MDMA-assisted psychotherapy

{{Short description|Controlled administration of psychoactive drug MDMA to facilitate psychotherapy efficacy}} {{Psychology sidebar}}

'''MDMA-assisted psychotherapy''' ('''MDMA-AT''') is the use of prescribed doses of MDMA as an adjunct to psychotherapy sessions. MDMA-assisted psychotherapy is an effective treatment for post-traumatic stress disorder (PTSD), including complex PTSD (C-PTSD). Furthermore, it is currently under investigation as a treatment for various other mental health disorders, including major depressive disorder, social anxiety in people with autism, alcohol use disorder, and mood disturbances in individuals facing life-threatening illnesses.

== Therapeutic effects == 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 (EMDR), and psychodynamic psychotherapy. However, over half of these patients continue to have PTSD after completing therapy, with results from war-related PTSD being especially poor.<ref>{{Cite journal |last1=Straud |first1=Casey L. |last2=Siev |first2=Jedidiah |last3=Messer |first3=Stephen |last4=Zalta |first4=Alyson K. |author-link4=Alyson Zalta |date=Oct 2019 |title=Examining military population and trauma type as moderators of treatment outcome for first-line psychotherapies for PTSD: A meta-analysis |journal=Journal of Anxiety Disorders |volume=67 |article-number=102133 |doi=10.1016/j.janxdis.2019.102133 |issn=1873-7897 |pmc=6739153 |pmid=31472332}}</ref>

PTSD is best treated when a patient is in the 'optimal arousal zone', in which emotions are engaged, yet not overwhelming. In this zone, four symptom clusters of PTSD are sedated:<ref name=":4">{{cite journal | vauthors = Morgan L | title = MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn't | journal = Annals of General Psychiatry | volume = 19 | issue = | page = 33 | year = 2020 | pmid = 32435270 | pmc = 7218633 | doi = 10.1186/s12991-020-00283-6 | doi-access = free }}</ref>

# re-experiencing # avoidance # negative alterations in cognition/mood # 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" />

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 reduce depression and anxiety. 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.<ref name=":4" /> By increasing feelings of closeness and empathy, it can improve the patient's trust in the therapist and encourage introspective thought to reassess memories and actions. Furthermore, research suggests that treatment may improve the quality of sleep of individuals affected by PTSD-related sleep disturbances.<ref>{{Cite journal |last1=Ponte |first1=Linnae |last2=Jerome |first2=Lisa |last3=Hamilton |first3=Scott |last4=Mithoefer |first4=Michael C. |last5=Yazar-Klosinski |first5=Berra B. |last6=Vermetten |first6=Eric |last7=Feduccia |first7=Allison A. |date=August 2021 |title=Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder |journal=Journal of Traumatic Stress |language=en |volume=34 |issue=4 |pages=851–863 |doi=10.1002/jts.22696 |issn=0894-9867 |pmc=8453707 |pmid=34114250}}</ref> It is believed that these factors may increase the success rate of psychotherapy.

Adverse effects, which can last from a few hours to several days, include diminished appetite, anxiety, headache, jaw tightness, tinnitus, nausea, asthenia (weakness), fatigue, sinusitis, nasopharyngitis, upper respiratory tract infection, disturbance in attention, tremor, tics, dysuria, erythema, and depression.<ref name="pmid34150406">{{cite journal | vauthors = Tedesco S, Gajaram G, Chida S, Ahmad A, Pentak M, Kelada M, Lewis L, Krishnan D, Tran C, Soetan OT, Mukona LT, Jolayemi A | display-authors = 6 | title = The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis | journal = Cureus | volume = 13 | issue = 5 | article-number = e15070 | date = May 2021 | pmid = 34150406 | pmc = 8207489 | doi = 10.7759/cureus.15070 | doi-access = free }}</ref>

== Research == In 2017, a Phase II clinical trial led to a breakthrough therapy designation by the U.S. Food and Drug Administration (FDA).<ref name="pmid29248945">{{cite journal | vauthors = Pitts EG, Curry DW, Hampshire KN, Young MB, Howell LL | title = (±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA | journal = Psychopharmacology | volume = 235 | issue = 2 | pages = 377–392 | date = February 2018 | pmid = 29248945 | pmc = | doi = 10.1007/s00213-017-4812-5 | s2cid = 3343930 }}</ref><ref name=":7">{{Cite web |title=FDA Designates MDMA As 'Breakthrough Therapy' For Post-Traumatic Stress |url=https://www.forbes.com/sites/janetwburns/2017/08/28/fda-designates-mdma-as-breakthrough-therapy-for-post-traumatic-stress/ |access-date=2019-07-19 |website=Forbes |language=en |vauthors=Burns J}}</ref> With that FDA approval, MDMA has been authorized for use in research related to psychotherapy.<ref name="pmid29248945" /> A large proportion of this research has been focused on treating PTSD and major depressive disorder.

