Marco Aqil, M.Sc.
Marco Aqil is a Ph.D. candidate at the Spinoza Centre for Neuroimaging in Amsterdam.View full profile ››
Edited by Jennifer Them & Lucca Jaeckel
- 10 minutes
- 28 února, 2019
- Implementation & Society
- Psychedelic Therapy
“Trasumanar significar per verba non si porìa; però l’essemplo basti a cui esperïenza grazia serba.”
Paradiso I, 70-72
Recently C.J. Büche wrote an in-depth analysis of the role of particular representations of psychedelics in popular media in the “psychedelic renaissance”1. In addition to his work, different ways of describing psychedelics can also be examined in scientific discourse. Paying attention to language choices may offer significant insight into the cultural and personal assumptions of the authors. With due exceptions: in some cases, researchers may have been constrained by funding agencies and ethical committees to describe psychedelics in negative terms, regardless of their own convictions, as a precondition to carry out and publish their studies.
Much like in general media, a variety of contrasting descriptions of psychedelics can be found in scientific media. At least three kinds of language can be identified: in the first, psychedelics are described as with no medical utility and high potential for abuse (“Schedule 1” drugs in all respects)2. In the second , they are considered potentially key to a better understanding of brain function3 and breakthrough treatments4 for otherwise untreatable psychiatric conditions. In the third kind of language, psychedelics are described only or mainly as “psychosis-inducing drugs”5, and considered medically useful in the study of psychotic disorders such as schizophrenia. This subdivision is of course a simplification to some degree: the same authors may use different language in different papers, and “mixed” accounts are also possible.
Schedule 1 Drugs
The first kind of language, summarized by the statement that psychedelics are drugs with a high potential for abuse and no medical utility, has little to no scientific basis6. This stigmatized view of psychedelics can be traced back to a political heritage of the 1970 Controlled Substances Act and the subsequent War on Drugs, and is rapidly disappearing from scientific publications in light of more recent and more rigorous evidence. Nonetheless, it is important to note that:
1) Contemporary clinical trials have been carried out with small sample sizes, highly restrictive screening processes, under constant professional medical supervision, and not always with the possibility of a fully double-blind placebo condition7. All these factors may have contributed to their success. This is not to diminish the impressive results of these rigorous and difficult studies (particularly in treatment-resistant populations); but rather to suggest avoiding hasty conclusions, such as that psychedelics may be risk-free panaceas for any and all psychiatric disorders.
2) While there is evidence that at the population level, the risks of psychedelics have been overstated8, there is no conclusive evidence for the safety of psychedelics at the individual level, and particularly little understanding of persisting effects such as HPPD9. Non-professional “therapeutic” practices involving the use of psychedelics outside clinical settings therefore present a significant amount of risk. This risk is potentially higher than with recreational use, not only because of the high variance in subjective and environmental factors already intrinsic in psychedelic experiences, but particularly because these practices target populations with potentially unaddressed neurobiological issues and high psychological sensitivity.
Tools and Medicines
The second kind of language, which describes psychedelics as useful medicines and important tools for scientific research, (re-)emerged recently with the contemporary and less politically-constrained wave of psychedelic research led by groups at Imperial College London and Johns Hopkins University, among others. The term “psychedelic renaissance” commonly refers to these lines of research, whose merits are many, undeniable, and documented extensively elsewhere10. In this context, it is worthwhile only to remark that some of these studies may also be criticized for using culturally specific terms (e.g. “mystical experiences”, “ego-dissolution”) under the implicit assumption that they reflect somewhat universal or biologically-grounded phenomena, which need not be the case.
For example, non-western cultures using psychedelics may lack the concept of a contemplative “mystical experience”, or the dualistic views of subject/object and internal/external implied by “ego-dissolution”. Therefore, they might experience and interpret the same neurological phenomena according to an entirely different ontology. Influential cognitive theories, such as predictive coding, indeed suggest that cultural and personal expectations (as well as language itself11) should powerfully shape the content and interpretation of psychedelic experiences, in agreement with a long history of observations12.
Models of Schizophrenia-Like Psychosis
The third kind of language is particularly interesting, because it has been and still is quite widespread, despite raising a host of scientific and philosophical questions of its own. Does it make sense to characterize psychedelics only or mainly as “psychosis-inducing drugs”? Is their psychiatric utility only or mainly to be found as models of “schizophrenia-like psychosis”5?
