New Treatments, Old Medicines

Drugs like psilocybin and ecstasy soon will be standard treatments for depression and Post Traumatic Stress Disorder (PTSD)

Clinicians are prying psychoactive medications like MDMA from the steely grasp of regulatory agencies. Banned from medical use for the last 40 years, these drugs are returning as treatment for serious illnesses like Post Traumatic Stress Disorder (PTSD), anxiety and depression.

In the US alone, the prevalence of PTSD is astounding. As of 30 June, 2016, more than 868,000 veterans with PTSD received disability benefits costing in sum $17 billion per year. In the general adult population who have not experienced active combat, 7.8 percent will suffer from PTSD during their lifetimes : that is approximately 24,874,200 people. Those with PTSD are more likely to develop coronary artery disease, have heart attacks, and develop Type 2 (adult onset) diabetes.

Changes in the regulatory climate can’t happen soon enough. In the US alone, PTSD resulting both from armed conflict and personal trauma have created a PTSD epidemic. SSRIs (selective seretonin reuptake inhibitors), developed to treat depression, are widely prescribed for PTSD as a pharmaceutical band aid. “Zoloft and Paxil [SSRI brand names] are relatively poor performers, when it comes to treating PTSD,” said Charles S. Grob MD, Professor of Psychiatry and Pediatrics, Harbor-UCLA Medical Center, and Principal Investigator on a study using MDMA to treat social anxiety in autistic adults, “but they are the only FDA-approved PTSD drugs available.”

MDMA is not a new drug. MDMA and other psychoactive drugs like psilocybin were used during the 1970s and early 1980s as an adjunct to psychotherapy to treat patients suffering from a variety of emotional disorders, including what was then termed ‘shell shock.’ The 1980s saw an explosion in the recreational use of MDMA, followed by a public controversy over the drug’s toxicity. The negative press eclipsed MDMA’s many therapeutic virtues. MDMA fell victim to the so-called “war on drugs.” In 1984 it was added to the list of Schedule I substances, having no legitimate medical use in the USA and a high potential for abuse, according to the DEA. Psychotherapeutic use of MDMA halted, leaving psychotherapists treating PTSD sufferers mostly empty handed.

Since the mid 1990s, thanks to pressure from a small but influential group of researchers who were convinced there was a compelling clinical argument for their legal reintroduction, the FDA and the National Institute on Drug Abuse have begun to loosen their chokehold on the clinical use of psychoactive drugs. Between 2010 and 2016, Phase 1 and Phase 2 clinical trials evaluating MDMA’s safety and efficacy and identifying side effects have been carried out in the US, Canada, Israel and Switzerland.

Having no fear of fear

Reaching a state of fearlessness toward painful memories is key to the success of MDMA therapy. For PTSD sufferers, this is not easy. The process of speaking about the traumatic events can by itself cause an extreme reaction. For many, it is as though they are reliving the events in real time. Some experience emotional flooding, a hyper-aroused state where feelings of fear or panic overwhelm all other thoughts and feelings. At the other extreme, patients dissociate, and become entirely numb, removing themselves from a present where they must re-experience the trauma. In both cases, cognitive processes are disabled. Patients cannot speak about their feelings rationally or coherently. Many cannot speak at all.

Michael Mithoefer, MD, a psychiatrist in Charleston, SC who conducted a Phase 2 clinical trial, specializes in treating PTSD.

“We do know that MDMA causes a decrease in activity in the amygdala [the brain structure associated with memory formation, emotional response, and decision making] and an increase in activity in the prefrontal cortex [the brain region where cognitive functions are processed, including ethical judgments, evaluating probable consequences of current behavior, and governing emotional responses],” said Dr Mithoefer. It also produces a marked increase in levels of the neurohormone oxytocin, the so-called “love hormone” which plays a role in social bonding.

Dr Mithoefer maintains identifying the drug’s exact mechanism of action is the least important part of what he does. Even though the drug’s biochemistry can be explained, he said, the reason it works remains something of a mystery.

From his years of treating PTSD sufferers, there are a several things he does know for certain: healing from trauma is process involving all parts of the brain, from the rational mind down to the so-called lizard brain — the limbic system — the brain region associated with emotional response and the autonomic nervous system, which controls unconscious bodily functions such as heart rate, digestion and respiration.

Therapeutically, MDMA helps “create a situation of emotional flexibility,” said Dr Mithoefer. “Patients are able to get out of their emotional rut.” MDMA unsticks PTSD sufferers from rigid patterns of emotional reaction brought about by fear. Drugs like MDMA are a catalyst, he said, allowing patients to process changes in their own feelings.

