Author: Alli Feduccia, PhD

Healing Trauma with MDMA: A New Study Published

Healing Trauma with MDMA: A New Study Published

by | Oct 29, 2018 | Research

Patchwork Art from MAPS Therapist Training Program 2017

Photo Credit: Alyssa Gursky

Findings from the last study in a series of six Phase 2 trials of MDMA-assisted psychotherapy for treatment of posttraumatic stress disorder (PTSD) was published today in the Journal of Psychopharmacology [1]. The clinical trial in Boulder, Colorado (MP-12) enrolled 28 participants suffering from chronic PTSD. Results showed that after two to three sessions of psychotherapy with active doses of MDMA (100-125 mg) PTSD symptoms were markedly reduced. Twelve months later most participants (76%) did not meet criteria for PTSD.

 After treatment, a great majority of our participants have reported feeling more connected to themselves and to others, more joy, more compassion, and with new skills for facing life’s challenges.

 

Marcela Ot’alora G.

Principal Investigator Boulder, CO

Decades in the Making

The Multidisciplinary Association for Psychedelic Studies (MAPS) was founded in 1986 with the intention to take MDMA through the FDA-regulated drug development pipeline. The non-profit organization faced many political and logistical hurdles to research MDMA, a schedule 1 controlled substance. The first randomized, blinded study investigating MDMA-assisted psychotherapy started in 2000 in Spain by MAPS. After treating six women survivors of sexual assault with no serious adverse effects and PTSD symptoms on decline, the study was suddenly halted due to political pressure from the Madrid Anti-Drug Authority in 2002 [2].

Marcela Ot’alora G., MA, LPC was a psychotherapist in this first study. A decade later in 2012 she became the first woman Principal Investigator for a MAPS-sponsored trial in the US. She trained and supervised nine therapy teams for the trial in Boulder, and treated 17 participants as the lead psychotherapist. Importantly, the positive results from this study showed that new therapy teams could replicate findings from previous studies (MP-1 [3], MP-8 [4]) that had a single therapy team – Michael Mithoefer, MD (Psychiatrist) and his wife Annie Mithoefer, BSN (Psychiatric Nurse). It was uncertain if interns and newly trained therapists would be able to produce significant results equivalent to the very experienced and compatible Mithoefer team.

Photo: Marcela Ot’alora G. and Bruce Poulter at their home in Boulder, CO. 

Marcela rotated amongst teams, pairing with her husband Bruce Poulter, MPH, RN to treat several participants. Six other therapists worked on the study, including Dr. Will Van Derveer, MD, ABOIM who acted as study physician and therapist, and is now a provider in the Psychedelic Support Network. Sara Gael Giron, MA, Director of MAPS Zendo Project, treated three participants and currently works in Boulder with Dr. Van Derveer at the Integrative Psychiatric Healing Center.

In the study publication, results were presented for both the intent-to-treat set, which refers to  the group of participants who completed at least one MDMA session, and the per protocol set, which included only participants who completed both blinded MDMA sessions and matched all criteria for being in the study. It was discovered during the study that three participants had mental health disorders that made them not meet all study criteria, thus they were excluded from the per protocol analysis.   The main measure of PTSD symptom severity was change in the Clinician Administered PTSD Scale (CAPS-IV) from baseline to one month after the second blinded MDMA session. During blinded sessions, participants were given MDMA at doses of 40 mg (active placebo), 100 mg or 125 mg (active doses). Before and after MDMA sessions, participants underwent non-drug therapy sessions for preparation and integration.

 

PTSD Symptoms Improve

The 100 mg and 125 mg doses had a medium to strong effect on PTSD symptoms, but only the per protocol set reached significant group differences at this point. Principal Investigator Marcela Ot’alora G. commented, “The results of the study indicate that this treatment has the potential to greatly improve the lives of people suffering from PTSD, regardless of the source of their trauma”. At this point, a month after both blinded sessions, participants learned what dose group they were in. Participants given 100 and 125 mg had a third open label session, and participants given 40 mg started a new, second part of the study, or a “cross-over” where they had three open-label MDMA sessions.

PTSD symptoms, including anxiety, sleep disturbance, and depression, continued to significantly improved after the third active dose session for the 100 mg and 125 mg group. The 40 mg group showed similar reductions in symptoms after they crossed over and had three open-label sessions with 100-125 mg MDMA. In the paper, the authors describe how the treatment is effective by saying, “an enhanced therapeutic alliance combined with reduced anxiety or discomfort around difficult memories, increased self-compassion, and openness to expanding meaning of thoughts, feelings or experiences may all contribute toward therapeutic effects.” [1]

An impressive finding from this study was the PTSD symptom (CAPS-IV) scores 12 months after completing treatment. Upon enrolling in the study, the average CAPS-IV score was 92, and at the 12-month follow-up, had decreased to 31. At 12-months, 76% of participants (n=25) did not meet criteria for PTSD.

