Why MDMA-assisted psychotherapy may become an FDA-approved treatment for PTSD within 2 years

For peo­ple with post-trau­mat­ic stress dis­or­der, recall­ing mem­o­ries of phys­i­cal or sex­u­al assault, com­bat or dis­as­ter-relat­ed events can induce intense anx­i­ety or pan­ic attacks as well as debil­i­tat­ing flashbacks.

In the U.S., about 7% of peo­ple suf­fer from PTSD and lose an aver­age of about four work­ing days each month as a result. Trau­ma-spe­cif­ic psy­chother­a­py, like cog­ni­tive pro­cess­ing or “talk” ther­a­py, is the cor­ner­stone of treat­ment for PTSD. But for approx­i­mate­ly half of peo­ple, these tra­di­tion­al approach­es are inef­fec­tive at ful­ly address­ing PTSD symp­toms over the long term. Anti­de­pres­sant drugs are fre­quent­ly used if psy­chother­a­py fails, or in com­bi­na­tion with it, but the effects are usu­al­ly modest.

MDMA (3,4‑methylenedioxymethamphetamine) is an active ingre­di­ent in the illic­it street drug known as ecsta­sy or mol­ly. Peo­ple in dance clubs and raves use illic­it MDMA because it ele­vates mood and ener­gy lev­els, induces a feel­ing of bond­ing with oth­ers and pro­duces a sur­re­al psy­che­del­ic effect. These same effects have been hypoth­e­sized to sup­port peo­ple with PTSD dur­ing psy­chother­a­py ses­sions, since they can make peo­ple more will­ing and able to share and explore their trau­mat­ic expe­ri­ences. Our new meta-analy­sis of clin­i­cal tri­als con­firms the ben­e­fits of MDMA-assist­ed psy­chother­a­py in the treat­ment of PTSD.

We are a phar­ma­cist and physi­cian team who inves­ti­gate the ben­e­fits and harms asso­ci­at­ed with sub­stances of abuse like bath salts, phenibut, cannabis and syn­thet­ic mar­i­jua­na. Through this work we have become intrigued about the ther­a­peu­tic poten­tial for some psy­che­del­ic drugs in the treat­ment of myr­i­ad psy­chi­atric dis­or­ders, from PTSD to major depres­sion, espe­cial­ly MDMA and psilo­cy­bin (hal­lu­cino­genic mushrooms).

It is impor­tant to state that using ecsta­sy or mol­ly prod­ucts from the street would not help PTSD symp­toms because the MDMA needs be used along with care­ful­ly craft­ed psy­chother­a­py in a safe, con­trolled envi­ron­ment. Ecsta­sy or mol­ly prod­ucts pur­chased illic­it­ly nev­er spec­i­fy the exact amount of MDMA they con­tain, so it is impos­si­ble to dose it prop­er­ly for PTSD. Tak­ing too much MDMA or exer­cis­ing while tak­ing MDMA can cause heart attacks, strokes, seizures and arrhyth­mias and can dam­age mus­cles and kidneys.

What is MDMA-assisted psychotherapy?

In an MDMA-assist­ed psy­chother­a­py ses­sion, patients take MDMA as a pill upon enter­ing a psychiatrist’s office and then work with a team of ther­a­pists who help them divulge trau­mat­ic events or dis­cuss aspects of those events over the course of sev­er­al hours. They usu­al­ly have non-MDMA ses­sions before the first MDMA ses­sion so they know what to expect. And they have at least one non-MDMA ses­sion after each MDMA one to work through the trau­mat­ic mem­o­ries that were revealed and to learn cop­ing strate­gies. A stan­dard treat­ment course includes two or three mul­ti­hour MDMA-assist­ed psy­chother­a­py ses­sions and sev­er­al non-MDMA sessions.

The MDMA prod­ucts used in these ses­sions are phar­ma­ceu­ti­cal grade. This means that, unlike illic­it­ly obtained street prod­ucts, they do not con­tain oth­er sub­stances of abuse, such as metham­phet­a­mine, or con­t­a­m­i­nants like heavy met­als, bac­te­ria or mold. Peo­ple with hyper­ten­sion or those at high risk of heart attacks, strokes or arrhyth­mias should not par­tic­i­pate, because they can have unsafe ele­va­tions in blood pres­sure and heart rate. In addi­tion, patients are not allowed to leave for eight hours, until the effects of MDMA have ful­ly worn off.

Assessing the effectiveness of MDMA-assisted psychotherapy

In 2014, we reviewed the avail­able ani­mal data and the few pre­lim­i­nary human stud­ies of MDMA-assist­ed psy­chother­a­py, but at the time, high­er-qual­i­ty clin­i­cal tri­als had not yet been com­plet­ed. But in the past few years, larg­er and high­er-qual­i­ty tri­als have been pub­lished, war­rant­i­ng an in-depth assessment.

