How Even a Microdose of LSD Might Expand Consciousness

I became a neuroscientist to help us understand how humans gain deeper insight and observation into themselves, life, and being during altered states of consciousness.

I never expected to write a post about a microdose of lysergic acid diethylamide (LSD).

When I graduated with a Ph.D. in neuroscience in 2019, I completed my thesis on synaptic plasticity in preclinical models of cocaine and methamphetamine addiction. I was eager to pursue work on humans. I arrived at the University of Chicago with the ambition of studying altered-state experiences, beginning with those induced by cannabis and its principal psychoactive constituent, THC.

“Cannabis?” I remember hearing this on my first day in the Human Behavioral Pharmacology Laboratory. “We have another study I’d like you to work on involving microdoses of LSD and another involving [methylenedioxy-methylamphetamine] MDMA; then maybe you can look into THC.”

I was exactly where I needed to be.

In integrated information theory, a hotly debated theory of consciousness, the more complex a model of consciousness, the higher the “level of consciousness.” In practice, neural complexity increases as a function of awareness or experience. For instance, there’s more complexity when you’re awake compared to when you’re asleep, or when your eyes are open rather than closed.

Curiously, complexity increases further after taking high doses of psychedelics. The increase in complexity after the use of psychedelics may be due to the serotonin receptor that the psychedelics act on, which increases the sensitivity of the neuron to respond.

In a theory of psychedelic medicine known as the entropic brain hypothesis, increased neural complexity during psychedelic therapy is central to therapeutic effects, helping patients to break out of rigid, maladaptive patterns. The hypothesis further suggests that the increased complexity also explains how the psychedelic-like altered state arises.

However, neural complexity, a.k.a. brain entropy, has not been empirically tested to explain the origin of altered-state effects. It was unknown whether increases in complexity might arise from other drugs that similarly induce altered states of consciousness, such as THC, or similarly increase arousal, such as methamphetamine.

As reported in the journal Neuropsychopharmacology, we used electroencephalography (EEG) to find the answer, which records brain activity during tasks and at rest. Our three EEG studies in healthy participants—low doses of LSD, moderate to high doses of THC, and moderate to high doses of methamphetamine—provided the opportunity to test the hypothesis that increases in neural complexity explain the origins of psychedelic-like altered states.

Based on our prior work establishing psychedelic-like altered states after high doses of THC, we hypothesized that THC, but not the low doses of LSD or moderate to high doses of methamphetamine, would increase neural complexity. Surprisingly, we found that only the low doses of LSD increased complexity in a dose-dependent manner, whereas the THC and methamphetamine doses did not.

While the higher of the two low LSD doses tested was just high enough to elicit some self-reported effects (relative to placebo), it was not high enough for participants to feel as if they were in an altered state. Participants did report feeling some effects of the drug, including feelings of elation and anxiety. Surprisingly, these feelings did not correlate with the increased complexity after LSD.

However, the low doses of LSD also reduced low-frequency delta and theta brainwave oscillations, which did correlate with the increased elation. We speculate that if additional surveys were included in the study, such as questions about feeling more present, experiencing a greater sense of smell, or noticing details in surrounding objects, these measures could have correlated with the increased complexity after the low doses of LSD. Our main finding was that a neural correlate of consciousness increases even after low doses of LSD, pointing to a shared therapeutic mechanism of action across both higher and microdoses of psychedelics.

Psychedelics Essential Reads

8 Ways to Learn About Psychedelics

LSD May Be More Effective When You’re Already Depressed

Our analysis also revealed that the psychedelic-like altered states of THC correlated with reduced alpha brainwave power, supporting prior literature suggesting that reduced alpha power could be the true marker of altered states. Indeed, prior reports have found that reduced alpha over the occipital lobe correlates to the visual effects one might experience after a high dose of LSD.

However, in our study, reduced alpha was negatively related to altered states and was primarily a frontal brain phenomenon. This suggests a greater cognitive effort to curb the immersive psychedelic-like effects of THC, thus leaving open the question as to their neural origins. Much unlike THC, the methamphetamine doses increased frontal alpha, possibly suggesting a more efficient or unoccupied cognitive state.

Finally, our study leveraged two age groups (adolescents and adults under placebo conditions), finding increased complexity and reduced delta and theta with brain maturation and development without changes in alpha, beta, or gamma waves, thus nearly mirroring the brain effects of the microdoses of LSD. Greater complexity has previously been reported to occur with brain development, whereas complexity is reduced in most psychiatric disorders, although findings with schizophrenia are mixed.

It cannot be overstated that there may be significant risks of repeated uses of psychedelics, even at the microdose level, on the mind, brain, heart, especially for young people whose brains are still developing. Much more preclinical and clinical work is needed to model and study healthy and patient populations across the lifespan. To date, only one placebo-controlled clinical trial (in New Zealand) has been conducted to assess the effects of a microdose regimen, with repeated low doses of LSD taken every three days over a six-week protocol. The trial found significantly improved mood on dose days relative to placebo but no changes in measures of emotion or cognition the rest of the time in a healthy male population.

In addition, whether there is any therapeutic, behavioral, or cognitive benefit to increased complexity after psychedelics, including whether it is evidence of an expanded state of consciousness or whether it is merely neural noise, is pending further analysis.

In the current analysis, we found that increases in neural complexity, or brain entropy, are not necessary for psychedelic-like altered states effects, nor are they sufficient for their induction. However, I speculate that the brain changes we observed help to generate positive anecdotal reports of microdosing, from “I feel more love for myself” to “The personal and spiritual growth I have experienced is significant.” Based on these new data, I imagine that, for those who benefit most from seeing the world in a brighter light, increases in neural complexity could act like a widening lens to enrich or restore one’s experience.

Our work does not discount the value of psychedelic-assisted therapy, where specially trained clinicians facilitate and integrate deeply meaningful insights and observations toward emotional breakthroughs and connectedness. The current work adds to a growing body of literature, helping us understand how these meaningful changes occur. I hope this work will inform appropriate doses in appropriate populations toward guiding positive outcomes while reducing unnecessary risks in the emerging landscape of psychedelic medicine.