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[[Posttraumatic stress disorder|Post-traumatic stress disorder]] (PTSD) is most commonly treated by [[cognitive behavioral therapy]] (particularly [[Prolonged exposure therapy|prolonged exposure]] and [[cognitive processing therapy]]), [[eye movement desensitization and reprocessing]], and [[psychodynamic psychotherapy]]. However, over half of these patients continue to suffer from PTSD after completing therapy, with results from military PTSD being especially poor.
[[Posttraumatic stress disorder|Post-traumatic stress disorder]] (PTSD) is most commonly treated by [[cognitive behavioral therapy]] (particularly [[Prolonged exposure therapy|prolonged exposure]] and [[cognitive processing therapy]]), [[eye movement desensitization and reprocessing]], and [[psychodynamic psychotherapy]]. However, over half of these patients continue to suffer from PTSD after completing therapy, with results from military PTSD being especially poor.


PTSD is best treated when a patient is in the ‘optimal arousal zone’. This is the zone in which emotions are engaged, yet not overwhelming. In this zone, the three key symptoms of PTSD are sedated.<ref name=":4">{{Cite journal|last=Hutchinson|first=Courtney | name-list-style =vanc |date=2018|title=MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder: Implications for Social Work Practice and Research|journal=Clinical Social Work Journal|volume=25|issue=4 |pages=421–430|doi=10.1007/s10615-018-0676-3|s2cid=150130179 }}</ref> These are:
PTSD is best treated when a patient is in the ‘optimal arousal zone’. This is the zone in which emotions are engaged, yet not overwhelming. In this zone, four symptom clusters of PTSD are sedated:<ref name=":4">{{cite journal| author=Morgan L| title=MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn't. | journal=Ann Gen Psychiatry | year= 2020 | volume= 19 | issue= | pages= 33 | pmid=32435270 | doi=10.1186/s12991-020-00283-6 | pmc=7218633 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32435270 }}</ref> These are:


1. &nbsp; &nbsp;Hyper-arousal: hyper-vigilance, insomnia, and aggression
1. &nbsp; &nbsp;re-experiencing,


2. &nbsp; &nbsp;Intrusion: flashbacks and nightmares
2. &nbsp; &nbsp;avoidance,


3. &nbsp; &nbsp;negative alterations in cognition/mood
3. &nbsp; &nbsp;Avoidance: avoiding all trauma-related stimuli and social withdrawal <ref name=":4" />

4. &nbsp; &nbsp;alterations in arousal and reactivity


Subjects with PTSD exhibit extreme emotional numbing or anxiety and struggle to remain in the optimal arousal zone during conservative therapies. Threatening interpretations of memories are reinforced when patients are in low emotional states.<ref name=":10">{{cite journal | vauthors = Thal SB, Lommen MJ | title = Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder | journal = Journal of Contemporary Psychotherapy | volume = 48 | issue = 2 | pages = 99–108 | date = 2018 | pmid = 29720767 | pmc = 5917000 | doi = 10.1007/s10879-017-9379-2 }}</ref> If traumatic memories are revisited in therapy when a patient is not within the optimal arousal state, therapy for PTSD can actually increase the patient's trauma.<ref name=":10" />
Subjects with PTSD exhibit extreme emotional numbing or anxiety and struggle to remain in the optimal arousal zone during conservative therapies. Threatening interpretations of memories are reinforced when patients are in low emotional states.<ref name=":10">{{cite journal | vauthors = Thal SB, Lommen MJ | title = Current Perspective on MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder | journal = Journal of Contemporary Psychotherapy | volume = 48 | issue = 2 | pages = 99–108 | date = 2018 | pmid = 29720767 | pmc = 5917000 | doi = 10.1007/s10879-017-9379-2 }}</ref> If traumatic memories are revisited in therapy when a patient is not within the optimal arousal state, therapy for PTSD can actually increase the patient's trauma.<ref name=":10" />

Revision as of 16:29, 30 December 2021

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MDMA-assisted psychotherapy is the use of prescribed doses of MDMA as an adjunct to psychotherapy sessions. The study of MDMA as an enhancer for psychotherapy has been constrained since 1985 when the drug was classified in the United States as a Schedule I controlled substance. Research by the Multidisciplinary Association for Psychedelic Studies (MAPS) has provided evidence that MDMA can help address trauma-related disease, in particular post-traumatic stress disorder. In 2017, a Phase II clinical trial led to a designation of breakthrough therapy status by the US Food and Drug Administration (FDA).[1][2]

The research is controversial due to the risks of taking MDMA recreationally, made evident by the illegal and unregulated use of MDMA in the form of ecstasy[3] and also due to its unpredictable neurochemical effects.[4][5] There were 92 MDMA related deaths in England and Wales in 2018, up from 56 the year before,[6] and 10,000 hospitalizations for MDMA related illness/injury in 2011 in the US.[3] However no such cases have been observed in clinical settings. Systematic reviews of a few trials with a small number of patients indicated that MDMA appeared to be potentially safe and effective in controlled clinical use.[7][8][9]

The use of psychedelics for therapy has been characterized as 'countercultural' in Western cultures.[10]

Post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is most commonly treated by cognitive behavioral therapy (particularly prolonged exposure and cognitive processing therapy), eye movement desensitization and reprocessing, and psychodynamic psychotherapy. However, over half of these patients continue to suffer from PTSD after completing therapy, with results from military PTSD being especially poor.

