I originally hypothesized that the opioid antagonist nalmefene, marketed in Europe and Israel as Selincro®, would reverse the numbing/deadness that people with PTSD experience. I conducted a one year 11 month open label pilot study using this drug to treat Vietnam combat veterans and one World War II veteran, results of which are published in the Israel Journal of Psychiatry.
Much to my amazement, nalmefene did so much more than I expected; it was serendipitous that it significantly reduced or remitted all symptoms of PTSD. Based on these findings, I conclude that the endogenous opioid system mediates the expression of all symptoms of PTSD. I believe the key to pharmacologic treatment of emotional numbing is the same key that unlocks the treatment for PTSD. This lead me to receive a patent, Method for treating post-traumatic stress disorder, in the U.S. (2021), Israel (2023), and the EU (2024). This patent is based on an accellerated dose titration method, which enables patients to reach an optimal dose in 2-3 weeks.
In 2021, Dr. Frank Enning, Vice Chairman of the Department of Psychosomatic Medicine and Psychotherapy, Central Institute for Mental Health, Mannheim, Germany, and Dr. Christian Schmahl, Medical Director of the Department of Psychosomatic and Psychotheraputic Medicine and Head of the Clinical Department of Research Group Experimental Psychopathology at the Central Institute of Mental Health, and Professor of Psychosomatics and Psychotheraputic Medicine at Heidelberg University, conducted a study in which patients diagnosed with borderline personality disorder and complex PTSD were administered nalmefene. Thirteen out of the 17 patients showed a significant reduction in dissociative phenomena during the course of treatment. It is important to note that Complex PTSD is associated with depression, anxiety, aggression and violence, drug abuse, dissociation, paranoia, and suicide.
One patient, who was diagnosed with Borderline Personality Disorder and PTSD, was abused physically and sexually on a regular basis from the ages of 4 to 18 by her father. She suffered from daily trauma-related dissociative seizures, which significantly diminished in frequency, intensity, and duration when she was administered higher doses of nalmefene. She also experienced severe mood swings, feelings of emptiness, suicidal ideation, self-harm by scalding, intrusive thoughts, and nightmares. In an email correspondence with Dr. Schmahl on December 2, 2024, he stated that he observed a clinical reduction of all of these symptoms in response to nalmefene.
It is important to note that patients in the Enning-Schmahl study only received 162 mg nalmefene once a day as the maximum available dose, rather than 200 mg twice a day in the study I conducted. Also, four patients had to be discontinued at a starting dose of 18 mg per day, and another patient at a starting dose of 36 mg per day. The accelerated method in my patent recommends a starting dose of 50 mg twice a day, which bypasses the opioid withdrawal symptoms that are observed at lower doses.
Results of the study, Treatment of dissociative symptoms with nalmefene in patients with borderline personality disorder and complex posttraumatic stress disorder, were published in Der Nervenarzt, 2022.
Between 1988-1990, I administered the opioid antagonist nalmefene to Vietnam combat veterans and one WWII veteran, all of whom were diagnosed with PTSD. The eight veterans who went to the highest dose of 200 milligrams twice a day reported that all of their symptoms of PTSD significantly improved or went into remission. My original hypothesis was that the drug would reverse the numbing response. The fact that all symptoms of PTSD (including nightmares, flashbacks, intrusive thoughts, emotional numbing and avoidance, feelings of detachment and estrangement from others, psychological and physiological reactions to reminders of trauma, hypervigilance, hyperarousal, exaggerated startle response, disturbed concentration and memory, angry outbursts and aggressive behaviors, irritability, feelings of vulnerability, mistrust of others, and dissociative symptoms, including amnesia) were remitted or significantly reduced led me to believe that the endogenous opioid system modulates the expression of traumatic symptoms.
I believe that one important way the endogenous opioid system does this is through specifically stimulating the kappa opioid receptor system. Stimulation of the kappa opioid receptors has been identified in experimental literature as being associated with inducing dysphoric mood states. This same receptor system is also associated with problems relating to stress, trauma and addictions. By contrast, the mu opioid receptor system is associated with pleasure and reward. I firmly believe the dysphoric mood state associated with stimulation of the kappa opioid receptor system is associated with the experience of being numb.
