Background: Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic hallucinogens including lysergic acid diethylamide (LSD) and psilocybin produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life, and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic hallucinogens may produce antinociceptive effects.
Objective and Design: The study aims to evaluate effects of LSD on psychosocial distress in 60 patients suffering from an end-stage fatal disease with a life expectancy ≥12wks and ≤2yrs in an active placebo-controlled double-blind parallel study. Patients will be allocated in a 2:1 ratio to one of the two intervention arms receiving either two moderate to high doses of LSD (100 µg and 100 µg or 100 µg and 200 µg) as intervention and two low doses of LSD (25 µg and 25 µg) as active-placebo control.

Start Date11 Jun 2024

Sponsor / Collaborator

Universitätsspital Basel

[+1]

NCT05474989 / Not yet recruitingPhase 2IIT

LSD Treatment for Persons With Alcohol Use Disorder: A Multicenter, Double-blind, Randomized, Active-placebo Controlled Phase II Study

Alcohol use causes more overall harm than any other drug and is the seventh leading risk factor for both deaths and disability-adjusted life years. Alcohol use disorders (AUD) are among the most common and undertreated mental disorders in developed countries. Pharmacological and psychotherapeutic treatments only show limited efficacy and around 60% of the patients relapse in the short-term after withdrawal.
Lysergic acid diethylamide (LSD) was investigated in numerous clinical trials during the 1950s and 1960s. Specifically, the use of LSD in the treatment of AUD was investigated extensively. A pooled analysis of six historical clinical trials demonstrated, that a single dose of LSD significantly reduced alcohol use at three and six months after LSD administration. However, these trials are limited by several factors, including the use of diagnostic standards that are no longer not up to date, single, high-dose treatment regimes, missing biological assessment for alcohol use, and no consequent assessment of blinding.
Therefore, the present study aims to evaluate the safety and efficacy of LSD for the treatment of AUD and addresses the shortcomings of previous studies. The trial has a double-blind, active placebo-controlled, randomized, parallel design and will be conducted in specialized treatment centers for addictive disorders in Switzerland. The study will include 126 patients after withdrawal treatment and will primarily assess the efficacy of LSD for the treatment of AUD. Patients will be treated using a 1:1 allocation. Each arm will last 20 weeks and will comprise nine study visits without drug administration and two study days involving LSD or active placebo administration. In the first session, patients in the treatment group will receive a dose of 150 µg LSD, followed by another 150 µg or 250 µg LSD in the second session, which will take place approximately 4 weeks after the first session.
The primary outcome is the mean of percent heavy drinking days after administration of two doses of LSD at 3 months follow-up. Additionally, the study will assess neurobiological mechanisms of action and several other measures.

Start Date01 Jun 2024

Sponsor / Collaborator

University of Bern

100 Clinical Results associated with Lysergic acid diethylamide

100 Translational Medicine associated with Lysergic acid diethylamide

100 Patents (Medical) associated with Lysergic acid diethylamide

5,082

Literatures (Medical) associated with Lysergic acid diethylamide

01 Apr 2024·Current neuropharmacology

The Psychedelic Future of Post-Traumatic Stress Disorder Treatment

Review

Author: Jagodnik, Kathleen M ; Antonio, Josimar Hernandez ; Lepow, Lauren ; Morrison, Morgan T ; MacLeod, Carolyn ; Bonanno, Philip A ; Zaretsky, Tamar Glatman ; Pierce, Charlotte ; Danias, George ; Yehuda, Rachel ; Barsic, Robert ; Saylor, Charles ; Carney, Hunter

Abstract::

Post-traumatic stress disorder (PTSD) is a mental health condition that can occur following exposure to a traumatic experience. An estimated 12 million U.S. adults are presently affected by this disorder. Current treatments include psychological therapies (e.g., exposure-based interventions) and pharmacological treatments (e.g., selective serotonin reuptake inhibitors (SSRIs)). However, a significant proportion of patients receiving standard-of-care therapies for PTSD remain symptomatic, and new approaches for this and other trauma-related mental health conditions are greatly needed. Psychedelic compounds that alter cognition, perception, and mood are currently being examined for their efficacy in treating PTSD despite their current status as Drug Enforcement Administration (DEA)- scheduled substances. Initial clinical trials have demonstrated the potential value of psychedelicassisted therapy to treat PTSD and other psychiatric disorders. In this comprehensive review, we summarize the state of the science of PTSD clinical care, including current treatments and their shortcomings. We review clinical studies of psychedelic interventions to treat PTSD, trauma-related disorders, and common comorbidities. The classic psychedelics psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) and DMT-containing ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA) and the dissociative anesthetic ketamine, are reviewed. For each drug, we present the history of use, psychological and somatic effects, pharmacology, and safety profile. The rationale and proposed mechanisms for use in treating PTSD and traumarelated disorders are discussed. This review concludes with an in-depth consideration of future directions for the psychiatric applications of psychedelics to maximize therapeutic benefit and minimize risk in individuals and communities impacted by trauma-related conditions.

