How Psychedelics May Be Used to Accelerate Psychotherapy

In this series of blog entries, I am discussing the emerging data on using psychedelic compounds, such as psilocybin (the active ingredient in “magic mushrooms”) and 3,4 methyelenedioxymethamphetamine (MDMA, commonly referred to as “ecstasy”) as a means of catalyzing psychotherapeutic change.

I recently wrote about about how conditions as diverse as posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), anxiety at the end of life, and substance use disorders may represent overly rigid and constrained brain networks. In this entry, I will discuss how MDMA and psilocybin may serve to relax these constraints, and I’ll briefly review some of the emerging data from clinical trials with these substances.

Psychedelics at Work 

MDMA is a ring-substituted phenethylamine with a chemical structure similar to amphetamine. However, unlike amphetamines, which are potent dopamine releasers and inhibitors of dopamine reuptake, MDMA primarily causes the release of serotonin and acts as a postsynaptic serotonin 1A and 2A receptor agonist. This action likely accounts for the transient  improvement in mood and decrease in anxiety reported by subjects during treatment with the drug. 

However, MDMA also acts as a potent releaser of oxytocin and prolactin. These two molecules, a neuropeptide and hormone respectively, are key modulators of prosocial behavior and pair bonding in mammals. It is this neurological trifecta that probably helps to account for how MDMA accelerates the psychotherapeutic treatment of PTSD. 

Neuroimaging with MDMA has shown that the drug may (results have been mixed) attenuate the hyperactivity of the amygdala and hippocampus when exposed to threatening stimuli (1,2). Later studies in a non-PTSD population (3), did not find this same association with amygdala deactivation when subjects were asked to recall negative memories under MDMA. However, there was a decrease in connectivity between the amygdala and the left temporal cortex, which may account for why subjects reported the unpleasant memories now felt less negative after MDMA treatment and fMRI scanning. This study has yet to be replicated in a PTSD population. 

A Careful Approach in Psychotherapy 

It is critical to understand that, unlike many of our pharmacology trials in which the only independent variable is the drug, these psychedelic compounds are carefully and deliberately used within an established therapeutic relationship. In the research protocol used by Mithoefer (4,5) MDMA is not even utilized until the third therapy meeting. 

During this meeting, which lasts an entire day, the patient is attended to by a male/female therapist dyad for the entirety of the drug experience. The patient is encouraged to explore the traumatic material but never forced to discuss it. Typically, the traumatic material arises in conversation spontaneously, and the therapists encourage the patient to stay with and work through the memories and attendant emotions (as opposed to the typical orientation to trauma memories, which is to avoid thinking about them). The MDMA session is processed during 3 subsequent non-drug sessions, before the drug session is again repeated and later processed during 3 additional non-drug therapy sessions. 

The outcomes of these studies are remarkable. The majority of the subjects are very ill with PTSD, with an average CAPS (Civilian Administered PTSD Scale) score of 80, indicating significant illness. Upon study completion, this score dropped, on average to 25.

What this means is that 83% of study subjects no longer met criteria for PTSD (compared to 25% who only received placebo MDMA). These outcomes persisted, with 88% of subjects maintaining the gains made in the study over an average 3.5 years of follow up. It is important to note that this study was small and is currently undergoing replication in a 3 site, phase II trial. Preliminary findings from these studies have echoed the outcomes from the earlier study. 

What Patients Say

Personal reports from treatment subjects are as compelling as the quantitative data. One subject reported, “I don’t think I would have survived another year. It’s like night and day for me compared to other methods of therapy. Without MDMA I didn’t even know where I needed to go. Maybe one of the things the drug does is let your mind relax and get out of the way because the mind is so protective about the injury.” 

Another subject remarked, "It's like PTSD changed my brain and MDMA changed it back.” This last remark raises the question—could MDMA create a kind of “reverse PTSD” that is ultimately curative? 

Psilocybin, the psychoactive compound in “magic mushrooms,” has been studied by the team of Roland Griffiths, PhD, at Johns Hopkins University in non-psychiatric subjects to understand the dose-response relationship and the potential for the drug to generate spiritual experiences (6,7). The Hopkins team has found a clear relationship between dose and the likelihood of the subject having a “mystical” experience (as measured on the Pahnke Mysticism Questionnaire). 

