Journal of Psychopharmacology
May 1, 2001
Nicholas Macinnes, Sheila L. Handley, G. F. A. Harding
120 citations
Former chronic users of MDMA (ecstasy) who now lead relatively drug-free lives report higher levels of depression than matched non-drug users. In a group of 29 respondents who had consumed an average of 527 tablets over their lifetime and none in the past 14 days, depression scores on the Beck Depression Inventory were significantly elevated compared to controls. Within the user group, depression levels were not related to current use of alcohol, cannabis, or amphetamine, but were positively correlated with an external locus of control and life stress. The strongest predictors of depression were frequent but mild life stress and the quantity of ecstasy tablets consumed over a 12-hour period.
Journal of Psychopharmacology
January 1, 2016
Jana Speth, Clemens Speth, Mendel Kaelen et al.
119 citations
A single dose of LSD (75 μg) reduced how often people spontaneously thought about the past, while thoughts about the present or future remained unchanged. In a placebo-controlled crossover study with 20 healthy volunteers, fewer references to past mental spaces appeared in reports collected about 2.5 hours after intravenous administration. This reduction correlated with the drug's subjective intensity and with decreased resting-state functional connectivity within the default-mode network, a brain system involved in autobiographical memory and rumination. The findings suggest LSD may reduce past-focused thinking, which could be relevant for treating conditions like depression where excessive reflection on the past is common.
Journal of Psychopharmacology
February 28, 2008
Ben Sessa
117 citations
Creativity is an important but hard-to-define cognitive process that presents a challenge for modern neuroscience, especially given the interest in cognitive enhancers. The traits of creative people resemble the psychological effects of psychedelic drugs, a phenomenon studied in small, anecdotal 1960s trials with inconclusive results. The current renaissance in psychedelic research and cognitive enhancement warrants revisiting these studies with contemporary methods.
Journal of Psychopharmacology
May 25, 2020
Bruno Romeo, Laurent Karila, Catherine Martelli et al.
115 citations
A meta-analysis of eight studies found that psychedelic drugs produce a rapid and sustained reduction in depressive symptoms, with effects appearing as early as day one and lasting up to six months. No serious adverse effects were reported, though transient increases in heart rate and blood pressure occurred compared to placebo. The analysis included studies published through April 2019.
Journal of Psychopharmacology
March 1, 2006
C. T. J. Lamers, A. Bechara, M. Rizzo et al.
113 citations
People who use both MDMA (ecstasy) and marijuana (THC) report more depression and anxiety than those who use only THC or no drugs. Memory is impaired in both drug-using groups. MDMA/THC users have slower psychomotor speed and less mental flexibility than non-users. THC users show less mental flexibility and worse decision-making than non-users, but these deficits are similar to those in MDMA/THC users. The findings suggest that some cognitive impairments previously attributed to MDMA may actually be due to concurrent THC use, while MDMA use is specifically linked to increased depression and anxiety.
Journal of Psychopharmacology
September 1, 2015
Peter S Hendricks, Matthew W Johnson, Roland R Griffiths
107 citations
Adults in the United States who had ever used psilocybin alone showed lower odds of past-month psychological distress (weighted OR = .81) and past-year suicidal thinking, planning, and attempt compared with those who had never used any classic psychedelic. Those who used psilocybin without other psychedelics also had reduced odds of psychological distress relative to users of other classic psychedelics. The findings suggest psilocybin may have therapeutic potential and a favorable safety profile, but do not directly address clinical applications or risk.
Journal of Psychopharmacology
March 30, 2006
Boris B. Quednow, Frank Jessen, Kai‐uwe Kühn et al.
105 citations
Chronic MDMA (ecstasy) use is linked to long-term serotonin depletion and memory deficits. Nineteen male abstinent MDMA users, 19 male abstinent cannabis users, and 19 male drug-naive controls took a German version of the Rey Auditory Verbal Learning Test. MDMA users showed widespread verbal memory deficits—in learning, consolidation, recall, and recognition—compared to both cannabis users and controls, while cannabis users performed similarly to controls. MDMA users also had worse recall consistency and strong retroactive interference, measures tied to frontal lobe function. Memory performance correlated with the amount of MDMA taken. The findings suggest MDMA-related memory deficits involve frontal cortex dysfunction, not just temporal or hippocampal damage.