01 Mar 2024·European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial

Article

Author: Palhano-Fontes, Fernanda ; Tullman, Sam ; Arichelle, Flávia ; Bolcont, Raynara ; Laborde, Sophie ; Falchi-Carvalho, Marcelo ; Galvão-Coelho, Nicole ; Assunção, Aline ; Barros, Handersson ; Silva, Sérgio Ruschi B ; Arcoverde, Emerson ; Pantrigo, Érica J ; Wießner, Isabel ; Silva-Costa, Natan ; Costa-Macedo, José Victor ; O Maia, Lucas ; Almeida, Raissa ; Araujo, Draulio B

Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at investigating the safety and tolerability of inhaled DMT (BMND01 candidate). We recruited 27 healthy volunteers to receive a first, lower dose and a second, higher dose (5/20 mg, 7.5/30 mg, 10/40 mg, 12.5/50 mg, or 15/60 mg) of inhaled DMT in an open-label, single-ascending, fixed-order, dose-response study design. We investigated subjective experiences (intensity, valence, and phenomenology), physiological effects (blood pressure, heart rate, respiratory rate, blood oxygen saturation, body temperature), biochemical markers (liver, kidney, and metabolic functions), and adverse events during the acute and post-acute effects of DMT. DMT dose-dependently increased intensity, valence and perceptual ratings. There was a mild, transient, and self-limited increase in blood pressure and heart rate. There were no changes in safety blood biomarkers and no serious adverse events. DMT dose-dependently enhanced subjective experiences and positive valence. Inhaled DMT might be an efficient, non-invasive, safe route of administration, which might simplify the clinical use of this substance. This is the first clinical trial to test the effects of inhaled DMT (BMND01 candidate).

01 Feb 2024·The Science of the total environment

Transcriptomic profiles of brains in juvenile Atlantic cod (Gadus morhua) exposed to pharmaceuticals and personal care products from a wastewater treatment plant discharge

Article

Author: Ræder, Erik Magnus ; Pampanin, Daniela M ; Magnuson, Jason T ; Schlenk, Daniel ; Sydnes, Magne O

Pharmaceuticals and personal care products (PPCPs) are frequently detected in marine environments, posing a threat to aquatic organisms. Our previous research demonstrated the occurrence of neuroactive compounds in effluent and sediments from a wastewater treatment plant (WWTP) in a fjord North of Stavanger, the fourth-largest city in Norway. To better understand the influence of PPCP mixtures on fish, Atlantic cod (Gadus morhua) were caged for one month in 3 locations: site 1 (reference), site 2 (WWTP discharge), and site 3 (6.7 km west of discharge). Transcriptomic profiling was conducted in the brains of exposed fish and detection of PPCPs in WWTP effluent and muscle fillets were determined. Caffeine (47.8 ng/L), benzotriazole (10.9 ng/L), N,N-diethyl-meta-toluamide (DEET) (5.6 ng/L), methyl-1H-benzotriazole (5.5 ng/L), trimethoprim (3.4 ng/L), carbamazepine (2.1 ng/L), and nortriptyline (0.4 ng/L) were detected in the WWTP effluent. Octocrylene concentrations were observed in muscle tissue at all sites and ranged from 53 to 193 ng/g. Nervous system function and endocrine system disorders were the top enriched disease and function pathways predicted in male and female fish at site 2, with the top shared canonical pathways involved with estrogen receptor and Sirtuin signaling. At the discharge site, predicted disease and functional responses in female brains were involved in cellular assembly, organization, and function, tissue development, and nervous system development, whereas male brains were involved in connective tissue development, function, and disorders, nervous system development and function, and neurological disease. The top shared canonical pathways in females and males were involved in fatty acid activation and tight junction signaling. This study suggests that pseudopersistent, chronic exposure of native juvenile Atlantic cod from this ecosystem to PPCPs may alter neuroendocrine and neuron development.

