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Microdosing Psilocybin

After nearly four decades of ironclad prohibition against research against psilocybin, the active alkaloid in ‘Magic Mushrooms’, its reemergence back into academia is offering some very interesting potential in regards to the treatment of depression. In turn, it is earning itself some well-deserved popularity in both the scientific and public eye.

For myself, fully psychoactive or ‘flood’ doses of psilocybin have played a key role in my journey of learning to live with depressive episodes and anxiety in a way that keeps me grateful and inspired by life. It has also been a primary area of research for me over the last several years. I have written two full-length books and given several lectures on the topic. As I have been following the research and the culture, I have noticed a fairly recent trend developing: microdosing.

‘Microdosing’ means taking a very small, ‘sub-perceptual’ dose of a psychedelic, such as LSD or psilocybin.

With the cultural explosion of microdosing psilocybin, there are an increasing number of anecdotes proposing benefits such as cognitive enhancement and problem solving, spiritual development and even the treatment of migraine and cluster headaches15.

There is also a developing hypothesis that microdosing psilocybin can be an effective means to treat depression. Along with increasing articles and videos on the Internet that present theories behind what this treatment can do for you, and even how to do it, there is also an increasing number of people who claim it worked for them.

But, anecdotal evidence is circumstantial, unverified and speculative and I believe these potentials deserve further investigation. So I did some research and found some pieces of information that I believe people should know before they jump on the bandwagon of microdosing psilocybin as a means to treat depression.

This essay is intended to offer people clarity around the psychopharmacological (and spiritual) mechanisms behind psilocybin in general, so that if one chooses to explore microdosing to treat depression, they do so with realistic expectations.

Neurological Mechanisms And Dispelling The Cumulative Theory

Over the last few years, there has been some wonderful development of the science around psilocybin14. For example, in fully psychoactive or ‘flood’ doses, psilocybin can catalyze mystical-type experiences11 and create long-lasting positive change in adult personality12. There is also evidence presenting psilocybin’s neurophysiological effect as being able to rescind the neurophysiological functions associated to anxiety and depression13.

In following the general discourse of microdosing psilocybin in the psychedelic subculture, I have noticed a tendency for people to list off effects found in these academic studies as warrant to microdose. This is a mistake.

Psilocybin’s effects are dose dependent and just because an effect has been observed within flood dose range don’t mean that those effects will be equivalent to but smaller within the microdose range. Nor is there any evidence that microdoses of psilocybin will cumulate in the brain to eventually equal out to a flood dose. In fact, the evidence states the contrary.

The only psychoactive metabolite of psilocybin is called psilocin6. It only takes about 40 minutes for psilocybin to be completely ‘dephosphorylated’ into psilocin6, which itself has a half-life of only 3 hours6. So microdosing with psilocybin is very unlikely to create a cumulative effect in the brain.

In comparison, ibogaine (the primary psychoactive alkaloid of the highly psychedelic African Iboga root) is one substance whose presence in the brain may accumulate through long-term microdosing to create a flood level effect 7. It converts into noribogaine and remains in the blood in significant concentrations even after 24 hours5. Ibogaine’s cumulative effect is likely sourced in the storage of noribogaine as it “possesses some of the same effect as ibogaine” and is believed to be “stored in fat tissue and released over the course of the following weeks or months”8.

Given how quickly the only known psychoactive metabolite of psilocybin is passed out of the body, a pharmacologically cumulative effect can probably be ruled out. Thus, we should probably stop touting flood doses’ effects as being translatable to microdoses’ potential, and instead start observing and mapping microdoses specific potentials.

Spiritual Mechanisms Of Psilocybin

Of course, speaking solely of neuropharmacology drastically misses the point when it comes to depression. Part of psilocybin’s capacity to create transformational change at flood dose ranges is its ability to loosen and override specific mechanisms of the personality. In doing so, it opens access to emotions and felt perceptions that are otherwise hidden from conscious awareness.

