FFor some, psychiatric medications are the difference between life and death. For others, they are the difference between life and chaos. The stakes are high for many people and that is why it is crucial to follow the medication process.
Ah, those college days when I took “mushrooms” and went to the planetarium. Who would have thought we would be talking about psilocybin 50 years later?
One in five American adults is believed to use psychiatric medications. The UK figures are similar.
Now, there are those who claim that psychiatric medications are not only useless, but also harmful. But for the sake of the people who believe in them (and trust them), as well as continuing the search for greater efficacy and fewer side effects, we must do it.
Let’s check the pipeline according to the mess. And as you can imagine, there’s a ton of information and there’s no way to do it justice in one piece.
So here we will address generalized anxiety disorder, major depressive disorder, and post-traumatic stress disorder. And we will return to the second part and address attention deficit hyperactivity disorder and schizophrenia.
While we’re on the subject, if you’re interested in participating in a US Food and Drug Administration (FDA) clinical trial for a drug in development anywhere in the world, hit the database. The UK offers the same in ScanMedicine.
Let’s get busy…
The psychiatric medication line: the latest
I have tried to keep the information you are about to read simple and brief. If you want every detail, there are links to my sources at the end.
Generalized anxiety disorder (GAD)
MM120
Mind Medicine has received breakthrough therapy designation from the FDA for its therapy with lysergide d-tartrate, MM120, by GAD. The company announced positive data from a phase 2b (of four) study.
MM120 is a tartrate salt of lysergide, a semi-synthetic hallucinogen commonly known as, yes, LSD.
According to study researcher David Feifel, MD, PhD…
I have conducted clinical research studies in psychiatry for more than two decades and have seen studies of many drugs in development for the treatment of anxiety. That MM120 exhibited rapid and robust efficacy, robustly sustained for 12 weeks after a single dose, is truly remarkable.
The study also demonstrated that MM120 was generally well tolerated, with most adverse events classified as mild to moderate, transient, and occurring on the day of administration.
Mind Medicine intends to begin a Phase 3 clinical trial of MM120 in the second half of 2024.
Major depressive disorder (MDD)
The first two medications we are going to analyze influence NMDA (north-methyl-D-aspartate) in the brain. Simply put, NMDA is a glutamate receptor, with glutamate being our most abundant excitatory (accelerator) neurotransmitter.
What makes glutamate receptors a great target is that they are involved in many important brain activities and diseases. One of the activities is neuroplasticity, responsible for the brain’s ability to adapt to various conditions: “neurons that activate together connect with each other.” Glutamate receptors are also one of the few that process opiate/opioid pain relievers in the brain.
Currently, there are two FDA-approved NMDA-targeting psychiatric medications: esketamine (Sprovato) and the combination of dextromethorphan and bupropion (Auvelity).
Esmethadone
Esmethadone It is an NMDA receptor antagonist It is believed to modulate the glutamate system, generating antidepressant effects.
We have all heard of methadone. Esmethadone is structurally different enough to eliminate the opioid effect while adding antidepressant action. It also increases levels of critically important BDNF.
In a phase 2a study, among participants who were inpatient psychiatric patients with MDD, esmethadone significantly outperformed placebo. Phase 3 studies are underway.
navacaprante
navacaprantedeveloped by Neumora Therapeutics, aims κ opioid receptors. In a recent phase 2 study, it demonstrated significant improvement in depressive symptoms, including anhedonia, in patients with moderate to severe MDD.
The impact of a variety of neurochemicals on the κ-opioid system is known to generate degrees of depression and anhedonia. The reverse action that navacaprant has on the system probably reduces these symptoms.
Neumora has started phase 3 studies.
psilocybin
Ah, those college days when I took “mushrooms” and went to the planetarium. Who would have thought we would be talking about psilocybin 50 years later?
Psilocybin has become a household word. Heck, I’ve even written about it. But keep in mind that notoriety can lead to misconceptions, including claims that psilocybin is safe and effective for treating depression.
