Psychedelics as anti-inflammatory agents

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT receptor in the inflammatory response, as well as highlight studies using the 5-HT agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.

Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review

“…From a biological perspective, MM serves to adjust prefrontal and limbic activity and HPA reactivity through repeated topdown control (129,138,184). Psilocybin, on the other hand, promotes global network disintegration and anti-inflammatory effects involving transient bottom-up processes (175,191). Pairing these effects may result in a two-way reorganization of neural networks, especially those involved in rumination, and downregulation of neuroendocrine and neuroinflammatory responses.…”

“…5-HT2A agonism has also been linked to major antiinflammatory action, as 5-HT2A receptors are integrated in an abundance of cells throughout the immune system (149,189,190). Psilocybin and related psychedelics are hypothesized to distort cell signaling within the immune system by selectively stimulating antiinflammatory pathways (191,192). Although this is yet to be tested with psilocybin, LSD, DMT, and 2,5-Dimethoxy-4iodoamphetamine (DOI) were found to have anti-inflammatory action, inhibiting the production of IL-6 (130, 149, 163) which might account for enduring antidepressant psychedelics effects (193).…”

“…With regard to psilocybin, and its mechanism of action, the discussion largely pertained to 5-HT2A agonism (67,136,143,149,175,(188)(189)(190)(191)204) while psilocybin is also known to act on other neurotransmitter systems (87) which might be relevant for the comparison with MM.…”

“…Further, in some of the included papers, hypotheses were proposed that have not been subjected to sufficient empirical testing, such as proposed mechanisms regarding the immunosuppressive action of psilocybin and BDNF-promoting effects of MM (67,68,110,191). To draw definite conclusions, premises based on concrete empirical evidence are needed, and therefore, the inferential power of the present review with regard to the aforementioned is limited.…”

Symposia, Case Conference, and Medical Update

“…Psychedelics have also been found to have anti-inflammatory effects which further suggests their therapeutic potential in psychiatric and other inflammatory disorders. 4 Conclusions and Scientific Significance: Peter Hendricks reported on his current placebo-controlled pilot study using psilocybin and CBT to treat patients with cocaine dependence. Preliminary results from the first 10 of 40 participants showed a statistically significant increase in the percentage of abstinent days 180 days following psilocybin administration, a Severity of Dependence Scale (SDS) score of zero at 180 days, and improvements in depression and overall life satisfaction.…”