Many of Dr. Griffiths’ subjects reported greater life satisfaction and the adoption of spiritual practices, such as meditation, following their participation in the psilocybin study. Remarkably, as many as 94% of the subjects listed the psilocybin experience as being in the top 5 spiritual and overall lifetime experiences, 14 months after taking the drug. 

Research Moves Forward

At University of California, Los Angeles; Johns Hopkins University; and New York University (8), psilocybin has been investigated as a tool to treat anxiety experienced by terminally ill patients. These relatively small studies found reductions in anxiety and improvement in mood following treatment with psilocybin. 

Also at Johns Hopkins, and at the University of New Mexico, investigators have looked at the possibility that psilocybin could be help to break the compulsive behavior patterns seen in substance use disorders (9,10,11). In these small, but compelling studies, 2 to 3 doses of psilocybin were used as part of a regimen of motivational interviewing and cognitive behavioral therapy to help patients reduce or cease their use of alcohol or tobacco. Eighty percent of subjects treated with psilocybin were able to quit smoking, and at 6 months 75% had remained free from tobacco. 

These findings are as fascinating as they are bewildering. Why should these fairly limited-time treatments bring about such enduring changes? Might the effect of the psilocybin be to disrupt overly rigid brain networks that support the behavior of tobacco or alcohol dependence? Is anxiety at the end of life a form of mental rigidity that results in existential distress? Or does the psilocybin bring about a spiritual experience that allows patients to be more at peace with their fate? 

There is much more research that needs to be done, but these findings should compel us to take these drugs seriously and see them as potentially important tools for making enduring change, a far more important use than their reputation as mere intoxicants would imply. 

This research continues to progress. There is a 3 site, phase II study underway looking to replicate the findings that MDMA was an effective adjunct to PTSD psychotherapy. The Multidisciplinary Association for Psychedelics Studies (MAPS.org), which is sponsoring the research, hopes to be given approval by the FDA to begin phase III clinical trials following the publication of ongoing phase II trials. Trials of psilocybin continue at University of Wisconsin, Madison; Johns Hopkins University; and New York University, in addition to Kings College, London and the University of Zurich. 

In my last blog entry in the series, I’ll talk about how we can discuss these findings with our patients, as well as future goals in the research domain. If this topic interests you, I hope you’ll join me in San Diego at the U.S. Psychiatric and Mental Health Congress where I’ll be presenting a talk entitled “Re-imagining a brave new world: Can psychedelics be catalysts for therapy?” 

References 

1. Bedi G et al. Psychopharmacology. 2009;207(1):73-83

2.  Carhart-Harris et al. Biol Psychiatry. 2014. https://dx.doi.org/10.1016/j.biopsych.2013.12.015 

3. Carhart-Harris. Intl J Neuropsychopharm. 2014;(17): 527-540.

4. Mithoefer MC, et al. J Psychopharmacol. 2011;25(4):439-452.

5. Mithoefer MC, et al. J Psychopharmacol. 2013;27(1):28-39. ClinicalTrials.gov Identifier: NCT01211405

6. Griffiths RR, et al. Psychopharmacology. 2006;187(3):268-283.

7. Griffiths RR, et al. Psychopharmacology. 2011;218(4):649-665.

8. Pollan M. The Trip Treatment. The New Yorker. February 9, 2015. ClinicalTrials.gov Identifier: NCT0095735

9. Johnson MW, et al. J Psychopharmacol. 2014;28(11):983-992.

10. Garcia-Romeu A, et al. Curr Drug Abuse Rev. 2014;7(3):157-164.

11. Bogenschutz MP, et al. J Psychopharmacol. 2015;29(3):289-299.

Andrew Penn was trained as an adult nurse practitioner and psychiatric clinical nurse specialist at the University of California, San Francisco. He is board certified as an adult nurse practitioner and psychiatric nurse practitioner by the American Nurses Credentialing Center. Currently, he serves as an Assistant Clinical Professor at the University of California-San Francisco School of Nursing. Mr. Penn is a psychiatric nurse practitioner with Kaiser Permanente in Redwood City, CA, where he provides psychopharmacological treatment for adult patients and specializes in the treatment of affective disorders and PTSD. He is a former board member of the American Psychiatric Nurses Association, California Chapter, and has presented nationally on improving medication adherence, emerging drugs of abuse, treatment-resistant depression, diagnosis and treatment of bipolar disorder, and the art and science of psychopharmacologic practice.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors. Blog entries are not medical advice.