Now, I know several people who currently use it for a variety of emotional and mental problems. But the fact is, although psilocybin is registered with the FDA and is being studied intensively, it is still under investigation.
Psilocybin is a natural molecule that exists in more than 200 species of Basidiomycota mushrooms. Clinical trials use psilocybin extracted from these mushrooms or a synthetic form.
Eyes are on you, friends. Keep up the good work.
Psilocybin is classified as a Schedule 1 hallucinogen. Like lysergic acid diethylamide (LSD) and mescaline, psilocybin’s primary mechanism of action appears to be its agonism in serotonin 5-HT2A receiver.
The action of this receptor is very important in psychopharmacology, since many drugs currently used to treat depression and psychotic disorders act on serotonin 5-HT.2A receivers. They include the antidepressants mirtazapine (Remeron) and trazodone (Desyrel), as well as most atypical antipsychotics, such as aripiprazole (Abilify).
As mentioned above, the FDA is also investigating the Schedule 1 hallucinogen LSD.
A phase 2 controlled trial compared psilocybin with escitalopram (Lexapro) in patients with moderate to severe MDD. The result favored psilocybin, but not by much. Phase 3 studies are underway for MDD and treatment-resistant depression (TRD).
Important: There appears to be a lot of momentum behind the FDA’s eventual approval of psilocybin for the treatment of depression, along with other clinical applications being investigated.
Post-traumatic stress disorder (PTSD)
Currently, a handful of psychotherapies are the primary treatment for PTSD: exposure-based therapy, trauma-focused cognitive-behavioral therapy, cognitive therapy, and eye movement desensitization and reprocessing (EMDR) therapy.
Frustratingly, there are only two medications approved by the FDA for the treatment of PTSD: sertraline (Zoloft) and paroxetine (Paxil). Frankly, neither offers much to write home about.
Current research supports a model that primarily uses tailored psychotherapy and includes the administration of 3,4-methylenedioxymethamphetamine (MDMA). is known as MDMA-assisted psychotherapy.
Yes, that MDMA – “ecstasy” – a Schedule 1 drug.
MDMA is a empathogen – a drug that increases a person’s feeling of empathy and benevolence toward others, as well as the feeling of being accepted and socially connected.
Empathogens do their job by increasing the presynaptic release of serotonin, as well as the release of neurohormones oxytocin, prolactin, and cortisol.
But the key here is the hypothesis that MDMA enhances fear extinction, modulates fear memory reconsolidation, increases confidence, and amplifies emotional learning.
Now, this model of medication-assisted psychotherapy has created an important model to be used in other treatments. I’m thinking psilocybin, for sure. And I would be willing to bet on MM120 and esmethadone if they are approved.
Huge: On December 12, 2023, MAPS Public Benefit Corp submitted an application to the FDA requesting approval of combining MDMA with psychotherapy for the treatment of post-traumatic stress disorder. The generic name of the drug is midomafetamine (capsules).
In response, the FDA granted priority review status on February 13, 2024. Sounds like a done deal to me.
Watch the second part
I worked a lot to put this one together. But you know what? You would do the same for me.
Hopefully, you’ll have learned a thing or two and will feel comforted in knowing that the wheels of research continue to turn.
Be sure to stay tuned for part two, where we’ll turn our attention to medications in development for ADHD and schizophrenia.
Primary information sources: Psychiatric Times: Drug Pipeline: Schizophrenia and Post-Traumatic Stress Disorder, Channeling of medications; Antidepressants and ADHD Rx and drug issues: FDA Grants Breakthrough Therapy Designation to LSD-Based Treatment for Generalized Anxiety Disorder.
A variety of emotional and mental health information and inspirational articles are at your fingertips. Examine the titles.
Bill White is not a doctor and provides this information for educational purposes only. Always contact your doctor if he has questions, advice or recommendations.
After a decades-long battle with panic, generalized anxiety, mood swings and alcohol dependence; Bill finally found his passion and life’s work: lending a hand to those in the same boat. At age 49 he entered graduate school and earned his counseling credentials. And he continues his service through Chipur and other projects.
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