Friday Factoid Catch-up: MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

 

A drug often known as “Ecstasy” or “Molly,” has for decades been used as a party drug in clubs and for all-night raves. But lately, ±3, 4-methylenedioxymethamphetamine (MDMD) is also being used in very different settings and for a very different purpose. Pharmacologically, MDMA acts as a serotonin-norepinephrine-dopamine releasing agent and reuptake inhibitor. Basically, MDMA massively increases the release of serotonin, dopamine, and oxytocin. Respectively, these chemicals in the brain help you feel relaxed and calm, help you stay alert, and help you bond with people and be more trusting. Increased feelings of trust and compassion towards others would allow people to process their trauma, which could make an ideal adjunct to psychotherapy for PTSD.

 

The Food and Drug Administration (FDA) has approved phase two clinical studies of the treatment, and they are now underway in four separate locations in South Carolina, Colorado, Canada, and Israel. Results so far have been promising. Preliminary studies have shown that MDMA in conjunction with psychotherapy can help people overcome PTSD and possibly other disorders as well. MDMA is not the same as “Ecstasy” or “Molly.” Substances sold on the street under these names may contain MDMA, but frequently also contain unknown and/or dangerous adulterants. In laboratory studies, pure MDMA has been proven sufficiently safe for human consumption when taken a limited number of times in moderate doses. In MDMA-assisted psychotherapy, MDMA is only administered a few times, unlike most medications for mental illnesses which are often taken daily for years, and sometimes over the course of a lifetime.

 

Recent test results have shown 83 percent of the subjects receiving MDMA-assisted psychotherapy in a pilot study no longer met the criteria for PTSD, and every patient who received a placebo and then went on to receive MDMA-assisted psychotherapy experienced significant and lasting improvements. Long-term follow-up of patients who received MDMA-assisted psychotherapy revealed that overall benefits were maintained an average of 3.8 years later. These results indicate a promising future for MDMA-assisted psychotherapy for PTSD and lay the groundwork for continued research into the safest and most effective ways to administer the treatment.

 

The Multidisciplinary Association for Psychedelic Studies (MAPS) is undertaking a roughly $20 million plan to make MDMA into a FDA approved prescription medicine by 2021, and is currently the only organization in the world funding clinical trials of MDMA-assisted psychotherapy. For-profit pharmaceutical companies are not interested in developing MDMA into a medicine because the patent for MDMA has expired. Data from Phase 2 studies will be used to plan Phase 3of MAPS’ drug development program. MAPS will work with the FDA to agree on a design for Phase 3 studies and submit the findings to the FDA in a New Drug Application (NDA) to approve MDMA-assisted psychotherapy as a prescription treatment for PTSD. Phase 3 of the development program will involve scores of therapists and hundreds of subjects in multiple countries and large multi-center trials. The challenge is no longer convincing regulatory agencies of the value of this research, but finding the financial resources for conducting the Phase 3 studies required to make MDMA-assisted psychotherapy a legally available treatment for those who need it most.

 

References:
Mithoefer, M.C., Wagner, M.T., Mithoefer, A.T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), 439-452.

 

Mithoefer, M.C., Wagner, M.T., Mithoefer, A.T., Jerome, L., Martin, S.F., Yazar-Klosinski, B.,…Doblin, R. (2012). Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology, 0 (0), 1-12. DOI: 10.1177/0269881112456611

 

Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2012). A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Journal of Psychopharmacology, 0, 1-13. DOI: 10.1177/0269881112464827

 

Jonathan Torres, M.S.
WKPIC Doctoral Intern

 

Friday Factoid: U.S. Preventative Services Task Force (USPSTF) Recommends Depression Screening for Older Adolescents

Counseling

National data suggest that up to 8 percent of U.S. adolescents experience an episode of major depression in a given year. Children and adolescents with Major Depressive Disorder (MDD) typically have functional impairments in their performance at school or work, as well as in their interactions with their families and peers. Depression in children and adolescents has been found to be strongly associated with recurrent depression in adulthood and increase the risk for suicidal ideation, suicide attempts, and suicide completion. Among children and adolescents aged 8 to 15 years, 2% of boys and 4% of girls reported having MDD in the past year.

 

In a new guideline, the USPSTF recommended that primary care clinicians should screen adolescents aged 12 to 18 years for MDD. There has been adequate evidence found that screening tests could help detect depressive symptoms and lead to appropriate treatments. Adolescents who are screened and identified in primary care settings as having MDD and then treated have a reduction in symptoms and an improvement in daily functioning. In drafting the guideline, Dr. Siu, chairperson of the USPSTF, identified five studies on the accuracy of screening for MDD in primary care facilities and six studies on the efficacy of treatment. The authors noted there was no direct evidence of harm for screening in a primary care facility and the screenings had “reasonable accuracy” for picking up adolescents with MDD. When treatment is provided, the degree of harm resulting from antidepressant-related adverse events, psychotherapy, and collaborative care appeared to be beneficial and were not associated with significant harm.

