In a potentially breakthrough study recently published in Nature magazine, scientists appear to have discovered two LSD-like compounds that successfully treat depression in mice without the hallucinogenic effects.
Consistent and growing clinical evidence has been demonstrating the strong efficacy of psychedelic substances like LSD & psilocybin in treating depression symptoms. Scientists believe that the antidepressant qualities of these substances are due to their binding interactions with the 5-HT2A receptors responsible for the regulation of serotonin in the brain. This is the same mechanism behind a category of antidepressant pharmaceuticals knowns as SSRIs.
While SSRIs take weeks and even months to begin delivering significant results and tend to diminish in efficacy over time, clinical research has demonstrated that a single guided large-dose psychedelic experience along with psychotherapy can have immediate and lasting results for many months and even years.
Although psychedelic-assisted therapy is extremely promising and likely to change the landscape of modern psychiatry and pharmacology for decades to come, it presents other challenges like equitable access to providers, availability of providers due to long session durations and high costs, legality hurdles, and the ability of some individuals to tolerate strong hallucinations. As a result, the psychedelic renaissance has also renewed interest in identifying alternatives that address some of the challenges and limitations of psychedelic therapy.
In this study, scientists used a novel computation system for drug discovery knowns as silico modeling to develop 3D simulations of more than 75 million compounds that interact with the 5-HT2A receptors in a similar fashion to psychedelics, including molecules that don't actually exist but could be produced. They then tested every molecule and identified 17 molecules with therapeutic potential. With further testing, they were able to narrow their focus to 2 compounds.
The scientists then administered these synthetic compounds to laboratory mice and observed their behavioral effects. The results of their findings demonstrated no hallucinogenic effects and no rewarding properties often associated with drug abuse.
More importantly, they found that these compounds produced both antidepressant and anti-anxiety effects. They appeared to facilitate a reduction in depression symptoms at 20-fold lower doses than Prozac (a common SSRI). The positive effects of a single dose also appeared to last for at least 14 days.
Additional research and human trials are needed to further assess the efficacy and safety of these compounds. The remarkable design and findings of this study demonstrate the promising potential of this type of visual modeling and analysis in accelerating and transforming pharmacology as a whole in the coming years.