Advances in pharmacology (San Diego, Calif.)
January 1, 2019
Jeffrey M Witkin, Anna E Martin, Lalit K Golani et al.
71 citations
A new class of antidepressants, emerging since 2006, offers rapid onset, large effect size, and efficacy after single or few doses, even in treatment-refractory patients and against symptoms like anhedonia. Controlled clinical studies have demonstrated rapid-acting effects for ketamine, other NMDA receptor antagonists, and scopolamine, with less clinical data for psychedelic drugs such as psilocybin, LSD, and ayahuasca. The mechanisms are not fully understood, but potentiation of AMPA receptor function appears to be a general trigger. Durability is limited for ketamine and scopolamine, while psychedelics may produce effects lasting months. Side effects and lack of enduring effects are primary impediments. Esketamine is FDA-approved; compounds in clinical development include (R)-ketamine, Rapastinel, and TAK-653. Preclinical evidence suggests potential for mGlu2/3 receptor antagonists, AMPA receptor potentiators, and GABAA(α5) negative allosteric modulators.
Advances in pharmacology (San Diego, Calif.)
January 1, 2020
Bashkim Kadriu, Elizabeth D Ballard, Ioline D Henter et al.
35 citations
Psychiatry is moving toward early identification and intervention to reduce the burden and duration of severe mental illnesses. The rapid-acting antidepressant ketamine has transformed understanding of antidepressant response and expanded treatment options for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response aim to identify biologically enriched subgroups more likely to benefit. This chapter reviews translational biomarkers from imaging, electrophysiology, sleep, circadian rhythms, HPA axis function, metabolism, immune, (epi)genetic, and neurotrophic systems. Ketamine's properties may model new rapid-acting treatments. However, most studies focus on acute effects, and no biomarkers are ready for clinical use.
Advances in pharmacology (San Diego, Calif.)
January 1, 2022
Justin C Strickland, Matthew W Johnson
13 citations
The past decade has seen rapid growth in research on the basic science and clinical understanding of psychedelics. This chapter reviews the human behavioral pharmacology of three classic psychedelics: psilocybin, LSD, and DMT. It covers historical background, drug classification, and special considerations such as set and setting, mystical experience measurement, blinding, placebos, and abuse liability. The subjective, physiological, and clinical effects of these substances are described, documenting a unique collection of acute and long-term behavioral changes. Clinical research shows potential therapeutic utility in difficult-to-treat conditions like treatment-resistant depression, alcohol use disorder, and cigarette smoking. Future work is needed to reveal mechanisms of behavior change.