“After treatment, a great majority of our participants have reported feeling more connected to themselves and to others, more joy, more compassion, and with new skills for facing life’s challenges” explained Marcela.

The average CAPS-IV (or PTSD symptom) score dropped 9.6 points from treatment exit to 12-month time point, demonstrating that MDMA therapy not only produced enduring reduction in PTSD symptoms but allowed for continued healing and growth long after the drug-therapy ended. With PTSD symptoms no longer interfering with emotional and cognitive processes, the participants were able to re-integrate into life and recover from PTSD. “What we see after reprocessing of memories and feelings,” says researcher Dr. Lisa Jerome, “is not only reduction in PTSD symptoms but improvement in other areas of their lives, including mood and sleep.”

Based on the positive safety and efficacy outcomes from this trial and the other similar Phase 2 studies, FDA granted Breakthrough Therapy Designation for this innovative treatment approach. Breakthrough Therapy is only given for drugs under development that have data indicating that they work better and/or more safe than current medications for a life-threatening illness. This designation is intended to speed up timelines in the path to FDA approval.

Though originally planned to start earlier, Phase 3 trials will start in November 2018 due to unforeseen delays with producing and encapsulating Good Manufacturing Practices (GMP) MDMA. If two trials have significant outcomes in 200-300 participants, MDMA-assisted psychotherapy could be an FDA-approved treatment by 2021.

What we see after reprocessing of memories and feelings is not only reduction in PTSD symptoms but improvement in other areas of their lives, including mood and sleep.

 

Dr. Lisa Jerome

MAPS PBC Researcher

In preparation for Phase 3 trials in the USA, Canada, Israel, and Europe, the MAPS Therapy Training Program has expanded to meet the need for well-trained therapists at new study sites. Therapists in this program are trained on the MDMA Treatment Manual, which was first authored by Michael Mithoefer and updated regularly as the therapeutic approach is fine-tuned.

Marcela is a lead trainer, along with the Mithoefers, and brings her passion for art to the training program. She teaches trainees about how art can be used as a non-verbal expression of internal processes and offers ways to bring art into therapy sessions during and after altered states of consciousness.

The Phase 3 MAPS Therapy Training Program consists of online e-learning modules, reading assignments, a 7-day in-person training to watch and discuss MDMA psychotherapy videos from completed studies, a 5-day in-person meeting for team building and role play, and supervision during an open-label Phase 2 MDMA study. The program will continue to scale and adapt to accommodate more trainees interested in providing MDMA therapy in Expanded Access and post-approval psychedelic clinics.

Boulder, CO will be one of approximately 15 study sites in the Phase 3 trials. Enrollment of new participants will start in November 2018. Visit maps.org for more information about study participation, therapist training, and research updates.

  1. Ot’alora, G., Marcela, Jim Grigsby, Bruce Poulter, Joseph William Van Derveer III, Sara Gael Giron, Lisa Jerome, Allison A. Feduccia, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Michael C. Mithoefer, Rick Doblin. “MDMA-assisted psychotherapy for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Phase 2 Controlled Trial.” Journal of Psychopharmacology. (2018). Full article link. 
  2. Bouso, José Carlos, Rick Doblin, Magí Farré, Miguel Ángel Alcázar, and Gregorio Gómez-Jarabo. “MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder.” Journal of Psychoactive Drugs. 40, no. 3 (2008): 225-236.
  3. Mithoefer, Michael C., Mark T. Wagner, Ann T. Mithoefer, Lisa Jerome, and Rick Doblin. “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, no. 4 (2011): 439-452.
  4. Mithoefer, Michael C., Ann T. Mithoefer, Allison A. Feduccia, Lisa Jerome, Mark Wagner, Joy Wymer, Julie Holland et al. “3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.” The Lancet Psychiatry. 5, no. 6 (2018): 486-497.
Alli Feduccia, PhD
Alli Feduccia, PhD Administrator
Dr. Alli Feduccia is a Co-Founder of Psychedelic Support and a Neuropharmacologist working as a Clinical Data Scientist at MAPS Public Benefit Corporation in support of the MAPS MDMA trials.
email
afeduccia@gmail.com

First Clinical Trial: Social Anxiety in Autistic Adults Successfully Treated with MDMA Therapy

First Clinical Trial: Social Anxiety in Autistic Adults Successfully Treated with MDMA Therapy

by | Sep 13, 2018 | Research

The first clinical trial in adults on the autism spectrum investigating MDMA, or any psychedelic substance for that matter, was published in Psychopharmacology this week [1]. This groundbreaking research looked at whether MDMA combined with psychotherapy could help with the severe social anxiety that autistic adults commonly experience.