PTSD is best treated when a patient is in the ‘optimal arousal zone’. This is the zone in which emotions are engaged, yet not overwhelming. In this zone, four symptom clusters of PTSD are sedated:[11] These are:

1.    re-experiencing,

2.    avoidance,

3.    negative alterations in cognition/mood

4.    alterations in arousal and reactivity

Subjects with PTSD exhibit extreme emotional numbing or anxiety and struggle to remain in the optimal arousal zone during conservative therapies. Threatening interpretations of memories are reinforced when patients are in low emotional states.[12] If traumatic memories are revisited in therapy when a patient is not within the optimal arousal state, therapy for PTSD can actually increase the patient's trauma.[12]

When used in therapy MDMA has been reported to increase empathy, closeness between patient and therapist, relaxation, motivation to engage with therapy and introspective thought, and to reduce depression and anxiety.[13] MDMA makes it easier for a patient to stay in the optimal arousal zone by decreasing feelings of anxiety and defensiveness when revisiting traumatic memories.[11] It also increases feelings of closeness and empathy, improving the patient's trust in the therapist, and encourages introspective thought to reassess memories and actions.[13] These factors may increase the success rate of psychotherapy. With the approval of the FDA in 2017, MDMA has been cleared for the use in assisting with psychotherapy.[14] A phase 3 study indicated that MDMA-assisted therapy represents a potential breakthrough treatment for severe PTSD that merits expedited clinical evaluation.[15] However, given the lack of blinding, several researchers have postulated that the results of the phase 3 trial might be heavily influenced by expectancy effects,[16][17] and there are no trials comparing MDMA-assisted psychotherapy to already existing first-line psychological treatments for PTSD, which based on indirect evidence seems to attain similar or elevated symptom reduction compared with that due to MDMA-assisted psychotherapy.[18] Further research in 14 study site across the United States and Canada has shown that manualized MDMA-assisted psychotherapy had high adherence rates from therapists and was successful at reducing PTSD symptoms in patients. This gives evidence that MDMA-assisted psychotherapy as a treatment modality is reproducible across different settings and effective at reducing PTSD symptoms.[19]

Side effects, which can last from a few hours to several days, include impaired balance, depression, fatigue, low mood, headache, nausea, loss of appetite, tightness and feeling cold.

Rationale for MDMA treatment

PTSD inhibits a subject's ability to respond appropriately to trauma-related stimuli.[11] The current model of PTSD proposes that it results from amplified and uncontrolled responses from the amygdala to trauma-specific cues.[20] Treatment with MDMA has been shown to reduce blood flow to the amygdala, while increasing blood flow to the occipital cortex and ventromedial prefrontal cortex. This state reduces fear while enhances consciousness.[21] MDMA also increases levels of the hormones serotonin, oxytocin, prolactin, and cortisol.[22] Neurochemically, MDMA activates 5-hydroxytryptamine, or 5-HT serotonin receptors, specifically at the 5-HT1A and 5-HT1B G-protein coupled receptors.[23] Additionally, the effect of MDMA on alpha-2 receptors is potentially believed to contribute to an effect in humans that paradoxically works to increase sedation and relaxation, which is further hypothesized to be conducive in the addressing trauma-induced hypervigilance.[24][25] Serotonin helps to regulate mood,[26] while oxytocin has been found to increase trust and emotional awareness and reduce amygdala response. It has been proposed that these effects foster memory reconsolidation by allowing the patient to access the traumatic memory while feeling detached from the sense of imminent threat.[12]

Procedure

In current studies of MDMA therapy a 125 mg capsule of MDMA is orally administered. The subject is monitored, listens to emotionally provocative music, and engages in conversation with the therapist. After 2 hours, a supplemental 62.5 mg dose of MDMA is administered orally. The therapist works with the patient for 6 hours, or until the psychedelic effects of the drug have worn off. Therapists encourage the patients to reach their own introspective conclusions, punctuated by discussion and collective reconsolidation of the memory.[12] The patient stays in the clinic overnight to be monitored.

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

Breakthrough therapy designation

In 2017, the treatment was granted breakthrough therapy status by the FDA, a designation that indicates that there is preliminary evidence that an intervention offers a substantial improvement over other options for a serious health condition.[2] Whether MDMA-assisted psychotherapy for PTSD represents a real, and not only by designation, treatment breakthrough for PTSD has been questioned.[18]

Social anxiety disorder

Researchers at the Los Angeles BioMedical Research Institute reported a study of MDMA-assisted psychotherapy for autistic adults with social anxiety disorder in 2018.[27] The goal of the study was to explore the feasibility of treating the patients' social anxiety with MDMA-assisted therapy, rather than to reduce atypical responses associated with autism. The study used the same procedure as the MDMA-assisted psychotherapy treatment for PTSD. The study also included mindfulness therapies, and was held in a room that included natural elements (e.g. fresh flowers), fidget objects, and other items that are helpful for many autistic adults.[27] Enrollment 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'.[27] This study compared the MDMA group with a placebo group. The MDMA group's reduction in anxiety was considerably greater than that for the placebo group, and was retained at 6-month follow up sessions. Side effects of anxiety, difficulty in concentrating, headache, fatigue and depression were noted, however.[27]

