Therapeutic Advances in Psychopharmacology
March 18, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Therapeutic Advances in Psychopharmacology
January 1, 2020
D. Matveychuk, Rejish K Thomas, Jennifer Swainson et al.
209 citations
Ketamine, an anesthetic from the 1960s, has gained attention as a treatment for major depressive disorder, especially treatment-resistant depression, with potential anti-suicidal effects. Unlike traditional antidepressants that take weeks, ketamine can produce rapid antidepressant effects within hours. Its mechanism involves glutamate modulation through NMDA and AMPA receptors, plus activation of BDNF and mTOR pathways to enhance synaptic plasticity. This paper reviews ketamine's pharmacology, toxicology, clinical trial status, and proposed antidepressant mechanisms, along with potential biomarkers—biochemical, inflammatory, metabolic, neuroimaging, sleep-related, and cognitive—for predicting or monitoring therapeutic response.
Therapeutic Advances in Psychopharmacology
February 23, 2017
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
167 citations
Ayahuasca, a hallucinogenic brew from the Northwestern Amazon, contains DMT, which acts on serotonin 5-HT2A receptors similarly to LSD and psilocybin. Controlled use of these substances is rarely linked to psychotic episodes, but little is known about use outside controlled settings. A systematic review of case reports identified three case series and two case reports of psychotic episodes after ayahuasca use, and three case reports after DMT use. Many cases involved individuals with personal or family histories of psychosis or other drug use, though some episodes occurred in people without such histories. Overall, psychotic episodes appear rare in both ritual and recreational settings. Psychiatric screening before hallucinogen administration in controlled settings may reduce adverse reactions; individuals with personal or family histories of psychotic illness or mania should avoid hallucinogens.
Therapeutic Advances in Psychopharmacology
January 26, 2015
David Baumeister, Luis M. Tojo, Derek K. Tracy
158 citations
A growing number of new or novel psychoactive substances (NPS), often called 'legal highs', are being produced by modifying existing drugs to circumvent bans. In 2013 alone, 81 new substances were identified. This rapid evolution has created confusion for clinicians and the public, partly because newer compounds can be more potent. This review categorizes NPS into five groups based on parent compounds: stimulants, cannabinoids, benzodiazepines, dissociatives, and classic hallucinogens. For each class, the paper describes pharmacodynamics, effects, harmfulness, dependency risk, and potential clinical uses. Clinicians may encounter NPS through acute intoxication, substance misuse, or longer-term health effects. Current knowledge is limited, and more research is urgently needed.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Michiel van Elk, Eiko I. Fried
126 citations
Despite a decade of optimism about psychedelics for treating mental disorders, psychedelic science faces serious challenges that threaten the validity of core findings. The paper identifies 10 pressing problems grouped into easy, moderate, and hard categories, showing how they undermine internal validity (treatment effects due to unrelated factors), external validity (lack of generalizability), construct validity (unclear working mechanisms), and statistical conclusion validity (conclusions not supported by data). These problems often co-occur, limiting conclusions about safety and efficacy. The authors provide a roadmap and checklist for stakeholders to assess study quality, emphasizing that addressing these issues is necessary to determine whether therapeutic optimism is warranted and to avoid repeating past mistakes.
Therapeutic Advances in Psychopharmacology
January 1, 2020
Kim P.C. Kuypers
83 citations
Microdosing psychedelics, the repeated use of small doses of LSD or psilocybin, has been claimed to help with depression, but scientific evidence is limited. This review of 14 experimental studies found that low doses (LSD 10–20 mcg, psilocybin <1–3 mg) produce subtle positive effects on cognitive processes like time perception and thinking, and affect brain regions involved in emotion. However, increased anxiety and cycling between depressive and euphoric moods also occurred. Low doses were well tolerated in healthy volunteers with minimal physiological effects. While therapeutic value for depression remains unclear, the effects on cognitive flexibility might reduce rumination. Placebo-controlled trials in depressed patients are needed.
Therapeutic Advances in Psychopharmacology
March 23, 2016
Saibal Das, Preeti Barnwal, Anand Ramasamy et al.
51 citations
Lysergic acid diethylamide (LSD), a classical hallucinogen accidentally discovered in the mid-20th century, has been used both as a substance of abuse and as a potential therapeutic adjunct. This review describes its receptor pharmacology, mechanism of action, effects on the body, and adverse effects, including its addictive potential and tolerance development. Therapeutic uses explored include anxiety relief, creativity enhancement, suggestibility, performance enhancement, and treatment of drug and alcohol dependence, as well as psychedelic peak therapy for terminally ill patients. Based on available evidence, LSD could be tried therapeutically under controlled settings, but its use requires expertise, caution, and ethical considerations due to safety concerns.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Ricarda Evens, Tomislav Majić, Timo Torsten Schmidt et al.
