Addiction
July 21, 2011
Celia J. A. Morgan, H. Valerie Curran
645 citations
Repeated misuse of ketamine, both acute and chronic, causes significant physical, psychological, and social harms. A major physical harm is ketamine-induced ulcerative cystitis, particularly linked to chronic, frequent use. Frequent daily use is also associated with neurocognitive impairment, most robustly deficits in working and episodic memory. Recent studies suggest neurological abnormalities that may underlie these cognitive effects. Many frequent users report trying but failing to stop using ketamine, indicating addiction concerns. Treatment for ketamine-induced ulcerative cystitis should coordinate urologists and addiction specialists. Neurocognitive impairment can negatively impact educational and work achievement and compound addiction. Prevention and harm minimization campaigns are needed to alert young people to these potentially chronic effects.
Biological Psychiatry
January 10, 2014
Robin Carhart-Harris, Kevin Murphy, Robert Leech et al.
182 citations
The medial temporal lobes (MTLs) are specifically involved in how MDMA works in the brain, though more research is needed to understand how the drug's characteristic subjective effects emerge from its modulation of spontaneous brain activity.
BJPsych Open
December 23, 2021
Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph M. Rootman et al.
180 citations
A systematic review of 83 studies found that subanesthetic doses of ketamine produce rapid, short-lived antidepressant and anti-suicidal effects. Evidence for other psychiatric conditions is less robust but suggests similarly positive but transient benefits. The conclusions are tentative due to high risk of bias across the included studies. Optimal dosing, administration methods, and best forms of adjunctive psychotherapy require further investigation.
Psychopharmacology
September 2, 2016
Will Lawn, Tom P. Freeman, Rebecca Pope et al.
177 citations
Cannabis containing only THC reduced the likelihood of choosing high-effort rewards compared to placebo, indicating a transient amotivational state, while adding CBD altered the effect of THC on expected value. Cannabis-dependent individuals showed preserved motivation but impaired reward learning compared to non-dependent controls, though depression may have influenced results.
American Journal of Psychiatry
January 11, 2022
Meryem Grabski, Amy Mcandrew, Will Lawn et al.
169 citations
Three weekly infusions of ketamine (0.8 mg/kg) helped people with severe alcohol use disorder stay abstinent more days over six months than placebo infusions did. The ketamine group averaged 10.1% more days abstinent than the placebo group. Combining ketamine with mindfulness-based relapse prevention therapy produced the largest improvement, with 15.9% more abstinent days compared with placebo plus alcohol education. No serious adverse events occurred. Relapse rates did not differ significantly between ketamine and placebo groups. The findings suggest ketamine is safe and may support abstinence, especially when paired with psychological therapy.
Lancet Psychiatry
April 5, 2017
Ilina Singh, Celia J. A. Morgan, Valerie H. Curran et al.
158 citations
Based on current evidence, off-label ketamine use for severe, treatment-resistant depression does not violate ethical principles, but clinicians and professional bodies must establish guidelines for good practice, register all trial data, and continuously monitor risks. The analysis reviews evidence for ketamine's antidepressant effects and safety profile, concluding with recommendations for oversight bodies to support safe, effective, and ethical treatment.
The International Journal of Neuropsychopharmacology
December 17, 2013
Robin Carhart-Harris, Matthew B. Wall, David Erritzøe et al.
110 citations
MDMA (ecstasy) makes recalling favorite autobiographical memories feel more vivid, emotionally intense, and positive, while making recall of worst memories feel less negative. In a double-blind, placebo-controlled fMRI study with 19 participants who had prior MDMA experience, 100 mg of MDMA altered brain activity during memory recall: it increased activation in the fusiform gyrus and somatosensory cortex for favorite memories and decreased activation in the left anterior temporal cortex for worst memories. These neural changes suggest MDMA creates a positive emotional bias, which may explain why it helps patients revisit traumatic memories during psychotherapy for PTSD.
Journal of Psychopharmacology
November 25, 2009
Celia J. A. Morgan, Leslie Muetzelfeldt, Mark Muetzelfeldt et al.
80 citations
A survey of 1501 UK residents with direct experience of 20 psychoactive substances asked them to rate each drug's physical, dependence-related, and social harms as well as benefits using the same scale previously used by experts. Users' harm rankings correlated very highly with expert rankings (r = 0.896). Alcohol, solvents, and tobacco were rated among the top ten most harmful drugs despite being unclassified under the Misuse of Drugs Act. No correlation existed between the legal classification of drugs and users' harm rankings. Ecstasy, cannabis, and LSD were rated highest by users for both acute and chronic benefits, suggesting users are relatively well informed and that the current legal classification does not inform users about harms.
Scientific Reports
November 3, 2017
Will Lawn, Jaime E. C. Hallak, José Alexandre S. Crippa et al.
