Emerging perspectives: The role of psychedelics to treat psychiatric disorders

Albert Hofmann discovered lysergic acid diethylamide (LSD) along with similar serotonin psychedelic psilocybin. The past decade has seen a resurrection in human psychedelic drug research, especially involving psilocybin. There were 2 drivers to this. The first was the discovery by Griffiths et al that a single high dose (25 mg) of psilocybin, given in a psychotherapeutic setting, produced enduring positive changes in mood and wellbeing in people who do not have depression. The second was discovered by Carhart-Harris et al by series of neuroimaging studies in healthy volunteers, which revealed that psilocybin produced profound and meaningful alterations in brain function, leading to an antidepressant effect.

These findings suggested the possible utility of psilocybin for treating depression and various studies further supported an antidepressant outcome from a single, 25-mg psilocybin dose in people with resistant depression and those with anxiety and depression symptoms provoked by life threatening cancer diagnoses.

Other arenas being currently explored for its utility are anorexia,obsessive-compulsive disorder, and addictions.

Psilocybin in depression:

In the depression trials, the treatment model is becoming standardized as a 4-stage process: assessment, preparation, experience, and integration.

(a) Assessment determines if the patient is suitable for psychedelic therapy, both from a mental and physical perspective.

Certain medications need to be stopped or at least reduced before the treatment, because they can block or attenuate the effect of the psychedelic. Specifically, medicines that block 5-HT2 A receptors need to be withdrawn, and serotonin reuptake inhibitors ideally stopped or, if that is not feasible, tapered down, because they produce subsensitivity of the 5-HT2 A receptor.

(b) Preparation sessions typically take place the day before the drug administration. An overview of the dynamics and nature of psychedelic experiences is explained, including how it can be challenging for many people, how the participant can get the most out of the experience etc.

(c) During the psychedelic experience, the individual is offered eye shades and ear phones to listen to a music compilation that has been prepared in advance(which they can specify) because music seems to enhance the therapeutic process. For oral psilocybin, the sessions last 4 to 5 hours.

Verbal engagement with the therapists is not expected, and most patients go deep into their own visions, thoughts, and memories and do not want to be disturbed. But the guide or guides are present, and with permission, they can hold the patient's hand to reassure the person that he or she is being looked after.

(d) The next day is the integration session—during which the guides talk through the experience and help the patient make sense of it. Insight is to be further integrated, and guidance given on how best to cultivate positive cognitive and lifestyle changes.

In the treatment studies conducted so far, the psychedelic is given just once or twice over a few weeks with psychotherapeutic input (which, in the case of addictions, can be a standard 10week to 20-week abstinence-based program).

Probable mechanism of action :

Neuroimaging studies reveal that psychedelics probably work by disrupting brain systems and circuits that encode these repetitive thoughts and behaviors. The psychedelic experience opens a therapeutic window that disrupts entrenched thinking and allows insight, which with psychotherapeutic support can lead to a recalibration of one's spectrum of associations. psychedelics work in such a wide range of disorders, this may be because these conditions are all internalizing disorders.

In depression, patients continually ruminate about their failings, reiterate thoughts of guilt, and engage in self-critical inner narratives. In addiction, drug craving drives behavior that is specific, narrow, and rigid; individuals with addiction ruminate on the drug, including where to get it, how to pay for it, etc. In obsessive-compulsive disorder and anorexia, there is excessive rumination about threats to the person,from contamination or the effects of eating or overeating, respectively.

In this regard, psychedelic treatments are being considered as a new paradigm in psychiatric medicine—that of drug-facilitated psychotherapy.

Once the regulatory-standard trials have been conducted, if the outcomes are positive, then it seems plausible that psilocybin will become a licensed medicine for some forms of mental illness when used in an approved treatment model.

Source: JAMA Psychiatry: doi:10.1001/jamapsychiatry.2020.2171