Serotonergic psychedelics, substances that alter perception and mood, such as psilocybin and LSD, have recently been attracting increasing attention from the medical community. Scientists are actively studying their potential in treating mental and neurological disorders, including depression, post-traumatic stress disorder (PTSD), Parkinson’s disease, and migraines. An international team of researchers recently published a systematic review and meta-analysis evaluating the anti-inflammatory and immunomodulatory properties of serotonergic psychedelics in cell, animal, and human studies.
What biological mechanism underlies the action of psychedelics?
Serotonergic psychedelic substances are structurally similar to serotonin — a neurotransmitter involved in mood regulation, communication between neurons, and modulation of the immune response. By interacting with serotonin receptors, psychedelics alter neuroplasticity — the brain’s ability to change, adapt, and establish new neural connections. This process may help alter neural processes associated with depression, anxiety, and addictions.
At the same time, it is suggested that the regulation of inflammatory processes is another possible mechanism of the therapeutic action of psychedelics. Chronic systemic inflammation is associated with various mental health disorders, although the existence of this link does not in itself confirm that reducing inflammation is the cause of the therapeutic effect of psychedelics.
Research methodology and key findings
Researchers searched six scientific databases and evaluated 9,195 studies. Ultimately, 61 studies met the criteria: 24 were conducted in cell cultures, 30 in animals, and 7 in humans. The studies involving humans covered 10 separate clinical trials.
Cellular and animal models
In 19 out of 24 cell studies and 25 out of 30 animal studies, an anti-inflammatory effect of psychedelics was recorded. This effect was particularly pronounced when inflammatory processes were induced in cells or animals.
Pooled data from mouse studies showed that serotonergic psychedelics reduced pro-inflammatory cytokine levels when baseline inflammation in the animals was already elevated. In healthy animals that did not have elevated inflammation initially, psychedelics had no significant effect on cytokine levels.
Specific targets of action
In the studies, the anti-inflammatory effect of psychedelics was linked to specific biological targets: DOI and psilocybin acted primarily through the serotonin 5-HT2A receptor, while DMT (dimethyltryptamine) exhibited its anti-inflammatory effect by acting on the sigma-1 receptor. These results indicate that different psychedelics may have distinct mechanisms of action on immune processes.
Is this effect confirmed in humans?
While the anti-inflammatory effect appeared relatively consistent in cellular and animal models, the results in human clinical trials were more mixed. Out of 10 clinical trials, a reduction in inflammatory markers was recorded in only 3. Researchers note that in 7 out of 10 human trials, patients with active inflammatory diseases were not included.
This is an important circumstance, as in animal models the anti-inflammatory effect of psychedelics manifested mainly against the background of already elevated inflammation. However, it is not yet known whether this effect extends to humans. To answer this question, additional clinical trials involving patients with active inflammatory diseases are needed.