145

News (Medical) associated with Lysergic acid diethylamide

10 Jun 2024

·www.biospace.com

Psychedelic Therapies Could Soon Break Through Against Addiction

Pictured: Bottles wrapped in an Iboga plant/Taylor Tieden for BioSpace Notoriously difficult to treat, substance use disorders are devastating individuals and healthcare systems across the globe. They are also a primary target of psychedelic drug developers who believe these novel therapeutics can help turn the tide. In 2018, the total medical costs of substance use disorder among people with U.S. employer-sponsored insurance came to an estimated $35.3 billion. Current treatment options include 12-step groups, detox programs and medicines such as disulfiram and acamprosate for alcohol use disorder (AUD) and buprenorphine for opioid use disorder (OUD). Despite the availability of such treatments, 3.2 million people died globally from SUD-related causes in 2019 alone. Several biopharma companies are placing bets that psychedelic therapies can help curb SUD. There are currently eight psychedelic candidates in development for SUDs, including AUD and OUD, according to Psychedelic Alpha, spanning modalities such as ketamine, psilocybin and DMT. Albert Garcia-Romeu, an associate professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine who studies psilocybin for addiction and other conditions, said the data generated so far “absolutely suggests” that psychedelics can be more effective than traditional treatments for SUDs. But as the field awaits the first FDA approval of a psychedelic for psychiatric use, substantial hurdles remain to development of the drugs for these conditions. Ketamine, LSD and Ibogaine In the 1950s and 1960s, before being outlawed, LSD was studied “heavily” as a potential treatment for SUDs, and “showed some promise in treating alcohol and opioid dependence,” Garcia-Romeu told BioSpace. However, he said, therapeutic research with classic psychedelics then stalled until the 2000s, “and most of the work since that time has really focused on psilocybin,” the active component of magic mushrooms. Other substances, including ketamine and ibogaine, have also shown some promise in treating addiction, he noted. New York–based MindMed is developing MM120, or LSD D-tartrate, for generalized anxiety disorder, among other therapeutic areas. Chief Medical Officer Daniel Karlin told BioSpace that while LSD has historically shown evidence of efficacy in SUD, its mechanism is not fully explained. But, he said, “LSD is neat because it has both a psychiatric psychological mechanism and it has a neurobiological mechanism,” with an acute neurobiological effect leading to an acute psychological experience. “We exist as a story we tell ourselves about ourselves,” Karlin said, “and for some people, that organization leads to neurotic unhappiness,” manifesting in anxiety, depression, or addiction. With LSD treatment, the mind’s organizational structures “come offline,” he explained. “This story you tell about yourself gets disorganized.” During this experience, people have the opportunity to see their narrative differently, Karlin said. After LSD treatment, the organization comes back online, but it comes back differently. Elsewhere, Toronto-based Awakn Life Sciences is in Phase III trials in the U.K. with AWKN-001, an s-ketamine–based therapy to be used in conjunction with cognitive behavioral therapy for severe AUD. “There’s a strong dissociative effect with ketamine delivered . . . at the doses we’re delivering it,” explained Anthony Tennyson, co-founder and CEO of Awakn. During a preparative therapy session, the reasons why an individual became addicted and the addiction’s effects on others surface, and ketamine then enables a different perspective on these experiences. “Getting a different perspective and a different view on things during this dissociative effect can help some people forgive themselves and forgive other people in a much more rapid and efficient way than just talk-based therapy by itself,” Tennyson told BioSpace. Ketamine also disrupts memories, which Tennyson said are “very often triggers for relapse.” Awakn pairs its ketamine therapy with a cognitive behavioral manual that is specifically designed to help people deal with the ketamine experience. In Phase II, treatment with the regimen led to an average of 86% abstinence over the six months following treatment versus 2% prior to the trial, Awakn reported. Meanwhile, Berlin and U.S.-based atai Life Sciences is tackling opioid use disorder with ibogaine, a psychoactive compound that comes from the iboga tree and has long been used in spiritual ceremonies by indigenous people in West Central Africa. Data have shown “marked benefits” of ibogaine on opioid use disorder, including on withdrawal and persistent changes in mood and craving behavior, Srinivas Rao, chief scientific officer at atai, told BioSpace. In a review of clinical results from an open-label case series of human volunteers seeking to detoxify from opioids or cocaine, ibogaine therapy diminished withdrawal symptoms and reduced drug cravings. Atai expects to begin a Phase I/IIa trial with an intravenous form of ibogaine, IBX-210, in the second half of this year. While atai considered other molecules, including LSD, the company decided to go with ibogaine because of “compelling” aggregate data in opioid use disorder. Like Awakn, Atai is planning to deliver IBX-210 with psychological support to help participants prepare for the dosing session and integrate it into their experience afterward. ‘Not a Cure-All’ While treatments like AWKN-001 and IBX-210 are intended for people with addictive personalities, “you need to consume [ketamine] in a very significantly greater quantity and on a far more regular and ongoing basis than our treatment cycle and treatment program requires” in order for addiction to be an issue with the drug, Tennyson said. Garcia-Romeu said that substances like psilocybin are not addictive in the sense that they don’t produce withdrawal and tolerance, but acknowledged that they can create a form of psychological dependence where people seek out the drug. In general, he said, “The drugs are pretty self-limiting.” Rao added that psychedelic therapies in development are intended to be administered in a supervised medical setting to mitigate their risks. “Regardless of whatever likeability any of these compounds have, none of them are being developed for at-home therapy, so that’s an important element.” Many treatment protocols—including Awakn’s AWKN-001—are combined with talk therapy, something Todd Berrios, a Veteran of the U.S. Army Special Forces who was wounded in combat was diagnosed with both alcohol dependency and post-traumatic stress disorder, told BioSpace is critical. In August 2023, through a grant sponsored by VETS, Berrios was treated with ibogaine and 5-MeO-DMT, a psychedelic found in a wide variety of plant species and secreted by the glands of at least one toad species. Since then, “I haven’t had the urge, want or need to drink alcohol, which I thought was pretty impressive,” he said. However, he emphasized that ibogaine and 5-MeO-DMT are not a “cure-all” and that patients need to put in work. “There’s never an end game, there’s never a finish line. It’s constant work,” said Berrios, who participates in weekly men’s calls, mindful medication calls and men’s calls hosted by VETS. And the psychedelic experience is not positive for everyone. In a mixed-method study published in PLOS ONE last year, 608 participants reported extended difficulties following psychedelic experiences, including feelings of anxiety and fear, existential struggle and social disconnection. The Road Ahead While the research appears promising, psychedelic therapies still have an uphill climb. Psilocybin and LSD are experimental, Garcia-Romeu said, and they are not legal in the U.S. or “in most countries.” Rao also acknowledged that working with Schedule 1 drugs adds “a lot more paperwork,” including with importation and exportation. Additionally, Garcia-Romeu said, “We don’t really know how it works. We also are kind of in this process of understanding what types of treatments are best paired with the psychedelic because it’s not just the drug that seems to help exert these effects, but it’s almost always incorporated within some form of counseling or psychotherapy.” The other main hurdle, Garcia-Romeu said, will be accessibility. “This will likely be an expensive type of treatment, because it’s very labor intensive,” he said, noting that a course of psychedelic therapy takes around three months to complete and requires hours of psychotherapy. “So even if this becomes an approved medicine, people’s ability to access these treatments may be slow, I would say, and probably limited to people of means.” Rao also noted the stigma, or “sociological overlay,” around psychedelics. “There’s just a lot of additional baggage.” Psychedelic therapies would also require a different kind of paradigm shift, he said. “Whether it’s depression or substance use disorder, we’re really looking at intermittent therapy rather than daily therapy.” Some of the baggage could be lessened this summer if Lykos Therapeutics wins FDA approval for its midomafetamine (MDMA) capsules to treat post-traumatic stress disorder. The FDA has set a PDUFA date of August 11, 2024. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

