PMID- 31634774 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20201123 IS - 1532-2777 (Electronic) IS - 0306-9877 (Linking) VI - 134 DP - 2020 Jan TI - The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. PG - 109406 LID - S0306-9877(19)30822-9 [pii] LID - 10.1016/j.mehy.2019.109406 [doi] AB - We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT(2A) receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process. CI - Copyright © 2019 Elsevier Ltd. All rights reserved. FAU - Germann, Christopher B AU - Germann CB AD - Marie Curie Alumnus, United Kingdom. Electronic address: christopher-germann@marie-curie-alumni.eu. LA - eng PT - Journal Article DEP - 20190924 PL - United States TA - Med Hypotheses JT - Medical hypotheses JID - 7505668 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotransmitter Agents) RN - 0 (Psychotropic Drugs) RN - 0 (SLC6A4 protein, human) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 2RV7212BP0 (Psilocybin) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Aging/*drug effects/genetics/psychology MH - Aging, Premature/drug therapy/genetics/prevention & control MH - Animals MH - Anxiety/drug therapy/genetics MH - Brain-Derived Neurotrophic Factor/physiology MH - Consciousness/drug effects MH - DNA Methylation/drug effects MH - Depression/drug therapy/genetics MH - Disease Models, Animal MH - Endocrine System/physiopathology MH - Humans MH - *Models, Genetic MH - *Models, Psychological MH - Neurotransmitter Agents/physiology MH - Oxidative Stress/drug effects MH - Personality/drug effects MH - Psilocybin/pharmacology/*therapeutic use MH - Psychotropic Drugs/pharmacology/*therapeutic use MH - Research Design MH - Serotonin Plasma Membrane Transport Proteins/physiology MH - Stress, Psychological/drug therapy/genetics MH - Telomere Shortening/*drug effects/physiology OTO - NOTNLM OT - Cellular senescence OT - Depression OT - Epigenetic clock OT - Genetic aging OT - Life extension OT - Neurophenomenology OT - Psilocybin OT - Rejuvenation OT - Rumination OT - Senotherapy OT - Telomeres EDAT- 2019/10/22 06:00 MHDA- 2020/11/24 06:00 CRDT- 2019/10/22 06:00 PHST- 2019/07/27 00:00 [received] PHST- 2019/09/21 00:00 [revised] PHST- 2019/09/24 00:00 [accepted] PHST- 2019/10/22 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2019/10/22 06:00 [entrez] AID - S0306-9877(19)30822-9 [pii] AID - 10.1016/j.mehy.2019.109406 [doi] PST - ppublish SO - Med Hypotheses. 2020 Jan;134:109406. doi: 10.1016/j.mehy.2019.109406. Epub 2019 Sep 24.