A number of recent studies have highlighted the potential of magic mushrooms to treat depression, although the exact mechanism behind this effect remains unclear. While some have speculated that emotional and insightful psychedelic trips are the key healing component, new research carried out in mice suggests that the drug’s active compound is capable of alleviating depression even when no psychedelic experience is produced.
The psychoactive ingredient in magic mushrooms, psilocybin, generates altered states of consciousness by interacting with a particular serotonin receptor known as the 5-HT2A receptor. The same mechanism underlies the activity of other psychedelics like LSD and ayahuasca, and while several such substances are thought to be effective at treating mental health disorders, the nature of the psychedelic experience makes them unsuitable for certain individuals.
For instance, anyone with a family history of schizophrenia or bipolar disorder is generally excluded from studies involving psychedelics, for fear that these drugs may trigger psychosis. Furthermore, the fact that psychedelic-assisted psychotherapy requires the supervision of specially trained medical professionals adds significantly to the cost of treatment, rendering it unaffordable for many patients.
In an attempt to sidestep some of these concerns, a team of researchers sought to determine whether psilocybin retains its ability to treat depression when the receptor responsible for generating psychedelic experiences is deactivated. To do so, they first subjected male mice to stressful lighting and noise for several weeks in order to generate an animal model of depression. This resulted in the rodents losing interest in pleasurable stimuli such as sugar-laced water or the scent of female mouse urine.
The study authors then treated the animals with psilocybin, along with a substance called ketanserin, which blocks the 5-HT2A receptor and therefore prevents the drug from producing any psychedelic effects. Reporting their findings in the Proceedings of the National Academy of Sciences, the researchers explain that this did not dampen the anti-depressant efficacy of psilocybin, as evidence by the rodent’s renewed interest in both sugar water and female urine after treatment.
Furthermore, an analysis of the animals’ brain tissue revealed that psilocybin sparked a strengthening of excitatory synapses in the hippocampus – an effect that is generally associated with fast-acting anti-depressants. That this was achieved without the activation of the 5-HT2A receptor adds to the robustness of the researchers’ claim that psychedelic experiences are not a necessary component of psilocybin-assisted therapy for depression.
Commenting on these findings, study author Dr Scott Thompson explained in a statement that “activation of the receptor causing the psychedelic effect isn’t absolutely required for the antidepressant benefits, at least in mice.”
This is highly encouraging, he says, as “the psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate.” Thompson and his colleagues suggest that combining psilocybin with a 5-HT2A inhibitor like ketanserin could make this type of therapy more accessible for larger numbers of patients.