The research is controversial<ref name=":9" /><ref name=":4" /> in part because recreational MDMA use has been associated with harmful effects among some users.<ref name=":3">{{Cite news|url=https://www.theguardian.com/society/2016/sep/16/mdma-ptsd-therapy-trauma-maps-medical-study|title='My therapist gave me a pill': can MDMA help cure trauma?| vauthors = Solon O |date=2016-09-16|work=The Guardian|access-date=2019-05-14|language=en-GB|issn=0261-3077}}</ref><ref name=":9" /><ref name="pmid18047478">{{cite journal | vauthors = Karlsen SN, Spigset O, Slørdal L | title = The dark side of ecstasy: neuropsychiatric symptoms after exposure to 3,4-methylenedioxymethamphetamine | journal = Basic & Clinical Pharmacology & Toxicology | volume = 102 | issue = 1 | pages = 15–24 | date = January 2008 | pmid = 18047478 | pmc = | doi = 10.1111/j.1742-7843.2007.00159.x }}</ref> A 2022 systematic review and meta-analysis found that MDMA-assisted psychotherapy reduced PTSD symptom severity compared to control conditions.<ref>{{Cite journal |last=Smith |first=Kimberly W. |last2=Sicignano |first2=Dakota J. |last3=Hernandez |first3=Adrian V. |last4=White |first4=C. Michael |date=April 2022 |title=MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis |url=https://pubmed.ncbi.nlm.nih.gov/34708874 |journal=Journal of Clinical Pharmacology |volume=62 |issue=4 |pages=463–471 |doi=10.1002/jcph.1995 |issn=1552-4604 |pmid=34708874}}</ref> <ref>{{cite journal | last1 = Smith | first1 = K. W. | title = MDMA-assisted psychotherapy for treatment of post-traumatic stress disorder: A systematic review with meta-analysis | journal = Journal of Clinical Psychopharmacology | year = 2022 }}</ref>

=== PTSD === Multiple 2020 and 2021 systematic reviews found MDMA-assisted psychotherapy to be an effective treatment for PTSD, more than any other pharmacological-assisted psychotherapy.<ref name="EJP2021">{{cite journal | first1= Mathew D |last1=Hoskins |first2=Robert |last2=Sinnerton |first3=Anna |last3=Nakamura |first4=Jack F G |last4=Underwood |first5=Alan |last5=Slater |first6=Catrin |last6=Lewis |first7=Neil P |last7=Roberts |first8=Jonathan I |last8=Bisson |first9=Matthew |last9=Lee |first10=Liam |last10=Clarke | title = Pharmacological-assisted Psychotherapy for Post Traumatic Stress Disorder: a systematic review and meta-analysis | journal = Eur J Psychotraumatol. | volume = 12 | issue = 1 | date = 15 January 2021 | article-number = 1853379 | pmid = 33680344 | pmc = 7874936 | doi = 10.1080/20008198.2020.1853379 }}</ref><ref>{{cite journal | vauthors = Bahji A, Forsyth A, Groll D, Hawken ER | title = Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 96 | article-number = 109735 | date = January 2020 | pmid = 31437480 | doi = 10.1016/j.pnpbp.2019.109735 | s2cid = 201069918 }}</ref><ref>{{cite journal | vauthors = Smith KW, Sicignano DJ, Hernandez AV, White CM | title = MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis | journal = Journal of Clinical Pharmacology | date = October 2021 | volume = 62 | issue = 4 | pages = 463–471 | pmid = 34708874 | doi = 10.1002/jcph.1995 | s2cid = 240072663 }}</ref><ref>{{cite journal | vauthors = Illingworth BJ, Lewis DJ, Lambarth AT, Stocking K, Duffy JM, Jelen LA, Rucker JJ | title = A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis | journal = Journal of Psychopharmacology | volume = 35 | issue = 5 | pages = 501–511 | date = May 2021 | pmid = 33345689 | doi = 10.1177/0269881120965915 | s2cid = 229341150 }}</ref>