The canonical definition of psychosis is based on hallucinations, aberrant salience, and delusional beliefs, and appears water-tight in identifying pathological cases. However, it is only so because it relies on a specific, shared set of beliefs and assumptions. Language characterizing psychedelics only or mainly as “psychosis-inducing drugs” cannot be fully justified empirically, but instead has to rely on a very specific a priori judgement about the content of psychedelic experiences, as well as unstated assumptions about what constitutes real, how much of it is socially constructed, and importantly in this context, how much of it is accessible through language.
These questions have been the subject of intense philosophical debate for millennia, but are glanced over in some scientific papers using this kind of language. “Reality” is implicitly assumed to be deterministic, mechanistic, and fully encompassed by analytic language and mathematical laws: a worldview still prevalent in life sciences today, inherited from 19th-century physical sciences. However, even physical sciences have long since moved away from this view: Gödel’s incompleteness theorem and the quantum mechanical uncertainty principle, like modern Pillars of Hercules, pose fundamental limits to the systematically knowable reality. Furthermore, the social sciences inform us that much of what we commonly refer to as “real”, or at least acceptable, is determined by societal consensus, not by scientific examination. The humanities posit that language itself, let alone reality, has countless possible interpretations (with the escape of pragmatism: not all interpretations are equally useful).
The definition of psychosis is therefore at least as much culturally and socially determined as it is scientific. Psychedelic experiences, too, are heavily influenced by culture, both in their content and its interpretation. This suggests that particularly in scientific papers regarding psychedelics, all assumptions (e.g. what constitutes “real”, how much of it can be conveyed through language) and constructs (e.g. “psychosis”, “mystical experience”) should not be taken for granted as if they were empirically determined scientific facts, but rather carefully examined to avoid potential confounds.
Is the psychiatric utility of psychedelics only or mainly to be found in modeling “schizophrenia-like psychosis”? At first glance, psychedelic experiences can indeed share common features of schizophrenic psychoses: hallucinations, mania, paranoia. However, research shows that there is no straightforward link between any substance model and schizophrenia13. From a metacognitive viewpoint, after taking psychedelics, most people maintain a sense of the induced experience being somehow different from the ordinary reality of everyday life (note that both may be experienced as “real”, but real in different ways)14. Some schizophrenic patients do exhibit such a “double bookkeeping” pattern, or the ability to distinguish between the ordinary and hallucinatory realities they experience. But this is not true in all cases: in “single-bookkeeping” schizophrenic psychoses, hallucinations and ordinary reality are not distinguishable, and both are automatically taken at face value. In such cases, other substance classes, for example anticholinergic hallucinogens15, would provide a more accurate model. Furthermore, auditory verbal hallucinations, an important hallmark of schizophrenic psychoses16, are not a prominent feature of psychedelic experiences. Once again, a different class of substances (amphetamines) and modality of use (chronic rather than acute) may provide a more suitable model17.
A fortiori, the evidence showing long-term, population-level positive effects of psychedelics on suicidality and mental distress18, as well as the recent clinical trials on depression in terminally ill cancer patients19, clearly show that the psychiatric utility of psychedelics goes far beyond modeling psychosis6. Even if the premise is accepted that psychedelics are only or mainly “psychosis-inducing drugs”, one would have to concoct a convincing explanation for why inducing a “schizophrenia-like psychosis” turns out to be a positive choice for mental health, both at the statistical level in the general population and in medically controlled clinical trials. The available scientific evidence therefore suggests that there is more to psychosis (and even more so to complex psychotic disorders such as schizophrenia) than psychedelics can teach us about it; and vice versa, there is far more to psychedelics than what they can teach us about psychoses and psychotic disorders.
The conclusion seems warranted that language characterizing psychedelics only or mainly as drugs inducing “schizophrenia-like psychosis”, or suggesting any straightforward relation between the two, is at best a limited account, at worst misleading, and based upon unstated and questionable assumptions. For completeness, it is worth remarking that a similar line of criticism could be raised against language characterizing psychedelics only or mainly as “mystical-experience-inducing drugs” or “ego-dissolving drugs”; but this has not been the case in any serious scientific publication to date, hence why the criticism here was directed specifically towards the language of “psychosis-inducing drugs”. The same goes for any other attempt to oversimplify these complex phenomena and reduce them to a single aspect without taking potential cultural and linguistic confounds into account.