The drug-therapy combo wasn’t intended to be a treatment for autism itself but was evaluated to see if it could possibly relieve some of the symptoms that limit social adaptability and often affect quality of life.

Twelve study participants were given MDMA or placebo during two all-day therapy sessions with additional non-drug preparatory and integrative therapy sessions. The main findings of this pilot study showed marked improvements in social anxiety and less avoidance of social interactions for the group that received MDMA. Most importantly, limited doses of MDMA in the controlled clinical setting was safe and well tolerated in adults on the autism spectrum.

 91% of participants reported “increased feelings of empathy/connectedness” and 86% experienced “ease of communication” during MDMA/Ecstasy that persisted after use

The rationale for this double-blind study came after a review of accounts in online discussion forums of unsolicited anecdotal reports of MDMA/Ecstasy use in autistic adults in non-medical settings suggested that some had better overall functioning and others had reduced symptoms of anxiety [2].

For her dissertation research, Dr. Alicia Danforth conducted interviews and collected survey data about the MDMA experiences of autistic adults. The survey found that 91% of participants reported “increased feelings of empathy/connectedness” and 86% experienced “ease of communication” during MDMA/Ecstasy that persisted after use.

In 2014, these findings supported the Multidisciplinary Association for Psychedelic Studies (MAPS)’s commitment to sponsor a Phase 2 randomized controlled trial of MDMA-assisted psychotherapy. Dr. Danforth and Dr. Charles Grob, a long-established researcher of psychedelic substances, led the trial at the Los Angeles BioMedical Research Institute at the Harbor-UCLA Medical Center and worked together as a co-therapy team for participants in MDMA-assisted psychotherapy.

The trial design was similar to methods used for MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD), but included some variations to meet the specific needs of the autistic population. Dr. Danforth said, “This study was the first of its kind, and one of the success factors was working with autistic consultants from protocol development through writing the findings paper. As a result, the investigators had a well-supported rationale for focusing on social anxiety and were able to create a setting that would feel safe and comfortable for a population that often struggles with novel situations and sensory overstimulation.”

For example, to assess whether autistic participants experienced similar subjective effects that would constitute a therapeutic window without becoming overwhelmed, the first four participants received MDMA in the initial session at a dose lower (75 mg) than the typical full dose in PTSD trials (100-125 mg). There were no issues with the 75 mg dose, therefore the dose was escalated to 100-125 mg for the rest of the sessions and participants.

The researchers also wove in mindfulness-based therapy since this approach has previously shown useful for autistic adults and other populations who struggle with emotion regulation, relationships, and tolerance of distress. Unlike the PTSD trials that require the participant to stay overnight in the clinic after MDMA sessions, participants in this study would leave after the session ended with a trusted Study Support Partner who would remain with them at home. This adaptation was made to best accommodate autistic adults who may have elevated anxiety from staying in a clinic setting overnight.

One month after the second experimental session (MDMA or placebo given during 8-hour psychotherapy sessions), the primary measure for gauging social anxiety, the Leibowitz Social Anxiety Scale (LSAS), showed that the group that received MDMA had significantly more improvement in social functioning and less distress in social situations than the placebo group. The large therapeutic effects remained six-months later.

One individual said, “Being a participant in the study affected me in many ways. My self-esteem increased, my social anxiety decreased, love flooded in, my heart healed, and I’m more resilient” [1].

Change in LSAS Total Scores

Baseline to One Month Post Second MDMA/Placebo Session

 

LSAS evaluates impact of social anxiety on areas of a patient’s life.

Beyond just changes in study measure scores, participants and their Study Support Partner reported tangible gains in both family and romantic relationships, with two participants feeling confident enough to start dating for the first time. A participant described this as, “… I have been able to sustain flirtatious conversations for a longer time. In these conversations, I realized communication is not just about talking. Now, I take time to notice my emotions and others’ emotions before talking” [1].

