How Could Psychedelics Possibly Help Treat Alzheimer’s and TBIs?
Almost 50 million people worldwide are currently living with Alzheimer’s or other dementia. 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.
Shlomi Raz, a former managing director at Goldman Sachs and founder of emerging biotech company Eleusis, is among those looking to bring low-dose LSD to market to target some of Alzheimer’s main markers.
There’s theoretical evidence that this could work. 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, they report that these doses didn’t seem to significantly impair cognition; but there weren’t any improvements, either, neither during nor after taking it twice a week for three weeks.[1]
This was just a Phase 1 study, so they weren’t testing volunteers with dementia or cognitive impairment just yet; that will come when Phase 2 rolls out.
Investigating potential mechanisms
Several studies have found LSD and other psychedelics working through the serotonin 2A receptor are surprisingly good at reducing inflammation,[2] sprouting new connections between neurons,[3] and even helping clear beta-amyloid,[1] features that also make them promising candidates for treating traumatic brain injuries (TBIs).
But several other lines of research suggest even more ways psychedelics could prove useful to those suffering from these conditions.
Expanded semantic association
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,[4] 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.[5]
Studies like these suggest that psychedelics can tilt activity in the brain toward a tendency to hyper-associate, wherein things like words and objects light up a more distantly related web of neighboring memories, features, facts, concepts, and ideas.
These results could be related to reduced self-monitoring, though, since participants were less likely to correct themselves when giving an inaccurate answer, they note. But interpreting results on tests like these isn’t straightforward, particularly when we consider that psychedelics increase distractibility:[6] Family quotes a participant in the picture-naming task, for instance, saying, “I was actually having a little experiment of how much I can think of other things while doing the task.”
Meaning-making
It’s somewhat unsurprising that participants would have trouble focusing on the task at the higher doses used in this experiment. Recent neuropsychopharmacological research demonstrates that psychedelic-induced 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, and a substantial re-surfacing of autobiographical[7] and semantic memory into primary experience.
Katrin Preller of Yale University and Psychiatric University Hospital Zürich led research suggesting 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. And at normal doses, such an effect might contributed to challenges in focus and attention to experimental tasks.
Protecting memory
Still other research finds implications for age-related memory loss. Froese, Leenen and Palenicek (2018)[8] re-analyzed data from a 2014 rat study and found that psilocybin administration surprisingly improved their ability to remember the location of a safe platform in a pool when sleep-deprived, 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.
Level of consciousness
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–thought 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]
Lack of low-dose research
Though some of these studies weren’t aimed directly at Alzheimer’s, their results demonstrate key mechanisms by which psychedelics could provide some relief for those suffering from neurodegeneration. 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 reliably from taking a substantial dose in a supportive environment.
All of this is, of course, purely mechanistic speculation, and all preliminary studies investigating pyschedelics for neurodegeneration remain to be confirmed by more rigorous trials.
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.