Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
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.
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.
Human Psychopharmacology Clinical and Experimental
October 1, 2003
Suzanne L. Verheyden, John A. Henry, H. Valerie Curran
171 citations
Regular MDMA users report both positive and negative psychological effects. Among 466 regular users, acute effects include positive and negative impacts on mental health and physical effects. Between sessions, 83% experienced low mood and 80% impaired concentration. Long-term effects include tolerance (59%), impaired concentration (38%), depression (37%), and feeling more open toward people (31%). Factors such as age, gender, extent of MDMA use, and use of cocaine or amphetamine influence these effects. Users' main concern about stopping MDMA is its long-term effects on mental health.
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.
Neuropsychobiology
January 1, 2000
H. Valerie Curran
143 citations
MDMA is neurotoxic in animals, and evidence for human neurotoxicity comes from three indirect research areas: neurobiological and neuroendocrine studies, psychological and somatic symptoms in users, and psychiatric case reports. The strength of causative links between observed effects, MDMA use, and human neurotoxicity varies across these study types. Methodological problems in human MDMA research complicate interpretation.
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
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.
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.
Journal of Psychopharmacology
February 21, 2019
Hina Akram, Claire Mokrysz, H. Valerie Curran
57 citations
Synthetic cannabinoids are more potent than natural cannabis because they fully activate the CB1 receptor, potentially causing more serious psychological effects. A review of 17 studies found that acute use impairs cognitive functioning and alters subjective psychological ratings compared to placebo. Non-intoxicated users show lower cognitive performance and elevated symptoms like paranoia compared to natural cannabis users and non-users. Methodological limitations across studies hinder conclusions about how dose, frequency, or type of synthetic cannabinoid influences outcomes. More research is urgently needed as use increases in at-risk populations.
Journal of Psychopharmacology
May 18, 2015
Sunjeev K. Kamboj, Emma J. Kilford, Stephanie Minchin et al.
43 citations
MDMA (ecstasy) and compassionate imagery both increase self-compassion and reduce self-criticism in recreational users. In a non-blind experiment, participants who consumed ecstasy showed similar pro-social effects to those produced by a contemplative compassion exercise, particularly in those with higher attachment-related avoidance. The findings suggest MDMA may enhance psychotherapy by fostering compassionate attitudes toward oneself. However, because the study was not blinded and drug purity was unknown, controlled trials with pharmaceutical-grade MDMA are needed to confirm these effects.
Addiction
February 8, 2023
Will Lawn, Katie Trinci, Claire Mokrysz et al.
36 citations
Adolescent cannabis users are neither more resilient nor more vulnerable than adult cannabis users to the acute psychotomimetic, verbal memory-impairing, or subjective effects of cannabis. In a randomized, double-blind, placebo-controlled crossover experiment with 24 adolescents (16-17 years old) and 24 adults (26-29 years old) who used cannabis 0.5-3 days per week, vaporized THC (8 mg for a 75 kg person) and THC plus CBD (24 mg) both significantly increased subjective drug effect, impaired verbal episodic memory, and increased psychotomimetic effects compared to placebo. There was no evidence that adolescents differed from adults in their responses, and CBD did not modulate the acute effects of THC.
Journal of Psychopharmacology
August 13, 2014
LH Stewart, B. Ferguson, CJA Morgan et al.
28 citations
Acute recreational use of MDMA (ecstasy) increases perceived trustworthiness of faces and cooperative behavior in economic games. In a study comparing 17 ecstasy users tested on the night of drug use and again three days later with 22 controls, users rated faces as more trustworthy and showed more cooperation on dictator and ultimatum games while intoxicated. By day three, no group differences remained on these tasks. Self-ratings showed typical acute effects such as euphoria and energy, with negative effects like reduced empathy and increased distrust emerging on day three. The findings suggest a single dose enhances aspects of empathy, which may contribute to its recreational popularity and potential therapeutic use.
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
August 5, 2020
Will Lawn, J. P. Hill, Chandni Hindocha et al.
23 citations
A single 600 mg oral dose of cannabidiol did not alter brain activity related to anticipating or receiving rewards in healthy adults. Using functional magnetic resonance imaging during a monetary incentive delay task, the expected reward-related brain regions—including the insula, caudate, nucleus accumbens, anterior cingulate, and orbitofrontal cortex—were activated, but no difference was observed between cannabidiol and placebo. Bayesian analyses confirmed that activity in these regions was similar under both conditions, and behavioral measures of motivation for reward also showed no significant difference. The findings suggest that acute cannabidiol does not affect the neural correlates of reward anticipation or feedback in healthy individuals.
Journal of Psychopharmacology
May 20, 2022
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha et al.
21 citations
THC strongly disrupts connectivity between the striatum and cortex, but co-administering CBD mitigates this effect in the limbic striatum network. In one study, inhaled cannabis with 8 mg THC or 8 mg THC plus 10 mg CBD disrupted associative and sensorimotor networks, while THC alone also disrupted the limbic striatum network. In a second study, oral 600 mg CBD increased connectivity in the associative network and caused minor disruptions in limbic and sensorimotor networks. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with implications for understanding cannabis-related disorders and developing cannabinoid therapeutics.
