Image by Keiji Uematsu, 1976
Since 1986, MAPS has been conducting research to create safe, legal, qualified access to psychedelic therapies for people who may benefit. As we conduct trials to inform our application for approval from the FDA, we continue to train therapists, educate our community, and build the foundation for accessible treatments once they are approved.
Alexander “Sasha” Shulgin and David Nichols were the first to report on the effects of MDMA in humans. In the 1970s, psychotherapists used MDMA-assisted psychotherapy to treat psychological disorders, including anxiety. Legal therapeutic use continued until its placement on the U.S. list of Schedule I drugs in 1985. An estimated 500,000 doses of MDMA were administered during psychotherapy sessions in North America prior to its scheduling. A few uncontrolled human studies of MDMA occurred in the 1980s, including Greer and Tolbert’s study of MDMA in a psychotherapeutic context.
Controlled human studies of MDMA commenced in the mid-1990s with a MAPS funded investigator-initiated Phase 1 dose-response safety study.
Psychotherapists in the U.S. began to use MDMA as an adjunct to psychotherapy in the mid to late 1970s, and narrative accounts describe therapeutic use prior to its scheduling. MDMA was administered to thousands of people in a therapeutic setting prior to scheduling, and has been administered to approximately 1437 people in controlled research settings as of 01 October 2017. These studies have demonstrated that MDMA can be safely administered to people with PTSD in a controlled clinical setting.
The Multidisciplinary Association for Psychedelic Studies (MAPS) is a 501(c)(3) non-profit research and educational organization that develops medical, legal, and cultural contexts for people to benefit from the careful uses of psychedelics and marijuana.
“In November 2020, MAPS Public Benefit Corporation (MAPS PBC) completed data analysis of the first of two Phase 3 trials of MDMA-assisted psychotherapy for treatment of posttraumatic stress disorder (PTSD). The results confirmed Phase 2 results and prior expectations from an independent interim analysis which determined there was a 90% or greater probability that the trial, when completed, would be of sufficient size to detect statistically significant results. Further, no unexpected or serious safety signals emerged during the course of the trial.
The results indicate MDMA-assisted psychotherapy for PTSD may be an effective treatment for PTSD resulting from various types of trauma, including trauma occurring in childhood and in patients with dissociative subtype of PTSD, pending assessment by the U.S. Food and Drug
Administration (FDA). Based on these results, MAPS will begin discussions with the FDA on ways to accelerate the timeframe for approval of this modality.”
Many therapies for PTSD involve the induction and extinction of abnormal autonomic responses through revisiting traumatic experiences in therapy with an appropriate level of emotional engagement. To be effective, exposure must be accompanied by a degree of emotional engagement or “fear activation” while avoiding dissociation or overwhelming emotion. This has been referred to as working within the “optimal arousal zone” or “window of tolerance”.
The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection. MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal in the context of therapy. PTSD increases amygdala activity, causing heightened encoding of fearful memories and decreasing blood flow in the prefrontal cortex. In contrast, MDMA acutely decreases activity in the amygdala, and there is some indication that MDMA may increase activity in the prefrontal cortex. Brain imaging after MDMA indicates less reactivity to angry facial expressions and greater reward in happy faces. This action is compatible with its reported reduction in fear or defensiveness, and is in contrast to the stimulation of the amygdala observed in animal models of conditioned fear, a state similar to PTSD. The reduction in stress- induced activation of the amygdala may be supported and enhanced by interacting with the therapy team during and after the MDMA experience. The subjective effects of MDMA create a productive psychological state that enhances the therapeutic process. MDMA is capable of inducing unique pharmacological effects, including decreased fear and increased wellbeing, sociability, interpersonal trust, acceptance of self and others, and ability to address these issues without extreme disorientation or ego loss due to alert state of consciousness. These factors taken together can provide the opportunity for a corrective emotional experience.
A combined treatment of MDMA and therapy may be especially useful for treating PTSD because MDMA can attenuate the fear response of a perceived threat to one’s emotional integrity and decrease defensiveness without blocking access to memories or preventing a deep and genuine experience of emotion. Elimination of these conditioned fear responses can lead to more open and comfortable communication about past traumatic events and greater access to information about them. Participants are able to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present. As a result, MDMA-assisted therapy may enable participants to restructure their intra-psychic realities and develop a wider behavioral and emotional repertoire with which to respond to anxiogenic stimuli.
The safety and efficacy of MDMA-assisted psychotherapy is currently under investigation. It has not yet been approved by the FDA, does not work for everyone, and carries risks even in therapeutic settings. These statements are no guarantee of future FDA approval or availability of MDMA-assisted psychotherapy. These statements necessarily involve known and unknown risks and uncertainties, which may cause actual outcomes to differ materially from our projections.