“In the therapeutic space, they revisit the trauma in a way that contradicts their sense of helplessness and powerlessness. It’s not just revisiting the traumatic experiences,” he said. “It’s a process of affirming a different experience on all levels, including in the body.” With the assistance of MDMA, it becomes possible for PTSD sufferers to revisit horrific memories without shutting down, dissociating, or — as can happen — panicking and high-tailing it out of the therapeutic space altogether.

Participants in PTSD clinical trials receive three therapeutic doses of MDMA several months apart in a hospital setting. Approximately one-third of patients receive a placebo rather than the drug. During the sessions, the participants are encouraged to interact with two psychotherapists — one male, one female — trained in treating PTSD. Participants who receive placebo during the first phase are given the option of two additional open-label sessions where they receive active doses of MDMA.

Psychiatrist Dr Ben Sessa, a senior research fellow at Bristol, Cardiff and Imperial College, London Universities, is conducting studies on the potential role for MDMA-assisted therapy for the treatment of PTSD and alcoholism. A consultant (specialist) child, adolescent and adult psychotherapist for the UK National Health Service, Dr Sessa’s practice includes evaluating abused and neglected children who are routinely referred to his office through the UK’s social welfare system. Often he must provide expert testimony in the courts on whether these children should be removed from their parents’ homes for their own safety.

“It’s easy to have compassion for the poor little child who has received abuse at the hands of his or her alcoholic or drug addicted parent,” said Dr Sessa. “We see them, huddled there crying and immediately want to help.”

But perceptions change once these children grow up. Dr Sessa has witnessed first hand the sequence of events that lands adult drug abusers in his office. Years on, he’s seen those he treated as children in his consulting room, now adolescents or adults, addicted to drugs or alcohol, self-medicating their PTSD with the some of the few means available to them. Drug or alcohol addiction as a result of trauma is not a lifestyle choice: it is a means of coping. Abused children elicit natural compassion “but by the time they’re adults, we’ve lost our empathy,” he said.

In his therapy work with trauma victims, Dr Sessa has found no other complementary medication that is as effective.

“MDMA can hold the patient in a place where they can access their trauma, and provide a safety zone wherein emotional healing work can take place” he said.

Those who benefit

No one is more grateful for MDMA’s return to the pharmacopoeia than Hania Withern. Hania was born in 1970 in Beirut, the city once known as ‘The Paris of the Middle East.’ Lebanon’s civil war began in 1975 when Hania was five.

“Once we drove the car to the local gas station to fill up, and there was a sniper on the roof, just shooting people,” said Hania.

Only after Hania left Beirut for college in New York state did she realize her childhood was not normal: it was pure “out of control craziness.”

By the time she married and moved to Colorado, Hania felt her life was stable. But two weeks after her son was born in 1999 came the massacre at Columbine High School — a mere 77 miles from her home.

“It was a slap in the face,” she said. “I realized there was no place to hide. Horror could always find me.” Hania’s daughter was born on September 10, 2001, a day before the 9/11 attacks on the World Trade Center. Her worst fears about the world were confirmed.

“I’d sit up all night when my husband was away, afraid that someone would break into the house and hurt me and my children,” she said. In 2013, she shut down completely.

In 2015, Hania took part in a Phase 2 MDMA clinical trial in conjunction with intensive short-term psychotherapy. Hania received three doses of MDMA two months apart. She stayed overnight in a hospital during each drug session. The therapeutic sessions lasted an entire day. Two trained psychotherapists, one male one female took part the entire time. At home, between drug sessions, she received supportive talk therapy.

Soon after taking the MDMA during her first session, Hania felt sure she received an active drug dose rather than a placebo. She felt different. Lighter, somehow. The nagging feeling of anxiety went away. Her hunch was confirmed later on, once her sessions were over and the experiment was unblinded. But taking MDMA, though it took her to an emotional place where she could process traumatic experiences, did not mean the sessions were easy.

“The sessions were awful. It was very rough to do the one thing I’d avoided my entire life,” she said. But in the long run it was worth the effort. “I experienced lasting perception shifts during the session,” said Hania. She feels MDMA assisted therapy allowed her to reclaim her life. Although some people experience nausea during the day of, or develop a headache the day after an MDMA dose, Hania did not experience any drug side effects. A few years on, she says her MDMA experience was among the most valuable experiences of her life. She is eternally grateful. Daily life still has its challenges, but they no longer overwhelm her. She’s no longer governed by fear, or by the need to avoid her feelings about what happened to her as a child.

