Mental health benefits of classic psychedelics

Clinical research over the past decade has found that taking a single dose of some psychedelics can produce long-term mental health benefits—from weeks to years. More interestingly, these drugs affect behaviors and personality traits that are normally considered relatively stable throughout adulthood. Psychiatrists have been impressed that they can produce effects in both mentally healthy individuals and patients diagnosed with neuropsychiatric disorders such as depression and anxiety.

It is important to recognize that research on the benefits of psychedelic treatment is particularly prone to suffer from the fact that it is incredibly difficult to properly blind study participants – after all, these drugs produce hallucinations! In one publication, it was observed that participants who claimed a higher degree of “openness” a year later also experienced a more mystical experience during their psilocybin session. Their personality changes and therapeutic benefits were directly related to the intensity of their mystical experience. A mystical experience is often as difficult to describe as it is to quantify.

Psychedelic drug therapy is also unique in that effects are often immediate after the first treatment session and do not always require additional treatments to maintain clinical benefits. These are the same therapeutic features that characterize the standard placebo effect. A recent review of 10 independent trials of psychedelic-assisted therapy in which patients with anxiety, depression, obsessive-compulsive, or substance abuse disorders were given psilocybin, ayahuasca, or LSD reported that the therapeutic benefits were long-lasting. ; for ayahuasca, up to a year.


Ten years after taking LSD, 247 people reported positive personality changes. Interestingly, only 23% of these subjects ever used LSD again. A recent study with rats concluded that LSD had positive nootropic effects.


N,N-Dimethyltryptamine (DMT), the main active ingredient in ayahuasca, when combined with a monoamine oxidase inhibitor, produces inconsistent effects on personality traits in a number of clinical trials. The benefits of ayahuasca may be limited to specific emotional problems; Findings from a very recent study did not support an anxiolytic effect of ayahuasca treatment.


Perhaps more is known about the mental health benefits of psilocybin than any other classic psychedelic. In a well-controlled longitudinal study of 52 healthy psychedelic-naive subjects who received varying doses of psilocybin, the personality trait of “Openness” increased immediately after one month and remained elevated for at least 14 months. Subjects who received higher doses reported greater positive effects. The beneficial effects of psilocybin have been replicated in several recent studies.

After 20 patients with moderate to severe, unipolar, treatment-resistant depression were treated with two doses of psilocybin (10 and 25 mg), they reported an increase in openness and extraversion and a decrease in neuroticism. These benefits lasted at least four months.


The psychedelic effects of psilocybin, ayahuasca, and LSD in humans are related to their action on a specific serotonin receptor called 5-HT2A, although other receptors may also be involved in the full effects of these drugs. The neurobiological mechanism underlying the benefits of psychedelic therapies may be due, at least in part, to this receptor and the molecular and cellular adaptations that are induced. Blocking this receptor with an antagonist drug abolished almost all the effects of psilocybin, LSD and ayahuasca in humans. Other studies in humans have shown that serum levels of the hormone BDNF are increased by ayahuasca and LSD. It is not known what effect this may have on the brain as BDNF cannot cross the blood/brain barrier.

In a longitudinal study, healthy volunteers given psilocybin (ever wonder where they find these volunteers?) were assessed with fMRI scans one day before, one week after, and one month after receiving a dose of 25 mg/ 70 kg. One week later, the response of the amygdala (a structure that controls emotional responses) to negative facial affect was reduced, while the responses of the dorsal lateral prefrontal and medial orbitofrontal cortex to emotionally conflicting stimuli were increased. These effects lasted only one week after treatment.

Currently available evidence strongly supports the need for additional studies of the ability of psychedelics to improve the emotional state of healthy people as well as those with neuropsychiatric disorders.

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