Expert Review of Clinical Pharmacology
May 26, 2021
Suresh Muthukumaraswamy, Anna Forsyth, Thomas Lumley
312 citations
Psychedelic drugs like psilocybin, LSD, and ketamine show promise for treating mental health disorders, but their effectiveness in randomized controlled trials may be overstated. Previous research indicates that participants in psychedelic trials often become unblinded—they can tell whether they received the drug or a placebo—and may have strong expectations of improvement. A systematic review of trials from 1990 to 2020 found that most did not measure pre-trial expectancy or check whether blinding was successful. The authors argue that reported treatment effect sizes are likely overestimated due to these confounds. They recommend routine measurement of de-blinding and expectancy, careful trial design, and caution when interpreting existing effect size estimates.
Expert Review of Clinical Pharmacology
August 13, 2018
Rafael G. Dos Santos, José Carlos Bouso, Miguel Ángel Alcázar‐córcoles et al.
231 citations
Serotonergic hallucinogens/psychedelics such as ayahuasca, psilocybin, and LSD show promise for reducing anxiety, depression, and substance dependence. Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence; ayahuasca reduced depression symptoms in treatment-resistant depression. However, many studies were open-label, few were randomized controlled trials, most had small sample sizes and short duration. Single or few doses appear well tolerated, but long-term studies are lacking. New RCTs with larger samples and longer duration are needed to confirm these findings.
Expert Review of Clinical Pharmacology
June 1, 2020
87 citations
Combinations of psychotherapy with antidepressants and psychedelic-assisted psychotherapy both work through complex, interactional mechanisms. A review of therapeutic mechanisms behind conventional and psychedelic paradigms, including the evolution of this knowledge and explanatory frameworks, finds that the contextual model of common factors in psychotherapy provides a powerful perspective on psychotherapy, antidepressants, psychedelics, MDMA, and ketamine. Conventional antidepressants and especially psychedelics may improve psychotherapy's efficacy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing knowledge and treatment of many forms of psychopathology.
Expert Review of Clinical Pharmacology
March 17, 2016
Fabrizio Schifano, Gabriele Duccio Papanti, Laura Orsolini et al.
66 citations
Novel psychoactive substances (NPS), including stimulants and hallucinogens, disrupt multiple neurotransmitter pathways, particularly dopamine, cannabinoid CB1, and 5-HT2A receptors. Their intake is almost never detected by standard drug screening tests. Acute management of NPS misusers should prioritize reducing self-directed and outward-directed aggression and agitation. Benzodiazepines are recommended as first-line treatment, with propofol or antipsychotics as alternatives. Treatment must also address possible rhabdomyolysis and hyperthermia. Future research is needed to develop better-tailored management strategies.
Expert Review of Clinical Pharmacology
November 2, 2023
Fabrizio Schifano, Alessandro Vento, Norbert Scherbaum et al.
30 citations
Clinicians need regular updates on novel psychoactive substances (NPS) and their acute and long-term medical, psychobiological, and psychopathological risks. Future research should combine pro-drug website analysis with computational chemistry to organize preclinical studies of new psychoactives. Psychedelic research should develop robust study designs to assess potential therapeutic benefits, as these molecules likely have limited dependence liability.
Expert Review of Clinical Pharmacology
July 10, 2020
Justin P. Reinert, Kayla N. Colunga, Alexandria Etuk et al.
11 citations
Use of salvia, kratom, and psilocybin mushrooms is rising globally, and healthcare practitioners should consider these substances when triaging overdose cases. Although overdoses from these agents are not typically fatal, clinicians need to be prepared to identify them as a possible cause and provide appropriate supportive care.
Expert Review of Clinical Pharmacology
October 3, 2025
Lorena Terene Lopes Guerra, Isabella Caroline Da Silva Dias, Jaime E. C. Hallak et al.
2 citations
Whether subjective experience contributes to therapeutic mechanisms of ayahuasca is debated and may depend on the targeted condition. Few controlled studies exist, limiting conclusions on safety and efficacy. Ayahuasca's highly variable composition poses an additional challenge, prompting studies using isolated compounds.