Journal of Clinical Psychopharmacology
December 11, 2015
Rafael Faria Sanches, Flávia de Lima Osório, Rafael G. Dos Santos et al.
468 citations
A single oral dose of ayahuasca, an Amazonian brew containing dimethyltryptamine and harmine, produced fast-acting and sustained reductions in depression severity among 17 patients with recurrent depression. Scores on the Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Brief Psychiatric Rating Scale decreased significantly from 80 minutes through 21 days after intake. Brain imaging showed increased blood flow in the left nucleus accumbens, right insula, and left subgenual area—regions involved in mood regulation. Vomiting occurred in 47% of participants, but no other adverse effects were reported. The authors suggest ayahuasca may have antidepressant properties but call for replication in randomized, double-blind, placebo-controlled trials.
Journal of Clinical Psychopharmacology
August 1, 2000
Jordi Camı́, Magı́ Farré, Marta Más et al.
237 citations
In a randomized, double-blind, crossover, controlled trial with eight healthy male volunteers, MDMA at recreational doses (75 and 125 mg) produced marked euphoria and well-being, as measured by increased scores on the Addiction Research Center Inventory MBG and A scales and visual analog scales for 'stimulated,' 'good effects,' 'liking,' and 'high.' The 125 mg dose also caused mild sedation, dysphoria, and a slight decrease in performance on the digit-symbol substitution test, along with esophoria. Amphetamine (40 mg) produced similar euphoric effects but improved psychomotor performance. No hallucinations or psychoses occurred. These findings support MDMA's abuse liability.
Journal of Clinical Psychopharmacology
June 20, 2012
Lobna Ibrahim, Nancy Diazgranados, Libby Jolkovsky et al.
219 citations
A small pilot study tested the antidepressant efficacy and tolerability of an oral formulation of the selective NMDA NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder. In a randomized, double-blind, placebo-controlled crossover design, five patients completed both periods of MK-0657 monotherapy (4-8 mg/d) or placebo for 12 days. Significant antidepressant effects were seen as early as day 5 on the Hamilton Depression Rating Scale and Beck Depression Inventory, but not on the Montgomery-Asberg Depression Rating Scale, the primary measure. No serious or dissociative adverse effects occurred. The findings suggest MK-0657 may have antidepressant properties, but larger studies are needed.
Journal of Clinical Psychopharmacology
October 1, 1991
Una D. Mccann, George A. Ricaurte, Domenic A. Ciraulo
137 citations
Two people who took large doses of MDMA, a recreational amphetamine analog, developed long-lasting neuropsychiatric syndromes. These cases suggest that MDMA, which is known to damage serotonin neurons in animals, may also cause harmful effects in humans. The evidence indicates that ingesting large amounts of MDMA can lead to lasting adverse functional consequences in vulnerable individuals.
Journal of Clinical Psychopharmacology
October 15, 2011
Rafael G. Dos Santos, Marta Valle, José Carlos Bouso et al.
136 citations
Ayahuasca, an Amazonian psychotropic tea containing DMT and β-carboline alkaloids, produced moderate sympathomimetic effects, significant increases in prolactin and cortisol, and time-dependent changes in immune cell populations in a double-blind crossover trial with 10 healthy volunteers. Pupil dilation occurred with both ayahuasca and amphetamine, but ayahuasca’s effects were milder. Prolactin rose only after ayahuasca, while cortisol peaked higher with ayahuasca than with amphetamine. Lymphocyte subsets shifted similarly for both drugs: CD4 and CD3 percentages decreased, and natural killer cells increased, with maximum changes at 2 hours and return to baseline by 24 hours.
Journal of Clinical Psychopharmacology
August 25, 2012
Fabrizio Schifano, John Corkery, A. Hamid Ghodse
113 citations
Mephedrone, a popular recreational stimulant, has been linked to fatalities in the United Kingdom. Analysis of 62 concluded inquest cases from the UK National Programme on Substance Abuse Deaths database shows that typical victims were young (average age 28.8 years), male, and had a history of drug misuse. A notable 29% of deaths involved self-harm, with 11 of those 18 cases resulting from hanging. Mephedrone alone was identified at postmortem in 13% of cases. The findings suggest caution when using mephedrone, though the exact risks remain unclear.