Journal of Psychopharmacology
December 1, 2003
C. T. J. Lamers, Johannes G. Ramaekers, N. D. Muntjewerff et al.
105 citations
A single 75 mg dose of MDMA improved psychomotor performance, including movement speed and tracking in both single and divided attention tasks, but impaired the ability to predict object movement under divided attention, which may indicate impairment of driving-relevant skills. No effect was found on visual search, planning, or semantic memory retrieval. Alcohol 0.5 g/kg was also tested but its effects are not described here. The findings suggest MDMA can both enhance and impair specific cognitive and motor functions relevant to driving.
Journal of Psychopharmacology
August 26, 2016
Anya K. Bershad, Melissa A. Miller, Matthew J. Baggott et al.
104 citations
MDMA, a recreational drug, enhances sociability and feelings of closeness more than other stimulants like dextroamphetamine, methamphetamine, and methylphenidate. This review compares human laboratory studies on the social effects of MDMA versus other stimulants, from simple ratings of sociability to complex social behaviors, and examines the neurochemical mechanisms involved. The findings suggest that MDMA's distinct prosocial effects may underlie its recreational use and potential as a psychotherapy aid, distinguishing it from typical stimulants.
Journal of Psychopharmacology
January 1, 2022
James Rucker, Lindsey Marwood, Riikka-Liisa Johanna Ajantaival et al.
101 citations
A single dose of 10 or 25 mg psilocybin, given simultaneously to up to six healthy adults with one-to-one psychological support, did not impair cognitive function or emotional processing. Over 500 treatment-emergent adverse events were reported, mostly mild and resolving within a day, with no serious events or study withdrawals. Cognitive performance, measured by a Cambridge Neuropsychological Test Automated Battery global composite score and domain scores, showed no clinically relevant differences between psilocybin and placebo groups. The findings suggest that these doses of psilocybin are generally well tolerated and safe for cognitive function in the short and long term.
Journal of Psychopharmacology
February 20, 2021
Albert Garcia‐romeu, Frederick S. Barrett, Theresa M. Carbonaro et al.
101 citations
Psilocybin, a naturally occurring psychedelic, shows promise for treating mood and substance use disorders when given in structured settings. Most trials have adjusted the dose by body weight, but fixed dosing is simpler and cheaper. Analyzing data from ten previous studies (total 288 participants) that used weight-adjusted doses of 20 or 30 mg per 70 kg, or a fixed dose approximating 25 mg, no significant associations emerged between body weight or sex and the subjective effects (mystical, challenging, or intensity). Across body weights from 49 to 113 kg, body weight did not affect psilocybin's subjective effects, suggesting fixed dosing is as effective and more practical than weight-adjusted dosing.
Journal of Psychopharmacology
November 27, 2013
Adam Winstock, Stephen J. Kaar, Rohan Borschmann
101 citations
Based on a large anonymous online survey of 22,289 people, lifetime use of the potent hallucinogen DMT was 8.9% and past-year use was 5.0%. Among 472 respondents who had recently tried DMT for the first time, the drug produced a strong, intense, short-lived psychedelic high with relatively few negative effects or comedown compared to psilocybin, LSD, and ketamine. DMT had a larger proportion of new users (24%) than the other substances, suggesting its popularity may increase. The authors conclude that DMT has a very desirable effect profile indicating high abuse liability, possibly offset by a low urge to use more.
Journal of Psychopharmacology
March 9, 2009
P.-ø. Johansen, Ts Krebs
98 citations
Exposure therapy is effective for anxiety disorders but is underused, with patients often prescribed SSRIs or benzodiazepines that may hinder extinction learning. Given trials testing MDMA with psychotherapy for treatment-resistant anxiety, three mechanisms are proposed: MDMA increases oxytocin, strengthening the therapeutic alliance; it increases ventromedial prefrontal activity and decreases amygdala activity, improving emotional regulation and reducing avoidance; and it increases norepinephrine and cortisol, facilitating emotional engagement and extinction of learned fear. These effects may allow patients to feel safe while processing emotions, as seen in case reports. Further studies are needed.