Language and Mechanisms: the Ineffable Medicine
For sake of brevity, let’s not discuss the languages of “unifying” theories of psychedelic effects20, which ultimately require a unified theory of conscious experience, an incredibly interesting but extremely difficult task for all the obvious reasons. There is no consensus in the scientific community when it comes to the specific mechanisms that should mediate the potential benefits of psychedelics for psychiatric conditions. Some researchers propose that they are due to reduced inflammation21, others to increased neuroplasticity22, others again (among which the key groups of the psychedelic renaissance) suggest that reaching an ineffable “mystical experience”19 or “ego-dissolving”23 psychological state is actually the crucial factor in the therapeutic process. Back to language again: “The Tao that can be spoken of is not the eternal Tao”. This age-old remark becomes relevant again in the context of psychedelic research. What is the most appropriate language to scientifically study experiences for which perhaps the most common subjective report is that the experience itself lies “beyond” or “outside” of language? Is there anything at all we can say about such ineffable concepts and experiences24?
The emerging picture is fascinatingly complex and far from settled. In the future, language choices will play a crucial role25, as they can build both bridges and walls between (apparently) contrasting theories. Psychedelics seem to resist all attempts at simplistic, systematic, complete characterization: even the most widely accepted neurophysiological mechanism of action (agonism at the 5HT-2A receptor26) does not directly explain why substances with entirely different receptor affinity profiles can have highly overlapping effects with those of psychedelics, for example Salvinorin A27, a kappa-opioid receptor agonist and the active compound in the plant Salvia Divinorum; or ketamine, an NMDA-receptor antagonist with hallucinogenic properties at specific doses28, capable also of increasing neuroplasticity22 and showing great promise in the treatment of depression29. Furthermore, the downstream effects of functional selectivity at the 5HT-2A receptor are still being worked out30, and recent analyses31 show that affinities for muscarinic and opioid receptors may also be relevant for predicting the reported subjective effects. These difficulties might discourage the scientific study of psychedelics, but seen in a different light, they greatly increase the potential contributions of these substances to science and medicine.
In conclusion, these reflections suggest a few general points that, if implicitly understood and explicitly implemented, might be useful to productively move forward in the field of psychedelic research:
- All assumptions and constructs should be double-checked with particular care to diminish cultural and linguistic confounds.
- Different scientific descriptions may be valid at the same time, although differing in scope and degree of supporting evidence.
- Theories should be treated as models and perspectives rather than complete and definitive explanations.
Psychedelic research is already stretching the boundaries of scientific language and methods. One might speculate that a paradigm shift in the way we view the relationship between brain processes and subjective experiences will be necessary in order to obtain a fully satisfactory, naturalistic account of these remarkable phenomena.
Or perhaps even that won’t do.
This article was first published on the APRA blog.
1. Büche CJ. The De-Politicisation of Psychedelics [Internet] [Master’s Thesis]. [London]: University College London; 2018 [cited 2019 Jan 30]. Available from: https://medium.com/@celestinjohannesbche/the-de-politicisation-of-psychedelics-bf89d280c9ef?fbclid=IwAR0UmOuaWSD-JkOcxKw0DM83kAxZh1n_8h98VGT82qsODMWIw9oinyA2l7I
2. Hu Q-D, Xu L-L, Gong Y, Wu G-H, Wang Y-W, Wu S-J, et al. Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress. Cutan Ocul Toxicol. 2018 Sep;37(3):233–9.
3. Kyzar EJ, Nichols CD, Gainetdinov RR, Nichols DE, Kalueff AV. Psychedelic Drugs in Biomedicine. Trends Pharmacol Sci. 2017 Nov;38(11):992–1005.
4. Schenberg EE. Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development. Front Pharmacol [Internet]. 2018 Jul 5 [cited 2019 Jan 30];9. Available from: https://www.frontiersin.org/article/10.3389/fphar.2018.00733/full
5. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998 Dec 1;9(17):3897–902.
6. Rucker JJH. Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential. BMJ. 2015 May 26;350(may26 20):h2902–h2902.
7. Carhart-Harris RL, Goodwin GM. The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology. 2017 Oct;42(11):2105–13.
8. Krebs TS, Johansen P-Ø. Psychedelics and Mental Health: A Population Study. Lu L, editor. PLoS ONE. 2013 Aug 19;8(8):e63972.
9. Litjens RPW, Brunt TM, Alderliefste G-J, Westerink RHS. Hallucinogen persisting perception disorder and the serotonergic system: A comprehensive review including new MDMA-related clinical cases. Eur Neuropsychopharmacol. 2014 Aug;24(8):1309–23.
10. Nichols D, Johnson M, Nichols C. Psychedelics as Medicines: An Emerging New Paradigm. Clin Pharmacol Ther. 2017 Feb;101(2):209–19.