Another two participants felt more at ease talking about and reflecting on gender identity, and overall participants were more adept and comfortable in interactions with friends, family, and the therapy team.

The effects lasted long after MDMA, with remarkable reductions of anxiety in triggering situations, such as entering a new social setting or speaking on the telephone. The investigators noted that they observed, “emergence of apparently intact latent social skills (e.g., ease of initiating and sustaining conversation) that manifested and became apparent to observers during experimental sessions with MDMA when participants relaxed” [1].

Dr. Lisa Jerome, one of the researchers on the team, elaborated on this idea about MDMA by saying, “These findings show that MDMA and psychotherapy can help people, maybe by giving them a whole new set of experiences with social interactions. MDMA isn’t giving people something they didn’t have already, it’s helping them use what they had all along.”

This pilot study was successful in establishing that MDMA-assisted psychotherapy can be used safely in adults on the autism spectrum, and is helpful in relieving severe social anxiety in this population. When asked if new trials would be started soon, Dr. Danforth said, “We hope that the good safety profile and encouraging reduction in social anxiety symptoms will inspire funding for new and larger studies. It remains to be seen how the mainstream autism science community will respond to the new data.”

More clinical trials are needed in a much larger sample of autistic adults before FDA could approve this treatment, but the initial findings are compelling enough to expand research into this novel approach. “We are looking forward to sharing what we learned with other researchers and communities who are committed to improving the quality of care for autistic adults and other populations who struggle with social anxiety,” says Danforth.

Until more data is generated in clinical trials of MDMA in autistic populations, Dr. Danforth strongly encourages autistic individuals to “wait until this type of therapy is more widely available in controlled settings with qualified therapists.” She goes on to say, “In the meantime, we saw an indication that mindfulness-based therapy can also improve social anxiety symptoms. That has certainly been the case in my private practice, where I also have to wait patiently until I can provide MDMA-assisted therapy outside of a clinical trial.”

Read the full text, open-access article here

[1] Danforth, Alicia L., Charles S. Grob Christopher M. Struble, Allison A. Feduccia, Nick Walker, Lisa Jerome, Berra Yazar-Klosinski, and Amy Emerson. “Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: A randomized, double-blind, placebo-controlled pilot study.” Psychopharmacology (2018): 1-12.
[2] Danforth, Alicia L., Christopher M. Struble, Berra Yazar-Klosinski, and Charles S. Grob. “MDMA-assisted therapy: a new treatment model for social anxiety in autistic adults.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 64 (2016): 237-249.

Alli Feduccia, PhD
Alli Feduccia, PhD Administrator
Dr. Alli Feduccia is a Co-Founder of Psychedelic Support and a Neuropharmacologist working as a Clinical Data Scientist at MAPS Public Benefit Corporation in support of the MAPS MDMA trials.
email
afeduccia@gmail.com
Do Psychedelics Have the Power to Change Minds?

Do Psychedelics Have the Power to Change Minds?

by | Sep 4, 2018 | Research

Originally published on Chacruna.net by Dr. Alli Feduccia

Clinical trials of MDMA, psilocybin, ketamine, and ayahuasca are offering a glimpse that the future may hold psychiatric treatments far different from daily drug prescriptions currently used for anxiety and addictive disorders. Research is only beginning to unravel how these experiences in altered states of consciousness produce large shifts in psychological functioning. Although a purely biochemical model is not inclusive of psycho-spiritual or transpersonal explanations, here I describe what scientific explorations are revealing about how the brain responds when … read full article.

Alli Feduccia, PhD
Alli Feduccia, PhD Administrator
Dr. Alli Feduccia is a Co-Founder of Psychedelic Support and a Neuropharmacologist working as a Clinical Data Scientist at MAPS Public Benefit Corporation in support of the MAPS MDMA trials.
email
afeduccia@gmail.com
How To Join a Psychedelic Clinical Trial

How To Join a Psychedelic Clinical Trial

by | Jul 30, 2018 | Research

You could be eligible to participate in a psychedelic research trial. Studies of psychedelics are at various stages, enrolling both healthy volunteers and individuals with specific mental health conditions. We’ve compiled a list here of all the current or planned clinical trials on MDMA, psilocybin, LSD, Cannabis, and more. Regulatory approvals over the last few decades gave way to MDMA and psilocybin pilot studies and clinical trials, while research around the world is exponentially growing. New investigations for the therapeutic use of psychedelics, as well as inquiries into how the brain works and what constitutes consciousness are appearing all the time.