In my own work, I propose that one of “the 4 archetypes of psilocybin” is that of Surrender10. Psilocybin takes down defenses that protect us from whatever emotional trauma we have buried deep inside of us and our only viable option is to surrender to an (often) unrelenting swell of emotional honesty. It brings repressed emotions to the surface of our awareness, allowing us the capacity to experience them from a place of loving surrender. In other words, “implicit memory fragments of emotionally difficult and traumatic experiences can be healed through recognition and reconsolidation”9.

At flood doses, it is our presence to a deeply personal vulnerability that is coupled with the sense of being held in spiritual reverence (“mystical-type experiences”11) that I believe is essential for lasting healing to take place. Yet, when only a small amount is taken, that vulnerability doesn’t fully emerge. The defenses remain mostly intact and can continue to inhibit emotional recognition and release.

[This isn’t to say there is no potential for vulnerability and a sense of oneness with microdosing, but that it is unlikely to emerge to the same depth and readiness as it would with flood doses. Thus, in my opinion and experience, microdosing requires much more active involvement with emergent vulnerability to gain perspective, but isn’t likely to allow the type of emotive-psychosynthesis flood doses offer.]

Psilocybin’s Neurological Similarity With SSRIs

There is growing anecdotal evidence online of using psilocybin microdoses to help alleviate depressive symptoms. This, I believe, is because it can help as a treatment for alleviating the symptoms. But there is a difference between healing and managing/treating symptoms. The former implies is that the depression is gone; the latter implies that the depression’s negative affects are controlled.

Currently, Selective Serotonin Reuptake Inhibitors (SSRIs) are a primary pharmacological treatment for depression in the Western medical model. The main criticism of SSRIs (beside being over-prescribed) is that they only alleviate the symptoms by creating pharmacological defenses that further inhibit emotionality. Interestingly, microdosing psilocybin may have very similar pharmacological action to SSRIs.

In order to fully grasp this, it is important to first dispel an outdated idea: SSRI’s don’t work because of correcting a ‘lack’ of serotonin or other neurotransmitters. They work because they and other types of antidepressants act to mitigate and even reverse the neurological changes brought on by long-term stress/depression17. In particular, they work to increase functional connectivity and even neurogenesis in the hippocampus17,18,19. These two mechanisms are also associated with psilocybin’s neurological effects3,4.

Also, more so than any of the other classical psychedelics, psilocybin has a high affinity with the serotonin HT2b receptor site1. Modulation of this particular site is associated with the effectiveness of SSRI medication. While damage to, or genetic lack of this receptor site is associated with SSRI-resistant depression2 (‘treatment-resistant depression’).

Psilocybin microdosing helps to alleviate depression with the same mechanism as SSRIs, which does not address the emotional roots of depression. Thus, if one chooses to microdose psilocybin without making any other lifestyle changes and eventually stops, the perceivable effects may wear off and the depression will likely return. Worse yet, the depression may even deepen due to a sense of yet another hopeful treatment gone wayward. [(I have received emails from people whom have suffered this exact situation.)] As well, given these similarities, if someone is already resistant to SSRI treatment, then microdosing psilocybin may not work at all.

Compared with SSRIs, I see psilocybin as increasing resilience and openness rather than creating a bland omission of stark emotional variances reported by those who take SSRIs. I propose this qualitative difference may have to do with the observation that psilocybin reduces activity in the amygdala3, the area of the brain assocaited to fear/threat response and is overactive in people with depression17. As far as I have read, long-term antidepressant use does not have this type of effect.

Understanding that both micordosing of psilocybin and SSRIs can alleviate symptoms means we may be able to move towards microdosing with psilocybin in conjunction with psychotherapy to effectively replace SSRIs. (How exciting!)

Microdosing Psilocybin Does NOT ‘Heal’ Depression

There are many possibilities that still wait on the horizon in this area of research and I deeply believe in the power of psilocybin to assist a person in their journey of self-discovery.