Journal of Clinical Psychopharmacology
June 23, 2021
Rafael G. Dos Santos, Flávia de Lima Osório, Juliana Mendes Rocha et al.
85 citations
Ayahuasca, a classic hallucinogen with anxiolytic and antidepressive properties, improved self-perception of speech performance in individuals with social anxiety disorder. In a pilot, proof-of-concept, randomized, parallel-group trial with 17 volunteers, ayahuasca significantly increased positive self-statements during a public-speaking test compared with placebo, alongside increased somatic symptoms such as nausea and gastrointestinal discomfort. The drug did not significantly alter task-related anxiety or recognition of emotions in facial expressions, suggesting a specific cognitive effect on speech performance. Ayahuasca was well tolerated overall, and further research is needed to understand the mechanisms involved.
Journal of Clinical Psychopharmacology
February 1, 2001
Alex Gamma, Alfred Buck, Thomas Berthold et al.
84 citations
Regular polytoxic Ecstasy users show higher levels of depressiveness than non-users, but their brain activity during a sustained-attention task does not differ from controls. Mood was assessed with the Hamilton Rating Scale for Depression and the EWL Mood Rating Scale, while regional cerebral blood flow was measured using positron emission tomography. Both groups performed equally on the cognitive task. The heightened depressiveness in Ecstasy users is consistent with previous studies and may relate to serotonergic hypofunction from repeated MDMA consumption, but the study cannot rule out that these mood differences existed before Ecstasy use.
Journal of Clinical Psychopharmacology
December 12, 2015
Yena Lee, Kahlood Syeda, Nadia A. Maruschak et al.
75 citations
A single, low-dose administration of ketamine can rapidly reduce depressive symptoms in adults with treatment-resistant mood disorders and may also have antisuicide effects. The antidepressant effects may be partly mediated by targeting neural circuits involved in executive function and cognitive emotional processing. Pretreatment cognitive function predicts treatment outcomes, suggesting that beneficial effects on cognition could be a proximate mechanism for symptom relief, even though ketamine is known to impair cognitive function. Recent reviews and meta-analyses conclude that ketamine has possible clinical benefits in refractory mood disorders, and its salutary effects, particularly on suicidality, may involve procognitive mechanisms.
Journal of Clinical Psychopharmacology
December 1, 2007
Sergio Abanades, Magı́ Farré, Diego Barral et al.
69 citations
A single oral dose of gamma-hydroxybutyric acid (GHB) at 40 or 60 mg/kg produces euphoria and pleasurable effects with slightly higher ratings than those from flunitrazepam (1.25 mg) or ethanol (0.7 g/kg) in healthy male recreational club drug users. GHB shows a biphasic time profile: an initial stimulant-like effect as plasma concentrations rise, followed by a later sedative effect unrelated to its kinetics. GHB increases blood pressure and pupil diameter, while flunitrazepam produces marked sedation. Both GHB and flunitrazepam impair psychomotor performance, including digit symbol substitution and balance tasks, whereas ethanol only mildly affects balance. The findings suggest a high abuse liability of GHB and flunitrazepam in this population.
Journal of Clinical Psychopharmacology
December 1, 2001
Karl R. Hanes
69 citations
A 26-year-old woman with lifelong depression marked by worthlessness, social disinterest, and lack of meaning first tried sertraline 50 mg daily for 3 months but stopped due to no benefit. A 6-month course of cognitive-behavioural therapy brought some improvement but not full resolution, with Hamilton Depression Rating Scale scores remaining in the moderately depressed range (19-21).
Journal of Clinical Psychopharmacology
September 12, 2008
Brian O’Mathúna, Magı́ Farré, Amin Rostami‐hodjegan et al.
68 citations
MDMA (ecstasy) strongly inhibits the liver enzyme CYP2D6, which is responsible for metabolizing many drugs. In a controlled trial with 15 healthy men, a single 1.5 mg/kg oral dose of MDMA increased blood levels of the probe drug dextromethorphan about tenfold and reduced its breakdown product dextrorphan. The urinary metabolic ratio rose nearly 100-fold, and two-thirds of participants temporarily showed a metabolic profile typical of poor metabolizers. CYP2D6 activity recovered after 10 days, with a half-life of 46.6 hours. Users should be warned that MDMA can dangerously alter the metabolism of other medications.
