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MDMA-Assisted Psychotherapy

MDMA
INN: Midomafetamine[1]
MDMA structure
Ball-and-stick model of an MDMA molecule
Legal status
Legal status
  (verify)

PTSD [2]
.

Used in therapy, MDMA increases empathy, closeness between patient and therapist, relaxation, motivation to engage with therapy, and introspective thought [4]. Simultaneously it reduces depression and anxiety [4]. Side effects of the treatment include impaired balance, fatigue, low mood, headache, nausea, loss of appetite, tightness and feeling cold [3]. The side effects can last from a few hours to several days [3]. Of the 780 subjects who have participated in MDMA psychotherapy trials, one has had a serious adverse effect [5].

The study is controversial due to the risks made of taking MDMA, made evident by the illegal use of MDMA in the form of ecstasy [5]. It has been noted in the media that there were 50 MDMA related deaths in the UK in 2014, and 10,000 hospitalisations for MDMA related illness/injury in 2011 in the US [5]. The use of psychedelics has been characterised as ‘countercultural’ in Western cultures [6].

PTSD Treatment

PTSD is most commonly treated by cognitive behavioural therapy (particularly Prolonged Exposure and Cognitive Processing Therapy), Eye Movement Desensitisation and Reprocessing, and psychodynamic psychotherapy [3]. However, following therapy, up to 58% of patients retain PTSD diagnosis after completing the therapy [7]. This figure rises to 72% of amongst veterans who participate in eye movement desensitisation and reprocessing therapy [8]. There are 22 potential psychoactive agents currently studied for treatment of PTSD, however no conclusive evidence was found to support their ability to alleviate PTSD symptoms [8].

PTSD is best treated when a patient is in the ‘optimal arousal zone’. This is the zone in which emotions are engaged, with yet are not overwhelming [3]. The three key symptoms of PTSD are sedated in the 'optimal arousal zone' [8]. These are:

1.    Hyper arousal: hyper vigilance, insomnia and aggression

2.    Intrusion: flashbacks and nightmares

3.    Avoidance: avoiding all trauma related stimuli and social withdrawal [8]

Subjects with PTSD exhibit extreme emotional numbing or anxiety, thus struggle to remain in this zone during conservative therapies [3]. Threatening interpretations of memories are reinforced when patients are in low emotional states [9]. If traumatic memories are revisited in therapy when a patient is not within the optimal arousal state, therapy for PTSD can harm a patient more than it does support them [9].

MDMA increases the size of the optimal arousal zone by decreasing feelings of anxiety and defensiveness when engaging with traumatic memories [8] . Feelings of closeness and empathy are simultaneously increased, producing greater patient to therapist trust [4] . MDMA also promotes motivation to engage in therapy, and introspective thought to reassess memories and actions [4] . Studies are showing that these factors increase the success rate of PTSD treatment. 83% of subjects in a Phase II clinical trial testing of MDMA assisted psychotherapy were no longer diagnosed with PTSD after MDMA psychotherapy. In contrast, a group undergoing the same psychotherapy with a placebo dose of MDMA had a 25% success rate.[2]

Psychology of MDMA assisted Psychotherapy for PTSD

Post Traumatic Stress Disorder inhibits a subject’s ability to rationally respond to trauma-related stimuli [8]. Traumatic experience transforms into PTSD when a subject’s amygdala responds in an amplified and uncontrolled manner to trauma-specific cues [7]. The amygdala is not effectively modulated by the ventromedial prefrontal cortex, the hippocampus and the orbitofrontal cortex; thus altering a subject’s response to trauma-specific cues [7].

MDMA places subjects in the Optimal Arousal Zone for treatment of PTSD by reducing blood flow to the amygdala, whilst increasing blood flow to the occipital cortex and ventromedial frontal cortex [3]. This state reduces fear, yet increases consciousness [10]. The drug also increases the hormones serotonin, oxytocin, prolactin, and cortisol [11]. Oxytocin has been found to increase trust and emotional awareness, whilst reducing amygdala response [3].


As the patient’s consciousness is not inhibited by MDMA, new neural pathways can be built while under the influence of the drug [10]. The enhanced activity in the frontal cortex allows traumatic memories to be recreated in a new context, dissociated from fear tags (due to the sedation at the amygdala) [10]. This process of memory reconsolidation remains after the psychedelic affects of the MDMA has warn off [9].

