Editors’ note: Jason Lupoi wrote this essay in November 2020. It appears unchanged; an editors’ postscript below covers what the research has shown since.
An ego is defined as “the self especially as contrasted with another self or the world.” Related to that term are concepts like self-esteem and self-conceit, thought exercises that the self creates around itself like a comforting blanket and simultaneous defense shield. An egotistical person is said to have an “exaggerated sense of self-importance,” a character trait that works against the currents of the community.
Interestingly, with the rise of social media, a twin monolith of egotism has spawned.[1] A once-convenient way to keep in touch with friends and family has become an addiction to some people[2], often in attempts to perpetually ego-boost from instant and likely validating feedback from “followers” who may have never met live and in-person.
Ultimately, like any drug, obsessively collecting followers and soliciting and monitoring this feedback can affect one’s job performance[3] and one’s mental status, as anxiety[4], depression[4], and suicide-related thoughts[5] have been linked to the web of the consequences of seemingly innocuous daily choices.
Concurrent to all this, humanity is looking towards once shunned botanicals like cannabis and psychedelic mushrooms as two life rafts in a techno-induced maelstrom. How these plants will correlate with current behaviors is for scientific investigation to tell, but our interest in doing so couldn’t be timelier and more relevant.
As an example, a recent study evaluated the effects of psilocybin on ego dissolution, or ego death.[6] This process recounts the psychedelic experience as illuminating the world around us such that we see ourselves as part of the whole, instead of a whole unto ourselves.
There are two pathways of ego death that differ in the mental states they invoke. A negatively experienced ego death, as per the study, involves anxiety ego dissolution (AED), defined as “the dimension encompassing the loss of autonomy and self-control of thought processes, intentionality, decision making, and spontaneous movements.”[6] AED-associated mood changes include paranoia, heightened awareness and attention to one’s surroundings, and acute (not long-term) anxiety.
Positively experienced ego dissolution is thought to arise from the breakdown of one’s self-image via a temporary loss of access to autobiographical details.
These researchers wanted to better sort out the chemical mechanism for why this happens.
It turns out that there’s a serotonin receptor linked to hallucinatory experiences; serotonin is that “feel good” chemical, or neurotransmitter, that plays an important role in mood. Other psychedelics like psilocybin (from “magic mushrooms”), lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT; often used with ayahuasca) also interact with these receptors.
But serotonin does not work alone to produce these effects. Another neurotransmitter called glutamate also regulates this activity. Glutamate is “excitatory,” meaning that it will cause a series of actions to occur in a neuron or brain cell. These actions at the chemical and cellular level influence important processes in the brain like creating connections that support learning and memory. So researchers sought to better understand how both serotonin and glutamate affect the overall psychedelic experience, with a focus on the ego.
The researchers investigated psilocybin’s acute effects on glutamate levels and the subsequent psychedelic-induced changes in brain function and behavior. They used an advanced technique called multimodal brain imaging to look at the specific regions of the brain that psilocybin “lights up” or activates. They found that participants in the psilocybin group given 0.17 mg/kg (versus the placebo group) had elevated glutamate levels in the medial prefrontal cortex (mPFC), a region important for decision making, and lower glutamate levels in the hippocampus, a region important for memory.
Interestingly, increased levels of glutamate in the mPFC best correlated with negatively experienced ego dissolution. Lower levels of glutamate in the hippocampus best correlated with positively experienced ego dissolution.
The study showed for the first time in humans that increases in glutamate via serotonin activation in the mPFC generates clearly distinct effects compared to the hippocampus. Increased mPFC glutamate provided the strongest predictor of AED. A secondary contributor to negatively experienced ego dissolution was “oceanic boundlessness,” a concept originating in conversations between Sigmund Freud and a mystic named Romain Rolland describing a sense of eternity and being one with the universe[7].
Interestingly, oceanic boundlessness provided a secondary contributor for positively experienced ego dissolution, too.[6]
Regardless of which path results in drug-induced ego demise, ego dissolution has been found to result in lasting clinical results for conditions like anxiety[8], depression[9], and addiction[10], as well as increases in well-being[11]. [Editor’s note, 2026: these are associations from uncontrolled or open-label studies; see the postscript.]