It seems we’ve reached a new frontier where many academic scientists and investigators in private psychiatric practices are able to pursue research on psychedelics without facing opposition based on stigma or antiquated information about safety concerns. While this may still not yet be the case for many Universities, the forerunners in this field will pave the way for others by contributing evidence-based findings to the body of knowledge. Since we have better technologically advanced tools and more rigorous study designs than ever before, all research in current day is extremely valuable.

 

Background: How does a clinical trial work?

Clinical trials collect data to evaluate safety and efficacy of drugs under investigation in research. Drugs must pass through a sequence of phases or stages to become approved and available to patients. A new substance is first thoroughly tested in human cells and/or animals to gain initial information about safety and toxicity. If enough research exists in scientific journals, sometimes an already known drug like some psychedelics, can go through less animal testing or wait till later in the process to complete. After review, FDA can grant approval to test the drug in a small number of healthy individuals (phase 1). The next phase of testing involves giving a drug to people who have a disease or condition (phase 2) to evaluate safety and effectiveness to reduce symptoms. If the drug appears safe and signals the potential to be a useful treatment, then a much larger number of people are tested in phase 3 trials at multiple study sites. For the FDA to approve a new drug for a specific condition or disease, two phase 3 trials must show significant benefit that outweighs the risks or negative side effects of taking the drug. After the drug is approved and sold in the consumer market, research continues in phase 4 known as post marketing surveillance trials. Phase 4 trials collect data on long-term effectiveness and safety, costs associated with treatment compared to other drugs in the market, and safety and effectiveness of the new drug versus other available treatment options.

Directories searched for trials:  clinicaltrials.gov; clinicaltrialsregister.eu; ensaiosclinicos.gov.br

Following is a list of current or planned clinical trials with psychedelics (as of December 2018) in healthy individuals and in people with a specific medical condition. We searched clinical trial registries for USA, EU, and Brazil. While we’ve attempted to make this list comprehensive, new trials are emerging often and our online search may not have revealed all. We plan to periodically update this list. If you know of clinical trials not listed here, please email us at info@psychedelic.support

Jump Ahead To:

MDMA

Psilocybin

LSD

Cannabis

Ketamine

Ibogaine

Salvinorin

MDMA

A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD

Open-Label Multi-Site Study of Safety and Effects of MDMA-Assisted Psychotherapy for Treatment of PTSD

Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD

Sponsor: MAPS

Population: PTSD

Location: Global

Background: The Multidisciplinary Association for Psychedelic Studies (MAPS) is recruiting participants with chronic PTSD for Phase 2/3 trials of MDMA-assisted psychotherapy at 15 study sites in the USA, Canada, and Israel. Follow the clinical trials record below to find the study site contact information.

Enrollment: Enrolling now

More Info: Open-label Clinical Trials record (US); Open-label Clinical Trials record (Canada); Phase 3 Clinical Trials record (contact sites directly, phone numbers/emails in clinicaltrials.gov record).

Learn more about safety and effectiveness from clinical research in the MDMA Investigator Brochure (2017)

 

Evaluation of MDMA on Startle Response

Sponsor: MAPS

Population: Healthy Volunteers

Location: Emory University, Atlanta, GA

Enrollment: Enrolling Now

More Info: Clinical Trial record

MDMA in Subjects With Moderate Hepatic Impairment and Subjects With Normal Hepatic Function

Sponsor: MAPS

Population: Healthy Volunteers/Hepatic Impaired Volunteers

Location: University of California, San Francisco, CA

Enrollment: Not Yet Recruiting

More Info: Clinical Trial record

Open-Label Proof of Concept Feasibility Study to Explore the Safety, Tolerability and Potential Role of MDMA-Assisted Psychotherapy for the Treatment of Detoxified Patients with Alcohol Use Disorder

Sponsor: Imperial College London

Population: Alcohol Use Disorders

Location: UK

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

3,4-Methylenedioxymethamphetamine (MDMA)-assisted Psychotherapy in the Treatment of Post-Traumatic Stress Disorder

Sponsor: Planting Consciousness Institute in collaboration with MAPS

Population: PTSD

Location: Brazil

Enrollment: Completed

More Info: Clinical Trials record

 

Effect of Methylenedioxymethamphetamine (MDMA) on Fear Extinction

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

 

Role of Dopamine, Serotonin, and 5-HT2A Receptors in Emotion Processing

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD

Sponsor: Yale University

Population: PTSD

Location: New Haven, CT

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

Psilocybin

Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study

Sponsor: John Hopkins School of Medicine in collaboration with Beckley Foundation and Heffter Research Institute

