PTSD is a chronic condition marked by abnormally persistent and distressing memories, with current treatments limited to psychotherapy and two FDA-approved drugs that reduce depression and anxiety but do not produce permanent remission. Early evidence suggests psychedelics like psilocybin, MDMA, LSD, cannabinoids, ayahuasca, and ketamine, especially combined with psychotherapy, may help by increasing trust and enabling modification of trauma-related memories. Research into memory reconsolidation has identified pharmacological targets to disrupt fear memories. Pre-clinical and clinical studies have investigated novel agents such as neuropeptide Y, oxytocin, cannabinoids, and neuroactive steroids. While many drugs show promise in pilot trials, large-scale clinical trials are needed for clinical adoption.
This review summarizes preclinical studies on how ketamine affects fear extinction, the process of learning that trauma-related cues are no longer threatening. Findings are inconsistent: ketamine may enhance, impair, have no effect, or produce mixed effects on fear extinction, depending on dosage, route, and timing of administration. The authors recommend future research include more female subjects, use clinically relevant doses and routes, and employ behavioral assays relevant to human PTSD to improve translation from animal studies to clinical treatment.
A preliminary investigation into altered states of consciousness (ASC) analyzed 300 narrative reports across 12 induction methods, including meditation, float tank, and several psychedelics. Most psychedelics (except LSD), along with salvia and ketamine, shared similar content with non-pharmacological methods. In qualitative analysis, most psychedelics except LSD were deemed both positive and authentic, with authenticity predicting positive sentiment across all methods. Latent themes charted a trajectory from baseline to metaphysical experience, and text-to-image AI illustrated the underlying structure. The findings suggest that some ASC induction methods, such as salvia, ketamine, or 5-MeO-DMT, may be characterized as 'mind-manifesting,' but not others like LSD, datura, or DPH.