussed in Jacob and Presti (2005). For example, DMT has been shown to induce anxiolytic and antidepressant effects (Sanches et al. 2016).
DMT is not only an agonist of serotonin 2A and 2C receptors (5-HT2A and 5-HT2C); it also binds to σ1 putative receptors and trace amine receptors (Vitale et al. 2011). In addition, its serotonergic analogues can influence immunoregulation, and may even prevent carcinogenesis (Frecska et al. 2012). DMT’s multifaceted interactions show that its effects are not limited to the central nervous system but may play a more crucial role in the body’s cellular protective mechanisms (Frecska et al. 2012).
Dr. Ede Frecska has published multiple papers on the effects of ayahuasca and DMT on creativity, tissue regeneration, and the interhemispheric fusion in altered states of consciousness (Frecska et al. 2016). With the recent discovery of DMT’s activation of the σ1 receptor , which plays a crucial role in protecting the body from undergoing oxidative stress, Dr. Frecska and his team are currently investigating DMT’s role in neuroprotection prior to clinical death (Frecska 2015).
σ1 receptors play a key role in neuroprotection by regulating both neuronal development and morphogenesis. This is done through the regulation and manipulation of oxidative stress and mitochondrial functions (Tuerxun et al. 2010). Agonists of σ1 receptors exacerbate neuroprotective effects by inhibiting intracellular calcium overload and by thwarting the activation of pro-apoptopic genes, as well as activating protective genes, as shown in stroke models (Zhang et al. 2012). This leads to the reduction of calcium neurotoxicity, prevents oxidative stress-induced cell death, and can stimulate neuronal plasticity (Kourrich et al. 2012). Most importantly, the constant activation of σ1 receptors during ischemia leads to a reduction of neurotoxicity (Katnik et al. 2006). Ultimately, this research suggests that DMT may have a role in reducing the hypoxic-anoxic damages such as local anoxia (e.g. stroke) or general hypoxia (e.g. cardiac arrest) (Kourrich et al. 2012).
DMT’s medicinal properties are not limited to neuroprotection, but can extend to immunoprotection as well. The 5HT2A receptors, as well as the sigma receptors, can profoundly influence the body’s immune system. Serotonin plays an important role in cellular immune functions, and more specifically in the elimination of pathogens and cancer cells (O’Connell et al. 2006). σ1 receptor agonists can increase the production of anti-inflammatory cytokines as well as reduce pro-inflammatory cytokines. Both these processes are important in reducing the cellular damage in case of injury or disease (Frecska et al. 2012).
Currently, there is only speculation that DMT is produced during near-death experiences, as there are few parallels between near-death experiences and DMT visions (Strassman 2001). However, based on limited information, one may conjecture the production of DMT during life-threatening situations. McEwen and Sober (1967) have demonstrated that when undergoing extreme environmental stress, rabbits produce vast quantities of DMT in the lungs, which are then released into the blood (McEwen & Sober 1967). DMT is then transported through the neural membranes within synaptic vesicles and delivered to the brain. Knowing the relationship between DMT and the σ1 receptors, it is hypothesised that DMT limits or reverses the accumulated oxidative stress. This serves as the foundation of Dr. Frecska’s hypothesis, and if evidence is found of DMT’s role in the neuroprotection of the human brain in the stages leading up to clinical death, then DMT would have the potential to be used as an emergency medicine. If successful, one could envision the use of DMT ampoules to be used intravenously in ambulances, operating rooms and in disaster zones. Clinical studies with humans are still necessary in order to define whether it is feasible or not.
Although Dr. Frescka’s studies focus on rats (pre-clinical studies), his studies have looked beyond DMT’s mere hallucinogenic relevance and have opened avenues into further studying DMT’s neuroprotective role. The potential medical ramifications are vast. The applications of DMT may be beyond what we can imagine, and certainly deserve to be systematically studied.
Frecska, E., 2015. What role does the ‘spirit molecule’ DMT play in the brain?.