Journal of Clinical Psychopharmacology
July 13, 2013
Cédric M. Hysek, Anja E. Fink, Linda D. Simmler et al.
57 citations
Blocking α₁-noradrenergic receptors with the drug doxazosin reduces MDMA-induced increases in blood pressure and body temperature, and moderately lessens positive mood, but enhances rapid heart rate. In a randomized, double-blind, placebo-controlled crossover study with 16 healthy participants, doxazosin (8 mg daily for 3 days before MDMA 125 mg) altered several acute effects of MDMA. The findings suggest that α₁-adrenergic receptors play a role in the cardiovascular stimulant effects of MDMA and, to a minor extent, its thermogenic and euphoric effects in humans.
Journal of Clinical Psychopharmacology
October 10, 2018
Susan Schenk, David Newcombe
53 citations
MDMA (ecstasy) shows some promise as an aid to psychotherapy for posttraumatic stress disorder (PTSD) by increasing prosocial feelings, possibly through oxytocin release and reduced fear conditioning. However, MDMA also carries risks of neurotoxicity and potential for misuse. The article weighs the pros and cons of using MDMA for PTSD, noting that while some evidence suggests it can help patients address underlying trauma, its significant adverse effects raise concerns. Alternative treatments based on MDMA's pharmacology but with fewer side effects are proposed. Further research into the mechanisms behind MDMA's beneficial effects may lead to safer treatment options.
Journal of Clinical Psychopharmacology
April 1, 1996
Karl R. Hanes
52 citations
Psilocybin-assisted psychotherapy may reduce symptoms of body dysmorphic disorder (BDD) by altering how individuals perceive and evaluate their own appearance. In a small open-label pilot study, participants with BDD received two doses of psilocybin combined with psychotherapy. Results suggest clinically meaningful reductions in BDD symptom severity and improvements in insight and quality of life at post-treatment and at 3-month follow-up. No serious adverse events were reported, though transient anxiety occurred during drug sessions. These preliminary findings indicate psilocybin-assisted therapy could be a promising treatment for BDD, a condition with limited effective options.
Journal of Clinical Psychopharmacology
June 1, 1996
Henry David Abraham, Anitra Mamen
50 citations
Risperidone, a medication that blocks serotonin-2 and dopamine D2 receptors, worsened symptoms in three patients with hallucinogen-persisting perception disorder (HPPD), a condition sometimes triggered by LSD that causes ongoing visual disturbances and panic. The exacerbation of LSD-like panic and visual symptoms suggests that HPPD may be a relative contraindication for risperidone use.
Journal of Clinical Psychopharmacology
November 1, 2020
Dorna Kheirabadi, Gholam Reza Kheirabadi, Zahra Mirlohi et al.
49 citations
A pilot study randomly assigned 45 adults with major depressive disorder to receive either intramuscular ketamine (0.5 mg/kg), oral ketamine (1 mg/kg), or electroconvulsive therapy (ECT) over 3 weeks. Depression and suicidal ideation scores improved significantly in all groups, with no meaningful differences between the three treatments. Ketamine caused brief, transient dissociative symptoms, whereas ECT led to memory loss lasting up to a month in some patients. Patients who received ketamine preferred it over ECT. The authors suggest that oral and intramuscular ketamine may have antidepressant effects equal to ECT, with possibly greater antisuicidal effects, fewer cognitive side effects, and higher patient preference.
Journal of Clinical Psychopharmacology
April 13, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
46 citations
A single dose of ayahuasca did not alter the recognition of emotions in facial expressions compared with placebo in healthy volunteers. The drug was well tolerated, producing nausea, gastrointestinal discomfort, and vomiting, with some reports of visual effects, tranquility, and well-being, and few reports of transient anxiety or confusion. No significant effects appeared on cardiovascular measures or brain-derived neurotrophic factor levels. A significant time-dependent deterioration of alkaloids, especially dimethyltryptamine, was observed. The absence of effects on emotion recognition may stem from the dose used, alkaloid degradation, learning effects, or the sample's high educational level.
Journal of Clinical Psychopharmacology
April 25, 2020
Marlene P. Freeman, Rebecca S. Hock, George I. Papakostas et al.
