The article by Catlow BJ et al. (Exp Brain Res. 2013 Jun 2. [Epub ahead of print]), demonstrates how a low dose (0.1 mg/kg) of psilocybin helps mice overcome a conditioned fear response significantly quicker than a medium (0.5 mg/kg) or high dose of psilocybin (1.0 mg/kg) and results in hippocampal neurogenesis while the higher doses result in a decrease in cell survival.
Griffiths et al. in their pioneering study (Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Griffiths RR, Richards WA, McCann U, Jesse R. Psychopharmacology (Berl). 2006 Aug;187(3):268-83; discussion 284-92. Epub 2006 Jul 7.PMID: 16826400) utilized approximately 0.4 mg/kg. This dose occasioned a mystical experience and a sense of oneness with the universe.
Subsequent fMRI studies demonstrated psilocybin has the effect of decreasing activity in key areas of the brain which help to eliminate the crosstalk between the medial prefrontal cortex and the posterior cingulate cortex. This physiological response may be responsible for the "oneness with the universe" experience often seen in psilocybin trials including an ongoing Clinical Trial on cancer patients at NYU. The higher doses of psilocybin may not result in neurogenesis as do the lower doses but may still be beneficial by shutting down the sense of self and allowing the individual to sense a universal connectedness.
In essence, the stronger the ego, the less an individual is able to sense the connectedness with all things. This realization has provided peace to numerous individuals inside and outside of Clinical Trials when done with the proper set and setting. In summary, both the lower and higher doses of psilocybin may have their therapeutic effects. Low dose psilocybin could be given on a weekly basis to promote neurogenesis, which is how SSRIs are thought to provide their therapeutic effects. The higher dose may have to be given only once, under therapeutic conditions to promote a sense of connectedness with a higher power to alleviate the existential crisis seen in PTSD and cancer patients.
More research is needed and this is a good opportunity for the DoD and/or VA to show the Active Duty Military and Veterans that they will do what it takes to help alleviate the epidemic of PTSD found in those populations.
Sunday, July 7, 2013
Low dose psilocybin erases conditioned fear in mice faster than high dose psilocybin and has potential as treatment for PTSD
Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning
Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.
Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos. J.
Exp Brain Res. 2013 Jun 2. [Epub ahead of print]
PMID: 23727882
(PDF)
Cited by (Google Scholar)
Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.
Catlow BJ, Song S, Paredes DA, Kirstein CL, Sanchez-Ramos. J.
Exp Brain Res. 2013 Jun 2. [Epub ahead of print]
PMID: 23727882
(PDF)
Cited by (Google Scholar)
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