Alcohol Use Disorder

There is currently an ongoing study at Bristol Imperial that is using MDMA assisted psychotherapy for people dealing with Alcohol Use Disorder. The study has two MDMA assisted psychotherapy sessions for the estimated 20 participants. The participants in the study are given 125 mg of MDMA as an initial dose and a 62.5 mg booster two hours later. The participants in the clinical trial are patients with alcohol use disorder post-detoxification. The study's estimated date of completion is June 12, 2020.[28] 2019 interim results of a study of four participants found that two participants completely stopped drinking alcohol and two participants each had just one low alcohol use incidents. None of the four used alcohol harmfully between the study and the follow up period.[29]

The study includes quotations from the four anonymous patients:[29]

"Participant 1: It’s not about the drinking, the MDMA healed me inside and the drinking looks after itself … I’m seeing things anew, nature for the first time … I’m in control of my decisions, I’ve got control back … Life is just good!

Participant 2: I’m pleased I’ve managed to get through both the MDMA sessions … The overall package (of the MDMA therapy course) has been put together well … I went into it expecting to feel strange … It’s called Ecstasy, but it was not an ecstatic feeling … (This course) is definitely a work in progress … I’m able to identify better when I am dealing with my feelings and when I’m doing things well … Its going to take quite a while to get fully better … I don’t know how much of the changes I’ve made are due to the MDMA or due to the (non-drug) psychotherapy sessions.

Participant 3: Better than other treatments, including inpatient detox … I enjoyed every moment of it. Thrilled to be part of the study … I feel energised … The treatment has worked for me, done me a lot of good. I’ve got a lot of confidence out of it. I’m calmer … It’s given me what I wanted; to be cured, to not have the cravings, to look at life differently. I’m not so angry at everything … Being under MDMA was beautiful. It showed me the real me; the me without alcohol.

Participant 4: A weight has been lifted off my shoulders. I haven’t felt like that for a long time. There are no nagging doubts. I’m getting my life back on track … Everything is so much clearer. It’s like a smog has been removed. I can see myself moving forward … It makes me think: why was I drinking that rubbish? I was just being stupid, idiotic, killing myself. There’s no reason to be doing that … Taking part in this study has helped me focus more on life and my goals … An uplifting experience that I would recommend to anyone."[29]

Other research

MDMA has been proposed as an adjunct for other psychiatric disorders. For example, MDMA-assisted psychotherapy has been tested in a pilot study of anxiety related to advanced stage cancer.[30] This study was terminated due to lack of funding and insufficient patient enrollment. Recreational users have published personal testimonies recounting positive body image experiences both during and following their use of MDMA,[31] and MDMA-assisted psychotherapy has been proposed as a potential treatment for eating disorders.[32]

MDMA molecular structure

Society and culture

Legality

MDMA was first synthesized by German pharmaceutical company Merck KGaA in the early 1900s as an intermediate in the synthesis of another compound.[26] Its psychedelic effects were not noted until the early 1960s.[20] In the 1960s and 1970s, the drug was used in psychotherapy, although it was not an approved drug and no clinical trials had been performed. The drug was studied in Switzerland for use in individual, couple, and group therapies until 1993.[33]

In 1985, MDMA was given Schedule I status in the United States due to its high potential for abuse, and most research was stopped.[11][34] Researchers interested in MDMA for use in psychotherapy founded and funded the Multidisciplinary Association for Psychedelic Studies (MAPS) in response. The US Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA) granted approval for researching MDMA's efficacy as an adjunct to psychotherapy in 2004, and the first trial was carried out in 2011.[11] Recently in January 2020, the FDA approved a MAPS request for an Extended Access Program for MDMA-assisted psychotherapy for people with PTSD.[35]

Controversy

MDMA is unpredictable and produces different responses in different people. The drug causes neurotransmitter activation across the main neural pathways (including serotonin and dopamine, noradrenaline) that can result in large mood swings and changes. The memories that emerge under the influence of MDMA can evoke unwanted emotions.[4] Side effects of MDMA use by recreational users include appetite fluctuations, food cravings, and disordered eating.[4]

Once the effects of MDMA wear off, there is a "period of neurochemical depletion" that invokes anhedonia, lethargy, anger, depression, irritability, brooding, greater everyday stress, altered pain thresholds, changes in sleep, and bad dreams, especially in female participants.[4] The symptoms are thought to be due to depletion of serotonin, as a result of the large release of serotonin triggered by MDMA,[26] and have been called "neurotoxic in terms of causing serotonergic dysfunction".[4]

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.[4] However, MDMA is described as a “self-limiting” drug as the intensity of the positive effects decreases with increased use, while negative effects increase.[26] Dependency rates are low compared to other illicit drugs, at 1% of users.[26]

See also

References

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External links

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