Clinical pharmacology and therapeutics
February 1, 2025
Ksenia A Vekhova, Eugenia D Namiot, Jörgen Jonsson et al.
43 citations
Between 2014 and 2024, 363 clinical trials on ketamine were registered. Most trials addressed FDA-approved uses: anesthesia (22%), pain management (28%), and esketamine for treatment-resistant depression (29%). Trials for treatment-resistant depression have reached phase III and IV. Combinations with electroconvulsive therapy, psychotherapy, virtual reality, or transcranial magnetic stimulation are common. Sub-anesthetic doses may offer new treatments for neuropsychiatric conditions involving glutamate excitotoxicity and oxidative stress, such as major depression, schizophrenia, and bipolar disorder. The number of ketamine studies is expected to grow, and new variants may be approved for additional indications.
Clinical pharmacology and therapeutics
November 1, 2024
Shruti M Raja, Jeffrey T Guptill, Michelle Mack et al.
34 citations
A metabolite of ketamine, (2R,6R)-hydroxynorketamine (RR-HNK), was tested in a Phase 1 study in healthy volunteers for safety and tolerability. RR-HNK lacks anesthetic and dissociative effects but retains antidepressant and analgesic activity in preclinical models. In single doses from 0.1 to 4 mg/kg and multiple doses of 1 and 2 mg/kg given intravenously over 40 minutes, RR-HNK showed minimal adverse events and no serious adverse events. It did not cause dissociation or sedation. Drug levels in the body increased proportionally with dose, and cerebrospinal fluid analysis confirmed it reached the central nervous system. Some participants showed increases in gamma brain wave activity at lower to mid doses. These results support moving to Phase 2 trials.
Clinical pharmacology and therapeutics
November 1, 2024
Andriy A Gorbenko, Jules A A C Heuberger, Linda E Klumpers et al.
17 citations
A clinical trial tested whether cannabidiol (CBD) can reduce the adverse effects of tetrahydrocannabinol (THC) and improve its tolerability as an analgesic. Healthy volunteers received THC alone or with different doses of CBD. Contrary to expectations, the highest CBD dose (450 mg) significantly increased THC's subjective, psychomotor, cognitive, and autonomous effects—for example, feeling high increased by 60.5%—and did not enhance pain relief. Lower CBD doses had no significant effect on THC's effects. CBD also increased blood levels of THC and its active metabolite. The findings do not support using CBD to reduce oral THC's adverse effects or to improve its analgesic properties.
Clinical pharmacology and therapeutics
June 1, 2025
Zhibin Wang, Lili Jiang, Wenzhuang Ma et al.
8 citations
A systematic review and meta-analysis of randomized controlled trials found that esketamine nasal spray, when used alongside an antidepressant, reduces depressive symptoms more than placebo in people with major depressive disorder. In patients without suicidal thoughts, symptoms improved by day 28; in those with suicidal thoughts, improvement was seen by day 2. Long-term relapse rates were 40% lower with esketamine than with placebo or quetiapine. The rate of suicidal ideation was similar between groups. The evidence was rated moderate to high certainty. Esketamine nasal spray appears to effectively control short- and long-term depressive symptoms with a manageable balance of benefits and risks.
Clinical pharmacology and therapeutics
May 26, 2025
Denis Arikci, Friederike Holze, Lorenz Mueller et al.
6 citations
LSD base and tartrate formulations taken orally are bioequivalent, meaning they produce the same drug levels in the body. The absolute oral bioavailability of LSD is 80%, and all tested oral forms—ethanolic base solution, watery tartrate solution, and rapid-dissolving tablet—show similar pharmacokinetics. Intravenous LSD causes stronger subjective effects like ego dissolution and anxiety compared to oral forms. These findings support interchangeable oral dosing in research and clinical use.
Clinical pharmacology and therapeutics
June 1, 2025
Evan D Kharasch
4 citations
The first clinical report and first-in-human study of the drug that became ketamine is described. Ketamine serves as an analgesic, anesthetic, antidepressant, and drug of misuse, and remains the only dissociative anesthetic. It has challenged classical pharmacologic theory and drug development paradigms, with its initial report unable to foresee the molecule's pharmacologic complexity or clinical utility.
Clinical pharmacology and therapeutics
July 1, 2026
Tijana Stojanović, Kent W Nilsson, Robert Fredriksson et al.
The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.