Journal of Psychopharmacology
March 1, 2020
P. Glue, Shona Neehoff, A. Sabadel et al.
97 citations
In a double-blind, psychoactive-controlled study, 12 patients with treatment-resistant generalized anxiety and social anxiety disorders who were not currently depressed received ascending doses of ketamine (0.25, 0.5, 1 mg/kg) at weekly intervals, with midazolam 0.01 mg/kg randomly inserted as a control. Improvements in anxiety ratings occurred within an hour of ketamine dosing and persisted for up to one week. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate. Midazolam had minor brief effects on anxiety ratings. Ketamine was safe and well tolerated. Ketamine may be a potential therapeutic option for these patients.
Journal of Psychopharmacology
July 10, 2017
Sarah Saleemi, Steven Pennybaker, Missi Wooldridge et al.
97 citations
Only 60% of 529 samples of substances sold as Ecstasy or Molly, collected at U.S. music festivals between 2010 and 2015, actually contained MDMA when tested with colorimetric reagent assays. No significant difference in MDMA content was found between products sold as Ecstasy versus Molly, contradicting the common belief that Molly is less adulterated. People who learned their sample did not contain MDMA were significantly less likely to report intending to use it (relative risk = 0.56). The findings indicate that pill-testing services can reduce intent to consume potentially dangerous substances and may deserve legal protection.
Journal of Psychopharmacology
March 30, 2006
Fabrizio Schifano, John Corkery, Paolo Deluca et al.
96 citations
Over the last decade, the UK saw a yearly increase in ecstasy-related deaths, with 394 mentions identified from 1994 to 2003. In 42% of cases, ecstasy was the sole drug mentioned. The number of fatalities correlated positively with past-year use, number of drug offenders, and number of seizures, but negatively with ecstasy price. Price negatively correlated with use and seizures, and positively with average MDMA dosage per tablet. Other related drugs (MDA, MDEA, MBDB) appeared significantly only up to 1997. Increasing production and falling prices may have boosted consumption and deaths. Only medical death certificates were analyzed, not coroners' reports.
Journal of Psychopharmacology
August 25, 2020
Johannes G. Ramaekers, Nadia R. P. W. Hutten, Natasha L. Mason et al.
95 citations
A low dose of LSD (20 micrograms) that does not cause a psychedelic experience can increase pain tolerance and reduce the unpleasantness of pain in healthy volunteers. In a controlled experiment with 24 participants, those given 20 µg of LSD kept their hand in cold (3°C) water longer and reported less pain than when given a placebo. Smaller doses (5 and 10 µg) did not produce the same effect. The 20 µg dose caused slight increases in blood pressure, anxiety, and dissociation, but no profound mind-altering effects. These findings suggest that very low doses of LSD may offer a new approach to pain management without the intense psychological effects of higher doses.
Journal of Psychopharmacology
October 17, 2017
Peter S. Hendricks, Michael Crawford, Karen L. Cropsey et al.
91 citations
Lifetime use of classic psychedelics, including psilocybin, is associated with lower odds of recent larceny/theft, assault, and arrests for property or violent crimes among over 480,000 U.S. adults surveyed from 2002 to 2014. In contrast, illicit use of other drugs generally increased the odds of these criminal behaviors. Lifetime classic psychedelic use was linked to higher odds of drug distribution, similar to other substances. The findings suggest a potential protective effect of psilocybin against antisocial criminal behavior and support further clinical research in forensic settings.
Journal of Psychopharmacology
March 30, 2006
Jonathon L. Reay, Colin Hamilton, David O. Kennedy et al.
91 citations
People who use MDMA (ecstasy) show impairments in specific cognitive processes—set shifting, memory updating, and social and emotional judgment—compared to polydrug users who do not take MDMA. These deficits remained significant even after accounting for use of other drugs. The findings suggest that recreational ecstasy use may harm prefrontal cortex functions.