Neuropsychopharmacology
May 28, 2024
Natalie Ertl, Tom P. Freeman, Claire Mokrysz et al.
19 citations
Cannabis use disrupts resting-state functional connectivity in key brain networks—default mode, executive control, salience, hippocampal, and limbic striatal—similarly in adolescents (16–17 years) and young adults (26–29 years). Cannabidiol (CBD) did not counteract the effects of delta-9-tetrahydrocannabinol (THC) and, in some cases, further reduced connectivity both within networks and across the whole brain. These findings challenge the assumption that CBD makes cannabis safer and indicate that the adolescent brain is not more vulnerable to cannabis-induced connectivity disruptions than the adult brain.
Journal of Psychopharmacology
July 29, 2023
Natalie Ertl, Will Lawn, Claire Mokrysz et al.
17 citations
Regular cannabis use is associated with localized increases in connectivity of the executive control network (ECN), which may reflect adaptive or compensatory changes in response to regular intoxication. Adolescents generally showed weaker connectivity than adults across multiple brain networks, consistent with normal developmental effects. However, there were no significant interactions between age group and cannabis user group, meaning the connectivity changes linked to cannabis use did not differ between adolescents and adults. No associations were found between cannabis use frequency and any connectivity measures.
Psychopharmacology (Berl)
February 1, 2018
H. Valerie Curran, David Nutt, Harriet de Wit
17 citations
Psychedelics and related drugs show therapeutic possibilities for mental health conditions, with research exploring their mechanisms, including brain modulation and neuroplasticity. The work discusses how these compounds may alter brain pathways and states of consciousness to produce therapeutic benefits. It also addresses the regulatory landscape for these substances in medical research and mental healthcare. The authors suggest that understanding the neurobiology and therapeutic mechanisms is crucial for advancing treatment research and medical innovation.
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.
Psychopharmacology
February 28, 2024
Daniel L. Hall, Will Lawn, Shelan Ofori et al.
5 citations
Acute intoxication with vaporized THC eliminated attentional bias away from cannabis-related cues in both adolescents and adults who used cannabis 0.5–3 days per week. In a randomized, double-blind, placebo-controlled crossover study with 48 participants (24 adolescents aged 16–17 and 24 adults aged 26–29), a weight-adjusted dose of 8 mg THC eliminated the bias, while adding 24 mg CBD did not alter this effect. There was no significant difference in response between age groups. The findings suggest that acute THC intoxication shifts attentional processing of cannabis cues, but CBD does not moderate this effect.
bioRxiv (Cold Spring Harbor Laboratory)
November 21, 2020
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha et al.
4 citations
preprint
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major cannabis constituents with contrasting actions: THC is psychoactive and addiction-promoting, while CBD may have opposite effects. In two placebo-controlled, double-blind studies, inhaled THC (8 mg) strongly disrupted functional connectivity in associative and sensorimotor striatal networks, and this disruption was selectively alleviated in the limbic striatum when co-administered with CBD (10 mg). Oral CBD (600 mg) alone increased connectivity in the associative network but caused minor decreases in limbic and sensorimotor networks. The insula emerged as a key region affected by cannabinoid-induced connectivity changes, with implications for cannabis-related disorders and cannabinoid therapeutics.
bioRxiv (Cold Spring Harbor Laboratory)
June 5, 2025
Ekaterina Shatalina, Natalie Ertl, Kat Petrilli et al.
1 citation
preprint
Inhaling cannabis with THC alone or THC plus CBD reduces resting-state functional connectivity in brain networks that are rich in CB1 and CB2 cannabinoid receptors. Co-administering CBD with THC produced more widespread reductions than THC alone, affecting regions involved in cognition and emotion such as the prefrontal cortex, cingulate cortex, insula, hippocampus, amygdala, and putamen. Higher THC levels in the blood were linked to greater connectivity decreases when CBD was also present. Subjective drug effects correlated with connectivity changes in a region-specific way. The findings suggest that CBD may enhance rather than dampen THC's effects on brain connectivity, contrary to some earlier expectations.
UNC Libraries
April 22, 2020
Peter J. Hellyer, Luke T. Williams, Ben Sessa et al.
1 citation
Lysergic acid diethylamide (LSD) in microgram doses produces profound, sometimes life-changing experiences and is a uniquely powerful psychoactive substance. In the first modern neuroimaging study of LSD, marked changes in brain blood flow, electrical activity, and network communication patterns were observed. These changes correlated strongly with the drug's hallucinatory and consciousness-altering properties. The findings have implications for understanding the neurobiology of consciousness and for potential applications of LSD in psychological research.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martine Skumlien, Tom P. Freeman, Daniel L. Hall et al.
In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and cannabidiol (CBD) does not moderate this effect. The adolescent reward circuitry is not differentially sensitive to the acute effects of cannabis on reward anticipation. This double-blind, placebo-controlled, crossover study with 23 adults (26-29 years) and 24 adolescents (16-17 years) used functional magnetic resonance imaging (fMRI) to measure brain activity during a monetary reward anticipation task after inhaling cannabis with tetrahydrocannabinol (THC), THC plus CBD, or placebo. THC acutely reduced reward anticipation activity in the ventral striatum and right insula compared with placebo. THC plus CBD also reduced activity in these regions. The effects were the same in adolescents and adults.