Researchers studying psychedelic therapies are asking a fundamental question: are the mind-altering effects of drugs like psilocybin and ketamine essential to their therapeutic benefits, or merely a side effect?
Interest in psychedelic therapies using ketamine, MDMA, and psilocybin for psychiatric conditions has grown steadily. The drugs produce profound changes in consciousness, including alterations in thinking, emotions, sense of time, and bodily awareness. However, the terminology is disputed. Early researchers proposed various names—hallucinogens, psychotomimetics (mimicking psychosis), phantastica, and psychedelics—reflecting disagreement over how to classify these substances. In a technical sense, most of these drugs rarely induce true hallucinations where individuals experience false perceptions they believe to be genuine; instead, perceptual alterations like pseudo-hallucinations and synaesthesia are common.
Research on ketamine shows modest links between subjective effects and therapeutic outcomes. An estimated 5-10% of variance in ketamine’s antidepressant benefits may be predicted by specific subjective effects such as a sense of unity or insight. For psilocybin, this relationship is stronger—closer to 24%—consistent with recent clinical trial data. However, some researchers argue these subjective effects may be unnecessary and perhaps undesirable side effects. Preclinical data points to neuroplasticity-enhancing and anti-inflammatory effects as potential biological mechanisms driving therapeutic benefits independent of hallucinogenic experiences. Scientists are now developing novel compounds to assess whether these biological effects can produce therapeutic efficacy without hallucinogenic effects, with promising early animal data supporting this approach.
Beyond the drugs themselves, structured therapy appears important. The field generally agrees that some form of structured support—including psychoeducation about drug effects, review of life history, and formation of treatment goals—helps facilitate therapeutic change. The therapeutic relationship between patient and therapist can impact outcomes, and factors such as environment, personality, and mindset influence subjective drug effects. Many questions remain unanswered regarding how to maintain research integrity when studying drugs with pronounced psychoactive effects and how to separate expectancy and placebo effects from therapeutic benefits, but continued research using modern neuroimaging promises insights into conscious experience and its relationship to neurobiology.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.nature.com/articles/s44277-025-00043-y