Classical Psychedelics for Alzheimer’s and TBIs?

Multiple lines of research suggest serotonergic psychedelics like LSD and DOI could be useful for treating dementia and traumatic brain injuries.

by Eric M. Fortier, B.A. | March 7, 2020

Almost 50 million people worldwide are living with Alzheimer’s or other dementia right now. Declines in learning, language processing, mood, and behaviour, and growing dependence on family and caregivers, make Alzheimer’s disease the main cause of disability in later years, costing the US and Canada a staggering 300 billion in healthcare this year alone. As the 5th leading cause of death in the world, one-third of seniors die with dementia, and so far, there’s no cure.

Now, Shlomi Raz, former managing director at Goldman Sachs and founder of emerging biotech company Eleusis, is looking to bring low-dose LSD to market to target some of Alzheimer’s main markers.

Its powerful anti-inflammatory effects, potential for up-regulating mitochondria, for clearing beta-amyloid, and for stimulating dopamine and other receptors, along with its increasingly apparent ability to promote neuroplasticity, make it a prime potential candidate for treating the devastating disease in its early stages, Raz outlines in Forbes, hoping that a series of low doses might help restore patients’ cognition and motor control.

Cognitive scientist and Director of Research at Eleusis, Neiloufar Family, Ph.D., led a Phase 1 study which showed that low-dose LSD (5, 10, and 20 µg) was safe and well-tolerated by healthy older volunteers. Surprisingly, it didn’t seem to significantly impair cognition, but there weren’t any improvements, either, during nor after taking it twice a week for three weeks.1 Still, this was just a Phase 1 study, so they weren’t testing volunteers with dementia or cognitive impairment just yet; that won’t be until Phase 2 comes around.

Some of the biggest challenges facing those with dementia involve language and communication, especially semantic language processing. In a separate small sample study investigating the effects of slightly stronger doses of LSD on healthy adults’ performance on a picture-naming task,2 Family found that LSD seemed to enrich access to extended semantic associations, supporting earlier findings from a word-association study conducted in the 1960s by Spitzer and colleagues.3 What these studies tell us is that psychedelics induced a kind of hyper-associative state in which things like words and objects light up a wider web of related features, facts, concepts, and ideas.

The results, they grant, could be related to reduced self-monitoring, though, because participants were less likely to correct themselves when giving an inaccurate answer. But interpreting results on tests like these isn’t straightforward, particularly when we consider that psychedelics increase distractability.4 Family quotes a participant in the picture-naming task, saying, “I was actually having a little experiment of how much I can think of other things while doing the task,” for example.

Either way, at the higher doses used in this experiment, it’s not surprising that participants would have trouble focusing on the task. Recent neuropsychopharmacological research demonstrates that unconstricted attention is accompanied by a dialed up meaning-making mode of mind, with an increased interpretation of the world in terms of self-relevance, with a substantial re-surfacing of autobiographical5 and semantic memory into primary experience. The study, led by Katrin Preller of Yale University and Psychiatric University Hospital Zürich, revealed that these effects could be explained by an observed increased excitability in the brain’s cortical midline structures (related to ‘core,’ ‘mental,’ or ‘minimal’ self) in response to sensory experience. At normal doses, this might cause challenges in focus and attention to experimental tasks.

Still other research suggests implications for psychedelics in age-related pathological memory loss. Froese, Leenen and Palenicek (2018)6 re-analyzed data from a 2014 rat study and found that psilocybin administration improved sleep-deprived rats’ ability to remember the location of a safe platform in a pool, suggesting that psychedelics could help prevent some of the effects of sleep loss on learning to navigate new environments, which is also commonly disrupted in Alzheimer’s disease.

Though some of these studies weren’t aimed directly at Alzheimer’s, their results demonstrate key features of psychedelic experience that could hold deep value for those suffering from it. However, many of these effects remain to be seen in lower dose ranges–noteworthy improvements in depression and anxiety from psychedelic therapy so far have been found to relate to meaningful experiences that only come from taking a substantial dose of the drug in a supportive environment.

The potential for LSD and other psychedelics working through the serotonin 2A receptor to block inflammation,7 to sprout new connections between neurons,8 to help clear beta-amyloid,1 as well as to increase what some scientists call “brain complexity,” also make them promising candidates for treating traumatic brain injuries (TBIs). Gregory Scott and Robin Carhart-Harris, of the Imperial College Center for Psychedelic Research, speculate in the journal Neuroscience and Consciousness (2019) that since psychedelics increase scores on measures of brain complexity–which is said to represent a reliable indicator of level of consciousness–a threshold perceptible dose a few times a week might enhance rehabilitative care of TBIs without too many side-effects.9

It’s still early days, though, and this isn’t medical advice. We need a lot more research before making any claims about effectively treating neurodegenerative diseases with LSD.

On that note, the new Johns Hopkins Center for Psychedelic and Consciousness Research is recruiting for an early Phase 1 study investigating the safety and efficacy of psilocybin for improving mood, physical and cognitive function, and quality of relationships in patients with mild cognitive impairment or early Alzheimer’s disease. If you or someone you know that lives in or near Baltimore, Maryland, meets the criteria for the study (see above link), and would like to participate, consider applying on Johns Hopkins’ website, or calling 410-550-5466 for details.

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[1] Family, N., Maillet, E. L., Williams, L. T. J., Krediet, E., Carhart-Harris, R. L., Williams, T. M., …Raz, S. (2020). Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers. Psychopharmacology, 237(3), 841–853.

[2] Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., & Carhart-Harris, R. L. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition and Neuroscience, 31(10), 1320–1327.

[3] Spitzer, M., Thimm, M., Hermle, L., Holzmann, P., Kovar, K. A., Heimann, H., …Schneider, F. (1996). Increased activation of indirect semantic associations under psilocybin. Biological psychiatry, 39(12), 1055–1057.

[4] Carter, O. L., Burr, D. C., Pettigrew, J. D., Wallis, G. M., Hasler, F., & Vollenweider, F. X. (2005). Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. Journal of cognitive neuroscience, 17(10), 1497–1508.

[5] Preller, K. H., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., …Vollenweider, F. X. (2017). The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation. Current biology : CB, 27(3), 451–457.

[6] Froese, T., Leenen, I., & Palenicek, T. (2018). A role for enhanced functions of sleep in psychedelic therapy? Adaptive Behavior, 26(3), 129–135.

[7] Nau, Jr., F., Yu, B., Martin, D., & Nichols, C. D. (2013). Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo. PLoS ONE, 8(10).

[8] Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., …Olson, D. E. (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell Reports, 23(11), 3170–3182.

[9] Scott, G., & Carhart-Harris, R. L. (2019). Psychedelics as a treatment for disorders of consciousness. Neuroscience of Consciousness, 2019(1).