Why Not Other Drugs?

PTSD treatment has been a hot topic in the news lately. From marijuana to ecstasy to swimming with sharks, there have been many headlines regarding different approaches to treating this disorder. These therapies may seem flashy and exciting, but they leave much to be desired. Neurovation Labs’ CEO Dr. Jennifer Perusini discusses some of these treatments with us.

Are street drugs really a viable approach to treating PTSD?

Dr. Perusini:  MDMA (ecstasy), ketamine (Special K), and even marijuana are being actively explored by others as potential treatments for PTSD. We have not yet seen scientific evidence to suggest these drugs are capable of providing a workable cure for PTSD. Here’s a brief overview of the drugs and their attempted application to PTSD treatment.

MDMA is a psychoactive drug that primarily acts as a releasing agent for serotonin, norepinephrine, and dopamine, which widely affect mood and behavior. Despite some promise in clinical trials, it has only been shown to be effective in conjunction with psychotherapy, and since it is a Schedule I drug with a huge potential for abuse, it must be used under the strict supervision of physicians. The aforementioned molecular targets of MDMA are modulated with PTSD and are involved in the fear/anxiety circuitry, but they aren’t at the root of the disorder. The best that MDMA can do is alter some of PTSD’s behavioral symptoms, but it will certainly not cure the disorder in its current state.

Ketamine, also called Special K, is another controlled substance with a long history of abuse. The street version of the drug is often made from animal tranquilizers and used to create ‘out of body’ experiences where the drug takers may become so disassociated from their bodies that they become immobilized. Scientifically, ketamine is a “dirty drug,” meaning it has many molecular targets instead of a more focused impact, but it works mainly by blocking glutamatergic NMDA receptors. It blocks neurotransmission, stopping signals in the brain. Preclinical and clinical research has been published on the use of ketamine and its analogs for PTSD, but consequent studies have failed to replicate these results in true preclinical PTSD models. Scientists have yet to figure out how ketamine really works. One theory holds that the antidepressant mechanism of action for ketamine may be through binding of our target, AMPA receptors (AMPA receptors are excitatory glutamate receptors in the brain that are essential for learning and memory, among other roles). Another percolating idea is the possibility of preventing PTSD with ketamine or its analogs (e.g., esketamine), essentially inoculating a person before a trauma occurs– so-called “resilience enhancers.” Not only is this approach scientifically unproven, it is completely impractical and cost prohibitive. Ketamine and other NMDA receptor antagonists do not offer the possibility of a real treatment for millions PTSD patients. While an esketamine nasal spray has recently been approved for treatment-resistant depression, it has not been validated in PTSD, a completely separate disorder, and is currently extremely limited in its use. 

Marijuana, for the past decade, has been explored as a treatment for a wide range of disorders, from glaucoma to cancer, so it was only a matter of time before someone explored its use for PTSD therapy. Marijuana works on the endocannabinoid system in the body, which mediates a variety of physiological processes, such as appetite, mood, and memory. There is some evidence to show that the endocannabinoid system in PTSD patients is slightly altered; therefore, short-term symptom relief has been anecdotally reported. However, the Department of Veteran Affairs cautions that marijuana has not been shown to be effective in treating PTSD and in fact can be harmful, causing a range of new medical and psychiatric problems. Marijuana is another example of a drug that has gained much attention in the media for PTSD treatment due to its popularity in recreational use.

What other drugs are being explored?

Dr. Perusini: Cyclobenzaprine is a muscle relaxant with a past fibromyalgia indication that is being explored in patients with military-related PTSD. As with the current drugs available for PTSD, cyclobenzaprine is a symptom reducer, and a weak one at that—it has only shown effectiveness in treating PTSD-induced sleep disturbances and has recently failed in clinical trials. 

Anesthetics, such as propofol, have been shown to have an effect on reconsolidating fear memories and is therefore being considered for use in PTSD patients.  Again, this is scientifically unproven, and the very limited clinical data on this class of drugs does not necessarily warrant trials that include PTSD patients.

A recent, more unconventional procedure is called Stellate Ganglion Block (SGB), which involves placing an anesthetic on a group of sympathetic nerves in the neck. While this is not a new technique and has been used to treat chronic pain for almost a century, new research has found that it may indirectly deactivate the amygdala. While this data supports Neurovation Labs’ research, very little work has been done on SGB and it is not a cure for PTSD.

 

Is there anything already FDA-approved for PTSD?

Dr. Perusini: Only two drugs are approved by the FDA to treat PTSD—Zoloft and Paxil. These fall into the class of selective serotonin reuptake inhibitor (SSRI) anti-depressants. They essentially increase the overall concentration of serotonin in the brain, which results in a positive change in mood. They have only seen marginal success for PTSD treatment. Depressive-like behavior is only one symptom of PTSD, and I cannot stress enough that depression and PTSD are NOT the same and should not be lumped into one class. Because there are only two drugs approved for PTSD, we are desperate to create new and better ones, which I believe is in part causing this surge in exploring already existing, albeit illicit, drugs for treatment. However, this desperation will only result in more mistakes—for example, ketamine has shown a bit of promise for treating intractable depression, but as we know from Zoloft and Paxil, anti-depressants do not work well and anhedonia is only a small part of PTSD as a mental disorder. This is the time to really determine the causes of PTSD, which Neurovation Labs believes we have in part done, so that we can move away from symptom bandaids to a more robust cure.

What is your take on non-medicinal treatments?

Dr. Perusini: PTSD therapies range from various psychotherapies (“talk therapies”) to activity-based therapies.  Psychotherapies include cognitive behavioral therapies (identifying and altering a patient’s negative thoughts about a trauma), exposure therapies (revisiting and confronting traumatic memories and feelings), and Eye Movement Desensitization and Reprocessing (EMDR) therapy (focusing on a back-and-forth motion or sound while thinking about traumatic memories to decrease their impact). Psychotherapy is useful in that it can be used to treat a wide range of trauma victims, but it is only marginally effective. Studies show that less than 50% of people officially go into remission from these treatments, and effectiveness can only be boosted when used in conjunction with medication.

Other therapies are more physical in nature, with a mentally soothing component, such as yoga or SCUBA diving. These therapies may help patients better control their emotional awareness and better tolerate physical or sensory effects associated with PTSD. Mindfulness training and meditative therapy is gaining popularity and does show some success in stress reduction in clinical trials. However, like psychotherapy, it does not work for everyone.

Non-medicinal therapies are not cures but rather help patients cope with PTSD and ideally ease the symptoms. While I encourage non-medical therapies for those who find it useful, PTSD does in fact have a molecular/physiological cause and will be most effectively treated with a medical intervention targeting this cause.

What is the take-away?

Dr. Perusini: We must really understand PTSD, or any psychiatric disorder for that matter, in order to create anything worthy of a treatment.  Many of the PTSD treatment approaches that attract headlines unfortunately are not premised on a fundamental understanding of PTSD and its underpinnings.  Instead, they address only select symptoms of the disorder.  At Neurovation Labs, we believe that we have identified the root physiological cause of the disorder, and are focusing on developing a diagnostic and eventually an individualized treatment plan for each PTSD patient. 

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