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Exploring Ketamine as a Promising Treatment for PTSD

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Disclaimer: Psychedelics are largely illegal substances, and we do not encourage or condone their use where it is against the law. However, we accept that illicit drug use occurs and believe that offering responsible harm reduction information is imperative to keeping people safe. For that reason, this document is designed to enhance the safety of those who decide to use these substances.

Frightening experiences often leave scars. For some people, scars manifest as physical marks as the memory of the event slowly fades. For others, life-threatening and boundary-crossing moments remain in the psyche, disrupting their nervous systems for years to come. 
This imbalanced state, known as post-traumatic stress disorder, or PTSD, impacts millions of people worldwide. 
Many turn to psychotherapy and medications to relieve symptoms. But over one-third of patients find no relief from traditional interventions. 
Pharmaceutical failures have led researchers to explore psychedelics like ketamine as modalities for PTSD. Since 2014, clinical studies have indicated ketamine for PTSD could effectively treat symptoms and prevent occurrence by amplifying emotional resilience. 
Understanding PTSD and its Symptoms
People frequently develop PTSD after facing a threatening situation, like sexual assault. Trauma resulting from other distressing events, such as combat exposure, natural disasters, or life-threatening accidents, can also serve as catalysts for the development of PTSD. Following the event, they experience distressing memories, nightmares, dissociative reactions, and irritability. 
People with PTSD and chronic PTSD often re-experience the event through flashbacks, nightmares, or intrusive thoughts. These re-exposure events incite anxiety, heart palpitations, and sweating. 
Most who suffer do everything they can to avoid the people, places, thoughts, or situations that trigger memories of the incident. 
PTSD symptoms are relentless, causing long-term effects of ketamine that prevent people’s ability to think, sleep, or relax. Most who suffer are easily startled and frequently tense. They may have sudden emotional outbursts.
Some people have trouble remembering details about the traumatic event. They may have negative thoughts about the world and themselves. Some feel shame or guilt over the incident, gradually losing interest in activities and practices they once enjoyed.
PTSD, which can result from various traumatic experiences such as sexual assault, combat exposure, or natural disasters, often leads to distressing symptoms like flashbacks, avoidance behaviors, emotional instability, and negative self-perception, profoundly affecting individuals’ daily lives.
Traditional Post-traumatic Stress Disorder Treatments 
Common treatment options for PTSD incorporate psychotherapy and medications. Therapeutic options include: 

Unfortunately, the above models often fall short. 
According to a review of military, veteran, and first responder PTSD, prolonged exposure therapy and cognitive processing therapy provided only marginally better results than non-trauma-focused treatments. 
In 2020, another review found similar results comparing leading trauma-focused treatment options to non-trauma-focused therapies. These therapies didn’t yield significantly different outcomes.
Instead, the effects were similar across the tested treatments, including therapy, medication, and transcendental meditation. In fact, the study posited that the treatments were emotionally demanding for patients because PTSD is characterized by a strong desire to avoid talking about the trauma and rekindling negative emotions. Further, it stated that traditional treatment options (PE/CPT) have been challenged in recent years because clinical trials have yielded mixed results, with patients not obtaining meaningful symptom improvement.
In some cases, traditional treatments fail to make any difference at all. As many as 50% of clinical trial patients are “nonresponsive,” while 5% to 79% drop out of trials altogether.Following traditional therapies, most patients continue suffering debilitating symptoms.
One 2020 study showed as many as 72% of patients still qualified for a PTSD diagnosis—only 31% of patients who underwent treatment recovered from the condition.In 2022, a study focused on hyperarousal following PTSD treatment in active-duty military personnel showed that 61% of participants were labeled as suboptimal responders after completing cognitive processing therapy, 21% were deemed to have recovered, and 18% of conditions had improved. This sparks the question: should traditional treatments be considered the first line of defense against PTSD at all?Overall, the lackluster success rates emphasize the need for more effective modalities.
Traditional treatments for PTSD, including psychotherapy and medications such as prolonged exposure therapy and cognitive processing therapy, often yield only marginal or non-significant improvements, with a significant percentage of patients remaining symptomatic or unresponsive, highlighting the need for more effective treatment modalities.
Ketamine for PTSD to Reshape Trauma through Psychedelic-Assisted Therapy
Ketamine seems like an unlikely PTSD treatment candidate, given its history. In 1970, the FDA approved ketamine as an anesthetic. Anesthesia remains its primary use today. However, clinical trials starting in 2000 showed ketamine could also treat various mental health conditions, including depression, treatment-resistant depression, and PTSD.
Ketamine administration, at sub-anesthetic doses, exhibits psychedelic and dissociative effects, including altered perceptions, floating sensations, and detachment from reality. 
In the context of depression and PTSD, researchers believe these effects facilitate a temporary “reset” of brain patterns, allowing patients to escape ruminative cycles and negative thought patterns that perpetuate their conditions. The psychedelic experience often allows for emotional and cognitive insights, providing patients with new perspectives on past traumas or current struggles. 
Neuroscientifically, ketamine affects multiple receptors and pathways in the brain and body. Primarily, it increases the release of glutamate neurotransmitters through its action on NMDA (n-methyl-d-aspartate) receptors. 

Here’s how ketamine works:

Ketamine Enters the Brain: After administration, ketamine crosses the blood-brain barrier and enters the brain’s neural network.

