Microdoses of LSD enhance neural complexity, study finds

A recent study has shown that even very low doses of LSD can enhance the complexity of brain activity, a finding that might have significant implications for our understanding of consciousness and possibly for therapeutic applications.

The study, published in the journal Neuropsychopharmacology, found that while substances like THC (tetrahydrocannabinol) and methamphetamine did not produce the same effect, LSD distinctly increased neural complexity and affected brain wave patterns associated with states of consciousness.

Neural complexity is a concept that attempts to quantify the intricate patterns of activity within the brain. This measure reflects the “richness” of one’s mental experience, which can vary dramatically from one state of consciousness to another. High levels of neural complexity are associated with a richer, more varied experience of consciousness, whereas lower levels are associated with reduced consciousness, such as in sleep or under the influence of certain sedatives.

The focus on neural complexity in this study stems from a theory known as the “entropic brain hypothesis,” which proposes that the therapeutic benefits of psychedelics are partly due to their ability to increase the brain’s level of entropy, thereby disrupting rigid, maladaptive patterns of thought and behavior.

The new study analyzed data from three separate drug trials conducted at the Human Behavioral Pharmacology Laboratory at the University of Chicago, that compared psychoactive substances (LSD, THC, and methamphetamine) against placebo conditions. A total of 73 healthy adults participated in these trials.

“I want to know how humans gain deeper insight and observation into themselves, life, and being during altered states of consciousness,” said study author Conor H. Murray, an assistant project scientist at UCLA and the founder of Psynautics.com. “Since I’m particularly interested in the neurobiological basis of consciousness and altered states, I decided to analyze all three studies to determine whether a neural correlate of consciousness was affected by the LSD microdoses vs, the THC doses vs, the meth doses.”

For LSD, doses of 13 or 26 micrograms (µg) were used. These amounts are substantially lower than the doses typically associated with a full psychedelic experience, which often exceeds 100 µg.

THC, the psychoactive component in cannabis, was administered in doses of 7.5 mg and 15 mg. These doses were intended to reflect the range of THC that might be consumed in a more controlled setting, producing subjective intoxication and performance impairments without reaching the higher levels often seen in recreational cannabis use.

Methamphetamine was administered in doses of 10 mg and 20 mg. These doses are based on prior studies that have identified them as effective in producing noticeable subjective, behavioral, and neural effects in healthy volunteers.

During each session, participants’ brain activity was recorded using electroencephalography (EEG), specifically focusing on neural complexity through the Limpel-Ziv complexity measure. This method quantifies the diversity of signal patterns in the EEG data, offering insights into the brain’s operational complexity. In addition to EEG recordings, participants provided self-reports on their mood states and perceived drug effects at various points throughout the session.

LSD emerged as the only substance among the three that dose-dependently increased neural complexity, suggesting a unique impact on brain function that may underpin its consciousness-expanding effects. This increase in neural complexity was also accompanied by reductions in delta and theta power, which are brain wave frequencies typically associated with deeper, less conscious states such as sleep.

These reductions in delta and theta power correlated with self-reported feelings of elation among participants, suggesting a link between the altered brain activity induced by LSD and the subjective experience of elevated mood or happiness.

The changes in brain activity were particularly intriguing because they were observed even at very low doses of LSD, well below those that induce the full psychedelic experience.

The findings provide evidence “that even very low doses of LSD might ‘expand consciousness’ as defined by a hotly debated theory of consciousness; but we still don’t know whether this is a good thing or not — we haven’t found out yet how this brain change might actually affect brain or mental health or cognitive function,” Murray told PsyPost.

Interestingly, while THC and methamphetamine also modulated brain activity, their effects did not mirror those of LSD. THC-induced reductions in alpha power were associated with altered states of consciousness, but the drug did not increase neural complexity in the way LSD did. Methamphetamine, on the other hand, showed stimulant-like responses without significant changes in neural complexity or consciousness states.

“I was surprised that neural complexity did not increase after THC, which induced psychedelic-like altered states; but did increase after the microdoses of LSD, which did not induce psychedelic-like altered states,” Murray said. “The field to this point had believed that neural complexity is the reason how psychedelic-like altered states happen. This surprising finding showed that this was not the case, that neural complexity was neither necessary nor sufficient for psychedelic-like altered states.”

The new research has some limitations to consider, including the pooling of data from three separate studies and the absence of measures for “richness of experience,” a factor previously associated with neural complexity. These limitations highlight the need for further research to deepen our understanding of how low doses of LSD and other psychedelics affect the brain and consciousness.

“The major caveat was that we didn’t ask participants about subtle changes in consciousness, like whether their sense of smell was enhanced, or whether they noticed intricacies after the microdoses of LSD that they didn’t notice on placebo,” Murray noted. “It’s possible that the increased entropy would be related to these subtle changes.”

“But since we only asked about large altered states effects, and stimulant effects, etc., none of that showed any association to the increased entropy, which begs the question as to whether entropy can increase even when consciousness is not altered at all – of course, the caveat again being that we did not have every subtle shade of minor alterations to ask about.”

The findings open up new avenues for exploring the therapeutic potential of psychedelics, particularly in microdosing practices. Future studies are needed to assess the long-term effects of these practices on mental health and well-being, as well as to explore the mechanisms behind the observed increase in neural complexity and its implications for consciousness and cognition.

“The immediate next step is to determine whether the increased neural complexity explains the improved behavioral responses we found in a facial recognition task after the low doses of LSD in the same study,” Murray told PsyPost. “Or maybe the increased complexity actually hindered those responses, we don’t know.”

“The real long-term goals are to understand what brain changes are occurring when people have meaningful insights and observations, so we can try to target these more specifically to refine and improve our ability to have meaningful therapeutic effects and scientific observations with high signal to noise ratio.”

The study, “Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine,” was authored by Conor H. Murray, Joel Frohlich, Connor J. Haggarty, Ilaria Tare, Royce Lee, and Harriet de Wit.