Ecstasy and LSD May Soon Be Used to Treat Mental Disturbances

06/17/2017 - 18h34

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MARCELO LEITE

illustration THIAGO MARTINS DE MELO

SUMMARY Mind-altering drugs have returned to the laboratories of scientists in search of therapies for mental disturbances. Ecstasy was the star attraction at a congress in the USA where it is entering the final phase of clinical tests for treating post-traumatic stress, a malady affecting war veterans and victims of urban violence, among others.

Around an hour after the individual doses of 120 milligrams of methylenedioxymethamphetamine (MDMA), better known as ecstasy, the group of ten people left the Courtyard Marriott Hotel. A chambermaid is startled by the number of people coming out into the corridor and shakes her head with disapproval.

After six days of presented works, the moment had come to commemorate the end of the 2017 Psychedelic Science Conference, which had united more than 3,000 people from 40 countries in Oakland, California, at the end of April. The mood was one of euphoria over the possibility of rehabilitating various drugs of dubious reputation, from LSD to psilocybin, as psychoactive remedies.

Guided by the researchers Alberto, Timóteo, Ricardo and Aldo (made-up names), I walk down to the street convinced that I am not under the influence of a controlled substance.

I am speaking more than usual, but I realize this and think it must be normal. At the corner of the hotel, an improvised lounge serves as a smoking space for aficionados of marijuana (consumption of which is legal in California).

While I chat fondly about my grandchildren to virtual strangers in whom, somewhat strangely, I trust, I catch sight of my own behavior and analyze it. I laugh at my sudden concern with the fact that my legs seem disembodied, while I simultaneously become intensely aware of the pounding of footsteps on the broad Oakland pavements.

Thiago Martins de Melo

The camaraderie is remarkable. In a few seconds, the consensus forms that the nightclub being sought, with its burly security guards and long queue at the door, is the last place where this group of Brazilians will feel comfortable. After a few desertions, we retreat to the warm embrace of the hotel room.

Days and weeks later, I was still breathing the refreshed and purified air that MDMA had diffused around me. More than one person afflicted by trauma, depression or addiction described the therapeutic effect of psychedelic drugs as a reset button: the hardware - the brain - is cleared of the residues that prevent the core of the affliction being seen with clarity.

As a result of this experience, it becomes easier to understand why MDMA has turned the head of war veterans, police officers and firefighters in the USA. Ecstasy is about to enter clinical trial phase 3 - the final regulatory barrier of the US Food and Drug Administration (FDA) - to become a recognized treatment for post-traumatic stress.

Opening the doors of respectability could also clear the way for psychedelic compounds considered problematic due to their hallucinogenic effects and their collateral physical and mental effects (such as triggering psychotic episodes). New therapies are being envisaged to treat depression, chemical dependency and other ailments resistant to the current pharmacological arsenal - and Brazilian researchers can play a prominent role in the rehabilitation of these substances.

SEROTONIN

Although it does not induce trips like LSD, MDMA is classified as a psychedelic drug since it acts on the serotonergic receptors 5HT2A and 5HT2C, increasing the levels of the neurotransmitter serotonin. Mood is improved and anxiety and depression reduced, altering the perceived meaning of experiences and feelings.

As always in the cerebral biochemical symphony, things are more complicated than this. Methylenedioxymethamphetamine also modulates other neurotransmitters and regulatory substances like dopamine, norepinephrine, noradrenaline, oxytocin, prolactin and cortisol. The concerted effect tends to be a reduction in fear and an increase in empathy, trust and intimacy (not to mention the risk of hyperthermia, or overheating, which has already led to the deaths of various ravers who failed to drink sufficient liquids).

"MDMA is the bonobo drug," says Sidarta Ribeiro, of the Brain Institute of the Federal University of Rio Grande do Norte (UFRN). One of the Brazilians present at the Oakland conference, he compares the effects of MDMA to the mild nature of this smaller variety of chimpanzee (Pan paniscus), disposed to sex and displays of affection. Stimulants like cocaine, to parallel his comparison, would be the drugs of the common chimp (Pan troglodytes), an aggressive troublemaker.

Like other psychedelics, MDMA relaxes the neural so called default mode network (DMN). This interaction of cerebral regions like the posterior cingulate cortex, the medial prefrontal cortex, the angular gyrus and the hippocampus, among others, automatically enters into action when the person is not paying attention to the outside world.