78 citations
Ayahuasca users reported greater well-being than both classic psychedelic users and non-psychedelic drug users, and less problematic drinking than classic psychedelic users, though both psychedelic groups reported more problematic drinking than non-psychedelic users. Ayahuasca's acute subjective effects typically lasted six hours, peaking one hour after consumption. These findings come from a large online survey of nearly 97,000 respondents, including 527 ayahuasca users. The authors call for longitudinal studies and randomized trials to further investigate ayahuasca's effects on well-being and alcohol use.
Frontiers in Psychiatry
June 9, 2021
Simon Ruffell, Nige Netzband, WaiFung Tsang et al.
74 citations
A naturalistic study of 63 people who participated in ayahuasca ceremonies at a retreat in the Peruvian Amazon found significant improvements in depression, anxiety, and overall psychological distress, along with increased self-compassion, immediately after the retreat and sustained at six months. Depression scores on the Beck Depression Inventory dropped from 13.9 to 6.1, anxiety scores on the State-Trait Anxiety Inventory fell from 44.4 to 34.3, and scores on the Clinical Outcomes in Routine Evaluation-Outcome Measure decreased from 37.3 to 22.3. Changes in memory valence were linked to these improvements. Epigenetic results were inconclusive but suggested further research on the SIGMAR1 gene is warranted.
The International Journal of Neuropsychopharmacology
August 30, 2017
Tom P. Freeman, Rebecca Pope, Matthew B. Wall et al.
67 citations
Cannabis dampens the brain's response to music in regions involved in reward and emotion, including the auditory cortex, hippocampus, amygdala, and ventral striatum. However, when cannabis also contains cannabidiol, these dampening effects are offset, and brain activity does not differ from placebo. Despite reduced neural responses, both types of cannabis increased participants' self-reported desire to listen to music and enhanced sound perception. The findings suggest that cannabidiol may mitigate some of cannabis's effects on brain reward systems.
Frontiers in Psychiatry
January 1, 2021
O Merve Mollaahmetoglu, Johanna Keeler, Katherine J Ashbullby et al.
62 citations
Ketamine treatment, provided in a supportive clinical setting, led to a significant change in participants' relationship with alcohol. Interviews with 12 people who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II randomized controlled trial revealed six key themes: multifaceted motivations for joining the trial; the influence of set and setting on the acute experience; inherent contradictions such as dissociation versus feelings of connection; rapidly fluctuating experiences; meaningful, mystical, and spiritual experiences; and transformational effects of the infusions. Participants reported that ego dissolution and dissociation were linked to these transformative changes. The authors suggest that the acute psychoactive effects of ketamine transcend its traditional label as a dissociative anesthetic and recommend developing new measures to capture the full spectrum of these effects.
Consciousness and Cognition
January 10, 2012
Gráinne Schäfer, Amanda Feilding, Celia J. A. Morgan et al.
60 citations
Cannabis acutely increases schizotypy and chronic use is linked to higher rates of psychosis. Creative individuals tend to have higher schizotypy, but the connection between cannabis, schizotypy, and creativity had not been studied. In 160 cannabis users tested sober and intoxicated, cannabis increased verbal fluency in low-creative individuals to the same level as high-creative individuals. Cannabis also increased state psychosis-like symptoms in both groups. High-creativity participants had significantly higher trait schizotypy, but this was not linked to the verbal fluency change. Acute cannabis use enhances divergent thinking, measured by verbal fluency, specifically in those with low trait creativity.
Current Opinion in Behavioral Sciences
November 15, 2016
Celia J. A. Morgan, Amy Mcandrew, Tobias Stevens et al.
41 citations
No Summary
BJPsych Open
January 18, 2022
Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph M. Rootman et al.
28 citations
No Summary
Psychological Medicine
April 28, 2020
Claire Mokrysz, Natacha D. C. Shaban, Tom P. Freeman et al.
24 citations
Inhaling cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may raise the incidence of speech illusion—hearing words in meaningless white noise. Cannabidiol (CBD) did not blunt these effects. In one study, adults had stronger psychotic-like symptom responses than adolescents, suggesting adolescents may be less vulnerable to the acute psychotic-like effects of cannabis. The odds of experiencing speech illusion were 3.1 times higher after inhaling cannabis with THC and negligible CBD compared to placebo.
Journal of Psychopharmacology
February 5, 2019
Molly Carlyle, Tobias Stevens, Leah Fawaz et al.
22 citations
People who use MDMA (ecstasy) recreationally over the long term show normal or even enhanced empathy compared to other drug users. In a study of 67 individuals, those who used MDMA scored higher on self-reported emotional empathy and on a computer task measuring cognitive empathy than poly-drug users who did not use MDMA. However, MDMA users did not differ from other groups in how they subjectively reacted to social exclusion. The amount or frequency of MDMA use was not linked to empathy levels. These findings suggest that moderate, long-term recreational MDMA use does not cause heightened social distress and may be associated with better empathy, supporting the drug's safety profile for potential therapeutic use.