Procedure

The procedure followed by current studies for MDMA therapy is an oral administration of 125mg of MDMA, in the form of a capsule [3]. The subject is monitored, listens to emotionally provocative music, and engages in conversation with the therapist [3]. After 2 hours, a subsequent 62.5mg of MDMA is administered via an oral capsule [3]. The therapist engages in psychotherapy with the patient for 6 hours, or until the psychedelic affects of the drug have warn off [3].  The psychotherapy is patient driven - the therapists encourage the patients to reach their own introspective conclusions, punctuated by discussion and collective reconsolidation of the memory [9]. The patient stays in the clinic overnight [3] .

The following morning, the patient and therapist have an integration session where they discuss the experimental session and process emotions [3]. Three 90-minute integration sessions are held in the subsequent month [3]. This process is repeated two or three times [3].

MDMA-Assisted Psychotherapy for Social Anxiety Disorder in Autistic Adults

A 2018 study approved by Los Angeles BioMedical Research Institute investigated MDMA-assisted psychotherapy for autistic adults with social anxiety disorder[12]. The study was to treat the patients' social anxiety, not reduce atypical responses associated with autism. The autistic population was targeted as they were seen by the researchers as an "underserved population"[12] . The study utilised the same procedure as the MDMA-psychotherapy treatment for PTSD. All of the patients took the subsequent 62.5mg of MDMA two hours after the initial treatment [12]. In addition to the PTSD treatment procedure, the study included mindfulness therapies (as these research has shown autistic adults feel more comfortable after mindfulness exercises) [12]. The procedure was held in a room that included elements of the environment, gidget objects, and other items of preference to many autistic adults [12]. Enrolment in the study was contingent on a score of more than 60 on the Liebowitz Social Anxiety Scale - a score that indicates difficulties functioning socially and distress.[12]

The results showed that the MDMA group had a stronger reduction in Liebowitz Social Anxiety Scale score than a placebo group [12]. The durability of improvements in social anxiety were affirmed, as reductions in the LSAS score were sustained at 6-month follow up sessions [12]. Side effects were present in the days following the study:

  • Anxiety: 75% in MDMA, 25% in placebo
  • Difficulty concentrating: 62.5% in MDMA, 25% in placebo
  • Headache and fatigue: 50% in MDMA, 0-25% in placebo
  • Depressed mood: 25% in MDMA, 0% in placebo

Society and Culture

Legality

MDMA was first synthesised by German pharmaceutical company Merck KGaA in 1914 with the purpose to control bleeding [3]. It's psychadellic affects were not noted until the early 1960s [7]. In the 1960s and 1970s, the drug was used in psychotherapy - however was not an approved drug, and had no clinical trials [13]. Up until 1993, the drug was being studied in Switzerland for use in individual, couple, and group therapies [14].

In 1985, the psychadellic was criminalised under schedule I status in the United States for high potential for abuse [8]. In response to this ruling, researchers who had been interested in MDMA for use in psychotherapy founded and funded the Multidisciplinary Association for Psychedelic Studies (MAPS)[2]. FDA and DEA approval for researching MDMA’s ability to aid psychotherapy was granted in 2004, and the first trial was carried out in 2011 [8].

The results of the trial were reviewed by the FDA, and the trial was subsequently granted “breakthrough therapy” status. This fast-tracks the approval process so that the drug may be legalised by 2021. For this to successfully happen, a phase III trial must be successful [15]. The phase III trial will involve a sample size of between 200 and 300 patients, in 16 sites across Israel, the United States, and Canada [13].

The terms of the approval of the drug have not been decided on, and questions surrounding what legal MDMA psychotherepy would look like have arisen in scientific and policy fields [16]. In trials, the drug has only been administered in clinics specifically designed for MDMA psychotherapy. Conversations have begun relating to what qualifications physicians will need in order to prescribe and administer the drug, how the drug will be produced and stored, and how to ensure equitable access [17].

Controversy

MDMA is unpredictable and produces different responses in different people [18]. The drug is not selective in which emotions it produces, as it causes neurotransmitter activation across the main neural pathways (which includes serotonin and dopamine, noradrenaline) that can cause large mood swings and changes[18]. The memories that emerge under the influence of MDMA can be confronting for trauma survivors, and unwanted emotions can ensue [18].

