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Evidence Supported Interventions: Psychedelic-Assisted Therapy

Jeanne Porges

Department of Psychology, DePaul University

PSY 358: Applied Psychology

Dr. Susan Tran

May 30, 2021

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Evidence Supported Interventions: Psychedelic-Assisted Therapy

After completing the majority of the spring quarter, many interventions have been

identified that help individuals in regards to their mental health. Some of these interventions may

include psychotherapy, cognitive-behavioral therapy, eye movement desensitization and

reprocessing, etc. One category of intervention that has been largely overlooked in this class has

been Psychedelic-Assisted Therapy. Psychedelic substances have been under Category 1

substances since the war on drugs began, and this has prevented research from being done on

psychedelic substances and their potential. For the last two decades, however, a non-profit

organization called the Multidisciplinary Association for Psychedelic Studies (MAPS) has been

pushing for research to be done on psychedelics, and their research has paved the way for

eventual legalization of these substances. MAPS has been focusing their research efforts

primarily on MDMA-assisted Psychotherapy, but MAPS also has a part in the research of many

other psychedelic-assisted therapies as well. Psychedelic-assisted therapy utilizes psychedelic

substances alongside therapy in order to promote healing in individuals, with a focus on

individuals who have treatment-resistant or chronic illnesses. Evidence shows that not only do

these Psychedelic-Assisted Therapies yield statistically significant results, but they are also

cost-effective as well. MDMA-assisted psychotherapy will be discussed in detail below, in

relation to what it is, how it works, and what the future looks like for psychedelic-assisted

therapy interventions.

First, I will discuss what MDMA-assisted psychotherapy is and what it does. MDMA is

an amphetamine; however it is known to have psychoactive qualities that influence many to

group it into the category of psychedelic substances. MDMA was synthesized in 1912, and

Alexander (Sasha) Shulgin began researching MDMA in 1976 (Benzenhöfer et al., 2010), with
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the intention of introducing the chemical to the field of psychology, but since it was an

unregulated drug, people began to abuse it, which led to its placement under Category 1

substances. Today, MDMA typically goes by the street name “molly” or “ecstasy” and is often

cut with impure and unsafe substances. For the past two decades, MAPS has taken on the

immense goal of legalizing MDMA-assisted psychotherapy, due to the therapeutic value that it

holds. How exactly does this substance work? MDMA is a serotonin agonist, which means it

mimics serotonin (5HT) and binds to serotonin receptors. In addition to being a serotonin

agonist, MDMA also increases serotonin production, dopamine production, and possibly

oxytocin production as well (Department of Health, 2002). This increase in serotonin and

dopamine is what primarily causes individuals to call this substance “ecstasy.” MDMA also

decreases activity in the parasympathetic nervous system, which turns off one’s fight or flight

response and allows individuals to re-experience and reprocess traumatic memories without the

response from the amygdala getting in the way of the processing of trauma (Clark et al., 2015).

Lastly, MDMA increases prosocial behavior (Clark et al., 2015) and openness (Wagner et al.,

2017), which can also help individuals to process trauma.

Now that I have discussed what MDMA is and what it does, it is important to examine

MAPS’ research on MDMA-Assisted Psychotherapy and what their studies yield. MAPS’

research on MDMA-Assisted Psychotherapy includes three phases of research, but due to the

first phase only determining the safety of MDMA as a therapeutic drug, I will be focusing

primarily on phase two and phase three trials, which used experimental methods in order to test

the effectiveness of this intervention. Phase two trials involved six double-blind, controlled

clinical trials (Mithoefer, et al., 2019). All participants were veterans with treatment-resistant

PTSD and in order to determine if they qualified, each participant completed the Clinician
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Administered PTSD Scale (CAPS-IV), which is a clinical test to determine if an individual fits

DSM-IV criteria for PTSD. Phase two trials used the DSM-IV throughout all trials in order to be

consistent, due to the fact that trials started in 2001, before the DSM-V was published. During

each phase two trial, a control group was given a placebo (0-40 mg of MDMA) during three

MDMA-assisted psychotherapy sessions. The experimental group was given between 75-125 mg

of MDMA during three MDMA-assisted psychotherapy sessions (Mithoefer, et al., 2019). In

addition, both groups underwent a pre-screening session, three prep sessions, and a two-month

followup in order to determine changes in CAPS-IV scores.

