1.1) There’s some weak wisdom of nature prior that blasting one of your neurotransmitter pathways for a short period is unlikely to be helpful.
The data doesn’t support this, and generally suggests that 1-3 psychedelic experiences can have beneficial effects lasting 6 months or longer. See for example Carhart-Harris et al. 2018:
“Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort.”
“High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety.”
“All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16 – 57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent.”
I get more sceptical as the number of (fairly independent) ‘upsides’ of a proposed intervention increases. The OP notes psychedelics could help with anxiety and depression and OCD and addiction and PTSD, which looks remarkably wide-ranging and gives suspicion of a ‘cure looking for a disease’.
I would push back against the idea that these upsides are as independent as they may seem. Depression and anxiety are often comorbid (Hirschfeld 2001) and often comorbid with addiction (Quello 2005), OCD (Tukel 2002) and eating disorders (Marucci 2018). It seems that similar neurological states and cognitive processes underly these mental disorders, which is why psychedelics can effectively treat them all.
“A sense of disconnection is a feature of many major psychiatric disorders, particularly depression, and a sense of connection or connectedness is considered a key mediator of psychological well-being, as well as a factor underlying recovery of mental health. One of the most curious aspects of the growing literature on the therapeutic potential of psychedelics is the seeming general nature of their therapeutic applicability, i.e. they have shown promise not just for the treatment of depression but for addictions, anxiety and obsessive-compulsive disorder. This raises the question of whether psychedelic therapy targets a core factor underlying mental health. We believe that it does, and that connectedness is the key.”
A secondary point here is that substances with different pharmacological and phenomenological effects are all grouped under the term “psychedelic”. MDMA, for example, works and feels differently from ketamine, which works and feels differently from “classical” psychedelics like LSD, psilocybin, and DMT. So while it may seem unlikely that psychedelics (understood as one uniform thing) could have a range of benefits, it makes more sense when psychedelics are understood as a category that includes different substances.
The data doesn’t support this, and generally suggests that 1-3 psychedelic experiences can have beneficial effects lasting 6 months or longer. See for example Carhart-Harris et al. 2018:
“Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort.”
Griffiths et al. 2016:
“High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety.”
Johnson et al. 2017:
“All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16 – 57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent.”
I would push back against the idea that these upsides are as independent as they may seem. Depression and anxiety are often comorbid (Hirschfeld 2001) and often comorbid with addiction (Quello 2005), OCD (Tukel 2002) and eating disorders (Marucci 2018). It seems that similar neurological states and cognitive processes underly these mental disorders, which is why psychedelics can effectively treat them all.
Carhart-Harris et al 2017, for example, suggest “connectedness” as the mechanism:
“A sense of disconnection is a feature of many major psychiatric disorders, particularly depression, and a sense of connection or connectedness is considered a key mediator of psychological well-being, as well as a factor underlying recovery of mental health. One of the most curious aspects of the growing literature on the therapeutic potential of psychedelics is the seeming general nature of their therapeutic applicability, i.e. they have shown promise not just for the treatment of depression but for addictions, anxiety and obsessive-compulsive disorder. This raises the question of whether psychedelic therapy targets a core factor underlying mental health. We believe that it does, and that connectedness is the key.”
A secondary point here is that substances with different pharmacological and phenomenological effects are all grouped under the term “psychedelic”. MDMA, for example, works and feels differently from ketamine, which works and feels differently from “classical” psychedelics like LSD, psilocybin, and DMT. So while it may seem unlikely that psychedelics (understood as one uniform thing) could have a range of benefits, it makes more sense when psychedelics are understood as a category that includes different substances.