Microdosing LSD Boosts the Brain’s Reward System, Study Finds

Microdosing LSD has grown in popularity in recent years, thanks to anecdotal reports that the practice can improve mood and boost wellbeing.

While interest is growing in the field of psychedelic science, there is much that is still unknown about these drugs. Microdosing – taking very low doses of a drug to the point where the hallucinogenic drug effects are often not felt at all – is one of these under-researched phenomena.

Now, new work published in Neuropsychopharmacology has found that a single microdose of LSD can increase brain activity related to its reward system. Specifically, LSD microdoses appeared to increase neural sensitivity to rewards and affect emotional processing.

The researchers say that these findings could have important consequences for treating depression, as those with depressive disorders also tend to have dysfunctional reward system activity.

One microdose can increase reward-related brain activity

For this double-blind study, a total of 18 participants were enrolled to take part in three experimental sessions. At each session the participants would randomly receive either a placebo, 13 micrograms of LSD (LSD-13), or 26 micrograms of LSD (LSD-26) sublingually. In all cases, the participants were told that they might receive a placebo, stimulant, sedative, or hallucinogenic drug to try and protect against expectancy effects.

During the experiment, the brain activity of participants was measured using scalp electroencephalography (EEG), which focused on three event-related potentials (ERPs).

One of these ERPs was reward-positivity (RewP), which is known to be attenuated in individuals with depression. The next ERP measured was feedback-P3 (FB-P3), which is associated with the motivational significance of various outcomes and plays a role in updating predictive models when thinking how to maximize future rewards. Finally, the researchers looked at late-positive potential (LPP), an ERP that is modulated by the emotional intensity of a stimulus and is heavily involved in emotional processing.

While connected to this EEG, participants completed a modified electrophysiological monetary incentive delay (eMID) task. The task began with a neutral or positive cue displayed on a computer screen – either a message indicating that the participant could win $1.50 for completing the task or a neutral message stating that there was no reward. Participants were then instructed to react quickly by clicking the mouse cursor when a white square appeared on screen, with quick reactions triggering a positive “win” message to appear and slower reactions giving a “lose” readout.

Unbeknownst to the participants, the win/loss result was secretly controlled by an algorithm designed to present positive and negative feedback around 50% of the time.

After studying the EEG data from all participants, the researchers found that, compared to the placebo, LSD-13 enhanced the “hedonic impact and affective impact” of rewards. In other words, participants liked receiving the rewards more, as evidenced by increased RewP and LPP amplitudes. Both LSD-13 and LSD-26 also increased the participants’ motivation to receive a positive reward, indicated by an increase in FB-P3 amplitudes.

Microdosing LSD could have applications in treating depression

The researchers behind this new study say that it is the first evidence supporting the idea that a single, low dose of LSD may increase reward-related activity in the brain. Additionally, since the three ERPs studied here are normally adversely affected in people with depression, it suggests that LSD microdosing may have potential as a treatment for depression.

“The present results are the first to show that a single, low dose of LSD (e.g., LSD-13) increased the RewP. This observation raises the possibility that repeated low doses of LSD may be able to alleviate certain symptoms of depression by reversing deficits in neural sensitivity to rewards,” the researchers wrote.

“Although speculative, it is possible that single, low doses of LSD may increase emotional sensitivity to reward feedback in a similar fashion while only producing modest subjective drug effects.”

The researchers do note several limitations on this research. For example, the sample size was very small and there were no controls for the menstrual cycle phase of the female participants; the menstrual cycle has previously been linked to reward-related brain activity. Additionally, depression scores on the mental health assessments given to the participants were low across the board, and so this study did not have the power to examine any associations with depression.

The researchers say that focusing on repeated LSD microdoses over longer timeframes and which enroll larger sample sizes and/or contain people with depression will be an important direction for future research. Should these results be held in larger studies, this would suggest that LSD microdosing may have an application as an alternative treatment option for those whose depression does not respond to traditional antidepressants.

LSD as medicine

LSD was originally developed for medical purposes, having been first synthesized by Dr. Albert Hofmann in the 1930s in an attempt to produce a respiratory and circulatory stimulant. LSD was ineffective at this and was originally discarded, but several years later Hofmann decided to retest the chemical. Somehow, Hofmann accidentally ingested a small amount of LSD and subsequently discovered its powerful hallucinogenic effects.

Hofmann believed that LSD improved his mental wellbeing and there was a flurry of LSD and psychedelics-related research that persisted for many decades after Hofmann’s discovery. But in the ‘60s and ‘70s, legislation restricting access to LSD began to be imposed in the US at the state and federal levels, then internationally.

It would take until the 1990s for interest in psychedelics research to once again flourish within mainstream circles. Today, researchers are keen to unravel the individual mechanisms behind LSD’s action in the brain and determine whether it may have therapeutic potential separate to its hallucinogenic properties.

One recent literature review of randomized controlled trials on LSD concluded that the compound does indeed have the potential “to reduce psychiatric symptomatology, mainly in alcoholism.” LSD has also been researched as a last resort treatment for cluster headache and migraine, where it appears to reduce headache severity and frequency.