A combined treatment of MDMA and psychotherapy may be especially useful for treating PTSD because MDMA can attenuate the fear response of a perceived threat to one’s emotional integrity and decrease defensiveness without blocking access to memories or preventing a deep and genuine experience of emotion. Elimination of these conditioned fear responses can lead to more open and comfortable communication about past traumatic events and greater access to information about them. Participants are able to experience and express fear, anger, and grief with less likelihood of feeling overwhelmed by these emotions. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. In addition, feelings of empathy, love, and deep appreciation often emerge, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present. As a result, MDMA-assisted psychotherapy may enable the participants to restructure their intra-psychic realities and develop a wider behavioral and emotional repertoire with which to respond to anxiogenic stimuli.
In comparison to anxiolytics, antidepressants, and atypical antipsychotics, MDMA does not require steady state levels in the blood to function as a catalyst to psychotherapy with rapid onset in some subjects. A limited number of exposures to MDMA, spaced approximately 1 month apart at moderate doses, are sufficient to obtain therapeutic outcomes. This intermittent dosing mitigates AE frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Based on the current state of scientific knowledge and the risk/benefit profile of therapeutic doses of MDMA, the sponsor concludes that it appears favorable to pursue the research of MDMA as a medicine used as an adjunct to psychotherapy.
Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.
PTSD is our top priority clinical indication in large part because MDMA possesses unique pharmacological and psychological properties that may make it especially well suited for use as an adjunct to psychotherapy with PTSD patients. In addition, PTSD is a worldwide public health problem and is typically a chronic illness associated with high rates of psychiatric and medical co-morbidity.
Currently, 8-10 million Americans currently live with PTSD. Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Left untreated, PTSD can lead to increased depression, anxiety, substance use disorder, high-cost healthcare utilization, fractured relationships, inability to maintain employment, suicide risk, diminished cognitive and psychosocial functioning.
Yes, there has been research on microdosing psychedelics in the past, but current research is limited. One example is the Beckley/Maastrict Programme which is conducting a series of placebo-controlled studies on the effects of LSD microdosing on humans, with a particular focus on mood, cognitive functions (including creativity), and pain management. Additionally, in 2019, researchers have published an article on “Psychedelic microdosing benefits and challenges: an empirical codebook” in the Harm Reduction Journal. The study is based on the qualitative reports of 278 microdosers who have ingested LSD and psilocybin microdoses in the past. James Fadiman, Ph.D. has spoken with MAPS on “Psychedelic Research and Creativity Studies” as well. For more information, in the MAPS store, we carry a book on The Science of Microdosing Psychedelics by Torsten Passie, M.D, which delves into the first-wave scientific literature on microdosing.
In July 2020, MAPS announced the publication of the long-term follow-up results of six Phase 2 clinical trials of MDMA-assisted psychotherapy for the treatment of posttraumatic stress disorder (PTSD) in the peer-reviewed journal Psychopharmacology. The paper is the most comprehensive analysis yet published of the safety and durability of treatment outcomes following MDMA-assisted psychotherapy for PTSD.
The results show that for a majority of participants, the benefits of MDMA-assisted psychotherapy for PTSD extended at least 12 months after the treatment sessions. Sponsored by MAPS, the controlled, randomized, double-blind trials found that, two months following their last session, 56% of 100 participants no longer met diagnostic criteria for PTSD. In the newly published analysis, 91 participants were interviewed at least 12 months later. Of these participants, 67% did not qualify for a PTSD diagnosis. One of the studies included data from an average of 3.8 years after treatment.
For the past nine years, the Zendo Project, a program of the Multidisciplinary Association for Psychedelic Studies (MAPS) harm reduction department, has supported people in transforming challenging psychedelic experiences into opportunities for self-exploration, growth, and healing. We provide professional comprehensive harm reduction education and support for communities to safely plan for and address psychedelic use -- and occasional difficult experiences. The Zendo Project is creating a world where communities are educated, resourced, and engaged in applying harm reduction principles to support individuals exploring psychedelic states.
The Zendo Project’s approach to working with challenging psychedelic experiences is rooted in the philosophies and principles of harm reduction. We aim to invite honest conversations about drug use which facilitate understanding and change the way we respond to those in need of support. We advocate for a compassionate response informed by clinical research and an understanding of the mental, emotional, and physical effects of psychedelic substances. Our approach focuses on de-escalation and supporting the safety and well-being of the individual.
Every year, millions of people will use psychedelics outside of supervised medical settings --many of them for the first time. As we explore the vast potential benefits of psychedelics, it is our responsibility to help people adequately understand and mitigate risk.
Honest and informed public education is necessary for individuals who choose to use psychedelics, the people they are in community with, and the psychedelic movement itself. Psychedelic harm reduction uses education, training, and safety tools to help prevent and transform difficult experiences while in a non-ordinary state of consciousness.
Much like driver’s education, speed limits, and seat belts reduce the risks of driving, MAPS’ approach to working with challenging psychedelic experiences is rooted in the philosophies and principles of harm reduction. We aim to invite honest conversations about drug use which facilitate understanding and change the way we respond to those in need of support. We advocate for a compassionate response informed by clinical research and an understanding of the mental, emotional, and physical effects of psychedelic substances. Our approach focuses on de-escalation and supporting the safety and well-being of the individual.
