Important Compound Classes
Title
Compositions Comprising 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) for use in Treating Mental Disorders
Patent Publication Number
WO 2020/169851 A1
Publication Date
August 27, 2020
Priority Application
19158806.0 EP
Priority Date
February 22, 2019
Inventors
Terwey, T.
Assignee Company
GH Research Limited [IE/IE]; Mespil House 4 Sussex Road, Dublin 4, D04 T4A6 (IE)
Disease Area
Mental disorders
Biological Target
Serotonin Receptor (SR)
Summary
The present Patent Highlight shows the use of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt in the treatment of mental disorders, including major depressive disorder, anxiety disorder, eating disorder, body dysmorphic disorder, persistent depressive disorder, post-traumatic stress disorder, obsessive–compulsive disorder, and psychoactive substance abuse. Patients with major depressive disorder were diagnosed by a licensed professional in accordance with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), which is published by the American Psychiatric Association. The severity of the disorder is indicated by a scoring rating. For example, the Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or more is indicative of moderate or severe major depressive disorder, whereas the Hamilton Depression Rating Scale (HAM-D) will indicate a score of 17 or more. On the other hand, a patient with severe major depressive disorder will have a MADRS score of 35 or greater and a HAM-D score of 25 or more.
Natural occurring psychedelics, such as psilocybin, mescaline, or DMT, have been used for centuries by indigenous cultures in naturalistic, ritual, or sociocultural contexts and in religious sacraments. Scientific investigations into their therapeutic potentials were not pursued until after the discovery of the synthetic ergoline LSD in 1943, which followed encouraging clinical experiences a decade later. Treatment program of alcoholism, where participants that received LSD in addition to psychotherapy, had higher rates of abstinence than patients who received psychotherapy alone. Furthermore, in the treatment of patients suffering from a terminal state of cancer or patients with anxiety or personality trait disturbance, where administration of LSD coupled with psychotherapy, two-thirds of patients saw varying degrees of improvement or an “improved” outcome of over 90% of patients, respectively.
Recently, there has been emerging knowledge about the molecular activity of psychedelic drugs, the modulation of serotonin in the system, and its role in brain function. A couple of concepts have been proposed: the “psycholytic therapy”, which indicates the ability of psychedelics to facilitate loosening of the psychological defensive mechanisms and, when combined with psychotherapy, allows a deep introspective insight that may lead to revival of traumata and their subsequent purgation. The other concept often reported is the “psychedelic therapy”, which indicates the ability of psychedelics at high doses to induce the loss of judgment to time, space, and the dissolution of ego boundaries that often culminates in a blissful state and feelings in harmonious existence to cosmic unity. This unique, overwhelming experience fill in intuitive perception of psychological integration and harmony may lead to subsequent self-improvements, joy in living, and a sense of inner peace.
The intensity of the acute psychedelic experience for long-term clinical improvement provides a broad range of therapeutic mental conditions, which is congruent with recent observations from human brain functional connectivity via resting state networks (RSNs). The RSNs are the source of complexity in various complex cognitive function, which can be perturbed in mental disorders, including major depressive disorder, anxiety disorder, persistent depressive disorder, post-traumatic stress disorder, body dysmorphic disorder, eating disorder, and psychoactive substance abuse.
An acute psychedelic effect after oral dosing lasts for several hours with psilocybin, which may be inconvenient for the patient and provider and may limit rapid therapeutic scale up. A shorter duration of psychedelic effects with a molecule such as 5-MeO-DMT would be beneficial not only for a shorter duration of psychedelic effects but also for a more rapid onset of clinical response compared to presently available treatment. The aim of the current Patent Application is to provide a compound with improved psychoactive therapies, dosing regiments, and route of administration: patients experienced significant clinical response, earlier onset and durable clinical response than previously described therapies.
A single dose of 12 mg of 5-MeO-DMT administered via inhalation was well-tolerated and induces a significant clinical response within 2 h in patients formally diagnosed with treatment-resistant major depressive disorder. Patients experienced clinical remission within 2 h after a single 5-MeO-DMT administration, which deepened over the 7 day follow-up period in spite of the absence of the drug, as shown by the pharmacokinetic data. Many end points were positively imparted, including suicidal ideation, anxiety, somatic concern, guild, and tension, which implied that 5-MeO-DMT could be used in patients with other mental diseases. Intensity of the acute psychedelic effects after 5-MeO-DMT administration varies with individual patients, which can be 6 mg, 18 mg high doses for others, and so on. Various safety-related measures were taken, including adverse event reporting, vital signs, ECG, safety laboratory analyses, and so forth.
Definitions
MADRS: This is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders such that each item is rated a score of 0 to 6 and 0–60 for the overall score. Diagnostic cutoff points are 0 to 6 = normal/symptom absent; 7 to 19 = mild depression; 20 to 34 = moderate depression and >34 = severe depression.
Patient Global Impression: Severity (PG1-S); it is a 7-point scale for depression that requires the patient to rate the severity of his/her depressive symptoms at the time of assessment. Diagnostic ratings are 1 = normal/no illness; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill.
Patient global impression–improvement (PGI-I): Another 7-point scale for depression that requires the patient to assess the change in his/her depressive symptoms on how improved or worsened relative to a baseline state at the beginning of the intervention. Diagnostic ratings are 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; and 7 = very much worse.
MADRS suicidal thoughts item: This scores suicidality of the patient, and ranges are 0 = enjoys life and makes it as it comes, and 6 = explicit plans for suicide when there is an opportunity and active preparations for suicide.
Columbia-suicide severity rating score (C-SSRS) suicidal ideation: Detailed questionnaire assessing both suicidal behavior and suicidal ideation, which score “yes” or “no” whether any of the suicidal ideation items were present.
Brief psychiatric rating scale (BPRS): This is a structured screen for the presence of various psychiatric symptoms. There are 18 symptom evaluations such as somatic concern, anxiety, hostility, motor retardation, unusual thought content, grandiosity, tension, and so forth. Each symptom is rated on a scale of 1 to 7, and the total BPRS scores are noted.
Key Structures
Data Collection
Two patients with major depressive disorder were diagnosed by a psychiatrist according to DSM-5 diagnostic criteria. In addition, the patients were considered treatment-resistant because they did not show adequate improvement with at least two adequate courses of pharmacological therapy in the current episode of depression.
Biological Data
The table below shows symptom scales
at baseline, 2 h, 1 day, and 7 days after 5-MeO-DMT administration.
Notably, patients 1 and 2 had a very similar intensity of psychedelic
effects, which correlated with similar antidepressive clinical response.
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The author declares no competing financial interest.