49 citations
A systematic review of 48 studies involving 1,774 participants found that classic serotonergic psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) produce a characteristic pattern of subacute effects lasting from one day to one month after use. These include reductions in psychopathological symptoms, increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes, along with mixed changes in personality and creativity. Subacute adverse effects included headaches, sleep disturbances, and individual cases of increased psychological distress, but no serious adverse events were reported. The findings support the existence of a 'psychedelic afterglow' phenomenon that may enhance psychotherapeutic interventions.
Therapeutic Advances in Psychopharmacology
January 1, 2019
Juliana Mendes Rocha, Flávia de Lima Osório, José Alexandre S. Crippa et al.
44 citations
A systematic review of 8 studies found that serotonergic hallucinogens such as LSD and psilocybin reduce the recognition of negative emotions in facial expressions and modulate amygdala activity in response to these stimuli. These effects correlated with antidepressive benefits in patients. The drugs were well tolerated. Although sample sizes were small, the results suggest that serotonergic hallucinogens may reverse deficits in emotion recognition associated with anxiety and mood disorders.
Therapeutic Advances in Psychopharmacology
January 1, 2020
P. Glue, N. Medlicott, Shona Neehoff et al.
43 citations
An extended-release oral ketamine tablet was tested in seven patients with treatment-resistant depression and anxiety who had previously responded to subcutaneous ketamine. Over 96 hours, all patients showed more than 50% improvement in mood ratings, with gradual reductions in anxiety and depression. The tablet was safe and well tolerated, with no changes in vital signs and only one brief report of dissociation. The ratio of norketamine to ketamine increased over time, suggesting ketamine may induce its own metabolism. Serum BDNF concentrations did not change. The findings suggest extended-release oral ketamine may improve safety and tolerability while offering a slightly delayed onset of mood improvement compared to injected forms.
Therapeutic Advances in Psychopharmacology
January 1, 2020
Matthew Butler, Mathieu Seynaeve, Timothy R. Nicholson et al.
38 citations
Functional neurological disorder (FND), previously called conversion disorder, is common in neurology clinics and causes substantial disability, but treatment options are limited. Psychedelics like psilocybin and LSD may help by altering brain circuits involved in self-representation, which is thought to be disrupted in FND. A systematic review of nine studies from 1954 to 1967, involving 26 patients, found that most received psychotherapy with variable adjunctive psychedelic use (psycholytic therapy). Of those treated, 69% (18 patients) showed at least some recovery on subjective clinician-rated criteria. Adverse events were mostly mild, though one patient withdrew due to distressing effects. All studies were low quality, lacking controls and valid outcome measures, so no conclusions on efficacy can be drawn.
Therapeutic Advances in Psychopharmacology
October 27, 2016
Ananya Mahapatra, Rishi Gupta
37 citations
Psilocybin, a naturally occurring alkaloid pharmacologically similar to LSD, is primarily used as a recreational drug or entheogen. Recent population-based studies indicate it does not cause serious physical or mental health problems or dependent use. Because of its novel mechanism as a 5-HT2A serotonin receptor agonist and its potential to increase subjective well-being, psilocybin is being investigated for therapeutic use in mood and anxiety disorders.
Therapeutic Advances in Psychopharmacology
January 1, 2023
Farhan Fancy, Sipan Haikazian, Danica E. Johnson et al.
23 citations
Ketamine given intravenously at subanesthetic doses (0.5–0.75 mg/kg) or as esketamine (28–84 mg) appears safe and effective as an add-on treatment for bipolar depression when combined with a mood stabilizer. Across eight studies (235 participants), 48% of those receiving ketamine achieved at least a 50% reduction in depression severity, compared with 5% on placebo. Real-world response rates were lower (30%) than in clinical trials (63%). Some studies noted reductions in suicidal ideation, though not all findings were statistically significant. Ketamine was generally well tolerated, but 2% of participants (five receiving ketamine) developed hypomanic or manic symptoms, and significant dissociative effects occurred at 40 minutes in some trials.
Therapeutic Advances in Psychopharmacology
January 1, 2022
Caroline Hayes, Mourad Wahba, Stuart Watson
17 citations
Psilocybin-assisted psychotherapy faces unique challenges as it moves from research into clinical practice. Patients often arrive with overly positive expectations shaped by media coverage, and the drug's effects can increase suggestibility, requiring specially trained therapists. The authors recommend measures for phase 3 trials and clinicians to address these issues, aiming to help psilocybin become a licensed medication that suitable patients can access relatively easily. Practicing psychiatrists should be aware of these potential pitfalls, as they will be responsible for future prescribing.
Therapeutic Advances in Psychopharmacology
January 1, 2024
Baeleigh VanderZwaag, Albert Garcia-Romeu, Mauricio A Garcia-Barrera
9 citations
Psychedelics were the third most used substance in the past year among athletes (35.8%), though regular use was low (7.5%). In a survey of 175 athletes and staff in Canada and the United States, 61.2% of athletes reported likely engaging in psilocybin-assisted therapy (PAT) for concussion recovery, and 71.1% of staff said they would support athletes using PAT. Attitudes toward psilocybin and knowledge of psilocybin predicted willingness to use or support PAT. The sports community may be receptive to PAT for managing persisting concussion symptoms.
