The Mental Health Benefits of Classical Psychedelics

Clinical research during the past decade has discovered that ingesting a single dose of some psychedelics can produce long-lasting mental health benefits—weeks to years. Most interesting is that these drugs affect behaviors and personality traits that are normally regarded as relatively stable throughout adulthood. Psychiatrists have been impressed that they can produce effects in both mentally healthy individuals as well as in 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 hard to appropriately blind the study participants – after all, these drugs produce hallucinations! In one publication, it was noted that participants who claimed a higher degree of “openness” one 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 the effects are often instantaneous after the first treatment session and do not always require additional treatments to maintain the 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 one year.

LSD

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

Ayahuasca

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

Psilocybin

More is probably known about the benefits of psilocybin for mental health than any of the other classical psychedelics. In a well-controlled longitudinal study of 52 psychedelic-naïve healthy subjects who received varying doses of psilocybin, the personality trait of “Openness” increased as soon as one month later and remained increased 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 or 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.

Neurobiology

The psychedelic effects of psilocybin, ayahuasca, and LSD in humans correlate with their action at a specific serotonin receptor called 5-HT2A, although other receptors may also be involved with the complete effects of these drugs. The neurobiological mechanism underlying the benefits of psychedelic therapies might be due, at least partly, to this receptor and the molecular and cellular adaptations that are induced. Blocking this receptor with an antagonist drug abolished virtually 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 unknown what effect this might have on the brain since BDNF cannot cross the blood/brain barrier.

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

The 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.