References
- Andreassen CS, Pallesen S, Griffiths MD. The relationship between addictive use of social media, narcissism, and self-esteem: Findings from a large national survey. Addict Behav. 2017;64:287-293.
- Blackwell D, Leaman C, Tramposch R, Osborne C, Liss M. Extraversion, neuroticism, attachment style and fear of missing out as predictors of social media use and addiction. Personality and Individual Differences. 2017;116:69-72.
- Zivnuska S, Carlson JR, Carlson DS, Harris RB, Harris KJ. Social media addiction and social media reactions: The implications for job performance. J Soc Psychol. 2019;159(6):746-760.
- Shensa A, Sidani JE, Dew MA, Escobar-Viera CG, Primack BA. Social media use and depression and anxiety symptoms: A cluster analysis. Am J Health Behav. 2018;42(2):116-128.
- Luxton DD, June JD, Fairall JM. Social media and suicide: A public health perspective. Am J Public Health. 2012;102 Suppl 2:S195-S200.
- Mason NL, Kuypers KPC, Müller F, et al. Me, myself, bye: Regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology. 2020;45(12):2003-2011.
- Freud S. Civilization and Its Discontents. Broadview Press; 1929.
- Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30:1181-97.
- Roseman L, Nutt DJ, Carhart-Harris RL. Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front Pharmacol. 2017;8:974.
- Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev. 2015;7:157-64.
- Uthaug M, Lancelotta R, van Oorsouw K, et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology. 2019;236:1-14.
What the research has added since 2020
Editors’ postscript, November 2026. Does the ego dissolution Jason Lupoi describes do the healing? Six years on, it predicts the healing; nobody has yet shown that it causes it.
In the trials that scored the experience, the people who rated it most intense did best. In the Imperial College pilot Lupoi cites, 20 patients with treatment-resistant depression took psilocybin, and the “oceanic boundlessness” score from the session predicted how far their depression fell five weeks later; the dread score predicted the opposite.[9] The Johns Hopkins cancer trial found the same pattern with its mystical-experience scale.[8] Both are correlations inside trials that cannot be blinded, so expectancy travels with the experience; the psilocybin flagship explains why that matters.
The question is now being tested directly. In mice, a redesigned ibogaine molecule that produces no sign of a trip still produced antidepressant-like behavior and cut alcohol-seeking, which says the two may be separable in rodents and nothing yet about people.[12] The human test is a trial in Toronto that gave depressed patients psilocybin with or without risperidone, an antipsychotic that blocks the receptor and with it the experience. It has finished; as of November 2026 its results have not been published.[13]
Two things about risk and dose. In a survey of 1,993 people describing their worst mushroom experience, 10.7% said they had put themselves or others at risk of physical harm, and of the 1,339 whose experience was more than a year old, 7.6% had sought professional treatment for lasting symptoms, which is why trials screen and supervise.[14] A 2026 national survey, covered in our brief, found a similar minority. Ego death is a high-dose phenomenon. Microdosing is the other end of the scale, and its trials are a separate story. The experience is something people seek out, and something that goes badly for some.
References (2026)
- Cameron LP, Tombari RJ, Lu J, et al. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature. 2021;589(7842):474–479.
- Centre for Addiction and Mental Health. Does psilocybin require psychedelic effects to treat depression? (PSI-RIS). ClinicalTrials.gov NCT05710237. Registered 2 February 2023; no results posted as of November 2026.
- Carbonaro TM, Bradstreet MP, Barrett FS, MacLean KA, Jesse R, Johnson MW, Griffiths RR. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol. 2016;30(12):1268–1278.
This article is an educational summary. It is not medical advice.
Updated November 2026: the editors added a postscript on whether the experience described here drives the clinical results, with the trials since; Jason Lupoi’s essay appears unchanged. Originally published 13 November 2020.
Featured image: Psilocybe mexicana, by Cactu, via Wikimedia Commons, licensed under CC BY-SA 3.0; cropped and resized.