Journal of Psychopharmacology
March 4, 2021
Tim Hirschfeld, Timo T Schmidt
90 citations
Psilocybin, the psychoactive compound in magic mushrooms, intensifies almost all characteristics of altered states of consciousness measured by standard questionnaires. A meta-analysis of data from the Altered States Database found that higher psilocybin doses correlated with stronger ratings of perceptual alterations and positively experienced ego dissolution, while measures of challenging experiences showed only small effects and were barely influenced by dose. These dose-response relationships were established in controlled laboratory experiments with healthy participants and patient groups, and may not apply to recreational use because individual and environmental factors also shape subjective experiences.
Journal of Psychopharmacology
June 26, 2021
Emma I Kopra, V. Mondelli, C. Pariante et al.
89 citations
Ketamine, a rapid-acting antidepressant for treatment-resistant depression, appears to reduce inflammation in at least some depressed patients. A systematic review of 9 human studies and 22 rodent studies found strong evidence in rodents that ketamine lowers pro-inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, and also affects tryptophan metabolism by decreasing the enzyme indoleamine 2,3-dioxygenase. Human studies showed less consistent results but most reported decreases in peripheral inflammation including the same cytokines. Preliminary evidence also suggested reduced activation of the neurotoxic arm of the kynurenine pathway. Future research should investigate markers in the central nervous system and the clinical relevance of these inflammatory changes.
Journal of Psychopharmacology
April 23, 2019
Matthew B. Wall, Rebecca Pope, Tom P. Freeman et al.
89 citations
Two strains of cannabis—one containing only THC (8 mg) and another containing THC plus CBD (8 mg THC + 10 mg CBD)—were compared with placebo in seventeen healthy, experienced but non-regular cannabis users. Using resting-state fMRI, both strains reduced functional connectivity in the default mode and salience networks relative to placebo, but with distinct spatial patterns. The THC-only strain specifically disrupted the posterior cingulate cortex within the default mode network, and this disruption correlated with subjective feelings of being 'stoned' and 'high'. The THC-plus-CBD strain produced less disruption of the salience network, suggesting CBD may buffer THC's effects on salience processing, which could underlie its potential therapeutic role in disorders like psychosis and addiction.
Journal of Psychopharmacology
April 26, 2016
Timothy Amoroso, Michael Workman
89 citations
For posttraumatic stress disorder (PTSD), MDMA-assisted psychotherapy (MDMA-AP) shows larger treatment effects than prolonged exposure (PE) therapy, the current standard. A meta-analysis comparing two MDMA-AP clinical trials with several PE trials found MDMA-AP had larger effect sizes for clinician-observed outcomes (Hedges' g = 1.17 vs. 1.08) and patient self-report outcomes (Hedges' g = 0.87 vs. 0.77). MDMA-AP also had a considerably lower dropout rate than PE. These results suggest MDMA-AP offers a promising alternative for PTSD treatment, especially for patients who find PE intolerable or ineffective.
Journal of Psychopharmacology
May 20, 2006
Jiansong Yang, Masoud Jamei, Amir Heydari et al.
89 citations
A physiologically-based model of drug metabolism predicted that a typical recreational dose of MDMA (ecstasy) inactivates most hepatic CYP2D6 within an hour, and that recovery to basal CYP2D6 levels takes at least 10 days. The analysis suggests that genetic polymorphism of CYP2D6 and coadministration of CYP2D6 inhibitors may have less impact on MDMA's pharmacokinetics and acute toxicity risk than previously thought, consistent with clinical observations showing no obvious link between inherited CYP2D6 deficiency and acute MDMA intoxication.
Journal of Psychopharmacology
April 3, 2017
Kim P. C. Kuypers, Patrick C. Dolder, Johannes G. Ramaekers et al.
88 citations
A pooled analysis of six placebo-controlled studies with 118 participants confirmed that a single dose of MDMA (75 or 125 mg) increases emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy, which involves recognizing others' emotions. The empathy boost was strongest for positive emotions and was linked to higher MDMA blood levels before testing. The effect was consistent across different labs and doses, and was not influenced by sex, prior drug use, or participants' baseline trait empathy. Although MDMA raised oxytocin levels, those increases did not explain the empathy changes.