LSD + Risperidone for Depression

(SLIM Trial)

This trial tests a combination of two drugs, LSD and risperidone, to determine their safety and effectiveness in treating depression. Researchers aim to discover if risperidone, an antipsychotic medication, can shorten LSD's effects, allowing individuals to benefit from LSD without a prolonged experience. Suitable candidates for this trial have a diagnosis of major depressive disorder and can manage daily life without a severe risk of suicide. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel treatment combination.

If you are currently taking antipsychotics, MAO inhibitors, or certain antidepressants, you will need to stop them before joining the trial. Some antidepressants require a washout period (time without taking the medication) of 4 weeks or five half-lives before treatment. If you are taking other specific medications, you may need to taper off them as well.

Research has shown that LSD and risperidone have been studied separately. A large study found that a single dose of LSD improved symptoms in about half of the participants with depression, suggesting its potential effectiveness, though the study did not focus on safety.

Risperidone, a medication used for conditions like schizophrenia and bipolar disorder, can cause side effects. Some serious ones include movement problems and a rare but severe reaction called neuroleptic malignant syndrome, which can lead to high fever and muscle stiffness.

When used together, risperidone has blocked some effects of LSD, potentially reducing the intense experiences caused by LSD. Previous trials indicate that risperidone is generally well-tolerated, but like any medication, it can have side effects.

Researchers are excited about the combination of LSD and Risperidone for treating depression because it offers a novel approach compared to traditional antidepressants. Unlike typical treatments that mainly target serotonin levels, LSD interacts with serotonin receptors in a unique way that may rapidly improve mood and perception. Risperidone, an antipsychotic, can help manage any potential hallucinogenic effects of LSD, making the combination potentially safer and more effective. This innovative blend could provide quicker relief and a new option for those who haven't responded well to existing medications.

Research has shown that risperidone may help treat depression. One study found that more participants taking risperidone improved compared to those taking a placebo (a pill with no active medicine). Specifically, 24.5% of patients on risperidone experienced significant improvement in their depression symptoms, compared to just 10.7% on placebo. Risperidone is also known for helping with severe mood disorders. This trial will investigate the combination of risperidone with LSD. Although few studies have explored the use of risperidone with LSD, risperidone's ability to improve mood and reduce depression might enhance its effectiveness when combined with LSD.¹⁶⁷⁸⁹