Population: Smokers

Location: Baltimore, MD

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Effects of Psilocybin on Major Depression

Sponsor: Johns Hopkins University

Population: Depression

Location: Baltimore, MD

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

The Effects of Psilocybin-Facilitated Experience on the Psychology and Effectiveness of Religious Professionals

Sponsor: Johns Hopkins University

Population: Religious Professionals

Location: Baltimore, MD

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Effects of Psilocybin on Behavior, Psychology and Brain Function in Long-term Meditators

Sponsor: Johns Hopkins University

Population: Long-term Meditators

Location: Baltimore, MD

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Persisting Effects of Psilocybin

Sponsor: Johns Hopkins University in collaboration with NIDA

Population: Healthy Volunteers

Location: Baltimore, MD

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Psilocybin-assisted Group Therapy for Demoralization in Long-term AIDS Survivors a Study on Distress, Depression, Grief, HIV/AIDS

Sponsor: University of California San Francisco

Population: HIV/AIDS

Location: San Francisco, CA

Enrollment: Enrolling Now

More Info:  Clinical Trials record

 

A Double-blind Trial of Psilocybin-assisted Treatment of Alcohol Dependence

Sponsor: New York University (NYU) School of Medicine in collaboration with Heffter Research and University of New Mexico

Population: Alcohol Use Disorders

Location: New York, NY

Enrollment: Enrolling Now

More Info:  Clinical Trials record

 

The Effects of Psilocybin-Facilitated Experience on the Psychology and Effectiveness of Religious Professionals

Sponsor: New York University (NYU) School of Medicine

Population: Religious Professionals

Location: New York, NY

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Psilocybin Cancer Anxiety Study

Sponsor: New York University (NYU) School of Medicine

Population: Cancer

Location: New York, NY

Enrollment: Active, Not Recruiting

More Info: Clinical Trials record

 

Psilocybin for Treatment of Obsessive Compulsive Disorder

Sponsor: University of Arizona

Population: OCD

Location: Tuscon, AZ

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

 

Efficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study

Sponsor: Yale University

Population: OCD

Location: New Haven, CT

Enrollment: Not Yet Recruiting

More Info:  Clinical Trials record

 

Psilocybin – Induced Neuroplasticity in the Treatment of Major Depressive Disorder

Sponsor: Yale University in collaboration with Heffter Research Institute

Population: Depression

Location: New Haven, CT

Enrollment: Enrolling Now

More Info:  Clinical Trials record

 

Psilocybin for the Treatment of Migraine Headache Yale University

Sponsor: Yale University

Population: Migraine

Location: New Haven, CT

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Psilocybin for the Treatment of Cluster Headache

Sponsor: Yale University in collaboration with Heffter Research Institute and Cluster Headache-Trigeminal Autonomic Cephalalgia LLC

Population: Cluster Headache

Location: New Haven, CT

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Psilocybin-facilitated Treatment for Cocaine Use

Sponsor: University of Alabama at Birmingham

Population: Cocaine Addiction

Location: Birmingham, AL

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Psilocybin and Depression

Sponsor: Helsinki University

Population: Depression

Location: Helsinki, Finland

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

 

Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms in a Randomized Controlled Trial

Sponsor: Imperial College London

Population: Depression

Location: UK

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

 

The Neurobiological Effect of 5-HT2AR Modulation

Sponsor: Gitte Moos Knudsen

Population: Healthy Volunteers

Location: Rigshospitalet, Denmark

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

 

Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

Clinical, Neurocognitive, and Emotional Effects of Psilocybin in Depressed Patients – Proof of Concept

Sponsor: University of Zurich

Population: Major Depression

Location: Zurich, Switzerland

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the Self

Sponsor: University of Zurich

Population: Healthy Volunteers

Location: Zurich, Switzerland

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression (P-TRD)

Sponsor: COMPASS Pathways

Population: Treatment Resistant Depression

Location: Wolfson Research Centre, Newcastle, UK

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

LSD

LSD Treatment in Persons Suffering From Anxiety Symptoms in Severe Somatic Diseases or in Psychiatric Anxiety Disorders (LSD-assist)

Population: Anxiety

Location: University Hospital, Basel, Switzerland

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Role of the Serotonin 5-HT2A Receptor in LSD-induced Altered States of Consciousness (LDR-Study)

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Enrolling Now

More Info: Clinical Trial record

 

Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Not Yet Recruiting

More Info: Clinical Trial record

 