45 citations
Higher body mass index (BMI) and obesity are linked to a stronger acute antidepressant effect from a single intravenous dose of ketamine in patients with treatment-resistant depression. In a randomized, double-blind, placebo-controlled trial, patients with obesity showed a significantly greater reduction in depression symptoms 24 hours after ketamine infusion compared to those with normal BMI. Overweight patients also showed a trend toward greater improvement. Similar but weaker effects were observed at 72 hours. The findings suggest that obesity may enhance the rapid antidepressant response to ketamine, which could have clinical relevance for the many patients with both major depressive disorder and obesity.
Journal of Clinical Psychopharmacology
María Gómez-sousa, Daniel Jiménez‐garrido, Genís Ona et al.
24 citations
Among 40 first-time ayahuasca ceremony participants, 7 reported intense challenging psychological effects. Four of those 7 had a pre-existing psychiatric diagnosis; one month after the ceremony, two no longer met diagnostic criteria and the other two showed considerably reduced symptoms, with effects persisting at six months. Poor setting and guidance contributed to some reactions. Six of the seven did not use ayahuasca again during the study. The findings suggest that acute negative psychological reactions during ayahuasca ceremonies can sometimes be followed by positive long-term effects, highlighting the need for prospective research on safety and contextual factors.
Journal of Clinical Psychopharmacology
August 20, 2021
Alberto Sainz-Cort, Daniel Jiménez‐garrido, Elena Muñoz Marrón et al.
17 citations
THC produces psychotomimetic effects, but when CBD is coadministered with THC, those effects are reduced. In a double-blind, placebo-controlled crossover trial with 18 cannabis social club members, participants given THC plus CBD reported lower psychotomimetic scores than those given THC alone. CBD alone and placebo showed no psychotomimetic effects. The findings support CBD's antipsychotomimetic properties in real-world settings and link the endocannabinoid system to psychotic-like symptoms, with implications for medical cannabis practice and schizophrenia.
Journal of Clinical Psychopharmacology
Nicole Ledwos, Joshua D. Rosenblat, Daniel M. Blumberger et al.
16 citations
A critical appraisal of clinical trials on serotonergic psychedelics for major depressive disorder and end-of-life distress finds that current evidence is low-level due to methodological limitations. Small randomized trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy to an active comparator, with similar preliminary positive effects for single-dose ayahuasca in treatment-resistant depression and lysergic acid diethylamide for end-of-life distress. Adverse events were mild and transient. However, small homogenous samples, expectancy bias, functional unblinding, and lack of standardized psychotherapy limit all studies. Psychedelics should remain experimental interventions used within clinical trials.
Journal of Clinical Psychopharmacology
Giordano Novak Rossi, Juliana Mendes Rocha, Flávia L. Osório et al.
12 citations
In a small preliminary trial, ayahuasca—with or without a 600 mg dose of cannabidiol (CBD) given 90 minutes beforehand—did not produce interactive effects on emotion recognition or empathy tasks. Both groups showed faster reaction times on these tasks and reported reduced anxiety, sedation, and discomfort, but there were no differences between the group that received CBD and the one that did not. Ayahuasca was well tolerated, causing mainly nausea and gastrointestinal discomfort, with no clinically significant changes in heart or liver measures. The safety of the combination suggests that both drugs could be tested in larger trials for anxiety disorders.
Journal of Clinical Psychopharmacology
March 14, 2022
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia L. Osório et al.
11 citations
Psychedelics show promise in treating brain disorders, with a study involving 200 participants revealing a 60% reduction in symptoms of depression and anxiety after a single dose. Tryptophan, a key amino acid, plays a crucial role in serotonin production, which is vital for mood regulation. Biochemical analysis and advanced sensing techniques have enhanced understanding of these substances' effects on the brain, highlighting their potential as innovative therapies for mental health challenges. This groundbreaking approach could reshape treatment paradigms for various conditions.
Journal of Clinical Psychopharmacology
October 19, 2018
Rafael G. Dos Santos, José Alexandre S. Crippa, Flávia de Lima Osório et al.
9 citations
Ayahuasca, a psychedelic brew containing dimethyltryptamine (DMT) and harmine, may help treat social anxiety disorder. In a controlled setting, a single dose of ayahuasca reduced anxiety symptoms in volunteers with social anxiety disorder compared to a placebo. The improvement was observed within hours and lasted for several days. The study suggests that ayahuasca could be a fast-acting treatment option for social anxiety, but the small sample size and lack of long-term follow-up limit the conclusions.