Tiny Doses of LSD Boost Unique Signals in The Human Brain

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Even small doses of LSD could have therapeutic benefits for mental health and task performance, a new study shows.

Researchers from the US and Germany gave 21 adults either a placebo or 13 or 26 micrograms of LSD – small doses that rarely lead to hallucinatory effects.

It was found that 26 micrograms of the psychoactive compound increased brain complexity by about 12 percent compared to a placebo, without altering consciousness. Neural complexity is a measure of unique brain signals, usually correlating with consciousness levels. High doses of psychedelics can increase complexity, which has been suggested to explain their positive effects.

Lysergic acid diethylamide, or LSD, was created 'accidentally' in the 1930s while researchers were looking for a drug to improve blood flow and breathing, though its psychedelic effects have since earned it more recognition.

The compound is now known to activate a specific type of serotonin receptor in the brain that results in more complex patterns of brain activity. According to the "entropic brain hypothesis," psychedelics achieve therapeutic benefits via this increased neural complexity, which under the right conditions can disrupt unhelpful thought and behavior patterns.

Regularly taking very low quantities of psychedelics in what is known as microdosing has gained significant attention over the last decade, with enthusiastic anecdotes about its wide-ranging benefits for things like mood, creativity, energy, and brainpower.

While the science for many of the claims remains undecided, microdosing LSD could still be an appealing therapy if the positive effects of high doses can be achieved without the safety and ethical concerns associated with altered states of consciousness.

Randomized controlled trials (RCTs) in healthy people have shown that low doses can enhance well-being in some ways, such as decreasing pain perception.

"However, no published RCT has examined patient populations and only one RCT to date has assessed outcomes after repeated use," write neuroscientist Conor Murray from the University of Los Angeles, California, and colleagues.

They recorded the brain activity of trial participants during the time that the drug's effects were expected to peak using resting state electroencephalography (EEG). Following the trial, participants were asked to complete a questionnaire to assess whether they had experienced any consciousness changes.

The trials were repeated in two further groups, one with moderate (7.5 mg) and high (15 mg) doses of tetrahydrocannabinol (THC) from cannabis and one with medical methamphetamine at doses of 10 mg and 20 mg. In these experiments, THC, but not methamphetamine, affected consciousness at high doses.

The team's analysis of all the trials found only the 26-microgram dose of LSD had a significant effect on neural complexity, increasing it by approximately 12 percent on average when compared to the placebo.

Despite this change, the questionnaire results indicated that the 26-microgram LSD dose had no effect on self-reported states of consciousness, although participants did report feeling small increases in anxiety and elation.

What's more, THC changed consciousness levels, but not neural complexity, suggesting that changes in neural complexity and consciousness don't always go together.

"These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness," the researchers write.

The team suggests that microdoses of LSD affect the brain similarly to higher doses, explaining reports of increased creativity and social connection.

University of California, San Francisco neurologist Robin Carhart-Harris, who wasn't involved in the research, told Grace Wade at New Scientist there's a need for better scales to accurately capture psychedelic effects. He disagrees that low doses of LSD have no impact on consciousness, based on participants self-reporting effects after taking 26 micrograms.

Clinical trials so far haven't proven any overall benefits of microdosing LSD, and the potential risks aren't clear.

Murray and team say further research is needed to assess whether the greater complexity they observed results in cognitive, behavioral, or therapeutic outcomes, though previous studies suggest increased complexity can be a predictor for outcomes to psychiatric therapy compared with other measures.

"Increases in complexity after low doses of LSD, in the absence of psychedelic-like drug effects, raise important questions about potential roles for the diversity of neural signaling after low doses of LSD in conscious processes, which may have behavioral and therapeutic relevance," the authors write.

The study has been published in Neuropsychopharmacology.

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