A recent study led by researchers from the University of Chicago in the US suggests we've got good reason to remain cautious in how we interpret the growing pile of evidence that seems to support 'microdosing' of this popular recreational drug.
Their study of 56 adult volunteers backs up similar studies that conclude although safe, repeated low doses of LSD aren't likely to improve our mood or our thinking as many claim.
"These drugs are already being used out in the world, and it's important for us to test them under controlled conditions, ensure their safety and see whether there's some validity to the benefits people claim," says behavioral neuroscientist Harriet de Wit.
"That's something that has been missing from the conversation."
'Accidentally' synthesized in the 1930s in search of a medication to stimulate breathing and circulation, lysergic acid diethylamide or LSD has since become better known for its hallucinogenic qualities.
Today, it's more commonly regarded as an illicit party drug, appreciated for its mind-altering, euphoria-inducing effects – with little thought spared for its role in medicine.
That perception is slowly changing as researchers and amateur enthusiasts alike explore the consequences of repeatedly taking relatively small doses of the compound.
It's called microdosing, and proponents argue trace levels of the pharmaceutical can generate a variety of benefits, from treating depression to improving our cognitive abilities.
It's not an unmerited idea. Since it's known to interact with the brain's serotonergic systems as a direct agonist, it's a small leap to assume LSD might trigger beneficial changes in neurology related to moods and memory.
Studies carried out on both animal and human subjects have also reported favorable results, encouraging further research into what could optimistically become a wonder drug for treating mood disorders that stubbornly resist other forms of therapy.
All that said, relatively few studies have critically examined the effects of repeated low doses of the hallucinogen under controlled laboratory conditions. Those that have are often underwhelming in their support of LSD as any kind of brain booster, leaving the door open for the possibility it's all a manifestation of the mind.
To weigh in on the debate over the role of the placebo effect accounting for perceived improvements, de Wit and her team randomly assigned volunteers to receive a solution containing either no LSD, or small doses of 13 or 26 micrograms.
For comparison, most people experience some kind of effect from LSD once the dose exceeds around 100 micrograms. So at less than a quarter of that concentration, doses are less likely to produce obvious sensations of pleasure or changes to perception.
Individuals in all three groups were given their respective dose every three to four days, sitting in a comfortable room where they could read or watch movies.
Critically, although all had taken either psychedelics or the mood-altering recreational drug MDMA in the past, none knew what kind of drug was being tested, making it harder for them to anticipate a reaction.
"We removed any expectations that this was a psychedelic drug," says de Wit.
"Because in the real world, people's expectations can strongly influence their responses."
Once an hour following their prescribed test treatment, subjects filled out a mood questionnaire and had their pulse measured. They also participated in a cognitive performance task to check their working memory.
When asked what drug they thought they'd received, fewer than half of the participants correctly reported LSD. Results varied widely on measures commonly used to study the hallucinogen's mind-altering effects, with impressions declining across the four sessions.
Most importantly, there was no evidence of changes to mood, emotion, or cognition.
"We can't say necessarily that microdosing doesn't work," says de Wit.
"All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn't see a robust effect."
Science doesn't turn on single studies, so the question remains open as to whether small amounts of psychotropic substances like LSD might still improve moods under specific circumstances, or if it's all purely psychological.
Given how much attention the idea of microdosing is getting today, researchers would be amiss if they didn't explore all the possibilities.
This research was published in Addiction Biology.