Therapeutic Advances in Psychopharmacology
January 1, 2024
Eduardo Ekman Schenberg
7 citations
A commentary responds to a call for greater methodological rigor in psychedelic research, agreeing that studies should adhere to principles of internal, external, and construct validity. The authors note that conclusions must not exceed what robust statistical inferences support. They find valuable the examples of past inadequacies and mistakes, including oversight by peer reviewers, and affirm that future research can benefit from increased rigor.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Stanley Wong, Gray Meckling, Nicholas Fabiano et al.
6 citations
A systematic review and meta-analysis of nine randomized controlled trials involving 593 adults with psychiatric diagnoses found that psilocybin therapy led to a small but significant decrease in suicidal ideation compared to control conditions. No studies reported suicide attempts or deaths. The analysis showed low heterogeneity and no publication bias, though two studies had a high risk of bias. Current evidence is limited by small sample sizes, insufficient follow-up data, and inadequate assessment of blinding.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Sally Meikle, Olivia Carter, Paul Liknaitzky et al.
2 citations
In an open-label pilot trial, two 25 mg doses of psilocybin combined with psychotherapy produced a clinically meaningful reduction in depressive symptoms at 3 weeks in people with treatment-resistant depression. The average improvement was sustained at 20 weeks, but individual responses varied: two participants showed lasting benefit, three relapsed, and two did not improve. Mindset before dosing, spiritual experiences, and perceptual changes during the session predicted treatment trajectory, whereas treatment expectations did not. No serious adverse events occurred. The findings support further research into tailoring psilocybin therapy to individual variability.
Therapeutic Advances in Psychopharmacology
March 1, 2026
Guillaume Thuery, Frank Crossen, Daniel Mc Loone et al.
1 citation
About 15% of pregnant women experience postpartum depression, and many remain impaired despite available antidepressants. Serotonergic psychedelics may offer a viable therapeutic approach for postpartum depression, though the benefit-risk ratio is unclear. This review summarizes immune, endocrine, and neural pathways underlying postpartum depression and explores how psychedelics interact with these pathways in relation to maternal motivation, bonding, and caregiving. Special considerations for psychedelic therapy in the postpartum period are outlined. Further research, especially longitudinal trials with adaptations for the postpartum context, is needed to determine efficacy and safety.
Therapeutic Advances in Psychopharmacology
June 8, 2025
Nadav Liam Modlin, Victoria Williamson, Carolina Maggio et al.
1 citation
PTSD is a common and debilitating condition that current treatments only partially address. This review examines psilocybin, a classical psychedelic, as a potential therapeutic agent. It synthesizes recent literature on psychedelic therapies for trauma-related conditions, including treatment-resistant depression and end-of-life anxiety. The authors propose a conceptual framework viewing PTSD as a maladaptive interpretive framework that psilocybin may disrupt through its psychopharmacological properties and subjective effects. A clinical narrative illustrates this process. Recommendations emphasize rigorous, trauma-informed protocols for safe administration in medical research settings.
Therapeutic Advances in Psychopharmacology
July 1, 2026
Karthika Kasiviswanathan, Dinuli Nilaweera, M Morando et al.
MDMA-assisted psychotherapy (MDMA-AP) may help treat not only PTSD but also complex PTSD and borderline personality disorder. A systematic review of 24 studies involving 335 participants found that most reported reduced PTSD symptoms after MDMA-AP, with some noting decreased dissociative symptoms at higher doses. Although no studies directly assessed MDMA-AP for complex PTSD or borderline personality disorder, improvements in emotional regulation, interpersonal functioning, identity coherence, and abandonment concerns were reported. Adverse drug reactions were mild to moderate, though specific safety concerns remain. These findings offer preliminary insights for future research and clinical considerations.
Therapeutic Advances in Psychopharmacology
March 1, 2026
Ana Deutsch, Luis E. Contreras, Sarah Kratina et al.
Mystical-type experiences induced by psychedelic therapy are commonly linked to reductions in anxiety and depression symptoms, according to a scoping review of 13 clinical trials involving 410 participants. Among studies with life-threatening disease populations, 80% reported a positive relationship between mystical-type experiences and mood improvement, compared to 63% of studies with depressive populations. The review suggests this relationship may depend on factors like timing of symptom assessments and therapeutic context. Future research should examine variables affecting mystical-type experiences and other aspects of set and setting to optimize positive outcomes.
Therapeutic Advances in Psychopharmacology
December 1, 2025
Tiago Machado, Ana Rodrigues, João Costa
Psilocybin, a hallucinogen known for its therapeutic potential in psychiatry, has shown remarkable promise in reducing depression. In a sample of 200 participants, 70% reported significant improvements in mood after treatment. Additionally, psilocybin was associated with a 50% decrease in suicidal thoughts among those with severe depression. This medicine not only offers hope for pain management but also raises intriguing questions about the placebo effect and its implications for mental health economics. Enhanced understanding could reshape approaches to suicide prevention and psychological well-being.