Phase 2Phase 3Clinical Result

05 Jun 2024

·www.drugs.com

FDA Panel Says No to MDMA as Treatment for PTSD

WEDNESDAY, June 5, 2024 -- A U.S. Food and Drug Administration advisory panel on Tuesday voted against recommending the psychedelic MDMA for the treatment of post-traumatic stress disorder ( PTSD ). In a 10-1 vote, the panel determined the evidence amassed so far fails to show the controversial drug's benefits outweigh its risks, the Associated Press reported. During the meeting, panel members pointed to flawed study data and significant drug risks, including the potential for heart problems, injury and abuse. “It seems like there are so many problems with the data -- each one alone might be OK, but when you pile them on top of each other … there’s just a lot of questions I would have about how effective the treatment is,” Dr. Melissa Decker Barone , a psychologist with the Department of Veterans Affairs, said during the meeting, the AP reported. The FDA is expected to make a final decision by August, but the panel's vote could bolster the agency’s reasoning for rejecting the treatment, the AP reported. MDMA is the first in a series of psychedelics -- including LSD and psilocybin -- that are expected to come before the FDA for review in the next few years, the AP reported. But on Tuesday, the FDA advisers pointed to flawed studies that could have skewed the results on MDMA, missing follow-up data on patient outcomes and a lack of diversity among participants. The vast majority of patients were white, with only five Black patients receiving MDMA, the AP reported. Lykos Therapeutics, the company behind the MDMA treatment, said it would work with regulators to address the panel’s concerns. "We are disappointed in today's vote, given the urgent unmet need in PTSD, and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy [MDMA] and psychological intervention," Lykos CEO Amy Emerson said in a statement released after the meeting. "We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system..." The panel members did note the difficulty of knowing how much of patients’ improvement came from MDMA versus the extensive therapy, which totaled more than 80 hours for many patients, the AP reported. Results were further muddied by a large number of patients who had previously used MDMA or other psychedelics recreationally. Not only that, but because MDMA causes intense experiences, almost all patients in two key studies of the drug were able to guess whether they had received the MDMA or a dummy pill, the AP reported. “I’m not convinced at all that this drug is effective based on the data I saw,” said Dr. Rajesh Narendran , a University of Pittsburgh psychiatrist who chaired the panel. The meeting concluded with several experts encouraging Lykos and the FDA to continue studying psychedelics for PTSD, the AP reported. “I think this is a really exciting treatment and I’m encouraged by the results to date, but from a safety and efficacy standpoint I feel it’s still premature,” said Dr. Paul Holtzheimer of the VA’s National Center for PTSD. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

04 Jun 2024

·www.prnewswire.com

Lykos Therapeutics Provides Update on FDA Advisory Committee Meeting for Investigational MDMA-Assisted Therapy for PTSD

