This post was commissioned by Numinus and Third Wave to present a balanced view on the potential role of ketamine in managing PTSD.
Post-Traumatic Stress Disorder (PTSD): The Persistence Of Trauma
Reports of violence, injury and death are a daily occurrence in our headlines; so it may come as little surprise that over 70% of adults worldwide experience a traumatic event at some point in their lives. Post-traumatic stress disorder (PTSD) is the most prevalent psychopathological consequence of this.
The core features of PTSD include the persistence of intense, distressing and fearfully avoidant reactions to reminders of the triggering event, alterations in mood and cognition, a pervasive sense of imminent threat, disturbed sleep, and hyper-vigilance.
The severity of these symptoms fluctuates over time, often reflecting sensitivity to co-occurring stressors such as illness, and life transitions. Some factors associated with increased susceptibility include female sex, childhood trauma, lower socioeconomic status, prior mental disorders, exposure to four or more traumatic events, and a history of exposure to interpersonal violence.
The intensity of the event is also a factor, with increased risk associated with exposure to death, torture, bodily disfigurement and traumatic brain injury, as well as an experience that is unexpected, inescapable or uncontrollable.
Mental Health Management: A Pressing Need For Novel Interventions
As psychological trauma is intangible, often aligns with complex co-morbidities, and presentation fluctuates – diagnosis can be difficult; patients may lack insight or suffer in silence, and biomarkers are lacking. Some physiological and neuroendocrine predictors of PTSD include elevated heart and respiration rates, and a low plasma cortisol level. But approaches to treatment need to take on multiple dimensions including the pharmacological, psychological, and social.
Most patients with PTSD receive some form of pharmacological treatment in the form of antidepressant SSRIs (89%), anxiolytic or sedative-hypnotics (61%), and antipsychotics (34%). However, many of these display few long-term benefits or efficacy. Antidepressants often alleviate symptoms but rarely induce remission, and there is a substantial risk of relapse upon discontinuation. On their own, they act as a band-aid that can provide temporary relief but does not fix the root cause.
In terms of acute psychological interventions, some survivors are given primary stress management in the form of psychological debriefing. This is a one-session intervention in which survivors review and discuss the event in the immediate aftermath. This is no longer recommended, as studies have shown that this rarely prevents PTSD from developing and may even have harmful consequences.
Instead, early CBT is the mainstay of preventive psychological intervention and is equally effective between 1-6 months after the event. But while positive results can be maintained for years, it is still ineffective for numerous survivors.
There is a pressing need for innovative therapies for PTSD diagnosis and management. Emerging areas include neurofeedback (training patients to regulate brain activity using real-time images), transcranial magnetic stimulation (sending magnetic pulses to brain areas to alter activity), and psychedelic therapies including medical cannabis, MDMA and ketamine.
“Depression is among the most concerning medical diseases [and] it’s common. It affects your life in terms of employment, relationships, your ability to experience pleasure. And in those patients who don’t respond to traditional anti-depressants, those symptoms are magnified – in that the patient feels hopeless. In the worst cases, they are suicidal. The fact that esketamine has been shown to effectively treat treatment-resistant depression, for many patients, this offers hope.” – Dennis Charney, MD, dean of the Icahn School of Medicine, Mount Sinai
Medicalising Ketamine: Contextualising Care
All drugs display duality. Ever since President Nixon officially declared the ‘War On Drugs’, psychedelic therapies have suffered the consequences of a binary agenda that removes contextual complexity. Frequently associated with ‘k-holing’ and ‘horse tranquilisation’, ketamine’s curative potential remains similarly controversial.
Paradoxically, ketamine produces transient dissociative and psychotic states that resemble the symptoms of PTSD. It may work on glutamate as an n-methyl-d-aspartate receptor antagonist and is more commonly used for the off-label treatment of treatment-resistant major depressive disorder (MDD). Given the treatment-resistant nature of PTSD and its co-morbidity with MDD for many patients, there is promising potential in developing safe ketamine therapy protocols.
Ketamine is already widely used as an analgesic and sedative in emergency care; however as with psychological debriefing, studies have shown that it might be one factor triggering, modulating, or exacerbating PTSD and acute stress disorder (ASD) in the acute trauma phase. This highlights the role of set and setting: illustrating the need to take holistic mind-body approaches to heightened neuroplasticity in acute states.
By contrast, in the chronic phase of PTSD, ketamine infusion has been associated with significant and rapid reduction in symptom severity compared with midazolam, alongside reduced co-morbid depressive symptoms. Research suggests that chronic PTSD impairs synaptic connectivity, which is mediated by glutamate, and that as ketamine enhances this connectivity, it reverses these effects.
When it comes to side-effects, a randomised controlled trial by Feder and colleagues using IV ketamine noted that one patient dropped out of the study due to dissociative effects, and three patients were treated with β-blockers due to increased blood pressure. Such symptoms are often managed by altering the dose or route of administration, for example oral ketamine has a lower bioavailability.
Other dose-dependent risks include laryngeal spasms or respiratory depression (especially if combined with substances that act as CNS depressants such as alcohol or opioids), chest pain, amnesia, urological problems and kidney toxicity with chronic abuse.
Many patients worry about addictive potential with ketamine treatment, and substance-use disorder (SUD) is often correlated with PTSD and chronic stress, as survivors attempt to self-soothe and search for symptomatic relief. However, addiction is a complex multidimensional disorder that includes a contextual and behavioural component, and some of the same substances that have abuse potential (such as cannabis and ketamine), are also used to help addicts overcome their dependencies within the clinical container.
