LSD Microdosing for Depression

There is an urgent need for new drugs to treat symptoms of depression. Depression is among the most prevalent and debilitating psychiatric disorders, yet current pharmacological treatments have serious limitations, including a delayed onset of effect, unwanted side effects, and unpredictable and variable effectiveness across individuals.  Recently, there have been a number of highly-publicized reports that very low doses of LSD taken at three- to four-day intervals (“microdosing”) improve mood.

There is a rational neurobiological basis for antidepressant effects of LSD: It acts on the same neurotransmitter system as classic serotonergic anti-depressant drugs (selective serotonin re-uptake inhibitors, or SSRI’s), but through a different receptor action.  Our previous work carried out as part of the Beckley/Imperial Research programme suggests that SSRI’s, which act nonspecifically on several 5HT receptors, produce their therapeutic effects by facilitating passive coping, whereas 5HT2A agonists such as LSD can produce beneficial effects by facilitating active coping. Until now, the effectiveness of microdosing has not been tested under rigorous, placebo-controlled double-blind conditions. With the prevalence of depression on the rise worldwide – especially among young people – studies of novel and effective treatments are urgently needed.

We are collaborating on a critical study to investigate the effects of repeated administration of microdoses of LSD at 3-day intervals, in participants who report some level of depressed mood.

This study will not only empirically test the claims of users, but it could also lead to a new understanding of serotonergic mechanisms of antidepressant action and a novel treatment approach for depression. The use of very low doses of a serotonin agonist suggests an exciting and novel approach to treating depression. The therapeutic effects may be evident without the long delays needed for SSRI’s, and patients who fail to respond to SSRI’s may benefit from a medication like this that acts by a different receptor action. We will also begin to investigate the neural basis of the drug’s effect, using EEG.