So we recent­ly reviewed the data com­par­ing anti­de­pres­sant use to place­bos for patients with PTSD and per­formed a meta-analy­sis study of the six dif­fer­ent clin­i­cal tri­als that assessed the use­ful­ness of MDMA-assist­ed psy­chother­a­py ver­sus psy­chother­a­py alone. All of the tri­als we ana­lyzed includ­ed both men and women who had expe­ri­enced a mul­ti­tude of trau­mat­ic events that led to PTSD. The stud­ies used the same points scale to deter­mine the effec­tive­ness of ther­a­py, mak­ing it eas­i­er to com­pare data across stud­ies. Scores above approx­i­mate­ly 50 points mean a patient has severe PTSD, and scores reduced by more than 10 points from base­line are clin­i­cal­ly meaningful.

We found that dai­ly anti­de­pres­sant ther­a­py reduced PTSD by 6 to 14 points com­pared with the place­bo, but a range of 27% to 47% of patients across the stud­ies with­drew before the end of the tri­als. In con­trast, MDMA-assist­ed psy­chother­a­py reduced the scores by 22 points com­pared with those receiv­ing psy­chother­a­py with place­bo, and patients were twice as like­ly to no longer meet the cri­te­ria for PTSD diag­no­sis by the end of the tri­als. In addi­tion, only 8% of patients with­drew from MDMA-assist­ed psy­chother­a­py tri­als. The main adverse effects includ­ed teeth grind­ing, jit­ter­i­ness, headache and nau­sea. One of these MDMA tri­als found that par­tic­i­pants’ blood pres­sure and heart rate were ele­vat­ed in the course of MDMA ther­a­py, but not to a con­cern­ing extent.

For sev­er­al of the tri­als in our meta-analy­sis, inves­ti­ga­tors sent a ques­tion­naire to par­tic­i­pants 12 months after their last MDMA ses­sion to assess the long-term impact. Over­all, 86% of par­tic­i­pants said they received sub­stan­tial ben­e­fits from the com­bined MDMA-assist­ed psy­chother­a­py. Eighty-four per­cent of par­tic­i­pants report­ed hav­ing improved feel­ings of well-being, 71% had few­er night­mares, 69% had less anx­i­ety and 66% had improved sleep. The results from across all of the stud­ies sug­gest­ed that MDMA-assist­ed ther­a­py was help­ing to alle­vi­ate the PTSD itself, not sim­ply sup­press­ing symptoms.

Looking ahead

The U.S. Drug Enforce­ment Admin­is­tra­tion iden­ti­fies MDMA and psilo­cy­bin as Sched­ule I con­trolled sub­stances. Accord­ing to the DEA, these sub­stances have no cur­rent­ly accept­ed med­ical use in the U.S. and come with high abuse potential.

How­ev­er, it’s worth not­ing an impor­tant excep­tion. Cannaba­di­ol, or CBD, a chem­i­cal that comes from the plant Cannabis sati­va, is clas­si­fied as a Sched­ule I drug. But the Food and Drug Admin­is­tra­tion approved its use in 2018 for the treat­ment of two rare and severe child­hood seizure dis­or­ders. That doesn’t mean that the CBD in your lotion or seltzer has proof of ben­e­fit for most of the ills peo­ple are using it for, but its full ther­a­peu­tic poten­tial is still being explored. Giv­en the strong con­sis­tent ben­e­fi­cial effects and man­age­able adverse events in the new­er tri­als designed with FDA input, we sus­pect that MDMA-assist­ed psy­chother­a­py will become an FDA-approved option for PTSD by the end of 2023. Psilo­cy­bin – com­mon­ly known as hal­lu­cino­genic mush­rooms – also shows promise for treat­ing major depres­sion, but fur­ther research is needed.

The DEA’s strin­gent poli­cies made it excep­tion­al­ly hard for sci­en­tists to con­duct research on Sched­ule I drugs for decades by crim­i­nal­iz­ing the pos­ses­sion of the prod­ucts, even in research set­tings. But in 2018, the agency stream­lined the appli­ca­tion process for secur­ing a waiv­er for research pur­pos­es. This made it eas­i­er for researchers to con­duct tri­als into the phar­ma­ceu­ti­cal val­ue of psy­che­del­ic drugs. With­in the next decade, this shift will almost cer­tain­ly accel­er­ate the dis­cov­ery of new treat­ments for patients suf­fer­ing from men­tal illness.

C. Michael White is Dis­tin­guished Pro­fes­sor and Head of the Depart­ment of Phar­ma­cy Prac­tice at the Uni­ver­si­ty of Con­necti­cut, and Adri­an V. Her­nan­dez is Asso­ciate Pro­fes­sor of Com­par­a­tive Effec­tive­ness and Out­comes Research, Uni­ver­si­ty of Con­necti­cut. This arti­cle was orig­i­nal­ly pub­lished on The Con­ver­sa­tion.

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SHARPBRAINS es un think-tank y consultoría independiente proporcionando servicios para la neurociencia aplicada, salud, liderazgo e innovación.

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