 

The USPSTF recommend screening this age group when adequate systems are “in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.” The recommendation grade of B was given which indicates there is moderate certainty that the net benefit is moderate to substantial.  There are several tools available for screening adolescents. The two most commonly studied are the Patient Health Questionnaire for Adolescents and the primary care version of the Beck Depression Inventory. The USPSTF opted not to issue any recommendation on screening for children aged 11 years and younger because of insufficient evidence. In addition, they note that more research is needed to better assess the effects of screening children on their health outcomes, the effect of comorbidities, the effectiveness of psychotherapy and combined-modality treatments, and the incidence of uncommon adverse events.

 

There are several risk factors that might help identify individuals who are at higher risk for developing symptoms of depression. These factors include, female gender, family (especially maternal) history of depression, prior episode of depression, other mental health or behavioral problems, chronic medical illness, overweight and obesity, and, in some studies, Hispanic race/ethnicity. Other psychosocial risk factors include childhood abuse or neglect, exposure to traumatic events (including natural disasters), loss of a loved one or romantic relationship, family conflict, uncertainty about sexual orientation, low socioeconomic status, and poor academic performance.

 

References:
London, S. (2016, February 9). USPSTF Recommends Depression Screening for Older Adolescents. Medscape. Retrieved from http://www.medscape.com/viewarticle/858653

 

Sui, A.L. (2016). Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine.

 

Jonathan Torres, M.S.
WKPIC Doctoral Intern

Friday Factoids Catch-Up: Optogenetics

 

Optogenetics involves tweaking the genes of neurons so that they become sensitive to light. By combining this technique with genetic and viral approaches, researchers can insert these channels into very specific populations of neurons. Ultimately, this approach allows researchers to control distinct groups of neurons and individual circuits of the brain by stimulating them with light-emitting devices inserted into the brain. First, researchers inject the subject with a genetically engineered virus, designed to infect brain tissue. These viruses aren’t harmful and have been engineered by scientists to deliver a benign DNA strand that code for special surface proteins, which respond to specific wavelengths of light. These single-celled organisms produce a protein called channelrhodopsin that makes them sensitive to sunlight.

 

At present, optogenetics can be used only on animals whose brain functions associated with elemental emotions, like fear and anxiety and reward, are similar to those in humans. Early tests have been successful in mice and primates to restore sight in blind test animals. Optogenetics was a major spur to the Obama Administration’s announcement, in 2013, of the BRAIN Initiative, a $300 million program for developing technologies to treat such neurological ailments as Alzheimer’s disease, autism, schizophrenia, and traumatic brain injury. It is possible that optogenetics could be used as a therapeutic tool in humans. Some clinicians are already looking at possible treatments in the peripheral nervous system

 

Optogenetics has given researchers unprecedented access to the workings of the brain, allowing them not only to observe its precise neural circuitry in lab animals but to control behavior through the direct manipulation of specific cells. The aim is to gain an understanding of brain functions such as attention, memory, social skills and emotions. For instance, a person diagnosed with schizophrenia displays cognitive impairment, which may hinder the performance of day-to-day tasks, such as showing up to work or the ability to make decisions. The challenge is to understand how the brain performs cognitive processes in the first place and how this is changed in psychiatric disorders. Several new studies have shown the potential of optogenetic stimulation to rapidly modify depression and anxiety related behaviors in animal models. It is potentially more effective and has fewer adverse effects than classic light therapy or pharmacological approaches to treat mental illness.

 

Circuit-level understanding of psychiatric symptoms is allowing more sophisticated pathophysiological hypotheses, which is important for replacing the current system of subjective report-based measures. Second, by combining patient interviews and personalized genomics, diagnoses of mental illnesses are well poised to change substantially in a manner that could improve both prevention and treatment. Third, direct knowledge of cells that are involved in psychiatric symptoms is facilitating identification of clinically relevant circuit biomarkers, which could revolutionize not only diagnosis but also prediction of treatment outcomes. It’s too early to say that optogenetics could inform the treatment in humans. But the research could enact changes on our models of mental illness.

 

References:
Albert, P.R. (2014). Light up your life: Optogenetics for depression? Journal of PsychiatryNeuroscience 39, 3-5.

 

Colapinto, J. (2015, May 18). Lighting the Brain. The New Yorker. Retrieved from http://www.newyorker.com/magazine/2015/05/18/lighting-the-brain

 

Myers, A. (2012, November 18). Optogenetics illuminates pathways of motivation through brain, study shows. Stanford Medicine. Retrieved from https://med.stanford.edu/news/all-news/2012/11/optogenetics-illuminates-pathways-of-motivation-through-brain-study-shows.html

 

Jonathan Torres, M.S.
WKPIC Doctoral Intern

 

[Director’s Note:  No, Dr. Greene, you may not go back to the rat lab just because this is interesting. Seriously. No.]