Side-effects can be equally contextual. Although dissociation may be considered undesirable from a biomedical standpoint, it shows beneficial potential when supported and integrated within a psychotherapeutic structure. While many physicians still see the glutamate hypothesis as a reason to isolate ketamine’s effects to a metabolite or analogue that lacks the psychedelic or mind-altering component, the role of the emergent, transpersonal or mystical experience pulls its own weight, and research by Jennifer Dore and colleagues highlights that:
‘No study to date, has demonstrated that absent some degree of perceived psychoactivity, there is an antidepressant effect’.
Ketamine is as much a clinical cure, as a shamanic science – with its ‘trance and transformation’ aspects being key elements of the holistic healing process. This benefit occurs not only across a range of doses, but also for a range of diagnoses.
Ketamine’s psychological effectiveness rests on its ability to provide time-out from the ordinary, usual mind, relief from negativity, and an openness to the expansiveness of self and life in a larger sense. These effects enhance a patient’s ability to engage in meaningful psychotherapy both during and after administration.
Within this experience, an anchoring of the essential elements can take many symbolic forms, including slogans, mantras, visions, internal movies, feelings, and metaphors. These components foster new perspectives by directing an unfolding process that allows us to understand ourselves in a new way: the missing link that gives hope to many sufferers who cannot achieve this reframing by other means.
“With appropriate preparation and dosing, ketamine can bring about a unique experience of time, space, and form, one that transcends ordinary consciousness to a state where the mind feels liberated… In this non-ordinary state of consciousness, the client has the opportunity to think and feel differently. They may more easily revisit past traumas and be better able to actively participate in the work that healing requires. This is why we’re so excited at Numinus about what can happen when ketamine is paired with psychotherapy for individuals with mental health conditions, especially ones that are lacking effective [alternatives].” – Dr. Reid Robison, Numinus Partner
Post Traumatic Growth: Trauma, Trance And Transformation
While trauma can invoke terrifying and debilitating responses, it can also be leveraged as a catalyst for positive change – sparking growth, strength, and resilience. Post traumatic growth is when adversity becomes advantage, with constructive meaning-making mechanisms providing new context to people’s lives.
Healing processes are non-linear and look different for everyone. There are no ‘one size fits all’ solutions or results. But some positive outcomes take the form of a mindfulness and gratitude for life in the present moment, and the prioritisation of relationships that the individual feels endured despite difficult times.
Rather than rushing to achieve a false sense of optimism, processing trauma takes time, and it’s important not to minimise the effects of the experience. While defining community and authenticity rests on a spectrum relative to individuality, some protective factors include a strong support system, personality traits such as openness, and personalised tools to integrate experiences into new belief systems.
Psychedelics have forever changed the landscape of mental healthcare, as in harnessing the vital role of the mind-body consciousness connection, they combine structured psychotherapy with embodied and mindfulness-based approaches to long-term outcomes.
Numinus are one example of a clinic taking this integrative approach to holistic health. They understand that psychedelics are powerful medicines, but not magic pills. While they can profoundly change lives, families, and communities – that success requires more than just a breakthrough experience – it also takes careful, sensitive attention to every individual’s story, mindful preparation, and a grounded, realistic plan for what comes next.
Clinical Containers: Science and Society
The difficulty with current approaches to research and treatment are the high rates of real-world variability. There are different types of PTSD, different routes of drug administration, different timescales for intervention, different interpretations and methods of qualitative and quantitative analysis, and different individuals and backgrounds. This makes it challenging to align the literature and find cohesion for an evidence-based approach to care, while appreciating individual needs.
Research rarely reflects the whole story, for example when it comes to differences in PTSD risk between genders, women are more likely than men to experience dissociative symptoms (the most common being time distortion), and are at greater risk of specific re-experiencing symptoms with similar situations or triggers afterwards. But they are also more likely to report such symptoms.
PTSD is a multidimensional interaction between a subject, a trauma, and a social context. Sex, social and situational factors all play a role in development, expression, and persistence of symptoms. For example, the cultural influence of gender roles affects how physical assault might be perceived differently by genders, and combatants trained to persevere may not readily admit to fear, helplessness, or terror.
A personalised bio-psycho-social approach to treatment appreciates these grey areas. Third wave CBT approaches such as Functional Analytic Psychotherapy (FAP) are rooted in the contextual behavioural tradition that focuses on the therapeutic relationship as the agent of change to improve interpersonal relating, by fostering strong authentic connection.
In other words, if the synergistic effects of the placebo response hint at anything, it’s that at the heart of many effective long-term interventions: pharmacological, psychological, psychedelic, and social – are trust and human connection, the damage of which, is so much at the core of trauma persistence.
Social connectivity to others, nature, the cosmos, and most importantly to an authentic sense of oneself, while promoting a sense of psychological wellbeing, peacefulness, and acceptance of one’s troubled past, is an underlying mechanism of reliable recovery.
Perhaps one of the most transformative potentials of the emerging psychedelic industry in particular, is its holistic mind-body approach to combining scientific rigour with cultural collaboration and contextual nuance, alongside the art of a professional intimacy that cultivates a responsible, compassionate, safe and therapeutic breathing space, for the intangible wounds of those in a vulnerable altered-state to heal.