Role of Dopamine, Serotonin and 5-HT2A Receptors in Emotion Processing

Sponsor: University Hospital, Basel, Switzerland

Population: Healthy Volunteers

Location: Basel, Switzerland

Enrollment: Enrolling Now

More Info: Clinical Trial record

KETAMINE

Too many to list! search clinicaltrials.gov

CANNABIS

Placebo-Controlled, Triple-Blind, Randomized Crossover Pilot Study of the Safety and Efficacy of Four Different Potencies of Smoked Marijuana in 76 Veterans with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

Sponsor: MAPS

Population: PTSD

Location: Phoenix, AZ

Enrollment: Complete

More Info: Clinical Trials record

 

Evaluating Safety and Efficacy of Cannabis in Participants With Chronic Posttraumatic Stress Disorder

Sponsor: Tilray in collaboration with University of British Columbia

Population: PTSD

Location: Kelowna, BC

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Effects of Delta-9 Tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R61 Study

Sponsor: Wayne State University

Population: PTSD

Location: Detroit, Michigan

Enrollment: Enrolling Now

More Info: Clinical Trials record

 

Cannabinoid Control of Fear Extinction Neural Circuits in Post-traumatic Stress Disorder

Sponsor: Wayne State University

Population: PTSD

Location: Detroit, Michigan

Enrollment: Enrolling Now

More Info: Clinical Trials record

Many more cannabis and cannabinoid trials for various psychiatric indications found at clinicaltrials.gov

IBOGAINE

Ibogaine in the Treatment of Alcoholism: a Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial

Sponsor: University of Sao Paulo

Population: Alcohol Use Disorders

Location: Ribeirao Preto, Sao Paulo, Brazil

Enrollment: Not Yet Recruiting

More Info: Clinical Trials record

SALVINORIN A

Effects of Salvinorin A in Healthy Controls

Sponsor: Yale University

Population: Healthy Volunteers

Location: West Haven, Connecticut

Enrollment: Active, not Recruiting

More Info: Clinical Trials record

Alli Feduccia, PhD
Alli Feduccia, PhD Administrator
Dr. Alli Feduccia is a Co-Founder of Psychedelic Support and a Neuropharmacologist working as a Clinical Data Scientist at MAPS Public Benefit Corporation in support of the MAPS MDMA trials.
email
afeduccia@gmail.com
How Psychedelics Help Neurons Grow

How Psychedelics Help Neurons Grow

by | Jun 13, 2018 | Research

A common question about the recent wave of psychedelic research is, “how do these mind-altering substances work in the brain to produce a rapid reduction of symptoms and long-lasting improvements for a variety of mental health disorders?” Beyond some scientifically well-founded hypotheses and pure speculation, we haven’t had enough experimental evidence on psychedelics to draw from to make any large claims about the mechanisms responsible for therapeutic response. MDMA and psilocybin, both showing promising results in clinical trials, are two very different drugs, in terms of how they make people feel and how they act in the brain.

Is it possible there is a common mechanism in the brain underlying the therapeutic effects of all psychedelics?

New findings published by Ly et al. in the prominent scientific journal Cell Reports are the first to show that classic psychedelics (DMT, LSD, psilocin), amphetamine analogs (MDMA, DOI), and ibogaine all converge at one target (mTor) in the brain to promote neuroplasticity [1]. This is a notable finding because depression and stress-related disorders, e.g. PTSD, can cause a loss of synaptic connectivity – the major way that neurons and supporting cells communicate [2, 3]. The researchers showed that when rodent cortical neurons were put into a dish with each of the before mentioned substances, the number and complexity of dendritic branches and arbors greatly increased, meaning the neurons were changing their structure to make new connections. You can think of a tree being sprinkled with natural fertilizer that causes bolting of new branches and leaves to support optimal functioning of the entire system. Reversal of synaptic loss is also observed with ketamine and antidepressant drugs, and thought to the primary way that they reduce depression symptoms [4, 5].

The research group at the University of California went on to show that the neuronal growth-enhancing properties of these substances occurred within a rodent brain, and not just in cell cultures. DMT infused into the prefrontal cortex of rats, a brain region that exhibits a lose in neurons in patients with neuropsychiatric illnesses, induced growth of dendritic spines comparable to ketamine. The elegant set of well-controlled experiments demonstrate that these drugs in fact do converge on a specific signaling pathway (BDNF – TrkB – mTOR) known to be involved in structural plasticity, and the effects are conserved across rodents and fruit flies. As previously documented [6, 7], the substances increase brain derived neurotropic factor (BDNF) either through the serotonin system or by enhancing glutamate levels, and now this new evidence points to how the brain is structurally and functionally modified to produce fast-acting antidepressant effects.