MDMA-assisted therapy for social anxiety in autistic adults

Those on the autism spectrum can have a particularly difficult time finding assistance with serious emotional issues. Autistic adults frequently suffer from anxiety as well as obsessive compulsive disorder, tics, and epilepsy. A new study at the Los Angeles Biomedical Research Institute lead by Dr Grob and psychologist Alicia Danforth is demonstrating that MDMA can be a safe and effective treatment for social anxiety in autistic adults.

Dr Danforth became curious about MDMA’s potential after meeting Dr Gary Fisher, a psychologist in California. During the 1960s, Dr Fisher used LSD and psilocybin to treat autistic children for social anxiety. Although Dr Fisher’s work was highly successful and signified a breakthrough in treating the psychosocial problems shared by many autistics, it was halted in the early 1970s.

In 2014, after perusing online forums where autistics freely discussed using MDMA recreationally as a means of reducing social anxiety, Dr Danforth created an online survey to find out whether this community felt they had needs not being met either by conventional therapy, or by medication.

The response was clear. As a group, autism-spectrum adults felt little was available to them outside self-medication. SSRIs and anxiolytics are mostly ineffective because, simply put, their brains are wired differently. Often, conventional talk therapy is of little value. The therapeutic setting itself often redoubles anxiety because of the problems posed by reading and interpreting interpersonal cues. Many autistics have difficulty talking about feelings; and many therapists lack skills to help them do it. True empathic connection between patient and therapist does not spring to life in this situation. As Dr Fisher put it: “Little of what may be called health or growth can occur without legitimate and honest relationships between people.”

Moved to help those grappling with mental health issues with limited treatment options, Dr Danforth designed a Phase 1 clinical trial to study MDMA’s usefulness in treating social anxiety in autistic adults. Study participants had to be 21 years of age or older, and have attended at least two years of college. All participants were required to learn self-awareness and meditation before their drug sessions, skills which have been shown to be useful to those on the autism spectrum. The study comprised two drug sessions a month apart. Like the other MDMA studies, the autism study was a placebo-controlled double blind study. Those who received a placebo were given the option of an open-label clinical dose after their second session.

Ju Park, a 25-year old college graduate, was one of the study’s participants. He says, “Before college, I was what I would call your functioning Asperger’s guy. I played video games. I had no real friends. It didn’t matter.”

At UCLA, Ju became involved in a liberal Christian campus ministry which embraces ethnic diversity. While attending a week-long conference the summer after sophomore year, Ju experienced ‘Agape,’ a transcendent, all-encompassing sense of God’s love.

On returning, Ju began attending an evangelical church whose membership consisted mostly of Asian undergraduates. One day, the pastor declared Ju did not belong in the congregation because he was not truly born again. Devastated, Ju once again became introverted and anxious. He wrote in a journal: “Give this world love and you will be stabbed.”

Plagued by anxiety and doubt, Ju reverted to avoiding social situations altogether.

Life began to change for Ju when he was accepted into Dr Danforth and Grob’s clinical trial. After his first session, Ju felt convinced he’d received a placebo — an impression later confirmed when the dosing regimen was unblinded. Ju elected to take part in the study’s second phase, where he was given an open-label dose of 75 mg of MDMA. When the dose did not seem to have an effect, Ju opted for a second dose, 125 mg. Then, he said, something changed. “The symptoms didn’t disappear but brokenness in my heart went away,” he said. Dr Danforth is optimistic about the promise MDMA holds for this group. “We’re not making bold claims here,” she cautions. The last thing she wants “would be for parents to go out and buy MDMA on the street for their autistic kids.”

Where from here

The results from the MDMA trials show great promise, where there has been little in the past. PTSD study participants say their lives have improved: 66.2 percent reported complete remission of symptoms a year after their final MDMA session. And there is further hope: the Multidisciplinary Association for Psychedelic Studies (MAPS), the not-for-profit organization that developed and funded the Phase 1 and Phase 2 studies has submitted Phase 3 clinical trial protocols to the FDA. Ten sites in the US, Canada and Israel will take part in the next phase, assessing drug efficacy and safety in 230 PTSD patients. MAPS intends to make MDMA into an FDA approved prescription medication by 2021.

MAPS Founder and Executive Director Rick Doblin is firmly convinced the path leads inexorably forward. At the MAPS conference in Oakland in April, 2017, he said: “The fact is, the need is great, and the therapy works. Funding is coming. We are building alliances with the Veteran’s Administration who are moving the process forward. The Trump administration is making it easer to get FDA approval for new drugs.” He paused. “No matter if it takes six months, one year or ten, twenty or fifty years, we are going to continue to work on it.”

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