Blocks NMDA Receptors: Ketamine primarily blocks a specific type of receptor called the NMDA receptor, interrupting communication between nerve cells.

Increases Glutamate Release: Blocking NMDA receptors indirectly increases a neurotransmitter, glutamate, critical for mood regulation.

Activates AMPA Receptors: The surge in glutamate activates another receptor called AMPA, further enhancing cell-to-cell communication.

Boosts Synaptic Plasticity: This receptor activation strengthens connections between neurons, a process known as synaptic plasticity. This mechanism can help form new, healthier thought patterns and counter depression’s adverse effects on the brain. 

Induces Dissociative and Psychedelic Effects: By disrupting normal neural signaling, ketamine creates feelings of dissociation from reality, altered perceptions, and even mystical experiences.

Emotional Insight and Perspective: These altered states can give individuals new perspectives on their issues or traumas, often described as a “reset” for the brain.

Rapid Antidepressant Effects: The combination of synaptic plasticity and emotional insight often results in a quick lift from depressive symptoms, unlike traditional antidepressants, which may take weeks to work.

Ketamine, when used as a treatment, influences the brain by helping to create new connections between brain cells, which can provide quick relief from depression. It also causes temporary changes in how people perceive things and can offer new insights into their problems.
How Does Ketamine Therapy Work as a PTSD Treatment?
Ketamine alone triggers rapid improvements in mood and depression symptoms. But like any powerful compound, ketamine works better with therapeutic support. 
Ketamine-assisted therapy for PTSD combines the drug’s administration with psychotherapy to maximize its efficacy. This dual approach aims to tackle the disorder’s biochemical and psychological aspects.
On the biochemical side, ketamine’s ability to enhance neuroplasticity creates a more fertile ground for the cognitive and emotional restructuring that takes place during psychotherapy.  Additionally, ketamine’s psychedelic and dissociative effects offer a profound emotional and cognitive reboot, allowing patients to distance themselves from past traumas and gain new perspectives.
On the psychological side, the psychotherapeutic component often involves methods like cognitive behavioral therapy (CBT) or eye movement desensitization and reprocessing (EMDR). These therapies work in tandem with ketamine’s neural effects to challenge the deeply-rooted thought patterns and behaviors that contribute to PTSD symptoms.
This multimodal approach provides a holistic treatment that can maximize and prolong mental health benefits.
Combining therapy with ketamine treatment can help improve mood and tackle the effects of past traumas on both the brain and the way we think, providing more comprehensive and long-lasting mental health benefits.
Ketamine Infusion: Testimonials from Patients 
Infusions of ketamine for PTSD have become commonplace in clinics nationwide. Countless patients have told their transformative stories. 
One former military patient stated that upon starting ketamine therapy, his PTSD symptoms vanished, and his anxiety symptoms became manageable. He had not experienced a panic attack since the start of treatment:

“I was referred [ketamine] by a close friend that also struggled with treatment-resistant depression and it saved his life. After starting treatment my PTSD symptoms are null, my depression is minimized, and my anxiety is at a tolerable level – no panic attacks since I started treatment! I have a level of clarity I have not had for so long. I am very excited about this treatment and would refer anyone that is in a similar situation. I have referred my family members already.”

One patient who started ketamine infusion therapy started off skeptical but was willing to try anything. They were experiencing severe anxiety, depression, and anger due to unresolved PTSD and weren’t responding to other treatments. They said ketamine therapy made them feel calmer and more in control of reactions:

“Things that would have previously caused a panic attack and a day of shame and recovery now don’t feel as terrifying.”

One anonymous ICU healthcare worker with PTSD (acquired after working during the pandemic) said that anxiety was nearly eradicated after just one treatment. They also reported less sleep loss and work-related anxiety:

“I have major PTSD from working COVID in the ICU. After one session, it’s already almost eradicated my anxiety going into work. I use to have major sleep loss and anxiety related to work but it’s already been a major improvement.”

Ketamine infusions for PTSD have become widely used in clinics across the country, and many patients have reported significant improvements, such as reduced anxiety, improved mood, and better control over their reactions, often experiencing relief after just a few sessions.
Considerations and Precautions
Ketamine can be incredibly effective for PTSD. However, not everyone is suited for this powerful dissociative medicine.
Patients must be aware of the safety concerns and possible side effects of ketamine they might experience.
Potential side effects of ketamine that accompany a single infusion of ketamine for PTSD include disorientation, numbness, difficulty speaking, and dissociation. These effects are short-lived, subsiding in about four hours following treatment. 
Ketamine is also an addictive substance when overused. This risk is why patients must seek structured ketamine protocols from a trusted medical clinic. 
The Bottom Line on Ketamine for PTSD
Ketamine therapy is a promising avenue for alleviating PTSD. By modulating NMDA receptors and enhancing neural activity, ketamine can relieve intrusive thoughts, nightmares, and emotional disturbances.
Testimonials highlight its transformative potential, while research reveals its rapid-acting effects. Early results depict a beacon of hope for those grappling with the debilitating symptoms. As science ventures deeper, ketamine could revolutionize PTSD treatment standards, offering immediate healing for those who need it most.
For more information about ketamine-assisted psychedelic therapy and finding a clinician near you, visit Third Wave’s directory.



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