Robin L Carhart-Harris, Leor Roseman, Mark Bolstridge
Lysia Demetriou, J Nienke Pannekoek, Matthew B Wall, Mark Tanner, Mendel Kaelen, John McGonigle, Kevin Murphy, Robert Leech, H Valerie Curran, David J Nutt
2017 · Scientific Reports
Abstract Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.
Metadata: Crossref. Abstracts retain their original authors’ rights.
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Apparently not that horrible, with 25mg of psilocybin: Treatment with psilocybin produced rapid and sustained antidepressant effects. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. https://www.nature.com/articles/s41598-017-13282-7
The poster asked for "access to psychedelics (and analogues) in a safe, professional setting", which ideally (if the treatment is one that indeed works and isn't placebo) would be one that is monitored by your doctor. I agree that self-medication is not idea. The issue here I think is that most current anti-depressants are currently of the SSRI / SNRI / tri-cyclic class. These treatments work great for some people, but do not work for everyone. In one case (ketamine), this particular hallucinogenic drug has emerged as a candidate for anti-depression therapy (at least in mechanism) that works quite a bit different than the above (acts on glutamate). Non-hallucinogenic…
glutamatergic anti-depression drugs are being developed as a result, but as one is well aware, this takes time. Until one of these drugs emerges (rapastinel seems furthest along at this time), off-label ketamine clinics do exist where you can take the drug with some degree of clinical supervision. I have not seen too much on the serotonin agonist hallucinogens in the past relieving depression, but Googling, there does seem to be a newish article on psilocybin (https://www.nature.com/articles/s41598-017-13282-7) that suggests it does offer a possible interesting anti-depression mechanism too. Possibly more exploration is needed here to confirm whether it works well (or not) and, if so, how. I don't think we've even come close to exploring all routes to resolving depression, so I think exploring as many routes as possible is a good path. (And I do think scientists are doing this -- the parent article was for instance the first time I've heard of a melatonin receptor agonist as an anti-depressant candidate! https://en.wikipedia.org/wiki/Agomelatine )
Some recent research: Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors http://journals.sagepub.com/doi/full/10.1177/026988111773127... Psilocybin for treatment-resistant depression: fMRI measured brain mechanisms https://www.nature.com/articles/s41598-017-13282-7.pdf
The key point from the paper [1]: >Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Small sample size, but definitely an interesting result. I was hoping they'd test again after a few months have passed, though. [1] https://www.nature.com/articles/s41598-017-13282-7
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