Results of the study showed that one to two months post-treatment, depression had

decreased in the active dose group, and 54.2 percent of participants in the active group no longer

fit criteria for PTSD (Mithoefer, et al., 2019). These results suggest that MDMA-assisted

psychotherapy predicts statistically significant changes in CAPS scores, which means that this

intervention has the potential to put PTSD into remission. Strikingly, the within-participant effect

size from pretest to posttest increased from 1.4 to 1.9 after three sessions of MDMA-assisted

psychotherapy and the between-groups effect size was .8 ((Mithoefer, et al., 2019), which

suggests that the changes in the experimental group are clinically and statistically significant.

This study and its results were essential in order to persuade the FDA to permit the start of phase

three trials, which will be discussed in more detail below.

Phase three trials of MDMA-assisted psychotherapy began with the goal of addressing

limitations from phase two trials, determining the most effective active dose of MDMA, and

accurately replicating the results of phase two trials. Phase three trials involve studies done in the

U.S., Canada, and Israel, with a total of 89 participants who were randomized in a

double-blinded procedure (Mitchell et al., 2021). The control group was given a placebo during
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three MDMA-assisted psychotherapy sessions, while the experimental group was given an active

dose which is not specified in the article. Each group also underwent a pre-screening session,

three prep sessions, and a two-month followup- in order to determine changes in CAPS-V scores

which align with the DSM-V, differing from the phase two trials, which tested CAPS-IV scores.

The between-group effect size was .91 and the mean change in CAPS-V scores was -24.4. This

effect size is noteworthy because the effect size of MDMA-assisted psychotherapy is larger than

the effect size of SSRIs like sertraline and paroxetine (Mitchell et al., 2021). This finding

suggests that MDMA-Assisted Psychotherapy is more effective than pharmaceutical

interventions for PTSD.

Ultimately, at the 18-week followup, 67 percent of participants in the experimental group

no longer fit criteria for PTSD and five percent of the experimental group met criteria for

remission (Mitchell et al., 2021). In addition, the active dose reduced clinician-rated function

impairment and the intervention was similar in effectiveness for those with the dissociative

subtype of PTSD (Mitchell et al., 2021). These results suggest that MDMA-Assisted

Psychotherapy is an effective treatment for treatment-resistant and dissociative PTSD. The

results also suggest that the changes in CAPS-V scores are statistically and clinically significant.

Further research needs to be done with participants who do not have treatment-resistant PTSD to

test for any changes between the two populations. In addition, further research and replications

are needed to support the effectiveness of this intervention and promote legalization by the FDA.

After examining phase two and phase three trials of MDMA-Assisted Psychotherapy, it is

important to discuss the future of psychedelic-assisted therapies. As stated previously,

MDMA-assisted Psychotherapy is a statistically significant intervention and the results not only

suggest that this intervention has the potential to cause PTSD to go into remission, but this
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intervention may be more effective than drug therapies like SSRIs as well. These results are

being used to support the legalization of MDMA-Assisted Psychotherapy, and if the extended

phase three trials yield strong results, the FDA is expected to legalize the intervention by 2023.

MDMA-Assisted Psychotherapy would be the first psychedelic therapy to be federally

legalized in the United States, and the implications for such an event are huge. Although Oregon

has legalized psilocybin-assisted psychotherapy and DC has decriminalized all psychedelics,

there has not been any action taken on a federal level. Legalizing a psychedelic substance for

therapeutic use on a federal level will set a new precedent for treatment options in the medical

field and psychology field, but most importantly, the legalization will set a precedent for future

legalization of psychedelic substances, both on a medical scale and recreational scale.

MDMA-Assisted Psychotherapy is just one intervention, and there are many other

Psychedelic-Assisted Therapies that hold statistical and clinical value as well. The legalization of

MDMA-Assisted Therapy is ultimately essential to shifting the paradigm of how mental health is

perceived and treated, and MAPS’s research has been a fundamental part of this paradigm shift.

Future research will benefit from exploring short-term versus long-term effects of psychedelic

substances, the effects of microdosing psychedelic substances on mental health, and the spiritual

versus mental health benefits of psychedelic substances.

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References

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https://doi.org/10.1111/j.1360-0443.2010.02948.x

Clark, C. M., Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2015). Acute effects of

MDMA on autonomic cardiac activity and their relation to subjective prosocial and

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Yazar-Klosinski, B., & Doblin, R. (2017). Therapeutic effect of increased openness:

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