[I believe that] At flood doses, it brings us into the roots of our trauma and beyond into the essence of life that animates us, enabling the capacity to reassemble who we are from a place of emotional integrity and resilience. At microdoses, it can be an asset to our healing journey by mitigating depressive symptoms, and perhaps softening our defenses just enough to enable us access to a deeper understanding of who we are, and who we want to be.

That being said, I want to prevent people from getting their hopes up based on other people’s unsubstantiated propositions. Microdosing psilocybin will not, in and of itself, heal depression, and the false hope that it will, may prove as more harm than help.

Neither microdoses nor flood doses alone will bring a person to resolve the root of their depression. There is no magic bullet for depression, regardless of dose level or what the subculture around psilocybin may tell us. It is a profoundly complex condition.

However, there are plenty of helpful and supportive means available to move through depression; namely, to buffer chronic stress while healing the brain and coming into awareness of the core traumas at the root of one’s depression. Perhaps microdosing psilocybin will be those means for some of us, just be careful not to lose hope if it doesn’t work.


EDIT (March 10, 2016): In a deepened review of this work, I have removed some sentences via a strike through, and added some comments via [crotchets]
Featured Image Courtesy Of A.Hasan. via Creative Commons

1- ‘Psychedelics and the Human Receptorome’ Thomas S. Ray, (Article In Digital Journal), 2010, PLOS ONE

2- ‘5-HT2B receptors are required for serotonin-selective antidepressant actions’ Silviana Laura Diaz et al., (Article In Print & Digital Journal), 2012, Molecular Psychiatry 17(2): 154–163.

3 -‘Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning’ Briony J Catlow et al., (Article In Journal), 2013, Experimental Brain Research [Volume 228, Issue 4, pp 481-491]

4 – ‘Homological scaffolds of brain functional networks’ Giovanni Petri et al., (Article In Digital Journal), 2014, Journal of The Royal Society: Interface

5 – ‘A preliminary report on the safety and pharmacokinetics of ibogaine’ D. C Marsh et al. (Article In Print Journal), 1995, Biological Psychiatry (37)9: 652

6 – ‘The pharmacology of psilocybin’ Torsten Passie et al. (Article In Print Journal), 2002, Addiction Biology 7: 357-364

7 – Jonathan Dickinson of The Global Ibogaine Therapy Alliance (Personal communication), 2016

8 – ‘Clinical Guidelines for Ibogaine-Assisted Detoxification’ Jonanthan Dickinson et al. (Digital Book In HTML Format), 2015, The Global Ibogaine Therapy Alliance

9 – Dr. Devon Christie, 2016, (Personal Communication regarding trauma-focused therapy)

10 – ‘Decomposing The Shadow: Lessons From The Psilocybin Mushroom’ James W, Jesso, 2013, (Print Book), Soulslantern Publishing

11 – ‘Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance’ Roland R. Griffiths et al., (Article in Journal), 2006, Psychopharmacology [Volume 187, Issue 3, pp 268-283]

12 – ‘Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness’ Katherine L. MacLean et al., (Article In Digital Journal), 2011, Journal Of Psychopharmacology

13 – ‘The Trip Treatment’ Michael Pollen, (Magazine Article), 2015, The New Yorker

14 – ‘A New Understanding: the science of psilocybin’ MYTHAPHI, (Video Documentary), 2015, MYTHAPHI

15 – ‘Everything You Wanted To Know About Microdosing (But Were Afraid To Ask)’ Carolyn Gregoire, 2016, (Digital Article), Huffington Post

16 – ‘The 4 Archetypes Of Psilocybin ~ Vancouver, BC ~ Oct . 29, 2013‘ James W. Jessso, (Audiobook), 2014, SoulsLantern Publishing

17 – ‘How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy’ Chittaranjan Andrade and N. Sanjay Kumar Rao, (Article In print Journal), 2010, Indian Journal Of Psychiatry, 52(4): 378–386

18 – ‘Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor’ C Anacker et. Al, (Article In Print Journal), 2011, Molecular Psychiatry, 16(7): 738–750

19 – ‘Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus’ Jessica E. Malberg et al., (Article In print Journal), 2000, The Journal Of Neuroscience, 20(24): 9104-9110


*** Copy Editing Credit To Lauren Cote

You can help James Jesso continue writing via his Patreon Page


  1. “James is a Candian author” <– I'm 90% sure you mean "Canadian"… You might want to fix that in your sidebar.