This network is believed to constitute the base of the self. It is shown to be more active at moments of introspection and when thinking of other people, and of the past or the future. It is a form of integration, an active search for meaning, and thus also steps in when we focus our attention on a book, movie or a story being told to us.

Its malfunctioning is associated with pathologies like Alzheimer's, autism, schizophrenia, depression and post-traumatic stress.

Psychedelic experience induces a relaxation of this network, enabling a more fluid interconnection between other cerebral areas, with a consequent reduction in self-referential consciousness - something described in the literature as an 'ego dissolution.'

The curative effect of ego dissolution stems from a surge of good feelings, the lowering of defenses and the willingness to face facts and painful memories. It increases the possibility of the patient opening up with psychotherapy.

In one of the most touching moments of the conference, the president of MAPS (Multidisciplinary Association for Psychedelic Studies), Rick Doblin, showed a video about a veteran of two tours in Iraq. As a turret gunner on a Humvee, this soldier had been involved in various combat situations.

After taking the MDMA dose in the presence of a couple of therapists and lying down with a blindfold over his eyes and earphones playing calm music, he tells of the feeling of peace provoked by MDMA. "I faced up to what I was capable of doing in Iraq," he said. "I know this is just part of the drug's effect, but I'll try to hold on to this feeling."

PATCHOULI

In the first row of the auditorium, an older, red-haired woman wearing a long striped skirt and a flowery frock wiped away a tear as she listened to the combatant's testimony. She had probably marched against the Vietnam War in the 1960s.

It would be rash to conclude from their appearance and from the smell of patchouli in the air that the Oakland conference was just a gathering of old hippies. Science occupied the front stage and it is indeed somewhat paradoxical that so many of those there see science today as the last chance to anchor a philosophy of life at whose epicenter is a quest to expand consciousness that borders on mysticism.

But science does not conceal the fact that several of these drugs may cause terrifying hallucinations and severe symptoms, like the nausea and vomiting typical of the peia [beating] that ayahuasca subjects its users to.

The Marketplace Hall was the locale with the most specimens of this fauna, mesmerized by the colors of the rainbow and by J.R.R. Tolkien, people capable of going out in public wearing unicorn tiaras and pointy gnome caps. The stalls of esoteric and psychedelic products and services trail into the distance: Botanical Dimensions, Awake Net, Essential Oil Wizardry...

The most notable point of contact between the United States and Europe is Amanda Feilding, a British countess who founded the Beckley Foundation in 1998 to stimulate research into consciousness, the treatment of mental disorders and creativity. Since 2005, its director of research has been David Nutt, from the Neuropsychopharmacology Centre of Imperial College, London.

Alongside Rick Doblin from MAPS, Feilding is behind the incipient renaissance in psychedelic studies. As well as raising funds and campaigning for reform of prohibitionist policies, she figures as a co-author in diverse works published in scientific journals. At the Oakland conference there was always an entourage around her.

The countess's biography includes an episode about which she now says little in public. In 1970, when she was 27 years old, she performed a self-trepanation, perforating her own skull with a dentist's drill. The rationale was to give more space for the brain to pulsate freely. Feilding recorded the performance in the short film 'Heartbeat in the Brain,' scenes of which can be found on the internet.

The trip of psychedelic science today finds itself on another level. At the third MAPS conference (the previous editions had been held in 2010 and 2013) no mention was made of 'trepanation' in the official sessions. The most common topic was PTSD, post-traumatic stress disorder, the passport of the US psychedelics for admission into the domains of presentable research.

FINAL PHASE

The undisputed leader is Rick Doblin. After years of pilot studies and lobbying of the FDA, his group is close to obtaining authorization for phase 3 clinical trials with MDMA for the treatment of the anxiety disturbances affecting war veterans, victims of urban violence, police officers and firefighters. Recalling traumatic events, these victims also relive the agony of the violent episode and suffer panic attacks.

In the United States, 2.1 million veterans received treatment between 2006 and 2010. The financial compensations for PTSD among them consumes a total US$ 17 billion per year. "An enormous burden," as Doblin stated at the opening of the conference.

In May, Doblin's team had a new meeting with the FDA on the phase 3 plans. Having overcome the final obstacles, MAPS does not foresee any difficulties for the approval of the final proposal of the protocol due to be submitted this month (June).

In order to increase the chances of licensing psychedelic treatment in 2021, the plan is to enroll at least 200 patients in the clinical study. To this end, MAPS needs to raise US$ 20.5 million - its campaign has already obtained half of this amount.

