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
February 1, 2015
Hannah Steeds, Robin Carhart-Harris, James Stone
132 citations
Schizophrenia involves positive, negative, and cognitive symptoms, and about one-third of patients do not respond to existing medications. This review evaluates how drugs acting on dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic, and kappa opioid systems model aspects of schizophrenia in animals and humans. Understanding interactions between these neurotransmitter systems and their links to symptoms is crucial for forming a coherent hypothesis of schizophrenia's pathogenesis and developing new therapies.
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
Anya Ragnhildstveit, Jeremy Roscoe, Lisa C. Bass et al.
49 citations
PTSD has few effective pharmacological treatments, and trauma-focused psychotherapies are limited by provider shortages and low patient engagement, often leading to chronic illness and reduced quality of life. Ketamine, an NMDA receptor antagonist already indicated for major depression with rapid antidepressant effects, shows transdiagnostic potential. A synthesis of clinical evidence—including case reports, chart reviews, open-label studies, and randomized trials—reveals high heterogeneity in presentation and treatment approach but encouraging signals of safety, efficacy, and durability. Future research directions are discussed.
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
April 1, 2017
Álvaro López-díaz, José Luis Fernández-gonzález, José Evaristo Luján-jiménez et al.
27 citations
A case report describes a female patient hospitalized for months with treatment-resistant bipolar depression and chronic suicidal behavior. After repeated intravenous ketamine infusions with no notable side effects, she achieved complete clinical recovery for four weeks following discharge. Depressive symptoms returned in the fifth week, leading to hospital readmission after a suicide attempt. The report highlights ketamine's rapid but temporary antidepressant effects and the risk of relapse, underscoring concerns about its off-label use in clinical practice despite its potential for refractory depression.
Therapeutic Advances in Psychopharmacology
January 1, 2022
Otto Simonsson, Peter S. Hendricks, Richard Chambers et al.
26 citations
In a US-representative sample of 2822 adults, lifetime use of classic psychedelics was linked to healthier tobacco-related and diet-related behaviors. Among the 613 who had used psychedelics, greater psychological insight during their most insightful experience was associated with healthier exercise habits, a healthy body mass index, and diet improvements. Psychological insight was also tied to self-reported health behavior improvements attributed to the psychedelic experience, including alcohol-related changes. The findings suggest that psychological insight during a classic psychedelic experience may promote positive health behavior change and better physical health, especially in weight management, though causality cannot be established.
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, 2023
Vivian W. L. Tsang, Brendan Tao, Shannon Dames et al.
19 citations
A retrospective chart review of 128 participants in a 12-week ketamine-assisted group therapy program found that the treatment was well tolerated, with no dropouts. Across 448 sessions, elevated blood pressure occurred after 49.16% of sessions, while nausea affected 12.05% of participant-sessions, vomiting 2.52%, headache 3.35%, and dizziness in seven participant-sessions. Adverse events were transient and resolved with rest or medication. The findings suggest good safety and tolerability for intramuscular and sublingual ketamine dosing in a community group psychotherapy setting.
Therapeutic Advances in Psychopharmacology
April 1, 2016
Jessica A Meisner, Susan R Wilcox, Jeremy B Richards
19 citations
A 40-year-old man who took ibogaine to manage heroin withdrawal suffered acute cardiac arrest, leading to cerebral edema and brain death. The case, consistent with ibogaine-induced cardiotoxicity, underscores significant clinical risks. A review of the literature on ibogaine's history, mechanisms, and adverse effects accompanies the report. Clinicians should be aware of ibogaine's potential to cause cardiac arrest and provide informed counseling about the dangers of using it for opioid detoxification.
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
Raymond Yan, Tyler Marshall, Atul Khullar et al.
11 citations
Over a 4-week course of eight intravenous ketamine infusions, adults with treatment-resistant depression reported improved sleep quality and an earlier circadian rhythm. Sleep quality, measured by the Pittsburgh Sleep Quality Index, improved significantly, as did depressive symptoms. Circadian rhythm, measured by the Morningness-Eveningness Questionnaire, shifted earlier. Improvements in sleep duration and daytime dysfunction were also observed. The effect on sleep quality was more prominent in patients with mixed features of depression, while the circadian shift was more prominent in those without mixed features. The study was small and uncontrolled, so findings are preliminary.
Therapeutic Advances in Psychopharmacology
January 1, 2024
Baeleigh VanderZwaag, Albert Garcia‐romeu, Mauricio A. García-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
September 1, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
8 citations
Psychedelic-assisted therapy (PAT) is a complex intervention combining pharmacological, psychotherapeutic, and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional randomized controlled trials may fail to capture these complexities. This position paper advocates applying the UK Medical Research Council's framework for complex interventions to PAT development and evaluation, emphasizing the need to articulate the theory of therapeutic change, structure intervention development into phases, account for contextual interactions, and incorporate stakeholder perspectives.
Therapeutic Advances in Psychopharmacology
January 1, 2021
Adam Włodarczyk, Wiesław Jerzy Cubała, Maria Gałuszko‐węgielnik et al.
8 citations
In treatment-resistant inpatients with major depressive disorder (MDD) or bipolar disorder (BP), intravenous ketamine was generally well-tolerated with no lasting neurological harm. However, certain concurrent medications were linked to more psychomimetic and dissociative symptoms. Patients taking the antidepressant citalopram reported greater psychomimetic effects. Classic mood stabilizers—lamotrigine, valproate, and lithium—were each significantly associated with increased scores on the Brief Psychiatric Rating Scale. No long-term adverse effects were observed. The findings suggest that ketamine treatment requires careful monitoring for dissociative and psychomimetic symptoms, especially when combined with specific psychotropic drugs.
Therapeutic Advances in Psychopharmacology
January 1, 2025
Ahmed Elmosalamy, Idil Tarikogullari, Liliana Patarroyo-Rodriguez et al.
7 citations
About one-third of people with depression do not respond to standard treatments, a condition known as treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (given IV or as a nasal spray) are newer options for TRD, but only the nasal spray version of esketamine is FDA-approved. A meta-analysis of eight studies with 978 adults directly comparing IV ketamine with esketamine found that both treatments produced similar rates of response and remission after acute treatment, with a slight but not statistically significant advantage for IV ketamine. IV ketamine may work faster, but the evidence is mostly from observational studies, and large randomized trials are needed to confirm these findings.