Individual and combined effects of Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) on striato-cortical connectivity in the human brain
Matthew B. Wall, Tom P. Freeman, Chandni Hindocha, Lysia Demetriou, Natalie Ertl, Abigail M. Freeman, A. Jones, Will Lawn, Rebecca Pope, Claire Mokrysz, Daniel Solomons, Ben Statton, Hannah Walker, Yumeya Yamamori, Zixu Yang, Jocelyn Ll Yim, David Nutt, Oliver Howes, Helen Valerie Curran, Michael Bloomfield
bioRxiv (Cold Spring Harbor Laboratory) November 21, 2020 preprint DOI: 10.1101/2020.11.20.391805 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind |
|---|---|
| Sample size | 40 |
| Population | Healthy adults |
| Interventions | THC CBD THC+CBD |
| Dose | 8mg THC, 8mg THC+10mg CBD, 600mg CBD |
| Topics | Addiction Cannabis CBD |
| Keywords | Striatum Psychotomimetic Cannabinoid Placebo Pharmacology Dopamine Nmda receptor Pathology |
| Citations | 4 |
| Key findings | THC strongly disrupts striato-cortical connectivity, and co-administration with CBD selectively mitigates this effect in the limbic striatum. |
Abstract
Abstract Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have somewhat opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Across two placebo-controlled, double-blind studies, we examine the effects of THC, CBD, and THC+CBD on the functional connectivity of striatal sub-divisions (associative, limbic, and sensorimotor) using resting-state functional Magnetic Resonance Imaging (fMRI) and seed-based functional connectivity analyses. Study 1 (N=17; inhaled 8mg THC, 8mg THC+10mg CBD, placebo) showed strong disruptive effects of both THC and THC+CBD conditions on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum, which was alleviated in the THC+CBD condition such that it did not differ from placebo. In Study 2 (N=23, oral 600mg CBD, placebo) CBD increased connectivity in the associative network, but relatively minor decreases/disruptions were found in the limbic and sensorimotor. In conclusion, THC strongly disrupts striato-cortical networks, and this effect is selectively mitigated in the limbic striatum when co-administered with CBD. When administered alone, 600mg oral CBD has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis related disorders, and the development of cannabinoid therapeutics.
Comparable studies
Other randomized controlled trials on cannabis for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity Regular drug users | 2015 | Three-way crossover study | n = 122 |
| The acute effects of cannabis, with and without cannabidiol, on attentional bias to cannabis related cues: a randomised, double-blind, placebo-controlled, cross-over study Adolescents (aged 16–17) and adults (aged 26–29) who used cannabis 0.5–3 days per week | 2024 | Randomized, double-blind, placebo-controlled, cross-over study | n = 48 |
| Brief report: The influence of childhood trauma on the effects of delta-9-tetrahydrocannabinol in persons with opioid use disorder. Persons receiving methadone for opioid use disorder | 2024 | Post-hoc analysis of a randomized, placebo-controlled, crossover trial | n = 25 |
| Value Signals Guiding Choices for Cannabis Versus Non-Drug Rewards in Regular Cannabis Users Near-daily cannabis users (≥4 days/week; non-treatment-seeking) | 2023 | Crossover experiment | n = 21 |
| The good, the bad, and the intoxicated Occasional cannabis users | 2021 | Double-blind, placebo-controlled study | n = 20 |