Once the affects of MDMA wear off, there is a "period of neurochemical depletion" that invokes anhedonia, lethargy, anger, depression, irritability, brooding, greater every day stress, altered pain thresholds, changes in sleep, and bad dreams [18]. These symptoms were more common and intense in female participants than male [18]. The symptoms are largely due to depleted natural sources of serotonin, contrasting the large release of serotonin whilst under the influence of MDMA [16]. One extreme example is a Special Air Forces soldier who participated in an MDMA psychotherapy session was arrested following his treatment for attacking a stranger. In court, he presented the case that the aggression was a result of the MDMA-assisted psychotherapy [18].

There are also concerns surrounding "drug-dependent learning" - the theory that patients will return to the drug to access the state they were in when on the drug in therapy [18] . However, MDMA MDMA is described as a “self limiting” drug as intensity of the positive effects decreases with increased use, whilst negative effects increase [16]. Dependency rates are therefore low (when compared to other illicit drugs), at 1% of users [16].

Controversy also surrounds the drug's neurotoxicity status, as recent studies have proposed that the "5-HT and SERT-depleting effects of MDMA [are] neurotoxic in terms of causing serotonergic dysfunction"[18]. It is thought to reduce memory and cause neurohormonal and psychobiological changes.

Appetite fluctuations, food cravings, and disordered eating are known affects of ecstasy amongst recreational users [18]. Following MDMA assisted psychotherapy, one patient has reported noticeable changes in appetite and has subsequently struggled to maintain regulated eating [18].

See Also


References


  1. ^ "FDA Substance Registration System". United States National Library of Medicine. Retrieved 31 August 2017.
  2. ^ a b c d "MDMA-Assisted Psychotherapy". MAPS. Retrieved 2019-05-14.
  3. ^ a b c d e f g h i j k l m n o p q Mithoefer, Michael (2010). "The Safety and Efficacy of 3,4 methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study". Journal of Psychopharmacology. 25: 439–452.
  4. ^ a b c d Sessa, Ben (2011). "Could MDMA be useful in the treatment of Post-Traumatic Stress Disorder?". Progress in Neurology and Psychiatry. 15: 4–7.
  5. ^
    ISSN 0261-3077
    . Retrieved 2019-05-14.
  6. ^ Valentish, Jenny (2018-08-30). "The hidden world of underground psychedelic psychotherapy". ABC News. Retrieved 2019-05-14.
  7. ^ a b c d Oehen, Peter (2013). ""A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)". Journal of Psychopharmacology. 27: 40–52.
  8. ^ a b c d e f g h Hutchinson, Courtney (2018). "MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder: Implications for Social Work Practice and Research". Clinical Social Work Journal. 25: 1–10.
  9. ^
    PMID 29720767. {{cite journal}}: Check |pmc= value (help
    )
  10. ^ a b c Sferios, Emmanuel (2018). Dead Dog on the Left. Viveka Films.
  11. ^ Mart, Wagner (2017). "Theraputic Effect of Increased Openness: Investigating Mechanism of Action in MDMA-assisted Psychotherapy". Journal of Psychopharmacology. 31: 967–974.
  12. ^ a b c d e f g h Danforth, Alicia (2018). "Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study". Psychopharmacology. 235: 3137–3148 – via Springer Link.
  13. ^ a b TEDx Talks (2018-04-05), MDMA, Psychotherapy, and the Future of PTSD Treatment | Brad Burge | TEDxSalem, retrieved 2019-05-28
  14. ISSN 1664-0640.{{cite journal}}: CS1 maint: unflagged free DOI (link
    )
  15. ^ KupferschmidtAug. 26, Kai; 2017; Pm, 6:30 (2017-08-24). "All clear for the decisive trial of ecstasy in PTSD patients". Science | AAAS. Retrieved 2019-05-14. {{cite web}}: |last2= has numeric name (help)CS1 maint: numeric names: authors list (link)
  16. ^ a b c d Lee, Nicole. "Weekly Dose: ecstasy, the party drug that could be used to treat PTSD". The Conversation. Retrieved 2019-05-30.
  17. ^ Bedi, Gillinder. "Is psychiatry ready for medical MDMA?". The Conversation. Retrieved 2019-05-30.
  18. ^ a b c d e f g h i j Parrott, Andrew (2014). "The Potential Dangers of Using MDMA in Psychotherapy". Journal of Psychoactive Drugs.
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