Psychoplastogen

Source: Wikipedia, the free encyclopedia.

Psychoplastogens are a group of

brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.[3]

Etymology and nomenclature

The term psychoplastogen comes from the Greek roots psych- (mind), -plast (molded), and -gen (producing) and covers a variety of chemotypes and receptor targets. It was coined by David E. Olson in collaboration with Valentina Popescu, both at the University of California, Davis.[3]

The term neuroplastogen is sometimes used as a synonym for psychoplastogen, especially when speaking to the biological substrate rather than the therapeutic.

Chemistry

Psychoplastogens come in a variety of chemotypes but, by definition, are small molecules.[1]

Pharmacology

Psychoplastogens exert their effects by promoting structural and functional neural plasticity through diverse targets including, but not limited to, 5-HT2A, NMDA, and muscarinic receptors. Some are biased agonists. While each compound may have a different receptor binding profile, signaling appears to converge at the tyrosine kinase B (TrkB) and mammalian target of rapamycin (mTOR) pathways.[3][4] Convergence at TrkB and mTOR parallels that of traditional antidepressants with known efficacies, but with more rapid onset.[5]

Due to their rapid and sustained effects, psychoplastogens could potentially be dosed intermittently.[6]

In addition to the neuroplasticity effects, these compounds can have other epiphenomena including sedation, dissociation, and hallucinations.[6]

Approved medical uses

Several psychoplastogens have either been approved or are in development for the treatment of a variety of brain disorders associated with neuronal atrophy where neuroplasticity can elicit beneficial effects.[6]

Esketamine, sold under the brand name Spravato and produced by Janssen Pharmaceuticals, was approved by the FDA in March 2019 for the treatment of Treatment-Resistant Depression (TRD) and suicidal ideation.[7] As of 2022, it is the only psychoplastogen approved in the US for the treatment of a neuropsychiatric disorder.[6] Esketamine is the S(+) enantiomer of ketamine and functions as an NMDA receptor antagonist.[8]

Clinical development

Other psychoplastogens that are being investigated in the clinic include:

  • MDMA-assisted psychotherapy is being investigated for treatment of PTSD. A recent placebo controlled Phase 3 trial found that 67% of participants in the MDMA+therapy group no longer met the diagnostic criteria for PTSD whereas 32% of those in the placebo+therapy group no longer met PTSD threshold.[9] MDMA-assisted psychotherapy is also currently in Phase 2 trials for eating disorders,[10] anxiety associated with life-threatening illness,[11] and social anxiety in autistic adults.[12]
  • psilocybin mushrooms that serves as a prodrug for psilocin, is currently being investigated in clinical trials of Hallucinogen-Assisted Therapy for a variety of neuropsychiatric disorders. To date studies have explored the utility of psilocybin in a variety of diseases, including TRD,[13][14] smoking addiction,[15][16] and anxiety and depression in people with cancer diagnoses.[17]
  • LSD is being tested in phase 2 trials for cluster headaches and anxiety.[18]
  • DMT is being studied for depression.[19]
  • 5-MeO-DMT is being studied for depression and eating disorders.[20]
  • Ibogaine and Noribogaine are being studied for addiction.[21][22][23]

List of known psychoplastogens

See also

References

  1. ^
    PMID 30262987
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  2. PMID 32150976
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  3. ^
    PMID 29898390
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  4. PMID 23751205
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  5. PMID 33312794
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  6. ^
    PMID 34671279
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  7. ^ Office of the Commissioner (2020-03-24). "FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor's office or clinic". U.S, Food and Drug Adminitartion. Retrieved 2021-08-26.
  8. ^ Olympic Behavioral Health
  9. PMID 33972795
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  10. ^ Clinical trial number NCT04454684 for "An Open-Label, Multi-Site Phase 2 Study of the Safety and Feasibility of MDMA-Assisted Psychotherapy for Eating Disorders" at ClinicalTrials.gov
  11. ^ Clinical trial number NCT02427568 for "A Randomized, Double-Blind, Placebo-Controlled Phase 2 Pilot Study of MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illnes" at ClinicalTrials.gov
  12. ^ Clinical trial number NCT02008396 for "A Placebo-controlled, Randomized, Blinded, Dose Finding Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults" at ClinicalTrials.gov
  13. PMID 29030624
    .
  14. ^ Clinical trial number NCT05029466 for "The Efficacy and Tolerability of Psilocybin in Participants With Treatment-Resistant Depression: a Phase 2, Randomized Feasibility Study" at ClinicalTrials.gov
  15. PMID 27441452
    .
  16. ^ Clinical trial number NCT01943994 for "Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study" at ClinicalTrials.gov
  17. PMID 27909165
    .
  18. ^ Clinical trial number NCT03781128 for "Safety and Efficacy of Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache: a Randomized, Double-blind, Placebo-controlled Phase II Study" at ClinicalTrials.gov
  19. PMID 35064294
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  20. PMID 30822141
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  21. ^ Parkins K (10 March 2021). "DemeRx and Atai get MHRA nod to start trial of ibogaine for opioid use disorder". Clinical Trials Arena. Retrieved 2022-05-11.
  22. PMID 30272050
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  23. ^ "Ibogaine Use in Addiction Treatment: An Overview". INN. 2022-02-23. Retrieved 2022-05-11.
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