Our volunteers are trained to provide a grounded and compassionate presence, to approach with kindness and openness, and create an environment of acceptance and compassion. We remind the individual that their experience is welcome and that whatever is arising for them emotionally or mentally is ok. We invite them to share their experience if they would like, making no expectations. The Zendo space is generally quiet with few inputs. We try to minimize bright lights, loud music, and other external stimulation that may contribute to disorientation.
During a psychedelic experience, language and words can often confuse or get in the way. We encourage our volunteers to use words sparingly unless the individual is desiring to engage in a dialogue about their process. Rather than analyze their experience, we listen with an open mind and heart. If engaged in dialogue, we ask questions which help the individual deepen into their experience. Listening from the heart and becoming curious about someone's reality can assist them in releasing resistance to the process and feeling more comfortable. We encourage the individual to come to their own insights or conclusions through compassionate inquiry.
We encourage and help individuals turn toward their experience rather than away from it. We encourage connecting to inner wisdom and guidance. We do not dismiss or invalidate someone’s perceived reality. We avoid rushing the experience. Rather than provide answers or solutions, we encourage exploration.
“Set” refers to the mindset of the participant: the person’s state of mind, expectations, personality, level of experience with psychedelics. The “setting” of is the environment, including who they are with and where they are. Set and setting are very important factors that greatly influence an individuals experience. From a harm reduction perspective, it is important to take these factors into consideration if you are considering taking a psychedelic substance. Care and attention to set and setting can help build a container of support where someone can feel safer exploring the psychedelic state. In the Zendo, our intention is to create a safe container where one may not exist. In therapeutic or ceremonial settings, there is explicit attention paid to set and setting. In recreational settings, this is not often the case. Yet the majority of individuals who take psychedelics do so outside of a clinical, therapeutic, or recreational context. As psychedelics become more integrated into our society, attention paid to set and setting is incredibly important to both reduce harm and optimize experiences.
The vast majority of psychedelic experiences have little to no severe physical or psychological adverse effects or impact, but emotionally or psychologically challenging or uncomfortable psychedelic experiences are not uncommon. The nature of the psychedelic experience can be disorienting, confusing, and at times frightening.
When psychedelics are used in a ceremonial or therapeutic setting, emotional and psychological challenge is expected and even welcomed as part of the experience. With certain substances like ayahuasca, it is commonly understood that facing the fears and inner struggles revealed by the medicine is part of the experience. In psychotherapy sessions using MDMA, accessing and processing suppressed memories is the mechanism through which individuals are able heal from trauma. However, in non-clinical or non-ceremonial contexts, whatever is being revealed or amplified by the psychedelic can catch someone off guard. In recreational settings, people are often not consciously seeking or intending to process their trauma or do have a therapeutic experience. This can mean that when these things come up, someone may not have the tools or awareness of how to deal with it. That’s where education and skilled external support come in.
The Zendo Project has been an effort to create a safe container for these difficult experiences, as well as educate individuals on ways to apply effective peer support strategies to their friends and communities. Being a calm and grounded presence will go along way in helping someone who is struggling. Reminding the individual that their experience may be an opportunity for them to look at aspects of themselves that want their attention in order to be healed can be helpful. Inviting in the possibility that they will emerge from the experience with new insights and understanding can help reframe a difficult experience.
MAPS’ Policy and Advocacy Department recently published an article, “Beyond Oregon: A New Drug Policy Horizon in the U.S.,” in the MAPS Bulletin which I highly recommend to readers:
Footnote: Some of the information in this interview was derived directly from the following sources:
Brad Burge, “MDMA-Assisted Psychotherapy May Have Lasting Benefits for PTSD, Results Published in Psychopharmacology,” last modified June 10, 2020, https://mapspublicbenefit.com/press-releases/press-release-mdma-assisted-psychotherapy-may-have-lasting-benefits-for-ptsd-results-published-in-psychopharmacology/
Ismail Lourido Ali, Leslie Booher, and Natalie Lyla Ginsberg. “Beyond Oregon: A New Drug Policy Horizon in the U.S.” MAPS Bulletin Winter 31, no. 1 (2021), https://maps.org/news/bulletin/articles/491-bulletin-winter-2021/8899-beyond-oregon-a-new-drug-policy-horizon-in-the-u-s
“Microdosing.” Beckley Foundation. Accessed April 5, 2021. https://www.beckleyfoundation.org/microdosing-lsd/
Multidisciplinary Association for Psychedelic Studies, “Jim Fadiman: Psychedelic Research & Creativity Studies at MAPS First Friday Art Tour,” YouTube, April 26, 2012, video, 42:46, https://www.youtube.com/watch?v=CoVEJtVo1go
“Multidisciplinary Association for Psychedelic Studies.” MAPS. Accessed April 5, 2021. https://maps.org/.
“MAPS Public Benefit Corporation” MAPS PBC. Accessed April 5, 2021. https://mapspublicbenefit.com.
Thomas Anderson et al. “Psychedelic microdosing benefits and challenges: an empirical codebook,” Harm Reduction Journal 16, no. 43 (2009), doi: https://doi.org/10.1186/s12954-019-0308-4