SAN JOSE, Calif., June 4, 2024 /PRNewswire/ -- Lykos Therapeutics ("Lykos"), a company dedicated to transforming mental healthcare, announced the outcome of the U.S. Food and Drug Administration's ("FDA") Psychopharmacologic Drugs Advisory Committee ("PDAC"), which discussed the Company's new drug application ("NDA") for midomafetamine (MDMA) capsules used in combination with psychological intervention ("MDMA-assisted therapy") for the treatment of post-traumatic stress disorder ("PTSD") in adults. PDAC voted 2 yes to 9 no on the question of whether the available data show that midomafetamine is effective in patients with PTSD. They also voted 1 yes to 10 no on the question of whether the benefits of midomafetamine with FDA's proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD. The FDA is not bound by PDAC's guidance but takes its advice into consideration. The role of PDAC is to provide the FDA with independent, expert advice and recommendations based on their review and evaluation of data concerning the safety and effectiveness of investigational medicines for use in the practice of psychiatry and related fields.1 The FDA's approval decision is expected by the Prescription Drug User Fee Act ("PDUFA") target action date of August 11, 2024. "We are disappointed in today's vote given the urgent unmet need in PTSD and appreciate that the committee faced a challenging and atypical assignment, which was to evaluate a therapeutic approach that combines drug therapy (MDMA) and psychological intervention," Amy Emerson, Chief Executive Officer of Lykos Therapeutics. "We remain committed to working with the FDA to address outstanding questions so that we may find a path forward to ensure the responsible and careful introduction of MDMA-assisted therapy into the healthcare system, if approved. We are grateful to the advocates, clinical trial participants and people living with PTSD who shared their testimony in the open public hearing and through written comments, and will continue to do everything we can to bring this potential new therapeutic option to people living with PTSD." PDAC's review included results from two randomized, double-blind, placebo-controlled Phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA used in combination with psychological intervention, which includes psychotherapy (talk therapy) and other supportive services provided by a qualified healthcare provider, versus placebo with psychological intervention in participants diagnosed with severe or moderate to severe PTSD, respectively. Both MAPP1 and MAPP2 studies met their primary and secondary endpoints and were published in Nature Medicine.2,3 "PTSD can result in debilitating symptoms that can significantly impact nearly all areas of a person's life and while we have available treatments, unfortunately many people don't respond or stop treatment early, making today's decision an important step forward to identifying new and effective evidenced-based treatment options,"4,5 said Jerry Rosenbaum, MD, Director of the Center for the Neuroscience of Psychedelics at Massachusetts General Hospital Research Institute and Stanley Cobb Professor of Psychiatry at Harvard Medical School. "Research has suggested the unique properties of MDMA may act as a catalyst to enhance psychotherapy, the current standard of care, by helping diminish the brain's fear and avoidance responses and extend the window of tolerance of painful emotions and memories, thereby allowing people to access and process painful memories without being overwhelmed."6 On February 9, 2024, the FDA accepted the company's NDA and granted the application Priority Review. The FDA grants Priority Review for drugs that, if approved, would represent significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.7 Midomafetamine (MDMA) capsules have not been approved by any regulatory agency. The safety and efficacy of midomafetamine have not been established for the treatment of PTSD. Investigational midomafetamine is also being studied in other indications. About PTSD Prevalence and symptoms PTSD is a serious mental health condition that can develop when a person experiences or witnesses a traumatic event.4 PTSD affects approximately 13 million Americans each year with women and disadvantaged or marginalized groups more likely to be affected.8,9 Military personnel also have a greater prevalence of PTSD than the general population.10 However, it may not be as widely known that the largest cause of PTSD is non-combat-related trauma (e.g., sexual violence, unexpected death of a loved one, life-threatening traumatic event or interpersonal violence).11 PTSD results in debilitating symptoms including