At higher doses of nalmefene (100 milligrams twice a day and above), the veterans felt increasingly more emotionally stable, self-confident, and were able to spontaneously discuss their combat experiences without any psychophysiological distress. They no longer felt as vulnerable as they did at doses below 100 mg twice a day.
The Asbury Park Press article, “Prescription for emotions running out,” was published after the study ended
and veterans were hanging on to the remaining amount of nalmefene they still had. It relays how nalmefene
dramatically changed their lives. Mike Winnick, a Vietnam combat medic and retired Director of Veteran
Services, Jewish War Veterans of the USA, was interviewed again in 2023 for an Israel National News article,
“How a Jewish Vietnam war vet overcame his PTSD.” Winnick reported that he continued to receive positive
benefits from nalmefene for twenty-three years after the drug study ended.
The Asbury Park Press article, “Prescription for emotions running out,” was published after the study ended and veterans were hanging on to the remaining amount of nalmefene they still had. It relays how nalmefene dramatically changed their lives. Mike Winnick, a Vietnam combat medic and retired Director of Veteran
Services, Jewish War Veterans of the USA, was interviewed again in 2023 for an Israel National News article, “How a Jewish Vietnam war vet overcame his PTSD.” Winnick reported that he continued to receive positive benefits from nalmefene for twenty-three years after the drug study ended.
Development and validation studies of the Glover
Vulnerability Scale are described in “Vulnerability
Scale: A Preliminary Report of Psychometric
Properties.”Psychological Reports 75, 1651-1668.
Glover, H., Ohlde. C. Silver, S., Packard, P.,
Goodnick, P., and Hamlin, C. The Revised Glover
Numbing Scale was copywritten in 2019.
Development and validation studies of the Glover Vulnerability Scale are described in “Vulnerability Scale: A Preliminary Report of Psychometric Properties.”Psychological Reports 75, 1651-1668. Glover, H., Ohlde. C. Silver, S., Packard, P., Goodnick, P., and Hamlin, C. The Revised Glover Numbing Scale was copywritten in 2019.
“Treatment of dissociative sympstoms with nalmefene in patients with borderline personality disorder and complex posttraumatic stress disorder.” Der Nervenarzt Volume 93, pages 503-505, (2022).
“Relationship of Numbing to Alexithymia, Apathy, and Depression.” Psychological Reports 88: 189-200.
“Critique of Fluoxetine study in PTSD.” Journal of Clinical Psychiatry 57: 373-374.
“Vulnerability Scale: a preliminary report of psychometric properties.” Psychological Reports 75: 1651-1668.
“Vulnerability Scale: a preliminary report of psychometric properties.” Psychological Reports 75: 1651-1668.
“Numbing Scale: Psychometric properties, a preliminary report.” Anxiety 1: 70-79
“A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder.“ Israel Journal of Psychiatry 30: 255-263.
“Emotional numbing: A possible endorphin mediated phenomenon associated with post-traumatic stress disorders and other allied psychopathologic states.” Journal of Traumatic Stress 5: 643-675.
“Post-traumatic stress disorder conflicts in Vietnam combat veterans: a confirmatory factor analytic study.” Journal of Traumatic Stress 3: 573-591.
“Four Syndromes of post-traumatic stress disorder: Stressors and conflicts of the traumatized with special focus on the Vietnam combat veteran.” Journal of Traumatic Stress 1: 57-78.
“Guilt and aggression in Vietnam veterans.” American Journal of Social Psychiatry 1: 15-18.
“Post-traumatic stress disorder conflicts in Vietnam combat veterans: a confirmatory factor analytic study.” American Journal of Psychotherapy 37: 445-452.
“Survival Guilt and the Vietnam Veteran.” Journal of Nervous and Mental Disease 172: 393-397.