Published later in 2021, a phase III study indicated that MDMA-assisted therapy represents a potential breakthrough treatment for severe PTSD that merits expedited clinical evaluation.<ref>{{cite journal |display-authors=6 |vauthors=Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora GM, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R |date=June 2021 |title=MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study |journal=Nature Medicine |volume=27 |issue=6 |pages=1025–1033 |doi=10.1038/s41591-021-01336-3 |pmc=8205851 |pmid=33972795 |doi-access=free}}</ref> Based on this study, MDMA-assisted psychotherapy was granted breakthrough therapy designation by the FDA, a designation that indicates that there is preliminary evidence that an intervention might offer a substantial improvement over other options for a serious health condition.<ref name=":7" /> However, given the lack of blinding, several researchers have postulated that the results of the phase III trial might be heavily influenced by expectancy effects.<ref>{{cite journal |vauthors=Burke MJ, Blumberger DM |date=October 2021 |title=Caution at psychiatry's psychedelic frontier |journal=Nature Medicine |volume=27 |issue=10 |pages=1687–1688 |doi=10.1038/s41591-021-01524-1 |pmid=34635858 |s2cid=238635462}}</ref><ref>{{cite journal |vauthors=Muthukumaraswamy SD, Forsyth A, Lumley T |date=September 2021 |title=Blinding and expectancy confounds in psychedelic randomized controlled trials |journal=Expert Review of Clinical Pharmacology |volume=14 |issue=9 |pages=1133–1152 |doi=10.1080/17512433.2021.1933434 |issn=1751-2433 |pmid=34038314 |s2cid=235215630}}</ref> There are no trials comparing MDMA-assisted psychotherapy to already existing first-line psychological treatments for PTSD which seems to attain similar or elevated symptom reduction compared with that due to MDMA-assisted psychotherapy based on indirect evidence.<ref name="Halvorsen 1689–1690">{{cite journal |vauthors=Halvorsen JØ, Naudet F, Cristea IA |date=October 2021 |title=Challenges with benchmarking of MDMA-assisted psychotherapy |url=https://hal.archives-ouvertes.fr/hal-03414583/file/Halvorsen%20et%20al%20-%202021%20-%20Challenges%20with%20benchmarking%20of%20MDMA-assisted%20psychotherapy.pdf |journal=Nature Medicine |volume=27 |issue=10 |pages=1689–1690 |doi=10.1038/s41591-021-01525-0 |pmid=34635857 |s2cid=238636360}}</ref>

=== Major depressive disorder === There have been several studies that investigated MDMA-assisted psychotherapy as a potential treatment for major depressive disorder (MDD). An analysis of six phase II trials showed a trend toward significance, while a phase III trial reported that MDMA-assisted psychotherapy had antidepressant effects. Given that unprocessed trauma is considered a causative factor in some individuals with depression, it has been proposed that the benefit observed in PTSD trials might be applicable to MDD as well.<ref>{{Cite journal |last1=Kvam |first1=Tor-Morten |last2=Goksøyr |first2=Ivar W. |last3=Stewart |first3=Lowan H. |last4=Repantis |first4=Dimitris |last5=Røssberg |first5=Jan Ivar |last6=Andreassen |first6=Ole A. |date=2022 |title=Study protocol for "MDMA-assisted therapy as a treatment for major depressive disorder: A proof of principle study" |journal=Frontiers in Psychiatry |volume=13 |article-number=954388 |doi=10.3389/fpsyt.2022.954388 |issn=1664-0640 |pmc=9645093 |pmid=36386973 |doi-access=free }}</ref>