nightmares and intrusive thoughts related to the trauma, mental and/or physical distress in response to trauma-related stimuli, avoidant behaviors, negative thoughts and feelings, and hyperarousal.12 These symptoms can impact nearly all aspects of a person's life, including their interpersonal relationships.4 PTSD can also be a chronic condition with a World Health Organization study showing that after ten years post-trauma, nearly a quarter of people had not recovered.13 Co-morbidities and economic impact People with PTSD frequently experience anxiety, depression, substance use disorder and suicidal ideation.14,15 They also may have a greater incidence of medical conditions that impact their physical health, including heart disease, metabolic syndrome and asthma.16,17,18,19 U.S. Army veterans who developed PTSD after military service have been shown to have an approximately two times greater risk of mortality than U.S. Army veterans who did not develop PTSD after military service.15 In addition to the significant personal impact, PTSD has an enormous economic impact resulting in an annual cost of over $232 billion in the United States.20 PTSD Treatment Trauma-focused talk therapy, which concentrates on memories of the traumatic event or thoughts and feelings associated with the traumatic event, is first-line treatment for PTSD, which can be used alone or in combination with medication.21 There are two SSRIs approved for the treatment of PTSD (sertraline and paroxetine).22 Studies have shown talk therapy lessens the severity of PTSD symptoms, however, improvements in functioning and quality of life have been modest.23,24 Trauma-focused talk therapy is associated with a high risk of dropout and lingering symptoms which occur in as many as two-thirds of people who complete treatment.25,26 Current treatments for PTSD are "reasonably efficacious" (Bryant, 2019, p.265), however many people don't respond to treatment or stop treatment early, underscoring the urgent need for new evidence-based therapies and approaches to address this important public health issue.27 While there have been advancements in the management of PTSD, there have been no new drug treatments approved by the FDA in over 20 years.28 About MDMA-Assisted Therapy MDMA (midomafetamine) is commonly known to mental health professionals. In the 1970s and early 1980s MDMA was used in conjunction with talk therapy by mental health providers to help enhance patients' access, processing and communication of difficult emotions and experiences.29 MDMA is an entactogen— a class of psychoactive compounds that are differentiated from classic psychedelics (i.e., psilocybin, mescaline and LSD) and are defined based on their mechanism and demonstrated effects of increasing self-awareness leading to introspection and personal reflection.30,31 In 1985, the U.S. Drug Enforcement Administration ("DEA") made MDMA a Schedule I drug under the Controlled Substances Act, preventing it from being used for recreational or medical use.32 Since then, research has suggested that MDMA may have potential as a catalyst to support psychotherapy by helping diminish the brain's fear response, allowing people to access and process painful memories without being overwhelmed.33 Lykos, with longstanding roots in advocacy for psychedelic medicine, was the first company to pioneer randomized, double-blind, placebo-controlled clinical trials evaluating the efficacy and safety of MDMA-assisted therapy as an investigational modality using midomafetamine (MDMA) in combination with psychological intervention and submit a New Drug Application to the FDA seeking approval for the treatment of PTSD in adults. If approved by the FDA, the DEA would be required to reschedule MDMA making it available for prescription medical use. Lykos Therapeutics At Lykos Therapeutics, a public benefit corporation (PBC) founded by MAPS, our mission is to transform mental healthcare. We're applying decades of evidence-based research to develop investigational psychedelics to catalyze therapeutic approaches for mental health conditions. We are relentlessly exploring and reimagining novel approaches to address unmet needs in the mental healthcare space, with an initial focus on PTSD. As a PBC, we are focused on delivering positive impact on our people, communities and society. To learn more visit us at and on LinkedIn, X, Instagram and Facebook. 1 FDA. Accessed May 29, 2024. Psychopharmacologic Drugs Advisory Committee | FDA 2 Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3 3 Mitchell JM, Ot'alora MG et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023 Sept 14 doi: 10.1038/s41591-023-02565-4 4 The Mayo Clinic, PTSD, Symptoms and Causes . Accessed January 2024. 