The 12 phase 2 trials initiated by MAPS in 2001 involved the participation of 107 people whose disturbance had not improved with conventional therapies. A third received MDMA two or three times, in 8-hour therapeutic sessions separated by intervals of three to five weeks, while the rest underwent traditional psychotherapy. The evidence obtained that MDMA is safe and effective for treating PTSD was sufficient for the pharmaceuticals agency to allow preparations for phase 3.

Plans involve training 120 therapists to accompany patients during the clinical sessions. The process includes a 14-hour online course, a seminar and at least two weeks of practice to monitor the patients in the sessions, since the proponents of MDMA argue for its therapeutic use in controlled environments only, such as clinics and hospitals.

The psychiatrists advocating use of the new drugs also see their potential approval as an opportunity to open up a market. "One day, there will be more jobs in psychedelic clinics than in [the] coal [sector]," Doblin said, alluding to the 131,000 jobs that President Donald Trump claimed to have saved by rejecting the Paris Climate Accord.

SUICIDES

Paul Stamets, author of various books on the medicinal use of mushrooms, began his presentation "The Mycology of Consciousness" by asking people to raise their hand if they had already ingested psilocybin-producing fungi, another psychedelic substance whose therapeutic effect is under investigation. Just 7 of the around 300 people present did not do so, a demonstration that contact with psychoactive drugs was the norm at the conference.

Nobody there, however, could be heard claiming that the compounds are harmless. Numerous recommendations were made for them never to be administered to patients with psychotic traits. The Multidisciplinary Association for Psychedelic Studies itself runs a program to promote safe trips, the Zendo harm reduction project.

The stigma of dangerous drugs is one of the biggest obstacles to the entry of substances like LSD and MDMA, use of which remained permitted for decades, into the psychiatric mainstream.

MDMA was synthesized and patented in 1912 by the pharmaceutical company Merck. Only studies with animals were conducted until the 1950s and no medicinal applications were encountered at the time.

In the 1980 when MDMA was rediscovered as an adjunct to psychotherapy, it caused a rage in nightclubs under the name of ecstasy, drawing the attention of the DEA (the US anti-drug agency), which outlawed the substance in 1985.

LSD was discovered in 1938 by Albert Hofmann (1906-2008) working for the pharmaceutical company Sandoz. It remained a curiosity until adopted by the counter-culture movement in the 1960s.

The hippies began the tradition of celebrating April the 19th as the Day of the Bicycle in honor of the first documented LSD trip, taken by Hofmann himself, in 1943, when he experienced fantastic visions as he was cycling home from the laboratory.

In 1979 Hofmann published the book LSD, My Problem Child. But it was not his name that became associated with lysergic acid, but that of Timothy Leary (1920-1996).

The restless and brilliant psychologist with a doctorate from the University of California at Berkeley took with him a turbulent personal history when he was hired by Harvard University in 1960.

While still at Berkeley, Leary had become famous for the wild alcoholic parties thrown by himself and his wife, Marianne. On his thirty-fifth birthday, Don Lattin tells us in The Harvard Psychedelic Club, Leary woke to find a note on Marianne's pillow.

The young woman had been depressed with the fact that her husband had a lover. Though they had an open marriage, Leary had broken their agreement not to become attached to any extramarital partners.

Alarmed, Leary jumped out of bed. He heard the sound of the car engine and ran, finding his wife already unconscious on the front seat and the garage door shut. Marianne would die some hours later in hospital.

The two children, Jack and Susan, witnessed everything. Their daughter would also kill herself, 35 years later, in the jail where she awaited trial for attempted murder.

PSYCHOLOGY

In the summer of the year that he arrived in Harvard, Leary had his first psychedelic experience ingesting hallucinogenic mushrooms in Cuernavaca, Mexico. He returned to the United States convinced that drugs like psilocybin and LSD would revolutionize psychology by opening the 'Doors of Perception' (the title of an influential book in which Aldous Huxley narrates his experiences with mescaline).

In one of his iconoclastic experiments, in 1961, Leary gave psilocybin to prisoners on a neighboring city, Concord. A year later he would give psilocybin to theology students.

Andrew Weil, a student who was denied access to the inner circle of Leary and Richard Alpert (who would later change his name to Ram Dass), wrote an article denouncing the pair in the campus newspaper, "Harvard Crimson." They ended up being expelled from university and became celebrities for a generation of young people seeking revelations mediated by drugs.

In the following years, Leary converted into an apostle of LSD and similar substances, which even assured him a few days in jail.