    I love the detail and research behind the post, and that you cited sources. So valuable in this space. I'll let you know when I'm (inevitably) putting a microdosing episode together. It seems to be all the rage right now.

    I hadn't heard the term "flood dose" before, but that's a great one as well. *Macrodose* would be catchy too. (Thanks, spellcheck!)

  2. Synch…!!

    Great well researched/linked article that *intensely* resonates with me…because I *have* been micro/medium dosing shrooms on a semi-regular basis for a couple of years now, after I decided [quasi-scientifically] to check out the anecdotes & ‘rumours’ I had come across on the www over the years.

    A recent offering is here:

    And i think it’s mentioned in passing in this 2006 book I’ve seen, & glanced thru several times, but have yet to read…you seen this too?

    Anyway i would have had up to 10 ‘minor/moderate’ trips spread over the last 2 years, from shrooms I gathered in mid 2014 & then dehydrated…certainly no flood doses, & i think they have perhaps slowly weakened over time since harvest…??…although I did get some smallish, but exciting, brightly twinkling tubes to surf on many occasion…all finished now though, bar 1 dose 🙂

    i experienced them, mostly alone, everywhere from the movies (Hunger Games sequel; I know, silly in a way!), walking in the bush, writing in my diary (a creative boost was apparent IMHO, & felt much more strongly than just a placebo BTW), as well as massaging the keyboard feed into the w.w.web, swimming, several times lying on the couch at night in the dark with my eyes closed, once having dinner at a restaurant with my family (after the movie) & also once at a rave concert with a friend, etc…

    Anyway, from my semi-scientific anecdotal experiences as above, i *whole-heartedly* corroborate what you say in your essay above; the value of micro-dosing is short lived, & fails to significantly shift habitual emotional [pre]thought forms that are etched deep into the neuro-matrix of my mind-brain interface…however, there is benefit, & I AGREE that there is a shift to a state of more openness for a few days or weeks, depending on external evironmental stressors & the prevalence of internal negative thought patterns re-emerging from those neural grooves beneath the psilocybin spit & polish.

    For lasting benefit, my own flood doses in the more distant past have had much more significant staying power, altho even those are well assisted by boosts in the appropriate set & setting. The lesson of ‘flood doses’ is, as was said by Huston Smith in the 60’s, perhaps purifying the message of his friend Leary:

    “The goal of spiritual life is not altered states, but altered traits.

    Para-phrasing yourself, it appears that depending on personal emotional & genetic history, the flood dose is by far best to ‘rewire’ the amygdala, ‘revisit’ & release the unconscious emotional ‘learnt mistakes’ of childhood, & right up to our most recent failed relationships, & with this clean slate consciously choose positive emotionally intelligent responses to various stressors.

    Must say it’s still way easier said in theory, than done in practice, however like you recommend, when done in conjunction with a meditative practice, regular exercise, & a healthy diet, in the broadest sense as adults, we truly begin to grok that, as Aristotle(?) said 2,500 years ago, ‘we are what we *eat*’, in all senses of the word ‘eat’; food, company we keep, thoughts/emotions we indulge in, the adventures in life that we enjoy…& not…

    Its still beyond boggling, but we can now easily see that the mind-brain is an evolving biological artwork of the most extraordinary complexity, so it is less of a mystery that i still struggle to understand my own deepest fears & loves…i have fairly relatively recently also concluded the message may be to surrender , to submit to the vulnerability, as you said…& paradoxically, the more i learn of it’s infinite mystery, the more eternally mysterious it seems…