Neuroplasticity, and the sprouting of new dendritic spines, is the basis for new learning.

Substances that can promote acquisition of new behaviors and ways of thinking are beneficial for treating mental health disorders, and may alleviate repetitive negative loops of thoughts, excessive rumination, and enable positive behavioral change. These experiments demonstrate neuroadaptations stimulated by many different psychedelics that follow a timeframe similar to the rapid onset of therapeutic effects with lasting gains even after the drug has left the body. The authors coined a new term to describe these related compounds, which could become in vogue if these underlying mechanisms prove correct in humans. “To classify the growing number of compounds capable of rapidly promoting induced plasticity, we introduce the term “psychoplastogen,” from the Greek roots psych- (mind), -plast (molded), and -gen (producing)” [1].

As exciting as these findings are, we must be cautious when extrapolating results from rodents and flies to humans. Little research has been done in humans with psychedelics and neuroimaging techniques. More is known about ketamine, which has been shown to reverse functional connectivity impairments in patients with major depressive disorder [8]. Could the same be true for the other psychedelics? The study published in Cell Reports also doesn’t address the added component of therapy that is used in human trials of psychedelic-assisted therapy. However, if neural networks are primed for change or new learning, then self-directed or therapist-directed processing of emotional memories could possibly guide the neuronal adaptations into a direction that supports positive behavioral change. The durable outcomes after MDMA-assisted psychotherapy, for example, suggests that brain circuits have been modified in some way [9].

This rigorous, well-designed study is particularly notable in present because many scientists and physicians are still skeptical about the large effects of psychedelics shown in recent clinical trials. By understanding neurobiological mechanisms, belief of the therapeutic potential of these substances will likely rapidly propagate amongst scientific communities, as seen with ketamine and cannabis. The expanding body of knowledge on mechanisms for therapeutic response will help fine-tune treatments and possibly aid in the discovery of new drugs for use in psychiatric medicine.

  1. Ly, C. Greb, AC, Cameron, P, Wong, JM, et al. “Psychedelics Promote Structural and Functional Neural Plasticity.” Cell Reports 23 (2018): 3170-3182.
  2. Arnsten, Amy FT. “Stress signalling pathways that impair prefrontal cortex structure and function.” Nature Reviews Neuroscience10, no. 6 (2009): 410.
  3. Christoffel, Daniel J., Sam A. Golden, and Scott J. Russo. “Structural and synaptic plasticity in stress-related disorders.” Reviews in the neurosciences22, no. 5 (2011): 535-549.
  4. Browne, Caroline Ann, and Irwin Lucki. “Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants.” Frontiers in pharmacology4 (2013): 161.
  5. Li, Nanxin, Boyoung Lee, Rong-Jian Liu, Mounira Banasr, Jason M. Dwyer, Masaaki Iwata, Xiao-Yuan Li, George Aghajanian, and Ronald S. Duman. “mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.” Science329, no. 5994 (2010): 959-964.
  6. Nichols, Charles D., and Elaine Sanders-Bush. “A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.” Neuropsychopharmacology26, no. 5 (2002): 634.
  7. Young, M. B., R. Andero, K. J. Ressler, and L. L. Howell. “3, 4-Methylenedioxymethamphetamine facilitates fear extinction learning.” Translational psychiatry5, no. 9 (2015): e634.
  8. Abdallah, Chadi G., Lynnette A. Averill, Katherine A. Collins, Paul Geha, Jaclyn Schwartz, Christopher Averill, Kaitlin E. DeWilde et al. “Ketamine treatment and global brain connectivity in major depression.” Neuropsychopharmacology42, no. 6 (2017): 1210.
  9. Mithoefer, M. C., M. T. Wagner, A. T. Mithoefer, L. Jerome, S. F. Martin, and B. Yazar-Klosinski. “Durability of improvement in PTSD symptoms and absence of harmful effects or drug dependency after MDMA-assisted psychotherapy: A prospective long-term follow-up study.” J Psychopharmacol27, no. 1 (2013): 28-39.
Alli Feduccia, PhD
Alli Feduccia, PhD Administrator
Dr. Alli Feduccia is a Co-Founder of Psychedelic Support and a Neuropharmacologist working as a Clinical Data Scientist at MAPS Public Benefit Corporation in support of the MAPS MDMA trials.
email
afeduccia@gmail.com

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