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.
Drug and Alcohol Dependence
August 11, 2023
Teuntje A. D. Pelgrim, Johannes G. Ramaekers, Matthew B. Wall et al.
3 citations
THC, the main psychoactive component of cannabis, reduces functional connectivity in the salience network—a brain system involved in processing awareness and salient information—specifically weakening connections from the right insula to the left insula and anterior cingulate cortex. A trend toward decreased connectivity was also observed in the hippocampus-midbrain-striatum network, which may relate to acute psychotic-like effects. The COMT Val158Met genotype modulated subjective responses: individuals with the Met/Met genotype experienced the strongest dysphoric reactions and showed reduced connectivity in the hippocampus-midbrain-striatum network after THC. These findings suggest that prefrontal dopamine levels influence the acute effects of cannabis.
June 30, 2022
Matthew B. Wall, Rebecca Harding, Rayyan Zafar et al.
3 citations
preprint
Psychedelic therapy shows potential for treating psychiatric disorders like depression, addiction, and PTSD. Classic serotonergic psychedelics such as psilocybin, LSD, DMT, and 5-MeO-DMT are the main focus, along with ketamine, MDMA, and ibogaine. The concurrent use of advanced neuroimaging methods, particularly PET and MRI, has allowed precise assessment of brain effects, benefiting the development of these treatments. The text identifies gaps in knowledge that future multimodal imaging studies could address, providing a stronger foundation for psychedelic therapy.
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.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
Mol Psychiatry
July 1, 2025
Rebecca Harding, Neomi Singer, Matthew B. Wall et al.
correction
In a study comparing psilocybin therapy (PT) to escitalopram for depression, brain responses to unexpected musical notes were measured. After PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. This suggests PT alters brain processing of unexpected events differently than escitalopram, potentially contributing to its therapeutic effects.
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.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.
The Biochemist
March 14, 2024
Natalie Ertl, Matthew B. Wall
Psychedelics have been used for ritual, spiritual, and medicinal purposes since prehistory across many cultures. Classic psychedelics like psilocybin act on the serotonin 5-HT2A receptor, while atypical ones like MDMA and ketamine have different mechanisms and produce less hallucination. They all induce profound shifts in consciousness, positive emotions, and feelings of connectedness. LSD, first synthesized in the early 1940s, began the first wave of Western psychedelic research. By the 1960s, thousands of patients had received LSD therapy for depression, anxiety, and addiction in the USA, UK, and Czech Republic, coinciding with the development of other psychiatric drugs like monoamine oxidase inhibitors and antipsychotics.