Subjective Effects of Psychedelic Tryptamines

One common question I'm asked is how the subjective experience of different psychedelic tryptamines are similar or different from one another. It's a good question because there are some pretty noticeable differences between the subjective experiences invoked by different psychedelics.

There are four psychedelic tryptamines that I wanted to touch upon including the three classic psychedelic tryptamines N,N-DMT, psilocybin, and LSD as well as the naturally occurring tryptamine 5-MeO-DMT. I chose these to focus on in this video both due to their relative popularity compared to other types of psychedelics and the availability of data or information to contrast effects to one another. 

On the one end of subjective experience is N,N-DMT or "the spirit molecule" which may represent quintessential 'hallucinogenic' as well as 'interactive-relational' psychedelic effects [1]. These two components tend to couple in the N,N-DMT experience, although perhaps could be considered separate phenomenon. N,N-DMT produces vivid and hyper fractalized types of visual imagery along with a sense of an 'other' or 'entity' being present [2]. With inhaled N,N-DMT reports of entities such as deities or extraterrestrials are common with higher doses, whereas when N,N-DMT is used orally in the ayahuasca brew it's oftentimes the 'spirit of ayahuasca' or 'mother ayahuasca' that is felt as the other. 

On the other end of subjective experience is 5-MeO-DMT  or "the God molecule" which may represent quintessential 'entheogenic' effects. The 5-MeO-DMT experience is often characterized by an experience of oneness or unity which is a 'non-dual' type of experience or experience in which the subjective-object relationship has collapsed and there is little to no sense of other [3, 4]. With 5-MeO-DMT, prominent hallucinogenic effects are usually lacking and may be limited to the first few minutes of the experience when they do occur. 

Tryptamines like psilocybin and related ergolines like LSD seem to have a spectrum of effects that have elements of both 'poles' of psychedelic experience. The presence of entities, 'machine elves', and extraterrestrials have occurred with use of psilocybin, yet it is also being studied and highlighted due to non-dual mystical experiences that are frequently occasioned in clinical settings [5-7]. At least according to the tools we have to measure effects of psychedelics today, it appears there is little difference between subjective effects of LSD and psilocybin [8]. What causes psilocybin to behave more like a hallucinogen or more like an entheogen is unknown, however could be a function of set and setting. For example, in one neuroimaging experiment conducted in a laboratory setting psilocybin displayed scores on the 5D-ASC that could be considered more 'hallucinogenic' whereas in another experiment conducted at a mindfulness retreat it appears more 'entheogenic' effects were present [9, 10]. 

It remains to be discovered just how important the role of subjective effects are in the therapeutic utilization of psychedelics and it may be that different substances and experiences can offer different things. It also remains to be discovered exactly what it is about the structures or pharmacology of different psychedelic tryptamines that drive the diversity in types of effects with different agents. At a less granular level it appears that regardless of the tryptamine used, when a ‘God encounter’ or ‘Ultimate Reality’ type of experience is felt that it has longstanding ramifications for the person’s beliefs and is one of their most meaningful life experiences [11].

References

1. Strassman, R.J., Human psychopharmacology of N,N-dimethyltryptamine. Behav Brain Res, 1996. 73(1-2): p. 121-4.
2. Davis, A.K., et al., Survey of entity encounter experiences occasioned by inhaled N,N-dimethyltryptamine: Phenomenology, interpretation, and enduring effects. 0(0): p. 0269881120916143.
3. Davis, A.K., et al., The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. J Psychopharmacol, 2018. 32(7): p. 779-792.
4. Barsuglia, J., et al., Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Front Psychol, 2018. 9: p. 2459.
5. Griffiths, R.R., et al., Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl), 2006. 187(3): p. 268-83; discussion 284-92.
6. Griffiths, R., et al., Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol, 2008. 22(6): p. 621-32.
7. Griffiths, R.R., et al., 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. J Psychopharmacol, 2018. 32(1): p. 49-69.
8. Holze, F., et al., Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology, 2022.
9. Smigielski, L., et al., Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat. Sci Rep, 2019. 9(1): p. 14914.
10. Lewis, C.R., et al., Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow. Neuroimage, 2017. 159: p. 70-78.
11. Griffiths, R.R., et al., Survey of subjective "God encounter experiences": Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT. PLoS One, 2019. 14(4): p. e0214377.