MDMA-assisted therapy and psilocybin currently lead the way with potential approvals by the FDA.
Psychedelic therapy might be closer to reality than previously thought, with big movements in 2024 for midomafetamine capsules (MDMA)-assisted therapy and a separate adjunct treatment with psilocybin for mental health disorders. MDMA-assisted therapy from Lykos Therapeutics is being evaluated in combination with psychological interventions, which include psychotherapy and other services from a health care provider, for posttraumatic stress disorder (PTSD). CYB003 (Cybin), a psilocybin compound, is being evaluated as an adjunctive treatment for major depressive disorder.1,2
Image Credit: Виктор Рак - stock.adobe.com
The FDA has accepted a new drug application (NDA) for MDMA-assisted therapy with priority review and a prescription drug user fee act target action date of August 11, 2024. If approved, this would call for a rescheduling of MDMA from Schedule I to acknowledge the medical benefits of the drug.
"MDMA is essentially a psychedelic amphetamine," explained expert Sa'ed Al-Olimat, PharmD, co-founder of the Psychedelic Pharmacists Association, in an interview with Pharmacy Times. "It's unique in that it binds to CERT, gets uptake into the presynaptic neuron, releases monoamines into the synaptic cleft, and, again, it's a psychedelic amphetamine."
MAPP1
Trial Name: A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD
ClinicalTrials.gov ID: NCT03537014
Sponsor: Lykos Therapeutics
Completion Date: August 21, 2020
MAPP2
Trial Name: A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD
ClinicalTrials.gov ID: NCT04077437
Sponsor: Lykos Therapeutics
Completion Date: November 2, 2022
The NDA was based on results from the phase 3 studies MAPP1 (NCT03537014) and MAPP2 (NCT04077437), both of which met their primary and secondary endpoints, including changes in symptom severity and functional impairment associated with PTSD. MAPP2 demonstrated that approximately 86.5% of those treated with MDMA responded with clinically meaningful improvements at 18 weeks compared to 69% on the placebo.1
The FDA has also recently granted breakthrough designation (BTD) to CYB003, a deuterated psilocybin analogue. The BTD was based on data from a phase 2 trial which demonstrated that individuals experienced sustained improvements at 4 months. Approximately 75% of individuals who received 2 doses at 16 mg achieved remission and no longer had signs of depression. Additionally, approximately 60% who received the 12 mg dose also achieved remission.2
As for adverse events, both MDMA and CYB003 showed no serious adverse events, with CYB003 demonstrating only mild or moderate AEs. Further, CYB003 also had no instances of individuals experiencing suicidal ideation or behaviors.1,2
"These protocols, they follow 1, 2, maybe 3 dose days, and in between those days there is an extended period of time for that participant to integrate, reflect, and prepare," Al-Olimat told Pharmacy Times. "Because of the limited amount of dose days t hat are taking place and the extensive preparation and screening that goes in before each dose day, and the integration...that takes place after the dose day, we don't really see any chronic conditions manifest or side effects manifest from these compounds. A lot of the side effects that are experienced are usually well tolerated and are acute, short acting, and short lasting."
However, all investigational medicines come with a myriad of obstacles that can block any major developments; psychedelic medicine is no exception, but a more intense example. There are cultural perceptions and difficulties in research that can slow these drugs from becoming a reality in the therapeutic space.
Because both medications are classified as Schedule 1 drugs, which are defined by the US Drug Enforcement Administration as “drugs with no currently accepted medical use and a high potential for abuse,” researching the drugs for therapeutic use can be difficult. Extensive paperwork must be submitted, including one form to allow investigators to work with Schedule I drugs, one to register the drug, one to administer the drug to patients, and one to allow psychedelic medicines to cross state lines. There are other individual state laws and licenses required for drug storage and distribution.3,4
Once a drug is officially registered, there are other obstacles in storing, handling, distributing, shipping, and record keeping for the drugs in accordance with the US Controlled Substance Act, according to a Pharmacy Times interview with Mark Bleackley, PhD, chief scientific officer at Incannex Healthcare Limited.4
Although there is a public perception of these drugs, these potential coming FDA approvals mark a cultural shift regarding psychedelic medicine. The future of psychedelic medicine is just around the corner, and it’s possible it could even be closer than originally imagined.
"[The approval of MDMA] is going to completely change the game," Al-Olimat said. "Really, it's about empowering the patient to take ownership over their own healing, to not passively cope...but to actively cope during the session and beyond, to really work through whatever they want to work through."