Friday Factoids: Social Psychology and Southern “Snow Panic”

 

Being a student of human behavior at times causes me to observe phenomena in my world with fascination. Social Psychology is widely defined as “the study of the manner in which the personality, attitudes, motivations, and behavior of the individual influence and are influenced by social groups.” One such phenomenon, which caught my attention was recently when many people in middle TN and Western KY were preparing for an upcoming winter weather event on the evening of 1/19. I needed to run a routine errand to a local grocery store pharmacy. I had noticed some jokes on my Facebook feed prior to going out. The jokes revolved around the tendency of people to swarm into grocery stores prior to winter weather events. I laughed it off as an exaggeration due to being new to this area of the country.

 

I knew something different was happening when I got to the store and the parking lot was full. This is not a usual occurrence on a week night. I entered the store and saw checkout lines snaking, through the aisles, and clear to the back of the store. After a sigh of relief that I did not have to get into those lines due to the nature of my errand, I was struck by the behaviors of the social group involved in this event.

 

I am fairly certain that people shopping in this grocery store were not aware of belonging to a social group. The first behaviors I identified were a group of people in a state of conflict and competition. The top items being “competed” for seemed to be mainly perishable food items like milk, eggs, and unfrozen meats. I noticed a smaller, but still significant number of people who were purchasing non-perishable items such as canned goods, bottled water, and breakfast cereal. Competition is a process that is always present among humans as a group but what I witnessed was the result of competition being converted into conflict during a time of perceived crisis the group primarily was competing for perishable goods that were perceived useful.

 

In actuality bread, milk, eggs and other perishables are not the go to items that will help the group survive in an actual crisis. One suggestion is that when the group is having an initial reaction to an impending storm situation the lean toward perishable items when preparing for a short term event. The drive toward choosing perishable items may be unconscious. The shoppers I saw with non-perishable items were largely in military uniforms and likely from nearby Fort Campbell. It has been suggested by some that when a person is seeking and competing for non-perishable items the unconscious drive is more driven by ideas that the crisis/storm event could be a longer term event. In a long term event perishables would quickly become useless. It is quite possible that individuals trained in the military are not functioning at an unconscious level as much as they are relying on a better awareness of what would help if they were stranded in their homes for multiple days.

 

While observing the aforementioned behaviors and patterns, a loud verbal argument began between two customers waiting in line. The two individuals seemed to be arguing because they felt the other had cut in front of them in line. A baseline sense of competition was already heightened and aggravated and a behavior that may have been met with irritation was met with aggression. The verbal conflict soon escalated into a physical fight with punches being thrown. Quickly, two uniformed military personnel came and broke up the fight. The two men in the fight were both people buying perishable goods. The military personnel both were consistent with their colleagues and had a cart full of canned goods, batteries and water. There may have been a higher level of urgency in the perishable food buyers because of the short sighted plans. They are seeking perishables to last over a short time period and then move on to the next crisis. The opposing group which had enough training to not fall into less viable crisis supplies were also those who retained order in the group as a whole.

 

Since the non-perishable buyers seemed so better adapted at handling uncontrollable circumstances it was curious to me that they too were out scrambling for their chosen crisis supplies literally hours before a storm. Noticing this again made me question why there was so much activity in the store. If a person is trained and prepared for disasters why did they not shop at a time when competition for goods was lower ? I think to some extent that even those who are prepared for a disaster may have been out obtaining even small items they thought they might happen to need. While people compete with one another in an outward group once back in our homes we tend to think more altruistically. If we have excess, we are more likely to share with our neighbors. The group in the store outside of their neighborhood group came to blows, but it is likely that if asked these individuals would share their perishable goods with their neighbors i.e. “can I borrow an egg.”

 

Overall while watching this scene unfold, my anxiety began to heighten because I thought “what if I run out of food.” Prior to entering the store I was not thinking about this at all and as I mentioned I was laughing at the “bread and milk before the snow” jokes on Facebook. I am not from the area and maybe the rest of the group who is established here should be followed. The thought seemed even more valid when I gauged the intensity of the group. I began to doubt my ability to make decisions as an individual. The group must know something I don’t. It was a hard conscious effort to resist getting a cart and grabbing a just a couple items, just in case they were needed. I took pause and thought about how our home is likely more prepared for disaster than average since I lived in an Earthquake area prior to TN. Shopping before an Earthquake is simply not an option so the whole paradigm for preparation is different. I was quite struck by the anxiety that rose up when watching the group and then a mental accounting for the supplies I knew I had on hand. Despite knowing that I was well supplied I literally fought an urge to get in the long lines with the rest of the group.

 

This trip on a basic errand transformed into an incredible, unplanned, observational experience of Social Psychology. I still after leaving the store have a pull toward thinking the group knows better than me even though I am certain that I have at least three weeks of emergency supplies, which are more substantial than bread and milk. Let’s just hope that I am prepared enough for the upcoming winter storm and that my effort against joining the group on this occasion will not backfire.

 

References
Dove, L (2015).Why do people buy up all the bread and milk before a storm hits: The psychology of stockpiling. http://science.howstuffworks.com/nature/natural-disasters/buy-bread-and-milk-before-storm1.htm

 

Nelson, Lowry, (1948). Rural sociology. American sociology series, (pp. 149-171). New York, NY, US: American Book Company, xvi, 567 pp.

 

Rain Blohm, MS
WKPIC Doctoral Intern