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.
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.
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.
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.
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
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.
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.
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.