=== Other === MDMA-assisted psychotherapy is currently under investigation as a treatment for various other mental health disorders, including social anxiety in people with autism, alcohol use disorder, and mood disturbances in individuals facing life-threatening illnesses.<ref name=":0">{{Cite journal |last1=Danforth |first1=Alicia L. |last2=Grob |first2=Charles S. |last3=Struble |first3=Christopher |last4=Feduccia |first4=Allison A. |last5=Walker |first5=Nick |last6=Jerome |first6=Lisa |last7=Yazar-Klosinski |first7=Berra |last8=Emerson |first8=Amy |date=2018-09-08 |title=Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study |journal=Psychopharmacology |volume=235 |issue=11 |pages=3137–3148 |doi=10.1007/s00213-018-5010-9 |issn=0033-3158 |pmc=6208958 |pmid=30196397 |doi-access=free}}</ref><ref name=":1">{{Cite journal |last1=Sessa |first1=Ben |last2=Higbed |first2=Laurie |last3=O'Brien |first3=Steve |last4=Durant |first4=Claire |last5=Sakal |first5=Chloe |last6=Titheradge |first6=Daniel |last7=Williams |first7=Tim M |last8=Rose-Morris |first8=Anna |last9=Brew-Girard |first9=Elsa |last10=Burrows |first10=Sam |last11=Wiseman |first11=Chantelle |last12=Wilson |first12=Sue |last13=Rickard |first13=James |last14=Nutt |first14=David J |date=April 2021 |title=First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder |url=http://journals.sagepub.com/doi/10.1177/0269881121991792 |journal=Journal of Psychopharmacology |language=en |volume=35 |issue=4 |pages=375–383 |doi=10.1177/0269881121991792 |issn=0269-8811 |pmid=33601929 |s2cid=231963534 |hdl-access=free |hdl=1983/c6e45e6e-b556-4a87-827b-6b3f4adfea7c|url-access=subscription }}</ref><ref name=":2">{{Cite journal |last1=Wolfson |first1=Philip E. |last2=Andries |first2=Julane |last3=Feduccia |first3=Allison A. |last4=Jerome |first4=Lisa |last5=Wang |first5=Julie B. |last6=Williams |first6=Emily |last7=Carlin |first7=Shannon C. |last8=Sola |first8=Evan |last9=Hamilton |first9=Scott |last10=Yazar-Klosinski |first10=Berra |last11=Emerson |first11=Amy |last12=Mithoefer |first12=Michael C. |last13=Doblin |first13=Rick |date=2020-11-24 |title=MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study |journal=Scientific Reports |language=en |volume=10 |issue=1 |page=20442 |bibcode=2020NatSR..1020442W |doi=10.1038/s41598-020-75706-1 |issn=2045-2322 |pmc=7686344 |pmid=33235285 |doi-access=free}}</ref> The research is controversial<ref name=":9" /><ref name=":4" /> in part because recreational MDMA use has been associated with harmful effects among some users.<ref name=":3">{{Cite news|url=https://www.theguardian.com/society/2016/sep/16/mdma-ptsd-therapy-trauma-maps-medical-study|title='My therapist gave me a pill': can MDMA help cure trauma?| vauthors = Solon O |date=2016-09-16|work=The Guardian|access-date=2019-05-14|language=en-GB|issn=0261-3077}}</ref><ref name=":9" /><ref name="pmid18047478">{{cite journal | vauthors = Karlsen SN, Spigset O, Slørdal L | title = The dark side of ecstasy: neuropsychiatric symptoms after exposure to 3,4-methylenedioxymethamphetamine | journal = Basic & Clinical Pharmacology & Toxicology | volume = 102 | issue = 1 | pages = 15–24 | date = January 2008 | pmid = 18047478 | pmc = | doi = 10.1111/j.1742-7843.2007.00159.x }}</ref>

