Psychedelic drugs are being widely touted as the future of anti-depressants, thanks to a wave of studies indicating that they may be effective at alleviating depression in people who have failed to respond to more conventional therapies. Yet not all substances in this category work in the same way, and a new study in the journal ACS Chemical Neuroscience reveals that some psychedelics are better than others when it comes to treating the condition.

It’s worth pointing out that the term "psychedelic" is loosely defined, and there is some debate over which drugs properly qualify for inclusion in this classification. The so-called classic psychedelics are substances that primarily interact with a serotonin receptor called 5-HT2A, and include psilocybin (the active ingredient in magic mushrooms), LSD and DMT (commonly found in ayahuasca), among others. Though none of these drugs are yet legal to use as therapeutic aids, many have been found to help treat conditions like depression and anxiety.

Numerous other chemicals are also sometimes referred to as psychedelic, despite not acting on the 5-HT2A receptor. Ketamine, for instance, binds with NMDA receptors, and while there is debate over whether it should rightly be given the title of psychedelic, it has been approved for use as an anti-depressant by the US FDA.

In the new study, rats were given either psilocybin, LSD or ketamine, before being subjected to a range of tests that measured their levels of depression and anxiety over the following five weeks.

To test for depression, the rodents were placed in a tank of water while the scientists observed their mobility levels as they attempted to stay afloat. In this test, immobility is seen as a sign of giving up, and therefore taken to be an indicator of an animal’s tendency to become depressed.

Rats that were given either psilocybin or LSD showed reductions in immobility that persisted for the entire five-week study period, suggesting that a one-off treatment with these drugs generates a lasting decrease in depression. While this effect did not diminish at all during the five weeks, it was considerably stronger in mice that had taken psilocybin than those that were administered LSD.

Rodents that received ketamine, however, displayed reduced immobility during the first two weeks after being treated with the drug, but by week three this improvement had entirely disappeared, indicating that the anti-depressant effect was of a more transient nature.

To measure anxiety, the study authors placed the rats in a structure that contained two large open spaces and two confined spaces. Because rats are normally nervous about being in open spaces, the amount of time spent exploring these chambers was used to measure anxiety levels.

Interestingly, rats that received psilocybin became less anxious and spent more time in the open spaces, but only if they were placed within this experimental structure once a week throughout the study period. Those that were exposed to this test only at the end of the fifth week did not show any increased tendency to explore the large chambers, even if they had received psilocybin.

The study authors therefore note that, rather than simply eliminating anxiety automatically, psilocybin may somehow increase the plasticity of rats’ brains so that they can learn to overcome their anxiety if given the opportunity to confront it repeatedly.

In contrast, rats that received ketamine did not show any increased tendency to explore the larger chambers, regardless of whether they were tested on a weekly basis or only after five weeks.

In conclusion, the study authors note that classic psychedelics appear to produce the most robust anti-depressant and anti-anxiolytic effects, writing that “5-HT2A receptor directed therapeutic strategies may be superior to ketamine-based treatments in the clinic for depression.”

Of course, this was carried out on rats, so further testing must be carried out on humans before drawing a strong conclusion.