11. Lupyan G, Clark A. Words and the World: Predictive Coding and the Language-Perception-Cognition Interface. Curr Dir Psychol Sci. 2015 Aug;24(4):279–84.
12. Al-Issa I. Social and cultural aspects of hallucinations. Psychol Bull. 1977;84(3):570–87.
13. Steeds H, Carhart-Harris RL, Stone JM. Drug models of schizophrenia. Ther Adv Psychopharmacol. 2015 Feb;5(1):43–58.
14. Fortier M. Sense of reality, metacognition, and culture in schizophrenic and drug-induced hallucinations [Internet]. Vol. 1. Oxford University Press; 2018 [cited 2019 Jan 30]. Available from:http://www.oxfordscholarship.com/view/10.1093/oso/9780198789710.001.0001/oso-9780198789710-chapter-16
15. Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, et al. DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens. ACS Chem Neurosci [Internet]. 2019 Jan 10 [cited 2019 Jan 30]; Available from: http://pubs.acs.org/doi/10.1021/acschemneuro.8b00615
16. Hugdahl K. Auditory hallucinations in schizophrenia: the role of cognitive, brain structural and genetic disturbances in the left temporal lobe. Front Hum Neurosci [Internet]. 2008 [cited 2019 Jan 30];1. Available from: http://journal.frontiersin.org/article/10.3389/neuro.09.006.2007/abstract
17. Bramness JG, Gundersen ØH, Guterstam J, Rognli EB, Konstenius M, Løberg E-M, et al. Amphetamine-induced psychosis – a separate diagnostic entity or primary psychosis triggered in the vulnerable? BMC Psychiatry [Internet]. 2012 Dec [cited 2019 Jan 30];12(1). Available from: http://bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-12-221
18. Hendricks PS, Thorne CB, Clark CB, Coombs DW, Johnson MW. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol (Oxf). 2015 Mar;29(3):280–8.
19. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, 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 (Oxf). 2016 Dec;30(12):1181–97.
20. Swanson LR. Unifying Theories of Psychedelic Drug Effects. Front Pharmacol [Internet]. 2018 Mar 2 [cited 2019 Jan 30];9. Available from: http://journal.frontiersin.org/article/10.3389/fphar.2018.00172/full
21. Flanagan TW, Nichols CD. Psychedelics as anti-inflammatory agents. Int Rev Psychiatry. 2018 Jul 4;30(4):363–75.
22. Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, et al. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018 Jun;23(11):3170–82.
23. Roseman L, Nutt DJ, Carhart-Harris RL. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression. Front Pharmacol [Internet]. 2018 Jan 17 [cited2019 Jan 30];8. Available from: http://journal.frontiersin.org/article/10.3389/fphar.2017.00974/full
24. Priest G. The logic of Buddhist philosophy goes beyond simple truth [Internet]. Aeon. 2014 [cited 2019 Jan 30]. Available from: https://aeon.co/essays/the-logic-of-buddhist-philosophy-goes-beyond-simple-truth
25. Slaney KL, Maraun MD. Analogy and Metaphor Running Amok: An Examination of the Use of Explanatory Devices in Neuroscience. J Theor Philos Psychol. 2005;25(2):153–72.
26. Halberstadt AL. Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behav Brain Res. 2015 Jan;277:99–120.
27. Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, et al. Salvinorin A: A potent naturally occurring nonnitrogenous opioid selective agonist. Proc Natl Acad Sci. 2002 Sep 3;99(18):11934–9.
28. Powers III AR, Gancsos MG, Finn ES, Morgan PT, Corlett PR. Ketamine-Induced Hallucinations. Psychopathology. 2015 Sep 12;48(6):376–85.
29. Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB, et al. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950–66.
30. Perez-Aguilar JM, Shan J, LeVine MV, Khelashvili G, Weinstein H. A Functional Selectivity Mechanism at the Serotonin-2A GPCR Involves Ligand-Dependent Conformations of Intracellular Loop 2. J Am Chem Soc. 2014 Nov 12;136(45):16044–54.
31. Zamberlan F, Sanz C, Martínez Vivot R, Pallavicini C, Erowid F, Erowid E, et al. The Varieties of the Psychedelic Experience: A Preliminary Study of the Association Between the Reported Subjective Effects and the Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines. Front Integr Neurosci [Internet]. 2018 Nov 8 [cited 2019 Jan 30];12. Available from: https://www.frontiersin.org/article/10.3389/fnint.2018.00054/full