This week the FDA did not approve MDMA (otherwise known as the party drug, ecstasy) to treat PTSD, a disappointment for many. Since the legalization of marijuana, the public is generally favorable to re-applying recreational drugs to medical use.
PTSD is usually treated with SSRIs (short for “selective serotonin reuptake receptors”), the same group of drugs usually used for depression. SSRIs like Prozac work by blocking serotonin receivers, creating more available serotonin. While this treatment works for many patients, today it is unknown exactly why it works for some but not everyone. It’s been an open secret that there is no conclusive evidence that depression is linked to serotonin levels – rendering the “chemical imbalance theory” obsolete. Today, the American Psychological Association website doesn’t touch on “the serotonin model” when describing SSRIs. MDMA is a drug that increases serotonin levels.
A small, recent study from Oxford used a medication typically used to treat a rare form of epilepsy that increases serotonin but promotes the brain to produce more serotonin rather than blocking receptors. Professor Catherine Harmer, Professor of Cognitive Neuroscience at the University of Oxford, and OH BRC Theme Lead for Depression Therapeutics said:
“Despite nearly a century of research, our understanding of how serotonin influences human behavior has remained unclear and controversial. Serotonin, which has been implicated in depression and in the effects of antidepressants, has more of a role in processing negative things, rather than boosting positive responses. Serotonin is often referred to colloquially as the ‘happy chemical’ but perhaps it is time we thought of it as the ‘not-so-bad chemical.“
Established connections between serotonin, mood, and cognitive performance have been shown in studies since 1979. Early research showed that low serotonin levels were associated with higher aggression in humans, other mammals, and non-mammals such as crickets and mollusks. As research continued, a pattern showed that low serotonin did not lead to premeditated violence; but rather it coincided with impulsive behavior which could lead to aggression, suicide, and erratic behavior. At the time without considering the genetics of serotonin uptake, this research looked dependable.
The promising studies on serotonin in the 1980s came at a time in psychiatry when the field was phasing out of the old Freudian models of the unconscious in favor of metrics that could be observed scientifically. A new wave of professionals took over the field, searching for a way to treat mental disorders the same way a diabetic is prescribed insulin.
In 1990 George HW Bush heralded the upcoming decade as “The Decade Of The Brain”. The “decade of the brain” was an optimistic time to pioneer new science and treat mental disorders more effectively than was before possible. This also ushered in “the Ritalin era”. The exciting advances in managing behavior by regulating serotonin levels led to the commonly used “chemical imbalance theory”. The chemical imbalance theory was just a theory that was quickly proved wrong; however, it was too late to change the public’s understanding after pharmaceutical marketing heavily promoted it to sell Prozac.
Robert M. Sapolsky puts forth in his book, “Behave” that studies on the genetics of serotonin receptors are “inconsistent messes”. He states: “Studies where serotonin breakdown products are measured in the body, or where serotonin levels are manipulated with drugs say that low serotonin = aggression. And the genetic studies say that high serotonin = aggression.” How could this work? Likely, the best guess is that serotonin levels altered by a drug are temporary while a genetic mutation that doesn’t process serotonin causes lifelong neural structural damage. Today, the answers are still unclear.
Further research in the early 2000s also shows that environmental context plays a big role in whether serotonin levels affect a person’s thoughts or behavior. One study found that a group with a genetic variation of receptors that don’t process serotonin was three times more likely to exhibit anti-social behavior and violent crimes if they had experienced childhood abuse. However, the genetic variation was not a predictor of behavior in those with normal childhoods. Studies like this show that if and when serotonin affects behavior can be highly contextual.
Treating mental health with medication is far more complicated than “a chemical imbalance”. SSRIs are useful for many. One UK-based psychiatrist explains, “many of us know that taking Tylenol can be helpful for headaches and I don’t think anyone believes that headaches are caused by not enough acetaminophen in the brain.”
MDMA was created by Merck in 1917 as an appetite suppressant for German WWI soldiers. In the field, it was promptly noticed that the effects of MDMA were not conducive to the demands of wartime troops. MDMA works by shutting down serotonin receptors, creating a flood of serotonin associated with high empathy, the ability to address fears, and a feeling of safety. However, MDMA is also associated with a crash after its effects wear off.
The FDA’s recent rejection of MDMA as a PTSD treatment has more to do with issues regarding the ethics of the pharmaceutical trials than the promise that it may be useful for some patients. Executives withheld financial conflicts of interest if MDMA were to be produced as a pharmaceutical. Additionally, it was evident study participants were able to deduce early on if they had been administered the real drug or the placebo… which skewed results. The FDA’s decision will set back the financial ability to do re-trials and release a pharmaceutical MDMA by several years.
