Psychedelics in psychiatry: can intoxication heal?

Intoxicating substances are increasingly coming into focus in the treatment of mentally ill people. This upcoming paradigm shift was discussed in a recent neurology congress.

What are psychedelics?

Psychedelics are hallucinogenic and psychotropic substances that can induce a psychedelic state of intoxication in higher doses. Two main groups are distinguished. On the one hand, there are the classical and serotonergic psychedelics such as psilocybin (active ingredient in hallucinogenic mushrooms), DMT (contained in ayahuasca) or LSD. On the other hand, there are the atypical psychedelics such as the emotion-enhancing MDMA (central active ingredient in ecstasy) or the dissociative ketamine.

The latter received approval in 2019 as a drug containing esketamine for treatment-resistant depression and psychiatric emergencies. The effects of ketamine as a pharmacon for treatment-resistant depression were described as early as 2006. The antidepressant effect was clear, but no longer measurable after 7 days. Nevertheless, interest in the substance grew and other psychedelics increasingly became the focus of research, despite some critical voices.

How do psychedelics work?

Prof. Uwe Herwig, chairman of the German Society for Psychedelic Research and Therapy (German acronym: DGPFT), described in his lecture the diverse modes of action of psychedelics. Results from human studies suggest that the psychedelic experience is partly caused by a reduction of the filter function in the hypothalamus with an overactivation of prefrontal areas. 

This would modulate neuronal networks responsible for sensory perceptions, self-awareness, mood regulation and associative network integrity, among other things. In this context, those treated reported dream-like immersion, outer-body self-observation, a dissolution of ego boundaries, increased empathy, intense feelings and an altered body perception.

This can also feel unsettling and threatening. At the same time, it is precisely the reduced associative network integrity that allows those being treated to deconstruct entrenched assumptions about themselves and the future. Repressed contents of consciousness and emotional experiences can be released and new perspectives can be developed with alternative processing modes.

Psychedelics in medical practice

Sergio Perez Rosal is an anaesthetist and managing director of the Ovid Praxis, which has been carrying out ketamine-assisted psychotherapies for two years. Here, he says, the proven effects of pharmacology are combined with the phenomenology of the effect, i.e. the mystical experience, and embedded in an integration-focused psychotherapy. This is crucial so that the experience can have long-term effects.

The therapy begins with an initial psychiatric and anaesthesiological examination, as the risks should not be greater than the benefits. Then there would be several preparatory sessions for exploration and non-pharmacological forms of altering consciousness (e.g. sessions with strobe lights). This would be followed by up to 5 or 6 weeks of psychotherapeutically supervised substance-induced experience.

The experience of ego dissolution, the release of heaviness, the feeling of leaving the body and disconnecting from one's own feelings has the potential to give the treated persons the insight that they are not only their thoughts (cognitive defusion). This could help them regain more self-determination and control over themselves and their lives.

What new studies are out there? Which are missing?

Increasingly, other psychedelics such as MDMA or psilocybin are the focus of research to be approved as a potential treatment for mental illness. A new study in the New England Journal of Medicine examined the effect of psilocybin in 230 patients with treatment-resistant depression. It showed a clear antidepressant effect that lasted up to 12 weeks.

Lea Julia Mertens from the Central Institute of Mental Health (in German: Zentralinstitut für seelische Gesundheit, Mannheim, Germany) is also working on a phase-2 study on the effectiveness of psilocybin in cooperation with the Charité University Hospital in Berlin. She could see similar effects, but does not see the active substance as an antidepressant. Psilocybin opens emotionally and destabilises fixed patterns, which can trigger processes of change, especially if they are psychotherapeutically embedded.

Further studies with longer treatment courses and more frequent substance applications are therefore just as necessary as studies on the application of psychedelics with comprehensive psychotherapy embedding. So far, these do not exist. It would still be valuable if, in addition to symptom burden, process variables such as attitudes to one's own self, life, or emotions (as a prerequisite for change) were also collected. Further studies on the risk assessment of psychedelics and the evaluation of their psychedelic effects are also necessary.

  1. Prime Session (In German only). "Psychedelika in psychiatrischer Forschung und Psychotherapie". DGPPN 2022. Berlin, 25.11.2022
  2. Goodwin et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med 2022; 387:1637-1648. DOI: 10.1056/NEJMoa2206443
  3. Zarate et al.  randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.