Psychedelic Breakthrough for PTSD
The first FDA approval for a psychedelic therapeutic is almost here.
The first psychedelic medicine likely to be approved by the FDA (coming as early as 2023) is 3,4-methylenedioxymethamphetamine, more commonly known as MDMA. MDMA, in conjunction with psychotherapy, will be up for approval for post-traumatic stress disorder (PTSD) – a disorder with a constellation of symptoms that arises after exposure to a terrifying or shocking event.
Results from clinical trials have been so promising that in 2017 the FDA granted MDMA-assisted psychotherapy with the status of breakthrough therapy, meaning that it demonstrated substantial improvement over available therapies for the disorder.
This treatment approval would be tremendously positive for a number of reasons, including:
MDMA-assisted psychotherapy for PTSD is far more effective for curing PTSD than previous treatments.
PTSD is a debilitating condition for individuals and a costly one for society.
PTSD is notoriously difficult to treat.
MDMA is not a classic hallucinogenic psychedelic and is thus more approachable for individuals who are psychedelic-hesitant.
People experiencing post-traumatic stress can live in a heightened stress response state and have a difficult time feeling safe because their minds/bodies don’t realize the traumatic event is over. The person can experience hyperarousal (panic attacks, overwhelming anger) and hypervigilance, flashbacks of the traumatic event, and a constellation of other symptoms. Emotional blunting. Low mood. Numbness. Detachment. Avoidance. Irritability. Tendency to isolate. Severe depression and suicidal ideation. Self-medicating with alcohol or substances. They avoid triggers of the event at all costs. In some cases of PTSD, dissociation can occur where the painful memories are broken off and isolated, preventing healing. When PTSD builds upon former lifetime traumas (e.g. childhood abuse, loss, disturbed attachments, etc), the condition is called complex PTSD, and can be more difficult to treat because there are layers of trauma that have not been processed. Often, the traumas are too difficult to repeat out loud. This is why regular psychotherapy often fails: the person can’t bear to face the trauma (1).
But the only way out of an emotion is through it. To heal from trauma, the traumatic event and associated emotions must be faced again and recontextualized. In order to do this, the person needs to have a deep knowing that they are safely in the present moment while the traumatic events are in the past (2). Then, they can confront the traumatic event to fully feel (and release) the core emotions (e.g. helplessness, loss of control), and gain a sense of empowerment (3). In other words, they can rewrite the story in their bodies and minds.
So, how can MDMA-assisted psychotherapy help?
In the latest MDMA-assisted psychotherapy phase 3 clinical trial, researchers found that after just three sessions (4,5):
67% of participants in the MDMA group no longer met the diagnostic criteria for PTSD 18 weeks after baseline, compared with 32% of those in the placebo group.
33% of the MDMA group (and 5% of participants in the placebo group) met the criteria for remission.
Depressive symptoms were significantly mitigated.
The treatment was effective even for participants with chronic, severe, and treatment-resistant PTSD.
The results are remarkable, considering the alternative treatment options for PTSD, and make clear why the FDA gave breakthrough status to the treatment. Standalone psychotherapy can go on indefinitely if the pain of the traumatic event is too much to revisit and is continually avoided. Pharmacotherapies solely mask symptoms. MDMA-assisted therapy for PTSD has been shown to be more effective than FDA-approved first-line pharmacotherapies, such as sertraline and paroxetine (4,6). In other words: MDMA-assisted psychotherapy for PTSD provides effective treatment to suffering individuals for whom other treatments have failed.
But what does the treatment program entail?
In the Multidisciplinary Association for Psychedelic Studies (MAPS) – the organization that has been driving this research for decades – MDMA-assisted psychotherapy protocol, the treatment program extends over three months and is comprised of:
Three 90-minute preparation sessions
Three 8-hour MDMA-assisted psychotherapy sessions
Three 90-minute integration sessions
Two co-therapists facilitate the psychotherapy sessions. MAPS designed the treatment program to allow space for the person’s innate capacity to heal, or inner healing intelligence, to do its job. This comes from the idea that the human mind/brain knows how to heal itself, just as the human body does. All we have to do is get out of the way.
But how and why does it work?
In short, the MDMA molecule increases positive affect, empathy, self-compassion, introspection, a sense of well-being, a sense of trust and reduces fear (7–11) – the sum total of which allows the person to feel safe to confront and reexperience the traumatic event without being overwhelmed by the associated emotions (12,13). They can describe what happened during the event, how they felt, and ultimately move through the emotion. With the help of the two therapists, the traumatic experience can be reframed, providing a sense of understanding and empowerment to the person by processing and releasing shame, guilt, pain, and anxiety from their minds and bodies. Ideally, there comes to be a healthy mourning of what has happened.
MDMA-assisted psychotherapy gets at the root of the problem, it doesn’t simply mask symptoms. It’s not the drugs or the therapist that do the healing – they simply create space for the mind/brain to process painful memories and heal itself.
We don’t know the exact mechanism by which MDMA causes its effect, but it is believed to be through increased neuroplasticity, and altered activity within and connectivity between areas of the brain involved in fear, anxiety, and memory (i.e. amygdala, insula, and hippocampus) – all through the release of serotonin, noradrenaline, oxytocin and cortisol.
While molecular models are helpful, we should also be asking: what are the independent, and overlapping, mechanisms of MDMA and psychotherapy? There are beautiful theoretical psychological-based descriptions of the program’s healing, and then also neuroscience-based descriptions of the MDMA molecular mechanisms. We need a full and integrated model. For example, how is the recovery of symbolization (the ability to imbue events with meaning and narrative) during MDMA-assisted psychotherapy modeled in the brain?
This is why I love psychedelic medicine research – it highlights the lack of convergence of these two fields: clinical psychology and neuroscience. Hopefully, it will force our hand to do this long overdue work.
To confuse matters even more, too often the body is left out of conversations of mental healing. How many people think of PTSD’s effect on and symptoms in the body in addition to those of the mind? A traumatic event doesn’t just happen in your mind; it engages your body, including your nervous system(s). Therapist Peter Levine, PhD proposes that to cure trauma one must allow the body to complete its natural response (e.g. shake, tremble) to a traumatic event so that it can release the energy generated by the event and go back to its relaxed state (14). The MAPS protocol for MDMA-assisted psychotherapy for PTSD recognizes bodywork as important in the healing process.
Moving forward in our understanding of healing, we will need to better map the relationship between the mind, brain, body, and trauma.
The last FDA-regulated phase 3 clinical trial of MDMA-assisted therapy for PTSD has begun phone screening and informed consent visits. The first participant was treated in a phase 2 open-label, randomized comparative effectiveness study for MDMA-assisted therapy in U.S. Military Veterans with Chronic PTSD. The research is well on its way.