5 Lewis, C., Roberts, N. P., Gibson, S., & Bisson, J. I.. Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: A systematic review and meta-analysis. European Journal of Psychotraumatology. 2020 Mar 9;11(1):1709709. 6 Yazar-Klosinski BB., Mithoefer MC. Potential Psychiatric Uses for MDMA. Clinical Pharmacology & Therapeutics. 2017;101(2):194-196. 7 FDA Priority Review. Accessed May 2024. 8 VA National Center for PTSD. US Department of Veterans Affairs. Accessed May 13, 2024. 9 Goldstein RB et al. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016; 51(8):1137–1148. 10 Lehavot K et al. Post-traumatic stress disorder by gender and veteran status. Am J Prev Med. 2018 Jan;54(1):e1-e9. doi: 10.1016/j.amepre.2017.09.008 11 Kessler RC, Rose S, Koenen KC, et al. How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental Health Surveys. World Psychiatry. 2014 Oct;13(3):265-74. doi: 10.1002/wps.20150 12 Bryant RA. Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry. 2019;18(3):259–269. 13 Rosellini AJ et al. Recovery from DSM-IV post-traumatic stress disorder in the WHO World Mental Health surveys. Psychol Med. 2018 Feb;48(3):437-450. doi: 10.1017/S0033291717001817 14 Grinage B.D. Diagnosis and management of post-traumatic stress disorder. Am Fam Physician. (2003);68(12):2401-2409. PMID: 14705759. 15 Rojas SM et al. Understanding PTSD comorbidity and suicidal behavior: associations among histories of alcohol dependence, major depressive disorder, and suicidal ideation and attempts. J Anxiety Disord. 2014 Apr;28(3):318-25. doi: 10.1016/j.janxdis.2014.02.004 16 Edmondson D, von Känel R. Post-traumatic stress disorder and cardiovascular disease. Lancet Psychiatry. 2017 Apr;4(4):320-329. doi: 10.1016/S2215-0366(16)30377-7 17 Krantz DS, Shank LM, Goodie JL. Post-traumatic stress disorder (PTSD) as a systemic disorder: Pathways to cardiovascular disease. Health Psychol. 2022 Oct;41(10):651-662. doi: 10.1037/hea0001127 18 Boscarino JA. Posttraumatic stress disorder and mortality among U.S. Army veterans 30 years after military service. Ann Epidemiol. 2006 Apr;16(4):248-56. doi: 10.1016/j.annepidem.2005.03.009 19 Nichter B, Norman S, Haller M, Pietrzak RH. Physical health burden of PTSD, depression, and their comorbidity in the U.S. veteran population: Morbidity, functioning, and disability. J Psychosom Res. 2019 Sep;124:109744. doi: 10.1016/j.jpsychores.2019.109744 20 Davis LL. The economic burden of posttraumatic stress disorder in the United States from a societal perspective. J Clin Psychiatry. (2022) Apr 25;83(3):21m14116. doi: 10.4088/JCP.21m14116 21 Watkins LE, Sprang KR, Rothbaum BO. Treating PTSD: A Review of Evidence-Based Psychotherapy Interventions. Front Behav Neurosci. 2018 Nov 2;12:258. doi: 10.3389/fnbeh.2018.00258 22 American Psychological Association. Clinical Practice Guidelines for the Treatment of PTSD. Medications (apa.org) Accessed February 5, 2024. 23 Cusack K, et al. Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2016;43:128-141. 24 Bonfils, KA et al, Functional outcomes from psychotherapy for people with posttraumatic stress disorder: A meta-analysis. J Anxiety Disorders. 2022;89:102576. 25 Lewis, C., Roberts, N. P., Gibson, S., & Bisson, J. I. (2020). Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis. European Journal of Psychotraumatology, 11(1). 26 Steenkamp, M. M., Litz, B. T., Hoge, C. W., & Marmar, C. R. (2015). Psychotherapy for Military-Related PTSD. JAMA, 314(5), 489. 27 Bryant RA. Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry. 2019;18(3):259–269. 28 Stein MB, Rothbaum BO. 175 Years of Progress in PTSD Therapeutics: Learning From the Past. Am J Psychiatry. 2018 Jun 1;175(6):508-516. doi: 10.1176/appi.ajp.2017.17080955. PMID: 29869547. 29 Wagner MT, Mithoefer MC, Mithoefer AT, MacAulay RK, Jerome L, Yazar-Klosinski B, Doblin R. Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. J Psychopharmacol. 2017 Aug;31(8):967-974. doi: 10.1177/0269881117711712 30 Nichols, David E. Entactogens: How the name for a novel class of psychoactive agents originated. Frontiers in Psychiatry. 2022 Mar 25;13:863088. doi:10.3389/fpsyt.2022.863088 31 Vollenweider, Franz X.,Dialogues Clin Neurosci. 2001 Dec; 3(4): 265–279. doi: 10.31887/DCNS.2001.3.4/fxvollenweider 32 National Institute on Drug Abuse (NIDA) (nih.gov) What is the history of MDMA? . Accessed, January 17, 2024. What is the history of MDMA? | National Institute on Drug Abuse (NIDA) (nih.gov) 33 Yazar-Klosinski B, Mithoefer MC. Potential psychiatric uses for MDMA. Clinical Pharmacology & Therapeutics. 2017 Feb;101(2):194-196. doi: 10.1002/cpt.565 SOURCE Lykos Therapeutics

