Mental health benefits of classical psychedelics

Clinical research over the past decade has found that ingesting a single dose of certain psychedelics can produce long-lasting mental health benefits—from weeks to years. Most interestingly, these drugs affect behavioral and personality traits that are generally considered to be relatively stable throughout adulthood. Psychiatrists have been impressed that they can affect both mentally healthy individuals as well as patients with neuropsychiatric disorders such as depression and anxiety.

It is important to recognize that research into the benefits of psychedelic treatments suffers in particular from the fact that it is incredibly difficult to properly blind study participants – after all, these drugs induce hallucinations! In one publication, it was noted that participants who claimed a higher degree of “openness” a year later also experienced more mystical experiences during their psilocybin sessions. Their personality changes and therapeutic gains were directly related to the intensity of their mystical experience. A mystical experience is often as difficult to describe as it is to measure.

Psychedelic drug therapy is also unique in that effects often occur immediately after the first treatment session and additional treatments are not always required to maintain clinical benefits. These are the same therapeutic features that characterize the standard placebo effect. A recent review of 10 independent psychedelic-assisted therapy trials in which patients with either anxiety, depression, obsessive-compulsive, or substance-abuse disorders were given either 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 used LSD again. Recent studies in rats have concluded that LSD has positive nootropic actions.


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


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

Twenty patients with moderate or severe, unipolar, treatment-resistant depression reported increases in openness and extraversion and decreases in neuroticism after being treated with two doses of psilocybin (10 and 25 mg). These benefits lasted for 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 mechanisms underlying the benefits of psychedelic therapies are, at least in part, linked to this receptor and the molecular and cellular adaptations that are induced. Blocking this receptor with an antagonist drug eliminated almost all of the effects of psilocybin, LSD, and ayahuasca in humans. Other studies in humans have shown that serum levels of the BDNF hormone are increased by ayahuasca and LSD. Because BDNF cannot cross the blood/brain barrier, it is not known what effects it may have on the brain.

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

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

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