Grief for the loss of a loved one is a natural and universal process influenced by personal, social, and cultural factors, ultimately making it a unique, personal, and non-transferable process. Difficulty accepting the loss, as well as a deterioration in personal and social well-being, are common characteristics of the grieving process (Rosner et al., 2021). Although, in most of the population, acute grief tends to diminish over time, around 10% continue to experience significant difficulties several months after the loss (Lundorff et al., 2017).
Currently, Complicated Grief is recognized as a clinical condition in the latest version of the International Classification of Diseases (ICD-18). This condition is characterized by:
(1) separation anxiety, manifested in a persistent response of longing and worry;
(2) intense emotional reactivity, which may include anger, denial, guilt, emotional numbness, a sense of emptiness, or avoidance; and
(3) significant functional impairment (Eisma, 2023; Shevlin et al., 2023). To be diagnosed, these symptoms must be present at a severe level for at least six months after the loss (WHO, 2022).
Recent meta-analyses have shown that psychological therapy has moderate efficacy in treating grief (Komischke-Konnerup et al., 2024; Johannsen et al., 2019). Furthermore, there is still no evidence of the effectiveness of any medication alone, including antidepressants (Shear et al., 2016; Bui et al., 2012). Given these limitations in the therapeutic tools available to date, new approaches have emerged to address prolonged grief, including psychedelic-assisted therapy or psychedelic therapy.
Over the past few years, several studies have highlighted the potential of psychedelic substances to facilitate acceptance of the irreversibility of death and promote continued bonds with loved ones (Gowda et al., 2016; Low et al., 2023; González et al., 2019; 2020). This preliminary evidence has led major institutions such as Johns Hopkins University (USA), Queensland University (Australia) and the Beckley Med Foundation (Spain) to conduct clinical studies on psychedelic-assisted therapy for grieving, achieving promising results that are difficult to achieve with standard therapy.
The therapeutic effect of psychedelics on grief, and particularly ketamine-assisted therapy (KAT), is based on different levels of evidence:
At the neurobiological level, ketamine promotes neurogenesis, neuronal plasticity, and metaplasticity (Deyama et al., 2023; Nardou et al., 2023), especially in areas such as the prefrontal cortex and hippocampus, which play a key role in learning, emotional regulation, and social behavior. This period of neuroplasticity is known as the “critical period,” and begins a few hours after administration and extends over several days. This time window favors learning, psychological flexibility, cognitive restructuring, and the adoption of new behavioral patterns (Gorman et al., 2021; Luoma et al., 2019), making it a particularly fertile period for further exploration during psychotherapy.
Furthermore, the therapeutic effect of ketamine on grief processes may also be enhanced by the phenomenological experience during the drug-induced altered state of consciousness (Low et al., 2023). Like other psychedelics, ketamine has been associated with experiences of acceptance, reappraisal of difficult events, and mystical experiences (Gowda et al., 2016).
The information that emerges during experiences induced by the administration of ketamine or other psychedelics can provide new perspectives that allow us to transform maladaptive narratives about ourselves and our loved ones (Carhart-Harris et al., 2019; Hartogsohn et al., 2018), as well as the ontological beliefs on which we base our understanding of life and death (Timmerman et al., 2021). Therefore, the most cutting-edge scientific knowledge seems to indicate that the process of psychedelic-assisted psychotherapy (PAT), including ketamine-assisted therapy (KAT), could help deepen and enrich the most effective therapeutic approaches available to date for the treatment of prolonged grief.
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