Phase 3NDAPriority Review

100 Deals associated with Lysergic acid diethylamide

External Link

KEGG	Wiki	ATC	Drug Bank
-	Lysergic acid diethylamide	N	DB04829

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cluster Headache	Phase 2	-	Radboud University Medical Center	01 Jan 2024
Social Behavior	Phase 2	NL	Maastricht University	01 Jan 2023
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Mind Medicine (MindMed), Inc.	30 Jan 2022
Generalized anxiety disorder	Phase 2	US	Mind Medicine (MindMed), Inc.	30 Jan 2022
Anxiety	Phase 2	CH	Universitätsspital Basel	23 Jun 2017
Anxiety Disorders	Phase 2	CH	Universitätsspital Basel	23 Jun 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05407064 (MMED008, BusinessWire) Manual	Phase 2	Generalized anxiety disorder	198	MM120 100 µg	tkazvzcvca(aodwqppczk) = tovopsijui jjpnlkalfu (btbtpnfzvy ) View more	Positive	07 Mar 2024
				placebo	tkazvzcvca(aodwqppczk) = uurfrwbgpq jjpnlkalfu (btbtpnfzvy )
NCT05407064 (MMED008, BusinessWire) Manual	Phase 2	Generalized anxiety disorder	198	MM-120 (100 μg or 200 μg)	kroyevalyq(hygksnvubh) = vrzfpyiomz icgsxkmsaq (hjwzchyohi ) View more	Positive	14 Dec 2023
				MM-120 (100 μg)	nvflrjzlww(ctxefkqlve) = kwmpunzulq lvjlzhfxdn (woorxieria ) View more
NCT03153579 (LSD-assist, SOBP2022) Manual	Phase 2	Anxiety	42	Lysergic Acid Diethylamide	kmquknyzco(lukwezfdhk) = zmcndklqkx mwubaelmwx (txcgqdflfk ) View more	Positive	02 Sep 2022
				Placebo	kmquknyzco(lukwezfdhk) = hnafghovws mwubaelmwx (txcgqdflfk ) View more
NCT00920387 (CTgov)	Phase 2	Anxiety	12	Therapy+200 mcg LSD (Full Dose LSD (200 mcg))	lwjcymkkxr(avdoutyyik) = yxabibjfzy mpobqrvzun (atynqpavzq, ajhjzhnntg - diiinrplvh) View more	-	08 Dec 2021
				Therapy+20 mcg LSD (Active Placebo LSD (20 mcg))	lwjcymkkxr(avdoutyyik) = aftrzqpxne mpobqrvzun (atynqpavzq, dzwsfplqoy - ubbjeqlulz) View more
NCT02308969 \| NCT01878942 (Pubmed \| Clin Pharmacokinet)	Not Applicable	-	-	LSD 100 µg	fxayongymv(ehchoylnxq) = vbhgyghiwi skytiaotvt (jodnnsvocs, 2.1) View more	-	01 Oct 2017
				LSD 200 µg	fxayongymv(ehchoylnxq) = odastjwarz skytiaotvt (jodnnsvocs, 1.7) View more

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