In 1966, the DEA included lysergic acid on its list of dangerous substances due to the high potential for abuse and due to its serious side-effects, such as acute panic attacks and psychotic episodes. Various US states prohibited its manufacture, possession and consumption, legislation that quickly spread around the world.

As well as LSD, MDMA and psilocybin, the Oakland conference discussed other compounds tested in a therapeutic context, such as ibogaine, salvinorin and cannabinoids.

The strongest challenger to MDMA as star attraction, however, came from a concoction for which Brazilian researchers encounter no rivals: ayahuasca. Also called daime, the beverage made from a vine (Banisteriopsis caapi) and other plants like chacrona (Psychotria viridis) lies at the center of rituals in religions like Santo Daime and União do Vegetal.

The three dozen researchers from Brazil attending the 2017 Psychedelic Science conference closed ranks around two figures: the anthropologist Beatriz (Bia) Caiuby Labate, from the Center for Research and Postgraduate Studies in Social Anthropology in Guadalajara, Mexico, and the physicist Dráulio Barros de Araújo, from the Brain Institute at UFRN.

PLANTS

Labate, the author of 17 books on the subject of ayahuasca, was a member of the conference's organizing team and put together the Plant Medicine track.

In her opening talk at the event, she argued that MAPS has become more multidisciplinary and inclusive, allowing space for the reflections of anthropologists concerning the traditional knowledge that has bequeathed science compounds like the combination of DMT (dimethyltryptamine) and harmine contained in daime and the mescaline of cactuses such as the Mexican peyote.

"It's not all about molecules," Labate said. "Plants are important." She was greeted with applause on calling for indigenous peoples' voices to be heard more.

The UFRN physicist can also be described as a restless spirit, albeit one very different to Timothy Leary. With Zen-like calm, the former parachutist, diving and yoga instructor and surfer presents the data from a study on ayahuasca use to treat depression. It is estimated that 350 million people worldwide suffer from this affliction, a third of them proving unresponsive to anti-depressive medication.

The UFRN group recruited 218 patients with treatment-resistant depression, 35 of which were selected for the ayahuasca trial (others were excluded due to problems such as schizophrenia in the family). The drink was given to 17 of them, in a single dose, while the other 18 received a bitter tea as a placebo.

Over the course of a week, participants were assessed using established ranking systems for depression. The scores of the ayahuasca group were found to be much lower than those taking the placebo.

A fisherman with a history of 20 years of depression had taken part in the experiment. Two days later, he told that he had dreamt of Iemanjá [a candomblé goddess] and had been surfing.

"Doctor, this Indian tea is a marvel. Do you know where I'm going now? To the beach. I want to ride a bike again."

WRONG ZIP CODE

Dráulio de Araújo was trained in physics at the University of Brasília (UnB), but became embroiled in the field of neuroscience and undertook a postgraduate course at the Ribeirão Preto campus of the University of São Paulo (USP), where he would later become a professor. There, in 2005, he took his first Santo Daime trip: he did not get to see the mirações (visions) and was left feeling very unwell, but not enough to dismiss the formula's potential.

"You don't drink ayahuasca to go to a party," the neuroscientist sums up, having avoided the beverage for seven years. "But it is safe when used appropriately [in a therapeutic session supervised by professionals]."

In the researcher's view, ayahuasca allows the person to see, literally, how thoughts take shape. "It is not a substance taken for pleasure, it's for work."

The study on depression is only available via the open repository bioRxiv (bit.ly/2s6QscK), due to publication difficulties. First the UFRN group submitted the work to the journal Lancet Psychiatry, when it received three favorable assessments from technical reviewers. Even so, the text was rejected the same day by the editor.

In 2016, however, the journal had accepted a study on psilocybin by David Nutt (the countess's partner at the Beckley Foundation) with less than half the number of patients and without a placebo control group.

For Labate, the problem is the zip code: a study in Natal (RN, Brazil) tends to be seen with suspicion by Europeans and Americans. But there is also the ayahuasca factor, a beverage that mixes together various components from two plants and cannot be reduced to pill form as easily as MDMA.

"I can't see how ayahuasca can become mainstream," observes Dráulio de Araújo. "How can it be prescribed? There are a lot of different taboos involved."

Read the article in the original language

MARCELO LEITE, 59, is a special reporter for Folha.

THIAGO MARTINS DE MELO, 35, artist, is exhibiting work at the Astrup Fearnley Museum in Oslo until 30/8.

Translated by DAVID RODGERS