== Mechanism of action == thumb|Chemical compound of MDMA PTSD inhibits a subject's ability to respond appropriately to trauma-related stimuli.<ref name=":4" /> The current model of PTSD proposes that it results from amplified and uncontrolled responses from the amygdala to trauma-specific cues.<ref name=":10" /> Oxytocin, which is increased by MDMA, has been found to increase trust and emotional awareness and reduce amygdala responses as well as reduce coupling of the amygdala to brainstem regions associated with autonomic and behavioral characteristics of fear.<ref name="pmid16339042">{{cite journal |display-authors=6 |vauthors=Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A |date=December 2005 |title=Oxytocin modulates neural circuitry for social cognition and fear in humans |journal=The Journal of Neuroscience |volume=25 |issue=49 |pages=11489–11493 |doi=10.1523/JNEUROSCI.3984-05.2005 |pmc=6725903 |pmid=16339042}}</ref><ref name="pmid26408071">{{cite journal |vauthors=Kamilar-Britt P, Bedi G |date=October 2015 |title=The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals |journal=Neuroscience and Biobehavioral Reviews |volume=57 |issue= |pages=433–446 |doi=10.1016/j.neubiorev.2015.08.016 |pmc=4678620 |pmid=26408071}}</ref><ref name="pmid33169032">{{cite journal |vauthors=Gangopadhyay P, Chawla M, Dal Monte O, Chang SW |date=January 2021 |title=Prefrontal-amygdala circuits in social decision-making |journal=Nature Neuroscience |volume=24 |issue=1 |pages=5–18 |doi=10.1038/s41593-020-00738-9 |pmc=7899743 |pmid=33169032}}</ref> 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.<ref name=":10" /> MDMA is believed to create neuroplasticity, which can help break habits associated with OCD and addiction.

== History == thumb|Alexander Shulgin, an American chemist who helped publish the first report on the effects of MDMA in humans MDMA was first synthesized by the German pharmaceutical company Merck KGaA in 1912 as an intermediate in the synthesis of a potential blood clotting medication. Its psychoactive effects were not noted until the early 1960s. In the 1970s and early 1980s, MDMA emerged as a novel psychotherapeutic tool. The medicine demonstrated a unique ability to create feelings of empathy, openness, and reduced fear. These early explorations laid the groundwork for its later use in treating conditions such as post-traumatic stress disorder (PTSD).<ref>Imperial College</ref>Alexander Shulgin, an American chemist, synthesized MDMA to investigate its properties and was responsible for introducing the compound to a small number of American psychiatrists in the early 1970s. Shuglin and another chemist, David E. Nichols, are credited with publishing the first report regarding the effects and pharmacology of MDMA in humans.<ref name=":52">{{cite journal |vauthors=Sessa B, Higbed L, Nutt D |date=2019 |title=A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy |journal=Frontiers in Psychiatry |language=English |volume=10 |page=138 |doi=10.3389/fpsyt.2019.00138 |pmc=6435835 |pmid=30949077 |doi-access=free}}</ref>

Psychotherapists using MDMA for therapeutic purposes initially desired to keep its use within the clinical research community; however, the medication gained popularity in the club scene in the early 1980s. This eventually led to the drug being classified as a Schedule I controlled substance by the U.S. Drug Enforcement Administration (DEA) in 1986. The scheduling of MDMA made it illegal to manufacture, possess, or distribute, essentially ending the practice of MDMA-assisted psychotherapy in the United States. Despite this, MDMA continued to be used recreationally in the club and rave scene.<ref name=":52"/>

Switzerland continued to study the drug for use in individual, couple, and group therapies until 1993, when the Swiss Ministry of Health withdrew permission to use MDMA and LSD by psychiatrists due to concerns about a lack of research methodology. Over 100 patients in Switzerland with a variety of mental illnesses were treated with MDMA-assisted psychotherapy during this time frame.<ref name=":52"/>

== Legality == In 1986, MDMA was classed as a Schedule I drug by the United Nations according to its Convention on Psychotropic Substances of 1971 due to increasing rates of non-clinical use and police seizures, along with its high potential for abuse.<ref name=":4" /><ref name=":52"/> MDMA has remained a Schedule I substance since 1986, and most research was stopped at that time. In response to this, researchers interested in MDMA for use in psychotherapy founded and funded the U.S.-based non-profit research organization, Multidisciplinary Association for Psychedelic Studies (MAPS).<ref name=":52"/> MAPS is now one of the leading organizations funding research on psychedelic and controlled substances.