Addiction (Abingdon, England)
April 28, 2025
Rebecca Harding, Tamsin Barton, Maeve Niepceron et al.
14 citations
Ketamine use disorder (KUD) is linked to frequent physical and psychological symptoms, including bladder problems (60%), nasal problems (60%), 'K-cramps' (56%), and abstinence-related cravings (71%), low mood (62%), and anxiety (59%). A survey of 274 current or former users, 40% treatment-seeking and 60% not, found that treatment-seeking individuals consumed more ketamine daily (2.67 g vs. 1.68 g). Despite these symptoms, 56% did not seek treatment; among those who did, only 36% were satisfied with care. Services were often seen as not tailored to ketamine (43%) and only somewhat effective (43%). Cost and affordability were the top factors for choosing treatment.
Journal of Psychopharmacology
January 9, 2021
Abigail M. Freeman, Claire Mokrysz, Chandni Hindocha et al.
6 citations
Tolerance to some acute effects of delta-9-tetrahydrocannabinol (THC) develops in a domain-specific way, with more frequent cannabis use linked to reduced intensity of subjective effects like feeling stoned and reduced psychosis-like effects. Tolerance to alertness reduction occurred more readily than tolerance to psychotomimetic effects, while tolerance to memory impairment was weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC. These findings come from a mega-analysis of 128 cannabis users across four double-blind, placebo-controlled studies.
Alcohol and alcoholism (Oxford, Oxfordshire)
May 14, 2025
Hannah Thurgur, Ben Sessa, Laurie Higbed et al.
3 citations
In an open-label feasibility study, 14 adults with alcohol use disorder who had recently completed detoxification underwent an eight-week course of ten psychotherapy sessions, including two sessions with MDMA. Bayesian analysis estimated a 55%–63% probability of a two-level reduction in World Health Organization drinking risk three months after treatment. Preliminary findings also indicated reductions in alcohol craving and improvements in sleep and aspects of psychosocial functioning at the three-month follow-up compared to baseline. The results provide initial insights into MDMA-assisted psychotherapy's potential to improve quality of life and well-being beyond reducing drinking.
Scientific Reports
February 28, 2018
Will Lawn, Jaime E. C. Hallak, J.a.s. Crippa et al.
3 citations
A correction to this article has been published and is linked from the HTML and PDF versions. The error has not been fixed in the paper.
Neuroscience and Biobehavioral Reviews
July 1, 2026
Marcus J. Glennon, Catherine Bird, Prateek Yadav et al.
2 citations
Setting up a psychedelic research study involves a long, arduous, and Kafkaesque process with many unstandardised challenges. These complexities challenge existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. This review brings together major UK psychedelic research teams to formalise these unique considerations, addressing sociocultural, political, legal, pharmacological, safety, study design, and experiential facets. It identifies continuing areas of debate and provides a practical, experience-based guide with recommendations for policymakers and future researchers intending to set up a psychedelic study or clinical trial.
J Psychopharmacol
October 27, 2025
David Nutt, Celia J. A. Morgan, David Erritzøe et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a promising treatment for severe depression and other psychiatric conditions, particularly in patients who have not responded to traditional therapies. The compound can provide rapid relief from depressive symptoms, often within hours, which contrasts with conventional antidepressants that may take weeks to work. This surprising discovery has opened a new frontier in mental health treatment, offering hope for those with challenging mood disorders. However, the use of ketamine in psychiatry also raises concerns about its potential for abuse and long-term side effects, necessitating careful clinical oversight.
Research Square
May 13, 2025
Eirini K. Argyri, Joy Krecké, Oliver Robinson et al.
2 citations
Professionals who support people after psychedelic experiences identify six common extended difficulties: existential struggle and ontological shock, anxiety and panic, self-perception issues, dissociative symptoms, resurfacing of repressed trauma, and disappointment from unmet expectations. Recommended support strategies include trauma-informed individual psychotherapy, grounding and mindfulness techniques, peer and community support, meaning-making and narrative reconstruction, and sometimes short-term psychiatric medication. Psychiatrists emphasize medical stabilization, while psychotherapists and coaches focus on existential meaning-making and emotional processing. The findings suggest that trauma-informed, cross-disciplinary approaches are needed for psychedelic integration as use expands.
Journal of psychopharmacology (Oxford, England)
June 1, 2026
Gabrielle Smith, Timothy Piatkowski, Jason Ferris et al.
1 citation
People who self-treat psychiatric conditions with unregulated drugs often use ketamine alongside other psychedelics. Among 5831 respondents to the 2020 Global Drug Survey who self-treated diagnosed psychiatric conditions, over 60% had prior psychiatric diagnoses, most commonly depression and anxiety. Those using both ketamine and other psychedelics attended festivals and clubs more often and used ketamine more frequently. Those using only non-ketamine psychedelics showed a significant reduction in ketamine use. Nearly half sought online advice before starting ketamine self-treatment, suggesting online platforms are key for harm reduction resources.