    The way i have intellectualized it, & thus struggle to *directly* connect with it, is to see vulnerability as a consciously evolved loving compassionate response, as opposed to the ‘primeval automaton’ stress induced flight or flight response from our bacterial genetic ancestors…for bacteria the nuances of the environment existed as limited largely to life/death, food/not food, & thus while there was stress incurred often, the ‘choices’ able to be made were severely limited…whereas the genetic progeny of our bacterial forefathers, who still outnumber us in single cellular genetic diversity within our bowels at a ratio of 10 trillion bacteria cells – 1 trillion human cells, couldn’t feel much emotion *individually*, their uncoordinated, yet *collective* ‘pulsing with life’, is what forms the basic basis of our modern human limbic systems emotional baseline state…the paradox is exquisite…

    If you haven’t seen this vdo below, i am sure it will also likely resonate with you…

    The Power of Vulnerability | Brene Brown | TED Talks I Jan 2013:

    Such a blessing to stumble across your essay tonight – THANK YOU for so accurately expressing in writing what i have been ‘feeling’ over the last few years..!!

    And also much thank you also to Graham Hancock’s Facebook page that i follow, that i should find your website link there…that’s the synch…!!

    …oh the mycelial mind moves in mysterious ways…

    My blog post below is one of my most recent creatively integrative efforts…still got my ‘L’ plate tho… 🙂

  3. While you might be right, not enough scientific research has been done on microdosing to make these claims. Definitely premature assumptions

    • Hey Be, good points. The article is going into other research to support some claims and dispel others. Conclusions would be premature, but the assumptions are IMO on time and open to be expanded, refined and released as more research emerges.

  4. As a preface, you might want to warn the reader that depression is highly correlated with nutritional deficiencies (e.g. amino acids) and endocrine dropout (esp. hypothyroidism). Much of what is called “SSRI-resistant depression) is failure of allopathic doctors to properly diagnose and treat nutritional and/or endocrine problems. I doubt any level of psilocybin therapy would help when these problems are present.

    • This is a great comment, thank you. I personally do think that the properly integrated psilocybin experience would help in these areas, at the very least temporarily. That being said, and true to your comment, with no change to the external life context from which depression emerged, no level of chemical intervention will prove entirely successful.

  5. “I propose this qualitative difference may have to do with the observation that psilocybin reduces activity in the amygdala, the area of the brain assocaited to fear/threat response and is overactive in people with depression. As far as I have read, long-term antidepressant use does not have this type of effect.”

    Actually, long term antidepressant use does have this effect. SSRI usage reduces activity in the amygdala. (see links to studies below)

    The effect that the SSRI has on subduing fear is profound for me, what with OCD and anxiety usually interfering with my life and amplifying fearfulness. If only the side effects were not so severe for me.

    I’m curious to know what the side effects from microdosing psilocybin might be and what the long term efficacy is like compared to SSRI use. Hopefully, we will have more insight into this matter in the coming years with personal experiences and further research.

    • Thanks for this info mate, I will read up on this study soon. I am surprised I missed it, though not that surprised. I really appreciate this kind of feedback!

  6. HiJames,
    Do you think you can cure some of you re depression with mushrroms? or is this just a condition you live with>?

    • Well, tough to say really cause I’m not sure depression is something that needs to be cured, in (and pardon me for making light of it) that indigestion needs to be cured. The root of what leads the mind and body to manifest the set of symptoms that we diagnose as depression can be addressed in a properly formulated and professionally held psilocybin session. That being said, the nuances of how to properly formulate and what type of professionalism is up for debate. I believe that what the psilocybin can do it help to remap and reassociate our inner sense of self, but it doesn’t just do it for us and if we do not have the support to do it properly the extent to which it will work is highly variable. So I guess I am saying “maybe, depends on what you mean; it’s complicated”.

      If you would like to be dialed into my most recent thoughts on depression and psilocybin, sign up for my newsletter. I will be releasing details on about a webinar I will be holding on this topic soon.

      • Thanks James, I will sign up. Love you’re work around depression 😉

        Thank you

  7. – Do you know how microdosing affect intelligence (IQ scores on mensa tests)?
    It shouldn’t be too difficult to organize.

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