=== Current legal status === The United States FDA and DEA granted approval for researching MDMA's efficacy as an adjunct to psychotherapy in 2004, and the first trial was carried out in 2011.<ref name=":4" /><ref name=":6" /> In 2023, MAPS announced that it is compiling data from 18 different phase II and phase III studies with plans to file a New Drug Application with the FDA. MAPS hopes to receive FDA approval by the end of 2024.<ref name=":6">{{Cite web |last=Colliver |first=Victoria |date=2023-09-18 |title=MDMA's Latest Trial Results Offer Hope for Patients with PTSD |url=https://www.ucsf.edu/news/2023/09/426116/mdmas-latest-trial-results-offer-hope-for-patients-ptsd |access-date=2023-11-06 |website=UC San Francisco |language=en}}</ref>

In July 2023, Australia became the first country to approve the legal use of MDMA-assisted psychotherapy for the treatment of depression and PTSD.<ref>{{Cite web |last=Carpenter |first=David E. |title=Australia The First Nation To Approve The Legal Use Of MDMA And Psilocybin |url=https://www.forbes.com/sites/davidcarpenter/2023/02/06/australia-the-first-nation-to-approve-the-legal-use-of-mdma-and-psilocybin/ |access-date=2023-11-13 |website=Forbes |language=en}}</ref>

== Controversy and safety == MDMA's effects vary across people and settings and include adverse outcomes.<ref name=":9" /><ref name="pmid18047478"/> The drug causes neurotransmitter activation across the main neural pathways (e.g., serotonin, dopamine, noradrenaline) that can result in large mood swings. The memories that emerge under the influence of MDMA can evoke unwanted emotions.<ref name=":9">{{cite journal | vauthors = Parrott AC | title = The potential dangers of using MDMA for psychotherapy | journal = Journal of Psychoactive Drugs | volume = 46 | issue = 1 | pages = 37–43 | date = 2014 | pmid = 24830184 | doi = 10.1080/02791072.2014.873690 | s2cid = 23485480 }}</ref> Side effects of MDMA use by recreational users include appetite fluctuations, food cravings, and disordered eating.<ref name=":9" />

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.<ref name=":9" /> The symptoms are thought to be due to the depletion of serotonin, as a result of the large release of serotonin triggered by MDMA and have been called "neurotoxic in terms of causing serotonergic dysfunction."<ref name=":9" />

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.<ref name=":9" />

There were 92 MDMA-related deaths in England and Wales in 2018, up from 56 the year before,<ref>{{Cite news|date=2019-08-15|title=Ecstasy 'too child-friendly' as deaths rise to record levels|language=en-GB|work=BBC News|url=https://www.bbc.co.uk/news/newsbeat-49357157|access-date=2020-10-22}}</ref> and 10,000 hospitalizations for MDMA-related illness/injury in 2011 in the United States.<ref name=":3" /> However, as of 2021, there have been no such cases reported for clinical settings.

Media reports and statements of academic authors have often transmitted the view of MDMA as a possible medicine or treatment rather than as an adjunct to psychotherapy.<ref name=":4" /> This approach, however, was criticized because it could lead people to believe that MDMA is an effective treatment alone, without concomitant psychotherapy.<ref name=":4" /> Some researchers have raised some concerns about the strength of the evidence, noting methodological limitations and difficulty separating the effects of MDMA from psychotherapy itself.<ref name=":5">{{Cite journal |last=Cristea |first=Ioana Alina |last2=Cuijpers |first2=Pim |last3=Halvorsen |first3=Joar Øveraas |date=2024-11-01 |title=The Psychotherapy in MDMA-Assisted Psychotherapy |url=https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2824481 |journal=JAMA Psychiatry |language=en |volume=81 |issue=11 |pages=1053 |doi=10.1001/jamapsychiatry.2024.2887 |issn=2168-622X|url-access=subscription }}</ref>

== References == {{Reflist}}

== External links == * [https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly MDMA Facts and Statistics] National Institute on Drug Abuse * [http://www.emcdda.europa.eu/publications/drug-profiles/mdma Methylenedioxymethamphetamine (MDMA or 'Ecstasy') drug profile] European Monitoring Centre for Drugs and Drug Addiction * [http://www.maps.org/research/mdma MDMA-Assisted Psychotherapy] Multidisciplinary Association for Psychedelic Studies * [http://deaddogontheleft.com/ Dead Dog on the Left] Documentary about MDMA-assisted treatment for military PTSD * [https://www.youtube.com/watch?v=UygZnBTWW0M Is MDMA psychiatry's antibiotic?] Tedx Talk by Ben Sessa. * [https://www.youtube.com/watch?v=KPMp7xEvcXk MDMA, Psychotherapy, and the Future of PTSD Treatment] TEDx talk by Brad Burge

Category:Euphoriants Category:Psychotherapy Category:Psychedelic-assisted therapy Category:Therapy